Brian T. Bateman

All Publications

• Risk of Autism after Prenatal Topiramate, Valproate, or Lamotrigine Exposure. The New England journal of medicine Hernández-Díaz, S., Straub, L., Bateman, B. T., Zhu, Y., Mogun, H., Wisner, K. L., Gray, K. J., Lester, B., McDougle, C. J., DiCesare, E., Pennell, P. B., Huybrechts, K. F. 2024; 390 (12): 1069-1079

  Abstract

  Maternal use of valproate during pregnancy has been associated with an increased risk of neurodevelopmental disorders in children. Although most studies of other antiseizure medications have not shown increased risks of these disorders, there are limited and conflicting data regarding the risk of autism spectrum disorder associated with maternal topiramate use.We identified a population-based cohort of pregnant women and their children within two health care utilization databases in the United States, with data from 2000 through 2020. Exposure to specific antiseizure medications was defined on the basis of prescription fills from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any antiseizure medication during pregnancy with respect to the risk of autism spectrum disorder. Valproate was used as a positive control, and lamotrigine was used as a negative control.The estimated cumulative incidence of autism spectrum disorder at 8 years of age was 1.9% for the full population of children who had not been exposed to antiseizure medication (4,199,796 children). With restriction to children born to mothers with epilepsy, the incidence was 4.2% with no exposure to antiseizure medication (8815 children), 6.2% with exposure to topiramate (1030 children), 10.5% with exposure to valproate (800 children), and 4.1% with exposure to lamotrigine (4205 children). Propensity score-adjusted hazard ratios in a comparison with no exposure to antiseizure medication were 0.96 (95% confidence interval [CI], 0.56 to 1.65) for exposure to topiramate, 2.67 (95% CI, 1.69 to 4.20) for exposure to valproate, and 1.00 (95% CI, 0.69 to 1.46) for exposure to lamotrigine.The incidence of autism spectrum disorder was higher among children prenatally exposed to the studied antiseizure medications than in the general population. However, after adjustment for indication and other confounders, the association was substantially attenuated for topiramate and lamotrigine, whereas an increased risk remained for valproate. (Funded by the National Institute of Mental Health.).

  View details for DOI 10.1056/NEJMoa2309359

  View details for PubMedID 38507750

• First Trimester Use of Buprenorphine or Methadone and the Risk of Congenital Malformations. JAMA internal medicine Suarez, E. A., Bateman, B. T., Straub, L., Hernández-Díaz, S., Jones, H. E., Gray, K. J., Connery, H. S., Davis, J. M., Lester, B., Terplan, M., Zhu, Y., Vine, S. M., Mogun, H., Huybrechts, K. F. 2024

  Abstract

  Use of buprenorphine or methadone to treat opioid use disorder is recommended in pregnancy; however, their teratogenic potential is largely unknown.To compare the risk of congenital malformations following in utero exposure to buprenorphine vs methadone.This population-based cohort study used health care utilization data from publicly insured Medicaid beneficiaries in the US from 2000 to 2018. A total of 13 360 pregnancies with enrollment from 90 days prior to pregnancy start through 1 month after delivery and first trimester use of buprenorphine or methadone were included and linked to infants. Data were analyzed from July to December 2022.A pharmacy dispensing of buprenorphine or a code for administration of methadone in the first trimester.Primary outcomes included major malformations overall and malformations previously associated with opioids (any cardiac malformations, ventricular septal defect, secundum atrial septal defect/nonprematurity-related patent foramen ovale, neural tube defects, clubfoot, and oral clefts). Secondary outcomes included other organ system-specific malformations. Risk differences and risk ratios (RRs) were estimated comparing buprenorphine with methadone, adjusting for confounders with propensity score overlap weights.The cohort included 9514 pregnancies with first-trimester buprenorphine exposure (mean [SD] maternal age, 28.4 [4.6] years) and 3846 with methadone exposure (mean [SD] maternal age, 28.8 [4.7] years). The risk of malformations overall was 50.9 (95% CI, 46.5-55.3) per 1000 pregnancies for buprenorphine and 60.6 (95% CI, 53.0-68.1) per 1000 pregnancies for methadone. After confounding adjustment, buprenorphine was associated with a lower risk of malformations compared with methadone (RR, 0.82; 95% CI, 0.69-0.97). Risk was lower with buprenorphine for cardiac malformations (RR, 0.63; 95% CI, 0.47-0.85), including both ventricular septal defect (RR, 0.62; 95% CI, 0.39-0.98) and secundum atrial septal defect/nonprematurity-related patent foramen ovale (RR, 0.54; 95% CI, 0.30-0.97), oral clefts (RR, 0.65; 95% CI, 0.35-1.19), and clubfoot (RR, 0.55; 95% CI, 0.32-0.94). Results for neural tube defects were uncertain given low event counts. In secondary analyses, buprenorphine was associated with a decreased risk of central nervous system, urinary, and limb malformations but a greater risk of gastrointestinal malformations compared with methadone. These findings were consistent in sensitivity and bias analyses.In this cohort study, the risk of most malformations previously associated with opioid exposure was lower in buprenorphine-exposed infants compared with methadone-exposed infants, independent of measured confounders. Malformation risk is one factor that informs the individualized patient decision regarding medications for opioid use disorder in pregnancy.

  View details for DOI 10.1001/jamainternmed.2023.6986

  View details for PubMedID 38252426

  View details for PubMedCentralID PMC10804281

• Buprenorphine versus Methadone for Opioid Use Disorder in Pregnancy. The New England journal of medicine Suarez, E. A., Huybrechts, K. F., Straub, L., Hernández-Díaz, S., Jones, H. E., Connery, H. S., Davis, J. M., Gray, K. J., Lester, B., Terplan, M., Mogun, H., Bateman, B. T. 2022; 387 (22): 2033-2044

  Abstract

  Opioid agonist therapy is strongly recommended for pregnant persons with opioid use disorder. Buprenorphine may be associated with more favorable neonatal and maternal outcomes than methadone, but existing data are limited.We conducted a cohort study involving pregnant persons who were enrolled in public insurance programs in the United States during the period from 2000 through 2018 in which we examined outcomes among those who received buprenorphine as compared with those who received methadone. Exposure to the two medications was assessed in early pregnancy (through gestational week 19), late pregnancy (gestational week 20 through the day before delivery), and the 30 days before delivery. Risk ratios for neonatal and maternal outcomes were adjusted for confounders with the use of propensity-score overlap weights.The data source for the study consisted of 2,548,372 pregnancies that ended in live births. In early pregnancy, 10,704 pregnant persons were exposed to buprenorphine and 4387 to methadone. In late pregnancy, 11,272 were exposed to buprenorphine and 5056 to methadone (9976 and 4597, respectively, in the 30 days before delivery). Neonatal abstinence syndrome occurred in 52.0% of the infants who were exposed to buprenorphine in the 30 days before delivery as compared with 69.2% of those exposed to methadone (adjusted relative risk, 0.73; 95% confidence interval [CI], 0.71 to 0.75). Preterm birth occurred in 14.4% of infants exposed to buprenorphine in early pregnancy and in 24.9% of those exposed to methadone (adjusted relative risk, 0.58; 95% CI, 0.53 to 0.62); small size for gestational age in 12.1% and 15.3%, respectively (adjusted relative risk, 0.72; 95% CI, 0.66 to 0.80); and low birth weight in 8.3% and 14.9% (adjusted relative risk, 0.56; 95% CI, 0.50 to 0.63). Delivery by cesarean section occurred in 33.6% of pregnant persons exposed to buprenorphine in early pregnancy and 33.1% of those exposed to methadone (adjusted relative risk, 1.02; 95% CI, 0.97 to 1.08), and severe maternal complications developed in 3.3% and 3.5%, respectively (adjusted relative risk, 0.91; 95% CI, 0.74 to 1.13). Results of exposure in late pregnancy were consistent with results of exposure in early pregnancy.The use of buprenorphine in pregnancy was associated with a lower risk of adverse neonatal outcomes than methadone use; however, the risk of adverse maternal outcomes was similar among persons who received buprenorphine and those who received methadone. (Funded by the National Institute on Drug Abuse.).

  View details for DOI 10.1056/NEJMoa2203318

  View details for PubMedID 36449419

• Association of Antidepressant Use During Pregnancy With Risk of Neurodevelopmental Disorders in Children. JAMA internal medicine Suarez, E. A., Bateman, B. T., Hernandez-Diaz, S., Straub, L., Wisner, K. L., Gray, K. J., Pennell, P. B., Lester, B., McDougle, C. J., Zhu, Y., Mogun, H., Huybrechts, K. F. 2022

  Abstract

  Importance: Antidepressant use during pregnancy has been associated with neurodevelopmental disorders in children in some studies. However, results may be explained by uncontrolled confounding by parental mental health status, genetics, and environmental factors.Objective: To evaluate the association between antidepressant use in pregnancy and neurodevelopmental outcomes in children.Design, Setting, and Participants: This cohort study of health care utilization data was separated into cohorts of publicly and privately insured pregnant individuals and their children nested in the Medicaid Analytic eXtract (MAX; 2000-2014) and the IBM MarketScan Research Database (MarketScan; 2003-2015). A total of 1.93 million pregnancies in MAX and 1.25 million pregnancies in MarketScan were recorded. Children were followed from birth until outcome diagnosis, disenrollment, death, or end of study (maximum 14 years). Analyses were conducted between August 2020 and July 2021.Exposures: Dispensing of antidepressant medication from gestational week 19 until delivery, the period of synaptogenesis.Main Outcomes and Measures: Neurodevelopmental disorders in children defined using validated algorithms. Early pregnancy exposure was considered in sensitivity analyses, and approaches to confounding adjustment included propensity score fine stratification, discontinuers comparison, and sibling analyses.Results: Among the individuals included in the analysis, there were 145 702 antidepressant-exposed and 3 032 745 unexposed pregnancies; the mean (SD) age among the antidepressant exposed and unexposed was 26.2 (5.7) and 24.3 (5.8) years in MAX and 32.7 (4.6) and 31.9 (4.6) years in MarketScan, respectively; and in MAX, which collected information on race and ethnicity, 72.4% of the antidepressant-exposed and 37.1% of the unexposed individuals were White. Crude results suggested up to a doubling in risk of neurodevelopmental outcomes associated with antidepressant exposure; however, no association was observed in the most fully adjusted analyses. When comparing antidepressant-exposed and unexposed siblings, hazard ratios were 0.97 (95% CI, 0.88-1.06) for any neurodevelopmental disorder, 0.86 (95% CI, 0.60-1.23) for autism spectrum disorder, 0.94 (95% CI, 0.81-1.08) for attention-deficit/hyperactivity disorder, 0.77 (95% CI, 0.42-1.39) for specific learning disorders, 1.01 (95% CI, 0.88-1.16) for developmental speech/language disorder, 0.79 (95% CI, 0.54-1.17) for developmental coordination disorder, 1.00 (95% CI, 0.45-2.22) for intellectual disability, and 0.95 (95% CI, 0.80-1.12) for behavioral disorders. Results were generally consistent for antidepressant classes and drugs and across exposure windows.Conclusions and Relevance: The results of this cohort study suggest that antidepressant use in pregnancy itself does not increase the risk of neurodevelopmental disorders in children. However, given strong crude associations, antidepressant exposure in pregnancy may be an important marker for the need of early screening and intervention.

  View details for DOI 10.1001/jamainternmed.2022.4268

  View details for PubMedID 36190722

• Obesity in Pregnancy. The New England journal of medicine Creanga, A. A., Catalano, P. M., Bateman, B. T. 2022; 387 (3): 248-259

  View details for DOI 10.1056/NEJMra1801040

  View details for PubMedID 35857661

• Neurodevelopmental Disorders Among Publicly or Privately Insured Children in the United States. JAMA psychiatry Straub, L., Bateman, B. T., Hernandez-Diaz, S., York, C., Lester, B., Wisner, K. L., McDougle, C. J., Pennell, P. B., Gray, K. J., Zhu, Y., Suarez, E. A., Mogun, H., Huybrechts, K. F. 1800

  Abstract

  Importance: Neurodevelopmental disorders are associated with poor health and social outcomes. Population-based data on incidence, age at diagnosis, and demographic variations are essential to identify modifiable risk factors and inform the planning of services and interventions.Objectives: To assess the incidence and timing of diagnosis of neurodevelopmental disorders during childhood in the US and to evaluate differences by population characteristics.Design, Setting, and Participants: This population-based cohort study used nationwide data on birth cohorts nested in the 2000-2014 Medicaid Analytic eXtract and the 2003-2015 IBM MarketScan Research Database on 2 070 541 publicly and 1 309 900 privately insured children enrolled at birth. Data were analyzed between May 1, 2020, and June 30, 2021.Main Outcomes and Measures: Neurodevelopmental disorders, autism spectrum disorders, attention-deficit/hyperactivity disorder, learning disabilities, speech or language disorders, developmental coordination disorders, intellectual disabilities, and behavioral disorders were identified based on validated algorithms. Kaplan-Meier analyses were used to estimate the incidence and timing of diagnosis, stratified by child's sex, birth year, maternal age at delivery, and race and ethnicity.Results: The cohorts comprised 2 070 541 publicly insured children (1 045 426 boys [50.5%]) and 1 309 900 privately insured children (667 607 boys [51.0%]) enrolled at birth. By 8 years of age, 23.9% of publicly insured children and 11.0% of privately insured children received a diagnosis of 1 or more neurodevelopmental disorders (autism spectrum disorder, 1.6% and 1.3%; attention-deficit/hyperactivity disorder, 14.5% and 5.8%; learning disability, 1.2% and 0.6%; speech or language disorder, 8.4% and 4.5%; developmental coordination disorder, 0.9% and 0.7%; intellectual disability, 0.7% and 0.1%; and behavioral disorder, 8.4% and 1.5%). Risks were substantially higher among boys (incidence of ≥1 neurodevelopmental disorder by age 8 years for boys vs girls: 30.7% vs 16.7% among publicly insured children and 15.0% vs 6.7% among privately insured children) and White children (30.2% vs 9.1% among Asian children, 23.0% among Black children, 15.4% among Hispanic children, and 22.7% among children of unknown race or ethnicity; information on race and ethnicity was available only for publicly insured children). The association of maternal age and birth year with incidence of neurodevelopmental disorders varied by outcome. Except for attention-deficit/hyperactivity disorder, the diagnosis tended to be established somewhat earlier for privately insured children. The association of race and ethnicity with age at diagnosis varied by outcome. Co-occurring neurodevelopmental disorders were common, especially among children with autism spectrum disorder and intellectual disability (>70% had ≥1 other disorder).Conclusions and Relevance: In this population-based cohort study, a relatively high incidence of and co-occurrence of neurodevelopmental disorders as well as the disparity in incidence and timing of diagnosis by insurance type and race and ethnicity were found. These findings represent important public health concerns and underscore the need for timely and accessible developmental assessments and educational services to help reduce the burden of these disorders.

  View details for DOI 10.1001/jamapsychiatry.2021.3815

  View details for PubMedID 34985527

• Association of first trimester prescription opioid use with congenital malformations in the offspring: population based cohort study. BMJ (Clinical research ed.) Bateman, B. T., Hernandez-Diaz, S., Straub, L., Zhu, Y., Gray, K. J., Desai, R. J., Mogun, H., Gautam, N., Huybrechts, K. F. 2021; 372: n102

  Abstract

  To evaluate the risk of first trimester exposure to prescription opioids for major congenital malformations, previously reported to be associated with such exposure.Population based cohort study.Nationwide sample of publicly and commercially insured pregnant women linked to their liveborn infants, nested in the Medicaid Analytic eXtract (MAX, 2000-14) and the MarketScan Research Database (MarketScan, 2003-15).1 602 580 publicly insured (MAX) and 1 177 676 commercially insured (MarketScan) pregnant women with eligibility from at least three months before pregnancy to one month after delivery; infants with eligibility for at least three months after birth.Use of prescription opioids was ascertained by requiring two or more dispensations of any opioid during the first trimester.Major malformations overall, cardiac malformations overall, ventricular septal defect, secundum atrial septal defect/patent foramen ovale, neural tube defect, clubfoot, and oral cleft, defined based on validated algorithms. Propensity score stratification was used to adjust for potential confounders and/or proxies for confounders. Estimates from each database were combined using meta-analysis.70 447 (4.4%) of 1 602 580 publicly insured and 12 454 (1.1%) of 1 177 676 commercially insured pregnant women had two or more dispensations of an opioid during the first trimester. Absolute risk of malformations overall was 41.0 (95% confidence interval 39.5 to 42.5) per 1000 pregnancies exposed to opioids versus 32.0 (31.7 to 32.3) per 1000 unexposed pregnancies in the MAX cohort, and 42.6 (39.0 to 46.1) and 37.3 (37.0 to 37.7) per 1000, respectively, in the MarketScan cohort. Pooled unadjusted relative risk estimates were raised for all outcomes but shifted substantially toward the null after adjustment; for malformations overall (relative risk 1.06, 95% confidence interval 1.02 to 1.10), cardiovascular malformations (1.09, 1.00 to 1.18), ventricular septal defect (1.07, 0.95 to 1.21), atrial septal defect/patent foramen ovale (1.04, 0.88 to 1.24), neural tube defect (0.82, 0.53 to 1.27), and clubfoot (1.06, 0.88 to 1.28). The relative risk for oral clefts remained raised after adjustment (1.21, 0.98 to 1.50), with a higher risk of cleft palate (1.62, 1.23 to 2.14).Prescription opioids used in early pregnancy are not associated with a substantial increase in risk for most of the malformation types considered, although a small increase in the risk of oral clefts associated with their use is possible.

  View details for DOI 10.1136/bmj.n102

  View details for PubMedID 33568363

  View details for PubMedCentralID PMC7873721

• Gabapentin in pregnancy and the risk of adverse neonatal and maternal outcomes: A population-based cohort study nested in the US Medicaid Analytic eXtract dataset. PLoS medicine Patorno, E., Hernandez-Diaz, S., Huybrechts, K. F., Desai, R. J., Cohen, J. M., Mogun, H., Bateman, B. T. 2020; 17 (9): e1003322

  Abstract

  Despite the widespread use, only sparse information is available on the safety of gabapentin during pregnancy. We sought to evaluate the association between gabapentin exposure during pregnancy and risk of adverse neonatal and maternal outcomes.Using the United States Medicaid Analytic eXtract (MAX) dataset, we conducted a population-based study of 1,753,865 Medicaid-eligible pregnancies between January 2000 and December 2013. We examined the risk of major congenital malformations and cardiac defects associated with gabapentin exposure during the first trimester (T1), and the risk of preeclampsia (PE), preterm birth (PTB), small for gestational age (SGA), and neonatal intensive care unit admission (NICUa) associated with gabapentin exposure early, late, or both early and late in pregnancy. Gabapentin-unexposed pregnancies served as the reference. We estimated relative risks (RRs) and 95% confidence intervals (CIs) using fine stratification on the propensity score (PS) to control for over 70 confounders (e.g., maternal age, race/ethnicity, indications for gabapentin, other pain conditions, hypertension, diabetes, use of opioids, and specific morphine equivalents). We identified 4,642 pregnancies exposed in T1 (mean age = 28 years; 69% white), 3,745 exposed in early pregnancy only (28 years; 67% white), 556 exposed in late pregnancy only (27 years; 60% white), and 1,275 exposed in both early and late pregnancy (29 years; 75% white). The reference group consisted of 1,744,447 unexposed pregnancies (24 years; 40% white). The adjusted RR for major malformations was 1.07 (95% CI 0.94-1.21, p = 0.33) and for cardiac defects 1.12 (0.89-1.40, p = 0.35). Requiring ≥2 gabapentin dispensings moved the RR to 1.40 (1.03-1.90, p = 0.03) for cardiac defects. There was a higher risk of preterm birth among women exposed to gabapentin either late (RR, 1.28 [1.08-1.52], p < 0.01) or both early and late in pregnancy (RR, 1.22 [1.09-1.36], p < 0.001), SGA among women exposed to gabapentin early (1.17 [1.02-1.33], p = 0.02), late (1.39 [1.01-1.91], p = 0.05), or both early and late in pregnancy (RR, 1.32 [1.08-1.60], p < 0.01), and NICU admission among women exposed to gabapentin both early and late in pregnancy (RR, 1.35 [1.20-1.52], p < 0.001). There was no higher risk of preeclampsia among women exposed to gabapentin after adjustment. Study limitations include the potential for residual confounding and exposure misclassification.In this large population-based study, we did not find evidence for an association between gabapentin exposure during early pregnancy and major malformations overall, although there was some evidence of a higher risk of cardiac malformations. Maternal use of gabapentin, particularly late in pregnancy, was associated with a higher risk of PTB, SGA, and NICUa.

  View details for DOI 10.1371/journal.pmed.1003322

  View details for PubMedID 32870921

  View details for PubMedCentralID PMC7462308

• Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study. BMJ (Clinical research ed.) Zhu, Y., Bateman, B. T., Gray, K. J., Hernandez-Diaz, S., Mogun, H., Straub, L., Huybrechts, K. F. 2020; 369: m1494

  Abstract

  To examine the risk of congenital malformations associated with exposure to oral fluconazole at commonly used doses in the first trimester of pregnancy for the treatment of vulvovaginal candidiasis.Population based cohort study.A cohort of pregnancies publicly insured in the United States, with data from the nationwide Medicaid Analytic eXtract 2000-14.Pregnancies of women enrolled in Medicaid from three or more months before the last menstrual period to one month after delivery, and infants enrolled for three or more months after birth.Use of fluconazole and topical azoles was established by requiring one or more prescriptions during the first trimester of pregnancy.Risk of musculoskeletal malformations, conotruncal malformations, and oral clefts (primary outcomes), associated with exposure to oral fluconazole, diagnosed during the first 90 days after delivery, were examined.The study cohort of 1 969 954 pregnancies included 37 650 (1.9%) pregnancies exposed to oral fluconazole and 82 090 (4.2%) pregnancies exposed to topical azoles during the first trimester. The risk of musculoskeletal malformations was 52.1 (95% confidence interval 44.8 to 59.3) per 10 000 pregnancies exposed to fluconazole versus 37.3 (33.1 to 41.4) per 10 000 pregnancies exposed to topical azoles. The risks of conotruncal malformations were 9.6 (6.4 to 12.7) versus 8.3 (6.3 to 10.3) per 10 000 pregnancies exposed to fluconazole and topical azoles, respectively; risks of oral clefts were 9.3 (6.2 to 12.4) versus 10.6 (8.4 to 12.8) per 10 000 pregnancies, respectively. The adjusted relative risk after fine stratification of the propensity score was 1.30 (1.09 to 1.56) for musculoskeletal malformations, 1.04 (0.70 to 1.55) for conotruncal malformations, and 0.91 (0.61 to 1.35) for oral clefts overall. Based on cumulative doses of fluconazole, the adjusted relative risks for musculoskeletal malformations, conotruncal malformations, and oral clefts overall were 1.29 (1.05 to 1.58), 1.12 (0.71 to 1.77), and 0.88 (0.55 to 1.40) for 150 mg of fluconazole; 1.24 (0.93 to 1.66), 0.61 (0.26 to 1.39), and 1.08 (0.58 to 2.04) for more than 150 mg up to 450 mg of fluconazole; and 1.98 (1.23 to 3.17), 2.30 (0.93 to 5.65), and 0.94 (0.23 to 3.82) for more than 450 mg of fluconazole, respectively.Oral fluconazole use in the first trimester was not associated with oral clefts or conotruncal malformations, but an association with musculoskeletal malformations was found, corresponding to a small adjusted risk difference of about 12 incidents per 10 000 exposed pregnancies overall.

  View details for DOI 10.1136/bmj.m1494

  View details for PubMedID 32434758

  View details for PubMedCentralID PMC7237981

• Intravenous Ondansetron in Pregnancy and Risk of Congenital Malformations. JAMA Huybrechts, K. F., Hernandez-Diaz, S., Straub, L., Gray, K. J., Zhu, Y., Mogun, H., Bateman, B. T. 2020; 323 (4): 372-374

  View details for DOI 10.1001/jama.2019.18587

  View details for PubMedID 31730152

  View details for PubMedCentralID PMC6865841

• Maternal and fetal outcomes following exposure to duloxetine in pregnancy: cohort study. BMJ (Clinical research ed.) Huybrechts, K. F., Bateman, B. T., Pawar, A., Bessette, L. G., Mogun, H., Levin, R., Li, H., Motsko, S., Scantamburlo Fernandes, M. F., Upadhyaya, H. P., Hernandez-Diaz, S. 2020; 368: m237

  Abstract

  To evaluate the risk of adverse maternal and infant outcomes following in utero exposure to duloxetine.Cohort study nested in the Medicaid Analytic eXtract for 2004-13.Publicly insured pregnancies in the United States.Pregnant women 18 to 55 years of age and their liveborn infants.Duloxetine exposure during the etiologically relevant time window, compared with no exposure to duloxetine, exposure to selective serotonin reuptake inhibitors, exposure to venlafaxine, and exposure to duloxetine before but not during pregnancy.Congenital malformations overall, cardiac malformations, preterm birth, small for gestational age infant, pre-eclampsia, and postpartum hemorrhage.Cohort sizes ranged from 1.3 to 4.1 million, depending on the outcome. The number of women exposed to duloxetine varied by cohort and exposure contrast and was around 2500-3000 for early pregnancy exposure and 900-950 for late pregnancy exposure. The base risk per 1000 unexposed women was 36.6 (95% confidence interval 36.3 to 36.9) for congenital malformations overall, 13.7 (13.5 to 13.9) for cardiovascular malformations, 107.8 (107.3 to 108.3) for preterm birth, 20.4 (20.1 to 20.6) for small for gestational age infant, 33.6 (33.3 to 33.9) for pre-eclampsia, and 23.3 (23.1 to 23.4) for postpartum hemorrhage. After adjustment for measured potential confounding variables, all baseline characteristics were well balanced for all exposure contrasts. In propensity score adjusted analyses versus unexposed pregnancies, the relative risk was 1.11 (95% confidence interval 0.93 to 1.33) for congenital malformations overall and 1.29 (0.99 to 1.68) for cardiovascular malformations. For preterm birth, the relative risk was 1.01 (0.92 to 1.10) for early exposure and 1.19 (1.04 to 1.37) for late exposure. For small for gestational age infants the relative risks were 1.14 (0.92 to 1.41) and 1.20 (0.83 to 1.72) for early and late pregnancy exposure, respectively, and for pre-eclampsia they were 1.12 (0.96 to 1.31) and 1.04 (0.80 to 1.35). The relative risk for postpartum hemorrhage was 1.53 (1.08 to 2.18). Results from sensitivity analyses were generally consistent with the findings from the main analyses.On the basis of the evidence available to date, duloxetine is unlikely to be a major teratogen but may be associated with an increased risk of postpartum hemorrhage and a small increased risk of cardiac malformations. While continuing to monitor the safety of duloxetine as data accumulate over time, these potential small increases in risk of relatively uncommon outcomes must be weighed against the benefits of treating depression and pain during pregnancy in a given patient.EUPAS 15946.

  View details for DOI 10.1136/bmj.m237

  View details for PubMedID 32075794

  View details for PubMedCentralID PMC7190016

• Association Between Number of In-Person Health Care Visits and SARS-CoV-2 Infection in Obstetrical Patients. JAMA Reale, S. C., Fields, K. G., Lumbreras-Marquez, M. I., King, C. H., Burns, S. L., Huybrechts, K. F., Bateman, B. T. 2020; 324 (12): 1210-1212

  View details for DOI 10.1001/jama.2020.15242

  View details for PubMedID 32797148

  View details for PubMedCentralID PMC7428807

• Association of Opioid Overdose With Opioid Prescriptions to Family Members. JAMA internal medicine Khan, N. F., Bateman, B. T., Landon, J. E., Gagne, J. J. 2019; 179 (9): 1186-1192

  Abstract

  Prescription opioid misuse is a public health problem that leads to overdose. Although existing interventions focus on limiting prescribing to patients at high risk, individuals may still access prescription opioids dispensed to family members.To determine whether opioid prescriptions to family members were associated with overdose for individuals who themselves did not have an opioid prescription.We conducted a 1:4 matched case-control study using health care utilization data from 2004 through 2015 from a large US commercial insurance company. Eligible individuals were required to have at least 12 months of continuous enrollment and 1 or more family members in the database. Individuals who experienced overdose were identified by their first opioid overdose after the baseline period and matched to control participants by time in the database, calendar time, age, sex, and number of individuals in the family unit. Both groups were restricted to individuals with no prior opioid dispensing of their own. Data analysis was conducted from January 2018 to August 2018.Any prior opioid dispensing to a family member, total morphine milligram equivalents dispensed to family members, and the type of opioid product dispensed.Individual odds of opioid overdose resulting in an emergency department visit or hospitalization were the primary end point. The primary analysis evaluated the odds of overdose among individuals whose family members had been dispensed an opioid. Sensitivity analyses examined the odds stratified by age and timing relative to the dispensing of opioids to family members.A total of 2303 individuals who experienced opioid overdose and 9212 matched control individuals were identified. The mean (SD) age was 23.2 (18.1) years; 1158 affected individuals and 4632 control individuals (50.3%) were female. The mean (SD) time in the database before an overdose case was 3.2 (3.3) years. Prior opioid dispensing to family members was associated with individual overdose (odds ratio [OR], 2.89 [95% CI, 2.59-3.23]). There was a significant dose-response association between increasing amounts of opioids dispensed to family members and odds of overdose (>0-<50 morphine milligram equivalents per day: OR, 2.71 [95% CI, 2.42-3.03]; 50-<90 morphine milligram equivalents per day: OR, 7.80 [95% CI, 3.63-16.78]; ≥90 morphine milligram equivalents per day: OR, 15.08 [95% CI, 8.66-26.27]).In this analysis, opioid prescriptions to family members were associated with overdose among individuals who do not receive opioid prescriptions. Interventions may focus on expanding access to opioid antagonists, locking prescription opioids in the home, and providing greater patient education to limit fatal overdose among family members.

  View details for DOI 10.1001/jamainternmed.2019.1064

  View details for PubMedID 31233088

  View details for PubMedCentralID PMC6593630

• Inappropriate opioid prescription after surgery. Lancet (London, England) Neuman, M. D., Bateman, B. T., Wunsch, H. 2019; 393 (10180): 1547-1557

  Abstract

  Worldwide, the use of prescription opioid analgesics more than doubled between 2001 and 2013, with several countries, including the USA, Canada, and Australia, experiencing epidemics of opioid misuse and abuse over this period. In this context, excessive prescribing of opioids for pain treatment after surgery has been recognised as an important concern for public health and a potential contributor to patterns of opioid misuse and related harm. In the second paper in this Series we review the evolution of prescription opioid use for pain treatment after surgery in the USA, Canada, and other countries. We summarise evidence on the extent of opioid overprescribing after surgery and its potential association with subsequent opioid misuse, diversion, and the development of opioid use disorder. We discuss evidence on patient, physician, and system-level predictors of excessive prescribing after surgery, and summarise recent work on clinical and policy efforts to reduce such prescribing while ensuring adequate pain control.

  View details for DOI 10.1016/S0140-6736(19)30428-3

  View details for PubMedID 30983590

  View details for PubMedCentralID PMC6556783

• β-Blocker Use in Pregnancy and the Risk for Congenital Malformations. Annals of internal medicine Bateman, B. T., Huybrechts, K. F., Hernandez-Diaz, S., Kieler, H., Zoega, H. 2019; 170 (12): 909-910

  View details for DOI 10.7326/L19-0157

  View details for PubMedID 31207630

• Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA Huybrechts, K. F., Hernández-Díaz, S., Straub, L., Gray, K. J., Zhu, Y., Patorno, E., Desai, R. J., Mogun, H., Bateman, B. T. 2018; 320 (23): 2429-2437

  Abstract

  Evidence for the fetal safety of ondansetron, a 5-HT3 receptor antagonist that is commonly prescribed for nausea and vomiting during pregnancy, is limited and conflicting.To evaluate the association between ondansetron exposure during pregnancy and risk of congenital malformations.A retrospective cohort study nested in the 2000-2013 nationwide Medicaid Analytic eXtract. The cohort consisted of 1 816 414 pregnancies contributed by 1 502 895 women enrolled in Medicaid from 3 months before the last menstrual period through 1 month or longer after delivery; infants were enrolled in Medicaid for at least 3 months after birth. The final date of follow-up was December 31, 2013. Analyses were conducted between November 1, 2017, and June 30, 2018. Propensity score stratification was used to control for treatment indication and other confounders.Ondansetron dispensing during the first trimester, the period of organogenesis.Primary outcomes were cardiac malformations and oral clefts diagnosed during the first 90 days after delivery. Secondary outcomes included congenital malformations overall and subgroups of cardiac malformations and oral clefts.Among 1 816 414 pregnancies (mean age of mothers, 24.3 [5.8] years), 88 467 (4.9%) were exposed to ondansetron during the first trimester. Overall, 14 577 of 1 727 947 unexposed and 835 of 88 467 exposed infants were diagnosed with a cardiac malformation, for an absolute risk of 84.4 (95% CI, 83.0 to 85.7) and 94.4 (95% CI, 88.0 to 100.8) per 10 000 births respectively. The absolute risk of oral clefts was 11.1 per 10 000 births (95% CI, 10.6 to 11.6; 1921 unexposed infants) and was 14.0 per 10 000 births (95% CI, 11.6 to 16.5; 124 exposed infants). The risk of any congenital malformation was 313.5 per 10 000 births (95% CI, 310.9 to 316.1; 54 174 unexposed infants) and was 370.4 (95% CI, 358.0 to 382.9; 3277 exposed infants). The adjusted relative risk (RR) for cardiac malformations was 0.99 (95% CI, 0.93 to 1.06) and the adjusted risk difference (RD) was -0.8 (95% CI, -7.3 to 5.7 per 10 000 births). For oral clefts, the adjusted RR was 1.24 (95% CI, 1.03 to 1.48) and the RD was 2.7 (95% CI, 0.2 to 5.2 per 10 000 births). The adjusted estimate for congenital malformations overall was an RR of 1.01 (95% CI, 0.98 to 1.05) and an RD of 5.4 (95% CI, -7.3 to 18.2 per 10 000 births).Among offspring of mothers enrolled in Medicaid, first-trimester exposure to ondansetron was not associated with cardiac malformations or congenital malformations overall after accounting for measured confounders but was associated with a small increased risk of oral clefts.

  View details for DOI 10.1001/jama.2018.18307

  View details for PubMedID 30561479

  View details for PubMedCentralID PMC6669077

• Association Between Methylphenidate and Amphetamine Use in Pregnancy and Risk of Congenital Malformations: A Cohort Study From the International Pregnancy Safety Study Consortium. JAMA psychiatry Huybrechts, K. F., Bröms, G., Christensen, L. B., Einarsdóttir, K., Engeland, A., Furu, K., Gissler, M., Hernandez-Diaz, S., Karlsson, P., Karlstad, Ø., Kieler, H., Lahesmaa-Korpinen, A. M., Mogun, H., Nørgaard, M., Reutfors, J., Sørensen, H. T., Zoega, H., Bateman, B. T. 2018; 75 (2): 167-175

  Abstract

  Given the rapidly increasing use of stimulant medications during pregnancy and among women of reproductive age who may become pregnant inadvertently, there is a need to better understand their safety.To examine the risk of congenital malformations associated with intrauterine exposure to stimulants.Cohort study of the Medicaid-insured population in the United States nested in the 2000-2013 US Medicaid Analytic eXtract, with follow-up of safety signals detected in the Medicaid Analytic eXtract data using the Nordic Health registries (2003-2013) (Denmark, Finland, Iceland, Norway, and Sweden). A total of 1 813 894 publicly insured pregnancies in the United States and 2 560 069 singleton pregnancies in the 5 Nordic countries ending in live births were included. Relative risks were estimated accounting for underlying psychiatric disorders and other potential confounders. Relative risk estimates for the US and Nordic data were pooled using a fixed-effects meta-analytic approach. The study was conducted from July 1, 2015, to March 31, 2017.Methylphenidate and amphetamines dispensed during the first trimester.Major congenital malformations and subgroup of cardiac malformations.In the US data, of the 1 813 894 pregnancies evaluated, 35.0 per 1000 infants not exposed to stimulants were diagnosed as having congenital malformations, compared with 45.9 per 1000 infants for methylphenidate and 45.4 for amphetamines. For cardiac malformations, the risks were 12.7 (95% CI, 12.6-12.9), 18.8 (95% CI, 13.8-25.6), and 15.4 (95% CI, 12.5-19.0) per 1000 infants, respectively. The adjusted relative risks for methylphenidate were 1.11 (95% CI, 0.91-1.35) for any malformation and 1.28 (95% CI, 0.94-1.74) for cardiac malformations. No increased risks were observed for amphetamines: 1.05 (95% CI, 0.93-1.19) for any malformations and 0.96 (95% CI, 0.78-1.19) for cardiac malformations. Findings were confirmed in sensitivity analyses accounting for proxies of unmeasured confounders and increasing the specificity of the exposure and outcome definitions. Replication of the analyses for methylphenidate using the Nordic data including 2 560 069 pregnancies yielded a relative risk of 1.28 (95% CI, 0.83-1.97) for cardiac malformations, resulting in a pooled estimate of 1.28 (95% CI, 1.00-1.64).These findings suggest a small increase in the risk of cardiac malformations associated with intrauterine exposure to methylphenidate but not to amphetamines. This information is important when weighing the risks and benefits of alternative treatment strategies for attention-deficit/hyperactivity disorder in women of reproductive age and during early pregnancy.

  View details for DOI 10.1001/jamapsychiatry.2017.3644

  View details for PubMedID 29238795

  View details for PubMedCentralID PMC5838573

• Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study. BMJ (Clinical research ed.) Park, Y., Bateman, B. T., Kim, D. H., Hernandez-Diaz, S., Patorno, E., Glynn, R. J., Mogun, H., Huybrechts, K. F. 2018; 360: k1218

  Abstract

  To compare the risk of in-hospital mortality associated with haloperidol compared with atypical antipsychotics in patients admitted to hospital with acute myocardial infarction.Cohort study using a healthcare database.Nationwide sample of patient data from more than 700 hospitals across the United States.6578 medical patients aged more than 18 years who initiated oral haloperidol or oral atypical antipsychotics (olanzapine, quetiapine, risperidone) during a hospital admission with a primary diagnosis of acute myocardial infarction between 2003 and 2014.In-hospital mortality during seven days of follow-up from treatment initiation.Among 6578 patients (mean age 75.2 years) treated with an oral antipsychotic drug, 1668 (25.4%) initiated haloperidol and 4910 (74.6%) initiated atypical antipsychotics. The mean time from admission to start of treatment (5.3 v 5.6 days) and length of stay (12.5 v 13.6 days) were similar, but the mean treatment duration was shorter in patients using haloperidol compared with those using atypical antipsychotics (2.4 v 3.9 days). 1:1 propensity score matching was used to adjust for confounding. In intention to treat analyses with the matched cohort, the absolute rate of death per 100 person days was 1.7 for haloperidol (129 deaths) and 1.1 for atypical antipsychotics (92 deaths) during seven days of follow-up from treatment initiation. The survival probability was 0.93 in patients using haloperidol and 0.94 in those using atypical antipsychotics at day 7, accounting for the loss of follow-up due to hospital discharge. The unadjusted and adjusted hazard ratios of death were 1.51 (95% confidence interval 1.22 to 1.85) and 1.50 (1.14 to 1.96), respectively. The association was strongest during the first four days of follow-up and decreased over time. By day 5, the increased risk was no longer evident (1.12, 0.79 to 1.59). In the as-treated analyses, the unadjusted and adjusted hazard ratios were 1.90 (1.43 to 2.53) and 1.93 (1.34 to 2.76), respectively.The results suggest a small increased risk of death within seven days of initiating haloperidol compared with initiating an atypical antipsychotic in patients with acute myocardial infarction. Although residual confounding cannot be excluded, this finding deserves consideration when haloperidol is used for patients admitted to hospital with cardiac morbidity.

  View details for DOI 10.1136/bmj.k1218

  View details for PubMedID 29592958

  View details for PubMedCentralID PMC5871903

• Opioid Overdose After Surgical Discharge. JAMA Ladha, K. S., Gagne, J. J., Patorno, E., Huybrechts, K. F., Rathmell, J. P., Wang, S. V., Bateman, B. T. 2018; 320 (5): 502-504

  View details for DOI 10.1001/jama.2018.6933

  View details for PubMedID 30087999

  View details for PubMedCentralID PMC6142985

• β-Blocker Use in Pregnancy and the Risk for Congenital Malformations: An International Cohort Study. Annals of internal medicine Bateman, B. T., Heide-Jørgensen, U., Einarsdóttir, K., Engeland, A., Furu, K., Gissler, M., Hernandez-Diaz, S., Kieler, H., Lahesmaa-Korpinen, A. M., Mogun, H., Nørgaard, M., Reutfors, J., Selmer, R., Huybrechts, K. F., Zoega, H. 2018; 169 (10): 665-673

  Abstract

  β-Blockers are a class of antihypertensive medications that are commonly used in pregnancy.To estimate the risks for major congenital malformations associated with first-trimester exposure to β-blockers.Cohort study.Health registries in the 5 Nordic countries and the U.S. Medicaid database.Pregnant women with a diagnosis of hypertension and their offspring.First-trimester exposure to β-blockers was assessed. Outcomes were any major congenital malformation, cardiac malformations, cleft lip or palate, and central nervous system (CNS) malformations. Propensity score stratification was used to control for potential confounders.Of 3577 women with hypertensive pregnancies in the Nordic cohort and 14 900 in the U.S. cohort, 682 (19.1%) and 1668 (11.2%), respectively, were exposed to β-blockers in the first trimester. The pooled adjusted relative risk (RR) and risk difference per 1000 persons exposed (RD1000) associated with β-blockers were 1.07 (95% CI, 0.89 to 1.30) and 3.0 (CI, -6.6 to 12.6), respectively, for any major malformation; 1.12 (CI, 0.83 to 1.51) and 2.1 (CI, -4.3 to 8.4) for any cardiac malformation; and 1.97 (CI, 0.74 to 5.25) and 1.0 (CI, -0.9 to 3.0) for cleft lip or palate. For CNS malformations, the adjusted RR was 1.37 (CI, 0.58 to 3.25) and the RD1000 was 1.0 (CI, -2.0 to 4.0) (based on U.S. cohort data only).Analysis was restricted to live births, exposure was based on dispensed medication, and cleft lip or palate and CNS malformations had few outcomes.The results suggest that maternal use of β-blockers in the first trimester is not associated with a large increase in the risk for overall malformations or cardiac malformations, independent of measured confounders.The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Söderström König Foundation.

  View details for DOI 10.7326/M18-0338

  View details for PubMedID 30326014

  View details for PubMedCentralID PMC6854680

• Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions: cohort study. BMJ (Clinical research ed.) Desai, R. J., Bateman, B. T., Huybrechts, K. F., Patorno, E., Hernandez-Diaz, S., Park, Y., Dejene, S. Z., Cohen, J., Mogun, H., Kim, S. C. 2017; 356: j895

  Abstract

  Objective To compare the risk of serious infections associated with use of systemic steroids, non-biologic agents, or tumor necrosis factor α (TNF) inhibitors in pregnancy.Design Observational cohort study.Setting Public (Medicaid, 2001-10) or private (Optum Clinformatics, 2004-15) health insurance programs in the US.Participants 4961 pregnant women treated with immunosuppressive drugs for rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, or inflammatory bowel disease.Exposure for observational studies Exposure was classified into steroid, non-biologic, or TNF inhibitors on first filled prescription during pregnancy. Because TNF inhibitors are not used to treat systemic lupus erythematosus, patients with this condition were excluded from comparisons involving TNF inhibitors.Main outcome measure The main outcome was occurrence of serious infections during pregnancy, defined by hospital admission for bacterial or opportunistic infections. Hazard ratios were derived using Cox proportional hazard regression models after adjustment for confounding with propensity score fine stratification. A logistic regression model was used to conduct a dose-response analysis among women filling at least one steroid prescription.Results 71 out of 4961 pregnant women (0.2%) treated with immunosuppressive agents experienced serious infections. The crude incidence rates of serious infections per 100 person years among 2598 steroid users, 1587 non-biologic users, and 776 TNF inhibitors users included in this study were 3.4 (95% confidence interval 2.5 to 4.7), 2.3 (1.5 to 3.5), and 1.5 (0.7 to 3.0), respectively. No statistically significant differences in the risk of serious infections during pregnancy were observed among users of the three immunosuppressive drug classes: non-biologics v steroids, hazard ratio 0.81 (95% confidence interval 0.48 to 1.37), TNF inhibitors v steroids 0.91 (0.36 to 2.26), and TNF inhibitors v non-biologics 1.36 (0.47 to 3.93). In the dose-response analysis, higher steroid dose was associated with an increased risk of serious infections during pregnancy (coefficient for each unit increase in average prednisone equivalent mg daily dose=0.019, P=0.02).Conclusions Risk of serious infections is similar among pregnant women with systemic inflammatory conditions using steroids, non-biologics, and TNF inhibitors. However, high dose steroid use is an independent risk factor of serious infections in pregnancy.

  View details for DOI 10.1136/bmj.j895

  View details for PubMedID 28264814

  View details for PubMedCentralID PMC6168035

• Lithium Use in Pregnancy and the Risk of Cardiac Malformations. The New England journal of medicine Patorno, E., Huybrechts, K. F., Bateman, B. T., Cohen, J. M., Desai, R. J., Mogun, H., Cohen, L. S., Hernandez-Diaz, S. 2017; 376 (23): 2245-2254

  Abstract

  There has been concern that exposure to lithium early in pregnancy may be associated with a marked increase in the risk of Ebstein's anomaly (a right ventricular outflow tract obstruction defect) in infants and overall congenital cardiac defects, but data are conflicting and limited.We conducted a cohort study involving 1,325,563 pregnancies in women who were enrolled in Medicaid and who delivered a live-born infant between 2000 and 2010. We examined the risk of cardiac malformations among infants exposed to lithium during the first trimester as compared with unexposed infants and, in secondary analyses, with infants exposed to another commonly used mood stabilizer, lamotrigine. Risk ratios and 95% confidence intervals were estimated with control for psychiatric and medical conditions, medications, and other potential confounders.Cardiac malformations were present in 16 of the 663 infants exposed to lithium (2.41%), 15,251 of the 1,322,955 nonexposed infants (1.15%), and 27 of the 1945 infants exposed to lamotrigine (1.39%). The adjusted risk ratio for cardiac malformations among infants exposed to lithium as compared with unexposed infants was 1.65 (95% confidence interval [CI], 1.02 to 2.68). The risk ratio was 1.11 (95% CI, 0.46 to 2.64) for a daily dose of 600 mg or less, 1.60 (95% CI, 0.67 to 3.80) for 601 to 900 mg, and 3.22 (95% CI, 1.47 to 7.02) for more than 900 mg. The prevalence of right ventricular outflow tract obstruction defects was 0.60% among lithium-exposed infants versus 0.18% among unexposed infants (adjusted risk ratio, 2.66; 95% CI, 1.00 to 7.06). Results were similar when lamotrigine-exposed infants were used as the reference group.Maternal use of lithium during the first trimester was associated with an increased risk of cardiac malformations, including Ebstein's anomaly; the magnitude of this effect was smaller than had been previously postulated. (Funded by the National Institute of Mental Health.).

  View details for DOI 10.1056/NEJMoa1612222

  View details for PubMedID 28591541

  View details for PubMedCentralID PMC5667676

• Risk of neonatal drug withdrawal after intrauterine co-exposure to opioids and psychotropic medications: cohort study. BMJ (Clinical research ed.) Huybrechts, K. F., Bateman, B. T., Desai, R. J., Hernandez-Diaz, S., Rough, K., Mogun, H., Kerzner, L. S., Davis, J. M., Stover, M., Bartels, D., Cottral, J., Patorno, E. 2017; 358: j3326

  Abstract

  Objectives To assess the impact of in utero co-exposure to psychotropic medications and opioids on the incidence and severity of neonatal drug withdrawal.Design Observational cohort study.Setting Nationwide sample of pregnancies in publicly insured women in the US, nested in the Medicaid Analytic eXtract (2000-10).Participants 201 275 pregnant women with public insurance who were exposed to opioids around the time of delivery and their liveborn infants.Interventions In utero exposure to psychotropic medications, in particular antidepressants, atypical antipsychotics, benzodiazepines, gabapentin, and non-benzodiazepine hypnotics (Z drugs), with prescriptions filled within the same time window as prescriptions for opioids.Main outcome measure Diagnosis of neonatal drug withdrawal in infants exposed in utero to opioids and psychotropic medications compared with opioids alone.Results The absolute risk for neonatal drug withdrawal ranged from 1.0% in infants exposed in utero to prescription opioids alone to 11.4% for those exposed to opioids co-prescribed with gabapentin. Among neonates exposed in utero to prescription opioids, the relative risk adjusted for propensity score was 1.34 (95% confidence interval 1.22 to 1.47) with concomitant exposure to antidepressants, 1.49 (1.35 to 1.63) with benzodiazepines, 1.61 (1.26 to 2.06) with gabapentin, 1.20 (0.95 to 1.51) with antipsychotics, and 1.01 (0.88 to 1.15) with Z drugs. In utero exposure to two or more psychotropic medications along with opioids was associated with a twofold increased risk of withdrawal (2.05, 1.77 to 2.37). The severity of the withdrawal seemed increased in neonates exposed to both opioids and psychotropic medications compared with opioids alone.Conclusions During pregnancy, the use of psychotropic medications in addition to prescription opioids is common, despite a lack of safety data. The current findings suggest that these drugs could further increase the risk and severity of neonatal drug withdrawal.

  View details for DOI 10.1136/bmj.j3326

  View details for PubMedID 28768628

  View details for PubMedCentralID PMC5538591

• Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA psychiatry Huybrechts, K. F., Hernández-Díaz, S., Patorno, E., Desai, R. J., Mogun, H., Dejene, S. Z., Cohen, J. M., Panchaud, A., Cohen, L., Bateman, B. T. 2016; 73 (9): 938-46

  Abstract

  The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations.To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs.This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015.Use of APs during the first trimester, the etiologically relevant period for organogenesis.Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery.Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4-33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5-48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6-54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24-1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81-1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96-1.16) for atypical APs and 0.90 (95% CI, 0.62-1.31) for typical APs. The findings for cardiac malformations were similar. For the individual agents examined, a small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02-1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81) was found for risperidone that was independent of measured confounders.Evidence from this large study suggests that use of APs early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. The small increase in the risk for malformations observed with risperidone requires additional study.

  View details for DOI 10.1001/jamapsychiatry.2016.1520

  View details for PubMedID 27540849

  View details for PubMedCentralID PMC5321163

• Limiting the Duration of Opioid Prescriptions: Balancing Excessive Prescribing and the Effective Treatment of Pain. JAMA internal medicine Bateman, B. T., Choudhry, N. K. 2016; 176 (5): 583-4

  View details for DOI 10.1001/jamainternmed.2016.0544

  View details for PubMedID 27043188

• Association of Labor Induction With Offspring Risk of Autism Spectrum Disorders. JAMA pediatrics Oberg, A. S., D'Onofrio, B. M., Rickert, M. E., Hernandez-Diaz, S., Ecker, J. L., Almqvist, C., Larsson, H., Lichtenstein, P., Bateman, B. T. 2016; 170 (9): e160965

  Abstract

  Induction of labor is a frequently performed obstetrical intervention. It would thus be of great concern if reported associations between labor induction and offspring risk of autism spectrum disorders (ASD) reflected causal influence.To assess the associations of labor induction with ASD, comparing differentially exposed relatives (siblings and cousins discordant for induction).Follow-up of all live births in Sweden between 1992 and 2005, defined in the Medical Birth Register. The register was linked to population registers of familial relations, inpatient and outpatient visits, and education records. Diagnoses of ASD were from 2001 through 2013, and data were analyzed in the 2015-2016 year.Induction of labor.Autism spectrum disorders identified by diagnoses from inpatient and outpatient records between 2001 and 2013. Hazard ratios (HRs) quantified the association between labor induction and offspring ASD. In addition to considering a wide range of measured confounders, comparison of exposure-discordant births to the same woman allowed additional control for all unmeasured factors shared by siblings.The full cohort included 1 362 950 births, of which 22 077 offspring (1.6%) were diagnosed with ASD by ages 8 years through 21 years. In conventional models of the full cohort, associations between labor induction and offspring ASD were attenuated but remained statistically significant after adjustment for measured potential confounders (HR, 1.19; 95% CI, 1.13-1.24). When comparison was made within siblings whose births were discordant with respect to induction, thus accounting for all environmental and genetic factors shared by siblings, labor induction was no longer associated with offspring ASD (HR, 0.99; 95% CI, 0.88-1.10).In this nationwide sample of live births we observed no association between induction of labor and offspring ASD within sibling comparison. Our findings suggest that concern for ASD should not factor into the clinical decision about whether to induce labor.

  View details for DOI 10.1001/jamapediatrics.2016.0965

  View details for PubMedID 27454803

  View details for PubMedCentralID PMC5297393

• Antidepressant use late in pregnancy and risk of persistent pulmonary hypertension of the newborn. JAMA Huybrechts, K. F., Bateman, B. T., Palmsten, K., Desai, R. J., Patorno, E., Gopalakrishnan, C., Levin, R., Mogun, H., Hernandez-Diaz, S. 2015; 313 (21): 2142-51

  Abstract

  The association between selective serotonin reuptake inhibitor (SSRI) antidepressant use during pregnancy and risk of persistent pulmonary hypertension of the newborn (PPHN) has been controversial since the US Food and Drug Administration issued a public health advisory in 2006.To examine the risk of PPHN associated with exposure to different antidepressant medication classes late in pregnancy.Cohort study nested in the 2000-2010 Medicaid Analytic eXtract for 46 US states and Washington, DC. Last follow-up date was December 31, 2010.A total of 3,789,330 pregnant women enrolled in Medicaid from 2 months or fewer after the date of last menstrual period through at least 1 month after delivery. The source cohort was restricted to women with a depression diagnosis and logistic regression analysis with propensity score adjustment applied to control for potential confounders. EXPOSURES FOR OBSERVATIONAL STUDIES: SSRI and non-SSRI monotherapy use during the 90 days before delivery vs no use.Recorded diagnosis of PPHN during the first 30 days after delivery.A total of 128,950 women (3.4%) filled at least 1 prescription for antidepressants late in pregnancy: 102,179 (2.7%) used an SSRI and 26,771 (0.7%) a non-SSRI. Overall, 7630 infants not exposed to antidepressants were diagnosed with PPHN (20.8; 95% CI, 20.4-21.3 per 10,000 births) compared with 322 infants exposed to SSRIs (31.5; 95% CI, 28.3-35.2 per 10,000 births), and 78 infants exposed to non-SSRIs (29.1; 95% CI, 23.3-36.4 per 10,000 births). Associations between antidepressant use and PPHN were attenuated with increasing levels of confounding adjustment. For SSRIs, odds ratios were 1.51 (95% CI, 1.35-1.69) unadjusted and 1.10 (95% CI, 0.94-1.29) after restricting to women with depression and adjusting for the high-dimensional propensity score. For non-SSRIs, the odds ratios were 1.40 (95% CI, 1.12-1.75) and 1.02 (95% CI, 0.77-1.35), respectively. Upon restriction of the outcome to primary PPHN, the adjusted odds ratio for SSRIs was 1.28 (95% CI, 1.01-1.64) and for non-SSRIs 1.14 (95% CI, 0.74-1.74).Evidence from this large study of publicly insured pregnant women may be consistent with a potential increased risk of PPHN associated with maternal use of SSRIs in late pregnancy. However, the absolute risk was small, and the risk increase appears more modest than suggested in previous studies.

  View details for DOI 10.1001/jama.2015.5605

  View details for PubMedID 26034955

  View details for PubMedCentralID PMC4761452

• Statins and congenital malformations: cohort study. BMJ (Clinical research ed.) Bateman, B. T., Hernandez-Diaz, S., Fischer, M. A., Seely, E. W., Ecker, J. L., Franklin, J. M., Desai, R. J., Allen-Coleman, C., Mogun, H., Avorn, J., Huybrechts, K. F. 2015; 350: h1035

  Abstract

  To examine the teratogenic potential of statins.Cohort study.United States.A cohort of 886,996 completed pregnancies linked to liveborn infants of women enrolled in Medicaid from 2000 to 2007.We examined the risk of major congenital malformations and organ specific malformations in offspring associated with maternal use of a statin in the first trimester. Propensity score based methods were used to control for potential confounders, including maternal demographic characteristics, obstetric and medical conditions, and use of other drugs.1152 (0.13%) women used a statin during the first trimester. In unadjusted analyses, the prevalence of malformations in the offspring of these women was 6.34% compared with 3.55% in those of women who did not use a statin in the first trimester (relative risk 1.79, 95% confidence interval 1.43 to 2.23). Controlling for confounders, particularly pre-existing diabetes, accounted for this increase in risk (1.07, 0.85 to 1.37). There were also no statistically significant increases in any of the organ specific malformations assessed after accounting for confounders. Results were similar across a range of sensitivity analyses.Our analysis did not find a significant teratogenic effect from maternal use of statins in the first trimester. However, these findings need to be replicated in other large studies, and the long term effects of in utero exposure to statins needs to be assessed, before use of statins in pregnancy can be considered safe.

  View details for DOI 10.1136/bmj.h1035

  View details for PubMedID 25784688

  View details for PubMedCentralID PMC4362473

• Exposure to prescription opioid analgesics in utero and risk of neonatal abstinence syndrome: population based cohort study. BMJ (Clinical research ed.) Desai, R. J., Huybrechts, K. F., Hernandez-Diaz, S., Mogun, H., Patorno, E., Kaltenbach, K., Kerzner, L. S., Bateman, B. T. 2015; 350: h2102

  Abstract

  To provide absolute and relative risk estimates of neonatal abstinence syndrome (NAS) based on duration and timing of prescription opioid use during pregnancy in the presence or absence of additional NAS risk factors of history of opioid misuse or dependence, misuse of other substances, non-opioid psychotropic drug use, and smoking.Observational cohort study.Medicaid data from 46 US states.Pregnant women filling at least one prescription for an opioid analgesic at any time during pregnancy for whom opioid exposure characteristics including duration of therapy: short term (<30 days) or long term (≥ 30 days); timing of use: early use (only in the first two trimesters) or late use (extending into the third trimester); and cumulative dose (in morphine equivalent milligrams) were assessed.Diagnosis of NAS in liveborn infants.1705 cases of NAS were identified among 290,605 pregnant women filling opioid prescriptions, corresponding to an absolute risk of 5.9 per 1000 deliveries (95% confidence interval 5.6 to 6.2). Long term opioid use during pregnancy resulted in higher absolute risk of NAS per 1000 deliveries in the presence of additional risk factors of known opioid misuse (220.2 (200.8 to 241.0)), alcohol or other drug misuse (30.8 (26.1 to 36.0)), exposure to other psychotropic medications (13.1 (10.6 to 16.1)), and smoking (6.6 (4.3 to 9.6)) than in the absence of any of these risk factors (4.2 (3.3 to 5.4)). The corresponding risk estimates for short term use were 192.0 (175.8 to 209.3), 7.0 (6.0 to 8.2), 2.0 (1.5 to 2.6), 1.5 (1.0 to 2.0), and 0.7 (0.6 to 0.8) per 1000 deliveries, respectively. In propensity score matched analyses, long term prescription opioid use compared with short term use and late use compared with early use in pregnancy demonstrated greater risk of NAS (risk ratios 2.05 (95% confidence interval 1.81 to 2.33) and 1.24 (1.12 to 1.38), respectively).Use of prescription opioids during pregnancy is associated with a low absolute risk of NAS in the absence of additional risk factors. Long term use compared with short term use and late use compared with early use of prescription opioids are associated with increased NAS risk independent of additional risk factors.

  View details for DOI 10.1136/bmj.h2102

  View details for PubMedID 25975601

  View details for PubMedCentralID PMC4431352

• Comparative safety of anesthetic type for hip fracture surgery in adults: retrospective cohort study. BMJ (Clinical research ed.) Patorno, E., Neuman, M. D., Schneeweiss, S., Mogun, H., Bateman, B. T. 2014; 348: g4022

  Abstract

  To evaluate the effect of anesthesia type on the risk of in-hospital mortality among adults undergoing hip fracture surgery in the United States.Retrospective cohort study.Premier research database, United States.73,284 adults undergoing hip fracture surgery on hospital day 2 or greater between 2007 and 2011. Of those, 61,554 (84.0%) received general anesthesia, 6939 (9.5%) regional anesthesia, and 4791 (6.5%) combined general and regional anesthesia.In-hospital all cause mortality.In-hospital deaths occurred in 1362 (2.2%) patients receiving general anesthesia, 144 (2.1%) receiving regional anesthesia, and 115 (2.4%) receiving combined anesthesia. In the multivariable adjusted analysis, when compared with general anesthesia the mortality risk did not differ significantly between regional anesthesia (risk ratio 0.93, 95% confidence interval 0.78 to 1.11) or combined anesthesia (1.00, 0.82 to 1.22). A mixed effects analysis accounting for differences between hospitals produced similar results: compared with general anesthesia the risk from regional anesthesia was 0.91 (0.75 to 1.10) and from combined anesthesia was 0.98 (0.79 to 1.21). Findings were also consistent in subgroup analyses.In this large nationwide sample of hospital admissions, mortality risk did not differ significantly by anesthesia type among patients undergoing hip fracture surgery. Our results suggest that if the previously posited beneficial effect of regional anesthesia on short term mortality exists, it is likely to be more modest than previously reported.

  View details for DOI 10.1136/bmj.g4022

  View details for PubMedID 24972901

  View details for PubMedCentralID PMC4073666

• Genetic contribution to postpartum haemorrhage in Swedish population: cohort study of 466,686 births. BMJ (Clinical research ed.) Oberg, A. S., Hernandéz-Diaź, S., Frisell, T., Greene, M. F., Almqvist, C., Bateman, B. T. 2014; 349: g4984

  Abstract

  To investigate the familial clustering of postpartum haemorrhage in the Swedish population, and to quantify the relative contributions of genetic and environmental effects.Register based cohort study.Swedish population (multi-generation and medical birth registers).Postpartum haemorrhage, defined as >1000 mL estimated blood loss.The first two live births to individuals in Sweden in 1997-2009 contributed to clusters representing intact couples (n = 366,350 births), mothers with separate partners (n = 53,292), fathers with separate partners (n = 47,054), sister pairs (n = 97,228), brother pairs (n = 91,168), and mixed sibling pairs (n = 177,944).Familial clustering was quantified through cluster specific tetrachoric correlation coefficients, and the influence of potential sharing of known risk factors was evaluated with alternating logistic regression. Relative contributions of genetic and environmental effects to the variation in liability for postpartum haemorrhage were quantified with generalised linear mixed models.The overall prevalence of postpartum haemorrhage after vaginal deliveries in our sample was 4.6%. Among vaginal deliveries, 18% (95% confidence interval 9% to 26%) of the variation in postpartum haemorrhage liability was attributed to maternal genetic factors, 10% (1% to 19%) to unique maternal environment, and 11% (0% to 26%) to fetal genetic effects. Adjustment for known risk factors only partially explained estimates of familial clustering, suggesting that the observed shared genetic and environmental effects operate in part through pathways independent of known risk factors. There were similar patterns of familial clustering for both of the main subtypes examined (atony and retained placenta), though strongest for haemorrhage after retained placenta.There is a maternal genetic predisposition to postpartum haemorrhage, but more than half of the total variation in liability is attributable to factors that are not shared in families.

  View details for DOI 10.1136/bmj.g4984

  View details for PubMedID 25121825

  View details for PubMedCentralID PMC4131501

• Internal validation of gestational age estimation algorithms in healthcare databases using pregnancies conceived with fertility procedures. American journal of epidemiology Chiu, Y. H., Huybrechts, K. F., Zhu, Y., Straub, L., Bateman, B. T., Logan, R., Hernández-Díaz, S. 2024

  Abstract

  Fertility procedures recorded in healthcare databases can be used to estimate the start of pregnancy, which can serve as a reference standard to validate gestational age estimates based on International Classification of Diseases (ICD) codes. In a cohort of 17,398 pregnancies conceived by fertility procedures in MarketScan (2011-2020), we estimated gestational age at the end of pregnancy using algorithms based on (1) days since fertility procedure (the reference); (2) ICD-9/ICD-10 (before/after October 2015) codes indicating gestational length recorded at the end of pregnancy (method A); and (3) ICD-10 enhanced with Z3A codes denoting specific gestation weeks recorded at prenatal visits (method B). We calculated the proportion of pregnancies with an estimated gestational age within 14 days of the reference. Method A accuracy was similar for ICD-9 and ICD-10 codes. After 2015, method B was more accurate than method A: For term births, within-14-day-agreements were 90.8% for method A and 98.7% for method B. Corresponding estimates were 70.1% and 95.6% for preterm births; 35.3% and 92.6% for stillbirths; 54.3% and 64.2% for spontaneous abortions; and 16.7% and 84.6% for elective terminations. ICD-10-based algorithms that incorporate Z3A codes improve the accuracy of gestational age estimation in healthcare databases, especially for preterm and non-live births.

  View details for DOI 10.1093/aje/kwae045

  View details for PubMedID 38583933

• Prescription Stimulant Use During Pregnancy and Risk of Neurodevelopmental Disorders in Children. JAMA psychiatry Suarez, E. A., Bateman, B. T., Hernandez-Diaz, S., Straub, L., McDougle, C. J., Wisner, K. L., Gray, K. J., Pennell, P. B., Lester, B., Zhu, Y., Mogun, H., Huybrechts, K. F. 2024

  Abstract

  Use of medications for attention-deficit/hyperactivity disorder (ADHD) during pregnancy is increasing in the US. Whether exposure to these medications in utero impacts the risk of neurodevelopmental disorders in children is uncertain.To evaluate the association of childhood neurodevelopmental disorders with in utero exposure to stimulant medications for ADHD.This cohort study included health care utilization data from publicly insured (Medicaid data from 2000 to 2018) and commercially insured (MarketScan Commercial Claims Database data from 2003 to 2020) pregnant individuals aged 12 to 55 years in the US with enrollment from 3 months prior to pregnancy through 1 month after delivery, linked to children. Children were monitored from birth until outcome diagnosis, disenrollment, death, or end of the study (December 2018 for Medicaid and December 2020 for MarketScan).Dispensing of amphetamine/dextroamphetamine or methylphenidate in the second half of pregnancy.Autism spectrum disorder, ADHD, and a composite of any neurodevelopmental disorder were defined using validated algorithms. Hazard ratios were estimated comparing amphetamine/dextroamphetamine and methylphenidate to no exposure.The publicly insured cohort included 2 496 771 stimulant-unexposed, 4693 amphetamine/dextroamphetamine-exposed, and 786 methylphenidate-exposed pregnancies with a mean (SD) age of 25.2 (6.0) years. The commercially insured cohort included 1 773 501 stimulant-unexposed, 2372 amphetamine/dextroamphetamine-exposed, and 337 methylphenidate-exposed pregnancies with a mean (SD) age of 31.6 (4.6) years. In unadjusted analyses, amphetamine/dextroamphetamine and methylphenidate exposure were associated with a 2- to 3-fold increased risk of the neurodevelopmental outcomes considered. After adjustment for measured confounders, amphetamine/dextroamphetamine exposure was not associated with any outcome (autism spectrum disorder: hazard ratio [HR], 0.80; 95% CI, 0.56-1.14]; ADHD: HR, 1.07; 95% CI, 0.89-1.28; any neurodevelopmental disorder: HR, 0.91; 95% CI, 0.81-1.28). Methylphenidate exposure was associated with an increased risk of ADHD (HR, 1.43; 95% CI, 1.12-1.82]) but not other outcomes after adjustment (autism spectrum disorder: HR, 1.06; 95% CI, 0.62-1.81; any neurodevelopmental disorder: HR, 1.15; 95% CI, 0.97-1.36). The association between methylphenidate and ADHD did not persist in sensitivity analyses with stricter control for confounding by maternal ADHD.The findings in this study suggest that amphetamine/dextroamphetamine and methylphenidate exposure in utero are not likely to meaningfully increase the risk of childhood neurodevelopmental disorders.

  View details for DOI 10.1001/jamapsychiatry.2023.5073

  View details for PubMedID 38265792

• Comparative Risk of Major Congenital Malformations With Antiseizure Medication Combinations vs Valproate Monotherapy in Pregnancy. Neurology Cohen, J. M., Alvestad, S., Suarez, E. A., Schaffer, A., Selmer, R. M., Havard, A., Bateman, B. T., Cesta, C. E., Zoega, H., Odsbu, I., Huybrechts, K. F., Kjerpeseth, L. J., Straub, L., Leinonen, M. K., Bjork, M., Norgaard, M., Gissler, M., Ulrichsen, S. P., Hernandez-Diaz, S., Tomson, T., Furu, K. 2024; 102 (2): e207996

  Abstract

  BACKGROUND AND OBJECTIVES: Valproate should be avoided in pregnancy, but it is the most effective drug for generalized epilepsies. Alternative treatment may require combinations of other drugs. Our objectives were to describe first trimester use of antiseizure medication (ASM) combinations that are relevant alternatives to valproate and determine whether specific combinations were associated with a lower risk of major congenital malformations (MCM) compared with valproate monotherapy.METHODS: We conducted a population-based cohort study using linked national registers from Denmark, Finland, Iceland, Norway, and Sweden and administrative health care data from the United States and New South Wales, Australia. We described first trimester use of ASM combinations among pregnant people with epilepsy from 2000 to 2020. We compared the risk of MCM after first trimester exposure to ASM combinations vs valproate monotherapy and low-dose valproate plus lamotrigine or levetiracetam vs high-dose valproate (≥1,000 mg/d). We used log-binomial regression with propensity score weights to calculate adjusted risk ratios (aRRs) and 95% CIs for each dataset. Results were pooled using fixed-effects meta-analysis.RESULTS: Among 50,905 pregnancies in people with epilepsy identified from 7.8 million total pregnancies, 788 used lamotrigine and levetiracetam, 291 used lamotrigine and topiramate, 208 used levetiracetam and topiramate, 80 used lamotrigine and zonisamide, and 91 used levetiracetam and zonisamide. After excluding pregnancies with use of other ASMs, known teratogens, or a child diagnosed with MCM of infectious or genetic cause, we compared 587 exposed to lamotrigine-levetiracetam duotherapy and 186 exposed to lamotrigine-topiramate duotherapy with 1959 exposed to valproate monotherapy. Pooled aRRs were 0.41 (95% CI 0.24-0.69) and 1.26 (0.71-2.23), respectively. Duotherapy combinations containing low-dose valproate were infrequent, and comparisons with high-dose valproate monotherapy were inconclusive but suggested a lower risk for combination therapy. Other combinations were too rare for comparative safety analyses.DISCUSSION: Lamotrigine-levetiracetam duotherapy in first trimester was associated with a 60% lower risk of MCM than valproate monotherapy, while lamotrigine-topiramate was not associated with a reduced risk. Duotherapy with lamotrigine and levetiracetam may be favored to treat epilepsy in people with childbearing potential compared with valproate regarding MCM, but whether this combination is as effective as valproate remains to be determined.CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in people with epilepsy treated in the first trimester of pregnancy, the risk of major congenital malformations is lower with lamotrigine-levetiracetam duotherapy than with valproate alone, but similar with lamotrigine-topiramate.

  View details for DOI 10.1212/WNL.0000000000207996

  View details for PubMedID 38165339

• Brief Assessment of Patient Phenotype to Explain Variability in Postsurgical Pain and Opioid Consumption after Cesarean Delivery: Performance of a Novel Brief Questionnaire Compared to Long Questionnaires. Anesthesiology He, J., Wilson, J. M., Fields, K. G., Flowers Zachos, K. M., Franqueiro, A. R., Reale, S. C., Farber, M. K., Bateman, B. T., Edwards, R. R., Rathmell, J. P., Soens, M., Schreiber, K. L. 2024

  Abstract

  Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery (CD) is crucial to building an evidence base for personalized prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A 3-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. We compared the explanatory ability of 3 models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (Long) including validated questionnaires (e.g., BPI, PROMIS) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (Brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, we explored the utility of adding a pragmatic quantitative sensory test (QST) to models.In this prospective, observational study, 545 women undergoing CD completed questionnaires pre-surgery. Pain during local anesthetic skin wheal prior to spinal placement served as a pragmatic QST. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 hours following surgery.A modest amount of variability was explained by each of the 3 models for postoperative pain and opioid consumption. Both Brief and Long questionnaire models performed better than the 3-item questionnaire, but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. QST was itself independently associated with pain across models, but only modestly improved models for postoperative pain.The Brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the 3-item questionnaire.

  View details for DOI 10.1097/ALN.0000000000004900

  View details for PubMedID 38207329

• In Reply. Obstetrics and gynecology Leonard, S. A., Phibbs, C. S., Main, E. K., Kozhimannil, K. B., Bateman, B. T. 2024; 143 (1): e18-e19

  View details for DOI 10.1097/AOG.0000000000005457

  View details for PubMedID 38096558

• Prescription Medication Use During Pregnancy in the United States 2011-2020: Trends and Safety Evidence. American journal of obstetrics and gynecology Mansour, O., Russo, R. G., Straub, L., Bateman, B. T., Gray, K. J., Huybrechts, K. F., Hernandez-Diaz, S. 2023

  Abstract

  Medication use during pregnancy has increased in the U.S. despite the lack of safety data for many medications.To inform research priorities by examining trends in medication use during pregnancy and identifying gaps in safety information among the most commonly prescribed medications.We identified population-based cohorts of commercially (MarketScan 2011-2020) and publicly (MAX/TAF 2011-2018) insured pregnancies ending in livebirth from two healthcare utilization databases. Medication use was based on filled prescriptions between the date of last menstrual period (LMP) through delivery, as well as pre-LMP and during specific trimesters. We also included a cross-sectional representative sample of pregnancies ascertained by the National Health and Nutrition Examination Study (NHANES 2011-2020), with information on prescription medication use during the preceding month obtained through maternal interviews. The Teratogen Information System (TERIS) was used to classify the available evidence on teratogenic risk.Among over 3 million pregnancies, the medications most commonly dispensed at any time during pregnancy were analgesics, antibiotics, and antiemetics. The top medications were ondansetron (16.8%), amoxicillin (13.5%) and azithromycin (12.4%) in MarketScan, nitrofurantoin (22.2%), acetaminophen (21.3%; the majority as part of acetaminophen-hydrocodone products), and ondansetron (19.5%) in MAX/TAF, and levothyroxine (5.0%), sertraline (2.9%), and insulin (2.9%) in NHANES. The most commonly dispensed suspected teratogens during the first trimester were antithyroid medications. The use of antidiabetic and psychotropic medications has continued to increase in the U.S. during the last decade, opioids dispensation has decreased by half, and antibiotics and antiemetics continue to be common. For one-quarter of medications, there is insufficient evidence available to characterize their safety profile in pregnancy.There is a need for more drug research in pregnant patients. Future research should focus on anti-infectives with high utilization and limited level of evidence on safety for use during pregnancy. While the lack of evidence is not evidence for safety, it is not evidence for risk either. In many instances the benefits outweigh the risks when these medications are used clinically; and some of the medications with no proven safety may be necessary to treat patients.

  View details for DOI 10.1016/j.ajog.2023.12.020

  View details for PubMedID 38128861

• Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy. JAMA internal medicine Cesta, C. E., Rotem, R., Bateman, B. T., Chodick, G., Cohen, J. M., Furu, K., Gissler, M., Huybrechts, K. F., Kjerpeseth, L. J., Leinonen, M. K., Pazzagli, L., Zoega, H., Seely, E. W., Patorno, E., Hernández-Díaz, S. 2023

  Abstract

  Increasing use of second-line noninsulin antidiabetic medication (ADM) in pregnant individuals with type 2 diabetes (T2D) may result in fetal exposure, but their teratogenic risk is unknown.To evaluate periconceptional use of second-line noninsulin ADMs and whether it is associated with increased risk of major congenital malformations (MCMs) in the infant.This observational population-based cohort study used data from 4 Nordic countries (2009-2020), the US MarketScan Database (2012-2021), and the Israeli Maccabi Health Services database (2009-2020). Pregnant women with T2D were identified and their live-born infants were followed until up to 1 year after birth.Periconceptional exposure was defined as 1 or more prescription fill of sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, or insulin (active comparator) from 90 days before pregnancy to end of first trimester.Relative risks (RRs) and 95% CIs for MCMs were estimated using log-binomial regression models, adjusting for key confounders in each cohort and meta-analyzed.Periconceptional exposure to second-line noninsulin ADMs differed between countries (32, 295, and 73 per 100 000 pregnancies in the Nordics, US, and Israel, respectively), and increased over the study period, especially in the US. The standardized prevalence of MCMs was 3.7% in all infants (n = 3 514 865), 5.3% in the infants born to women with T2D (n = 51 826), and among infants exposed to sulfonylureas was 9.7% (n = 1362); DPP-4 inhibitors, 6.1% (n = 687); GLP-1 receptor agonists, 8.3% (n = 938); SGLT2 inhibitors, 7.0% (n = 335); and insulin, 7.8% (n = 5078). Compared with insulin, adjusted RRs for MCMs were 1.18 (95% CI, 0.94-1.48), 0.83 (95% CI, 0.64-1.06), 0.95 (95% CI, 0.72-1.26), and 0.98 (95% CI, 0.65-1.46) for infants exposed to sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors, respectively.Use of second-line noninsulin ADMs is rapidly increasing for treatment of T2D and other indications, resulting in an increasing number of exposed pregnancies. Although some estimates were imprecise, results did not indicate a large increased risk of MCMs above the risk conferred by maternal T2D requiring second-line treatment. Although reassuring, confirmation from other studies is needed, and continuous monitoring will provide more precise estimates as data accumulate.

  View details for DOI 10.1001/jamainternmed.2023.6663

  View details for PubMedID 38079178

  View details for PubMedCentralID PMC10714281

• Rates and costs of drug testing practices for private payors in the outpatient setting in the United States, 2015-2019. Journal of substance use and addiction treatment Barenie, R. E., Bateman, B. T., Connery, H. S., Tsacogianis, T., Kesselheim, A. S. 2023: 209243

  Abstract

  Clinical practice guidelines recommend drug testing patients who are receiving opioids chronically for pain or medication for a substance use disorder (SUD)-particularly opioid use disorder (OUD)-but practices vary due to a lack of consensus on testing frequency during follow-up. This study aimed to evaluate rates and costs of outpatient drug testing practices for patients receiving opioids for chronic pain or medication for an SUD.Using claims data from a large de-identified claims data warehouse, we conducted a retrospective cohort study of chronic opioid, buprenorphine, and naltrexone users between January 2015 and December 2019. We identified two cohorts-chronic opioid medication cohort (CO) and SUD-indicated medication cohort (SUD). We assessed drug testing rates during follow-up using procedure codes and costs using copayment, deductible, co-insurance, and out-of-pocket data.Among 6,657,515 eligible claimants, 367,118 (5.5 %) received opioids chronically and 73,303 (1.1 %) received an SUD-indicated medication. The cumulative proportion of drug testing during follow-up was similar between cohorts (CO: 36 %; SUD: 35 %), but rate of testing was consistently twice as frequent for the SUD cohort. All cost variables for the first drug test were higher on average in the SUD cohort than the CO cohort except copay: deductible (SUD: $18.54; CO: $7.33); co-insurance (SUD: $10.36; CO: $2.53); out-of-pocket (SUD: $29.39; CO: $10.57); copay (CO: $0.71; SUD: $0.49) (all p < 0.001).Overall proportion of drug testing was similar between cohorts, but testing frequency was at least double during follow-up in the SUD cohort. Most cost variables were higher in the SUD cohort. Whether the high cost of drug testing is a barrier to medication use or is associated with treatment discontinuation should be evaluated.

  View details for DOI 10.1016/j.josat.2023.209243

  View details for PubMedID 38052268

• Intravenous Calcium to Decrease Blood Loss During Intrapartum Cesarean Delivery: A Randomized Controlled Trial. Obstetrics and gynecology Ansari, J. R., Yarmosh, A., Michel, G., Lyell, D., Hedlin, H., Cornfield, D. N., Carvalho, B., Bateman, B. T. 2023

  Abstract

  OBJECTIVE: To evaluate whether prophylactic administration of 1 g of intravenous calcium chloride after cord clamping reduces blood loss from uterine atony during intrapartum cesarean delivery.METHODS: This single-center, block-randomized, placebo-controlled, double-blind superiority trial compared the effects of 1 g intravenous calcium chloride with those of saline placebo control on blood loss at cesarean delivery. Parturients at 34 or more weeks of gestation requiring intrapartum cesarean delivery after oxytocin exposure in labor were enrolled. Calcium or saline placebo was infused over 10 minutes beginning 1minute after umbilical cord clamping in addition to standard care with oxytocin. The primary outcome was quantitative blood loss, analyzed by inverse Gaussian regression. Planned subgroup analysis excluded nonatonic bleeding, such as hysterotomy extension, arterial bleeding, and occult placenta accreta. We planned to enroll 120 patients to show a 200-mL reduction in quantitative blood loss in planned subgroup analysis, assuming up to 40% incidence of nonatonic bleeding (80% power, alpha<0.05).RESULTS: From April 2022 through March 2023, 828 laboring parturients provided consent and 120 participants were enrolled. Median blood loss was 840 mL in patients allocated to calcium chloride (n=60) and 1,051 mL in patients allocated to placebo (n=60), which was not statistically different (mean reduction 211 mL, 95% CI -33 to 410). In the planned subgroup analysis (n=39 calcium and n=40 placebo), excluding cases of surgeon-documented nonatonic bleeding, calcium reduced quantitative blood loss by 356 mL (95% CI 159-515). Rates of reported side effects were similar between the two groups (38% calcium vs 42% placebo).CONCLUSION: Prophylactic intravenous calcium chloride administered during intrapartum cesarean delivery after umbilical cord clamping did not significantly reduce blood loss in the primary analysis. However, in the planned subgroup analysis, calcium infusion significantly reduced blood loss by approximately 350 mL. These data suggest that this inexpensive and shelf-stable medication warrants future study as a novel treatment strategy to decrease postpartum hemorrhage, the leading global cause of maternal morbidity and mortality.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05027048.

  View details for DOI 10.1097/AOG.0000000000005441

  View details for PubMedID 37917943

• Association between Surgeon/anesthesiologist Sex Discordance and One-year Mortality Among Adults Undergoing Noncardiac Surgery: A Population-based Retrospective Cohort Study. Annals of surgery Etherington, C., Boet, S., Chen, I., Duffy, M., Mamas, M. A., Eddeen, A. B., Bateman, B. T., Sun, L. Y. 2023

  Abstract

  To investigate the association between surgeon-anesthesiologist sex discordance and patient mortality after noncardiac surgery.Evidence suggests different practice patterns exist amongst female and male physicians. However, the influence of physician sex on team-based practices in the operating room and subsequent patient outcomes remains unclear in the context of noncardiac surgery.We conducted a population-based, retrospective cohort study of adult Ontario residents who underwent index, inpatient noncardiac surgery between January 2007 and December 2017. Primary exposure was physician sex discordance (i.e., surgeon and anesthesiologist were of the opposite sex). The primary outcome was 1-year mortality. The association between physician sex discordance and patient outcomes was modeled using multivariable Cox proportional hazard regression with adjustment for relevant physician, patient, and hospital characteristics.Of 541,209 patients, 158,084 (29.2%) were treated by sex-discordant physician teams. Physician sex discordance was associated with a lower rate of mortality at 1 year (5.2% vs. 5.7%; adjusted HR 0.95 [0.91-0.99]). Patients treated by teams composed of female surgeons and male anesthesiologists were more likely to be alive at 1 year than those treated by all-male physician teams (adjusted HR 0.90 [0.81-0.99]).Noncardiac surgery patients had a lower likelihood of 1-year mortality when treated by sex discordant surgeon-anesthesiologist teams. The likelihood of mortality was further reduced if the surgeon was female. Further research is needed to explore the underlying mechanisms of these observations and design strategies to diversify OR teams to optimize performance and patient outcomes.

  View details for DOI 10.1097/SLA.0000000000006111

  View details for PubMedID 37791498

• Social and demographic disparities in the adherence to antihypertensive medication during pregnancy Dicesare, E. C., Huybrechts, K. F., Bateman, B. T., Lii, J., Straub, L. WILEY. 2023: 134-135

  View details for Web of Science ID 001091511700254

• Journal-related Activities and Other Special Activities at the 2023 American Society of Anesthesiologists Meeting ANESTHESIOLOGY Avram, M. J., Bateman, B. T., Culley, D. J., Fernandez-Bustamante, A., Houle, T. T., London, M. J., Rathmell, J. P., Schreiber, K. L., Melo, M. 2023; 139 (4): 377-386

  View details for DOI 10.1097/ALN.0000000000004707

  View details for Web of Science ID 001144382600001

• Using tree-based scan statistics for signal identification: Screening for elevated congenital malformation risk following prenatal antipsychotic exposure Straub, L., Wang, S. V., Hernandez-Diaz, S., Vine, S., Russo, M., Bateman, B. T., Zhu, Y., Huybrechts, K. F. WILEY. 2023: 61

  View details for Web of Science ID 001091511700113

• A comparison of postpartum opioid consumption and opioid discharge prescriptions among opioid naive patients and those with opioid use disorder Gibbs, L. R., Holland, E., Spence, N. Z., Young, M., Werler, M. M., Guang, Z., Saia, K. A., Bateman, B. T., Achu-Lopes, R., Wachman, E. WILEY. 2023: 521-522

  View details for Web of Science ID 001091511702263

• Increase in mental health conditions and psychotropic prescribing in teenage girls during the COVID-19 pandemic in the US Straub, L., Bateman, B. T., Huybrechts, K. F., Vine, S. WILEY. 2023: 33-34

  View details for Web of Science ID 001091511700060

• Benzodiazepine use early in pregnancy and risk of congenital malformations Sujan, A. C., Bateman, B. T., Straub, L., Hernandez-Diaz, S., Zhu, Y., Brill, G., Huybrechts, K. F. WILEY. 2023: 69

  View details for Web of Science ID 001091511700128

• Risk of opioid overdose with concomitant use of oxycodone and selective serotonin reuptake inhibitors Bykov, K., Basham, C., Khan, N. F., Vine, S., Edrees, H. H., Mastrorilli, J., Bateman, B. T., Glynn, R. J., Huybrechts, K. F. WILEY. 2023: 49-50

  View details for Web of Science ID 001091511700091

• Opioid overdose risk after oxycodone initiation during CYP3A4-inhibiting versus non-inhibiting calcium channel blocker therapy Basham, C., Edrees, H. H., Vine, S., Mastrorilli, J., Oduol, T., Bateman, B. T., Glynn, R. J., Huybrechts, K. F., Bykov, K. WILEY. 2023: 588

  View details for Web of Science ID 001091511702398

• Trends in use of antipsychotics and psychoactive drugs in older patients after major surgery. Journal of the American Geriatrics Society Kim, D. H., Lee, H., Pawar, A., Lee, S. B., Park, C. M., Levin, R., Metzger, E., Bateman, B. T., Ely, E. W., Pandharipande, P. P., Pisani, M. A., Hohmann, S. F., Marcantonio, E. R., Inouye, S. K. 2023

  Abstract

  Professional society guidelines recommend limiting the use of antipsychotics in older patients with postoperative delirium. How these recommendations affected the use of antipsychotics and other psychoactive drugs in the postoperative period has not been studied.This retrospective cohort study included patients 65 years or older without psychiatric diagnoses who underwent major surgery in community hospitals (CHs) and academic medical centers (AMCs) in the United States. The outcome was the rate of hospital days exposed to antipsychotics, antidepressants, antiepileptics, benzodiazepines, hypnotics, and selective alpha-2 receptor agonist dexmedetomidine in the postoperative period by hospital type.The study included 4,098,431 surgical admissions from CHs (mean age 75.0 [standard deviation, 7.1] years; 50.8% female) during 2008-2018 and 2,310,529 surgical admissions from AMCs (75.0 [7.4] years; 49.4% female) during 2009-2018. In the intensive care unit (ICU) setting, the number of exposed days per 1000 hospital-days declined for haloperidol (CHs: 33-21 days [p < 0.01]; AMCs: 24-15 days [p < 0.01]) and benzodiazepines (CHs: 261-136 days [p < 0.01]; AMCs: 150-77 days [p < 0.01]). The use of atypical antipsychotics, antidepressants, antiepileptics, and dexmedetomidine increased, while hypnotic use varied by the hospital type. In the non-ICU setting, the rate declined for haloperidol in CHs but not in AMCs (CHs: 10-6 days [p < 0.01]; AMCs: 4-3 days [p = 0.52]) and for benzodiazepines in both settings (CHs: 126-56 days [p < 0.01]; AMCs: 30-27 days [p < 0.01]). The use of antiepileptics and antidepressants increased, while the use of atypical antipsychotics and hypnotics varied by the hospital type.The use of haloperidol and benzodiazepines in the postoperative period declined at both CHs and AMCs. These trends coincided with the increasing use of other psychoactive drugs.

  View details for DOI 10.1111/jgs.18580

  View details for PubMedID 37676699

• Chronic Hypertension in Pregnancy and Racial-Ethnic Disparities in Complications. Obstetrics and gynecology Leonard, S. A., Formanowski, B. L., Phibbs, C. S., Lorch, S., Main, E. K., Kozhimannil, K. B., Passarella, M., Bateman, B. T. 2023

  Abstract

  To evaluate whether there are individual- and population-level associations between chronic hypertension and pregnancy complications, and to assess differences across seven racial-ethnic groups.This population-based study used linked vital statistics and hospitalization discharge data from all live and stillbirths in California (2008-2018), Michigan (2008-2020), Oregon (2008-2020), Pennsylvania (2008-2014), and South Carolina (2008-2020). We used multivariable log-binomial regression models to estimate risk ratios (RRs) and population attributable risk (PAR) percentages with 95% CIs for associations between chronic hypertension and several obstetric and neonatal outcomes, selected based on prior evidence and pathologic pathways. We adjusted models for demographic factors (race and ethnicity, payment method, educational attainment), age, body mass index, obstetric history, delivery year, and state, and conducted analyses stratified across seven racial-ethnic groups.The study included 7,955,713 pregnancies, of which 168,972 (2.1%) were complicated by chronic hypertension. Chronic hypertension was associated with several adverse obstetric and neonatal outcomes, with the largest adjusted PAR percentages observed for preeclampsia with severe features or eclampsia (22.4; 95% CI 22.2-22.6), acute renal failure (13.6; 95% CI 12.6-14.6), and pulmonary edema (10.7; 95% CI 8.9-12.6). Estimated RRs overall were similar across racial-ethnic groups, but PAR percentages varied. The adjusted PAR percentages (95% CI) for severe maternal morbidity-a widely used composite of acute severe events-for people who were American Indian or Alaska Native, Asian, Black, Latino, Native Hawaiian or Other Pacific Islander, White, and Multiracial or Other were 5.0 (1.1-8.8), 3.7 (3.0-4.3), 9.0 (8.2-9.8), 3.9 (3.6-4.3), 11.6 (6.4-16.5), 3.2 (2.9-3.5), and 5.5 (4.2-6.9), respectively.Chronic hypertension accounts for a substantial fraction of obstetric and neonatal morbidity and contributes to higher complication rates, particularly for people who are Black or Native Hawaiian or Other Pacific Islander.

  View details for DOI 10.1097/AOG.0000000000005342

  View details for PubMedID 37678888

• Comparative Safety Analysis of Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery : A Nationwide Cohort Study. Annals of internal medicine Kim, D. H., Lee, S. B., Park, C. M., Levin, R., Metzger, E., Bateman, B. T., Ely, E. W., Pandharipande, P. P., Pisani, M. A., Jones, R. N., Marcantonio, E. R., Inouye, S. K. 2023

  Abstract

  Antipsychotics are commonly used to manage postoperative delirium. Recent studies reported that haloperidol use has declined, and atypical antipsychotic use has increased over time.To compare the risk for in-hospital adverse events associated with oral haloperidol, olanzapine, quetiapine, and risperidone in older patients after major surgery.Retrospective cohort study.U.S. hospitals in the Premier Healthcare Database.17 115 patients aged 65 years and older without psychiatric disorders who were prescribed an oral antipsychotic drug after major surgery from 2009 to 2018.Haloperidol (≤4 mg on the day of initiation), olanzapine (≤10 mg), quetiapine (≤150 mg), and risperidone (≤4 mg).The risk ratios (RRs) for in-hospital death, cardiac arrhythmia events, pneumonia, and stroke or transient ischemic attack (TIA) were estimated after propensity score overlap weighting.The weighted population had a mean age of 79.6 years, was 60.5% female, and had in-hospital death of 3.1%. Among the 4 antipsychotics, quetiapine was the most prescribed (53.0% of total exposure). There was no statistically significant difference in the risk for in-hospital death among patients treated with haloperidol (3.7%, reference group), olanzapine (2.8%; RR, 0.74 [95% CI, 0.42 to 1.27]), quetiapine (2.6%; RR, 0.70 [CI, 0.47 to 1.04]), and risperidone (3.3%; RR, 0.90 [CI, 0.53 to 1.41]). The risk for nonfatal clinical events ranged from 2.0% to 2.6% for a cardiac arrhythmia event, 4.2% to 4.6% for pneumonia, and 0.6% to 1.2% for stroke or TIA, with no statistically significant differences by treatment group.Residual confounding by delirium severity; lack of untreated group; restriction to oral low-to-moderate dose treatment.These results suggest that atypical antipsychotics and haloperidol have similar rates of in-hospital adverse clinical events in older patients with postoperative delirium who receive an oral low-to-moderate dose antipsychotic drug.National Institute on Aging.

  View details for DOI 10.7326/M22-3021

  View details for PubMedID 37665998

• Achieving comparability in glycemic control between antidiabetic treatment strategies in pregnancy when using real world data. Pharmacoepidemiology and drug safety Cesta, C. E., Hernandez-Diaz, S., Huybrechts, K. F., Bateman, B. T., Vine, S., Seely, E. W., Patorno, E. 2023

  Abstract

  PURPOSE: Healthcare utilization databases often lack information on glycemic control, a key confounder when studying the safety of antidiabetic treatments, since patients with worse control are channeled to second-line agents, in particular insulin, versus first-line agents such as metformin. We evaluated whether adjustment for measured characteristics attains balance in glycemic control when comparing antidiabetic treatment strategies in pregnant women with pregestational type 2 diabetes (T2DM).METHODS: In a US insurance claims database, we identified 3360 women with T2DM pregnant between 2004 and 2015, of whom a subset of 996 had data on hemoglobin A1c (HbA1c ) levels. We selected insulin only as the comparator group and used propensity score (PS)-matching on comorbidities and proxies of diabetes severity, but not on HbA1c , to adjust for confounding. We used standardized differences (st.diff) to assess balance in claims-based covariates and mean HbA1c (%±SD) in the subset.RESULTS: There were imbalances in claims-based covariates before PS-matching, with smaller differences when both treatment strategies included insulin. After PS-matching, balance was achieved in most claims-based covariates (st.diff <0.1). Mean HbA1c was similar before and after PS-matching when both treatments included insulin (e.g., 7.1±1.5 vs. 7.7±1.8 and 7.1±1.5 vs. 7.5±1.7, respectively, for metformin+insulin vs. insulin only). Differences in mean HbA1c remained after PS-matching when non-insulin treatments were compared to treatments including insulin (e.g., 6.3±1.1 vs. 7.6±1.7 for metformin only vs. insulin only).CONCLUSIONS: Balance in both claims-based characteristics and glycemic control was attained after restricting the population to women with T2DM and comparing treatment strategies indicated for patients with similar diabetes severity. When comparing treatment strategies with versus without insulin, differences in glycemic control persisted after PS-matching even when balance was attained for other measured characteristics.

  View details for DOI 10.1002/pds.5665

  View details for PubMedID 37461243

• Buprenorphine Versus Methadone for Opioid Use Disorder in Pregnancy OBSTETRICAL & GYNECOLOGICAL SURVEY Suarez, E. A., Huybrechts, K. F., Straub, L., Hernandez-Diaz, S., Jones, H. E., Connery, H. S., Davis, J. M., Gray, K. J., Lester, B., Terplan, M., Mogun, H., Bateman, B. T. 2023; 78 (6): 325-327

  View details for DOI 10.1097/01.ogx.0000943156.17246.fa

  View details for Web of Science ID 001005632500006

• A comparison of postpartum opioid consumption and opioid discharge prescriptions among opioid naïve patients and those with opioid use disorder. American journal of obstetrics & gynecology MFM Holland, E., Gibbs, L., Spence, N. Z., Young, M., Werler, M. M., Guang, Z., Saia, K., Bateman, B. T., Achu, R., Wachman, E. M. 2023: 101025

  Abstract

  Management of patients with opioid use disorder (OUD) during the acute postpartum period remains clinically challenging as obstetricians aim to mitigate post-delivery pain while optimizing recovery support.To evaluate postpartum opioid consumption and opioids prescribed at discharge among patients with OUD treated with methadone, buprenorphine, and no medication for OUD, as compared with opioid naïve counterparts.We conducted a retrospective cohort study of pregnant patients who underwent delivery greater than 20 weeks gestation at a tertiary academic hospital between May 2014 and April 2020. The primary outcome of this analysis was the mean daily quantity of oral opioids consumed after delivery while inpatient in milligrams of morphine equivalents (MME). Secondary outcomes included: 1) quantity of oral opioids prescribed at discharge, and 2) prescription for oral opioids in the 6 weeks after hospital discharge. Multiple linear regression was used to compare differences in the primary outcome.A total of 16,140 pregnancies were included. Patients with OUD (n=553) consumed 14 MME/d greater quantities of opioids postpartum than opioid-naïve women (n=15,587), (95% CI 11, 17). Patients with OUD undergoing cesarean delivery consumed 30 MME/d greater quantities of opioids than opioid-naïve counterparts (95% CI 26, 35). Among patients who underwent vaginal delivery, there was no difference in opioid consumption among patients with and without OUD. Compared to patients prescribed methadone, patients prescribed buprenorphine, and those prescribed no medication for OUD consumed similar opioid quantities postpartum following both vaginal and cesarean delivery. Among patients undergoing cesarean delivery, opioid naïve patients were more likely to receive a discharge prescription for opioids than patients with OUD (77% versus 68%, p=0.002), despite lower pain scores and less in-hospital opioid consumption.Patients with OUD, regardless of treatment with methadone, buprenorphine, or no medication for OUD consumed significantly greater quantities of opioids after cesarean delivery but received fewer opioid prescriptions at discharge.

  View details for DOI 10.1016/j.ajogmf.2023.101025

  View details for PubMedID 37211090

• Screening for Elevated Congenital Malformation Risk Following Prenatal Antipsychotic Exposure Using Tree-Based Scan Statistics for Signal Identification Straub, L., Wang, S., Hernandez-Diaz, S., Vine, S., Russo, M., Bateman, B. T., Zhu, Y., Huybrechts, K. F. WILEY. 2023: 856

  View details for Web of Science ID 001042910700046

• Prevalence of Mental Health Diagnoses in Commercially Insured Children and Adolescents in the US Before and During the COVID-19 Pandemic. JAMA network open Straub, L., Bateman, B. T., Vine, S., Huybrechts, K. F. 2023; 6 (5): e2314415

  Abstract

  This cross-sectional study examines trends in the prevalence of various mental health diagnoses in children and adolescents in the US, stratified by age and sex, before and during the COVID-19 pandemic.

  View details for DOI 10.1001/jamanetworkopen.2023.14415

  View details for PubMedID 37213104

• Comparative Analysis of Low-Dose Oral Antipsychotics for In-Hospital Adverse Clinical Events in Older Adults After Major Surgery Park, C., Kim, D., Lee, S., Levin, R., Metzger, E., Bateman, B., Ely, W., Pandharipande, P., Pisani, M., Jones, R., Marcantonio, E., Inouye, S. WILEY. 2023: S132

  View details for Web of Science ID 000990199800378

• Buprenorphine versus Methadone in Pregnancy. Reply. The New England journal of medicine Suarez, E. A., Huybrechts, K. F., Bateman, B. T. 2023; 388 (10): 957-958

  View details for DOI 10.1056/NEJMc2300439

  View details for PubMedID 36884335

• Buprenorphine versus Methadone in Pregnancy The authors reply NEW ENGLAND JOURNAL OF MEDICINE Suarez, E. A., Huybrechts, K. F., Bateman, B. T. 2023; 388 (10): 957-958

  View details for Web of Science ID 000999779400021

• Postpartum Opioid-Related Mortality in Patients With Public Insurance. Obstetrics and gynecology Suarez, E. A., Huybrechts, K. F., Straub, L., Hernandez-Diaz, S., Creanga, A. A., Connery, H. S., Gray, K. J., Vine, S. M., Jones, H. E., Bateman, B. T. 2023

  Abstract

  OBJECTIVE: To assess the incidence and risk factors for postpartum opioid overdose death and describe other causes of postpartum death in individuals with opioid use disorder (OUD).METHODS: We conducted a cohort study that used health care utilization data from the Medicaid Analytic eXtract linked to the National Death Index in the United States from 2006 to 2013. All pregnant individuals with live births or stillbirths and continuous enrollment for 3 months before delivery were eligible, including 4,972,061 deliveries. A subcohort of individuals with a documented history of OUD in the 3 months before delivery was identified. We estimated the cumulative incidence of death as occurring between delivery and 1 year postpartum among all individuals and individuals with OUD. Risk factors for opioid overdose death were assessed using odds ratios (ORs) and descriptive statistics, including demographics, health care utilization, obstetric conditions, comorbidities, and medications.RESULTS: The incidence of postpartum opioid overdose death per 100,000 deliveries was 5.4 (95% CI 4.5-6.4) among all individuals and 118 (95% CI 84-163) among individuals with OUD. Individuals with OUD had a sixfold higher incidence of all-cause postpartum death than all individuals. Common causes of death in individuals with OUD were other drug- and alcohol-related deaths (47/100,000), suicide (26/100,000), and other injuries, including accidents and falls (33/100,000). Risk factors strongly associated with postpartum opioid overdose death included mental health and other substance use disorders. Among patients with OUD, postpartum use of medication to treat OUD was associated with 60% lower odds of opioid overdose death (OR 0.4, 95% CI 0.1-0.9).CONCLUSION: Postpartum individuals with OUD have a high incidence of postpartum opioid overdose death and other preventable deaths, including nonopioid substance-related injuries, accidents, and suicide. Use of medications for OUD is strongly associated with lower opioid-related mortality.

  View details for DOI 10.1097/AOG.0000000000005115

  View details for PubMedID 36897177

• Emulating a Target Trial of Interventions Initiated During Pregnancy with Healthcare Databases: The Example of COVID-19 Vaccination. Epidemiology (Cambridge, Mass.) Hernández-Díaz, S., Huybrechts, K. F., Chiu, Y. H., Yland, J. J., Bateman, B. T., Hernán, M. A. 2023; 34 (2): 238-246

  Abstract

  Observational studies are often the only option to estimate effects of interventions during pregnancy. Causal inference from observational data can be conceptualized as an attempt to emulate a hypothetical pragmatic randomized trial: the target trial.To provide a step-by-step description of how to use healthcare databases to estimate the effects of interventions initiated during pregnancy. As an example, we describe how to specify and emulate a target trial of COVID-19 vaccination during pregnancy, but the framework can be generally applied to point and sustained strategies involving both pharmacologic and non-pharmacologic interventions.First, we specify the protocol of a target trial to evaluate the safety and effectiveness of vaccination during pregnancy. Second, we describe how to use observational data to emulate each component of the protocol of the target trial. We propose different target trials for different gestational periods because the outcomes of interest vary by gestational age at exposure. We identify challenges that affect (i) the target trial and thus its observational emulation (censoring and competing events), and (ii) mostly the observational emulation (confounding, immortal time, and measurement biases).Some biases may be unavoidable in observational emulations, but others are avoidable. For instance, immortal time bias can be avoided by aligning the start of follow-up with the gestational age at the time of the intervention, as we would do in the target trial. Explicitly emulating target trials at different gestational ages can help reduce bias and improve the interpretability of effect estimates for interventions during pregnancy.

  View details for DOI 10.1097/EDE.0000000000001562

  View details for PubMedID 36722806

• Data-driven longitudinal characterization of neonatal health and morbidity. Science translational medicine De Francesco, D., Reiss, J. D., Roger, J., Tang, A. S., Chang, A. L., Becker, M., Phongpreecha, T., Espinosa, C., Morin, S., Berson, E., Thuraiappah, M., Le, B. L., Ravindra, N. G., Payrovnaziri, S. N., Mataraso, S., Kim, Y., Xue, L., Rosenstein, M. G., Oskotsky, T., Marić, I., Gaudilliere, B., Carvalho, B., Bateman, B. T., Angst, M. S., Prince, L. S., Blumenfeld, Y. J., Benitz, W. E., Fuerch, J. H., Shaw, G. M., Sylvester, K. G., Stevenson, D. K., Sirota, M., Aghaeepour, N. 2023; 15 (683): eadc9854

  Abstract

  Although prematurity is the single largest cause of death in children under 5 years of age, the current definition of prematurity, based on gestational age, lacks the precision needed for guiding care decisions. Here, we propose a longitudinal risk assessment for adverse neonatal outcomes in newborns based on a deep learning model that uses electronic health records (EHRs) to predict a wide range of outcomes over a period starting shortly before conception and ending months after birth. By linking the EHRs of the Lucile Packard Children's Hospital and the Stanford Healthcare Adult Hospital, we developed a cohort of 22,104 mother-newborn dyads delivered between 2014 and 2018. Maternal and newborn EHRs were extracted and used to train a multi-input multitask deep learning model, featuring a long short-term memory neural network, to predict 24 different neonatal outcomes. An additional cohort of 10,250 mother-newborn dyads delivered at the same Stanford Hospitals from 2019 to September 2020 was used to validate the model. Areas under the receiver operating characteristic curve at delivery exceeded 0.9 for 10 of the 24 neonatal outcomes considered and were between 0.8 and 0.9 for 7 additional outcomes. Moreover, comprehensive association analysis identified multiple known associations between various maternal and neonatal features and specific neonatal outcomes. This study used linked EHRs from more than 30,000 mother-newborn dyads and would serve as a resource for the investigation and prediction of neonatal outcomes. An interactive website is available for independent investigators to leverage this unique dataset: https://maternal-child-health-associations.shinyapps.io/shiny_app/.

  View details for DOI 10.1126/scitranslmed.adc9854

  View details for PubMedID 36791208

• Atomoxetine in Early Pregnancy and the Prevalence of Major Congenital Malformations: A Multi ational Study. The Journal of clinical psychiatry Broms, G., Hernandez-Diaz, S., Huybrechts, K. F., Bateman, B. T., Kristiansen, E. B., Einarsdottir, K., Engeland, A., Furu, K., Gissler, M., Karlsson, P., Klungsoyr, K., Lahesmaa-Korpinen, A., Mogun, H., Norgaard, M., Reutfors, J., Sorensen, H. T., Zoega, H., Kieler, H. 2023; 84 (1)

  Abstract

  Objective: Most research on safety of attention-deficit/hyperactivity disorder (ADHD) medications during pregnancy concerns central nervous system stimulants, while little is known about the safety of atomoxetine, a primary treatment alternative. We assessed the prevalence of major congenital malformations overall, and cardiac malformations and limb malformations specifically, after first-trimester exposure.Methods: In this cohort study, we included all approximately 2.4 million pregnancies ending in live births recorded in the population-based nationwide health registers of Denmark, Iceland, Norway, and Sweden (2003-2017) and approximately 1.8 million publicly insured pregnancies ending in live births recorded in the US Medicaid Analytic eXtract (MAX, 2001-2013) health care claims database. We compared the prevalence of major congenital malformations in the newborn among pregnancies exposed and unexposed to atomoxetine. For each country, we calculated prevalence ratios (PRs), crude and stratified by propensity scores (PSs). We pooled the country-specific PS strata to obtain a PR adjusted for potential confounding factors.Results: We identified 368 pregnancies exposed to atomoxetine during the first trimester in the 4 Nordic countries and 622 in the US. The pooled crude PR for any major congenital malformation was 1.18 (95% CI, 0.88-1.60), and the adjusted PR was 0.99 (95% CI, 0.74-1.34). For cardiac malformations, the adjusted PR was 1.34 (95% CI, 0.86-2.09). For limb malformations, the adjusted PR was 0.90 (95% CI, 0.38-2.16).Conclusions: After atomoxetine exposure in early pregnancy, we observed no increase in major congenital malformations overall and, although with some uncertainty due to sample size, no statistically increased risk estimates for cardiac malformations and limb malformations.

  View details for DOI 10.4088/JCP.22m14430

  View details for PubMedID 36652686

• Development and Validation of Algorithms to Estimate Live Birth Gestational Age in Medicaid Analytic eXtract Data. Epidemiology (Cambridge, Mass.) Zhu, Y., Thai, T. N., Hernandez-Diaz, S., Bateman, B. T., Winterstein, A. G., Straub, L., Franklin, J. M., Gray, K. J., Wyss, R., Mogun, H., Vine, S., Taylor, L. G., Ouellet-Hellstrom, R., Ma, Y., Qiang, Y., Hua, W., Huybrechts, K. F. 2023; 34 (1): 69-79

  Abstract

  While healthcare utilization data are useful for postmarketing surveillance of drug safety in pregnancy, the start of pregnancy and gestational age at birth are often incompletely recorded or missing. Our objective was to develop and validate a claims-based live birth gestational age algorithm.Using the Medicaid Analytic eXtract (MAX) linked to birth certificates in three states, we developed four candidate algorithms based on: preterm codes; preterm or postterm codes; timing of prenatal care; and prediction models - using conventional regression and machine-learning approaches with a broad range of prespecified and empirically selected predictors. We assessed algorithm performance based on mean squared error (MSE) and proportion of pregnancies with estimated gestational age within 1 and 2 weeks of the gold standard, defined as the clinical or obstetric estimate of gestation on the birth certificate. We validated the best-performing algorithms against medical records in a nationwide sample. We quantified misclassification of select drug exposure scenarios due to estimated gestational age as positive predictive value (PPV), sensitivity, and specificity.Among 114,117 eligible pregnancies, the random forest model with all predictors emerged as the best performing algorithm: MSE 1.5; 84.8% within 1 week and 96.3% within 2 weeks, with similar performance in the nationwide validation cohort. For all exposure scenarios, PPVs were >93.8%, sensitivities >94.3%, and specificities >99.4%.We developed a highly accurate algorithm for estimating gestational age among live births in the nationwide MAX data, further supporting the value of these data for drug safety surveillance in pregnancy. See video abstract at, http://links.lww.com/EDE/B989.

  View details for DOI 10.1097/EDE.0000000000001559

  View details for PubMedID 36455247

• Obesity in Pregnancy OBSTETRICAL & GYNECOLOGICAL SURVEY Creanga, A. A., Catalano, P. M., Bateman, B. T. 2023; 78 (1): 11-14

  View details for Web of Science ID 001076275200001

• Hospital intrapartum practices and disparities in severe maternal and neonatal morbidity Leonard, S. A., Xu, X., Davies-Balch, S., Main, E., Bateman, B. T., Rehkopf, D., Lee, H. C., Illuzzi, J., Igbinosa, I., Iwekaogwu, I., Lyell, D. J. MOSBY-ELSEVIER. 2023: S233

  View details for Web of Science ID 000909337400348

• Implication of Maternal Continuous Enrollment on Stillbirth Gestational Age Distributions and Maternal Characteristics in Medicaid Enrollees. American journal of epidemiology Thai, T. N., Rasmussen, S. A., Smolinski, N. E., Nduaguba, S., Zhu, Y., Bateman, B. T., Huybrechts, K. F., Hernandez-Diaz, S., Winterstein, A. G. 2022

  View details for DOI 10.1093/aje/kwac206

  View details for PubMedID 36482740

• Association of In Utero Antipsychotic Medication Exposure With Risk of Congenital Malformations in Nordic Countries and the US. JAMA psychiatry Huybrechts, K. F., Straub, L., Karlsson, P., Pazzagli, L., Furu, K., Gissler, M., Hernandez-Diaz, S., Nørgaard, M., Zoega, H., Bateman, B. T., Cesta, C. E., Cohen, J. M., Leinonen, M. K., Reutfors, J., Selmer, R. M., Suarez, E. A., Ulrichsen, S. P., Kieler, H. 2022

  Abstract

  Psychiatric disorders are common among female individuals of reproductive age. While antipsychotic medication use is increasing, the safety of such medications in pregnancy is an area with large evidence gaps.To evaluate the risk of first-trimester antipsychotic exposure with respect to congenital malformations, focusing on individual drugs and specific malformation subtypes.This cohort study used data from nationwide health registers from the 5 Nordic countries and the US and spanned 1996 to 2018. The Nordic cohort included all pregnancies resulting in singleton live-born infants, and the US cohort consisted of publicly insured mothers linked to their live-born infants nested in the nationwide Medicaid Analytic eXtract. Data were analyzed from November 2020 to April 2022.One or more first-trimester dispensing of any atypical, any typical, and individual antipsychotic drugs.Any major congenital malformation and specific malformation subtypes previously suggested to be associated with antipsychotic exposure in utero: cardiovascular malformations, oral clefts, neural tube defects, hip dysplasia, limb reduction defects, anorectal atresia/stenosis, gastroschisis, hydrocephalus, other specific brain anomalies, and esophageal disorders. Propensity score stratification was used to control for potential confounders. Pooled adjusted estimates were calculated using indirect standardization.A total of 6 455 324 unexposed mothers (mean maternal age range across countries: 24-31 years), 21 751 mothers exposed to atypical antipsychotic drugs (mean age range, 26-31 years), and 6371 mothers exposed to typical antipsychotic drugs (mean age range, 27-32 years) were included in the study cohort. Prevalence of any major malformation was 2.7% (95% CI, 2.7%-2.8%) in unexposed infants, 4.3% (95% CI, 4.1%-4.6%) in infants with atypical antipsychotic drug exposure, and 3.1% (95% CI, 2.7%-3.5%) in infants with typical antipsychotic drug exposure in utero. Among the most prevalent exposure-outcome combinations, adjusted relative risks (aRR) were generally close to the null. One exception was olanzapine exposure and oral cleft (aRR, 2.1 [95% CI, 1.1-4.3]); however, estimates varied across sensitivity analyses. Among moderately prevalent combinations, increased risks were observed for gastroschisis and other specific brain anomalies after atypical antipsychotic exposure (aRR, 1.5 [95% CI, 0.8-2.6] and 1.9 [95% CI, 1.1-3.0]) and for cardiac malformations after chlorprothixene exposure (aRR, 1.6 [95% CI, 1.0-2.7]). While the association direction was consistent across sensitivity analyses, confidence intervals were wide, prohibiting firm conclusions.In this study, considering the evidence from primary and sensitivity analyses and inevitable statistical noise for very rare exposure-outcome combinations, in utero antipsychotic exposure generally was not meaningfully associated with an increased risk of malformations. The observed increased risks of oral clefts associated with olanzapine, gastroschisis, and other specific brain anomalies with atypical antipsychotics and cardiac malformations with chlorprothixene requires confirmation as evidence continues to accumulate.

  View details for DOI 10.1001/jamapsychiatry.2022.4109

  View details for PubMedID 36477338

• Validation of Claims-based Algorithms to Identify Non-Live Birth Outcomes. Pharmacoepidemiology and drug safety Zhu, Y., Bateman, B. T., Hernandez-Diaz, S., Gray, K. J., Straub, L., Reimers, R. M., Manning-Geist, B., Yoselevsky, E., Taylor, L. G., Ouellet-Hellstrom, R., Ma, Y., Qiang, Y., Hua, W., Huybrechts, K. F. 2022

  Abstract

  PURPOSE: Perinatal epidemiology studies using healthcare utilization databases are often restricted to live births, largely due to the lack of established algorithms to identify non-live births. The study objective was to develop and validate claims-based algorithms for the ascertainment of non-live births.METHODS: Using the Mass General Brigham Research Patient Data Registry 2000-2014, we assembled a cohort of women enrolled in Medicaid with a non-live birth. Based on ≥1 inpatient or ≥2 outpatient diagnosis/procedure codes, we identified and randomly sampled 100 potential stillbirth, spontaneous abortion, and termination cases each. For the secondary definitions, we excluded cases with codes for other pregnancy outcomes within ±5days of the outcome of interest and relaxed the definitions for spontaneous abortion and termination by allowing cases with one outpatient diagnosis only. Cases were adjudicated based on medical chart review. We estimated the positive predictive value (PPV) for each outcome.RESULTS: The PPV was 71.0% (95% CI, 61.1 - 79.6) for stillbirth; 79.0% (69.7 - 86.5) for spontaneous abortion, and 93.0% (86.1 - 97.1) for termination. When excluding cases with adjacent codes for other pregnancy outcomes and further relaxing the definition, the PPV increased to 80.6% (69.5 - 88.9) for stillbirth, 86.6% (80.5 - 91.3) for spontaneous abortion and 94.9% (91.1 - 97.4) for termination. The PPV for the composite outcome using the relaxed definition was 94.4% (92.3 - 96.1).CONCLUSIONS: Our findings suggest non-live birth outcomes can be identified in a valid manner in epidemiological studies based on healthcare utilization databases.

  View details for DOI 10.1002/pds.5574

  View details for PubMedID 36420643

• Non-opioid analgesic prescriptions filled after surgery among older adults in Ontario, Canada: a population-based cohort study. Anesthesiology Jivraj, N. K., Ladha, K., Goel, A., Hill, A., Wijeysundera, D. N., Bateman, B. T., Neuman, M., Wunsch, H. 2022

  Abstract

  BACKGROUND: The objective was to assess changes over time in prescriptions filled for non-opioid analgesics for older post-operative patients in the immediate post-discharge period. We hypothesized that the number of patients who filled a non-opioid analgesic prescription increased over the study period.METHODS: We performed a population-based cohort study, using linked health administrative data, of 278,366 admissions ≥66 years undergoing surgery between fiscal year 2013 and 2019 in Ontario, Canada. The primary outcome was the percentage of patients with new filled prescriptions for non-opioid analgesics within 7 days of discharge, and a secondary outcome was the analgesic class. We assessed whether patients filled prescriptions for a non-opioid only, an opioid only, both opioid and non-opioid prescriptions, or a combination opioid/non-opioid.RESULTS: Overall, 22% (n=60,181) of patients filled no opioid prescription, 2% (n=5,534) filled a non-opioid only, 21% (n=59,608) filled an opioid only, and 55% (n=153,043) filled some combination of opioid and non-opioid. The percentage of patients who filled a non-opioid prescription within 7 days post-operatively increased from 9% (n=2,119) in 2013 to 28% (n=13,090) in 2019, with the greatest increase for acetaminophen: 3% (n=701) to 20% (n=9,559). The percentage of patients who filled a combination analgesic prescription decreased from 53% (n=12,939) in 2013 to 28% (n=13,453) in 2019. However, the percentage who filled both an opioid and nonopioid prescription increased: 4% (n=938) to 21% (n=9,880) so that the overall percentage of patients who received both an opioid and a non-opioid remained constant over time 76% (n= 18,642) in 2013 to 75% (n=35,391) in 2019.CONCLUSIONS: The proportion of post-operative patients who fill prescriptions for non-opioid analgesics has increased. However, rather than a move to use of non-opioids alone for analgesia, this represents a shift away from combination medications towards separate prescriptions for opioids and non-opioids.

  View details for DOI 10.1097/ALN.0000000000004443

  View details for PubMedID 36512729

• Obesity in Pregnancy. Reply. The New England journal of medicine Creanga, A. A., Catalano, P. M., Bateman, B. T. 2022; 387 (14): 1339

  View details for DOI 10.1056/NEJMc2210921

  View details for PubMedID 36198192

• A Systematic Scoping Review of Peridelivery Pain Management for Pregnant People With Opioid Use Disorder: From the Society for Obstetric Anesthesia and Perinatology and Society for Maternal Fetal Medicine. Anesthesia and analgesia Lim, G., Soens, M., Wanaselja, A., Chyan, A., Carvalho, B., Landau, R., George, R. B., Klem, M. L., Osmundson, S. S., Krans, E. E., Terplan, M., Bateman, B. T. 2022

  Abstract

  The prevalence of pregnant people with opioid use disorder (OUD), including those receiving medications for opioid use disorder (MOUD), is increasing. Challenges associated with pain management in people with OUD include tolerance, opioid-induced hyperalgesia, and risk for return to use. Yet, there are few evidence-based recommendations for pain management in the setting of pregnancy and the postpartum period, and many peripartum pain management studies exclude people with OUD. This scoping review summarized the available literature on peridelivery pain management in people with OUD, methodologies used, and identified specific areas of knowledge gaps. PubMed and Embase were comprehensively searched for publications in all languages on peripartum pain management among people with OUD, both treated with MOUD and untreated. Potential articles were screened by title, abstract, and full text. Data abstracted were descriptively analyzed to map available evidence and identify areas of limited or no evidence. A total of 994 publications were imported for screening on title, abstracts, and full text, yielding 84 publications identified for full review: 32 (38.1%) review articles, 14 (16.7%) retrospective studies, and 8 (9.5%) case reports. There were 5 randomized controlled trials. Most studies (64%) were published in perinatology (32; 38.1%) journals or anesthesiology (22; 26.2%) journals. Specific areas lacking trial or systematic review evidence include: (1) methods to optimize psychological and psychosocial comorbidities relevant to acute pain management around delivery; (2) alternative nonopioid and nonpharmacologic analgesia methods; (3) whether or not to use opioids for severe breakthrough pain and how best to prescribe and monitor its use after discharge; (4) monitoring for respiratory depression and sedation with coadministration of other analgesics; (5) optimal neuraxial analgesia dosing and adjuncts; and (6) benefits of abdominal wall blocks after cesarean delivery. No publications discussed naloxone coprescribing in the labor and delivery setting. We observed an increasing number of publications on peripartum pain management in pregnant people with OUD. However, existing published works are low on the pyramid of evidence (reviews, opinions, and retrospective studies), with a paucity of original research articles (<6%). Opinions are conflicting on the utility and disutility of various analgesic interventions. Studies generating high-quality evidence on this topic are needed to inform care for pregnant people with OUD. Specific research areas are identified, including utility and disutility of short-term opioid use for postpartum pain management, role of continuous wound infiltration and truncal nerve blocks, nonpharmacologic analgesia options, and the best methods to support psychosocial aspects of pain management.

  View details for DOI 10.1213/ANE.0000000000006167

  View details for PubMedID 36135926

• Perioperative Gabapentin Use and In-Hospital Adverse Clinical Events Among Older Adults After Major Surgery. JAMA internal medicine Park, C. M., Inouye, S. K., Marcantonio, E. R., Metzger, E., Bateman, B. T., Lie, J. J., Lee, S. B., Levin, R., Kim, D. H. 2022

  Abstract

  Importance: Gabapentin has been increasingly used as part of a multimodal analgesia regimen to reduce opioid use in perioperative pain management. However, the safety of perioperative gabapentin use among older patients remains uncertain.Objective: To examine in-hospital adverse clinical events associated with perioperative gabapentin use among older patients undergoing major surgery.Design, Setting, and Participants: This retrospective cohort study using data from the Premier Healthcare Database included patients aged 65 years or older who underwent major surgery at US hospitals within 7 days of hospital admission from January 1, 2009, to March 31, 2018, and did not use gabapentin before surgery. Data were analyzed from June 14, 2021, to May 23, 2022.Exposures: Gabapentin use within 2 days after surgery.Main Outcomes and Measures: The primary outcome was delirium, identified using diagnosis codes, and secondary outcomes were new antipsychotic use, pneumonia, and in-hospital death between postoperative day 3 and hospital discharge. To reduce confounding, 1:1 propensity score matching was performed. Risk ratios (RRs) and risk differences (RDs) with 95% CIs were estimated.Results: Among 967 547 patients before propensity score matching (mean [SD] age, 76.2 [7.4] years; 59.6% female), the rate of perioperative gabapentin use was 12.3% (119 087 patients). After propensity score matching, 237 872 (118 936 pairs) gabapentin users and nonusers (mean [SD] age, 74.5 [6.7] years; 62.7% female) were identified. Compared with nonusers, gabapentin users had increased risk of delirium (4040 [3.4%] vs 3148 [2.6%]; RR, 1.28 [95% CI, 1.23-1.34]; RD, 0.75 [95% CI, 0.75 [0.61-0.89] per 100 persons), new antipsychotic use (944 [0.8%] vs 805 [0.7%]; RR, 1.17 [95% CI, 1.07-1.29]; RD, 0.12 [95% CI, 0.05-0.19] per 100 persons), and pneumonia (1521 [1.3%] vs 1368 [1.2%]; RR, 1.11 [95% CI, 1.03-1.20]; RD, 0.13 [95% CI, 0.04-0.22] per 100 persons), but there was no difference in in-hospital death (362 [0.3%] vs 354 [0.2%]; RR, 1.02 [95% CI, 0.88-1.18]; RD, 0.00 [95% CI, -0.04 to 0.05] per 100 persons). Risk of delirium among gabapentin users was greater in subgroups with high comorbidity burden than in those with low comorbidity burden (combined comorbidity index <4 vs ≥4: RR, 1.20 [95% CI, 1.13-1.27] vs 1.40 [95% CI, 1.30-1.51]; RD, 0.41 [95% CI, 0.28-0.53] vs 2.66 [95% CI, 2.08-3.24] per 100 persons) and chronic kidney disease (absence vs presence: RR, 1.26 [95% CI, 1.19-1.33] vs 1.38 [95% CI, 1.27-1.49]; RD, 0.56 [95% CI, 0.42-0.69] vs 1.97 [95% CI, 1.49-2.46] per 100 persons).Conclusion and Relevance: In this cohort study, perioperative gabapentin use was associated with increased risk of delirium, new antipsychotic use, and pneumonia among older patients after major surgery. These results suggest careful risk-benefit assessment before prescribing gabapentin for perioperative pain management.

  View details for DOI 10.1001/jamainternmed.2022.3680

  View details for PubMedID 36121671

• Perioperative gabapentin use and adverse clinical events in older adults after major surgery: A retrospective cohort study Park, C., Lie, J., Sharon, K., Marcantonio, E., Metzger, E. D., Bateman, B., Lee, S., Levin, R., Kim, D. WILEY. 2022: 392-393

  View details for Web of Science ID 000859084401393

• Exposure to non-insulin 2nd-line glucose-lowering medications in early pregnancy and risk of major congenital malformations Hernandez Diaz, S., Rotem, R., Huybrechts, K. F., Bateman, B. T., Furu, K., Chodick, G., Seely, E. W., Patorno, E., Cesta, C. E. SPRINGER. 2022: S144-S145

  View details for Web of Science ID 000841795900275

• Psychostimulant use during pregnancy and the risk of neurodevelopmental disorders in children Suarez, E., Bateman, B., Hernandez-Diaz, S., Straub, L., Zhu, Y., Mogun, H., Huybrechts, K. WILEY. 2022: 10

  View details for Web of Science ID 000859084400016

• The use of type 2 diabetes mellitus medications during pregnancy in the United States Wood, M., Patorno, E., Huybrechts, K. F., Bateman, B. T., Gray, K., Seely, E. W., Vine, S., Hernandez-Diaz, S. WILEY. 2022: 651-652

  View details for Web of Science ID 000859084402504

• Validity of healthcare administrative data to identify infants with low birth weight Straub, L., Bateman, B., Zhu, Y., Hernandez-Diaz, S., Vine, S., Huybrechts, K. WILEY. 2022: 249-250

  View details for Web of Science ID 000859084401099

• Hierarchical clustering analysis to inform classification of congenital malformations for surveillance of medication safety in pregnancy Straub, L., Hernandez-Diaz, S., Wang, S., Gray, K., Holmes, L., Bateman, B., Mogun, H., Huybrechts, K. WILEY. 2022: 102

  View details for Web of Science ID 000859084400197

• Initiation of atenolol versus methyldopa during pregnancy and the risk of intrauterine growth restriction/small for gestational age Bateman, B., Zhu, Y., Huybrechts, K., Hernandez-Diaz, S., Taylor, L., Ouellet-Hellstrom, R., Ma, Y., Qiang, Y., Sun, J., Straub, L., Suarez, E., Vine, S., Hua, W. WILEY. 2022: 20

  View details for Web of Science ID 000859084400036

• Neonatal and maternal adverse outcomes following use of buprenorphine and methadone for treatment of opioid use disorder in pregnancy Suarez, E., Huybrechts, K., Straub, L., Hernandez Diaz, S., Jones, H., Connery, H., Davis, J., Gray, K., Lester, B., Terplan, M., Mogun, H., Bateman, B. WILEY. 2022: 242

  View details for Web of Science ID 000859084401083

• Exposure to non-insulin second-line antidiabetic medications in early pregnancy and risk of major congenital malformations Cesta, C., Rotem, R., Huybrechts, K., Bateman, B., Chodick, G., Seely, E. W., Patorno, E., Hernandez Diaz, S. WILEY. 2022: 247

  View details for Web of Science ID 000859084401094

• Development and validation of claims-based algorithms for estimating gestational age of spontaneous abortion and termination Huybrechts, K., Zhu, Y., Hernandez-Diaz, S., Bateman, B., Gray, K., Straub, L., Taylor, L., Ouellet-Hellstrom, R., Ma, Y., Qiang, Y., Vine, S., Mogun, H., Hua, W. WILEY. 2022: 101

  View details for Web of Science ID 000859084400195

• Topiramate during pregnancy and the risk of neurodevelopmental disorders in children Hernandez-Diaz, S., Straub, L., Bateman, B., Suarez, E., Zhu, Y., Mogun, H., Pennell, P., Huybrechts, K. WILEY. 2022: 11

  View details for Web of Science ID 000859084400018

• Hospital-level variation in rates of postpartum hemorrhage in California. Transfusion Davis, R., Guo, N., Bentley, J., Sie, L., Ansari, J., Bateman, B., Main, E., Butwick, A. J. 2022

  Abstract

  BACKGROUND: To examine the extent of hospital-level variation in risk-adjusted rates of postpartum hemorrhage (PPH).STUDY DESIGN AND METHODS: We performed a cross-sectional study examining live births in 257 California hospitals between 2011 and 2015 using linked birth certificate and maternal discharge data. PPH was measured using International Classification of Diseases Codes version 9. Mixed-effects logistic regression models were used to examine the presence and extent of hospital-level variation in PPH before and after adjustment for patient-level risk factors and select hospital characteristics (teaching status and annual delivery volume). Risk-adjusted rates of PPH were estimated for each hospital. The extent of hospital variation was evaluated using the median odds ratio (MOR) and intraclass correlation coefficient (ICC).RESULTS: Our study cohort comprised 1,904,479 women who had a live birth delivery hospitalization at 247 hospitals. The median, lowest, and highest hospital-specific rates of PPH were 3.48%, 0.54%, and 12.0%, respectively. Similar rates were observed after adjustment for patient and hospital factors (3.44%, 0.60%, and 11.48%). After adjustment, the proportion of the total variation in PPH rates attributable to the hospital was low, with a MOR of 2.02 (95% confidence interval [CI]: 1.89-2.15) and ICC of 14.3% (95% CI: 11.9%-16.3%).DISCUSSION: Wide variability exists in the rate of PPH across hospitals in California, not attributable to patient factors, hospital teaching status, and hospital annual delivery volume. Determining whether differences in hospital quality of care explain the unaccounted-for variation in hospital-level PPH rates should be a public health priority.

  View details for DOI 10.1111/trf.17036

  View details for PubMedID 35920049

• Characteristics of Prescription Opioid Analgesics in Pregnancy and Risk of Neonatal Opioid Withdrawal Syndrome in Newborns. JAMA network open Esposito, D. B., Huybrechts, K. F., Werler, M. M., Straub, L., Hernandez-Diaz, S., Mogun, H., Bateman, B. T. 2022; 5 (8): e2228588

  Abstract

  Importance: Prescription opioids are often used during pregnancy even though they are associated with neonatal opioid withdrawal syndrome (NOWS). Most studies of adverse outcomes of opioid use for pain have assessed only the class-wide outcome despite the pharmacodynamic and pharmacokinetic heterogeneity across opioid medications.Objective: To compare the risk of NOWS across common types of opioids when prescribed as monotherapy during the last 3 months of pregnancy.Design, Setting, and Participants: This cohort study analyzed administrative claims data of Medicaid-insured mothers and newborns in 46 states and Washington DC from January 1, 2000, through December 31, 2014. Participants were mothers with 2 or more dispensed opioid prescriptions within 90 days before delivery and their eligible live-born neonates. Data were analyzed from February 2020 to March 2021.Exposure: Different types of opioid medications were compared by agonist strength (strong vs weak) and half-life (medium vs short and long vs short) of the opioid active ingredient.Main Outcomes and Measures: The primary outcome was NOWS, which was identified using an International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code in the 30 days after delivery. Relative risks (RRs) were adjusted for an exposure propensity score, including demographic characteristics, comorbidities, other medication use, and opioid treatment characteristics (including morphine milligram equivalents), using fine stratification.Results: The cohort comprised 48 202 opioid-exposed pregnancies with live newborns. A total of 1069 neonates (2.2%) had NOWS and 559 (1.2%) had severe NOWS. Opioid exposure during pregnancy included 16 202 pregnancies exposed to codeine, 4540 to oxycodone, 1244 to tramadol, 260 to methadone (dispensed for pain), 90 to hydromorphone, and 63 to morphine compared with 25 710 exposed to hydrocodone. Demographic characteristics varied across opioids, with tramadol, oxycodone, methadone, hydromorphone, and morphine being more commonly dispensed at older maternal age (≥35 years). Compared with hydrocodone, codeine had a lower adjusted RR of NOWS (0.57; 95% CI, 0.46-0.70), with a similar adjusted RR for tramadol (RR, 1.06; 95% CI, 0.73-1.56), and 2- to 3-fold higher adjusted RRs for oxycodone (1.87; 95% CI, 1.66-2.11), morphine (2.84; 95% CI, 1.30-6.22), methadone (3.02; 95% CI, 2.45-3.73), and hydromorphone (2.03; 95% CI, 1.09-3.78). Strong agonists were associated with a higher risk of NOWS than weak agonists (RR, 1.97; 95% CI, 1.78-2.17), and long half-life opioids were associated with an increased risk compared with short half-life products (RR, 1.33; 95% CI, 1.12-1.56). Findings were consistent across sensitivity and subgroup analyses.Conclusions and Relevance: Results of this study show higher risk of NOWS and severe NOWS among neonates with in utero exposure to strong agonists and long half-life prescription opioids. Information on the opioid-specific risk of NOWS may help prescribers select opioids for pain management in late stages of pregnancy.

  View details for DOI 10.1001/jamanetworkopen.2022.28588

  View details for PubMedID 36001312

• Tranexamic Acid Administered During Cesarean Delivery in High-Risk Patients: Maternal Pharmacokinetics, Pharmacodynamics, and Coagulation Status. American journal of obstetrics and gynecology Seifert, S. M., Lumbreras-Marquez, M. I., Goobie, S. M., Carusi, D. A., Fields, K. G., Bateman, B. T., Farber, M. K. 2022

  Abstract

  BACKGROUND: Tranexamic acid is frequently administered for postpartum hemorrhage. The World Health Organization recommends 1g intravenous dosing repeated once at 30 minutes for ongoing bleeding. Understanding the pharmacokinetics and pharmacodynamics of tranexamic acid in patients at high risk for PPH may enable dosage tailoring for optimal antifibrinolysis with minimal adverse events such as thrombosis or renal cortical necrosis.OBJECTIVES: We report tranexamic acid pharmacokinetics and pharmacodynamics after 1g IV dosing during cesarean delivery in patients at risk for hemorrhage. The primary endpoint was tranexamic acid plasma concentration >10mug/mL, known to inhibit 80% of fibrinolysis. Correlation with patient demographics and rotational thromboelastometry coagulation changes were also analyzed.STUDY DESIGN: In this prospective study we recruited 20 women aged 18-50 years, ≥23 weeks' gestation undergoing cesarean delivery with at least (1) major (placenta previa, suspected placenta accreta spectrum, active bleeding) or (2) minor (>2 prior cesarean deliveries, prior postpartum hemorrhage, chorioamnionitis, polyhydramnios, macrosomia, obesity, or suspected placental abruption) risk factors for PPH. Exclusion criteria were allergy to tranexamic acid, inherited thrombophilia, prior or current thrombosis, seizure history, renal or liver dysfunction, anticoagulation, or category III fetal heart tracing. Tranexamic acid 1g was administered after umbilical cord clamping. Blood samples were drawn at 3, 7, 15, and 30 minutes, then at 30-minute intervals up to 5 hours. Plasma concentrations were evaluated as mean (standard error). Serial rotational thromboelastometry was performed and correlated with tranexamic acid plasma concentrations.RESULTS: Median age of participants was 37.5 years (interquartile range [IQR] 35-39.5) and median body mass index (BMI) was 28.6 kg/m2 (IQR 24.9-35). Median blood loss (estimated or quantitative) was 1,500 mL (IQR 898.5-2,076). Nine of 20 (45%) received a transfusion of packed red blood cells (PRBCs). The mean peak tranexamic acid plasma concentration at 3 minutes was 59.8 +/- 4.7 mug/mL. All patients had a plasma concentration above 10mug/mL for one hour following infusion. Plasma concentration was >10mug/mL in more than half of patients at 3 hours and fell below 10mug/mL in all patients at 5 hours. There was a moderate negative correlation between body mass index and the plasma concentration area under the curve (AUC; r = -0.49, 95% confidence interval [CI] -0.77, -0.07, P=0.026). Rotational thromboelastometry EXTEM-maximum clot firmness had a weak positive correlation with longitudinal plasma concentration (r = 0.32, 95% CI 0.21, 0.46, P<0.001). EXTEM-maximum clot lysis was 0% post-infusion in 18 (90%) of patients and no patients in the study demonstrated a maximum lysis >15% at any interval from 3 minutes to 5 hours. There was no significant correlation between EXTEM-LY30 and longitudinal TXA plasma concentrations (r = 0.10, 95% CI -0.20, 0.19, P=0.252).CONCLUSIONS: After standard 1g IV dosing of tranexamic acid during cesarean delivery in patients at high-risk for hemorrhage, a plasma concentration of >10mug/mL was sustained for at least 60 minutes. Plasma tranexamic acid levels correlated inversely with body mass index. Concurrent use of rotational thromboelastometry may demonstrate tranexamic acid impact on clot firmness but not a hyperfibrinolysis-derived trigger for therapy.

  View details for DOI 10.1016/j.ajog.2022.06.001

  View details for PubMedID 35679896

• Tendances de la prescription dopioides postoperatoires en Ontario entre 2013 et 2019 : une etude de cohorte axee sur la population. Canadian journal of anaesthesia = Journal canadien d'anesthesie Jivraj, N. K., Ladha, K., Goel, A., Hill, A., Wijeysundera, D. N., Bateman, B. T., Wunsch, H. 2022

  Abstract

  PURPOSE: Many hospital and provincial-level recommendations now advise a tailored approach to postoperative opioid prescribing; recent trends in postoperative prescribing at the population level have not been well described.METHODS: This population-based cohort study included opioid-naive patients ≥ 18 yr of age who underwent one of 16 surgical procedures with varying anticipated postoperative pain between July 2013 and March 2020. We evaluated the rate of filled opioid prescriptions within seven days postoperatively, the total morphine milligram equivalent (MME) dose, duration, and type of the first opioid prescription. We then compared the MMEs in initial opioid prescriptions with available procedure-specific recommendations.RESULTS: The sample included 900,989 opioid-naive patients (mean [standard deviation (SD)] age of 50 [17] 31 yr; 66% women). The percentage of patients filling an opioid prescription within 7 days postoperatively increased from 65% in 2013 to 69% in 2016, and returned to the baseline (65%) in 2019. The mean (SD) MMEs dispensed increased until 2015/2016 and then declined (226 [176] MMEs in 2013, 240 [202] MMEs in 2016, and 175 [175] MMEs in 2019). The most frequently prescribed opioid in 2013 was oxycodone compared with hydromorphone in 2019. Among patients who filled an opioid prescription in 2013, 67% were prescribed an opioid dose higher than those in one set of available prescribing recommendations, while in 2019, 41% were prescribed doses above those stated in recommendations.CONCLUSION: While the proportion of patients filling an opioid prescription postoperatively remained s during the study period, MMEs decreased after 2016. Opioid prescribing remained significantly higher than available prescribing recommendations, particularly among low pain procedures. These findings highlight the need to identify strategies that improve adherence to surgery-specific prescribing guidelines in North America.

  View details for DOI 10.1007/s12630-022-02266-5

  View details for PubMedID 35534769

• Topiramate during Pregnancy and the Risk of Neurodevelopmental Disorders in Children HERNANDEZ-DIAZ, S., STRAUB, L., BATEMAN, B. T., SUAREZ, E. A., ZHU, Y., PENNELL, P. B., HUYBRECHTS, K. F. WILEY. 2022: 387-388

  View details for Web of Science ID 000789456900062

• Classification of Congenital Malformations Informed by Machine Learning with Human Adjudication Straub, L., huybrechts, K. F., Wang, S., Gray, K. J., Holmes, L. B., Bateman, B. T., Mogun, H., Hernandez-diaz, S. WILEY. 2022: 384

  View details for Web of Science ID 000789456900056

• Obstetric comorbidity index and the odds of general vs. neuraxial anesthesia in women undergoing cesarean delivery: a retrospective cohort study. International journal of obstetric anesthesia Singh, S., Farber, M. K., Bateman, B. T., Lumbreras-Marquez, M. I., Richey, C. J., Easter, S. R., Fields, K. G., Tsen, L. C. 2022: 103546

  Abstract

  BACKGROUND: Maternal and fetal concerns have prompted a significant reduction in general anesthesia (GA) use for cesarean delivery (CD). The obstetric comorbidity index (OB-CMI) is a validated, dynamic composite score of comorbidities encountered in an obstetric patient. We sought to estimate the association between OB-CMI and odds of GA vs. neuraxial anesthesia (NA) use for CD.METHODS: In this single-center, retrospective cohort study conducted at a large academic hospital in the United States of America, OB-CMI was calculated on admission and every 12 h for women undergoing CD at ≥23 weeks' gestation (n=928). The CD urgency, anesthesia type, and most recent OB-CMI were extracted from the medical record. The association between OB-CMI and GA use was estimated by logistic regression, with and without adjustment for CD urgency, parity and race.RESULTS: Each one-point increase in OB-CMI was associated with a 32% (95% confidence interval [CI] 17% to 48%) increase in the odds of GA use (Model 1, area under the receiver operating characteristic curve [AUC] 0.708, 95% CI 0.610 to 0.805). The AUC improved to 0.876 (95% CI 0.815 to 0.937) with the addition of emergent CD (Model 2, P <0.001 vs. Model 1), but not parity and race (Model 3, AUC 0.880, 95% CI 0.824 to 0.935;P=0.616 vs. Model 2).CONCLUSIONS: The OB-CMI is associated with increased odds of GA vs. NA use for CD, particularly when emergent. Collected in real time, the OB-CMI may enable prophylaxis (e.g. comorbidity modification, earlier epidural catheter placement, elective CD) or preparation for GA use.

  View details for DOI 10.1016/j.ijoa.2022.103546

  View details for PubMedID 35473812

• Association of Antipsychotic Drug Exposure in Pregnancy With Risk of Neurodevelopmental Disorders: A National Birth Cohort Study. JAMA internal medicine Straub, L., Hernandez-Diaz, S., Bateman, B. T., Wisner, K. L., Gray, K. J., Pennell, P. B., Lester, B., McDougle, C. J., Suarez, E. A., Zhu, Y., Zakoul, H., Mogun, H., Huybrechts, K. F. 2022

  Abstract

  Importance: Although antipsychotic drugs cross the placenta and animal data suggest potential neurotoxic effects, information regarding human neurodevelopmental teratogenicity is limited.Objective: To evaluate whether children prenatally exposed to antipsychotic medication are at an increased risk of neurodevelopmental disorders (NDD).Design, Settings, and Participants: This birth cohort study used data from the Medicaid Analytic eXtract (MAX, 2000-2014) and the IBM Health MarketScan Research Database (MarketScan, 2003-2015) for a nationwide sample of publicly (MAX) and privately (MarketScan) insured mother-child dyads with up to 14 years of follow-up. The MAX cohort consisted of 2 034 883 children who were not prenatally exposed and 9551 who were prenatally exposed to antipsychotic medications; the MarketScan consisted of 1 306 408 and 1221 children, respectively. Hazard ratios were estimated through Cox proportional hazards regression, using propensity score overlap weights for confounding control. Estimates from both cohorts were combined through meta-analysis.Exposures: At least 1 dispensing of a medication during the second half of pregnancy (period of synaptogenesis), assessed for any antipsychotic drug, at the class level (atypical and typical), and for the most commonly used drugs (aripiprazole, olanzapine, quetiapine, risperidone, and haloperidol).Main Outcomes and Measures: Autism spectrum disorder, attention-deficit/hyperactivity disorder, learning disability, speech or language disorder, developmental coordination disorder, intellectual disability, and behavioral disorder, identified using validated algorithms, and the composite outcome of any NDD. Data were analyzed from April 2020 to January 2022.Results: The MAX cohort consisted of 2 034 883 unexposed pregnancies and 9551 pregnancies with 1 or more antipsychotic drug dispensings among women with a mean (SD) age of 26.8 (6.1) years, 204 (2.1%) of whom identified as Asian/Pacific Islander, 2720 (28.5%) as Black, 500 (5.2%) as Hispanic/Latino, and 5356 (56.1%) as White. The MarketScan cohort consisted of 1 306 408 unexposed and 1221 exposed pregnancies among women with a mean (SD) age of 33.1 (5.0) years; race and ethnicity data were not available. Although the unadjusted results were consistent with an approximate 2-fold increased risk for most exposure-outcome contrasts, risks were no longer meaningfully increased after adjustment (eg, pooled unadjusted vs adjusted hazard ratios [95% CI] for any NDD after any antipsychotic exposure: 1.91 [1.79-2.03] vs 1.08 [1.01-1.17]), with the possible exception of aripiprazole (1.36 [1.14-1.63]). Results were consistent across sensitivity analyses.Conclusions and Relevance: The findings of this birth cohort study suggest that the increased risk of NDD seen in children born to women who took antipsychotic drugs late in pregnancy seems to be explained by maternal characteristics and is not causally related with prenatal antipsychotic exposure. This finding highlights the importance of closely monitoring the neurodevelopment of the offspring of women with mental illness to ensure early intervention and support. The potential signal for aripiprazole requires replication in other data before causality can be assumed.

  View details for DOI 10.1001/jamainternmed.2022.0375

  View details for PubMedID 35343998

• Frequency and Risk Factors for Difficult Intubation in Women Undergoing General Anesthesia for Cesarean Delivery: A Multicenter Retrospective Cohort Analysis. Anesthesiology Reale, S. C., Bauer, M. E., Klumpner, T. T., Aziz, M. F., Fields, K. G., Hurwitz, R., Saad, M., Kheterpal, S., Bateman, B. T. 2022

  Abstract

  BACKGROUND: Estimates for the incidence of difficult intubation in the obstetric population vary widely, though prior studies reporting rates of difficult intubation in obstetrics are older and limited by smaller samples. The goals of this study were to provide a contemporary estimate of the frequency of difficult and failed intubation in women undergoing general anesthesia for cesarean delivery and to elucidate risk factors for difficult intubation in women undergoing general anesthesia for cesarean delivery.METHODS: This is a multicenter, retrospective cohort study utilizing the Multicenter Perioperative Outcomes Group database. The study population included women aged 15-44 undergoing general anesthesia for cesarean delivery between 2004 and 2019 at one of 45 medical centers. Co-primary outcomes included the frequencies of difficult and failed intubation. Difficult intubation was defined as Cormack-Lehane view ≥3, intubation attempts ≥3, rescue fiberoptic intubation, rescue supraglottic airway, or surgical airway. Failed intubation was defined as any attempt at intubation without successful endotracheal tube placement. Rates of difficult and failed intubation were assessed. Several patient demographic, anatomical, and obstetric factors were evaluated for potential associations with difficult intubation.RESULTS: We identified 14,748 cases of cesarean delivery performed under general anesthesia. There were 295 cases of difficult intubation, with a frequency of 1:49 (95% CI: 1:55, 1:44) (n=14,531). There were 18 cases of failed intubation, with a frequency of 1:808 (95% CI: 1:1,276, 1:511) (n=14,537). Factors with the highest point estimates for the odds of difficult intubation included increased body mass index, Mallampati score III or IV, small hyoid to mentum distance, limited jaw protrusion, limited mouth opening, and cervical spine limitations.CONCLUSIONS: In this large, multi-center, contemporary study of over 14,000 general anesthetics for cesarean delivery, we observed an overall risk of difficult intubation of 1:49 and a risk of failed intubation of 1:808. Most risk factors for difficult intubation were non-obstetric in nature. These data demonstrate that difficult intubation in obstetrics remains an ongoing concern.

  View details for DOI 10.1097/ALN.0000000000004173

  View details for PubMedID 35188971

• The use of glucose-lowering medications for the treatment of type 2 diabetes mellitus during pregnancy in the United States. Endocrinology, diabetes & metabolism Wood, M. E., Patorno, E., Huybrechts, K. F., Bateman, B. T., Gray, K. J., Seely, E. W., Vine, S., Hernandez-Diaz, S. 1800: e00319

  Abstract

  INTRODUCTION: Some guidelines allow for the use of either insulin or noninsulin antidiabetic agents for gestational diabetes, but only insulin is recommended for pregnant women with preexisting type 2 diabetes mellitus (T2DM). We aimed to document treatment patterns in routine care for women with preexisting T2DM.METHODS: We identified pregnancy cohorts within 2 US claims databases for publicly and privately insured individuals: the Medicaid Analytical eXtract (2000-2014) and OptumClinformatics (2004-2014). T2DM was classified with a validated algorithm using ICD-9-CM and CPT codes. We assessed medication usage over the years of the study, and changes in medication use before and after the beginning of pregnancy, using prescription fills as a proxy for the use of insulin, metformin, sulphonylureas and other noninsulin antidiabetic agents before pregnancy and during each trimester.RESULTS: Among 12,631 women with T2DM, insulin use in pregnancy was stable over the study years (55%-60% in the 2nd trimester), but 2nd trimester use of metformin increased from <5% to 20%. Over the study period, 41% of women filled a prescription for metformin before pregnancy, 37% in the 1st trimester and 17% in the 2nd trimester. By the 2nd trimester, few women used sulphonylureas (11%) or other noninsulin antidiabetic agents (1%). Of the women on metformin only before pregnancy, 36% switched to insulin only by 2nd trimester, 11% added insulin and 16% continued on metformin only. Of the women on metformin and insulin before pregnancy, 61% switched to insulin only by 2nd trimester, 22% continued with metformin and insulin and <5% used only metformin.CONCLUSION: The use of insulin-metformin combinations and other noninsulin antidiabetic drugs during pregnancy has increased. Safety studies for these medication regimens are needed.

  View details for DOI 10.1002/edm2.319

  View details for PubMedID 34953068

• Association of Neuraxial Labor Analgesia for Vaginal Childbirth With Risk of Autism Spectrum Disorder. JAMA network open Straub, L., Huybrechts, K. F., Mogun, H., Bateman, B. T. 1800; 4 (12): e2140458

  Abstract

  Importance: Recent studies have reported conflicting findings regarding a potential association between analgesia used during labor and autism spectrum disorder in the offspring.Objective: To evaluate whether neuraxial labor analgesia increases the risk of autism spectrum disorder in the offspring.Design, Setting, and Participants: This cohort study included mother-child dyads who underwent vaginal delivery and were exposed to neuraxial labor analgesia. Delivery data were collected from the Medicaid Analytic eXtract (2005-2014) for mothers with public insurance and the IBM Health MarketScan Research Database (2005-2015) for mothers with private insurance. Data analysis was conducted from January to October 2021.Exposures: Presence of a procedure code indicating neuraxial labor analgesia.Main Outcomes and Measures: Children with autism spectrum disorder, identified using a validated algorithm (positive predictive value: 94% [95% CI, 83%-99%]). Cumulative incidence curves stratified by exposure were assessed using Kaplan-Meier analyses. Hazard ratios were estimated through Cox proportional hazards regression, using propensity-score fine stratification for confounding control. Estimates from both insurance cohorts were combined through fixed-effects meta-analysis. Subsequently, results from these analyses were combined with existing published studies.Results: The cohort of mother-child dyads with public insurance consisted of 910 696 deliveries (mean [SD] maternal age, 24.3 [5.7] years; 286 025 [31.4%] Black mothers; 374 282 [41.1%] White mothers), with 484 752 (53.2%) being exposed to neuraxial labor analgesia. The cohort of mother-child dyads with private insurance included 696 883 deliveries (mean [SD] maternal age, 31.0 [4.5] years; race and ethnicity data not available), with 513 347 (73.7%) being exposed. Cumulative incidence of autism spectrum disorder by 10 years of age was 1.93% (95% CI, 1.73%-2.13%) among children in the exposed group vs 1.64% (95% CI, 1.51%-1.76%) among children in the unexposed group in the publicly insured cohort. Respective numbers were 1.33% (95% CI, 1.19%-1.46%) and 1.19% (95% CI, 0.99%-1.38%) in the privately insured cohort. Adjusting for potential confounders and pooling across both cohorts resulted in a hazard ratio of 1.08 (95% CI, 1.02-1.15). Results were consistent when additionally adjusting for empirically identified variables through high-dimensional propensity score analyses (pooled hazard ratio, 1.07; 95% CI, 1.00-1.14) or expanding the cohorts to include cesarean deliveries and assisted vaginal deliveries (pooled hazard ratio, 1.07; 95% CI, 1.03-1.12). Meta-analysis of this study and recently published observational studies yielded similar findings with a pooled hazard ratio of 1.10 (95% CI, 1.06-1.13).Conclusions and Relevance: Although a small increase in risk cannot be ruled out, the combined evidence from observational studies does not support the notion that neuraxial labor analgesia is associated with an increased risk of autism spectrum disorder.

  View details for DOI 10.1001/jamanetworkopen.2021.40458

  View details for PubMedID 34935925

• Surgeon Postoperative Opioid Prescribing Intensity and Risk of Persistent Opioid Use among Opioid-naive Adult Patients: A Population-based Cohort Study. Annals of surgery Wunsch, H., Hill, A. D., Bethell, J., Fu, L., Bateman, B. T., Ladha, K. S., Wijeysundera, D. N., Neuman, M. D. 2021

  Abstract

  OBJECTIVE: The aim of this study was to determine the relationship between surgeon opioid prescribing intensity and subsequent persistent opioid use among patients undergoing surgery.SUMMARY BACKGROUND DATA: The extent to which different postoperative prescribing practices lead to persistent opioid use among surgical patients is poorly understood.METHODS: Retrospective population-based cohort study assessing opioid-naive adults who underwent one of four common surgeries. For each surgical procedure, the surgeons' opioid prescribing intensity was categorized into quartiles based on the median daily dose of morphine equivalents of opioids dispensed within 7 days of the surgical visit for all the surgeons' patients. The primary outcome was persistent opioid use in the year following surgery, defined as 180 days or more of opioids supplied within the year after the index date excluding prescriptions filled within 30 days of the index date. Secondary outcomes included a refill for an opioid within 30 days and emergency department visits and hospitalizations within 1 year.RESULTS: Among 112,744 surgical patients, patients with surgeons in the highest intensity quartile (Q4) were more likely to fill an opioid prescription within 7 days after surgery compared with those in the lowest quartile (Q1) (83.3% Q4 vs 65.4% Q1). In the primary analysis, the incidence of persistent opioid use in the year after surgery was rare in both highest and lowest quartiles (0.3% Q4 vs 0.3% Q1), adjusted odds ratio (AOR) of 1.18, 95% CI 0.83-1.66). However, multiple analyses using stricter definitions of persistent use that included the requirement of a prescription filled within 7 days of discharge after surgery showed a significant association with surgeon quartile (up to an AOR 1.36, 95% CI 1.25, 1.47). Patients in Q4 were more likely to refill a prescription within 30 days (4.8% Q4 vs 4.0% Q1, AOR 1.14, 95% CI 1.04-1.24).CONCLUSIONS: Surgeons' overall prescribing practices may contribute to persistent opioid use and represent a target for quality improvement. However, the association was highly sensitive to the definition of persistent use used.

  View details for DOI 10.1097/SLA.0000000000005318

  View details for PubMedID 35129483

• Feasibility of using healthcare utilization data to identify neurodevelopmental disorders for transgenerational pharmacoepidemiology Straub, L., Bateman, B. T., Hernandez-Diaz, S., Suarez, E. A., York, C., Zhu, Y., Mogun, H., Huybrechts, K. F. WILEY. 2021: 66

  View details for Web of Science ID 000687807300132

• The comparative safety of antiseizure medication polytherapy versus valproate in pregnancy and risk of major congenital malformations Cohen, J. M., Alvestad, S., Suarez, E. A., Schaffer, A., Selmer, R., Havard, A., Bateman, B. T., Zoega, H., Kieler, H., Odsbu, I., Huybrechts, K. F., Kjerpeseth, L. J., Straub, L., Leinonen, M. K., Bjork, M., Norgaard, M., Gissler, M., Ulrichsen, S. P., Hernandez-Diaz, S., Tomson, T., Furu, K. WILEY. 2021: 73-74

  View details for Web of Science ID 000687807300147

• The impact of in-utero antipsychotic drug exposure on congenital malformations: An international cohort study Huybrechts, K. F., Straub, L., Karlsson, P., Pazzagli, L., Hernandez-Diaz, S., Cohen, J. M., Bateman, B. T., Selmer, R. M., Suarez, E. A., Furu, K., Norgaard, M., Gissler, M., Leinonen, M. K., Zoega, H., Kieler, H. WILEY. 2021: 74-75

  View details for Web of Science ID 000687807300148

• Antidepressant use during pregnancy and the risk of neurodevelopmental disorders in children Suarez, E. A., Bateman, B. T., Hernandez-Diaz, S., Straub, L., Zhu, Y., Mogun, H., Huybrechts, K. F. WILEY. 2021: 72

  View details for Web of Science ID 000687807300144

• Validating an optimized live birth gestational age algorithm in a nationwide Medicaid sample and quantifying the misclassification of exposure due to estimated gestational age Zhu, Y., Thai, T., Bateman, B. T., Hernandez-Diaz, S., Straub, L., Franklin, J., Gray, K., Winterstein, A. G., Taylor, L. G., Ouellet-Hellstrom, R. P., Ma, Y., Qiang, Y., Hua, W., Huybrechts, K. F. WILEY. 2021: 68

  View details for Web of Science ID 000687807300136

• The impact of in-utero antipsychotic exposure on neurodevelopmental disorders in children Straub, L., Bateman, B. T., Hernandez-Diaz, S., Suarez, E. A., York, C., Zhu, Y., Mogun, H., Huybrechts, K. F. WILEY. 2021: 75

  View details for Web of Science ID 000687807300149

• Implication of maternal continuous enrollment on stillbirth gestational age distributions and maternal characteristics in Medicaid enrollees Thai, T., Rasmussen, S. A., Smolinski, N. E., Nduaguba, S., Zhu, Y., Bateman, B. T., Huybrechts, K. F., Hernandez-Diaz, S., Winterstein, A. G. WILEY. 2021: 66-67

  View details for Web of Science ID 000687807300133

• Authorship and Publication Matters: Credit and Credibility ANESTHESIOLOGY Kharasch, E. D., Avram, M. J., Bateman, B. T., Clark, J., Culley, D. J., Davidson, A. J., Houle, T. T., Jiang, Y., Levy, J. H., London, M. J., Sleigh, J. W., Vutskits, L. 2021; 135 (1): 1-8

  View details for DOI 10.1097/ALN.0000000000003830

  View details for Web of Science ID 000658897100001

  View details for PubMedID 34046664

• Chronic opioid use and complication risks in women with endometriosis: A cohort study in US administrative claims. Pharmacoepidemiology and drug safety Chiuve, S. E., Kilpatrick, R. D., Hornstein, M. D., Petruski-Ivleva, N., Wegrzyn, L. R., Dabrowski, E. C., Velentgas, P., Snabes, M. C., Bateman, B. T. 2021; 30 (6): 787-796

  Abstract

  Women with endometriosis are prescribed opioids for pain relief but may be vulnerable to chronic opioid use given their comorbidity profile.A cohort study was conducted in the Clinformatics™ DataMart database between 2006 and 2017 comparing women aged 18-50 years with endometriosis (N = 36 373) to those without (N = 2 172 936) in terms of risk of chronic opioid use, opioid dependence diagnosis, and opioid overdose. Chronic opioid use was defined as ≥120 days' supply dispensed or ≥10 fills of an opioid during any 365-day interval. Among women with endometriosis, we evaluated factors associated with higher risk of chronic opioid use and quantified the risk of complications associated with the use of opioids.Women with endometriosis were at greater risk for chronic opioid use (OR: 3.76; 95%CI: 3.57-3.96), dependence (OR: 2.73, 95%CI: 2.38-3.13) and overdose (OR: 4.34, 95%CI: 3.06-6.15) compared to women without. Chronic users displayed dose escalation and increase in days supplied over time, as well as co-prescribing with benzodiazepines and sedatives. Approximately 34% of chronic users developed constipation, 20% experienced falls, and 8% reported dizziness. Among endometriosis patients, women in younger age groups, those with other comorbidities associated with pain symptoms, as well as those with depression or anxiety were at a higher risk of developing chronic opioid use.Women with endometriosis had a four times greater risk of chronic opioid use compared to women without. Multimorbidity among these patients was associated with the elevated risk of chronic opioid use and should be taken into account during treatment selection.

  View details for DOI 10.1002/pds.5209

  View details for PubMedID 33611812

  View details for PubMedCentralID PMC8251707

• Unintended consequences of the 2016 CDC opioid prescribing guidelines on opioid dispensing after surgery Sutherland, T., Wunsch, H. M., Pinto, R., Newcomb, C., Brensinger, C., Gaskins, L., Bateman, B., Neuman, M. D. LIPPINCOTT WILLIAMS & WILKINS. 2021: 843-844

  View details for Web of Science ID 000752526600363

• Association of Epidural Labor Analgesia With Offspring Risk of Autism Spectrum Disorders. JAMA pediatrics Wall-Wieler, E., Bateman, B. T., Hanlon-Dearman, A., Roos, L. L., Butwick, A. J. 2021

  Abstract

  Importance: Epidural labor analgesia (ELA) has been associated with an increased offspring risk of autism spectrum disorder (ASD). Whether this finding may be explained by residual confounding remains unclear.Objective: To assess the association between ELA and offspring risk of ASD.Design, Setting, and Participants: Longitudinal cohort study of vaginal deliveries of singleton live infants born from 2005 to 2016 from a population-based data set linking information from health care databases in Manitoba, Canada; offspring were followed from birth until 2019 or censored by death or emigration. Data were analyzed from October 19, 2020, to January 22, 2021.Exposures: Epidural labor analgesia.Main Outcomes and Measures: At least 1 inpatient or outpatient diagnosis of ASD in offspring aged at least 18 months. For the full population and a sibling cohort, inverse probability of treatment-weighted Cox proportional hazards regression analyses were used to control for potential confounders.Results: Of the 123 175 offspring included in this study (62 647 boys [50.9%]; mean [SD] age of mothers, 28.2 [5.8] years), 47 011 (38.2%) were exposed to ELA; 2.1% (985 of 47 011) of exposed vs 1.7% (1272 of 76 164) of unexposed offspring were diagnosed with ASD in the follow-up period (hazard ratio [HR], 1.25; 95% CI, 1.15-1.36). After adjusting for maternal sociodemographic, prepregnancy, pregnancy, and perinatal covariates, ELA was not associated with an offspring risk of ASD (inverse probability of treatment-weighted HR, 1.08; 95% CI, 0.97-1.20). In the within-siblings design adjusting for baseline covariates, ELA was not associated with ASD (inverse probability of treatment-weighted HR, 0.97; 95% CI, 0.78-1.22). Results from sensitivity analyses restricted to women without missing data who delivered at or after 37 weeks of gestation, firstborn infants only, and offspring with ASD classified with at least 2 diagnostic codes were consistent with findings from the main analyses.Conclusions and Relevance: In a Canadian population-based birth cohort study, no association between ELA exposure and an increased offspring risk of ASD was found.

  View details for DOI 10.1001/jamapediatrics.2021.0376

  View details for PubMedID 33871547

• Trajectories of Prescription Opioid Utilization During Pregnancy Among Pre-Pregnancy Chronic Users and Risk of Neonatal Opioid Withdrawal Syndrome. American journal of epidemiology Straub, L., Huybrechts, K. F., Hernandez-Diaz, S., Zhu, Y., Vine, S., Desai, R. J., Gray, K. J., Bateman, B. T. 2021

  Abstract

  Little is known about the impact of dose, duration and timing of prenatal prescription opioid exposure on the risk of neonatal opioid withdrawal syndrome (NOWS). Using a cohort of 18,869 pre-pregnancy chronic opioid users nested in the 2000-2014 Medicaid Analytic eXtract, we assessed average opioid dosage within bi-weekly gestational age intervals, created group-based trajectory models and evaluated the association between trajectory groups and NOWS risk. Women were grouped into 6 distinct trajectories which, based on observed patterns, were categorized as (1) continuous very low dose use, (2) continuous low use, (3) initial moderate use with gradual decrease to very low/no use, (4) initial high use with gradual decrease to very low use, (5) continuous moderate use, and (6) continuous high use. Absolute risk of NOWS per 1,000 livebirths was 7.7 for group 1 (=reference group); 28.8 for group 2 (relative risk [RR]: 3.7, 95% CI 2.8-5.0), 16.5 for group 3 (RR=2.2, 1.5-3.1), 64.9 for group 4 (RR=8.4, 5.6-12.6), 77.3 for group 5 (RR=10.0, 7.5-13.5), and 172.4 for group 6 (RR=22.4, 16.1-31.2). Trajectory models - which capture dose, duration and timing of exposure - are useful to gain insight into clinically relevant groupings to evaluate the risk of prenatal opioid exposure.

  View details for DOI 10.1093/aje/kwab249

  View details for PubMedID 34643225

• Labor prior to cesarean delivery associated with higher post-discharge opioid consumption. PloS one Ende, H. B., Landau, R., Cole, N. M., Burns, S. M., Bateman, B. T., Bauer, M. E., Booth, J. L., Flood, P., Leffert, L. R., Houle, T. T., Tsen, L. C. 2021; 16 (7): e0253990

  Abstract

  BACKGROUND: Severe acute post-cesarean delivery (CD) pain has been associated with an increased risk for persistent pain and postpartum depression. Identification of women at increased risk for pain can be used to optimize post-cesarean analgesia. The impact of labor prior to CD (intrapartum CD) on acute post-operative pain and opioid use is unclear. We hypothesized that intrapartum CD, which has been associated with both increased inflammation and affective distress related to an unexpected surgical procedure, would result in higher postoperative pain scores and increased opioid intake.METHODS: This is a secondary analysis of a prospective cohort study examining opioid use up to 2 weeks following CD. Women undergoing CD at six academic medical centers in the United States 9/2014-3/2016 were contacted by phone two weeks following discharge. Participants completed a structured interview that included questions about postoperative pain scores and opioid utilization. They were asked to retrospectively estimate their maximal pain score on an 11-point numeric rating scale at multiple time points, including day of surgery, during hospitalization, immediately after discharge, 1st week, and 2nd week following discharge. Pain scores over time were assessed utilizing a generalized linear mixed-effects model with the patient identifier being a random effect, adjusting for an a priori defined set of confounders. A multivariate negative binomial model was utilized to assess the association between intrapartum CD and opioid utilization after discharge, also adjusting for the same confounders. In the context of non-random prescription distribution, this model was constructed with an offset for the number of tablets dispensed.RESULTS: A total of 720 women were enrolled, 392 with and 328 without labor prior to CD. Patients with intrapartum CD were younger, less likely to undergo repeat CD or additional surgical procedures, and more likely to experience a complication of CD. Women with intrapartum CD consumed more opioid tablets following discharge than women without labor (median 20, IQR 10-30 versus 17, IQR 6-30; p = 0.005). This association persisted after adjustment for confounders (incidence rate ratio 1.16, 95% CI 1.05-1.29; p = 0.004). Pain scores on the day of surgery were higher in women with intrapartum CD (difference 0.91, 95% CI 0.52-1.30; adj. p = <0.001) even after adjustment for confounders. Pain scores at other time points were not meaningfully different between the two groups.CONCLUSION: Intrapartum CD is associated with worse pain on the day of surgery but not other time points. Opioid requirements following discharge were modestly increased following intrapartum CD.

  View details for DOI 10.1371/journal.pone.0253990

  View details for PubMedID 34242277

• The Society for Obstetric Anesthesia and Perinatology (SOAP) COVID-19 Registry: An analysis of outcomes among pregnant women delivering during the initial SARS-CoV-2 outbreak in the United States. Anesthesia and analgesia Katz, D. n., Bateman, B. T., Kjaer, K. n., Turner, D. P., Spence, N. Z., Habib, A. S., George, R. B., Toledano, R. D., Grant, G. n., Madden, H. E., Butwick, A. J., Lynde, G. n., Minehart, R. D., Beilin, Y. n., Houle, T. T., Sharpe, E. E., Kodali, B. n., Bharadwaj, S. n., Farber, M. K., Palanisamy, A. n., Prabhu, M. n., Gonzales, N. Y., Landau, R. n., Leffert, L. n. 2021

  Abstract

  Early reports associating SARS-CoV-2 infection with adverse pregnancy outcomes were biased by including only women with severe disease without controls. The Society for Obstetric Anesthesia and Perinatology (SOAP) COVID Registry was created to compare peripartum outcomes and anesthetic utilization in women with and without SARS-CoV-2 infection delivering at institutions with widespread testing.Deliveries from 14 U.S. medical centers, March 19-May 31, 2020, were included. Peripartum infection was defined as a positive SARS-CoV-2 polymerase chain reaction test within 14 days of delivery. Consecutive SARS-CoV-2 infected patients with randomly selected control patients were sampled (1:2 ratio) with controls delivering during the same day without a positive test. Outcomes were obstetric (e.g., delivery mode, hypertensive disorders of pregnancy, delivery < 37 weeks), an adverse neonatal outcome composite measure (primary), and anesthetic utilization (e.g., neuraxial labor analgesia and anesthesia). Outcomes were analyzed using generalized estimating equations to account for clustering within centers. Sensitivity analyses compared symptomatic and asymptomatic patients to controls.1454 peripartum women were included: 490 with SARS-CoV-2 infection [176 (35.9%) symptomatic]; 964 controls. SARS-CoV-2 patients were slightly younger, more likely non-nulliparous, non-white, and Hispanic than controls. They were more likely to have diabetes, obesity, or cardiac disease and less likely to have autoimmune disease. After adjustment for confounders, individuals experiencing SARS-CoV-2 infection exhibited an increased risk for delivery < 37 weeks gestation compared to controls, 73 (14.8%) vs. 98 (10.2%) [adjusted odds ratio (aOR): 1.47 95% CI (1.03-2.09)]. Effect estimates for other obstetric outcomes and the neonatal composite outcome measure were not meaningfully different between SARS-CoV-2-patients versus controls. In sensitivity analyses, compared to controls, symptomatic SARS-CoV-2 patients exhibited: increases in cesarean delivery [aOR: 1.57 95% CI (1.09-2.27)]; postpartum length of stay [aOR 1.89 95% CI (1.18-2.60)]; delivery < 37 weeks gestation [aOR 2.08 95% CI (1.29-3.36)]. These adverse outcomes were not found in asymptomatic women versus controls. SARS-CoV-2 patients (asymptomatic and symptomatic) were less likely to receive neuraxial labor analgesia [aOR: 0.52 95% CI (0.35-0.75)] and more likely to receive general anesthesia for cesarean delivery [aOR: 3.69 95% CI (1.40-9.74)] due to maternal respiratory failure.In this large, multicenter U.S. cohort study of women with and without peripartum SARS-CoV-2 infection, differences in obstetric and neonatal outcomes seem to be mostly driven by symptomatic patients. Lower utilization of neuraxial analgesia in laboring patients with asymptomatic or symptomatic infection compared to patients without infection requires further investigation.

  View details for DOI 10.1213/ANE.0000000000005592

  View details for PubMedID 33830956

• Preoperative Sedative-hypnotic Medication Use and Adverse Postoperative Outcomes. Annals of surgery Gaulton, T. G., Wunsch, H., Gaskins, L. J., Leonard, C. E., Hennessy, S., Ashburn, M., Brensinger, C., Newcomb, C., Wijeysundera, D., Bateman, B. T., Bethell, J., Neuman, M. D. 2021; 274 (2): e108-e114

  Abstract

  To determine the association between preoperative benzodiazepine and nonbenzodiazepine receptor agonist ("Z-drugs") use and adverse outcomes after surgery.Prescriptions for benzodiazepines and Z-drugs have increased over the past decade. Despite this, the association of preoperative benzodiazepines and Z-drug receipt with adverse outcomes after surgery is unknown.Using the Optum Clinformatics Datamart, we performed a retrospective cohort study of adults 18 years or older who underwent any of 10 common surgical procedures between 2010 and 2015. The principal exposure was one or more filled prescriptions for a benzodiazepine or Z-drug in the 90 days before surgery. The primary outcome was any emergency department visit or hospital admission for either (1) a drug related adverse medical event or overdose or (2) a traumatic injury in the 30 days after surgery.Of 785,346 patients meeting inclusion criteria, 94,887 (12.1%) filled a preoperative prescription for a benzodiazepine or Z-drug. From multivariable logistic regression, benzodiazepine or Z-drug use was associated with an increased odds of an adverse postoperative event [odds ratio 1.13; 95% confidence interval: 1.08-1.18). In a separate regression, coprescription of benzodiazepines or Z-drugs with opioids was associated with a 1.45 odds of an adverse postoperative event (95% confidence interval: 1.37-1.53).Preoperative benzodiazepines and Z-drug use is common and associated with increased odds of adverse outcomes after surgery, particularly when coprescribed with opioids. Counseling on appropriate benzodiazepine and Z-drug use in advance of elective surgery may potentially increase the safety of surgical care.

  View details for DOI 10.1097/SLA.0000000000003556

  View details for PubMedID 31415004

  View details for PubMedCentralID PMC7053280

• Risk of pre-eclampsia in patients with a maternal genetic predisposition to common medical conditions: a case-control study. BJOG : an international journal of obstetrics and gynaecology Gray, K. J., Kovacheva, V. P., Mirzakhani, H., Bjonnes, A. C., Almoguera, B., Wilson, M. L., Ingles, S. A., Lockwood, C. J., Hakonarson, H., McElrath, T. F., Murray, J. C., Norwitz, E. R., Karumanchi, S. A., Bateman, B. T., Keating, B. J., Saxena, R. 2021; 128 (1): 55-65

  Abstract

  To assess whether women with a genetic predisposition to medical conditions known to increase pre-eclampsia risk have an increased risk of pre-eclampsia in pregnancy.Case-control study.Pre-eclampsia cases (n = 498) and controls (n = 1864) in women of European ancestry from five US sites genotyped on a cardiovascular gene-centric array.Significant single-nucleotide polymorphisms (SNPs) from 21 traits in seven disease categories (cardiovascular, inflammatory/autoimmune, insulin resistance, liver, obesity, renal and thrombophilia) with published genome-wide association studies (GWAS) were used to create a genetic instrument for each trait. Multivariable logistic regression was used to test the association of each continuous scaled genetic instrument with pre-eclampsia. Odds of pre-eclampsia were compared across quartiles of the genetic instrument and evaluated for significance.Genetic predisposition to medical conditions and relationship with pre-eclampsia.An increasing burden of risk alleles for elevated diastolic blood pressure (DBP) and increased body mass index (BMI) were associated with an increased risk of pre-eclampsia (DBP, overall OR 1.11, 95% CI 1.01-1.21, P = 0.025; BMI, OR 1.10, 95% CI 1.00-1.20, P = 0.042), whereas alleles associated with elevated alkaline phosphatase (ALP) were protective (OR 0.89, 95% CI 0.82-0.97, P = 0.008), driven primarily by pleiotropic effects of variants in the FADS gene region. The effect of DBP genetic loci was even greater in early-onset pre-eclampsia cases (at <34 weeks of gestation, OR 1.30, 95% CI 1.08-1.56, P = 0.005). For other traits, there was no evidence of an association.These results suggest that the underlying genetic architecture of pre-eclampsia may be shared with other disorders, specifically hypertension and obesity.A genetic predisposition to increased diastolic blood pressure and obesity increases the risk of pre-eclampsia.

  View details for DOI 10.1111/1471-0528.16441

  View details for PubMedID 32741103

  View details for PubMedCentralID PMC7736250

• Active Surveillance of the Safety of Medications Used During Pregnancy. American journal of epidemiology Huybrechts, K. F., Kulldorff, M., Hernández-Díaz, S., Bateman, B. T., Zhu, Y., Mogun, H., Wang, S. V. 2021; 190 (6): 1159-1168

  Abstract

  The scientific community relies on postmarketing approaches to define the risk of using medications in pregnancy because information available at the time of drug approval is limited. Most studies carried out in pregnancy focus on a single outcome or selected outcomes. However, women must balance the benefit of treatment against all possible adverse effects. We aimed to apply and evaluate a tree-based scan statistic data-mining method (TreeScan; Martin Kulldorff, Harvard Medical School, Boston, Massachusetts) as a safety surveillance approach that allows for simultaneous evaluation of a comprehensive range of adverse pregnancy outcomes, while preserving the overall rate of false-positive alerts. We evaluated TreeScan with a cohort design and adjustment via propensity score techniques, using 2 test cases: 1) opioids and neonatal opioid withdrawal syndrome and 2) valproate and congenital malformations, implemented in pregnancy cohorts nested within the Medicaid Analytic eXtract (January 1, 2000-December 31, 2014) and the IBM MarketScan Research Database (IBM, Armonk, New York) (January 1, 2003-September 30, 2015). In both cases, we identified known safety concerns, with only 1 previously unreported alert at the preset statistical alerting threshold. This evaluation shows the promise of TreeScan-based approaches for systematic drug safety monitoring in pregnancy. A targeted screening approach followed by deeper investigation to refine understanding of potential signals will ensure that pregnant women and their physicians have access to the best available evidence to inform treatment decisions.

  View details for DOI 10.1093/aje/kwaa288

  View details for PubMedID 33423046

• Nonopioid, Multimodal Analgesia as First-line Therapy After Otolaryngology Operations: Primer on Nonsteroidal Anti-inflammatory Drugs (NSAIDs). Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Cramer, J. D., Barnett, M. L., Anne, S., Bateman, B. T., Rosenfeld, R. M., Tunkel, D. E., Brenner, M. J. 2021; 164 (4): 712-719

  Abstract

  To offer pragmatic, evidence-informed advice on nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy after surgery. This companion to the American Academy of Otolaryngology-Head & Neck Surgery (AAO-HNS) clinical practice guideline (CPG), "Opioid Prescribing for Analgesia After Common Otolaryngology Operations," presents data on potency, bleeding risk, and adverse effects for ibuprofen, naproxen, ketorolac, meloxicam, and celecoxib.National Guidelines Clearinghouse, CMA Infobase, National Library of Guidelines, NICE, SIGN, New Zealand Guidelines Group, Australian National Health and Medical, Research Council, TRIP database, PubMed, Guidelines International Network, Cochrane Library, EMBASE, CINAHL, BIOSIS Previews, ISI Web of Science, AHRQ, and HSTAT.AAO-HNS opioid CPG literature search strategy, supplemented by PubMed/MEDLINE searches on NSAIDs, emphasizing systematic reviews and randomized controlled trials.NSAIDs provide highly effective analgesia for postoperative pain, particularly when combined with acetaminophen. Inconsistent use of nonopioid regimens arises from common misconceptions that NSAIDs are less potent analgesics than opioids and have an unacceptable risk of bleeding. To the contrary, multimodal analgesia (combining 500 mg acetaminophen and 200 mg ibuprofen) is significantly more effective analgesia than opioid regimens (15 mg oxycodone with acetaminophen). Furthermore, selective cyclooxygenase-2 inhibition reliably circumvents antiplatelet effects.The combination of NSAIDs and acetaminophen provides more effective postoperative pain control with greater safety than opioid-based regimens. The AAO-HNS opioid prescribing CPG therefore prioritizes multimodal, nonopioid analgesia as first-line therapy, recommending that opioids be reserved for severe or refractory pain. This state-of-the-art review provides strategies for safely incorporating NSAIDs into acute postoperative pain regimens.

  View details for DOI 10.1177/0194599820947013

  View details for PubMedID 32806991

• Antiemetic Drugs During Pregnancy: What Can We Learn From Spontaneous Reporting System Database Analyses?-Reply. JAMA pediatrics Huybrechts, K. F., Hernández-Díaz, S., Bateman, B. T. 2021; 175 (3): 327-328

  View details for DOI 10.1001/jamapediatrics.2020.5177

  View details for PubMedID 33427855

• Association of Selective Serotonin Reuptake Inhibitors With the Risk of Type 2 Diabetes in Children and Adolescents. JAMA psychiatry Sun, J. W., Hernández-Díaz, S., Haneuse, S., Bourgeois, F. T., Vine, S. M., Olfson, M., Bateman, B. T., Huybrechts, K. F. 2021; 78 (1): 91-100

  Abstract

  Concerns exist that use of selective serotonin reuptake inhibitors (SSRIs) increases the risk of developing type 2 diabetes (T2D) in adults, but evidence in children and adolescents is limited. In the absence of a randomized clinical trial, evidence must be generated using real-world data.To evaluate the safety of SSRI use in children and adolescents with respect to the associated risk of T2D.This cohort study of patients aged 10 to 19 years with a diagnosis for an SSRI treatment indication was conducted within the nationwide Medicaid Analytic eXtract (MAX; January 1, 2000, to December 31, 2014) and the IBM MarketScan (January 1, 2003, to September 30, 2015) databases. Data were analyzed from November 1, 2018, to December 6, 2019.New users of an SSRI medication and comparator groups with no known metabolic adverse effects (no antidepressant exposure, bupropion hydrochloride exposure, or psychotherapy exposure). Within-class individual SSRI medications were compared with fluoxetine hydrochloride.Incident T2D during follow-up. Intention-to-treat effects were estimated using Cox proportional hazards regression models, adjusting for confounding through propensity score stratification. As-treated effects to account for continuous treatment were estimated using inverse probability weighting and marginal structural models.A total of 1 582 914 patients were included in the analysis (58.3% female; mean [SD] age, 15.1 [2.3] years). The SSRI-treated group included 316 178 patients in the MAX database (publicly insured; mean [SD] age, 14.7 [2.1] years; 62.2% female) and 211 460 in the MarketScan database (privately insured; mean [SD] age, 15.8 [2.3] years; 63.9% female) with at least 2 SSRI prescriptions filled, followed up for a mean (SD) of 2.3 (2.0) and 2.2 (1.9) years, respectively. In publicly insured patients, initiation of SSRI treatment was associated with a 13% increased hazard of T2DM (intention-to-treat adjusted hazard ratio [aHR], 1.13; 95% CI, 1.04-1.22) compared with untreated patients. The association strengthened for continuous SSRI treatment (as-treated aHR, 1.33; 95% CI, 1.21-1.47), corresponding to 6.6 (95% CI, 4.2-10.4) additional cases of T2D per 10 000 patients treated for at least 2 years. Adjusted HRs were lower in privately insured patients (intention-to-treat aHR, 1.01 [95% CI, 0.84-1.23]; as-treated aHR, 1.10 [95% CI, 0.88-1.36]). Findings were similar when comparing SSRI treatment with psychotherapy (publicly insured as-treated aHR, 1.44 [95% CI, 1.25-1.65]; privately insured as-treated aHR, 1.21 [95% CI, 0.93-1.57]), whereas no increased risk was observed compared with bupropion treatment publicly insured as-treated aHR, 1.01 [95% CI, 0.79-1.29]; privately insured as-treated aHR, 0.87 [95% CI, 0.44-1.70]). For the within-class analysis, no medication had an increased hazard of T2D compared with fluoxetine.These findings suggest that children and adolescents initiating SSRI treatment may be at a small increased risk of developing T2D, particularly publicly insured patients. The magnitude of association was more modest than previously reported, and the absolute risk was small. The potential small risk should be viewed in relation to the efficacy of SSRIs for its major indications in young patients.

  View details for DOI 10.1001/jamapsychiatry.2020.2762

  View details for PubMedID 32876659

  View details for PubMedCentralID PMC7489393

• Hydroxychloroquine early in pregnancy and risk of birth defects. American journal of obstetrics and gynecology Huybrechts, K. F., Bateman, B. T., Zhu, Y., Straub, L., Mogun, H., Kim, S. C., Desai, R. J., Hernandez-Diaz, S. 2021; 224 (3): 290.e1-290.e22

  Abstract

  Hydroxychloroquine is generally considered safe in pregnancy for the treatment of rheumatic conditions, but studies have been too small to evaluate teratogenicity. Quantifying the risk of congenital malformations associated with early pregnancy exposure to hydroxychloroquine is important in both the context of its ongoing use for rheumatological disorders and its potential future use for coronavirus disease 2019 prophylaxis, for which a number of clinical trials are ongoing despite initial trials for coronavirus disease 2019 treatment having been negative.The study objective was to evaluate the risk of major congenital malformations associated with exposure to hydroxychloroquine during the first trimester of pregnancy, the period of organogenesis.We performed a population-based cohort study nested in the Medicaid Analytic eXtract (MAX, 2000-2014) and IBM MarketScan Research Database (MarketScan, 2003-2015). The source cohort included 2045 hydroxychloroquine-exposed pregnancies and 3,198,589 pregnancies not exposed to hydroxychloroquine continuously enrolled in their respective insurance program for 3 months before the last menstrual period through at least 1 month after delivery; infants were enrolled for at least 3 months after birth. We compared the risk of congenital malformations in women using hydroxychloroquine during the first trimester of pregnancy with that of those not using hydroxychloroquine, restricting the cohort to women with rheumatic disorders and using propensity score matching to control for indication, demographics, medical comorbidities, and concomitant medications (1867 hydroxychloroquine-exposed pregnancies and 19,080 pregnancies not exposed to hydroxychloroquine). The outcomes considered included major congenital malformations diagnosed during the first 90 days after delivery and specific malformation types for which there were at least 5 exposed events: oral cleft, cardiac, respiratory, gastrointestinal, genital, urinary, musculoskeletal, and limb defects.Overall, 54.8 per 1000 infants exposed to hydroxychloroquine were born with a major congenital malformation versus 35.3 per 1000 unexposed infants, corresponding to an unadjusted relative risk of 1.51 (95% confidence interval, 1.27-1.81). Patient characteristics were balanced in the restricted, propensity score-matched cohort. The adjusted relative risk was 1.26 (95% confidence interval, 1.04-1.54); it was 1.33 (95% confidence interval, 1.08-1.65) for a daily dose of ≥400 mg and 0.95 (95% confidence interval, 0.60-1.50) for a daily dose of <400 mg. Among the different malformation groups considered, more substantial increases in the risk of oral clefts, respiratory anomalies, and urinary defects were observed, although estimates were imprecise. No pattern of malformation was identified.Our findings suggest a small increase in the risk of malformations associated with first-trimester hydroxychloroquine use. For most patients with autoimmune rheumatic disorders, the benefits of treatment during pregnancy will likely outweigh this risk. If hydroxychloroquine were shown to be effective for coronavirus disease 2019 prophylaxis in ongoing trials, the risk of malformations would need to be balanced against such benefits.

  View details for DOI 10.1016/j.ajog.2020.09.007

  View details for PubMedID 32961123

  View details for PubMedCentralID PMC7501839

• Antidiabetic medication use in commercially insured children and adolescents in the United States from 2004 to 2019. Diabetes, obesity & metabolism Sun, J. W., Hernández-Díaz, S., Bourgeois, F. T., Haneuse, S., Brill, G., Bateman, B. T., Huybrechts, K. F. 2021; 23 (2): 444-454

  Abstract

  To describe the patterns of non-insulin antidiabetic medication use, initiation and adherence in the paediatric population.We conducted a descriptive study of non-insulin antidiabetic medication use in children and adolescents (aged 10-18 years) using real-world data from a nationwide US commercial claims database (January 2004-September 2019). Trends in the prevalence of non-insulin antidiabetic medication use overall and by class were evaluated. Among new users of non-insulin antidiabetic agents, medication adherence was examined using group-based trajectory models.In a cohort of more than 1 million paediatric patients, the prevalence of any non-insulin antidiabetic medication use was 75.7 per 100 000 patients in 2004 and more than doubled to 162.0 per 100 000 in 2019. Biguanides (metformin) was by far the most widely used medication class. The use of newer classes was low (<10 per 100 000), but there was an uptake in the use of glucagon-like peptide-1 receptor agonists after liraglutide received paediatric approval in 2019. Medication adherence was poor during the 18 months after treatment initiation: 79.6% of initiators experienced an early treatment interruption (median time to interruption: 90 days among metformin monotherapy initiators) and 21% of initiators did not return for a prescription refill after the first month.There was a substantial increase in non-insulin antidiabetic medication use among commercially insured paediatric patients from 2004 to 2019. Nearly all patients were treated with metformin, while the use of newer agents remained low. Despite the increase in medication use, short treatment episodes were observed, even among patients with a diagnosis of type 2 diabetes, raising concern over poor adherence.

  View details for DOI 10.1111/dom.14237

  View details for PubMedID 33118291

• Development and Validation of a Pediatric Comorbidity Index. American journal of epidemiology Sun, J. W., Bourgeois, F. T., Haneuse, S., Hernández-Díaz, S., Landon, J. E., Bateman, B. T., Huybrechts, K. F. 2021; 190 (5): 918-927

  Abstract

  Comorbidity scores are widely used to help address confounding bias in nonrandomized studies conducted within health-care databases, but existing scores were developed to predict all-cause mortality in adults and might not be appropriate for use in pediatric studies. We developed and validated a pediatric comorbidity index, using health-care utilization data from the tenth revision of the International Classification of Diseases. Within the MarketScan database of US commercial claims data, pediatric patients (aged ≤18 years) continuously enrolled between October 1, 2015, and September 30, 2017, were identified. Logistic regression was used to predict the 1-year risk of hospitalization based on 27 predefined conditions and empirically identified conditions derived from the most prevalent diagnoses among patients with the outcome. A single numerical index was created by assigning weights to each condition based on its β coefficient. We conducted internal validation of the index and compared its performance with existing adult scores. The pediatric comorbidity index consisted of 24 conditions and achieved a C statistic of 0.718 (95% confidence interval (CI): 0.714, 0.723). The index outperformed existing adult scores in a pediatric population (C statistics ranging from 0.522 to 0.640). The pediatric comorbidity index provides a summary measure of disease burden and can be used for risk adjustment in epidemiologic studies of pediatric patients.

  View details for DOI 10.1093/aje/kwaa244

  View details for PubMedID 33124649

• Drug-drug interactions in pregnancy: An important frontier for pharmacoepidemiology. Paediatric and perinatal epidemiology Bateman, B. T., Huybrechts, K. F. 2021; 35 (2): 194-195

  View details for DOI 10.1111/ppe.12733

  View details for PubMedID 33350487

• Postoperative inpatient utilization of opioid and opioid-sparing analgesics in the United States hospitals, 2007-2017. Pharmacoepidemiology and drug safety Bykov, K., Patorno, E., Franklin, J. M., Vine, S. M., Bateman, B. T. 2021; 30 (3): 390-394

  Abstract

  To evaluate recent trends in inpatient postoperative utilization of opioid and non-opioid analgesics in US hospitals.Using Premier Research database (October 2007-September 2017), we identified adults who were hospitalized for inpatient surgical procedures (N = 6 068 133). For each month, we calculated proportion of patients admitted that month who were administered (1) opioids, (2) acetaminophen, (3) non-steroidal anti-inflammatory drugs (NSADs), and (4) gabapentinoids (gabapentin or pregabalin) during the postoperative period, defined as inpatient postoperative days 1-7, unless discharged earlier. For patients administered opioids, we estimated total and average daily postoperative opioid dose in morphine milligram equivalents (MMEs). Monthly measures were standardized to the distribution of surgeries and the length of postoperative stay within each surgery during the last year of available data.Overall, 90.8% of patients were administered opioids postoperatively; mean total postoperative dose was 304 MMEs (median 130). Both the frequency and the amount of opioids administered remained stable over 2007-2017. Postoperative use of acetaminophen increased from mean standardized monthly prevalence of 78% in 2007-2008 to 85% in 2017, while the use of NSAIDs remained stable at a standardized mean of 37%. The use of gabapentinoids increased from below 10% in 2007-2008 to the mean standardized monthly prevalence of 23% in 2017.Despite growing awareness of risks associated with postoperative opioid use, we observed no change in postoperative utilization of opioids in US hospitals. Increasing the use of non-opioid pain management approaches could constitute an important target in our efforts to curtail US opioid epidemic.

  View details for DOI 10.1002/pds.5187

  View details for PubMedID 33368798

  View details for PubMedCentralID PMC7854478

• Validity of claims-based algorithms to identify neurodevelopmental disorders in children. Pharmacoepidemiology and drug safety Straub, L., Bateman, B. T., Hernandez-Diaz, S., York, C., Zhu, Y., Suarez, E. A., Lester, B., Gonzalez, L., Hanson, R., Hildebrandt, C., Homsi, J., Kang, D., Lee, K. W., Lee, Z., Li, L., Longacre, M., Shah, N., Tukan, N., Wallace, F., Williams, C., Zerriny, S., Mogun, H., Huybrechts, K. F. 2021

  Abstract

  To validate healthcare claim-based algorithms for neurodevelopmental disorders (NDD) in children using medical records as the reference.Using a clinical data warehouse of patients receiving outpatient or inpatient care at two hospitals in Boston, we identified children (≤14 years between 2010 and 2014) with at least one of the following NDDs according to claims-based algorithms: autism spectrum disorder/pervasive developmental disorder (ASD), attention deficit disorder/other hyperkinetic syndromes of childhood (ADHD), learning disability, speech/language disorder, developmental coordination disorder (DCD), intellectual disability, and behavioral disorder. Fifty cases per outcome were randomly sampled and their medical records were independently reviewed by two physicians to adjudicate the outcome presence. Positive predictive values (PPVs) and 95% confidence intervals (CIs) were calculated.PPVs were 94% (95% CI, 83%-99%) for ASD, 88% (76%-95%) for ADHD, 98% (89%-100%) for learning disability, 98% (89%-100%) for speech/language disorder, 82% (69%-91%) for intellectual disability, and 92% (81%-98%) for behavioral disorder. A total of 19 of the 50 algorithm-based cases of DCD were confirmed as severe coordination disorders with functional impairment, with a PPV of 38% (25%-53%). Among the 31 false-positive cases of DCD were 7 children with coordination deficits that did not persist throughout childhood, 7 with visual-motor integration deficits, 12 with coordination issues due to an underlying medical condition and 5 with ADHD and at least one other severe NDD.PPVs were generally high (range: 82%-98%), suggesting that claims-based algorithms can be used to study NDDs. For DCD, additional criteria are needed to improve the classification of true cases.

  View details for DOI 10.1002/pds.5369

  View details for PubMedID 34623720

• Risk of Overdose Associated With Co-prescription of Antipsychotics and Opioids: A Population-Based Cohort Study. Schizophrenia bulletin Szmulewicz, A. G., Bateman, B. T., Levin, R., Huybrechts, K. F. 2021

  Abstract

  The US FDA issued a black-box warning against co-prescription of antipsychotic (AP) agents and opioids due to the risk of respiratory depression, but evidence on the comparative safety of sedating vs nonsedating APs is lacking. We classified APs as sedating (eg, quetiapine, olanzapine, and chlorpromazine) and nonsedating (eg, aripiprazole, haloperidol, and risperidone) based on their affinity to the histamine-1 neuroreceptor (Ki < or ≥20, respectively) and sought to compare the rate of overdose between patients using sedating vs nonsedating APs plus opioids. We constructed a population-based cohort nested in the IBM MarketScan database (2004-2017). Patients with concomitant use of sedating APs and prescription opioids ("exposed") were 1:1 matched to patients with concomitant use of nonsedating APs and prescription opioids ("referent") based on the propensity score (PS). The primary outcome was any hospitalization or emergency department visit due to an overdose within 30 days. The final cohort comprised 62 604 exposed and an equal number of PS-matched reference patients. Characteristics of matched exposed and reference patients were similar. There were 178 overdose events among the exposed (35.3 events per 1000 person-years [PY]) vs 133 among the reference group (26.4 events per 1000 PY), for an adjusted hazard ratio of 1.34 (95% CI: 1.07-1.68). This finding was consistent across sensitivity and subgroup analyses. Among patients receiving prescription opioids, concomitant use of sedating APs was associated with an increased risk of overdose compared with nonsedating APs. Caution is required when co-prescribing opioids and APs. If co-prescription is needed, choosing a nonsedating agent should be preferred whenever possible given the clinical context.

  View details for DOI 10.1093/schbul/sbab116

  View details for PubMedID 34582543

• Response to Invited Commentary: Intermittent opioid use and ischemic placental disease: study quantifies risks, raises questions. American journal of epidemiology Esposito, D. B., Bateman, B., Werler, M., Straub, L., Mogun, H., Hernandez-Diaz, S., Huybrechts, K. 2021

  View details for DOI 10.1093/aje/kwab226

  View details for PubMedID 34528055

• Prescription opioid fills following surgical abortion. Contraception Gibbs, L. R., Pisc, J. A., Braaten, K. P., Bateman, B. T., Garry, E. M. 2021

  Abstract

  To characterize opioid fills after surgical abortion among US commercially-insured women.We identified women aged 15-50 years with an outpatient claim for dilation and curettage or evacuation surgical abortion (D&C/D&E) in IBM MarketScan 2015-2018 and excluded patients with > 1 opioid fill in the prior 90 days, evidence of opioid dependence or abuse in the prior 180 days (baseline), miscarriage in 7 days prior, or mifepristone use in 3 to 7 days prior. We describe the frequency of an oral opioid fill within 7 days after abortion, refill within 42 days of initial fill, and chronic use (≥ 6 fills) in 1 year after abortion. We used multivariable logistic regression to evaluate predictors of opioid fill including patient and procedure characteristics.Among 28,252 patients who underwent induced surgical abortion, 2,340 (8.3%) filled an opioid prescription within 7 days. The strongest predictors of opioid fill were non-Northeast region, use of moderate sedation for the procedure, and baseline depression. Among 2,250 patients with an initial fill and sufficient follow-up, 10.0% had a refill within 42 days of initial fill. Among 15,353 patients with sufficient follow-up, patients with an opioid fill after abortion had a higher percentage of subsequent chronic use than those without (2.1% and 0.4%, respectively).The frequency of an opioid fill after surgical abortion among commercially-insured women was notable given it is not recommended for post-procedural analgesia. Opioid prescribing contrary to recommendations may be associated with subsequent chronic use or abuse.Despite public health efforts to decrease opioid prescribing, these findings suggest opioid prescribing after surgical abortion as a potential source of overprescribing among commercially insured patients in the United States. As surgical abortion is a minimally-invasive procedure, prescribing opioids for use in this setting may contribute to chronic use.

  View details for DOI 10.1016/j.contraception.2021.07.106

  View details for PubMedID 34329609

• Validation of a Claims-based Algorithm to Identify Pregestational Diabetes Among Pregnant Women in the United States. Epidemiology (Cambridge, Mass.) Wood, M. E., Chen, S. T., Huybrechts, K. F., Bateman, B. T., Gray, K. J., Seely, E. W., Zhu, Y., Mogun, H., Patorno, E., Hernández-Díaz, S. 2021; 32 (6): 855-859

  Abstract

  Identifying pregestational diabetes in pregnant women using administrative claims databases is important for studies of the safety of antidiabetic treatment in pregnancy, but limited data are available on the validity of case-identifying algorithms. The purpose of this study was to evaluate the validity of an administrative claims-based algorithm to identify pregestational diabetes.Using a cohort of pregnant women nested within the Medicaid Analytic Extract (MAX) database, we developed an algorithm to identify pregestational type 1 and type 2 diabetes, distinct from gestational diabetes. Within a single large healthcare system in the Boston area, we identified women who delivered an infant between 2000 and 2010 and were covered by Medicaid, and linked their electronic health records to their Medicaid claims within MAX. Medical records were reviewed by two physicians blinded to the algorithm classification to confirm or rule out pregestational diabetes, with disagreements resolved by discussion. We calculated positive predictive values with 95% confidence intervals using the medical record as the reference standard.We identified 49 pregnancies classified by the claims-based algorithm as pregestational diabetes that were linked to the electronic health records and had records available for review. The PPV for any pregestational diabetes was 92% [95% confidence interval (CI) 82%, 97%], type 2 diabetes 87% (68%, 95%), and type 1 diabetes 57% (37%, 75%).The claims-based algorithm for pregestational diabetes and type 2 diabetes performed well; however, the PPV was low for type 1 diabetes.

  View details for DOI 10.1097/EDE.0000000000001397

  View details for PubMedID 34183529

  View details for PubMedCentralID PMC8478806

• Ischemic Placental Disease, Preterm Delivery, and their Association with Opioid Use During Pregnancy. American journal of epidemiology Esposito, D. B., Bateman, B., Werler, M., Straub, L., Mogun, H., Hernandez-Diaz, S., Huybrechts, K. 2021

  Abstract

  Opioids affect placental development and function in animal models, but human data on their association with ischemic placental disease are limited. Using a cohort of pregnant women in the US nationwide Medicaid Analytic eXtract (2000-2014), we compared women with ≥2 opioid dispensings in pregnancy to unexposed women. Given an uncertain etiologically relevant window, we assessed exposure occurring in early pregnancy, late and not early pregnancy, and both early and late pregnancy. For placental abruption, preterm delivery, small for gestational age (SGA), and preeclampsia, we estimated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusting for demographics, indications/comorbidities, and medications. Of 1,833,871 eligible pregnancies, ≥2 opioid dispensings were filled by 6.5%. We observed an early exposure aHR of 1.34 (95% CI 1.26-1.43) for placental abruption, 1.21 (1.18-1.23) for preterm delivery, 1.13 (1.09-1.17) for SGA, and 0.95 (0.91-0.98) for preeclampsia. Estimates for late exposure were attenuated. Early and late exposure was associated with higher aHRs for placental abruption (1.62, 1.47-1.78), preterm delivery (1.37, 1.33-1.42) and SGA (1.26, 1.19-1.33), but not preeclampsia (0.99, 0.93-1.05). Prescription opioids may modestly increase risk of placental abruption, preterm birth and SGA, but they do not appear to be associated with preeclampsia.

  View details for DOI 10.1093/aje/kwab132

  View details for PubMedID 34165143

• Maternal morbidity and mortality associated with epilepsy. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Gyamfi-Bannerman, C., Huang, Y., Bateman, B. T., Benson, R. J., Pack, A. M., Wright, J. D., D'Alton, M. E., Friedman, A. M. 2021: 1-7

  Abstract

  Prior research demonstrated large increased risk for maternal mortality among women with epilepsy. The objective of this study was to estimate risk for adverse maternal outcomes during delivery hospitalizations among women with epilepsy.Truven Health MarketScan databases were used to compare risk for adverse maternal outcomes during delivery hospitalizations based upon whether there was diagnosis of epilepsy and receipt of anti-epileptic drugs prior to delivery. Outcomes included: (i) death during delivery hospitalization, (ii) severe maternal morbidity, (iii) cesarean delivery, (iv) postpartum hemorrhage, (v) placental abruption, (vi) preeclampsia, (vii) preterm delivery, (viii) premature rupture of membranes, and (ix) stillbirth. Adjusted models including hospital and demographic factors were performed with adjusted risk ratios (aRR) with 95% CIs as measures of effect.Women with epilepsy prior to delivery who received antiepileptic drugs (n = 6019) during pregnancy were not at increased risk for mortality with no deaths occurring in this group (p = .27). Risk for severe maternal morbidity in this group was approximately double (aRR 2.16, 95% CI 1.86-2.51) with risks for other outcomes including placental abruption (aRR 1.29, 95% CI 1.04-1.60), cesarean delivery (aRR 1.14, 95% CI 1.10-1.18), and preterm delivery (aRR 1.25, 95% CI 1.15-1.35) slightly increased compared to women without seizures.No significant difference in mortality risk was found for women with epilepsy. Increased risk for other adverse maternal outcomes for women with epilepsy on antiepileptics was modest.

  View details for DOI 10.1080/14767058.2021.1938528

  View details for PubMedID 34154486

• Association of the 2016 US Centers for Disease Control and Prevention Opioid Prescribing Guideline With Changes in Opioid Dispensing After Surgery. JAMA network open Sutherland, T. N., Wunsch, H., Pinto, R., Newcomb, C., Brensinger, C., Gaskins, L., Bateman, B. T., Neuman, M. D. 2021; 4 (6): e2111826

  Abstract

  While the 2016 US Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids for chronic pain was not intended to address postoperative pain management, observers have noted the potential for the guideline to have affected postoperative opioid prescribing.To assess changes in postoperative opioid dispensing after vs before the CDC guideline release in March 2016.This cross-sectional study included 361 556 opioid-naive patients who received 1 of 8 common surgical procedures between March 16, 2014, and March 15, 2018. Data were retrieved from a private insurance database, and a retrospective interrupted time series analysis was conducted. Data analysis was conducted from March 2014 to April 2018.Outcomes were measured before and after release of the 2016 CDC guideline.The primary outcome was the total amount of opioid dispensed in the first prescription filled within 7 days following surgery in morphine milligram equivalents (MMEs); secondary outcomes included the total amount of opioids prescribed and the incidence of any opioid refilled within 30 days after surgery. To characterize absolute opioid dispensing levels, the amount dispensed in initial prescriptions was compared with available procedure-specific recommendations.The sample included 361 556 opioid-naive patients undergoing 8 general and orthopedic surgical procedures; 164 009 (45.4%) were male patients, and the median (interquartile range) age of the sample was 58 (45 to 69) years. The total amount of opioids dispensed in the first prescription after surgery decreased in the 2 years following the CDC guideline release, compared with an increasing trend in the 2 years prior (prerelease trend: 1.43 MME/month; 95% CI, 0.62 to 2.24 MME/month; P = .001; postrelease trend: -2.18 MME/month; 95% CI, -3.01 to -1.35 MME/month; P < .001; trend change: -3.61 MME/month; 95% CI, -4.87 to -2.35 MME/month; P < .001). Changes in initial dispensing amount trends were greatest for patients undergoing hip or knee replacement (-8.64 MME/month; 95% CI, -11.68 to -5.60 MME/month; P < .001). Minimal changes were observed in rates of refills over time (net change: 0.14% per month; 95% CI, 0.06% to 0.23% per month; P = .001). Absolute amounts prescribed remained high throughout the period, with nearly half of patients (47.7%; 95% CI, 47.4%-47.9%) treated in the postguideline period receiving at least twice the initial opioid dose anticipated to treat postoperative pain based on available procedure-specific recommendations.In this study, opioid dispensing after surgery decreased substantially after the 2016 CDC guideline release, compared with an increasing trend during the 2 years prior. Absolute amounts prescribed for surgery remained high during the study period, supporting the need for further efforts to improve postoperative pain management.

  View details for DOI 10.1001/jamanetworkopen.2021.11826

  View details for PubMedID 34115128

  View details for PubMedCentralID PMC8196343

• Exploring New Risk Factors for Postpartum Hemorrhage: Time to Consider Gestational Age? Anesthesiology Reale, S. C., Bateman, B. T., Farber, M. K. 2021; 134 (6): 832-834

  View details for DOI 10.1097/ALN.0000000000003775

  View details for PubMedID 33909879

• The Risk of Overdose With Concomitant Use of Z-Drugs and Prescription Opioids: A Population-Based Cohort Study. The American journal of psychiatry Szmulewicz, A., Bateman, B. T., Levin, R., Huybrechts, K. F. 2021; 178 (7): 643-650

  Abstract

  The Z-drugs (zolpidem, zopiclone, zaleplon) are widely used to treat insomnia in patients receiving prescription opioids, and the risk of overdose resulting from this coprescription has not been explored. The authors compared the rates of overdose among patients using opioids plus Z-drugs and patients using opioids alone.All individuals 15 to 85 years of age receiving prescription opioids, regardless of underlying indication and without evidence of cancer, were identified in the IBM MarketScan database (2004-2017). Patients with concomitant exposure to Z-drugs were matched 1:1 to patients with exposure to prescription opioids alone based on opioid prescribed, morphine equivalents, number of days' supply, and hospitalization within the past 30 days. The primary outcome was any hospitalization or emergency department visit due to an overdose within 30 days, using an intention-to-treat approach. Fine stratification on the propensity score was used to control for confounding.A total of 510,529 exposed patients and an equal number of matched reference patients were analyzed. There were 217 overdose events among the exposed patients (52.5 events per 10,000 person-years) and 57 events among the reference patients (14.4 events per 10,000 person-years), corresponding to an unadjusted hazard ratio of 3.67 (95% CI=2.75, 4.90). Using fine stratification on the propensity score (c-statistic: 0.66), the adjusted hazard ratio was 2.29 (95% CI=1.79, 2.91). Results were consistent across sensitivity analyses.Among patients receiving prescription opioids, after controlling for all confounding factors, concomitant treatment with Z-drugs was associated with a substantial relative increase in the risk of overdose. The potential implications are significant given the large number of opioid-treated patients receiving Z-drugs.

  View details for DOI 10.1176/appi.ajp.2020.20071038

  View details for PubMedID 33900810

• Safety of Tenofovir Disoproxil Fumarate (TDF) for Pregnant Women facing the COVID-19 Pandemic. American journal of epidemiology Hernandez-Diaz, S., Bateman, B. T., Straub, L., Zhu, Y., Mogun, H., Fischer, M., Huybrechts, K. F. 2021

  Abstract

  We assessed the teratogenicity of tenofovir, a human immunodeficiency virus (HIV) drug similar to remdesivir currently being evaluated for the treatment of coronavirus disease 2019 (COVID-19). Using US Medicaid Analytic Extract (MAX) claims data (2000-2014), we identified a population-based pregnancy cohort of women with HIV who filled ≥1 prescription for antiretroviral therapies (ART) during the first trimester. Women on tenofovir disoproxil fumarate (TDF) were compared with women receiving ART without TDF. Major malformations were identified by ICD-9 codes using validated algorithms. Relative risks (RR) and 95% confidence intervals (CI) were estimated using propensity score (PS) stratification to control for potential confounders. We incorporated the results into prior knowledge by conducting a systematic literature review and a meta-analysis. Major congenital malformations were diagnosed in 37 out of 866 (4.27%) infants exposed to TDF and 38 out of 1,020 (3.73%) infants exposed to ART other than TDF; the adjusted RR was 1.21 (95% CI 0.77 to 1.90). Estimates for specific malformations were imprecise. The pooled RR from the meta-analysis with six prior studies was 0.88 (0.75 to 1.03). Based on evidence accumulated in patients with HIV, first trimester TDF use does not increase the risk of major congenital malformations overall in the newborn compared to other ART.

  View details for DOI 10.1093/aje/kwab109

  View details for PubMedID 33847737

  View details for PubMedCentralID PMC8083317

• Associations of thrombocytopenia, transaminase elevations, and transfusion with laboratory coagulation tests in women with preeclampsia: a cross-sectional study. International journal of obstetric anesthesia Combs, D. J., Gray, K. J., Schulman, S., Bateman, B. T. 2021; 46: 102972

  Abstract

  Women with preeclampsia may develop coagulopathy, predisposing to bleeding complications. Although guidelines and prior studies conflict, we hypothesized that in preeclampsia, abnormal coagulation test results are more common in women with thrombocytopenia or transaminase elevations and increase the transfusion risk. Our objectives were to investigate: 1. patterns of coagulation testing; 2. relationships between platelet count, transaminase level, and the risk of abnormal coagulation tests; 3. risk of bleeding complications; and 4. characteristics of patients with markedly abnormal coagulation parameters.We conducted a cross-sectional study of deliveries of women with preeclampsia who had undergone activated partial thromboplastin time (aPTT) or international normalized ratio (INR) testing at one of two hospitals between 1994 and 2018.Of 10 699 women with preeclampsia, 3359 (32.7%) had coagulation testing performed and aPTT or INR elevations were present in 124 (3.7 %). Coagulation abnormalities were more common in women with thrombocytopenia or transaminase elevations (n=82) compared with those without (n=42) (6.7%, 95% CI 5.5 to 8.2 vs 1.8%, 95% CI 1.3 to 2.5). Transfusion was more common among women with abnormal coagulation parameters (n=124) compared with those without (n=39) (33.1 vs 7.0%, P <0.001). Among 26 patients with an aPTT ≥40 s or an INR ≥1.4, six required transfusion (all had placental abruption and disseminated intravascular coagulopathy).Coagulation testing was inconsistently performed in this cohort. Platelet counts and transaminase levels inadequately detected abnormal coagulation test results. Abnormal coagulation test results were associated with a markedly higher risk for red blood cell transfusion.

  View details for DOI 10.1016/j.ijoa.2021.102972

  View details for PubMedID 33798794

  View details for PubMedCentralID PMC8144064

• The Patterns of Use of Medications for Inflammatory Bowel Disease During Pregnancy in the US and Sweden Are Changing. Inflammatory bowel diseases Bröms, G., Friedman, S., Kim, S. C., Wood, M. E., Hernandez-Diaz, S., Brill, G., Bateman, B. T., Huybrechts, K. F., Desai, R. J. 2021; 27 (9): 1427-1434

  Abstract

  Population-level data spanning different countries describing oral and parenteral treatment in pregnant women with inflammatory bowel disease (IBD) are scarce. We studied treatment with sulfasalazine/5-aminosalicylates, corticosteroids, thiopurines/immunomodulators, and tumor necrosis factor (TNF)-inhibitors in the United States (Optum Clinformatics Data Mart and the Medicaid Analytics Extract [MAX]) and in the Swedish national health registers.We identified 2975 pregnant women in Optum (2004-2013), 3219 women in MAX (2001-2013), and 1713 women in Sweden (2006-2015) with a recorded diagnosis of IBD. We assessed patterns of use for each drug class according to filled prescriptions, assessing frequency of treatment continuation in those that were treated in the prepregnancy period.The proportion of women with Crohn's disease and ulcerative colitis on any treatment during pregnancy was 56.1% and 56.3% in Optum, 47.5% and 49.3% in MAX, and 61.3% and 64.7% in Sweden, respectively, and remained stable over time. Sulfasalazine/5-aminosalicylates was the most commonly used treatment in Crohn's disease, ranging from 25.1% in MAX to 31.8% in Optum, and in ulcerative colitis, ranging from 34.9% in MAX to 53.6% in Sweden. From 2006 to 2012, the TNF-inhibitor use increased from 5.0% to 15.5% in Optum, from 3.6% to 8.5% in MAX, and from 0.7% to 8.3% in Sweden. Continuing TNF-inhibitor treatment throughout pregnancy was more common in Optum (55.8%) and in MAX (43.0%) than in Sweden (11.8%).In this population-based study from 2 countries, the proportion of women with IBD treatment in pregnancy remained relatively constant. TNF-inhibitor use increased substantially in both countries.

  View details for DOI 10.1093/ibd/izaa294

  View details for PubMedID 33751058

• The interrater reliability and agreement of a 0 to 10 uterine tone score in cesarean delivery. American journal of obstetrics & gynecology MFM Cole, N. M., Abushoshah, I., Fields, K. G., Carusi, D. A., Robinson, J. N., Bateman, B. T., Farber, M. K. 2021; 3 (3): 100342

  Abstract

  Postpartum hemorrhage is a leading source of maternal morbidity and mortality worldwide with uterine atony identified as the underlying cause in up to 80% of cases. Several measures have been utilized to report uterine tone. The most commonly reported measure is a 0 to 10 numeric rating scale, but this scale has not been tested for reliability or agreement between different raters.The primary purpose of this study was to evaluate the interrater reliability and agreement of the 0 to 10 visual numeric rating scale of uterine tone during cesarean delivery. A secondary purpose was to obtain estimates of scale responsiveness and minimal clinically important difference.Between August and November of 2018, obstetricians used a 0 to 10 numeric rating score to independently rate uterine tone at 3 and 10 minutes after cesarean delivery by palpation of the uterus. Of note, "0" represented "no tone" and "10" represented excellent tone. Each obstetrician independently and blinded to the other's score pointed to a numeric rating scale held by the anesthesiologist through a clear sterile drape. Intraclass correlation coefficients and Bland-Altman analysis were used to assess interrater reliability and agreement, respectively. Standardized response mean and standard error of measurement were used to obtain estimates of responsiveness and minimal clinically important difference, respectively.A total of 82 and 84 pairs of scores were collected at 3 and 10 minutes, respectively, from pairs of 62 unique obstetricians. The mean±standard deviation difference in scores between rater 1 and rater 2 was 0.4±1.4 at 3 minutes and 0.1±1.1 at 10 minutes. Intraclass correlation coefficients for a future single rater (intraclass correlation coefficient [1, 1]) at 3 and 10 minutes were 0.67 (95% confidence interval, 0.53-0.77) and 0.61 (95% confidence interval, 0.46-0.73), and for the average between 2 future raters (intraclass correlation coefficient [1, 2]), they were 0.80 (95% confidence interval, 0.71-0.87) and 0.76 (95% confidence interval, 0.63-0.84), indicating good and excellent reliability, respectively. Bland-Altman analysis estimated 95% limit of agreement between raters of -2.4 (95% confidence interval, -3.0 to -1.9) to 3.1 (95% confidence interval, 2.6-3.7) at 3 minutes and -2.1 (95% confidence interval, -2.5 to -1.7) to 2.4 (95% confidence interval, 2.0-2.8) at 10 minutes, consistent with good interrater agreement at both time points. The standardized response mean from 3 to 10 minutes after delivery was 1.1 (n=81). Standard error of measurement was 1.0 (95% confidence interval, 0.9-1.1) at 3 minutes and 0.8 (95% confidence interval, 0.7-0.9) at 10 minutes.The 0 to 10 numeric rating scale for uterine tone demonstrated good to excellent interrater reliability with 1 and 2 raters, respectively, and good interrater agreement. The scale was responsive to within-parturient change in tone, and preliminary estimates of the minimal clinically important difference were obtained. The 0 to 10 numeric rating scale for uterine tone may be a reliable, standardized tool for future research in reporting degree of uterotonic contraction during cesarean delivery.

  View details for DOI 10.1016/j.ajogmf.2021.100342

  View details for PubMedID 33652161

• Patient characteristics associated with SARS-CoV-2 infection in parturients admitted for labour and delivery in Massachusetts during the spring 2020 surge: A prospective cohort study. Paediatric and perinatal epidemiology Reale, S. C., Lumbreras-Marquez, M. I., King, C. H., Burns, S. L., Fields, K. G., Diouf, K., Goldfarb, I. T., Ciaranello, A. L., Robinson, J. N., Gregory, K. E., Huybrechts, K. F., Bateman, B. T. 2021; 35 (1): 24-33

  Abstract

  While studies from large cities affected by coronavirus disease 2019 (COVID-19) have reported on the prevalence of SARS-CoV-2 in the context of universal testing during admission for delivery, the patient demographic, social and clinical factors associated with SARS-CoV-2 infection in pregnant women are not fully understood.To evaluate the epidemiological factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in women admitted for labour and delivery, in the context of universal screening at four Boston-area hospitals.In this prospective cohort study, we reviewed the health records of all women admitted for labour and delivery at four hospitals from the largest health system in Massachusetts between 19 April 2020 and 27 June 2020. We calculated the risk of SARS-CoV-2 infection, including asymptomatic infection. We calculated associations between SARS-CoV-2 infection and demographic and clinical characteristics.A total of 93 patients (3.2%, 95% confidence interval 2.5, 3.8) tested positive for SARS-CoV-2 infection on admission for labour and delivery out of 2945 patients included in the analysis; 80 (86.0%) of the patients who tested positive were asymptomatic at the time of testing. Factors associated with SARS-CoV-2 infection included the following: younger age, obesity, African American or Hispanic race/ethnicity, residence in heavily affected communities (as measured in cases reported per capita), presence of a household member with known SARS-CoV-2 infection, non-health care essential worker occupation and MassHealth or Medicaid insurance compared to commercial insurance. 93.8% of patients testing positive for SARS-CoV-2 on admission had one or more identifiable factors associated with disease acquisition.In this large sample of deliveries during the height of the surge in infections during the spring of 2020, SARS-CoV-2 infection was largely concentrated in patients with distinct demographic characteristics, those largely from disadvantaged communities. Racial disparities seen in pregnancy persist with respect to SARS-CoV-2 infection.

  View details for DOI 10.1111/ppe.12743

  View details for PubMedID 33496995

  View details for PubMedCentralID PMC8014491

• Hydroxychloroquine early in pregnancy and risk of birth defects: absence of evidence is not the same as evidence of absence. American journal of obstetrics and gynecology Huybrechts, K. F., Bateman, B. T., Hernandez-Diaz, S. 2021; 224 (5): 549-550

  View details for DOI 10.1016/j.ajog.2020.12.1219

  View details for PubMedID 33434554

• Chronic prescription opioid use in pregnancy in the United States. Pharmacoepidemiology and drug safety Straub, L., Huybrechts, K. F., Hernandez-Diaz, S., Zhu, Y., Vine, S., Desai, R. J., Gray, K. J., Bateman, B. T. 2021; 30 (4): 504-513

  Abstract

  To evaluate chronic opioid utilization patterns during pregnancy using nationwide data from publicly and commercially insured women.Pregnancy cohorts were identified using data from the Medicaid Analytic eXtract 2008-2014 and the IBM Health MarketScan Research Database 2008-2015. Opioid dispensing was evaluated using claims from filled prescriptions. Two different definitions of chronic opioid use were employed: ≥90 days' supply and ≥180 days' supply of prescription opioids during pregnancy. Patient characteristics were assessed and variations in the prevalence of chronic opioid therapy were described by geographic region and over time.1.50% of 975 169 Medicaid-insured and 0.32% of 1 037 599 commercially insured beneficiaries filled opioid prescriptions for ≥90 days' supply; 0.78% (Medicaid) and 0.17% (commercially insured) filled prescriptions for ≥180 days' supply. Prevalence approximately doubled in Medicaid beneficiaries during the study period, while it remained relatively stable for commercial insurance beneficiaries. The most commonly prescribed opioid for chronic therapy was hydrocodone, followed by oxycodone and tramadol. Indications commonly associated with chronic use were back/neck pain, abdominal/pelvic pain, musculoskeletal pain and migraine/headache. Substantial regional variation was observed, with several states reporting a frequency of ≥90 days' supply in excess of 3% in Medicaid-insured patients.Despite growing awareness of the risks associated with chronic opioid use and emphasis on improving opioid prescription patterns, prevalence of chronic use in pregnancy among publicly insured women nearly doubled from 2008-2014 and was 5-fold more common when compared to commercially insured women. Findings call for the development of guidelines on chronic pain management during pregnancy.

  View details for DOI 10.1002/pds.5194

  View details for PubMedID 33428239

• Prescription opioid use after vaginal delivery and subsequent persistent opioid use and misuse. American journal of obstetrics & gynecology MFM Zhu, Y., Huybrechts, K. F., Desai, R. J., Franklin, J. M., Hernandez-Diaz, S., Krumme, A., Straub, L., Neuman, M., Wunsch, H., Levin, R., Mogun, H., Bateman, B. T. 2021; 3 (2): 100304

  Abstract

  Vaginal delivery is the most common reason for hospitalization in the United States, and approximately 30% of women fill an opioid prescription after vaginal delivery, making this a common source of opioid exposure in women of reproductive age.This study aimed to evaluate the effect of receiving an opioid prescription after vaginal delivery on the risk of subsequent persistent opioid use, opioid use disorders, and overdose.We assembled a nationwide cohort of Medicaid beneficiaries in the United States using the Medicaid Analytic eXtract 2009-2014. The study population included pregnant women who delivered vaginally between 2009 and 2013 and were continuously enrolled in Medicaid from 90 days before to 365 days after delivery. We identified patients with prescription opioids dispensed within 7 days of the date of vaginal delivery. Persistent opioid use was defined as ≥10 opioid fills or >120 days' supply dispensed from 30 to 365 days after delivery. Incident diagnoses of opioid use disorder and overdose were ascertained during the same interval. Propensity score matching was used to control for potential confounding factors.Among 459,829 pregnancies ending in vaginal deliveries, 140,807 (30.62%) had an opioid dispensed within 7 days of delivery. Overall, 5770 of 140,807 (4.10%) women who filled an opioid prescription vs 2668 of 319,022 (0.84%) unexposed women had subsequent persistent opioid use, with an unadjusted relative risk of 4.90 (95% confidence interval, 4.68-5.13) and a risk difference of 3.26% (95% confidence interval, 3.15-3.37). After propensity score matching, the risk remained higher among pregnancies with an opioid prescription dispensed, with a relative risk of 2.57 (95% confidence interval, 2.43-2.72) and a risk difference of 2.21% (95% confidence interval, 2.08-2.33), which was confirmed by the instrumental variable analysis with a risk difference of 1.31% (95% confidence interval, 1.06-1.56) by using the rate of opioid prescribing at the delivery facility in a given geographic region as the instrument. The adjusted relative risk of newly diagnosed opioid use disorder and overdose was 1.48 (95% confidence interval, 1.40-1.57) and 1.92 (95% confidence interval, 1.20-3.09), respectively.Opioid dispensing following vaginal delivery is associated with future persistent opioid use and misuse, independent of confounding factors. Opioid prescriptions to women after vaginal delivery should be avoided, except in rare circumstances.

  View details for DOI 10.1016/j.ajogmf.2020.100304

  View details for PubMedID 33383232

• Implementation of an Interdisciplinary Severe Maternal Morbidity Review Committee to Improve Identification Through a Hospital-Specific Protocol Manganaro, K., Sweeney, V., Saadeh, M., Easter, S., Bateman, B. T., Robinson, J. ELSEVIER SCIENCE INC. 2020: S41

  View details for Web of Science ID 000583918100064

• Frequency of opioid dispensing after surgical abortion in the United States Gibbs, L. R., Pisc, J. A., Braaten, K. P., Bateman, B. T., Garry, E. M. WILEY. 2020: 223

  View details for Web of Science ID 000577640500472

• Treescan for active surveillance of the safety of medications used in pregnancy Huybrechts, K. F., Kulldorff, M., Hernandez-Diaz, S., Bateman, B. T., Zhu, Y., Mogun, H., Wang, S. V. WILEY. 2020: 521-522

  View details for Web of Science ID 000577640501490

• The risk of overdose associated with concomitant use of antipsychotic agents and prescription opioids Szmulewicz, A., Bateman, B., Levin, R., Huybrechts, K. WILEY. 2020: 120-121

  View details for Web of Science ID 000577640500252

• Development and validation of a pediatric comorbidity index to predict the risk of hospitalization in the ICD-10-CM era Sun, J. W., Bourgeois, F. T., Haneuse, S., Hernandez-Diaz, S., Bateman, B. T., Huybrechts, K. F. WILEY. 2020: 448

  View details for Web of Science ID 000577640501331

• Validation of claims-based algorithms to identify specific major congenital malformations Straub, L., Huybrechts, K. F., Hernandez-Diaz, S., Zhu, Y., Gray, K. J., Bateman, B. T. WILEY. 2020: 534-535

  View details for Web of Science ID 000577640501517

• Concomitant use of gabapentinoids and opioids following surgery and the risk of opioid-related adverse events Bykov, K., Bateman, B. T., Franklin, J. M., Patorno, E. WILEY. 2020: 480

  View details for Web of Science ID 000577640501402

• Chronic prescription opioid use in pregnancy in the United States Straub, L., Huybrechts, K. F., Hernandez-Diaz, S., Zhu, Y., Vine, S., Desai, R. J., Gray, K. J., Bateman, B. T. WILEY. 2020: 533-534

  View details for Web of Science ID 000577640501515

• Antidiabetic medication use in children and adolescents from 2004 to 2019: Real world data from a commercially insured population in the United States Sun, J. W., Hernandez-Diaz, S., Bourgeois, F. T., Haneuse, S., Bateman, B. T., Patorno, E., Huybrechts, K. F. WILEY. 2020: 231

  View details for Web of Science ID 000577640500489

• Opioid use during pregnancy and ischemic placental disease Esposito, D. B., Bateman, B., Werler, M., Straub, L., Hernandez-Diaz, S., Mogun, H., Huybrechts, K. WILEY. 2020: 549-550

  View details for Web of Science ID 000577640501549

• Trajectories of prescription opioid utilization during pregnancy among pre-pregnancy chronic users and risk of neonatal abstinence syndrome Straub, L., Huybrechts, K. F., Hernandez-Diaz, S., Zhu, Y., Vine, S., Desai, R. J., Gray, K. J., Bateman, B. T. WILEY. 2020: 526-527

  View details for Web of Science ID 000577640501501

• Validity of claims-based algorithms to identify developmental disorders in children Straub, L., Hernandez-Diaz, S., Bateman, B. T., Zhu, Y., Gray, K. J., Huybrechts, K. F. WILEY. 2020: 535

  View details for Web of Science ID 000577640501518

• Patterns of antibiotic medication use during pregnancy among publicly and commercially insured women in the United States Zhu, Y., Bateman, B. T., Hernandez-Diaz, S., Gray, K. J., Mogun, H., Huybrechts, K. F. WILEY. 2020: 547

  View details for Web of Science ID 000577640501544

• Association of Gabapentinoids With the Risk of Opioid-Related Adverse Events in Surgical Patients in the United States. JAMA network open Bykov, K., Bateman, B. T., Franklin, J. M., Vine, S. M., Patorno, E. 2020; 3 (12): e2031647

  Abstract

  The use of gabapentinoids in multimodal postoperative analgesia is increasing; however, when coadministered with opioids, these drugs may potentiate central nervous system and respiratory depression.To evaluate the association between perioperative coadministration of gabapentinoids and opioids with inpatient opioid-related adverse events in surgical patients.This cohort study used propensity score trimming, stratification, and weighting of adults admitted for a major surgery between October 2007 and December 2017 who were treated with opioids on the day of surgery and included in the Premier Research database. Data analysis was conducted from February to April 2020.Gabapentinoids (gabapentin or pregabalin) coadministered with opioids starting the day of surgery vs opioid therapy without gabapentinoids.Primary outcome was opioid overdose. Secondary outcomes included respiratory complications, unspecified adverse effects of opioid use, and a composite of these 3 outcomes. Patients were followed up for as long as 30 days from the day of surgery until deviation from the initial treatment regimen or discharge.Gabapentinoids with opioids were administered to 892 484 of 5 547 667 eligible admissions (16.1%; mean [SD] age, 63.5 [11.8] years; 353 315 [39.6%] men). Among the 4 655 183 patients who received opioids only, the mean (SD) age was 63.7 (14.7) years, and 1 913 284 (41.1%) were men. Overall, 441 overdose events were identified, with absolute risks of 1.4 per 10 000 patients with gabapentinoid exposure and 0.7 per 10 000 patients receiving opioids only. Following propensity score trimming, the cohort included 737 383 patients exposed to gabapentinoids and 3 002 480 patients receiving opioids only. The primary analysis yielded the adjusted hazard ratio of 1.95 (95% CI, 1.49-2.55), and the number needed to treat for an additional overdose to occur was 16 914 patients (95% CI, 11 556-31 537 patients). Adjusted hazard ratios for secondary outcomes were 1.68 (95% CI, 1.59-1.78) for respiratory complications, 1.77 (95% CI, 1.61-1.93) for unspecified adverse effects of opioids, and 1.70 (95% CI, 1.62-1.79) for the composite outcome. The results were consistent across sensitivity analyses and subgroups identified by key clinical factors.In this real-world cohort study of patients who underwent major surgery, concomitant use of gabapentinoids with opioids was associated with increased risk of opioid overdose and other opioid-related adverse events; however, the absolute risk of adverse events was low.

  View details for DOI 10.1001/jamanetworkopen.2020.31647

  View details for PubMedID 33372975

  View details for PubMedCentralID PMC7772715

• Delays in administration of antihypertensive medication for hypertensive emergencies at a tertiary care center Seifert, S., Molitor, R., Holland, E., Bateman, B. T., Robinson, J. N., Farber, M. MOSBY-ELSEVIER. 2020: S590-S591

  View details for DOI 10.1016/j.ajog.2019.11.962

  View details for Web of Science ID 000504997301273

• Comparison of strategies to screen for severe maternal morbidity Easter, S., Saadeh, M., Sweeney, V. H., Manganaro, K., Reiff, E., Bateman, B. T., Robinson, J. N. MOSBY-ELSEVIER. 2020: S552

  View details for DOI 10.1016/j.ajog.2019.11.897

  View details for Web of Science ID 000504997301208

• Optimizing the Maternal Early Warning System for clinical use Easter, S., Fields, K. G., Gagne, J. J., Bateman, B. T., Robinson, J. N. MOSBY-ELSEVIER. 2020: S153

  View details for DOI 10.1016/j.ajog.2019.11.236

  View details for Web of Science ID 000504997300220

• Drug Enforcement Agency 2014 Hydrocodone Rescheduling Rule and Opioid Dispensing after Surgery. Anesthesiology Neuman, M. D., Hennessy, S., Small, D. S., Newcomb, C., Gaskins, L., Brensinger, C. M., Wijeysundera, D. N., Bateman, B. T., Wunsch, H. 2020; 132 (5): 1151-1164

  Abstract

  In 2014, the U.S. Drug Enforcement Agency reclassified hydrocodone from Schedule III to Schedule II of the Controlled Substances Act, resulting in new restrictions on refills. The authors hypothesized that hydrocodone rescheduling led to decreases in total opioid dispensing within 30 days of surgery and reduced new long-term opioid dispensing among surgical patients.The authors studied privately insured, opioid-naïve adults undergoing 10 general or orthopedic surgeries between 2011 and 2015. The authors conducted a differences-in-differences analysis that compared overall opioid dispensing before versus after the rescheduling rule for patients treated by surgeons who frequently prescribed hydrocodone before rescheduling (i.e., patients who were functionally exposed to rescheduling's impact) while adjusting for secular trends via a comparison group of patients treated by surgeons who rarely prescribed hydrocodone (i.e., unexposed patients). The primary outcome was any filled opioid prescription between 90 and 180 days after surgery; secondary outcomes included the 30-day refill rate and the amount of opioids dispensed initially and at 30 days postoperatively.The sample included 65,136 patients. The percentage of patients filling a prescription beyond 90 days was similar after versus before rescheduling (absolute risk difference, -1.1%; 95% CI, -2.3% to 0.1%; P = 0.084). The authors estimated the rescheduling rule to be associated with a 45.4-mg oral morphine equivalent increase (difference-in-differences estimate; 95% CI, 34.2-56.7 mg; P < 0.001) in initial opioid dispensing, a 4.1% absolute decrease (95% CI, -5.5% to -2.7%; P < 0.001) in refills within 30 days, and a 37.7-mg oral morphine equivalent increase (95% CI, 20.6-54.8 mg; P = 0.008) in opioids dispensed within 30 days.Among patients treated by surgeons who frequently prescribed hydrocodone before the Drug Enforcement Agency 2014 hydrocodone rescheduling rule, rescheduling did not impact long-term opioid receipt, although it was associated with an increase in opioid dispensing within 30 days of surgery.

  View details for DOI 10.1097/ALN.0000000000003188

  View details for PubMedID 32101973

  View details for PubMedCentralID PMC7160003

• Validation of algorithms to identify adverse perinatal outcomes in the Medicaid Analytic Extract database. Pharmacoepidemiology and drug safety He, M., Huybrechts, K. F., Dejene, S. Z., Straub, L., Bartels, D., Burns, S., Combs, D. J., Cottral, J., Gray, K. J., Manning-Geist, B. L., Mogun, H., Reimers, R. M., Hernandez-Diaz, S., Bateman, B. T. 2020; 29 (4): 419-426

  Abstract

  The Medicaid Analytic eXtract (MAX) is a health care utilization database from publicly insured individuals that has been used for studies of drug safety in pregnancy. Claims-based algorithms for defining many important maternal and neonatal outcomes have not been validated.To validate claims-based algorithms for identifying selected pregnancy outcomes in MAX using hospital medical records.The medical records of mothers who delivered between 2000 and 2010 within a single large healthcare system were linked to their claims in MAX. Claims-based algorithms for placental abruption, preeclampsia, postpartum hemorrhage, small for gestational age, and noncardiac congenital malformation were defined. Fifty randomly sampled cases for each outcome identified using these algorithms were selected, and their medical records were independently reviewed by two physicians to confirm the presence of the diagnosis of interest; disagreements were resolved by a third physician reviewer. Positive predictive values (PPVs) and 95% confidence intervals (CIs) of the claims-based algorithms were calculated using medical records as the gold standard.The linked cohort included 10,899 live-birth pregnancies. The PPV was 92% (95% CI, 82%-97%) for placental abruption, 82% (95% CI, 70%-91%) for preeclampsia, 74% (95% CI, 61%-85%) for postpartum hemorrhage, 92% (95% CI, 82%-97%) for small for gestational age, and 86% (95% CI, 74%-94%) for noncardiac congenital malformation.Across the perinatal outcomes considered, PPVs ranged between 74% and 92%. These PPVs can inform bias analyses that correct for outcome misclassification.

  View details for DOI 10.1002/pds.4967

  View details for PubMedID 32124511

• Cephalic Elevation Device for Second-Stage Cesarean Delivery: A Randomized Controlled Trial. Obstetrics and gynecology Lassey, S. C., Little, S. E., Saadeh, M., Patton, N., Farber, M. K., Bateman, B. T., Robinson, J. N. 2020; 135 (4): 879-884

  Abstract

  A cephalic elevation device is an inflatable device that elevates the fetal head. We sought to evaluate whether such a device reduces time to delivery after hysterotomy and lowers morbidity in cesarean deliveries during the second stage of labor.We conducted a double-blind randomized controlled trial among nulliparous, term women aged 18-50 years with vertex singleton pregnancies. Women were eligible if they were to undergo cesarean delivery in the second stage of labor. All participating women had the cephalic elevation device inserted by the delivering provider and were randomly allocated to inflation or noninflation of the device. Inflation was performed in a blinded fashion. The primary outcome was time from hysterotomy to delivery. A sample size of 30 per group (N=60 participants) was planned to detect a 50% decrease in time to delivery after hysterotomy with cephalic elevation device inflation.From January 2018 through July 2019, 60 women who underwent cesarean delivery in the second stage were randomized. Analysis was by intention to treat. Women in the inflation group were older (33 vs 30.5 years), but the groups were otherwise similar. In both groups, most women had a low-transverse hysterotomy (93%). The median time from hysterotomy to delivery was significantly shorter in the inflation group (31 vs 54 seconds; P<.01). There was no significant difference in neonatal outcomes.Use of the cephalic elevation device during second-stage cesarean delivery led to a 23-second reduction time from hysterotomy to delivery.ClinicalTrials.gov, NCT03342508.The cephalic elevation devices used in this study were donated by Safe Obstetrics Systems.

  View details for DOI 10.1097/AOG.0000000000003746

  View details for PubMedID 32168216

  View details for PubMedCentralID PMC7098440

• Rates and Costs of Dispensing Naloxone to Patients at High Risk for Opioid Overdose in the United States, 2014-2018. Drug safety Barenie, R. E., Gagne, J. J., Kesselheim, A. S., Pawar, A., Tong, A., Luo, J., Bateman, B. T. 2020; 43 (7): 669-675

  Abstract

  Clinical practice guidelines recommend co-prescribing naloxone to patients at high risk of opioid overdose, but few such patients receive naloxone. High costs of naloxone may contribute to limited dispensing.The aim of this study was to evaluate rates and costs of dispensing naloxone to patients receiving opioid prescriptions and at high risk for opioid overdose.Using claims data from a large US commercial insurance company, we conducted a retrospective cohort study of new opioid initiators between January 2014 and December 2018. We identified patients at high risk for overdose defined as a diagnosis of opioid use disorder, prior overdose, an opioid prescription of ≥ 50 mg morphine equivalents/day for ≥ 90 days, and/or concurrent benzodiazepine prescriptions.Among 5,292,098 new opioid initiators, 616,444 (12%) met criteria for high risk of overdose during follow-up, and, of those, 3096 (0.5%) were dispensed naloxone. The average copayment was US$24.83 for naloxone (standard deviation [SD] 67.66) versus US$9.74 for the index opioid (SD 19.75). The average deductible was US$6.18 for naloxone (SD 27.32) versus US$3.74 for the index opioid (SD 25.56), with 94% and 88% having deductibles of US$0 for their naloxone and opioid prescriptions, respectively. The average out-of-pocket cost was US$31.01 for naloxone (SD 73.64) versus US$13.48 for the index opioid (SD 34.95).Rates of dispensing naloxone to high risk patients were extremely low, and prescription costs varied greatly. Since improving naloxone's affordability may increase access, whether naloxone's high cost is associated with low dispensing rates should be evaluated.

  View details for DOI 10.1007/s40264-020-00923-6

  View details for PubMedID 32180134

• Persistent Postoperative Opioid Use: A Systematic Literature Search of Definitions and Population-based Cohort Study. Anesthesiology Jivraj, N. K., Raghavji, F., Bethell, J., Wijeysundera, D. N., Ladha, K. S., Bateman, B. T., Neuman, M. D., Wunsch, H. 2020; 132 (6): 1528-1539

  Abstract

  While persistent opioid use after surgery has been the subject of a large number of studies, it is unknown how much variability in the definition of persistent use impacts the reported incidence across studies. The objective was to evaluate the incidence of persistent use estimated with different definitions using a single cohort of postoperative patients, as well as the ability of each definition to identify patients with opioid-related adverse events.The literature was reviewed to identify observational studies that evaluated persistent opioid use among opioid-naive patients requiring surgery, and any definitions of persistent opioid use were extracted. Next, the authors performed a population-based cohort study of opioid-naive adults undergoing 1 of 18 surgical procedures from 2013 to 2017 in Ontario, Canada. The primary outcome was the incidence of persistent opioid use, defined by each extracted definition of persistent opioid use. The authors also assessed the sensitivity and specificity of each definition to identify patients with an opioid-related adverse event in the year after surgery.Twenty-nine different definitions of persistent opioid use were identified from 39 studies. Applying the different definitions to a cohort of 162,830 opioid-naive surgical patients, the incidence of persistent opioid use in the year after surgery ranged from 0.01% (n = 10) to 14.7% (n = 23,442), with a median of 0.7% (n = 1,061). Opioid-related overdose or diagnosis associated with opioid use disorder in the year of follow-up occurred in 164 patients (1 per 1,000 operations). The sensitivity of each definition to identify patients with the composite measure of opioid use disorder or opioid-related toxicity ranged from 0.01 to 0.36, while specificity ranged from 0.86 to 1.00.The incidence of persistent opioid use reported after surgery varies more than 100-fold depending on the definition used. Definitions varied markedly in their sensitivity for identifying adverse opioid-related event, with low sensitivity overall across measures.

  View details for DOI 10.1097/ALN.0000000000003265

  View details for PubMedID 32243330

  View details for PubMedCentralID PMC8202398

• Methodological Challenges in Conducting Large-Scale Real-World Data Analyses on Opioid Use in Musculoskeletal Disorders. The Journal of bone and joint surgery. American volume Kim, S. C., Bateman, B. T. 2020; 102 Suppl 1: 10-14

  View details for DOI 10.2106/JBJS.20.00121

  View details for PubMedID 32251129

• The Most Influential Publications in Obstetric Anesthesiology, 1998-2017: Utilizing the Delphi Method for Expert Consensus. Anesthesia and analgesia Reale, S. C., Tsen, L. C., Camann, W. R., Bateman, B. T., Farber, M. K. 2020; 131 (1): 239-244

  Abstract

  There have been many advances in obstetric anesthesiology in the past 2 decades. We sought to create a list of highly influential publications in the field using the Delphi method among a group of obstetric anesthesiology experts to create an important educational, clinical, and research resource.Experts in the field, defined as obstetric anesthesiologists selected to present the Gerard W. Ostheimer Lecture at the Society for Obstetric Anesthesia and Perinatology (SOAP) annual meeting within the past 20 years, were recruited to participate. The Delphi technique was used by administering 3 rounds of surveys. Participants were initially asked to identify the highly influential publications from the year they presented the Ostheimer lecture, in addition to the most influential publications from the time period overall. Highly influential publications were defined as those that changed traditional views, invoked meaningful practices, catalyzed additional research, and fostered ideas or practices that had durability over time. After each round of surveys, responses were collected and used as choices for subsequent surveys with the goal of obtaining group consensus.We determined expert consensus on 22 highly influential publications from 1998 to 2017. The focus of these publications ranged from disease entities, interventions, treatment methodologies, and complications.Key themes in the publications chosen included the reduction of maternal morbidity and mortality and refinements in the analgesic and anesthetic management of labor and delivery.

  View details for DOI 10.1213/ANE.0000000000004753

  View details for PubMedID 32282388

• Antipsychotic drug use in pregnancy: A multinational study from ten countries. Schizophrenia research Reutfors, J., Cesta, C. E., Cohen, J. M., Bateman, B. T., Brauer, R., Einarsdóttir, K., Engeland, A., Furu, K., Gissler, M., Havard, A., Hernandez-Diaz, S., Huybrechts, K. F., Karlstad, Ø., Leinonen, M. K., Li, J., Man, K. K., Pazzagli, L., Schaffer, A., Schink, T., Wang, Z., Yu, Y., Zoega, H., Bröms, G. 2020; 220: 106-115

  Abstract

  To compare the prevalence and trends of antipsychotic drug use during pregnancy between countries across four continents.Individually linked health data in Denmark (2000-2012), Finland (2005-2014), Iceland (2004-2017), Norway (2005-2015), Sweden (2006-2015), Germany (2006-2015), Australia (New South Wales, 2004-2012), Hong Kong (2001-2015), UK (2006-2016), and the US (Medicaid, 2000-2013, and IBM MarketScan, 2012-2015) were used. Using a uniformed approach, we estimated the prevalence of antipsychotic use as the proportion of pregnancies where a woman filled at least one antipsychotic prescription within three months before pregnancy until birth. For the Nordic countries, data were meta-analyzed to investigate maternal characteristics associated with the use of antipsychotics.We included 8,394,343 pregnancies. Typical antipsychotic use was highest in the UK (4.4%) whereas atypical antipsychotic use was highest in the US Medicaid (1.5%). Atypical antipsychotic use increased over time in most populations, reaching 2% in Australia (2012) and US Medicaid (2013). In most countries, prochlorperazine was the most commonly used typical antipsychotic and quetiapine the most commonly used atypical antipsychotic. Use of antipsychotics decreased across the trimesters of pregnancy in all populations except Finland. Antipsychotic use was elevated among smokers and those with parity ≥4 in the Nordic countries.Antipsychotic use during pregnancy varied considerably between populations, partly explained by varying use of the typical antipsychotic prochlorperazine, which is often used for nausea and vomiting in early pregnancy. Increasing usage of atypical antipsychotics among pregnant women reflects the pattern that was previously reported for the general population.

  View details for DOI 10.1016/j.schres.2020.03.048

  View details for PubMedID 32295750

  View details for PubMedCentralID PMC7306443

• Ondansetron Use in Pregnancy and Congenital Malformations-Reply. JAMA Huybrechts, K. F., Hernandez-Diaz, S., Bateman, B. T. 2020; 323 (20): 2097-2098

  View details for DOI 10.1001/jama.2020.5067

  View details for PubMedID 32453362

• Trends in Postpartum Hemorrhage in the United States From 2010 to 2014. Anesthesia and analgesia Reale, S. C., Easter, S. R., Xu, X., Bateman, B. T., Farber, M. K. 2020; 130 (5): e119-e122

  Abstract

  Postpartum hemorrhage (PPH) is a leading cause of morbidity and mortality in the United States; its prevalence increased during the 1990s-2000s. The purpose of this study was to reevaluate trends in PPH using the National Inpatient Sample. From 2010 to 2014, the prevalence of PPH increased from 2.9% (95% confidence interval [CI], 2.7%-3.1%) to 3.2% (95% CI, 3.1%-3.3%) of deliveries. Adjusting for PPH risk factors did not substantially attenuate this trend. Among patients with PPH, there was a decline in associated coagulopathy, acute respiratory failure, and maternal death, but an increase in sepsis and acute renal failure. Continued focus on PPH management is warranted.

  View details for DOI 10.1213/ANE.0000000000004424

  View details for PubMedID 31567319

• Cannabis Use Disorder and Perioperative Outcomes in Major Elective Surgeries: A Retrospective Cohort Analysis. Anesthesiology Goel, A., McGuinness, B., Jivraj, N. K., Wijeysundera, D. N., Mittleman, M. A., Bateman, B. T., Clarke, H., Kotra, L. P., Ladha, K. S. 2020; 132 (4): 625-635

  Abstract

  Although cannabis is known to have cardiovascular and psychoactive effects, the implications of its use before surgery are currently unknown. The objective of the present study was to determine whether patients with an active cannabis use disorder have an elevated risk of postoperative complications.The authors conducted a retrospective population-based cohort study of patients undergoing elective surgery in the United States using the Nationwide Inpatient Sample from 2006 to 2015. A sample of 4,186,622 inpatients 18 to 65 yr of age presenting for 1 of 11 elective surgeries including total knee replacement, total hip replacement, coronary artery bypass graft, caesarian section, cholecystectomy, colectomy, hysterectomy, breast surgery, hernia repair, laminectomy, and other spine surgeries was selected. The principal exposure was an active cannabis use disorder, as defined by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) diagnostic codes for cannabis dependence and cannabis abuse. The primary outcome was a composite endpoint of in-hospital postoperative myocardial infarction, stroke, sepsis, deep vein thrombosis, pulmonary embolus, acute kidney injury requiring dialysis, respiratory failure, and in-hospital mortality. Secondary outcomes included hospital length of stay, total hospital costs, and the individual components of the composite endpoint.The propensity-score matched-pairs cohort consisted of 27,206 patients. There was no statistically significant difference between patients with (400 of 13,603; 2.9%) and without (415 of 13,603; 3.1%) a reported active cannabis use disorder with regard to the composite perioperative outcome (unadjusted odds ratio = 1.29; 95% CI, 1.17 to 1.42; P < 0.001; Adjusted odds ratio = 0.97; 95% CI, 0.84 to 1.11; P = 0.63). However, the adjusted odds of postoperative myocardial infarction was 1.88 (95% CI, 1.31 to 2.69; P < 0.001) times higher for patients with a reported active cannabis use disorder (89 of 13,603; 0.7%) compared with those without (46 of 13,603; 0.3%) an active cannabis use disorder (unadjusted odds ratio = 2.88; 95% CI, 2.34 to 3.55; P < 0.001).An active cannabis use disorder is associated with an increased perioperative risk of myocardial infarction.

  View details for DOI 10.1097/ALN.0000000000003067

  View details for PubMedID 31789638

• Response to Letter. Obstetrics and gynecology Easter, S. R., Robinson, J. N., Menard, M. K., Creanga, A. A., Xu, X., Little, S. E., Bateman, B. T. 2020; 135 (1): 220-221

  View details for DOI 10.1097/AOG.0000000000003641

  View details for PubMedID 31856111

• Using nationally representative survey data for external adjustment of unmeasured confounders: An example using the NHANES data. Pharmacoepidemiology and drug safety Hernández-Díaz, S., Bateman, B. T., Palmsten, K., Schneeweiss, S., Huybrechts, K. F. 2020; 29 (9): 1151-1158

  Abstract

  To evaluate the use of data from population-based surveys such as the National Health and Nutrition Examination Survey (NHANES) for external adjustment for confounders imperfectly measured in health care databases in the United States.Our example study used Medicaid Analytic eXtract (MAX) data to estimate the relative risk (RR) for prenatal serotonin-norepinephrine reuptake inhibitors (SNRIs) exposure and cardiac defects. Smoking and obesity are known confounders poorly captured in databases. NHANES collects information on lifestyle factors, depression, and prescription medications. External adjustment requires information on the prevalence of confounders and their association with SNRI use; which was obtained from the NHANES. It also requires estimates of their association with the outcome, which were based on the literature and allowed us to correct the RR using sensitivity analyses.In MAX, the RR for the association between prenatal SNRI exposure and cardiac defects was 1.51 unadjusted and 1.20 adjusted for measured confounders and restricted to women with depression. In NHANES, among women of childbearing age with depression, the prevalence of smoking was 60.2% (95% Confidence Interval 43.2, 74.3) for SNRI users and 44.1% (39.6, 48.8) for nonusers of antidepressants. The corresponding estimates for obesity were 59.2% (43.2, 74.3) and 40.5% (35.9, 45.0), respectively. If the associations between smoking and obesity with cardiac defects are independent from each other and from other measured confounders, additional adjustment for smoking and obesity would move the RR from 1.20 to around 1.10.National surveys like NHANES are readily available sources of information on potential confounders and they can be used to assess and improve the validity of RR estimates from observational studies missing data on known risk factors.

  View details for DOI 10.1002/pds.4946

  View details for PubMedID 31863536

• Perinatal Outcomes Associated with Maternal Asthma and Its Severity and Control During Pregnancy. The journal of allergy and clinical immunology. In practice Yland, J. J., Bateman, B. T., Huybrechts, K. F., Brill, G., Schatz, M. X., Wurst, K. E., Hernández-Díaz, S. 2020; 8 (6): 1928-1937.e3

  Abstract

  Estimates of the effects of maternal asthma on pregnancy outcomes are inconsistent across studies, possibly because of differences in exposure definition.To evaluate the risk of adverse perinatal outcomes associated with maternal asthma diagnosis, severity, and control in a large, nationally representative cohort.This study was conducted within the IBM Health MarketScan Commercial Claims and Encounters Database (2011-2015) and the Medicaid Analytic eXtract database (2000-2014). Asthma was identified by diagnosis and treatment codes, severity was based on medications dispensed, and control was based on short-acting β-agonist dispensations and exacerbations. We estimated the relative risks (RRs) of stillbirth, spontaneous abortion, preterm birth, small for gestational age (SGA), neonatal intensive care unit (NICU) admission, and congenital malformations, comparing pregnancies with differing asthma disease status.We identified 29,882 pregnancies complicated by asthma in the MarketScan database and 160,638 in the Medicaid Analytic eXtract database. We observed no consistent associations between asthma diagnosis, severity, or control, and stillbirth, abortions, or malformations. However, we observed increased risks of prematurity, SGA, and NICU admission among women with asthma compared with those without asthma. Compared with women with well-controlled asthma, women with poor control late in pregnancy had an increased risk of preterm birth (relative risk, 1.39; 95% CI, 1.32-1.46) and NICU admission (relative risk, 1.26; 95% CI, 1.17-1.35). More severe asthma was associated with SGA (relative risk, 1.18; 95% CI, 1.07-1.30).We did not observe an increased risk of pregnancy losses or malformations among women with asthma. However, we found an association between asthma severity and SGA, and between exacerbations late in pregnancy and preterm delivery and NICU admission.

  View details for DOI 10.1016/j.jaip.2020.01.016

  View details for PubMedID 31981730

• Age and postoperative opioid prescriptions: a population-based cohort study of opioid-naïve adults. Pharmacoepidemiology and drug safety Bethell, J., Neuman, M. D., Bateman, B. T., Hill, A. D., Ladha, K. S., Wijeysundera, D. N., Wunsch, H. 2020; 29 (4): 504-509

  Abstract

  Opioids are commonly prescribed for acute pain after surgery. However, it is unclear whether these prescriptions are usually modified to account for patient age and, in particular, opioid-related risks among older adults. We therefore sought to describe postoperative opioid prescriptions filled by opioid-naïve adults undergoing four common surgical procedures.This retrospective cohort study used individually linked surgery and prescription opioid dispensing data from Ontario, Canada to create a population-based sample of 135 659 opioid-naïve adults who underwent one of four surgical procedures (laparoscopic cholecystectomy, laparoscopic appendectomy, knee meniscectomy, or breast excision) between 2013 and 2017. Patient age, in years, was categorized as 18 to 64, 65 to 69, 70 to 74, and 75 and over. Postoperative opioid prescriptions were identified as those filled on or within 6 days of surgical discharge date. For those who filled a prescription, we assessed the total morphine milligram equivalent (MME) dose, types of opioids, and any subsequent opioid prescriptions filled within 30 days of surgical discharge date. Results were presented stratified by surgical procedure.For three of the four surgical procedures we assessed, the proportion of patients who filled a postoperative opioid prescription decreased with age (P < 0.001 for trend), and there was a small shift in the type of opioid (more codeine or tramadol and less oxycodone; P < 0.001 for trend). However, the total MME dose of the initial prescription(s) filled showed minimal age-related trends.The proportion of opioid-naïve patients filling postoperative opioid prescriptions decreases with age. However, postoperative opioid prescription dosage is not typically different in older adults.

  View details for DOI 10.1002/pds.4964

  View details for PubMedID 32056336

  View details for PubMedCentralID PMC7188586

• Predicting overdose among individuals prescribed opioids using routinely collected healthcare utilization data. PloS one Sun, J. W., Franklin, J. M., Rough, K., Desai, R. J., Hernández-Díaz, S., Huybrechts, K. F., Bateman, B. T. 2020; 15 (10): e0241083

  Abstract

  With increasing rates of opioid overdoses in the US, a surveillance tool to identify high-risk patients may help facilitate early intervention.To develop an algorithm to predict overdose using routinely-collected healthcare databases.Within a US commercial claims database (2011-2015), patients with ≥1 opioid prescription were identified. Patients were randomly allocated into the training (50%), validation (25%), or test set (25%). For each month of follow-up, pooled logistic regression was used to predict the odds of incident overdose in the next month based on patient history from the preceding 3-6 months (time-updated), using elastic net for variable selection. As secondary analyses, we explored whether using simpler models (few predictors, baseline only) or different analytic methods (random forest, traditional regression) influenced performance.We identified 5,293,880 individuals prescribed opioids; 2,682 patients (0.05%) had an overdose during follow-up (mean: 17.1 months). On average, patients who overdosed were younger and had more diagnoses and prescriptions. The elastic net model achieved good performance (c-statistic 0.887, 95% CI 0.872-0.902; sensitivity 80.2, specificity 80.1, PPV 0.21, NPV 99.9 at optimal cutpoint). It outperformed simpler models based on few predictors (c-statistic 0.825, 95% CI 0.808-0.843) and baseline predictors only (c-statistic 0.806, 95% CI 0.787-0.26). Different analytic techniques did not substantially influence performance. In the final algorithm based on elastic net, the strongest predictors were age 18-25 years (OR: 2.21), prior suicide attempt (OR: 3.68), opioid dependence (OR: 3.14).We demonstrate that sophisticated algorithms using healthcare databases can be predictive of overdose, creating opportunities for active monitoring and early intervention.

  View details for DOI 10.1371/journal.pone.0241083

  View details for PubMedID 33079968

  View details for PubMedCentralID PMC7575098

• Reductions in commuting mobility correlate with geographic differences in SARS-CoV-2 prevalence in New York City. Nature communications Kissler, S. M., Kishore, N., Prabhu, M., Goffman, D., Beilin, Y., Landau, R., Gyamfi-Bannerman, C., Bateman, B. T., Snyder, J., Razavi, A. S., Katz, D., Gal, J., Bianco, A., Stone, J., Larremore, D., Buckee, C. O., Grad, Y. H. 2020; 11 (1): 4674

  Abstract

  SARS-CoV-2-related mortality and hospitalizations differ substantially between New York City neighborhoods. Mitigation efforts require knowing the extent to which these disparities reflect differences in prevalence and understanding the associated drivers. Here, we report the prevalence of SARS-CoV-2 in New York City boroughs inferred using tests administered to 1,746 pregnant women hospitalized for delivery between March 22nd and May 3rd, 2020. We also assess the relationship between prevalence and commuting-style movements into and out of each borough. Prevalence ranged from 11.3% (95% credible interval [8.9%, 13.9%]) in Manhattan to 26.0% (15.3%, 38.9%) in South Queens, with an estimated city-wide prevalence of 15.6% (13.9%, 17.4%). Prevalence was lowest in boroughs with the greatest reductions in morning movements out of and evening movements into the borough (Pearson R = -0.88 [-0.52, -0.99]). Widespread testing is needed to further specify disparities in prevalence and assess the risk of future outbreaks.

  View details for DOI 10.1038/s41467-020-18271-5

  View details for PubMedID 32938924

  View details for PubMedCentralID PMC7494926

• Trends in Human Papillomavirus Vaccination in Commercially Insured Children in the United States. Pediatrics Chen, S. T., Huybrechts, K. F., Bateman, B. T., Hernández-Díaz, S. 2020; 146 (4)

  Abstract

  The human papillomavirus (HPV) vaccine was recommended in 2006 for girls and in 2011 for boys. The Healthy People 2020 goal for 2-dose HPV vaccination coverage is 80% by age 15 for girls and boys. We used nationwide population-based data to describe trends in HPV vaccination in children.We conducted a cohort study nested within the MarketScan health care database between January 2003 and December 2017. Children were followed from the year they turned 9 until HPV vaccination, insurance disenrollment, or the end of the year when they turned 17, whichever came first. We estimated the cumulative incidence of at least 1- and 2-dose HPV vaccination, stratified by birth year, sex, and state. In secondary analyses, we evaluated the association between state-level vaccination policies and HPV vaccination coverage.This study included 7 837 480 children and 19.8 million person-years. The proportion of 15-year-old girls and boys with at least a 1-dose HPV vaccination increased from 38% and 5% in 2011 to 57% and 51% in 2017, respectively; the proportion with at least a 2-dose vaccination went from 30% and 2% in 2011 to 46% and 39% in 2017, respectively. By 2017, 2-dose HPV vaccination coverage varied from 80% in Washington, District of Columbia, among girls to 15% in Mississippi among boys and was positively correlated with legislation for HPV vaccine education and pediatrician availability.Despite the increasing trends in uptake, HPV vaccine coverage among commercially insured children in the United States remains behind target levels, with substantial disparities by state.

  View details for DOI 10.1542/peds.2019-3557

  View details for PubMedID 32928985

• Association Between Congenital Cytomegalovirus and the Prevalence at Birth of Microcephaly in the United States. JAMA pediatrics Messinger, C. J., Lipsitch, M., Bateman, B. T., He, M., Huybrechts, K. F., MacDonald, S., Mogun, H., Mott, K., Hernández-Díaz, S. 2020; 174 (12): 1159-1167

  Abstract

  Congenital cytomegalovirus (cCMV) has received far less clinical and public health attention as a teratogenic infection than the Zika virus epidemic. However, cCMV may be responsible for a large fraction of microcephaly cases in the United States.To evaluate the association between cCMV and the prevalence at birth of microcephaly in the United States.This population-based cohort study included pregnant women and their newborns identified in 2 insurance claims databases from the United States: Medicaid Analytic eXtract (January 1, 2000, to December 31, 2013) and IBM Research MarketScan, a database for employer-sponsored private health insurance (January 1, 2011, to September 30, 2015). All pregnancies that resulted in live births in women with full health benefits were included. Analysis began June 2016 and ended May 2020.Congenital cytomegalovirus infection documented in inpatient or outpatient newborn claims records.The primary outcome was microcephaly at birth documented in inpatient or outpatient newborn and/or maternal claims records. Cases with chromosomal abnormalities or neural tube defects were excluded. The association between cCMV and microcephaly was estimated in the pooled cohort using prevalence ratios (PRs) and 95% CIs.In the pooled cohort of 2 338 580 pregnancies (2 075 410 pregnancies [88.7%] were among women younger than 35 years), 336 infants (0.014%) had a cCMV diagnosis. The prevalence of microcephaly among newborns with and without a cCMV diagnosis was 655 and 2.8 per 10 000 live births, respectively (PR, 232; 95% CI, 154-350). After restricting to CMV-tested newborns (572 [0.024%]) to correct for preferential testing of infants with microcephaly, the PR was 15 (95% CI, 5.2-41). However, this PR is biased if other cCMV-related outcomes (eg, hearing loss) trigger testing because cCMV prevalence in tested infants, with ([46%]) or without microcephaly (22 of 559 [3.9%]), would overestimate that in the source population. Therefore, the prevalence of cCMV in overall infants with microcephaly (22 of 669 [3.2%]) was compared with that from an external unbiased sample of US infants screened at birth (449 of 100 332 [0.45%]) to estimate a PR of 7.4 (95% CI, 4.8-11.5) as a conservative lower bound.Congenital cytomegalovirus infection increases the prevalence of microcephaly at birth by at least 7-fold. Prevention of CMV infection during pregnancy might substantially reduce the number of newborns with microcephaly and other cCMV-related outcomes in the United States.

  View details for DOI 10.1001/jamapediatrics.2020.3009

  View details for PubMedID 32926077

  View details for PubMedCentralID PMC7490747

• Getting Risk Prediction Right. Obstetrics and gynecology Bateman, B. T., Robinson, J. N. 2020; 136 (3): 437-439

  View details for DOI 10.1097/AOG.0000000000004060

  View details for PubMedID 32769635

• In utero opioid exposure and risk of infections in childhood: A multinational Nordic cohort study. Pharmacoepidemiology and drug safety Mahic, M., Hernandez-Diaz, S., Wood, M., Kieler, H., Odsbu, I., Nørgaard, M., Öztürk, B., Bateman, B. T., Hjellvik, V., Skurtveit, S., Handal, M. 2020; 29 (12): 1596-1604

  Abstract

  There is an increasing number of children with in utero exposure to opioids. Knowledge about opioid safety in pregnancy, particularly for outcomes later in childhood is scarce. It has been suggested that opioids can modulate immune system and increase the risk of infections. Our goal was to study the impact of in utero opioid exposure on the immune system and the risk of infections in childhood.This population-based cohort study used nationwide registers from Denmark, Norway, and Sweden. Among pregnant women we identified users of opioids for two different indications, opioids used in opioid maintenance therapy (OMT) and opioids used for treatment of pain. We followed the exposed children and studied susceptibility for infections measured as number of antibiotic prescriptions expressed as Incidence rate ratios (IRRs) and diagnoses in specialist health care expressed as hazard ratios (HRs).After adjustment we did not observe increased risk for filling antibiotic prescriptions in children exposed to OMT opioids compared with OMT discontinuers (IRR, 1.08; 95% CI 0.81-1.44 in Norway and Sweden, and IRR, 0.74; 95% CI 0.63-0.88 in Denmark), or for diagnosis of infection in specialist health care (HR 0.83; 95% CI 0.55-1.26 in Norway and Sweden, and 0.82; 95% CI 0.62-1.10 in Denmark).In this population-based cohort study, we did not observe increased risk of infections among children prenatally exposed to OMT opioids when compared to OMT discontinuers, nor long-term analgesic opioids exposed when compared to short-term analgesic opioids exposed.

  View details for DOI 10.1002/pds.5088

  View details for PubMedID 32767610

• Association between mothers' postoperative opioid prescriptions and opioid-related events in their children: A population-based cohort study. Health reports Bethell, J., Neuman, M. D., Bateman, B. T., Ladha, K. S., Hill, A., Li, G., Wijeysundera, D. N., Wunsch, H. 2020; 31 (6): 12-19

  Abstract

  Postoperative opioid prescriptions may be associated with risks of unintentional poisoning and drug diversion in other household members. The objective of this study was to explore the association between mothers' postoperative opioid prescriptions and incidence of opioid-related events in their children (aged 1 to 24 years).This retrospective cohort study used individually linked administrative health data from Ontario, Canada. A population-based sample of 170,156 opioid-naïve mothers (aged 15 to 64) (see Figure 1) who underwent surgery between 2013 and 2017 in Ontario was linked through birth records to create a cohort of their 283,550 opioid-naïve children (aged 1 to 24). The association between postoperative opioid analgesic prescriptions filled by mothers within seven days of discharge after surgery and opioid-related events (emergency department presentations or inpatient admissions for opioid poisoning, or mental and behavioural disorders attributable to opioid use) in their children within one year of their mother's discharge was assessed.Overall, 60.4% of the children in the cohort had a mother who filled a postoperative opioid prescription. The incidence of opioid-related events in children in the year after a mother's surgery was low overall (n=36/283,550, 0.01%), but higher among children whose mother filled a postoperative opioid prescription (n=29/171,139, 0.02%, vs. n=7/112,411, 0.01%, p=0.02), including in an analysis adjusting for child's age, mother's age, rural residence, neighbourhood income quintile and mother's Charlson comorbidity index score (adjusted odds ratio, 2.42 [95% confidence interval (CI), 1.05 to 5.54], p=0.04).Postoperative opioid prescriptions for mothers may contribute to opioid-related events in their children. These findings further underscore the importance of safe, effective opioid prescribing, as well as of patient and public education about the use, storage and disposal of these medications.

  View details for DOI 10.25318/82-003-x202000600002-eng

  View details for PubMedID 32672924

  View details for PubMedCentralID PMC8201592

• Extracorporeal Life Support in Pregnancy: A Systematic Review. Journal of the American Heart Association Naoum, E. E., Chalupka, A., Haft, J., MacEachern, M., Vandeven, C. J., Easter, S. R., Maile, M., Bateman, B. T., Bauer, M. E. 2020; 9 (13): e016072

  Abstract

  Background The use of extracorporeal life support (ECLS) has expanded to include unique populations such as peripartum women. This systematic review aims to (1) quantify the number of cases and indications for ECLS in women during the peripartum period reported in the literature and (2) report maternal and fetal complications and outcomes associated with peripartum ECLS. Methods and Results This review was registered in PROSPERO (CRD42018108142). MEDLINE, Embase, and CINAHL were searched for case reports, case series, and studies reporting cases of ECLS during the peripartum period that reported one or more of the following outcomes: maternal survival, maternal complications, fetal survival, and/or fetal complications. Qualitative assessment of 221 publications evaluated the number of cases, clinical details, and maternal and fetal outcomes of ECLS during the peripartum period. There were 358 women included and 68 reported fetal outcomes in cases where the mother was pregnant at the time of cannulation. The aggregate maternal survival at 30 days was 270 (75.4%) and at 1 year was 266 (74.3%); fetal survival was 44 (64.7%). The most common indications for ECLS overall in pregnancy included acute respiratory distress syndrome 177 (49.4%), cardiac failure 67 (18.7%), and cardiac arrest 57 (15.9%). The most common maternal complications included mild to moderate bleeding 66 (18.4%), severe bleeding requiring surgical intervention 48 (13.4%), and intracranial neurologic morbidity 19 (5.3%). The most commonly reported fetal complications included preterm delivery 33 (48.5%) and neonatal intensive care unit admission 19 (27.9%). Conclusions Reported rates of survival in ECLS in pregnant and postpartum women are high and major complications relatively low.

  View details for DOI 10.1161/JAHA.119.016072

  View details for PubMedID 32578471

  View details for PubMedCentralID PMC7670512

• Contextualizing Potential Risks of Medications in Pregnancy for the Newborn-the Case of Ondansetron. JAMA pediatrics Huybrechts, K. F., Hernández-Díaz, S., Bateman, B. T. 2020; 174 (8): 747-748

  View details for DOI 10.1001/jamapediatrics.2020.1325

  View details for PubMedID 32478805

• Addressing Racial and Ethnic Disparities in Pain Management in the Midst of the Opioid Crisis. Obstetrics and gynecology Bateman, B. T., Carvalho, B. 2019; 134 (6): 1144-1146

  View details for DOI 10.1097/AOG.0000000000003590

  View details for PubMedID 31764722

• Opioid prescription use after vaginal delivery and subsequent persistent opioid use and misuse Zhu, Y., Huybrechts, K. F., Desai, R. J., Krumme, A., Straub, L., Levin, R., Mogun, H., Hernandez-Diaz, S., Bateman, B. T. WILEY. 2019: 214

  View details for Web of Science ID 000481785601193

• Switching patterns of antidiabetic medications during pregnancy in women with pre-gestational diabetes in publicly or privately insured US populations Tsao, N., Hernandez-Diaz, S., Bateman, B., Vine, S., Huybrechts, K. WILEY. 2019: 377

  View details for Web of Science ID 000481785603001

• Fetal outcomes associated with maternal asthma: Evidence from a large healthcare database in the United States Yland, J., Bateman, B. T., Huybrechts, K. F., Schatz, M., Wurst, K. E., Hernandez-Diaz, S. WILEY. 2019: 370

  View details for Web of Science ID 000481785602245

• Oral Fluconazole Use in Pregnancy and the Risk of Birth Defects Zhu, Y., Bateman, B. T., Hernandez-Diaz, S., Gray, K. J., Mogun, H., Huybrechts, K. F. WILEY. 2019: 14-15

  View details for Web of Science ID 000481785600021

• Trends in human papillomavirus vaccination uptake in girls and boys in the United States: real-world evidence from 2003 to 2016 Chen, S., Huybrechts, K. F., Bateman, B. T., Hernandez-Diaz, S. WILEY. 2019: 411-412

  View details for Web of Science ID 000481785603072

• Concomitant use of Z-drugs with prescribed opioid agents and the risk of overdose: A cohort study Szmulewicz, A., Bateman, B., Levin, R., Huybrechts, K. WILEY. 2019: 323

  View details for Web of Science ID 000481785602145

• Validation of ICD-9-CM coding algorithms to identify non-live birth outcomes in an automated database Zhu, Y., Gray, K., Bateman, B. T., Hernandez-Diaz, S., Straub, L., Reimers, R. M., Manning-Geist, B., Yoselevsky, E., Qiang, Y., Taylor, L. G., Hua, W., Huybrechts, K. WILEY. 2019: 236

  View details for Web of Science ID 000481785601238

• Development and validation of algorithms to estimate live birth gestational age in Medicaid analytic extract data Zhu, Y., Thai, T. N., Bateman, B. T., Hernandez-Diaz, S., Franklin, J. M., Straub, L., Winterstein, A. G., Gray, K. J., Qiang, Y., Hua, W., Taylor, L. G., Huybrechts, K. F. WILEY. 2019: 235

  View details for Web of Science ID 000481785601235

• Inflammatory bowel disease treatment in pregnancy in the US and Sweden Broms, G., Friedman, S., Kim, S., Brill, G., Wood, M., Hernandez-Diaz, S., Bateman, B., Huybrechts, K., Desai, R. J. WILEY. 2019: 376

  View details for Web of Science ID 000481785602258

• Selective serotonin reuptake inhibitors and type 2 diabetes in adolescents and youths Sun, J. W., Bateman, B. T., Hernandez-Diaz, S., Haneuse, S., Bourgeois, F. T., Huybrechts, K. F. WILEY. 2019: 447

  View details for Web of Science ID 000481785603144

• Determinants of missing or delayed prenatal screening in Florida, New Jersey, and Texas Medicaid populations 1999 to 2010 Thai, T. N., Henriksen, C., Gray, K. J., Bateman, B. T., Hernandez-Diaz, S., Zhu, Y., Straub, L., Huybrechts, K. F., Winterstein, A. G. WILEY. 2019: 372

  View details for Web of Science ID 000481785602249

• The Impact of In-Utero Prescription Opioid Exposure on Congenital Malformations Straub, L., Huybrechts, K. F., Hernandez-Diaz, S., Mogun, H., Bateman, B. T. WILEY. 2019: 15

  View details for Web of Science ID 000481785600022

• Substance use disorders in pregnancy: clinical, ethical, and research imperatives of the opioid epidemic: a report of a joint workshop of the Society for Maternal-Fetal Medicine, American College of Obstetricians and Gynecologists, and American Society of Addiction Medicine. American journal of obstetrics and gynecology Ecker, J., Abuhamad, A., Hill, W., Bailit, J., Bateman, B. T., Berghella, V., Blake-Lamb, T., Guille, C., Landau, R., Minkoff, H., Prabhu, M., Rosenthal, E., Terplan, M., Wright, T. E., Yonkers, K. A. 2019; 221 (1): B5-B28

  View details for DOI 10.1016/j.ajog.2019.03.022

  View details for PubMedID 30928567

• Use of real-world evidence from healthcare utilization data to evaluate drug safety during pregnancy PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Huybrechts, K. F., Bateman, B. T., Hernandez-Diaz, S. 2019; 28 (7): 906-922

  Abstract

  Because preapproval clinical trials typically exclude pregnant women, the evidence on drug safety during pregnancy required to inform drug labeling must come from postapproval controlled observational studies. Common designs have included pregnancy registries and case-control studies. Recently, pregnancy cohorts nested within healthcare utilization databases are increasingly being used. Despite clear advantages, these databases share some important limitations that may threaten the validity of studies emerging from them.This paper describes the distinctive methodological aspects of conducting drug safety studies in healthcare utilization databases with special emphasis on design and analytic approaches to minimize biases.We describe considerations for study design, cohort definition, and follow-up. We then address issues related to exposure ascertainment based on prescription fills, including the importance of the etiologically relevant window and of properly accounting for preterm births. This is followed by a discussion of advantages and challenges when ascertaining maternal and infant outcomes based on secondary data. We then explore useful approaches to address confounding within the context of pregnancy research and of the potential for selection bias when restricting the cohort to live births. Finally, we consider issues related to external validity and statistical significance. The examples are mainly drawn from a pregnancy cohort nested in the Medicaid Analytic Extract.The approaches presented provide guidance regarding the important methodological considerations that need to be attended to in order to generate valid, minimally biased risk when using large healthcare utilization databases for drug safety surveillance in pregnancy.

  View details for DOI 10.1002/pds.4789

  View details for Web of Science ID 000477681400002

  View details for PubMedID 31074570

  View details for PubMedCentralID PMC6823105

• An Innovative, Nurse-Driven Approach for Identifying Women at Risk for Severe Maternal Morbidity Sweeney, V., Manganaro, K., Easter, S., Bateman, B. T., Robinson, J. N., Lassey, S. C. ELSEVIER SCIENCE INC. 2019: S21-S22

  View details for DOI 10.1016/j.jogn.2019.04.036

  View details for Web of Science ID 000469359700035

• The Impact of In Utero Prescription Opioid Exposure on Congenital Malformations Straub, L., Huybrechts, K. F., Hernandez-Diaz, S., Mogun, H., Bateman, B. T. WILEY. 2019: 494

  View details for Web of Science ID 000468051600082

• Oral Fluconazole Use in Pregnancy and the Risk of Birth Defects Zhu, Y., Bateman, B. T., Hernandez-Diaz, S., Gray, K. J., Mogun, H., Huybrechts, K. F. WILEY. 2019: 500

  View details for Web of Science ID 000468051600094

• THE IMPACT OF CANNABIS USE DISORDER ON PERIOPERATIVE OUTCOMES IN MAJOR ELECTIVE SURGERIES: RESULTS FROM A NATIONALLY REPRESENTATIVE SAMPLE Goel, A., Mcguinness, B., Jivraj, N., Wijeysundera, D. N., Clarke, H., Bateman, B., Ladha, K. LIPPINCOTT WILLIAMS & WILKINS. 2019: 782-788

  View details for Web of Science ID 000619263200365

• Nocturnal desaturation early after delivery: impact of delivery type and the beneficial effects of Fowler's position. British journal of anaesthesia Fujita, N., Grabitz, S. D., Shin, C. H., Hess, P. E., Mueller, N., Bateman, B. T., Ecker, J. L., Takahashi, O., Houle, T. T., Nagasaka, Y., Eikermann, M. 2019; 122 (4): e64-e66

  View details for DOI 10.1016/j.bja.2019.01.007

  View details for PubMedID 30857611

  View details for PubMedCentralID PMC6435910

• Risk Facts for Major Postpartum Hemorrhage Associated with Manual Removal of the Placenta. Perlman, N. C., Fadayomi, A. B., Bateman, B. T., Carusi, D. A. SAGE PUBLICATIONS INC. 2019: 145A

  View details for Web of Science ID 000459610400241

• Defining definitions: a Delphi study to develop a core outcome set for conditions of severe maternal morbidity. BJOG : an international journal of obstetrics and gynaecology Schaap, T., Bloemenkamp, K., Deneux-Tharaux, C., Knight, M., Langhoff-Roos, J., Sullivan, E., van den Akker, T. 2019; 126 (3): 394-401

  Abstract

  Develop a core outcome set of international consensus definitions for severe maternal morbidities.Electronic Delphi study.International.Eight expert panels.All 13 high-income countries represented in the International Network of Obstetric Surveillance Systems (INOSS) nominated five experts per condition of morbidity, who submitted possible definitions. From these suggestions, a steering committee distilled critical components: eclampsia: 23, amniotic fluid embolism: 15, pregnancy-related hysterectomy: 11, severe primary postpartum haemorrhage: 19, uterine rupture: 20, abnormally invasive placentation: 12, spontaneous haemoperitoneum in pregnancy: 16, and cardiac arrest in pregnancy: 10. These components were assessed by the expert panel using a 5-point Likert scale, following which a framework for an encompassing definition was constructed. Possible definitions were evaluated in rounds until a rate of agreement of more than 70% was reached. Expert commentaries were used in each round to improve definitions.Definitions with a rate of agreement of more than 70%.The invitation to participate in one or more of eight Delphi processes was accepted by 103 experts from 13 high-income countries. Consensus definitions were developed for all of the conditions.Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process. These should be used in national registrations and international studies, and should be taken up by the Core Outcomes in Women's and Newborn Health initiative.Consensus definitions for eight morbidity conditions were successfully developed using the Delphi process.

  View details for DOI 10.1111/1471-0528.14833

  View details for PubMedID 28755459

• Fetal Outcomes Among Women with Asthma during Pregnancy: Evidence from a Large Healthcare Database in the United States Yland, J. J., Bateman, B., Huybrechts, K. F., Schatz, M., Wurst, K., Hernandez-Diaz, S. MOSBY-ELSEVIER. 2019: AB422

  View details for DOI 10.1016/j.jaci.2018.12.949

  View details for Web of Science ID 000457771200934

• Antidiabetic medication use during pregnancy: an international utilization study. BMJ open diabetes research & care Cesta, C. E., Cohen, J. M., Pazzagli, L., Bateman, B. T., Bröms, G., Einarsdóttir, K., Furu, K., Havard, A., Heino, A., Hernandez-Diaz, S., Huybrechts, K. F., Karlstad, Ø., Kieler, H., Li, J., Leinonen, M. K., Gulseth, H. L., Tran, D., Yu, Y., Zoega, H., Odsbu, I. 2019; 7 (1): e000759

  Abstract

  Diabetes in pregnancy and consequently the need for treatment with antidiabetic medication (ADM) has become increasingly prevalent. The prevalence and patterns of use of ADM in pregnancy from 2006 onward in seven different countries was assessed.Data sources included individually linked data from the nationwide health registers in Denmark (2006-2016), Finland (2006-2016), Iceland (2006-2012), Norway (2006-2015), Sweden (2006-2015), state-wide administrative and claims data for New South Wales, Australia (2006-2012) and two US insurance databases: Medicaid Analytic eXtract (MAX; 2006-2012, public) and IBM MarketScan (2012-2015, private). The prevalence of ADM use was calculated as the proportion of pregnancies with at least one filled prescription of an ADM in the 90 days before pregnancy or within the three trimesters of pregnancy.Prevalence of any ADM use in 5 279 231 pregnancies was 3% (n=147 999) and varied from under 2% (Denmark, Norway, and Sweden) to above 5% (Australia and US). Insulin was the most used ADM, and metformin was the most used oral hypoglycemic agent with increasing use over time in all countries. In 11.4%-62.5% of pregnancies with prepregnancy use, ADM (primarily metformin) was discontinued. When ADM treatment was initiated in late pregnancy for treatment of gestational diabetes mellitus, insulin was most often dispensed, except in the US, where glibenclamide was most often used.Prevalence and patterns of use of ADM classes varied between countries and over time. While insulin remained the most common ADM used in pregnancy, metformin use increased significantly over the study period.

  View details for DOI 10.1136/bmjdrc-2019-000759

  View details for PubMedID 31798900

  View details for PubMedCentralID PMC6861111

• Evaluation of a quality improvement intervention to decrease post-cesarean opioid use across a multi-hospital system Holland, E., Yao, Y., Bateman, B. T., Taggart, A., Sugrue, R., Sequist, T. D., Robinson, J. N. MOSBY-ELSEVIER. 2019: S43

  View details for DOI 10.1016/j.ajog.2018.11.059

  View details for Web of Science ID 000454249400054

• Prospective clinical validation of the obstetric comorbidity index for maternal risk assessment Easter, S., Sweeney, V., Manganaro, K., Lassey, S. C., Bateman, B. T., Robinson, J. N. MOSBY-ELSEVIER. 2019: S198-S199

  View details for DOI 10.1016/j.ajog.2018.11.299

  View details for Web of Science ID 000454249401065

• Addressing Racial and Ethnic Disparities in Pain Management in the Midst of the Opioid Crisis. Obstetrics and gynecology Bateman, B. T., Carvalho, B. n. 2019

  View details for DOI 10.1097/AOG.0000000000003590

  View details for PubMedID 31698386

• Using prescription claims to detect aberrant behaviors with opioids: comparison and validation of 5 algorithms. Pharmacoepidemiology and drug safety Rough, K., Huybrechts, K. F., Hernandez-Diaz, S., Desai, R. J., Patorno, E., Bateman, B. T. 2019; 28 (1): 62-69

  Abstract

  Compare and validate 5 algorithms to detect aberrant behavior with opioids: Opioid Misuse Score, Controlled Substance-Patterns of Utilization Requiring Evaluation (CS-PURE), Overutilization Monitoring System, Katz, and Cepeda algorithms.We identified new prescription opioid users from 2 insurance databases: Medicaid (2000-2006) and Clinformatics Data Mart (CDM; 2004-2013). Patients were followed 1 year, and aberrant opioid behavior was defined according to each algorithm, using Cohen's kappa to assess agreement. Risk differences were calculated comparing risk of opioid-related adverse events for identified aberrant and nonaberrant users.About 3.8 million Medicaid and 4.3 million CDM patients initiated prescription opioid use. Algorithms flagged potential aberrant behavior in 0.02% to 12.8% of initiators in Medicaid and 0.01% to 7.9% of initiators in CDM. Cohen's kappa values were poor to moderate (0.00 to 0.50 in Medicaid; 0.00 to 0.30 in CDM). Algorithms varied substantially in their ability to predict opioid-related adverse events; the Overutilization Monitoring System had the highest risk differences between aberrant and nonaberrant users (14.0% in Medicaid; 13.4% in CDM), and the Katz algorithm had the lowest (0.96% in Medicaid; 0.47% in CDM).In 2 large databases, algorithms applied to prescription data had varying accuracy in identifying increased risk of adverse opioid-related events.

  View details for DOI 10.1002/pds.4443

  View details for PubMedID 29687539

  View details for PubMedCentralID PMC6200661

• What Is New in Obstetric Anesthesia: The 2017 Gerard W. Ostheimer Lecture. Anesthesia and analgesia Bateman, B. T. 2019; 128 (1): 123-127

  Abstract

  The Gerard W. Ostheimer lecture is given each year at the Society for Obstetric Anesthesia and Perinatology annual meeting and is intended to summarize important new scientific literature relevant to practicing obstetric anesthesiologists. This review highlights some of the most consequential papers covered in this lecture. It discusses landmark clinical trials that are likely to change the practice of obstetrics and obstetric anesthesia. It summarizes several articles that focus on how to optimize the provision of neuraxial anesthesia and postoperative pain control. Finally, it reviews studies aimed at identifying systems-based interventions that can improve obstetrical outcomes. A proposed "to-do" list focused on quality improvement initiatives that can be implemented on labor and delivery units is provided.

  View details for DOI 10.1213/ANE.0000000000003760

  View details for PubMedID 30198933

• What's New in Obstetric Anesthesia: a focus on maternal morbidity and mortality. International journal of obstetric anesthesia Bateman, B. T. 2019; 37: 68-72

  Abstract

  The Ostheimer lecture is given each year at the annual meeting of the Society for Obstetric Anesthesia and Perinatology. It summarizes "What's New in Obstetric Anesthesia" based on a systematic evaluation of the relevant literature published in the previous calendar year. In this review I consider studies published in 2016 focused on the prevalence of, and risk factors for, maternal morbidity and mortality. I also discuss novel therapeutic approaches to the prevention and treatment of major sources of maternal morbidity and mortality.

  View details for DOI 10.1016/j.ijoa.2018.09.004

  View details for PubMedID 30336973

• Trends in Opioid Prescription in Children and Adolescents in a Commercially Insured Population in the United States, 2004-2017. JAMA pediatrics Gagne, J. J., He, M., Bateman, B. T. 2019; 173 (1): 98-99

  View details for DOI 10.1001/jamapediatrics.2018.3668

  View details for PubMedID 30419137

  View details for PubMedCentralID PMC6583437

• Evaluation of a Quality Improvement Intervention That Eliminated Routine Use of Opioids After Cesarean Delivery. Obstetrics and gynecology Holland, E., Bateman, B. T., Cole, N., Taggart, A., Robinson, L. A., Sugrue, R., Xu, X., Robinson, J. N. 2019; 133 (1): 91-97

  Abstract

  To evaluate the effects of eliminating the routine use of oral opioids for postcesarean delivery analgesia on postcesarean opioid consumption.At a tertiary care center, we implemented a quality improvement intervention among faculty practice patients undergoing cesarean delivery, which consisted of 1) eliminating routine ordering of oral opioids after cesarean delivery, 2) implementing guidelines for ordering a short course of opioids when deemed necessary, and 3) coupling opioid prescribing at discharge to patterns of opioid use in-hospital combined with shared decision-making. All patients, both before and after the intervention, were administered neuraxial opioids and scheduled acetaminophen and nonsteroidal antiinflammatory medications in the absence of contraindications. The primary outcome was the percentage of women who used any opioids postoperatively in-hospital. Secondary outcomes included the percentage of women discharged with a prescription for opioids, the quantity of opioids used in-hospital, pain scores, satisfaction, opioid-related side effects, and opioid prescriptions ordered in the 6 weeks after delivery. The effects of this intervention were assessed based on a chart review of patient data and a survey of patients in the 12 weeks before and 12 weeks after the intervention.We evaluated the records of 191 postcesarean delivery patients before and 181 after the intervention. Less than half of women used oral opioids in-hospital after the intervention, 82 (45%) compared with 130 (68%) before (P<.001). However, there was no change in pain scores or overall satisfaction with pain relief. Postintervention, only 40% of patients were discharged with prescriptions for opioids compared with 91% of patients before the intervention (P<.001).Eliminating routine ordering of oral opioids after cesarean delivery is associated with a significant decrease in opioid consumption while maintaining the same levels of pain control and patient satisfaction. Oral opioids are not needed by a large proportion of women after cesarean delivery.

  View details for DOI 10.1097/AOG.0000000000003010

  View details for PubMedID 30531571

• Prospective observational cohort study on grading the severity of postoperative complications in global surgery research. The British journal of surgery 2019; 106 (2): e73-e80

  Abstract

  The Clavien-Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien-Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs).This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien-Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs.A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien-Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59).Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally.

  View details for DOI 10.1002/bjs.11025

  View details for PubMedID 30620066

• Postoperative Opioid Consumption After Scheduled Compared With Unscheduled Cesarean Delivery. Obstetrics and gynecology Prabhu, M., Dolisca, S., Wood, R., James, K., Bateman, B. T., Barth, W. H., Wylie, B. J. 2019; 133 (2): 354-363

  Abstract

  To identify characteristics associated with high inpatient daily opioid consumption after cesarean delivery.This is a retrospective cohort study of all cesarean deliveries performed under neuraxial anesthesia with neuraxial morphine, at a single institution from January 1, 2015, to December 31, 2015. Women with preoperative opioid use disorder or chronic opioid use were excluded. Sociodemographic data, medical comorbidities, use of anxiolytics or antidepressants, smoking history, nonopioid substance use, intrapartum and cesarean delivery characteristics, and opioid consumption data (converted to morphine milligram equivalents) were abstracted. We defined high opioid use as a mean daily opioid consumption, standardized to the postoperative length of stay (excluding the first 24 postoperative hours to account for neuraxial morphine), greater than the 75th percentile of all opioid consumption. We used multivariable Poisson regression, stratified by whether or not cesarean delivery was scheduled, to identify characteristics associated with high opioid consumption.Among 949 women who underwent cesarean delivery, the mean (SD) and median (interquartile range) daily opioid consumption was 48.6 (22.8) and 44.6 (36.6-66.6) morphine milligram equivalents, respectively. Among those women with high opioid consumption, the mean (SD) and median (interquartile range) daily opioid consumption was 78.8 (8.5) and 78.3 (72.9-83.5) morphine milligram equivalents, respectively. Daily opioid consumption among those with high consumption was similar among women with scheduled compared with unscheduled cesarean delivery. Sociodemographic characteristics were similar among women with and without high opioid consumption. No sociodemographic, antepartum, or intrapartum characteristics were associated with high opioid consumption for either women having unscheduled or scheduled cesarean deliveries.For a quarter of women undergoing cesarean delivery, daily consumption of opioids is equivalent to 10 tablets of oxycodone 5 mg daily. No characteristics were associated with high opioid use for women having a scheduled or unscheduled cesarean delivery. Understanding opioid consumption after cesarean delivery is critical to managing women's postoperative pain while decreasing opioid exposure and risks of long-term opioid use disorder.

  View details for DOI 10.1097/AOG.0000000000003087

  View details for PubMedID 30633140

• Association of Geography and Access to Health Care Providers With Long-Term Prescription Opioid Use in Medicare Patients With Severe Osteoarthritis: A Cohort Study. Arthritis & rheumatology (Hoboken, N.J.) Desai, R. J., Jin, Y., Franklin, P. D., Lee, Y. C., Bateman, B. T., Lii, J., Solomon, D. H., Katz, J. N., Kim, S. C. 2019; 71 (5): 712-721

  Abstract

  To evaluate the variation in long-term opioid use in osteoarthritis (OA) patients according to geography and health care access.We designed an observational cohort study among OA patients undergoing total joint replacement (TJR) in the Medicare program (2010 through 2014). The independent variables of interest were the state of residence and health care access, which was quantified at the primary care service area (PCSA) level as categories of number of practicing primary care providers (PCPs) and categories of rheumatologists per 1,000 Medicare beneficiaries. The percentage of OA patients taking long-term opioids (≥90 days in the 360-day period immediately preceding TJR) within each PCSA was the outcome variable in a multilevel, generalized linear regression model, adjusting for case-mix at the PCSA level and for policies, including rigor of prescription drug monitoring programs and legalized medical marijuana, at the state level.A total of 358,121 patients with advanced OA, with a mean age of 74 years, were included from 4,080 PCSAs. The unadjusted mean percentage of long-term opioid users varied widely across states, ranging from 8.9% (Minnesota) to 26.4% (Alabama), and this variation persisted in the adjusted models. Access to PCPs was only modestly associated with rates of long-term opioid use between PCSAs with highest (>8.6) versus lowest (<3.6) concentration of PCPs (adjusted mean difference 1.4% [95% confidence interval 0.8%, 2.0%]), while access to rheumatologists was not associated with long-term opioid use.We note a substantial statewide variation in rates of long-term treatment with opioids in OA, which is not fully explained by the differences in access to health care providers, varying case-mix, or state-level policies.

  View details for DOI 10.1002/art.40834

  View details for PubMedID 30688044

  View details for PubMedCentralID PMC6483834

• Acute Fatty Liver of Pregnancy: Pathophysiology, Anesthetic Implications, and Obstetrical Management. Anesthesiology Naoum, E. E., Leffert, L. R., Chitilian, H. V., Gray, K. J., Bateman, B. T. 2019; 130 (3): 446-461

  View details for DOI 10.1097/ALN.0000000000002597

  View details for PubMedID 30707120

  View details for PubMedCentralID PMC7037575

• Days' Supply of Initial Opioid Analgesic Prescriptions and Additional Fills for Acute Pain Conditions Treated in the Primary Care Setting - United States, 2014. MMWR. Morbidity and mortality weekly report Mundkur, M. L., Franklin, J. M., Abdia, Y., Huybrechts, K. F., Patorno, E., Gagne, J. J., Meyer, T. E., Staffa, J., Bateman, B. T. 2019; 68 (6): 140-143

  Abstract

  During 2017, opioids were associated with 47,600 deaths in the United States, approximately one third of which involved a prescription opioid (1). Amid concerns that overprescribing to patients with acute pain remains an essential factor underlying misuse, abuse, diversion, and unintentional overdose, several states have restricted opioid analgesic prescribing (2,3). To characterize patterns of opioid analgesic use for acute pain in primary care settings before the widespread implementation of limits on opioid prescribing (2,3), patients filling an opioid analgesic prescription for acute pain were identified from a 2014 database of commercial claims. Using a logistic generalized additive model, the probability of obtaining a refill was estimated as a function of the initial number of days supplied. Among 176,607 patients with a primary care visit associated with an acute pain complaint, 7.6% filled an opioid analgesic prescription. Among patients who received an initial 7-day supply, the probability of obtaining an opioid analgesic prescription refill for nine of 10 conditions was <25%. These results suggest that a ≤7-day opioid analgesic prescription might be sufficient for most, but not all, patients seen in primary care settings with acute pain who appear to need opioid analgesics. However, treatment strategies should account for patient and condition characteristics, which might alternatively reduce or extend the anticipated duration of benefit from opioid analgesic therapy.

  View details for DOI 10.15585/mmwr.mm6806a3

  View details for PubMedID 30763301

  View details for PubMedCentralID PMC6375655

• Anesthesia considerations and post-operative pain management in pregnant women with chronic opioid use. Seminars in perinatology Soens, M. A., He, J., Bateman, B. T. 2019; 43 (3): 149-161

  Abstract

  The prevalence of opioid use disorder in pregnancy has escalated markedly in recent years. Chronic opioid use during pregnancy poses several challenges for providing adequate analgesia and anesthesia in the peripartum period. These challenges include the potential for withdrawal, opioid tolerance and opioid-induced hyperalgesia. Here we discuss alterations in analgesic pharmacokinetics and pharmacodynamics that are associated with chronic opioid use. In addition, when treating pain in patients with opioid use disorder it is important to distinguish between different subgroups. In this review, we will discuss practical management strategies for parturients with (1) untreated opioid use disorder, (2) parturients on medication-assisted treatment (methadone, buprenorphine) and (3) patients recovering from opioid use disorder that are currently abstinent. Finally, we offer an overview of non-opioid strategies that may be utilized as part of a multimodal approach to providing optimal analgesia in this patient population.

  View details for DOI 10.1053/j.semperi.2019.01.004

  View details for PubMedID 30791974

• Culture-Negative and Culture-Positive Sepsis: A Comparison of Characteristics and Outcomes. Anesthesia and analgesia Sigakis, M. J., Jewell, E., Maile, M. D., Cinti, S. K., Bateman, B. T., Engoren, M. 2019; 129 (5): 1300-1309

  Abstract

  The primary objective of this study was to compare the characteristics of culture-positive and culture-negative status in septic patients. We also determined whether culture status is associated with mortality and whether unique variables are associated with mortality in culture-positive and culture-negative patients separately.Utilizing patient records from intensive care units, emergency department, and general care wards in a large academic medical center, we identified adult patients with suspected infection and ≥2 systemic inflammatory response syndrome criteria between January 1, 2007, and May 31, 2014. We compared the characteristics between culture-positive and culture-negative patients and used binary logistic regression to identify variables independently associated with culture status and mortality. We also did sensitivity analyses using patients with Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria for sepsis.The study population included 9288 culture-negative patients (89%) and 1105 culture-positive patients (11%). Culture-negative patients received more antibiotics during the 48 hours preceding diagnosis but otherwise demonstrated similar characteristics as culture-positive patients. After adjusting for illness severity, a positive culture was not independently associated with mortality (odds ratio = 1.01 [95% CI, 0.81-1.26]; P = .945). The models predicting mortality separately in culture-negative and culture-positive patients demonstrated very good and excellent discrimination (C-statistic ± SD, 0.87 ± 0.01 and 0.92 ± 0.01), respectively. In the sensitivity analyses using patients with sepsis by Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria, after adjustments for illness severity, positive cultures were still not associated with mortality (odds ratio = 1.13 [95% CI, 0.86-1.43]; P = .303; and odds ratio = 1.05 [95% CI, 0.83-1.33]; P = .665), respectively. In all models, physiological derangements were associated with mortality.While culture status is important for tailoring antibiotics, culture-negative and culture-positive patients with sepsis demonstrate similar characteristics and, after adjusting for severity of illness, similar mortality. The most important factor associated with negative cultures is receipt of antibiotics during the preceding 48 hours. The risk of death in patients suspected of having an infection is most associated with severity of illness. This is aligned with the Sepsis-3 definition using Sequential Organ Failure Assessment score to better identify those suspected of infection at highest risk of a poor outcome.

  View details for DOI 10.1213/ANE.0000000000004072

  View details for PubMedID 30829670

  View details for PubMedCentralID PMC7577261

• Obstetric Anesthesia: Leading the Way in Patient Safety. Obstetrics and gynecology clinics of North America Birnbach, D. J., Bateman, B. T. 2019; 46 (2): 329-337

  Abstract

  The subspecialty of obstetric anesthesiology has embraced patient safety research, which has led to a reduction in obstetric anesthesia-related morbidity and mortality. Although there are innumerable individual improvements, this article highlights the following innovations: safer and more effective labor analgesia, safer treatments for hypotension associated with neuraxial blockade, advances in spinal and epidural techniques for operative deliveries, lower incidence of postdural puncture headache through improved technology, safer parental agents for labor analgesia, improved safety of general anesthesia in obstetrics, improved education and the use of simulation including team training, and reductions in operating room-related infections.

  View details for DOI 10.1016/j.ogc.2019.01.015

  View details for PubMedID 31056134

• Measuring What Matters to Moms Most. Anesthesiology Mhyre, J. M., Bateman, B. T. 2019; 131 (2): 223-225

  View details for DOI 10.1097/ALN.0000000000002794

  View details for PubMedID 31094752

• A comorbidity-based screening tool to predict severe maternal morbidity at the time of delivery. American journal of obstetrics and gynecology Easter, S. R., Bateman, B. T., Sweeney, V. H., Manganaro, K., Lassey, S. C., Gagne, J. J., Robinson, J. N. 2019; 221 (3): 271.e1-271.e10

  Abstract

  The obstetric comorbidity index summarizes the burden of maternal comorbidities into a single number and holds promise as a maternal risk-assessment tool.The aim of this study was to assess the clinical performance of this comorbidity-based screening tool to accurately identify women on labor and delivery who are at risk of severe maternal morbidity on labor and delivery in real time.All patients with pregnancies ≥23 weeks gestation presenting to labor and delivery at a single tertiary-care center from February through July 2018 were included in the study. The patient's primary labor and delivery nurse assessed patient comorbidities and calculated the patient's obstetric comorbidity index. The score was recalculated at each 12-hour shift change. A multidisciplinary panel of clinicians determined whether patients experienced severe maternal morbidity based on the American College of Obstetrics and Gynecology and Society for Maternal-Fetal Medicine consensus definition, blinded to the patient's obstetric comorbidity index score. We analyzed the association between the obstetric comorbidity index score and the occurrence of severe maternal morbidity.The study included 2828 women, of whom 1.73% experience severe maternal morbidity (n=49). The obstetric comorbidity index ranged from 0-15 for women in the study cohort, with a median obstetric comorbidity index of 1 (interquartile range, 0-3). The median obstetric comorbidity index score for women who experienced the severe maternal morbidity was 5 (interquartile range, 3-7) compared with a median of 1 (interquartile range, 0-3) for those without severe maternal morbidity (P<.01). The frequency of severe maternal morbidity increased from 0.41% for those with a score of 0 to 18.75% for those with a score ≥9. For every 1-point increase in the score, patients experienced a 1.55 increase in odds of severe maternal morbidity (95% confidence interval, 1.42-1.70). The c-statistic for the obstetric comorbidity index score was 0.83 (95% confidence interval, 0.76-0.89), which indicated strong discrimination.The obstetric comorbidity index can prospectively identify women at risk of severe maternal morbidity in a clinical setting. A particular strength of the obstetric comorbidity index is its ability to integrate multiple compounding comorbidities and highlight the cumulative risk that is associated with the patients' conditions. Routine clinical use of the obstetric comorbidity index has the potential to identify at-risk women whose condition warrants increased surveillance and targeted care to prevent adverse maternal outcomes.

  View details for DOI 10.1016/j.ajog.2019.06.025

  View details for PubMedID 31229427

• Anticonvulsant Mood Stabilizer and Lithium Use and Risk of Adverse Pregnancy Outcomes. The Journal of clinical psychiatry Cohen, J. M., Huybrechts, K. F., Patorno, E., Desai, R. J., Mogun, H., Bateman, B. T., Hernández-Díaz, S. 2019; 80 (4)

  Abstract

  To determine the comparative safety of mood stabilizers with respect to risk of preeclampsia, placental abruption, growth restriction, and preterm birth.A cohort study was carried out using Medicaid Analytic eXtract data for pregnant women linked to live born infants enrolled from 2000 to 2010. Exposure to lamotrigine, valproate, topiramate, carbamazepine, oxcarbazepine, and lithium during the first 20 weeks of pregnancy was assessed. The reference group did not fill a prescription for an anticonvulsant or lithium during the 3 months prior to conception or the first half of pregnancy. Women who continued mood stabilizer monotherapy after 20 weeks were also compared to those who discontinued. Risk ratios (RRs) and 95% CIs were estimated with propensity score stratification to control for confounding.Among 1,472,672 pregnancies, 10,575 (0.7%) were exposed to anticonvulsant mood stabilizer or lithium monotherapy and 917 (0.06%) were exposed to polytherapy. In unadjusted analyses, exposure to each specific mood stabilizer and polytherapy was associated with increased risks of all adverse outcomes considered compared to no exposure (RR ranged from 1.15 to 1.56). However, these RR estimates were not meaningfully elevated with adjustment for confounding (0.89 to 1.16). Continuation of mood stabilizers was not associated with an increased risk for any outcomes compared to discontinuation and was associated with a reduced risk of placental abruption and growth restriction.Anticonvulsant mood stabilizers and lithium are not associated with an increased risk of placenta-mediated complications or preterm birth after accounting for confounding by indication.

  View details for DOI 10.4088/JCP.18m12572

  View details for PubMedID 31237992

• The Impact of Technology on the Diagnosis of Congenital Malformations. American journal of epidemiology Straub, L., Huybrechts, K. F., Bateman, B. T., Mogun, H., Gray, K. J., Holmes, L. B., Hernandez-Diaz, S. 2019; 188 (11): 1892-1901

  Abstract

  As technology improves and becomes more widely accessible, more subclinical congenital malformations are being detected. Using a cohort of 1,780,156 pregnant women and their offspring nested in the 2000-2013 US Medicaid Analytic eXtract, we contrasted time trends in malformations which do not necessarily present with overt clinical symptoms early in life and are more likely to be diagnosed via imaging (secundum atrial septal defect, patent ductus arteriosus, ventricular septal defect, pulmonary artery anomalies, pulmonary valve stenosis, hydrocephalus) with trends in malformations that are unlikely to escape clinical diagnosis (tetralogy of Fallot, coarctation of the aorta, transposition of the great vessels, hypoplastic left heart syndrome, oral cleft, abdominal wall defect). Logistic regression was used to account for trends in risk factors while assessing the impact of increased screening intensity. Prevalence of the diagnosis of secundum atrial septal defect rose from 2.3‰ in 2000-2001 to 7.5‰ in 2012-2013, of patent ductus arteriosus from 1.9‰ to 4.1‰, and of ventricular septal defect from 3.6‰ to 4.5‰. Trends were not explained by changes in the prevalence of risk factors but were attenuated when accounting for screening tests. The other malformations showed no temporal trends. Findings suggest that increased screening partially explains the observed increase in diagnosis of milder cases of select common malformations.

  View details for DOI 10.1093/aje/kwz153

  View details for PubMedID 31241162

  View details for PubMedCentralID PMC6825822

• Poorly Controlled Asthma During Pregnancy Remains Common in the United States. The journal of allergy and clinical immunology. In practice Cohen, J. M., Bateman, B. T., Huybrechts, K. F., Mogun, H., Yland, J., Schatz, M., Wurst, K. E., Hernandez-Diaz, S. 2019; 7 (8): 2672-2680.e10

  Abstract

  Asthma is among the most common preexisting medical conditions in pregnancy. Uncontrolled asthma may increase the risk of adverse pregnancy outcomes.To describe the prevalence, severity, and control of asthma during pregnancy in the United States.We identified 2 cohorts of pregnancies ending in a live birth within 2 large US health care claims databases: the Truven Health MarketScan Commercial Claims and Encounters Database (MarketScan, private insurance) for the period 2011 to 2015 and the nationwide Medicaid Analytic eXtract (MAX, public insurance) for the period 2000 to 2013. We defined asthma prevalence, severity, and control on the basis of International Classification of Diseases, 9th Revision diagnoses and asthma-related treatments. Severe asthma was defined as dispensing of 1 or more medium/high-dose inhaled corticosteroid plus additional therapy within the 12 months preceding delivery. Poor control was defined as having at least 1 of the following: 1 or more exacerbation (asthma-related hospitalization or emergency room visit, or a course of oral corticosteroids) or 5 or more filled prescriptions for short-acting β-agonists between the last menstrual period and delivery.Among 604,420 pregnant women in MarketScan and 2,071,359 in MAX, 20,104 (3.3%) and 120,745 (5.8%) had asthma, respectively. Among pregnant women with asthma, 19.0% and 18.8% had severe asthma and 16.5% and 28.0% had poorly controlled asthma in MarketScan and MAX, respectively. Many women with poorly controlled asthma during pregnancy were not dispensed a long-term controller (38.4% in MarketScan and 43.3% in MAX). Within both cohorts, women with poor control were more often smokers and obese, had more comorbidities, and used more concomitant nonasthma medications.Poorly controlled asthma is more frequent among publicly versus privately insured pregnancies in the United States. Dispensing of long-term controller medications during pregnancy remains low, even for symptomatic patients.

  View details for DOI 10.1016/j.jaip.2019.05.043

  View details for PubMedID 31257187

• Obstetric Comorbidity and Severe Maternal Morbidity Among Massachusetts Delivery Hospitalizations, 1998-2013. Maternal and child health journal Somerville, N. J., Nielsen, T. C., Harvey, E., Easter, S. R., Bateman, B., Diop, H., Manning, S. E. 2019; 23 (9): 1152-1158

  Abstract

  The rate of severe maternal morbidity in the United States increased approximately 200% during 1993-2014. Few studies have reported on the health of the entire pregnant population, including women at low risk for maternal morbidity. This information might be useful for interventions aimed at primary prevention of pregnancy complications. To better understand this, we sought to describe the distribution of comorbid risk among all delivery hospitalizations in Massachusetts and its association with the distribution of severe maternal morbidity.Using an existing algorithm, we assigned an obstetric comorbidity index (OCI) score to delivery hospitalizations contained in the Massachusetts pregnancy to early life longitudinal (PELL) data system during 1998-2013. We identified which hospitalizations included severe maternal morbidity and calculated the rate and frequency of these hospitalizations by OCI score.During 1998-2013, PELL contained 1,185,182 delivery hospitalizations; of these 5325 included severe maternal morbidity. Fifty-eight percent of delivery hospitalizations had an OCI score of zero. The mean OCI score increased from 0.60 in 1998 to 0.82 in 2013. Hospitalizations with an OCI score of zero comprised approximately one-third of all deliveries complicated by severe maternal morbidity, but had the lowest rate of severe maternal morbidity (22.8/10,000 delivery hospitalizations).The mean OCI score increased during the study period, suggesting that an overall increase in risk factors has occurred in the pregnant population in Massachusetts. Interventions that can make small decreases to the mean OCI score could have a substantial impact on the number of deliveries complicated by severe maternal morbidity. Additionally, all delivery facilities should be prepared for severe complications during low-risk deliveries.

  View details for DOI 10.1007/s10995-019-02796-3

  View details for PubMedID 31267339

  View details for PubMedCentralID PMC7281820

• Impact of State Laws Restricting Opioid Duration on Characteristics of New Opioid Prescriptions. Journal of general internal medicine Dave, C. V., Patorno, E., Franklin, J. M., Huybrechts, K., Sarpatwari, A., Kesselheim, A. S., Bateman, B. T. 2019; 34 (11): 2339-2341

  View details for DOI 10.1007/s11606-019-05150-z

  View details for PubMedID 31309407

  View details for PubMedCentralID PMC6848320

• Potential Effects of Regionalized Maternity Care on U.S. Hospitals. Obstetrics and gynecology Easter, S. R., Robinson, J. N., Menard, M. K., Creanga, A. A., Xu, X., Little, S. E., Bateman, B. T. 2019; 134 (3): 545-552

  Abstract

  To examine the current patterns of care for women at high risk for delivery-related morbidity to inform discussions about the feasibility of this regionalized approach.We performed a cross-sectional study and linked 2014 American Hospital Association survey and State Inpatient Database data from seven representative states. We used American Hospital Association-reported hospital characteristics and State Inpatient Database procedure codes to assign a level of maternal care to each hospital. We then assigned each patient to a minimum required level of maternal care (I-IV) based on maternal comorbidities captured in the State Inpatient Database. Our outcome was delivery at a hospital with an inappropriately low level of maternal care. Comorbidities associated with delivery at an inappropriate hospital were assessed using descriptive statistics.The analysis included 845,545 deliveries occurring at 556 hospitals. The majority of women had risk factors appropriate for delivery at level I or II hospitals (85.1% and 12.6%, respectively). A small fraction (2.4%) of women at high risk for maternal morbidity warranted delivery in level III or IV hospitals. The majority (97.6%) of women delivered at a hospital with an appropriate level of maternal care, with only 2.4% of women delivering at a hospital with an inappropriate level of maternal care. However, 43.4% of the 19,988 high-risk patients warranting delivery at level III or IV hospitals delivered at level I or II hospitals. Women with comorbidities likely to benefit from specialized care (eg, maternal cardiac disease, placenta previa with prior uterine surgery) had high rates of delivery at hospitals with an inappropriate level of maternal care (68.2% and 37.7%, respectively).Though only 2.41% of deliveries occurred at hospitals with an inappropriate level of maternal care, a substantial fraction of women at risk for maternal morbidity delivered at hospitals potentially unequipped with resources to manage their needs. Promoting triage of high-risk patients to hospitals optimized to provide risk-appropriate care may improve maternal outcomes with minimal effect on most deliveries.

  View details for DOI 10.1097/AOG.0000000000003397

  View details for PubMedID 31403590

• Opioid Prescribing After Surgery in the United States, Canada, and Sweden. JAMA network open Ladha, K. S., Neuman, M. D., Broms, G., Bethell, J., Bateman, B. T., Wijeysundera, D. N., Bell, M., Hallqvist, L., Svensson, T., Newcomb, C. W., Brensinger, C. M., Gaskins, L. J., Wunsch, H. 2019; 2 (9): e1910734

  Abstract

  Small studies and anecdotal evidence suggest marked differences in the use of opioids after surgery internationally; however, this has not been evaluated systematically across populations receiving similar procedures in different countries.To determine whether there are differences in the frequency, amount, and type of opioids dispensed after surgery among the United States, Canada, and Sweden.This cohort study included patients without previous opioid prescriptions aged 16 to 64 years who underwent 4 low-risk surgical procedures (ie, laparoscopic cholecystectomy, laparoscopic appendectomy, arthroscopic knee meniscectomy, and breast excision) between January 2013 and December 2015 in the United States, between July 2013 and March 2016 in Canada, and between January 2013 and December 2014 in Sweden. Data analysis was conducted in all 3 countries from July 2018 to October 2018.The main outcome was postoperative opioid prescriptions filled within 7 days after discharge; the percentage of patients who filled a prescription, the total morphine milligram equivalent (MME) dose, and type of opioid dispensed were compared.The study sample consisted of 129 379 patients in the United States, 84 653 in Canada, and 9802 in Sweden. Overall, 52 427 patients (40.5%) in the United States were men, with a mean (SD) age of 45.1 (12.7) years; in Canada, 25 074 patients (29.6%) were men, with a mean (SD) age of 43.5 (13.0) years; and in Sweden, 3314 (33.8%) were men, with a mean (SD) age of 42.5 (13.0). The proportion of patients in Sweden who filled an opioid prescription within the first 7 days after discharge for any procedure was lower than patients treated in the United States and Canada (Sweden, 1086 [11.1%]; United States, 98 594 [76.2%]; Canada, 66 544 [78.6%]; P < .001). For patients who filled a prescription, the mean (SD) MME dispensed within 7 days of discharge was highest in United States (247 [145] MME vs 169 [93] MME in Canada and 197 [191] MME in Sweden). Codeine and tramadol were more commonly dispensed in Canada (codeine, 26 136 patients [39.3%]; tramadol, 12 285 patients [18.5%]) and Sweden (codeine, 170 patients [15.7%]; tramadol, 315 patients [29.0%]) than in the United States (codeine, 3210 patients [3.3%]; tramadol, 3425 patients [3.5%]).The findings indicate that the United States and Canada have a 7-fold higher rate of opioid prescriptions filled in the immediate postoperative period compared with Sweden. Of the 3 countries examined, the mean dose of opioids for most surgical procedures was highest in the United States.

  View details for DOI 10.1001/jamanetworkopen.2019.10734

  View details for PubMedID 31483475

  View details for PubMedCentralID PMC6727684

• Risk Factors, Etiologies, and Screening Tools for Sepsis in Pregnant Women: A Multicenter Case-Control Study. Anesthesia and analgesia Bauer, M. E., Housey, M., Bauer, S. T., Behrmann, S., Chau, A., Clancy, C., Clark, E. A., Einav, S., Langen, E., Leffert, L., Lin, S., Madapu, M., Maile, M. D., McQuaid-Hanson, E., Priessnitz, K., Sela, H. Y., Shah, A., Sobolewski, P., Toledo, P., Tsen, L. C., Bateman, B. T. 2019; 129 (6): 1613-1620

  Abstract

  Given the significant morbidity and mortality of maternal sepsis, early identification is key to improve outcomes. This study aims to evaluate the performance characteristics of the systemic inflammatory response syndrome (SIRS), quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA), and maternal early warning (MEW) criteria for identifying cases of impending sepsis in parturients. The secondary objective of this study is to identify etiologies and risk factors for maternal sepsis and to assess timing of antibiotics in patients diagnosed with sepsis.Validated maternal sepsis cases during the delivery hospitalization from 1995 to 2012 were retrospectively identified at 7 academic medical centers in the United States and Israel. Control patients were matched by date of delivery in a 1:4 ratio. The sensitivity and specificity of SIRS, qSOFA, and MEW criteria for identifying sepsis were calculated. Data including potential risk factors, vital signs, laboratory values, and clinical management were collected for cases and controls.Eighty-two sepsis cases during the delivery hospitalization were identified and matched to 328 controls. The most common causes of sepsis were the following: chorioamnionitis 20 (24.4%), endometritis 19 (23.2%), and pneumonia 9 (11.0%). Escherichia coli 12 (14.6%), other Gram-negative rods 8 (9.8%), and group A Streptococcus 6 (7.3%) were the most commonly found pathogens. The sensitivities and specificities for meeting criteria for screening tools were as follows: (1) SIRS (0.93, 0.63); (2) qSOFA (0.50, 0.95); and (3) MEW criteria for identifying sepsis (0.82, 0.87). Of 82 women with sepsis, 10 (12.2%) died. The mortality rate for those who received antibiotics within 1 hour of diagnosis was 8.3%. The mortality rate was 20% for the patients who received antibiotics after >1 hour.Chorioamnionitis and endometritis were the most common causes of sepsis, together accounting for about half of cases. Notable differences were observed in the sensitivity and specificity of sepsis screening tools with the highest to lowest sensitivity being SIRS, MEW, and qSOFA criteria, and the highest to lowest specificity being qSOFA, MEW, and SIRS. Mortality was doubled in the cohort of patients who received antibiotics after >1 hour. Clinicians need to be vigilant to identify cases of peripartum sepsis early in its course and prioritize timely antibiotic therapy.

  View details for DOI 10.1213/ANE.0000000000003709

  View details for PubMedID 31743182

  View details for PubMedCentralID PMC7543988

• Ondansetron and the risk of congenital malformations Huybrechts, K. F., Hernandez-Diaz, S., Straub, L., Gray, K., Patorno, E., Desai, R., Mogun, H., Bateman, B. T. WILEY. 2018: 15

  View details for Web of Science ID 000441893800027

• Gabapentin use in pregnancy and the risk of maternal and neonatal outcomes Patorno, E., Hernandez-Diaz, S., Huybrechts, K. F., Cohen, J. M., Desai, R. J., Mogun, H., Bateman, B. T. WILEY. 2018: 14

  View details for Web of Science ID 000441893800025

• Opioid dispensing after vaginal delivery Prabhu, M., Garry, E., Hernandez-Diaz, S., MacDonald, S. C., Huybrechts, K. F., Bateman, B. T. WILEY. 2018: 16

  View details for Web of Science ID 000441893800030

• Antidiabetic medication in pregnancy: An international drug utilization study Cesta, C. E., Cohen, J. M., Pazzagli, L., Bateman, B. T., Broms, G., Einarsdottir, K., Furu, K., Gissler, M., Heino, A., Hernandez-Diaz, S., Huybrechts, K. F., Karlstad, O., Li, J., Reutfors, J., Selmer, R., Yu, Y., Zoega, H., Odsbu, I. WILEY. 2018: 178

  View details for Web of Science ID 000441893801158

• A novel claims-based algorithm to predict opioid overdose in the United States Sun, J. W., Franklin, J. M., Rough, K., Desai, R. J., Hernandez-Diaz, S., Huybrechts, K. F., Bateman, B. T. WILEY. 2018: 373-374

  View details for Web of Science ID 000441893803138

• Opioid dispensing patterns after oocyte retrieval Bortoletto, P., Garry, E., Huybrechts, K. F., Anchan, R. M., Bateman, B. T. WILEY. 2018: 238

  View details for Web of Science ID 000441893802066

• Estimating probability of refills after initial opioid analgesic prescriptions for acute pain in primary care settings Mundkur, M. L., Franklin, J., Huybrecths, K., Patorno, E., Gagne, J. J., Meyer, T., Staffa, J., Bateman, B. T. WILEY. 2018: 424-425

  View details for Web of Science ID 000441893804022

• Psychotropic polytherapy among publicly insured pregnant women in the United States Cantarutti, A., Bateman, B. T., Patorno, E., Bellocco, R., White-Bateman, S., Hernandez-Diaz, S., Huybrechts, K. F. WILEY. 2018: 175

  View details for Web of Science ID 000441893801151

• Algorithms to estimate the timing of pregnancy for stillbirths in pregnancy safety studies Cantarutti, A., Bateman, B. T., Hernandez-Diaz, S., Gray, K. J., Patorno, E., Corrao, G., Desai, R. J., Huybrechts, K. WILEY. 2018: 352

  View details for Web of Science ID 000441893803094

• The epidemiology of pre-existing chronic kidney disease in a cohort of pregnant women in the USA Spoendlin, J., Paik, J., Mogun, H., Hernandez-Diaz, S., Patorno, E., Gray, K., Bateman, B., Huybrechts, K., Desai, R. J. WILEY. 2018: 232-233

  View details for Web of Science ID 000441893802054

• Disparities in asthma prevalence, severity, and control in pregnancy. Evidence from two health care databases in the United States Cohen, J. M., Bateman, B. T., Huybrechts, K. F., Schatz, M., Wurst, K. E., Hernandez-Diaz, S. WILEY. 2018: 31-32

  View details for Web of Science ID 000441893800062

• Disease modifying therapy dispensing during pregnancy: A multidatabase pregnancy cohort of women with multiple sclerosis MacDonald, S. C., Huybrechts, K. F., Bateman, B. T., Desai, R. J., McElrath, T. F., Hernandez-Diaz, S. WILEY. 2018: 320-321

  View details for Web of Science ID 000441893803024

• Antipsychotic drug use in pregnancy: A multinational database study Reutfors, J., Zoega, H., Cesta, C., Bateman, B. T., Cantarutti, A., Cohen, J., Corrao, G., Einarsdottir, K., Engeland, A., Furu, K., Havard, A., Hernandez-Diaz, S., Huybrechts, K. F., Karlsson, P., Karlstad, O., Li, J., Schaffer, A., Yu, Y., Broms, G. WILEY. 2018: 235

  View details for Web of Science ID 000441893802059

• The impact of technology on the prevalence of congenital malformations Straub, L., Huybrechts, K. F., Bateman, B. T., Mogun, H., Hernandez-Diaz, S. WILEY. 2018: 239-240

  View details for Web of Science ID 000441893802069

• Surveillance of Microcephaly and Neurotropic Infections Using Healthcare Databases Messinger, C. J., He, M., Huybrechts, K. F., Bateman, B., Hernandez-Diaz, S. WILEY. 2018: 757

  View details for Web of Science ID 000433565700078

• The Impact of Technology on the Prevalence of Congenital Malformations Straub, L., Huybrechts, K. F., Bateman, B., Mogun, H., Hernandez-Diaz, S. WILEY. 2018: 766

  View details for Web of Science ID 000433565700096

• Ondansetron and the Risk of Congenital Malformations Huybrechts, K. F., Hernandez-Diaz, S., Straub, L., Gray, K., Patorno, E., Desai, R., Mogun, H., Bateman, B. WILEY. 2018: 758

  View details for Web of Science ID 000433565700081

• Risk for postpartum hemorrhage, transfusion, and hemorrhage-related morbidity at low, moderate, and high volume hospitals. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Merriam, A. A., Wright, J. D., Siddiq, Z., D'Alton, M. E., Friedman, A. M., Ananth, C. V., Bateman, B. T. 2018; 31 (8): 1025-1034

  Abstract

  The objective of this study was to characterize risk for and temporal trends in postpartum hemorrhage across hospitals with different delivery volumes.This study used the Nationwide Inpatient Sample (NIS) to characterize risk for postpartum hemorrhage from 1998 to 2011. Hospitals were classified as having either low, moderate or high delivery volume (≤1000, 1001 to 2000, >2000 deliveries per year, respectively). The primary outcomes included postpartum hemorrhage, transfusion, and related severe maternal morbidity. Adjusted models were created to assess factors associated with hemorrhage and transfusion.Of 55,140,088 deliveries included for analysis 1,512,212 (2.7%) had a diagnosis of postpartum hemorrhage and 361,081 (0.7%) received transfusion. Risk for morbidity and transfusion increased over the study period, while the rate of hemorrhage was stable ranging from 2.5 to 2.9%. After adjustment, hospital volume was not a major risk factor for transfusion or hemorrhage.While obstetric volume does not appear to be a major risk factor for either transfusion or hemorrhage, given that transfusion and hemorrhage-related maternal morbidity are increasing across hospital volume categories, there is an urgent need to improve obstetrical care for postpartum hemorrhage. Those risk factors are able to discriminate women at increased risk supports routine use of hemorrhage risk assessment.

  View details for DOI 10.1080/14767058.2017.1306050

  View details for PubMedID 28367647

  View details for PubMedCentralID PMC6112239

• Predictors of excess postoperative opioid consumption after cesarean delivery among opioid naive women Prabhu, M., Dolisca, S., Wood, R., Gonzalez, J., James, K., Bateman, B. T., Wylie, B. J., Barth, W. H. MOSBY-ELSEVIER. 2018: S333-S334

  View details for Web of Science ID 000423616600057

• Opioid prescribing after vaginal and cesarean delivery Prabhu, M., Garry, E. M., Bateman, B. T. MOSBY-ELSEVIER. 2018: S138

  View details for Web of Science ID 000422946900210

• Effect of Maternal Body Mass Index on Postpartum Hemorrhage. Anesthesiology Butwick, A. J., Abreo, A. n., Bateman, B. T., Lee, H. C., El-Sayed, Y. Y., Stephansson, O. n., Flood, P. n. 2018

  Abstract

  It is unclear whether obesity is a risk factor for postpartum hemorrhage. The authors hypothesized that obese women are at greater risk of hemorrhage than women with a normal body mass index.The authors conducted a cohort study of women who underwent delivery hospitalization in California between 2008 and 2012. Using multilevel regression, the authors examined the relationships between body mass index with hemorrhage (primary outcome), atonic hemorrhage, and severe hemorrhage (secondary outcomes). Stratified analyses were performed according to delivery mode.The absolute event rate for hemorrhage was 60,604/2,176,673 (2.8%). In this cohort, 4% of women were underweight, 49.1% of women were normal body mass index, 25.9% of women were overweight, and 12.7%, 5.2%, and 3.1% of women were in obesity class I, II, and III, respectively. Compared to normal body mass index women, the odds of hemorrhage and atonic hemorrhage were modestly increased for overweight women (hemorrhage: adjusted odds ratio [aOR], 1.06; 99% CI, 1.04 to 1.08; atonic hemorrhage: aOR, 1.07; 99% CI, 1.05 to 1.09) and obesity class I (hemorrhage: aOR, 1.08; 99% CI, 1.05 to 1.11; atonic hemorrhage; aOR, 1.11; 99% CI, 1.08 to 1.15). After vaginal delivery, overweight and obese women had up to 19% increased odds of hemorrhage or atonic hemorrhage; whereas, after cesarean delivery, women in any obesity class had up to 14% decreased odds of severe hemorrhage.The authors' findings suggest that, at most, maternal obesity has a modest effect on hemorrhage risk. The direction of the association between hemorrhage and body mass index may differ by delivery mode.

  View details for PubMedID 29346134

• Anticonvulsants and the risk of perinatal bleeding complications: A pregnancy cohort study. Neurology Panchaud, A., Cohen, J. M., Patorno, E., Huybrechts, K. F., Desai, R. J., Gray, K. J., Mogun, H., Hernandez-Diaz, S., Bateman, B. T. 2018; 91 (6): e533-e542

  Abstract

  To examine the risk of postpartum hemorrhage (PPH) and neonatal bleeding complications associated with late-pregnancy exposure to anticonvulsant drugs (ACDs) that induce cytochrome P450 enzymes (ACDi) and alter the metabolism of vitamin K compared to other ACDs.We used a population-based cohort study stemming from a nationwide sample of publicly insured pregnant women with a liveborn infant from the 2000 to 2010 Medicaid Analytic eXtract. ACDi (carbamazepine, phenobarbital, phenytoin, oxcarbazepine, topiramate) were compared to other ACDs dispensed during the last month of pregnancy. Relative risks (RRs) and 95% confidence intervals (CIs) of PPH and neonatal bleeding complications were estimated using generalized linear models with fine stratification on the propensity score to control for indication and other potential confounders.Among 11,572 women with an ACD prescription overlapping delivery, 2.6% (135/5,109) in the ACDi group and 3.6% (231/6,463) in the other ACDs group had a diagnosis of PPH: unadjusted RR 0.74 (95% CI 0.60-0.91), adjusted RR 0.77 (95% CI 0.58-1.00). The prevalence of neonatal bleeding complications was 3.1% (157/5,109) in the ACDi group and 3.5% (229/6,463) in the other ACDs group: unadjusted RR 0.87 (95% CI 0.71-1.06), adjusted RR 0.83 (95% CI 0.64-1.08).Evidence from this large observational study suggests that use of ACDi near delivery does not increase the risk of bleeding complications compared to other ACDs in clinical settings where neonatal intramuscular or oral vitamin K administration is considered standard of care. These findings provide reassurance for clinicians and pregnant women successfully treated with ACDi.

  View details for DOI 10.1212/WNL.0000000000005944

  View details for PubMedID 29980637

  View details for PubMedCentralID PMC6105051

• Continuation of Atypical Antipsychotic Medication During Early Pregnancy and the Risk of Gestational Diabetes. The American journal of psychiatry Park, Y., Hernandez-Diaz, S., Bateman, B. T., Cohen, J. M., Desai, R. J., Patorno, E., Glynn, R. J., Cohen, L. S., Mogun, H., Huybrechts, K. F. 2018; 175 (6): 564-574

  Abstract

  Some atypical antipsychotics are associated with metabolic side effects, which are risk factors for gestational diabetes. The authors examined the risk of developing gestational diabetes associated with the continuation of treatment with aripiprazole, ziprasidone, quetiapine, risperidone, and olanzapine during pregnancy compared with discontinuation of these antipsychotic drugs.Nondiabetic pregnant women who were linked to a live-born infant and enrolled in Medicaid (2000-2010) and who received one or more prescriptions dispensed for an antipsychotic drug during the 3 months before pregnancy were included in the analyses. Among 1,543,334 pregnancies, some expectant mothers at baseline were receiving treatment with aripiprazole (N=1,924), ziprasidone (N=673), quetiapine (N=4,533), risperidone (N=1,824), or olanzapine (N=1,425). For each antipsychotic drug, women with two or more dispensings ("continuers") were compared with women with no dispensings ("discontinuers") during the first half of pregnancy. A generalized linear model and propensity-score stratification were used to obtain absolute and relative risks of developing gestational diabetes, with adjustment for confounders.Women who continued antipsychotic treatment during pregnancy generally had higher comorbidity and longer baseline antipsychotic use. The crude risk of developing gestational diabetes among continuers compared with discontinuers, respectively, was 4.8% and 4.5% for aripiprazole, 4.2% and 3.8% for ziprasidone, 7.1% and 4.1% for quetiapine, 6.4% and 4.1% for risperidone, and 12.0% and 4.7% for olanzapine. The adjusted relative risks were 0.82 (95% CI=0.50-1.33) for aripiprazole, 0.76 (95% CI=0.29-2.00) for ziprasidone, 1.28 (95% CI=1.01-1.62) for quetiapine, 1.09 (95% CI=0.70-1.70) for risperidone, and 1.61 (95% CI=1.13-2.29) for olanzapine.Compared with women who discontinued use of an atypical antipsychotic medication before the start of pregnancy, women who continued treatment with olanzapine or quetiapine had an increased risk of gestational diabetes that may be explained by the metabolic effects associated with these two drugs.

  View details for DOI 10.1176/appi.ajp.2018.17040393

  View details for PubMedID 29730938

  View details for PubMedCentralID PMC5988929

• Liposomal Bupivacaine Block at the Time of Cesarean Delivery to Decrease Postoperative Pain: A Randomized Controlled Trial. Obstetrics and gynecology Prabhu, M., Clapp, M. A., McQuaid-Hanson, E., Ona, S., OʼDonnell, T., James, K., Bateman, B. T., Wylie, B. J., Barth, W. H. 2018; 132 (1): 70-78

  Abstract

  To evaluate whether a liposomal bupivacaine incisional block decreases postoperative pain and represents an opioid-minimizing strategy after scheduled cesarean delivery.In a single-blind, randomized controlled trial among opioid-naive women undergoing cesarean delivery, liposomal bupivacaine or placebo was infiltrated into the fascia and skin at the surgical site, before fascial closure. Using an 11-point numeric rating scale, the primary outcome was pain score with movement at 48 hours postoperatively. A sample size of 40 women per group was needed to detect a 1.5-point reduction in pain score in the intervention group. Pain scores and opioid consumption, in oral morphine milligram equivalents, at 48 hours postoperatively were summarized as medians (interquartile range) and compared using the Wilcoxon rank-sum test.Between March and September 2017, 249 women were screened, 103 women enrolled, and 80 women were randomized. One woman in the liposomal bupivacaine group was excluded after randomization as a result of a vertical skin incision, leaving 39 patients in the liposomal bupivacaine group and 40 in the placebo group. Baseline characteristics between groups were similar. The median (interquartile range) pain score with movement at 48 hours postoperatively was 4 (2-5) in the liposomal bupivacaine group and 3.5 (2-5.5) in the placebo group (P=.72). The median (interquartile range) opioid use was 37.5 (7.5-60) morphine milligram equivalents in the liposomal bupivacaine group and 37.5 (15-75) morphine milligram equivalents in the placebo group during the first 48 hours postoperatively (P=.44).Compared with placebo, a liposomal bupivacaine incisional block at the time of cesarean delivery resulted in similar postoperative pain scores in the first 48 hours postoperatively.ClinicalTrials.gov, NCT02959996.

  View details for DOI 10.1097/AOG.0000000000002649

  View details for PubMedID 29889750

• Structure, Process, and Outcome Data of AWHONN's Postpartum Hemorrhage Quality Improvement Project. Journal of obstetric, gynecologic, and neonatal nursing : JOGNN Bingham, D., Scheich, B., Bateman, B. T. 2018; 47 (5): 707-718

  Abstract

  To describe the structures and processes implemented during the Association of Women's Health, Obstetric, and Neonatal Nurses Postpartum Hemorrhage (AWHONN PPH) Project.An 18-month, multiregion, multihospital quality improvement project.Fifty-eight hospitals located in Washington, DC; Georgia; and New Jersey.Volunteer registered nurse hospital leaders implemented the AWHONN PPH bundle, which consisted of structure and process improvements.The process and effectiveness of the implementation of the interventions were measured and compared between baseline and after implementation.All structures and processes showed improvement but were not fully implemented at all sites. Registered nurse participation in drills increased from 0% to 92%, quantification of blood loss increased from 5% to 45%, hemorrhage risk assessment increased from 10% to 70%, prebirth risk assessment increased from 2% to 52%, postbirth risk assessment increased from 2% to 57%, and debriefing increased from 1% to 13%. No statistically significant differences were found in the pre- and postimplementation outcomes measured (maternal deaths, blood products transfused, women with massive transfusions, peripartum hysterectomies during the birth admission, and ICU admissions for women who gave birth and/or had a postpartum hemorrhage). Participants' self-assessments of their monthly implementation efforts (leader intensity) were not correlated with implementation fidelity (the degree to which the intervention was provided as proposed).None of the 58 hospitals were able to implement all of the structure and process changes before the end of the 18-month implementation phase. This suggests that an 18-month implementation phase may be too short.

  View details for DOI 10.1016/j.jogn.2018.05.002

  View details for PubMedID 29940149

• Gene-Centric Analysis of Preeclampsia Identifies Maternal Association at PLEKHG1. Hypertension (Dallas, Tex. : 1979) Gray, K. J., Kovacheva, V. P., Mirzakhani, H., Bjonnes, A. C., Almoguera, B., DeWan, A. T., Triche, E. W., Saftlas, A. F., Hoh, J., Bodian, D. L., Klein, E., Huddleston, K. C., Ingles, S. A., Lockwood, C. J., Hakonarson, H., McElrath, T. F., Murray, J. C., Wilson, M. L., Norwitz, E. R., Karumanchi, S. A., Bateman, B. T., Keating, B. J., Saxena, R. 2018; 72 (2): 408-416

  Abstract

  The genetic susceptibility to preeclampsia, a pregnancy-specific complication with significant maternal and fetal morbidity, has been poorly characterized. To identify maternal genes associated with preeclampsia risk, we assembled 498 cases and 1864 controls of European ancestry from preeclampsia case-control collections in 5 different US sites (with additional matched population controls), genotyped samples on a cardiovascular gene-centric array composed of variants from ≈2000 genes selected based on prior genetic studies of cardiovascular and metabolic diseases and performed case-control genetic association analysis on 27 429 variants passing quality control. In silico replication testing of 9 lead signals with P<10-4 was performed in independent European samples from the SOPHIA (Study of Pregnancy Hypertension in Iowa) and Inova cohorts (212 cases, 456 controls). Multiethnic assessment of lead signals was then performed in samples of black (26 cases, 136 controls), Hispanic (132 cases, 468 controls), and East Asian (9 cases, 80 controls) ancestry. Multiethnic meta-analysis (877 cases, 3004 controls) revealed a study-wide statistically significant association of the rs9478812 variant in the pleiotropic PLEKHG1 gene (odds ratio, 1.40 [1.23-1.60]; Pmeta=5.90×10-7). The rs9478812 effect was even stronger in the subset of European cases with known early-onset preeclampsia (236 cases diagnosed <37 weeks, 1864 controls; odds ratio, 1.59 [1.27-1.98]; P=4.01×10-5). PLEKHG1 variants have previously been implicated in genome-wide association studies of blood pressure, body weight, and neurological disorders. Although larger studies are required to further define maternal preeclampsia heritability, this study identifies a novel maternal risk locus for further investigation.

  View details for DOI 10.1161/HYPERTENSIONAHA.117.10688

  View details for PubMedID 29967039

  View details for PubMedCentralID PMC6043396

• Variability in the Use of Protective Mechanical Ventilation During General Anesthesia. Anesthesia and analgesia Ladha, K. S., Bateman, B. T., Houle, T. T., De Jong, M. A., Vidal Melo, M. F., Huybrechts, K. F., Kurth, T., Eikermann, M. 2018; 126 (2): 503-512

  Abstract

  The purpose of this study was to determine whether significant variation exists in the use of protective ventilation across individual anesthesia providers and whether this difference can be explained by patient, procedure, and provider-related characteristics.The cohort consisted of 262 anesthesia providers treating 57,372 patients at a tertiary care hospital between 2007 and 2014. Protective ventilation was defined as a median positive end-expiratory pressure of 5 cm H2O or more, tidal volume of <10 mL/kg of predicted body weight and plateau pressure of <30 cm H2O. Analysis was performed using mixed-effects logistic regression models with propensity scores to adjust for covariates. The definition of protective ventilation was modified in sensitivity analyses.In unadjusted analysis, the mean probability of administering protective ventilation was 53.8% (2.5th percentile of provider 19.9%, 97.5th percentile 80.8%). After adjustment for a large number of covariates, there was little change in the results with a mean probability of 51.1% (2.5th percentile 24.7%, 97.5th percentile 77.2%). The variations persisted when the thresholds for protective ventilation were changed.There was significant variability across individual anesthesia providers in the use of intraoperative protective mechanical ventilation. Our data suggest that this variability is highly driven by individual preference, rather than patient, procedure, or provider-related characteristics.

  View details for DOI 10.1213/ANE.0000000000002343

  View details for PubMedID 28763357

  View details for PubMedCentralID PMC6696999

• Patterns of opioid initiation at first visits for pain in United States primary care settings. Pharmacoepidemiology and drug safety Mundkur, M. L., Rough, K., Huybrechts, K. F., Levin, R., Gagne, J. J., Desai, R. J., Patorno, E., Choudhry, N. K., Bateman, B. T. 2018; 27 (5): 495-503

  Abstract

  The primary objective of this study was to characterize variation in patterns of opioid prescribing within primary care settings at first visits for pain, and to describe variation by condition, geography, and patient characteristics.2014 healthcare utilization data from Optum's Clinformatics™ DataMart were used to evaluate individuals 18 years or older with an initial presentation to primary care for 1 of 10 common pain conditions. The main outcomes assessed were (1) the proportion of first visits for pain associated with an opioid prescription fill and (2) the proportion of opioid prescriptions with >7 days' supply.We identified 205 560 individuals who met inclusion criteria; 9.1% of all visits were associated with an opioid fill, ranging from 4.1% (headache) to 28.2% (dental pain). Approximately half (46%) of all opioid prescriptions supplied more than 7 days, and 10% of prescriptions supplied ≥30 days. We observed a 4-fold variation in rates of opioid initiation by state, with highest rates of prescribing in Alabama (16.6%) and lowest rates in New York (3.7%).In 2014, nearly half of all patients filling opioid prescriptions received more than 7 days' of opioids in an initial prescription. Policies limiting initial supplies have the potential to substantially impact opioid prescribing in the primary care setting.

  View details for DOI 10.1002/pds.4322

  View details for PubMedID 28971545

  View details for PubMedCentralID PMC5880749

• Topiramate use early in pregnancy and the risk of oral clefts: A pregnancy cohort study. Neurology Hernandez-Diaz, S., Huybrechts, K. F., Desai, R. J., Cohen, J. M., Mogun, H., Pennell, P. B., Bateman, B. T., Patorno, E. 2018; 90 (4): e342-e351

  Abstract

  To assess the relative risk of oral clefts associated with maternal use of high and low doses of topiramate during the first trimester for epilepsy and nonepilepsy indications.This population-based study nested in the US 2000-2010 Medicaid Analytic eXtract included a cohort of 1,360,101 pregnant women with a live-born infant enrolled in Medicaid from 3 months before conception through 1 month after delivery. Oral clefts were defined as the presence of a recorded diagnosis in claims during the first 90 days after birth. Women with a topiramate dispensing during the first trimester were compared with those without any dispensing and with an active reference group of women with a lamotrigine dispensing during the first trimester. Risk ratios (RRs) were estimated with generalized linear models with fine stratification on the propensity score of treatment to control for potential confounders. Stratified analyses by indication of use and dose were conducted.The risk of oral clefts at birth was 4.1 per 1,000 in the 2,425 infants born to women exposed to topiramate compared with 1.1 per 1,000 in the unexposed group (RR 2.90, 95% confidence interval [CI] 1.56-5.40). The RR among women with epilepsy was 8.30 (95% CI 2.65-26.07); among women with other indications such as bipolar disorder, it was 1.45 (95% CI 0.54-3.86). The median daily dose for the first prescription filled during the first trimester was 200 mg for women with epilepsy and 100 mg for women without epilepsy. For topiramate monotherapy, the RR for oral clefts associated with doses ≤100 mg was 1.64 (95% CI 0.53-5.07) and for doses >100 mg it was 5.16 (95% CI 1.94-13.73). Results were similar when lamotrigine was used as a reference group.The increased risk of oral clefts associated with use of topiramate early in pregnancy was more pronounced in women with epilepsy, who used higher doses.

  View details for DOI 10.1212/WNL.0000000000004857

  View details for PubMedID 29282333

  View details for PubMedCentralID PMC5798655

• Trends in use of hydroxychloroquine during pregnancy in systemic lupus erythematosus patients from 2001 to 2015. Lupus Bermas, B. L., Kim, S. C., Huybrechts, K., Mogun, H., Hernandez-Diaz, S., Bateman, B. T., Desai, R. J. 2018; 27 (6): 1012-1017

  Abstract

  Evidence suggests that continuing hydroxychloroquine (HCQ) during pregnancy in women with systemic lupus erythematosus (SLE) improves outcomes. We sought to describe time trends in the continuation, initiation, and duration of HCQ in a large population-based cohort of pregnant SLE women.A cohort of pregnant women with SLE enrolled continuously in public (Medicaid, 2001-2010) or private (Optum Clinformatics, 2003-2015) health insurance between three months prior to conception and one month after delivery was identified. We assessed the proportion of women initiating or continuing HCQ and the duration of therapy during each calendar year in the study.A total of 5300 women with SLE were included. Of these, 852 (16.1%) were on HCQ treatment in the three-month period prior to their pregnancy. During pregnancy, the overall proportion of women with SLE taking HCQ increased from 12.4% in 2001 to 37.7% in 2015. Initiation of HCQ therapy during pregnancy increased from 2.7% in 2001 to 7.5% in 2010 ( p = 0.0002) (Medicaid) and from 4.9% in 2003 to 13.6% in 2015 ( p = 0.0001) (Clinformatics). Continuation of HCQ during pregnancy did not change significantly over time in either data set. The average cumulative day-supply of HCQ prescriptions during pregnancy increased from 37 days in 2001 to 77 days in 2010 ( p = 0.05) among HCQ initiators and from 79 days in 2001 to 125 days in 2010 ( p = 0.0009) among HCQ continuers in Medicaid. Among privately insured women, the average cumulative day-supply of HCQ prescriptions among HCQ continuers increased from 84 in 2004 to 163 in 2015 ( p = 0.0006) but did not change significantly among HCQ initiators.The proportion of women initiating HCQ during pregnancy and the average cumulative day-supply of HCQ increased from 2001 to 2015. While these findings are encouraging, overall HCQ use during pregnancy remains low.

  View details for DOI 10.1177/0961203317749046

  View details for PubMedID 29301469

• The Role of the Anesthesiologist in Preventing Severe Maternal Morbidity and Mortality. Clinical obstetrics and gynecology McQUAID, E., Leffert, L. R., Bateman, B. T. 2018; 61 (2): 372-386

  Abstract

  Anesthesiologists are responsible for the safe and effective provision of analgesia for labor and anesthesia for cesarean delivery and other obstetric procedures. In addition, obstetric anesthesiologists often have a unique role as the intensivists of the obstetric suite. The anesthesiologist is frequently the clinician with the greatest experience in the acute bedside management of a hemodynamically unstable patient and expertise in life-saving interventions. This review will discuss (1) risks associated with neuraxial and general anesthesia for labor and delivery, and (2) clinical scenarios in which the obstetric anesthesiologist is commonly called upon to function as a "peridelivery intensivist."

  View details for DOI 10.1097/GRF.0000000000000350

  View details for PubMedID 29319586

• The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis. British journal of anaesthesia Abbott, T. E., Ahmad, T., Phull, M. K., Fowler, A. J., Hewson, R., Biccard, B. M., Chew, M. S., Gillies, M., Pearse, R. M. 2018; 120 (1): 146-155

  Abstract

  The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool.Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals.We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32-0.77); P<0.01], but no difference in complication rates [OR 1.02 (0.88-1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62-0.92); P<0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61-0.88); P<0.01; I2=89%).Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine.

  View details for DOI 10.1016/j.bja.2017.08.002

  View details for PubMedID 29397122

• Opioid Use Disorders and the Risk of Postoperative Pulmonary Complications. Anesthesia and analgesia Sayal, P., Bateman, B. T., Menendez, M., Eikermann, M., Ladha, K. S. 2018; 127 (3): 767-774

  Abstract

  As the rate of opioid use disorders continues to rise, perioperative physicians are increasingly faced with the challenge of providing analgesia to these patients after surgery. Due to the likelihood of opioid dose escalation in the perioperative period, we hypothesized that opioid-dependent patients would be at increased risk for postoperative pulmonary complications.A retrospective cross-sectional analysis of patients undergoing 6 representative elective surgical procedures was performed using the Nationwide Inpatient Sample from 2002 to 2011. The primary outcome was a composite including prolonged mechanical ventilation, reintubation, and acute respiratory failure. Secondary outcomes were length of stay, in-hospital mortality, and total hospital costs. Both multivariable logistic regression and propensity score matching were used to determine the impact of opioid use disorder on outcomes.The total sample-weighted cohort consisted of 7,533,050 patients. Patients with opioid use disorders were more likely to suffer pulmonary complications, with a frequency of 4.2% compared to 1.6% in the nonopioid-dependent group (P < .001), and had a 1.62 times higher odds (95% confidence interval [CI], 1.16-2.27) in multivariable regression analysis. In a secondary subgroup analysis, only patients undergoing a colectomy had a greater odds of suffering pulmonary complications (odds ratio, 2.64; 95% CI, 1.42-4.91; P = .0021). Additionally, patients with an opioid use disorder had a longer length of stay (0.84 days [95% CI, 0.52-1.16; P < .001]) and greater costs ($1816 [95% CI, 935-2698; P < .001]).This study demonstrates that patients with opioid use disorders are at increased risk for postoperative pulmonary complications, and have prolonged length of stay and resource utilization. Further research is needed regarding interventions to reduce the risk of complications in this subset of patients.

  View details for DOI 10.1213/ANE.0000000000003307

  View details for PubMedID 29570152

• Estimating pediatric general anesthesia exposure: Quantifying duration and risk. Paediatric anaesthesia Bartels, D. D., McCann, M. E., Davidson, A. J., Polaner, D. M., Whitlock, E. L., Bateman, B. T. 2018; 28 (6): 520-527

  Abstract

  Understanding the duration of pediatric general anesthesia exposure in contemporary practice is important for identifying groups at risk for long general anesthesia exposures and designing trials examining associations between general anesthesia exposure and neurodevelopmental outcomes.We performed a retrospective cohort analysis to estimate pediatric general anesthesia exposure duration during 2010-2015 using the National Anesthesia Clinical Outcomes Registry.A total of 1 548 021 pediatric general anesthetics were included. Median general anesthesia duration was 57 minutes (IQR: 28-86) with 90th percentile 145 minutes. Children aged <1 year had the longest median exposure duration (79 minutes, IQR: 39-119) with 90th percentile 210 minutes, and 13.7% of this very young cohort was exposed for >3 hours. High ASA physical status and care at a university hospital were associated with longer exposure times.While the vast majority (94%) of children undergoing general anesthesia are exposed for <3 hours, certain groups may be at increased risk for longer exposures. These findings may help guide the design of future trials aimed at understanding neurodevelopmental impact of prolonged exposure in these high-risk groups.

  View details for DOI 10.1111/pan.13391

  View details for PubMedID 29722100

  View details for PubMedCentralID PMC6291204

• Frequency of Opioid Dispensing After Vaginal Delivery. Obstetrics and gynecology Prabhu, M., Garry, E. M., Hernandez-Diaz, S., MacDonald, S. C., Huybrechts, K. F., Bateman, B. T. 2018; 132 (2): 459-465

  Abstract

  To describe nationwide patterns in outpatient opioid dispensing after vaginal delivery.Using the Truven Health Analytics MarketScan database, we performed a large, nationwide retrospective cohort study of commercially insured beneficiaries who underwent vaginal delivery between 2003 and 2015 and who were opioid-naive for 12 weeks before the delivery admission. We assessed the proportion of women dispensed an oral opioid within 1 week of discharge, the associated median oral morphine milligram equivalent dose dispensed, and the frequency of opioid refills during the 6 weeks after discharge. We evaluated predictors of opioid dispensing using multivariable logistic regression.Among 1,345,244 women undergoing vaginal delivery, 28.5% were dispensed an opioid within 1 week of discharge. The most commonly dispensed opioids were hydrocodone (44.7%), oxycodone (34.6%), and codeine (13.1%). The odds of filling an opioid were higher among those using benzodiazepines (adjusted odds ratio [OR] 1.87, 95% CI 1.73-2.02) and antidepressants (adjusted OR 1.63, 95% CI 1.59-1.66), smokers (adjusted OR 1.44, 95% CI 1.38-1.51), and among those undergoing tubal ligation (adjusted OR 3.77, 95% CI 3.67-3.87), operative vaginal delivery (adjusted OR 1.52, 95% CI 1.49-1.54), and higher order perineal laceration (adjusted OR 2.15, 95% CI 2.11-2.18). The median (interquartile range, 10th-90th percentile) dose of opioids dispensed was 150 (113-225, 80-345) morphine milligram equivalents, equivalent to 20 tablets (interquartile range 15-30, 10th-90th percentile 11-46) of 5 mg oxycodone. Six weeks after discharge, 8.5% of women filled one or more additional opioid prescriptions.Opioid dispensing after vaginal delivery is common and often occurs at high doses. Given the frequency of vaginal delivery, this may represent an important source of overprescription of opioids in the United States.

  View details for DOI 10.1097/AOG.0000000000002741

  View details for PubMedID 29995732

  View details for PubMedCentralID PMC6060020

• Implementation of a Quality Improvement Initiative to Decrease Opioid Prescribing After Cesarean Delivery. Obstetrics and gynecology Prabhu, M., Dubois, H., James, K., Leffert, L. R., Riley, L. E., Bateman, B. T., Henderson, M. 2018; 132 (3): 631-636

  Abstract

  To assess whether a multiphase, departmental quality improvement effort decreases opioid prescribing and increases multimodal analgesic use after cesarean delivery.This is a prospective quality improvement study. In phase 1 of the protocol, discharge providers implemented counseling regarding expectations for pain, typical need for opioids, and importance of multimodal nonopioid analgesic use and used shared decision-making to determine the number of opioids prescribed. Patients could select up to a maximum of 30 tablets of 5 mg oxycodone (or equivalent opioid), lower than the previous routine discharge prescription of 40 opioid tablets. The primary outcome was the mean (SD) number of opioid tablets prescribed on discharge with secondary outcomes including opioid refill rate within 30 days of discharge and rates of nonopioid analgesic prescriptions on discharge. In phase 2, using these results, we adjusted the protocol's maximum opioid prescription to 25 opioid tablets, but no other aspects of the protocol were changed. All data were analyzed with t test and χ analyses.Data from 624 women who underwent cesarean deliveries were analyzed. Opioids, most commonly oxycodone, were prescribed after 95% of all cesarean deliveries. The mean (SD) number of opioid tablets prescribed decreased from 33.2 (9.3) to 26.5 (6.7; P<.01) with the implementation of phase 1 having no effect on the opioid refill rate, 8.9% vs 8.1% (P=.79). These results allowed adjustment of the maximum recommended prescription to 25 opioid tablets, introducing phase 2 of the study, during which the mean (SD) number of opioid tablets prescribed further decreased from 24.9 (7.5) to 21.5 (6.3; P<.01) with no effect on the opioid refill rate, 6.3% vs 5.1% (P=.72). Overall, this represents a 35% decrease in opioid prescribing (P<.01). Rates of ibuprofen prescribing were 98% or higher throughout the study, but rates of acetaminophen prescribing increased from 32.6% before phase 1 to 92.0% after phase 2 (P<.001).Implementation of a multiphase quality improvement protocol to decrease opioid prescribing, combined with iterative review of discharge data, resulted in a significant decrease in the number of opioid tablets prescribed after cesarean delivery.

  View details for DOI 10.1097/AOG.0000000000002789

  View details for PubMedID 30095765

  View details for PubMedCentralID PMC6105442

• Longitudinal Trends and Variation in Antipsychotic Use in Older Adults After Cardiac Surgery. Journal of the American Geriatrics Society Kim, D. H., Mahesri, M., Bateman, B. T., Huybrechts, K. F., Inouye, S. K., Marcantonio, E. R., Herzig, S. J., Ely, E. W., Pisani, M. A., Levin, R., Avorn, J. 2018; 66 (8): 1491-1498

  Abstract

  To evaluate temporal trends and between-hospital variation in off-label antipsychotic medication (APM) use in older adults undergoing cardiac surgery.Retrospective cohort study.National administrative database including 465 U.S. hospitals.Individuals aged 65 and older without known indications for APMs who underwent cardiac surgery from 2004 to 2014 (N=293,212).Postoperative exposure to any APMs and potentially excessive dosing were examined. Hospital-level APM prescribing intensity was defined as the proportion of individuals newly treated with APMs in the postoperative period.The rate of APM use declined from 8.8% in 2004 to 6.2% in 2014 (p<.001). Use of haloperidol (parenteral 7.0% to 4.5%, p<.001; oral: 1.9% to 0.5%, p<.001), and risperidone (1.1% to 0.3%, p<.001) declined, whereas quetiapine use tripled (0.6% to 1.9%, p=.03). Hospital APM prescribing intensity varied widely, from 0.3% to 35.6%, across 465 hospitals. Treated individuals at higher-prescribing hospitals were more likely to receive APMs on the day of discharge (highest vs lowest quintile: 15.1% vs 9.6%; p<.001) and for a longer duration (4.8 vs 3.7 days; p<.001) than those at lower-prescribing hospitals. Delirium was the strongest risk factor for APM exposure (odds ratio=9.73, 95% confidence interval=9.02-10.5), whereas none of the hospital characteristics were significantly associated. The rate of potentially excessive dosing declined (60.7% to 44.9%, p<.001), and risk factors for potentially excessive dosing were similar to those for any APM exposure.Our findings suggest highly variable prescribing cultures and raise concerns about inappropriate use, highlighting the need for better evidence to guide APM prescribing in hospitalized older adults after cardiac surgery.

  View details for DOI 10.1111/jgs.15418

  View details for PubMedID 30125337

  View details for PubMedCentralID PMC6217828

• Opioid dispensing patterns after oocyte retrieval. Fertility and sterility Bortoletto, P., Prabhu, M., Garry, E. M., Huybrechts, K. F., Anchan, R. M., Bateman, B. T. 2018; 110 (5): 905-909

  Abstract

  To study opioid dispensing patterns following oocyte retrieval.Retrospective cohort.Not applicable.Women undergoing oocyte retrieval with a maximum of 1 opioid prescription in the 12 weeks prior to the procedure, without an opioid use or other substance use disorder.None.We measured the frequency of opioids dispensed within 3 days of oocyte retrieval, most common opioids dispensed; and quantity dispensed, in median (interquartile range [IQR] and 10th-90th percentile ranges) oral morphine milligram equivalents (MME). Multivariate regression analyses were used to calculate odds ratios and 95% confidence intervals (CI) to examine the association between patient characteristics and the occurrence of an opioid dispensing.In total, 61,463 women with an oocyte retrieval met the criteria for analysis. After oocyte retrieval, 11.9% were dispensed an opioid, most commonly hydrocodone (48.5%), codeine (23.0%), and oxycodone (17.7%). The median (IQR; 10th-90th percentile) oral MME dose dispensed after retrieval was 90 (50-125; 50-207). Women with mood disorders (adjusted odds ratio [aOR] 1.17, 95% CI 1.00-1.36), tobacco use (aOR 1.67, 95% CI 1.18-2.37), or anti-depressant use (aOR 1.62, 95% CI 1.47-1.80) were more likely to fill an opioid prescription, compared to those without these diagnoses.Although only a small proportion of women fill a prescription for opioids after oocyte retrieval, there is substantial variation in the amount dispensed. Patients with a concurrent mood disorder or those taking anti-depressants were more likely to fill an opioid prescription.

  View details for DOI 10.1016/j.fertnstert.2018.06.023

  View details for PubMedID 30316436

• Preeclampsia and academic performance in children: A nationwide study from Iceland. PloS one Sverrisson, F. A., Bateman, B. T., Aspelund, T., Skulason, S., Zoega, H. 2018; 13 (11): e0207884

  Abstract

  Hypertensive disorders complicate up to 10% of pregnancies. Evidence suggests a potential association between maternal hypertensive disorders during pregnancy, particularly preeclampsia, and adverse neurodevelopment in the offspring, but existing studies are subject to limitations. We aimed to assess whether in-utero exposure to preeclampsia/eclampsia negatively impacts academic performance at ages 9, 12 and 15 years.Using individually linked, nationwide data from the Icelandic registries we followed all children born in 1989-2004 (N = 68,580), from birth until the end of 2014, thereof 63,014 (91.9%) took at least one standardized test. Using a stepwise, mixed-effects approach, we modelled the hypothesized relationship while adjusting for maternal, perinatal and childhood variables of interest. We compared test scores, measured on a normalized scale ranging from 0-60 with a mean of 30 and a standard deviation of 10, in the 4th, 7th, and 10th grades, between children exposed to preeclampsia or eclampsia in-utero versus children from normotensive pregnancies in the population.Children exposed to preeclampsia/eclampsia scored lower than those unexposed in mathematics across all grade levels, corresponding to a difference of 0.44 points (95% CI: 0.00, 0.89), 0.59 points (95% CI: 0.13, 1.06) and 0.59 points (95% CI: 0.08, 1.10), respectively. No differences were observed in the language arts.Our findings suggest a minimal effect of maternal preeclampsia/eclampsia on children's academic performance at ages 9, 12 and 15 years. The differences observed in mathematic scores between exposed and unexposed children were minimal, less than one tenth of a standard deviation per measurement occasion.

  View details for DOI 10.1371/journal.pone.0207884

  View details for PubMedID 30462738

  View details for PubMedCentralID PMC6249018

• OPIOID PRESCRIBING PATTERNS AFTER EGG RETRIEVAL. Bortoletto, P., Prabhu, M., Garry, E., Huybrechts, K. F., Anchan, R. M., Bateman, B. T. ELSEVIER SCIENCE INC. 2017: E64

  View details for DOI 10.1016/j.fertnstert.2017.07.202

  View details for Web of Science ID 000409446000156

• Patterns of Prescription Opioid Utilization Prior to Opioid Overdose in a Commercially Insured Population Dejene, S. Z., Rough, K., Huybrechts, K. F., Hernandez-Diaz, S., Levin, R., Desai, R. J., Patorno, E., Bateman, B. T. WILEY. 2017: 493-494

  View details for Web of Science ID 000437104300415

• Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery BRITISH JOURNAL OF ANAESTHESIA Ahmad, T., Bouwman, R. A., Grigoras, I., Aldecoa, C., Hofer, C., Hoeft, A., Holt, P., Fleisher, L. A., Buhre, W., Pearse, R. 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Papakonstantinou, N., Tsigou, E., Xifara, A., Zoulamoglou, M., Gkioni, P., Karatzas, S., Kyparissi, A., Mainas, E., Papapanagiotou, I., Papavasilopoulou, T., Fragandreas, G., Georgopoulou, E., Katsika, E., Psarras, K., Synekidou, E., Verroiotou, M., Vetsiou, E., Zaimi, D., Anagnou, A., Apostolou, K., Melissopoulou, T., Rozenberg, T., Tsigris, C., Boutsikos, G., Kalles, V., Kotsalas, N., Lavdaiou, C., Paikou, F., Panagou, G., Spring, A., Arvaniti, K., Botis, I., Drimala, M., Georgakakis, G., Kiourtzieva, E., Ntouma, P., Prionas, A., Xouplidis, K., Dalampini, E., Giannaki, C., Iasonidou, C., Ioannidis, O., Lavrentieva, A., Lavrentieva, A., Papageorgiou, G., Kokkinoy, M., Stafylaraki, M., Gaitanakis, S., Karydakis, P., Paltoglou, J., Ponireas, P., Chaloulis, P., Provatidis, A., Sousana, A., Gardikou, V., Konstantivelli, M., Lataniotou, O., Lisari, E., Margaroni, M., Stamatiou, K., Nikolaidis, E., Pnevmatikos, I., Sertaridou, E., Andreou, A., Arkalaki, E., Athanasakis, E., Chaniotaki, F., Chatzimichali, C., Christofaki, M., Dermitzaki, D., Fiorentza, K., Frantzeskos, G., Geromarkaki, E., Kafkalaki, K., Kalogridaki, M., Karydi, K., Kokkini, S., Kougentakis, G., Lefaki, T., Lilitsis, E., Makatounaki, A., Malliotakis, P., Michelakis, D., Neonaki, M., Nyktari, V., Palikyra, I., Papadakis, E., Papaioannou, A., Sfakianakis, K., Sgouraki, M., Souvatzis, X., Spartinou, A., Stefanidou, N., Syrogianni, P., Tsagkaraki, G., Arnaoutoglou, E., Arnaoutoglou, C., Bali, C., Bouris, V., Doumos, R., Gkini, K., Kapaktsi, C., Koulouras, V., Lena, A., Lepida, D., Michos, E., Papadopoulos, D., Paschopoulos, M., Rompou, V., Siouti, I., Tsampalas, S., Ververidou, O., Zilis, G., Charlalampidoy, A., Christodoulidis, G., Flossos, A., Stamoulis, K., Chan, M., Tsang, M., Tsang, M., Lai, M., Yip, C., Chan, H., Law, B., Li, W., Chu, H., Koo, E., Lam, C., Cheng, K., Lam, T., Chu, S., Lam, W., Wong, K., Kwok, D., Hung, C., Chan, W., Wong, W., Chung, C., Ma, S., Kaushik, S., Shah, B., Shah, D., Shah, S., Ar, P., Muthuchellappan, R., Agarwal, V., Divatia, J., Kulkarni, A., Mishra, S., Nimje, G., Pande, S., Savarkar, S., Shrivastava, A., Thomas, M., Yegnaram, S., Hidayatullah, R., Chandra, S., Tantri, A., Puar, N., Niman, S., Indra, I., Hamzah, Z., Yuliana, A., Abidin, U., Dursin, A., Kurnia, A., Susanti, A., Handayani, D., Alit, M., Arya, A., Senapathi, T., Utara, U., Wid, W., Wima, S., Wir, W., Jehosua, B., Kaunang, J., Lantang, E., Najoan, R., Waworuntu, N., Awad, H., Fuad, A., Geddoa, E., Geddoa, B., Khalaf, A., Al hussaini, S., Albaj, S., Kenber, M., Bettinelli, A., Spadaro, S., Volta, C., Giancarlo, L., Sottosanti, V., Copetti, E., Della Rocca, G., Spagnesi, L., Toretti, I., Alloj, C., Cardellino, S., Carmino, L., Costanzo, E., Fanfani, L., Novelli, M., Roasio, A., Bellandi, M., Beretta, L., Bignami, E., Bocchino, S., Cabrini, L., Corti, D., Landoni, G., Meroni, R., Moizo, E., Monti, G., Pintaudi, M., Plumari, V., Taddeo, D., Testa, V., Winterton, D., Zangrillo, A., Cloro, L., Colangelo, C., Colangelo, A., Rotunno, G., Paludi, M., Maria, C., Pata, A., Parrini, V., Gatta, A., Nastasi, M., Tinti, C., Baroselli, A., Arrigo, M., Benevento, A., Bottini, C., Cannavo, M., Gastaldi, C., Marchesi, A., Pascazio, A., Pata, F., Pozzi, E., Premoli, A., Tessera, G., Boschi, L., D'Andrea, R., Ghignone, F., Poggioli, G., Sibilio, A., Taffurelli, M., Ugolini, G., Ab Majid, M., Ab Rahman, R., Joseph, J., Pathan, F., Shah, M., Yap, H., Cheah, S., Chin, I., Looi, J., Tan, S., Visvalingam, S., Kwok, F., Lee, C., Tan, T., Wong, S., Abdullah, N., Liew, C., Luxuman, L., Zin, N., Norddin, M., Alias, R., Wong, J., Yong, J., Bin Mustapha, M., Chan, W., Dzulkipli, N., Kuan, P., Lee, Y., Alias, A., Guok, E., Jee, C., Ramon, B., Wong, C., Ghafar, F., Aziz, F., Hussain, N., Lee, H., Sukawi, I., Woon, Y., Hadi, H., Azam, U., Alias, A., Kesut, S., Lee, J., Ooi, D., Sulaiman, H., Lih, T., Mansor, M., Veerakumaran, J., Luna, P., Rojas, E., Resendiz, G., Zapata, D., Lopez, J., Flores, A., Amador, J., Avila, E., Aquino, L., Rodriguez, R., Landa, M., Urias, E., Hollmann, M., Hulst, A., Preckel, O., Koopman-van Gemert, A., Bouwman, A., Buise, M., Tolenaar, N., Weber, E., de Fretes, J., Houweling, P., Ormskerk, P., Van Bommel, J., Buhre, W., Lance, M., Smit-Fun, V., van Zundert, T., Baas, P., de Boer, H., Sprakel, J., Elferink-Vonk, R., Noordzij, P., van Zeggeren, L., Brand, B., Spanjersberg, R., ten Bokkel-Andela, J., Numan, S., van Klei, W., van Zaane, B., Boer, C., van Duivenvoorde, Y., Hering, J., van Rossum, S., Zonneveldt, H., Campbell, D., Hoare, S., Santa, S., Ali, M., Allen, S., Beavis, V., Bell, R., Campbell, D., Choi, H., Drake, M., Farrell, H., Hayes, K., Higgie, K., Holmes, K., Jenkins, N., Kim, C., Kim, S., Law, K., McAllister, D., Park, K., Pedersen, K., Pfeifer, L., Pozaroszczyk, A., Salmond, T., Steynor, M., Tan, M., Short, T., Waymouth, E., Ab Rahman, A., Armstrong, J., Dudson, R., Jenkins, N., Nilakant, J., Richard, S., Virdi, P., Dixon, L., Donohue, R., Farrow, M., Kennedy, R., Marissa, H., McKellow, M., Nicola, D., Pascoe, R., Roberts, S., Rowell, G., Sumner, M., Templer, P., Chandrasekharan, S., Fulton, G., Jammer, I., More, R., Wilson, L., Chang, Y., Foley, J., Fowler, C., Panckhurst, J., Sara, R., Stapelberg, F., Cherrett, V., Ganter, D., McCann, L., Gilmour, F., Lumsden, R., Moores, M., Olliff, S., Sardareva, E., Tai, J., Wikner, M., Wong, C., Chaddock, M., Czepanski, C., McKendry, P., Polakovic, D., Polakovich, D., Robert, A., Belda, M., Norton, T., Alherz, F., Barneto, L., Ramirez, A., Sayeed, A., Smith, N., Bennett, C., McQuoid, S., Jansen, T., Nico, Z., Scott, J., Freschini, D., Freschini, A., Hopkins, B., Manson, L., Stoltz, D., Bates, A., Davis, S., Freeman, V., McGaughran, L., Williams, M., Sharma, S., Burrows, T., Byrne, K., English, D., Johnson, R., Manikkam, B., Naidoo, S., Rumball, M., Whittle, N., Franks, R., Gibson-Lapsley, H., Salter, R., Walsh, D., Cooper, R., Perry, K., Obobolo, A., Sule, U., Ahmad, A., Atiku, M., Mohammed, A., Sarki, A., Adekola, O., Akanmu, O., Durodola, A., Olukoju, O., Raji, V., Olajumokex, T., Oyebamiji, E., Adenekan, A., Adetoye, A., Faponle, F., Olateju, S., Owojuyigbe, A., Talabi, A., Adenike, O., Adewale, B., Collins, N., Ezekiel, E., Fatungase, O., Grace, A., Sola, S., Stella, O., Ademola, A., Adeolu, A. A., Adigun, T., Akinwale, M., Fasina, O., Gbolahan, O., Idowu, O., Olonisakin, R., Osinaike, B., Asudo, F., Mshelia, D., Abdur-Rahman, L., Agodirin, O., Bello, J., Bolaji, B., Oyedepo, O., Ezike, H., Iloabachie, I., Okonkwo, I., Onuora, E., Onyeka, T., Ugwu, I., Umeh, F., Alagbe-Briggs, O., Dodiyi-Manuel, A., Echem, R., Obasuyi, B., Onajin-Obembe, B., Bandeira, M., Martins, A., Tome, M., Martins Costa, A., Krystopchuk, A., Branco, T., Esteves, S., Melo, M., Monte, J., Rua, F., Martins, I., Pinho-Oliveira, V., Rodrigues, C., Cabral, R., Marques, S., Rego, S., Teixeira Jesus, J., Marques, M., Romao, C., Dias, S., Santos, A., Alves, M., Salta, C., Cruz, S., Duarte, C., Furtado Paiva, A., Cabral, T., Faria e Maia, D., Correia da Silva, R., Langner, A., Resendes, H., Soares, M., Abrunhosa, A., Faria, F., Miranda, L., Pereira, H., Serra, S., Ionescu, D., Margarit, S., Mitre, C., Vasian, H., Manga, G., Stefan, A., Tomescu, D., Filipescu, D., Paunescu, M., Stefan, M., Stoica, R., Gavril, L., Patrascanu, E., Ristescu, I., Rusu, D., Diaconescu, C., Iosep, G., Pulbere, D., Ursu, I., Balanescu, A., Grintescu, I., Mirea, L., Rentea, I., Vartic, M., Lupu, M., Stanescu, D., Streanga, L., Antal, O., Hagau, N., Patras, D., Petrisor, C., Tosa, F., Tranca, S., Copotoiu, S., Ungureanu, L., Harsan, C., Papurica, M., Cernea, D., Dragoescu, N., Aflori, L., Vaida, C., Ciobotaru, O., Aignatoaie, M., Carp, C., Cobzaru, I., Mardare, O., Purcarin, B., Tutunaru, V., Ionita, V., Arustei, M., Codita, A., Busuioc, M., Chilinciuc, I., Ciobanu, C., Belciu, I., Tincu, E., Blaj, M., Grosu, R., Sandu, G., Bruma, D., Corneci, D., Dutu, M., Krepil, A., Copaciu, E., Dumitrascu, C., Jemna, R., Mihaescu, F., Petre, R., Tudor, C., Ursache, E., Kulikov, A., Lubnin, A., Grigoryev, E., Pugachev, S., Protsenko, D., Tolmasov, A., Hussain, A., Ilyina, Y., Kirov, M., Roshchina, A., Iurin, A., Ayyaz, H., Chazova, E., Dunay, A., Karelov, A., Khvedelidze, I., Voldaeva, O., Belskiy, V., Dzhamullaev, P., Grishkowez, E., Kretov, V., Levin, V., Molkov, A., Puzanov, S., Samoilenko, A., Tchekulaev, A., Tulupova, V., Utkin, I., Allorto, N., Bishop, D., Builu, P., Cairns, C., Dasrath, A., de Wet, J., den Hoedt, M., Grey, B., Hayes, M., Kusel, B., Shangase, N., Wise, R., Cacala, S., Farina, Z., Govindasamy, V., Kruse, C., Lee, C., Marais, L., Naidoo, T., Rajah, C., Rodseth, R., Ryan, L., von Rhaden, R., Adam, S., Alphonsus, C., Ameer, Y., Anderson, F., Basanth, S., Bechan, S., Bhula, C., Biccard, B. M., Biyase, T., Buccimazza, I., Cardosa, J., Chen, J., Daya, B., Drummond, L., Elabib, A., Goad, E., Goga, I. E., Goga, R., Harrichandparsad, R., Hodgson, R. E., Jordaan, J., Kalafatis, N., Kampik, C., Landers, A. T., Loots, E., Madansein, R., Madaree, A., Madiba, T. E., Manzini, V. T., Mbuyisa, M., Moodley, R., Msomi, M., Mukama, I., Naidoo, D., Naidoo, R., Naidu, T. K., Ntloko, S., Padayachee, E., Padayachee, L., Phaff, M., Pillay, B., Pillay, D., Pillay, L., Ramnarain, A., Ramphal, S. R., Ryan, P., Saloojee, A., Sebitloane, M., Sigcu, N., Taylor, J. L., Torborg, A., Visser, L., Anderson, P., Conradie, A., de Swardt, M., de Villiers, M., Eikman, J., Liebenberg, R., Mouton, J., Paton, A., van der Merwe, L., Wilscott-Davids, C., Barrett, W., Bester, M., de Beer, J., Geldenhuys, J., Gouws, H., Potgieter, J., Strydom, M., Turton, E., Chetty, R. R., Chirkut, S., Cronje, L., de Vasconcellos, K., Dube, N. Z., Gama, N., Green, G. M., Green-Thompson, R., Kinoo, S., Kistnasami, P., Maharaj, K., Moodley, M. S., Mothae, S. J., Naidoo, R., Noorbhai, M. F., Rughubar, V., Reddy, J., Singh, A., Skinner, D. L., Smith, M. J., Singh, B., Misra, R., Naidoo, M., Ramdharee, P., Selibea, Y., Sewpersad, S., Sham, S., Wessels, J. D., Africander, C., Bejia, T., Blakemore, S. P., Botes, M., Bunwarie, B., Hernandez, C. B., Jeeraz, M. A., Legutko, D. A., Lopez, A. G., De Meyer, J. N., Muzenda, T., Naidoo, N., Patel, M., Pentela, R., Junge, M., Mansoor, N., Rademan, L., Scislowski, P., Seedat, I., van den Berg, B., van der Merwe, D., van Wyk, S., Govender, K., Naicker, D., Ramjee, R., Saley, M., Kuhn, W., Matos-Puig, R., Moolla, Z., Lisi, A., Perez, G., Valle Beltran, A., Lozano, A., Delgado Navarro, C., Duca, A., Martinez Ernesto, E., Ferrando, C., Fuentes, I., Luisa Garcia-Perez, M., Gracia, E., Izquierdo Palomares, A., Katime, A., Minana, A., Raul Incertis, R., Romero, E., Romero Garcia, C., Rubio, C., Socorro Artiles, T., Soro, M., Valls, P., Alaman Laguarda, G., Benavent, P., Chisbert Cuenca, V., Cueva, A., Lafuente, M., Marques Parra, A., Romero Rodrigo, A., Sanchez-Morcillo, S., Tormo, S., Javier Redondo, F., De Andres Ibanez, J., Gomez Diago, L., Hernandez Cadiz, M., Gil Manuel, G., Peris, R., Saiz, C., Tatay Vivo, J., Tebar Soto, M., Brunete, T., Cancho, D., Delgado Garcia, D. R., Zamudio, D., Garcia Del Valle, S., Luz Serrano, M., Alonso, E., Anillo, V., Maseda, E., Salgado, P., Suarez, L., Suarez-de-la-Rica, A., Jose Villagran, M., Aldecoa, C., Ignacio Alonso, J., Cabezuelo, E., Garcia-Saiz, I., Lopez del Moral, O., Martin, S., Perez Gonzalez, A., Tovar Doncel, M., Aguero Vera, M., Avila Sanchez, F., Castano, B., Castano Moreira, B., Flores Risco, S., Paz Martin, D., Perez Martin, F., Poza, P., Ruiz, A., Serna Martinez, W., Vazquez Vicente, B., Velaz Dominguez, S., Fernandez, S., Munoz-Lopez, A., Jose Bernat, M., Mas, A., Planas, K., Jawad, M., Saeed, Y., Hedin, A., Levander, H., Chew, M., Holmstrom, S., Lonn, D., Zoerner, F., Akring, I., Widmark, C., Zettergren, J., Liljequist, V., Nystrom, L., Odeberg-Wernerman, S., Oldner, A., Fagerlund, M., Reje, P., Lyckner, S., Sperber, J., Adolfsson, A., Klarin, B., Ogren, K., Barras, J., Buhrer, T., Despotidis, V., Helmy, N., Holliger, S., Raptis, D., Schmid, R., Meyer, A., Jaquet, Y., Kessler, U., Muradbegovic, M., Nahum, S. R., Rotunno, T., Schiltz, B., Voruz, F., Worreth, M., Christoforidis, D., Popeskou, S., Furrer, M., Prevost, G., Stocker, A., Lang, K., Breitenstein, S., Ganter, M. T., Geisen, M., Soll, C., Korkmaz, M., Lubach, I., Schmitz, M., Schwabedissen, M., Moritz, M., Zingg, U., Hillermann, T., Wildi, S., Hofer, C., Pinto, B., Walder, B., Hubner, M., Mariotti, G., Slankamenac, K., Namuyuga, M., Kyomugisha, E., Kituuka, O., Shikanda, A., Kakembo, N., Tom, C., Antonina, W., Bua, E., Ditai, J., Ssettabi, E., Epodoi, J., Kabagenyi, F., Kirya, F., Dempsey, G., Seasman, C., Khan, R., Kurasz, C., Macgregor, M., Shawki, B., Francis, D., Hariharan, V., Chau, S., Ellis, K., Butt, G., Chicken, D., Christmas, N., Allen, S., Daniel, G., Dempster, A., Kemp, J., Matthews, L., Mcglone, P., Tambellini, J., Trodd, D., Freitas, K., Garg, A., Gupta, J., Karpate, S., Kulkarni, A., O'Hara, C., Troko, J., Angus, K., Bradley, J., Brennan, E., Brooks, C., Brown, J., Brown, G., Finch, A., Gratrix, K., Hesketh, S., Hill, G., Jeffs, C., Morgan, M., Pemberton, C., Slawson, N., Spickett, H., Swarbrick, G., Thomas, M., Van Duyvenvoorde, G., Brennan, A., Briscoe, R., Cooper, S., Lawton, T., Northey, M., Senaratne, R., Stanworth, H., Burrows, L., Cain, H., Craven, R., Davies, K., Jonas, A., Pachucki, M., Walkden, G., Davies, H., Gudaca, M., Hobrok, M., Arawwawala, D., Fergey, L., Gardiner, M., Gunn, J., Johnson, L., Lofting, A., Lyle, A., Mc Neela, F., Smolen, S., Topliffe, J., Williams, S., Bland, M., Balaji, P., Kaura, V., Lanka, P., Naylor, C., Smith, N., Ahmed, A., Myatt, J., Shenoy, R., Soon, W., Tan, J., Karadia, S., Self, J., Durant, E., Tripathi, S., Bullock, C., Campbell, D., Ghosh, A., Hughes, T., Zsisku, L., Bengeri, S., Cowton, A., Khalid, M., Limb, J., McAdam, C., Porritt, M., Rafi, M., Shekar, P., Adams, D., Harden, C., Hollands, H., King, A., March, L., Minto, G., Patrick, A., Squire, R., Waugh, D., Kumara, P., Simeson, K., Yarwood, J., Browning, J., Hatton, J., Julian, H., Mitra, A., Newton, M., Pernu, P., Wilson, A., Commey, T., Foot, H., Glover, L., Gupta, A., Lancaster, N., Levin, J., Mackenzie, F., Mestanza, C., Nofal, E., Pout, L., Varden, R., 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Copley, E., Dunk, N., Kulkarni, R., Kumar, P., Metodiev, Y., Ncomanzi, D., Raithatha, B., Raymode, P., Szafranski, J., Twohey, L., Watt, P., Weatherall, L., Weatherill, J., Whitman, Z., Wighton, E., Abayasinghe, C., Chan, A., Darwish, S., Gill, J., Glasgow, E., Hadfield, D., Harris, C., Hopkins, P., Kochhar, A., Kunst, G., Mellis, C., Pool, A., Riozzi, P., Selman, A., Smith, E., Vele, L., Gercek, Y., Guy, K., Holden, D., Watson, N., Whysall, K., Andreou, P., Hales, D., Thompson, J., Bowrey, S., McDonald, S., Gilmore, J., Hills, V., Kelly, C., Kelly, S., Lloyd, G., Abbott, T., Gall, L., Torrance, H., Vivian, M., Berntsen, E., Nolan, T., Turner, A., Vohra, A., Brown, A., Clark, R., Coughlan, E., Daniel, C., Patvardhan, C., Pearson, R., Predeep, S., Saad, H., Shanmugam, M., Varley, S., Wylie, K., Cooper, L., Makowski, A., Misztal, B., Moldovan, E., Pegg, C., Donovan, A., Foot, J., Large, S., Claxton, A., Netke, B., Armstrong, R., Calderwood, C., Kwok, A., Mohr, O., Oyeniyi, P., Patnaik, L., Post, B., Ali, S., Arshad, H., Baker, G., Brenner, L., Brincat, M., Brunswicker, A., Cox, H., Cozar, O., Cheong, E., Durst, A., Fengas, L., Flatt, J., Glister, G., Narwani, V., Photi, E., Rankin, A., Rosbergen, M., Tan, M., Beaton, C., Horn, R., Hunt, J., Rousseau, G., Stancombe, L., Absar, M., Allsop, J., Drinkwater, Z., Hodgkiss, T., Smith, K., Brown, J., Alexander-Sefre, F., Campey, L., Dudgeon, L., Hall, K., Hitchcock, R., James, L., Smith, K., Winstone, U., Ahmad, N., Bauchmuller, K., Harrison, J., Jeffery, H., Miller, D., Pinder, A., Pothuneedi, S., Rosser, J., Sanghera, S., Swift, D., Walker, R., Bester, D., Cavanagh, S., Cripps, H., Daniel, H., Lynch, J., Paton, A., Pyke, S., Scholefield, J., Whitworth, H., Bottrill, F., Ramalingam, G., Webb, S., Akerman, N., Antill, P., Bourner, L., Buckley, S., Castle, G., Charles, R., Eggleston, C., Foster, R., Gill, S., Lindley, K., Lklouk, M., Lowery, T., Martin, O., Milne, D., O'Connor, P., Ratcliffe, A., Rose, A., Smith, A., Varma, S., Ward, J., Barcraft-Barnes, H., Camsooksai, J., Colvin, C., Reschreiter, H., Tbaily, L., Venner, N., Hamilton, C., Kelly, L., Toth-Tarsoly, P., Dodsworth, K., Foord, D., Gordon, P., Hawes, E., Lamb, N., Mouland, J., Nightingale, J., Rose, S., Schrieber, J., Al 'Amri, K., Aladin, H., Arshad, M., Barraclough, J., Bentley, C., Bergin, C., Carrera, R., Clarkson, A., Collins, M., Cooper, L., Denham, S., Griffiths, E., Ip, P., Jeyanthan, S., Joory, K., Kaur, S., Marriott, P., Mitchell, N., Nagaiah, S., Nilsson, A., Parekh, N., Pope, M., Seager, J., Serag, H., Tameem, A., Thomas, A., Thunder, J., Torrance, A., Vohra, R., whitehouse, A., Wong, T., Blunt, M., Wong, K., Giles, J., Reed, I., Weller, D., Bell, G., Birch, J., Damant, R., Maiden, J., Mewies, C., Prince, C., Radford, J., Reynolds, T., Balain, B., Banerjee, R., Barnett, A., Ben Burston, Davies, K., Edwards, J., Evans, C., Ford, D., Gallacher, P., Hill, S., Jaffray, D., Karlakki, S., Kelly, C., Kennedy, J., Kiely, N., Lewthwaite, S., Marquis, C., Ockendon, M., Phillips, S., Pickard, S., Richardson, J., Roach, R., Smith, T., Spencer-Jones, R., Steele, N., Steen, J., Van Liefland, M., White, S., Faulds, M., Harris, M., Kelly, C., Nicol, S., Pearson, S., Chukkambotla, S., Andrew, A., Attrill, E., Campbell, G., Datson, A., Fouracres, A., Graterol, J., Graves, L., Hong, B., Ishimaru, A., Karthikeyan, A., King, H., Lawson, T., Lee, G., Lyons, S., Hall, A., Mathoulin, S., Mcintyre, E., Mclaughlin, D., Mulcahy, K., Paddle, J., Ratcliffe, A., Robbins, J., Sung, W., Tayo, A., Trembath, L., Venugopal, S., Walker, R., Wigmore, G., Boereboom, C., Downes, C., Humphries, R., Melbourne, S., Smith, C., Tou, S., Ullah, S., Batchelor, N., Boxall, L., Broomby, R., Deen, T., Hellewell, A., Helliwell, L., Hutchings, M., Hutchins, D., Keenan, S., Mackie, D., Potter, A., Smith, F., Stone, L., Thorpe, K., Wassall, R., Woodgate, A., Baillie, S., Campbell, T., James, S., King, C., de Araujo, D., Martin, D., Morkane, C., Neely, J., Rajendram, R., Burton, M., James, K., Keevil, E., Minik, O., Morgan, J., Musgrave, A., Rajanna, H., Roberts, T., Szakmany, T., Adamson, M., Jumbe, S., Kendall, J., Muthuswamy, M., Anderson, C., Cruikshanks, A., Wrench, I., Zeidan, L., Ardern, D., Harris, B., Hellstrom, J., Martin, J., Thomas, R., Varsani, N., Brown, C., Docherty, P., Gillies, M., McGregor, E., Usher, H., Craig, J., Smith, A., Ahmad, T., Bodger, P., Creary, T., Everingham, K., Fowler, A., Hewson, R., Ijuo, E., Januszewska, M., Jones, T., Kantsedikas, I., Lahiri, S., McLean, A., Niebrzegowska, E., Phull, M., Wang, D., Wickboldt, N., Baldwin, J., Doyle, D., Mcmullan, S., Oladapo, M., Owen, T., Williams, A., Daniel, H., Gregory, P., Husain, T., Kirk-Bayley, J., Mathers, E., Montague, L., Harper, M., White, S., Jack, J., Ridley, C., Avis, J., Cook, T., Dali-Kemmery, L., Kerslake, I., Lambourne, V., Pearson, A., Boyd, C., Callaghan, M., Lawson, C., McCrossan, R., Nesbitt, V., O'connor, L., Scott, J., Sinclair, R., Farid, N., Morgese, C., Bhatia, K., Karmarkar, S., Ahmed, J., Branagan, G., Hutton, M., Swain, A., Brookes, J., Cornell, J., Dolan, R., Hulme, J., van Vuuren, A., Jowitt, T., Kalashetty, G., Lloyd, F., Patel, K., Sherwood, N., Brown, L., Chandler, B., Deighton, K., Emma, T., Haunch, K., Cheeseman, M., Dent, K., Garg, S., Gray, C., Hood, M., Jones, D., Juj, J., Rao, R., Walker, T., Al Anizi, M., Cheah, C., Cheing, Y., Coutinho, F., Gondo, P., Hadebe, B., Hove, M., khader, A., Krishnachetty, B., Rhodes, K., Sokhi, J., Baker, K., Bertram, W., Looseley, A., Mouton, R., Hanna, G., Arnold, G., Arya, S., Balfoussia, D., Baxter, L., Harris, J., Jones, C., Knaggs, A., Markar, S., Perera, A., Scott, A., Shida, A., Sirha, R., Wright, S., Frost, V., Gray, C., Andrews, E., Arrandale, L., Barrett, S., Cifra, E., Cooper, M., Dragnea, D., Elna, C., Maclean, J., Meier, S., Milliken, D., Munns, C., Ratanshi, N., Ramessur, S., Salvana, A., Watson, A., Ali, H., Campbell, G., Critchley, R., Endersby, S., Hicks, C., Liddle, A., Pass, M., Ritchie, C., Thomas, C., Too, L., Welsh, S., Gill, T., Johnson, J., Reed, J., Davis, E., Papadopoullos, S., Attwood, C., Biffen, A., Boulton, K., Gray, S., Hay, D., Mills, S., Montgomery, J., Riddell, R., Simpson, J., Bhardwaj, N., Paul, E., Uwubamwen, N., Alexander, M., Arrich, J., Arumugam, S., Blackwood, D., Boggiano, V., Brown, R., Chan, Y., Chatterjee, D., Chhabra, A., Christian, R., Costelloe, H., Matthewman, M., Dalton, E., Darko, J., Davari, M., Dave, T., Deacon, M., Deepak, S., Edmond, H., Ellis, J., El-Sayed, A., Eneje, P., English, R., Ewe, R., Foers, W., Franklin, J., Gallego, L., Garrett, E., Goldberg, O., Goss, H., Greaves, R., Harris, R., Hennings, C., Jones, E., Kamali, N., Kokkinos, N., Lewis, C., Lignos, L., Malgapo, E., Malik, R., Milne, A., Mulligan, J., Nicklin, P., Palipane, N., Parsons, T., Piper, R., Prakash, R., Ramesh, B., Rasip, S., Reading, J., Rela, M., Reyes, A., Stephens, R., Rooms, M., Shah, K., Simons, H., Solanki, S., Spowart, E., Stevens, A., Thomas, C., Waggett, H., Yassaee, A., Kennedy, A., Scott, S., Somanath, S., Berg, A., Hernandez, M., Nanda, R., Tank, G., Wilson, N., Wilson, D., Al-Soudaine, Y., Baldwin, M., Cornish, J., Davies, Z., Davies, L., Edwards, M., Frewer, N., Gallard, S., Glasbey, J., Harries, R., Hopkins, L., Kim, T., Koompirochana, V., Lawson, S., Lewis, M., Makzal, Z., Scourfield, S., Ahmad, Y., Bates, S., Blackwell, C., Bryant, H., Collins, H., Coulter, S., Cruickshank, R., Daniel, S., Daubeny, T., Edwards, M., Golder, K., Hawkins, L., Helen, B., Hinxman, H., Levett, D., Salmon, K., Seaward, L., Skinner, B., Tyrell, B., Wadams, B., Walsgrove, J., Dickson, J., Constantin, K., Karen, M., O'Brien, P., O'Donohoe, L., Payne, H., Sundayi, S., Walker, E., Brooke, J., Cardy, J., Humphreys, S., Kessack, L., Kubitzek, C., Kumar, S., Cotterill, D., Hodzovic, E., Hosdurga, G., Miles, E., Saunders, G., Campbell, M., Chan, P., Jemmett, K., Raj, A., Naik, A., Oshowo, A., Ramamoorthy, R., Shah, N., Sylvan, A., Blyth, K., Burtenshaw, A., Freeman, D., Johnson, E., Lo, P., Martin, T., Plunkett, E., Wollaston, J., Allison, J., Carroll, C., Craw, N., Craw, S., Pitt-Kerby, T., Rowland-Axe, R., Spurdle, K., McDonald, A., Simon, D., Sinha, V., Smith, T., Banner-Goodspeed, V., Boone, M., Campbell, K., Lu, F., Scannell, J., Sobol, J., Balajonda, N., Clemmons, K., Conde, C., Elgasim, M., Funk, B., Hall, R., Hopkins, T., Olaleye, O., Omer, O., Pender, M., Porto, A., Stevens, A., Waweru, P., Yeh, E., Bodansky, D., Evans, A., Kleopoulos, S., Maril, R., Mathney, E., Sanchez, A., Tinuoye, E., Bateman, B., Eng, K., Jiang, N., Ladha, K., Needleman, J., Chen, L., Lane, R., Robinowitz, D., Ghushe, N., Irshad, M., O'Connor, J., Patel, S., Takemoto, S., Wallace, A., Mazzeffi, M., Rock, P., Wallace, K., Zhu, X., Chua, P., Fleisher, L., Mattera, M., Sharar, R., Thilen, S., Treggiari, M., Morgan, A., Sofjan, I., Subramaniam, K., Avidan, M., Maybrier, H., Muench, M., Wildes, T., Int Surgical Outcomes Study ISOS 2017; 119 (2): 258-266

  Abstract

  The incidence and impact of postoperative complications are poorly described. Failure-to-rescue, the rate of death following complications, is an important quality measure for perioperative care but has not been investigated across multiple health care systems.We analysed data collected during the International Surgical Outcomes Study, an international 7-day cohort study of adults undergoing elective inpatient surgery. Hospitals were ranked by quintiles according to surgical procedural volume (Q1 lowest to Q5 highest). For each quintile we assessed in-hospital complications rates, mortality, and failure-to-rescue. We repeated this analysis ranking hospitals by risk-adjusted complication rates (Q1 lowest to Q5 highest).A total of 44 814 patients from 474 hospitals in 27 low-, middle-, and high-income countries were available for analysis. Of these, 7508 (17%) developed one or more postoperative complication, with 207 deaths in hospital (0.5%), giving an overall failure-to-rescue rate of 2.8%. When hospitals were ranked in quintiles by procedural volume, we identified a three-fold variation in mortality (Q1: 0.6% vs Q5: 0.2%) and a two-fold variation in failure-to-rescue (Q1: 3.6% vs Q5: 1.7%). Ranking hospitals in quintiles by risk-adjusted complication rate further confirmed the presence of important variations in failure-to-rescue, indicating differences between hospitals in the risk of death among patients after they develop complications.Comparison of failure-to-rescue rates across health care systems suggests the presence of preventable postoperative deaths. Using such metrics, developing nations could benefit from a data-driven approach to quality improvement, which has proved effective in high-income countries.

  View details for DOI 10.1093/bja/aex185

  View details for Web of Science ID 000406549900063

  View details for PubMedID 28854536

• Pregabalin Use Early in Pregnancy and the Risk of Major Congenital Malformations Patorno, E., Bateman, B. T., Huybrechts, K. F., MacDonald, S. C., Cohen, J. M., Desai, R. J., Panchaud, A., Mogun, H., Pennell, P. B., Hernandez-Diaz, S. WILEY. 2017: 215-216

  View details for Web of Science ID 000437103900355

• The Safety of Gabapentin in Pregnant Women with Regard to the Risk of Congenital Malformations Patorno, E., Hernandez-Diaz, S., Huybrechts, K. F., Cohen, J. M., Desai, R. J., Mogun, H., Bateman, B. T. WILEY. 2017: 221-222

  View details for Web of Science ID 000437103900365

• Antidepressant Use in Pregnancy and the Risk of Low Apgar Score Cantarutti, A., Patorno, E., Corrao, G., Merlino, L., Hernandez-Diaz, S., Bateman, B. T., Huybrechts, K. F. WILEY. 2017: 406

  View details for Web of Science ID 000437104300272

• ADHD Drugs During Pregnancy and the Risk of Congenital Malformations: A Study from the International Pregnancy Safety Study (InPreSS) Consortium Broms, G., Hernandez-Diaz, S., Bateman, B., Einarsdottir, K., Furu, K., Huybrechts, K., Karlsson, P., Lahesmaa-Korpinen, A., Norgaard, M., Reutfors, J., Zoega, H., Kieler, H. WILEY. 2017: 468-469

  View details for Web of Science ID 000437104300374

• ADHD Medication Use in Pregnancy and Risk of Preeclampsia and Small for Gestational Age Birth Cohen, J. M., Hernandez-Diaz, S., Bateman, B. T., Park, Y., Desai, R., Mogun, H., Huybrechts, K. F. WILEY. 2017: 502-503

  View details for Web of Science ID 000437104300429

• Bypassing Agents and Thromboembolic Events in Patients with Hemophilia and Inhibitors Bykov, K., Bohn, R. L., Ewenstein, B. M., Seeger, J. D., Avorn, J., Bateman, B. T. WILEY. 2017: 191-192

  View details for Web of Science ID 000437103900314

• Beta Blocker Use in Pregnancy and the Risk of Congenital Malformations: A Study from the International Pregnancy Safety Study (InPreSS) Consortium Bateman, B. T., Heide-Jorgensen, U., Furu, K., Gissler, M., Hernandez-Diaz, S., Huybrechts, K. F., Kieler, H., Norgaard, M., Reutfors, J., Zoega, H. WILEY. 2017: 220

  View details for Web of Science ID 000437103900362

• Detecting the Etiologically Relevant Risk Window for Medications Used in Pregnancy Huybrechts, K. F., Mogun, H., Bateman, B. T., Hernandez-Diaz, S., Cohen, J. M., Wang, S., Desai, R., Patorno, E., Rough, K., Kulldorff, M. WILEY. 2017: 469-470

  View details for Web of Science ID 000437104300375

• Variation in Antipsychotic Use in Hospitalized Older Adults After Cardiac Surgery Kim, D., Mahesri, M., Bateman, B., Huybrechts, K., Inouye, S., Marcantonio, E., Herzig, S., Ely, E., Pandharipande, P., Pisani, M., Avorn, J. WILEY. 2017: 334-335

  View details for Web of Science ID 000437104300153

• Zidovudine Use in Pregnancy and Congenital Malformations: Bayesian Methods to Interpret New Data in the Context of Existing Evidence Rough, K., Sun, J., Seage, G. R., Williams, P. L., Huybrechts, K. F., Bateman, B. T., Hernandez-Diaz, S. WILEY. 2017: 418

  View details for Web of Science ID 000437104300292

• Validation of Algorithms to Identify Perinatal Outcomes in Large Claims Databases He, M., Cottral, J. A., Bartels, D. D., Dejene, S. Z., Mogun, H., Huybrechts, K. F., Hernandez-Diaz, S., Bateman, B. T. WILEY. 2017: 98-99

  View details for Web of Science ID 000437103900159

• Critical care admission following elective surgery was not associated with survival benefit: prospective analysis of data from 27 countries. Intensive care medicine Kahan, B. C., Koulenti, D., Arvaniti, K., Beavis, V., Campbell, D., Chan, M., Moreno, R., Pearse, R. M. 2017; 43 (7): 971-979

  Abstract

  As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality.Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests.44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10-5.21]; p < 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings.We did not identify any survival benefit from critical care admission following surgery.

  View details for DOI 10.1007/s00134-016-4633-8

  View details for PubMedID 28439646

• Risk of Epidural Hematoma after Neuraxial Techniques in Thrombocytopenic Parturients: A Report from the Multicenter Perioperative Outcomes Group. Anesthesiology Lee, L. O., Bateman, B. T., Kheterpal, S., Klumpner, T. T., Housey, M., Aziz, M. F., Hand, K. W., Maceachern, M., Goodier, C. G., Bernstein, J., Bauer, M. E., Lirk, P., Wilczak, J., Soto, R., Tom, S., Cuff, G., Biggs, D. A., Coffman, T., Saager, L., Levy, W. J., Godbold, M., Pace, N. L., Wethington, K. L., Paganelli, W. C., Durieux, M. E., Domino, K. B., Nair, B., Ehrenfeld, J. M., Wanderer, J. P., Schonberger, R. B., Berris, J., Lins, S., Coles, P., Cummings, K. C., Maheshwari, K., Berman, M. F., Wedeven, C., LaGorio, J., Fleishut, P. M., Ellis, T. A., Molina, S., Carl, C., Kadry, B., van Klei, W. A., Pasma, W., Jameson, L. C., Helsten, D. L., Avidan, M. S. 2017; 126 (6): 1053-1063

  Abstract

  Thrombocytopenia has been considered a relative or even absolute contraindication to neuraxial techniques due to the risk of epidural hematoma. There is limited literature to estimate the risk of epidural hematoma in thrombocytopenic parturients. The authors reviewed a large perioperative database and performed a systematic review to further define the risk of epidural hematoma requiring surgical decompression in this population.The authors performed a retrospective cohort study using the Multicenter Perioperative Outcomes Group database to identify thrombocytopenic parturients who received a neuraxial technique and to estimate the risk of epidural hematoma. Patients were stratified by platelet count, and those requiring surgical decompression were identified. A systematic review was performed, and risk estimates were combined with those from the existing literature.A total of 573 parturients with a platelet count less than 100,000 mm who received a neuraxial technique across 14 institutions were identified in the Multicenter Perioperative Outcomes Group database, and a total of 1,524 parturients were identified after combining the data from the systematic review. No cases of epidural hematoma requiring surgical decompression were observed. The upper bound of the 95% CI for the risk of epidural hematoma for a platelet count of 0 to 49,000 mm is 11%, for 50,000 to 69,000 mm is 3%, and for 70,000 to 100,000 mm is 0.2%.The number of thrombocytopenic parturients in the literature who received neuraxial techniques without complication has been significantly increased. The risk of epidural hematoma associated with neuraxial techniques in parturients at a platelet count less than 70,000 mm remains poorly defined due to limited observations.

  View details for DOI 10.1097/ALN.0000000000001630

  View details for PubMedID 28383323

• Lack of Association Between the Use of Nerve Blockade and the Risk of Postoperative Chronic Opioid Use Among Patients Undergoing Total Knee Arthroplasty: Evidence from the Marketscan Database. Anesthesia and analgesia Sun, E. C., Bateman, B. T., Memtsoudis, S. G., Neuman, M. D., Mariano, E. R., Baker, L. C. 2017

  Abstract

  Total knee arthroplasty (TKA) is associated with high rates of prolonged opioid use after surgery (10%-34%). By decreasing opioid use in the immediate postoperative period, perioperative nerve blockade has been hypothesized to decrease the risk of persistent opioid use.Using health care utilization data, we constructed a sample of 120,080 patients undergoing TKA between 2002 and 2012 and used billing data to identify the utilization of peripheral or neuraxial blockade. We then used a multivariable logistic regression to estimate the association between nerve blockade and the risk of chronic opioid use, defined as having filled ≥10 prescriptions or ≥120 days' supply for an opioid in the first postsurgical year. Our analyses were adjusted for an extensive set of potential confounding variables, including -medical comorbidities, previous opioid use, and previous use of other medications.We did not find an association between nerve blockade and the risk of postsurgical chronic opioid use across any of these 3 groups: adjusted relative risk (ARR) 0.984 for patients opioid-naïve in the year before surgery (98.3% confidence interval [CI], 0.870-1.12, P = .794), ARR 1.02 for intermittent opioid users (98.3% CI, 0.948-1.09, P = .617), and ARR 0.986 (98.3% CI, 0.963-1.01, P = .257) for chronic opioid users. Similar results held for alternative measures of postsurgical opioid use.Although the use of perioperative nerve blockade for TKA may improve short-term outcomes, the analyzed types of blocks do not appear to decrease the risk of persistent opioid use in the longer term.

  View details for DOI 10.1213/ANE.0000000000001943

  View details for PubMedID 28430692

• OPIOID PRESCRIBING AT INITIAL ENCOUNTERS FOR PAIN IN UNITED STATES PRIMARY CARE SETTINGS Mundkur, M., Rough, K., Huybrechts, K., Levin, R., Gagne, J., Desai, R., Patorno, E., Choudhry, N. K., Bateman, B. SPRINGER. 2017: S257

  View details for Web of Science ID 000440259000391

• Difficult Airway Management Caused by Local Anesthetic Allergy During Emergent Cesarean Delivery: A Case Report. A & A case reports Maxey-Jones, C. L., Palmerton, A., Farmer, J. R., Bateman, B. T. 2017; 9 (3): 84-86

  Abstract

  Difficult airway management in the gravid patient is a well-described phenomenon. We present a case of emergent cesarean delivery complicated by a "cannot intubate, cannot ventilate" scenario that was later determined to be secondary to an allergic, IgE-mediated reaction to epidurally administered local anesthetic.

  View details for DOI 10.1213/XAA.0000000000000533

  View details for PubMedID 28448320

• Shared decision-making for opioid prescribing after cesarean delivery Prabhu, M., McQuaid-Hanson, E., Hopp, S., Kaimal, A., Leffert, L., Bateman, B. T. MOSBY-ELSEVIER. 2017: S469

  View details for DOI 10.1016/j.ajog.2016.11.726

  View details for Web of Science ID 000414256403136

• Patterns of Opioid Prescription and Use After Cesarean Delivery. Obstetrics and gynecology Bateman, B. T., Cole, N. M., Maeda, A. n., Burns, S. M., Houle, T. T., Huybrechts, K. F., Clancy, C. R., Hopp, S. B., Ecker, J. L., Ende, H. n., Grewe, K. n., Raposo Corradini, B. n., Schoenfeld, R. E., Sankar, K. n., Day, L. J., Harris, L. n., Booth, J. L., Flood, P. n., Bauer, M. E., Tsen, L. C., Landau, R. n., Leffert, L. R. 2017; 130 (1): 29–35

  Abstract

  To define the amount of opioid analgesics prescribed and consumed after discharge after cesarean delivery.We conducted a survey at six academic medical centers in the United States from September 2014 to March 2016. Women who had undergone a cesarean delivery were contacted by phone 2 weeks after discharge and participated in a structured interview about the opioid prescription they received on discharge and their oral opioid intake while at home.A total of 720 women were enrolled; of these, 615 (85.4%) filled an opioid prescription. The median number of dispensed opioid tablets was 40 (interquartile range 30-40), the median number consumed was 20 (interquartile range 8-30), and leftover was 15 (interquartile range 3-26). Of those with leftover opioids, 95.3% had not disposed of the excess medication at the time of the interview. There was an association between a larger number of tablets dispensed and the number consumed independent of patient characteristics. The amount of opioids dispensed did not correlate with patient satisfaction, pain control, or the need to refill the opioid prescription.The amount of opioid prescribed after cesarean delivery generally exceeds the amount consumed by a significant margin, leading to substantial amounts of leftover opioid medication. Lower opioid prescription correlates with lower consumption without a concomitant increase in pain scores or satisfaction.

  View details for PubMedID 28594763

  View details for PubMedCentralID PMC5600205

• Not Too Little, Not Too Much: Finding the Goldilocks Zone for Spinal Anesthesia to Facilitate External Cephalic Version. Anesthesiology Carvalho, B. n., Bateman, B. T. 2017; 127 (4): 596–98

  View details for PubMedID 28799953

• Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic. Anesthesia and analgesia Hah, J. M., Bateman, B. T., Ratliff, J. n., Curtin, C. n., Sun, E. n. 2017; 125 (5): 1733–40

  Abstract

  Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.

  View details for PubMedID 29049117

• In Response. Anesthesia and analgesia Sun, E. C., Bateman, B. T., Memtsoudis, S. G., Neuman, M. D., Mariano, E. R., Baker, L. C. 2017

  View details for PubMedID 29239946

• Evaluation of algorithms to identify delirium in administrative claims and drug utilization database. Pharmacoepidemiology and drug safety Kim, D. H., Lee, J., Kim, C. A., Huybrechts, K. F., Bateman, B. T., Patorno, E., Marcantonio, E. R. 2017; 26 (8): 945-953

  Abstract

  To evaluate the performance of delirium-identification algorithms in administrative claims and drug utilization data.We used data from a prospective study of 184 older adults who underwent aortic valve replacement at a single academic medical center to evaluate the following delirium-identification algorithms: (1) International Classification of Diseases (ICD) diagnosis codes for delirium; (2) antipsychotics use; (3) either ICD diagnosis codes or antipsychotics use; and (4) both ICD diagnosis codes and antipsychotics use. These algorithms were evaluated against a validated bedside assessment, the Confusion Assessment Method, and a validated delirium severity scale, the CAM-S.Delirium occurred in 66 patients (36%), of which 14 (21%) had hyperactive or mixed features and 15 (23%) had severe delirium. ICD diagnosis codes for delirium were present in 15 patients (8%). Antipsychotics were used in 13 patients (7%). ICD diagnosis codes alone and antipsychotics use alone had comparable sensitivity (18% vs. 18%) and specificity (98% vs. 99%). Defining delirium using either ICD diagnosis codes or antipsychotics use, sensitivity improved to 30% with little change in specificity (97%). This algorithm showed higher sensitivity for hyperactive or mixed delirium (64%) and severe delirium (73%). Requiring both ICD diagnosis codes and antipsychotics use resulted in perfect specificity but low sensitivity (6%).Delirium-identification algorithms in claims data have low sensitivity and high specificity. Defining delirium using ICD diagnosis codes or antipsychotics use performs better than considering either type of information alone. This information should inform the design and interpretation of claims-based comparative effectiveness and safety research. Copyright © 2017 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pds.4226

  View details for PubMedID 28485014

  View details for PubMedCentralID PMC5583076

• Zidovudine use in pregnancy and congenital malformations. AIDS (London, England) Rough, K., Sun, J. W., Seage, G. R., Williams, P. L., Huybrechts, K. F., Bateman, B. T., Hernandez-Diaz, S. 2017; 31 (12): 1733-1743

  Abstract

  There is inconsistent evidence that zidovudine use during pregnancy increases overall, cardiac, and male genital malformations.We conducted a systematic review and meta-analysis of zidovudine use and malformations and, using Bayesian methods, combined it with data from a cohort study of mother-infant pairs in the nationwide Medicaid Analytic eXtract (MAX).Using MAX data (2000-2010), we identified pregnant women with HIV treated with antiretroviral therapy (ART). Women with at least one zidovudine dispensing during the first trimester were compared to women receiving ART without zidovudine in the first trimester. Malformation outcomes were defined using diagnosis/procedure codes. To adjust for confounding, we performed 1 : 1 propensity score matching. Bayesian methods require specification of a prior, which we developed in the meta-analysis. Logistic regression models combined MAX data with the prior, estimating odds ratios (ORs) and 95% credible intervals.Fourteen articles contributed information on overall malformations, seven on cardiac malformations, and five on male genital malformations. In MAX, matching led to a sample of 735 women each in the zidovudine and comparator groups. When comparing first trimester zidovudine use to other ART, the Bayesian procedure yielded OR estimates slightly above the null for overall [OR = 1.11, 95% credible interval (0.80-1.55)] and cardiac [OR = 1.30 (0.63-2.71)] malformations. There were no zidovudine-exposed cases of male genital malformations in MAX, but the meta-analysis yielded elevated OR estimates [OR = 2.57 (1.26-5.24)].For most malformations, first-trimester zidovudine was not associated with increased risk. The potential increase in male genital malformations was small in absolute terms, and should be evaluated further.

  View details for DOI 10.1097/QAD.0000000000001549

  View details for PubMedID 28537936

  View details for PubMedCentralID PMC5534355

• A Family-Based Study of the Association Between Labor Induction and Offspring Attention-Deficit Hyperactivity Disorder and Low Academic Achievement. Behavior genetics Wiggs, K. K., Rickert, M. E., Hernandez-Diaz, S., Bateman, B. T., Almqvist, C., Larsson, H., Lichtenstein, P., Oberg, A. S., D'Onofrio, B. M. 2017; 47 (4): 383-393

  Abstract

  The current study examined associations between labor induction and both (1) offspring attention-deficit hyperactivity disorder (ADHD) diagnosis in a Swedish birth cohort born 1992-2005 (n = 1,085,008) and (2) indices of offspring low academic achievement in a sub-cohort born 1992-1997 (n = 489,196). Associations were examined in the entire sample (i.e., related and unrelated individuals) with adjustment for measured covariates and, in order to account for unmeasured confounders shared within families, within differentially exposed cousins and siblings. We observed an association between labor induction and offspring ADHD diagnosis and low academic achievement in the population. However, these associations were fully attenuated after adjusting for measured covariates and unmeasured factors that cousins and siblings share. The results suggest that observed associations between labor induction and ADHD and low academic achievement may be due to genetic and/or shared environmental factors that influence both mothers' risk of labor induction and offspring neurodevelopment.

  View details for DOI 10.1007/s10519-017-9852-4

  View details for PubMedID 28551761

• A Shared Decision-Making Intervention to Guide Opioid Prescribing After Cesarean Delivery. Obstetrics and gynecology Prabhu, M., McQuaid-Hanson, E., Hopp, S., Burns, S. M., Leffert, L. R., Landau, R., Lauffenburger, J. C., Choudhry, N. K., Kaimal, A., Bateman, B. T. 2017; 130 (1): 42-46

  Abstract

  To assess whether a shared decision-making intervention decreases the quantity of oxycodone tablets prescribed after cesarean delivery.A tablet computer-based decision aid formed the basis of a shared decision-making session to guide opioid prescribing after cesarean delivery. Women first received information on typical trajectories of pain resolution and expected opioid use after cesarean delivery and then chose the number of tablets of 5 mg oxycodone they would be prescribed up to the institutional standard prescription of 40 tablets.From April 11, 2016, to June 10, 2016, 105 women were screened, 75 were eligible, and 51 consented to participate; one patient was excluded after enrollment as a result of prolonged hospitalization. The median number of tablets (5 mg oxycodone) women chose for their prescription was 20.0 (interquartile range 15.0-25.0), which was less than the standard 40-tablet prescription (P<.001).A shared decision-making approach to opioid prescribing after cesarean delivery was associated with approximately a 50% decrease in the number of opioids prescribed postoperatively in this cohort compared with our institutional standard prescription. This approach is a promising strategy to reduce the amount of leftover opioid medication after treatment of acute postcesarean pain.ClinicalTrials.gov, NCT02770612.

  View details for DOI 10.1097/AOG.0000000000002094

  View details for PubMedID 28594762

  View details for PubMedCentralID PMC5482786

• Phenylephrine Infusion: Driving a Wedge in Our Practice of Left Uterine Displacement? Anesthesiology Farber, M. K., Bateman, B. T. 2017; 127 (2): 212-214

  View details for DOI 10.1097/ALN.0000000000001738

  View details for PubMedID 28598893

• Antipsychotic Medication Use Among Publicly Insured Pregnant Women in the United States. Psychiatric services (Washington, D.C.) Park, Y., Huybrechts, K. F., Cohen, J. M., Bateman, B. T., Desai, R. J., Patorno, E., Mogun, H., Cohen, L. S., Hernandez-Diaz, S. 2017; 68 (11): 1112-1119

  Abstract

  Given the increasing use and broadening of indications for use of antipsychotic medications in the general population, as well as the paucity of information on the safety of this drug class during pregnancy, the study documented patterns of antipsychotic medication use among pregnant women.Medicaid Analytic eXtract data (2001-2010) from pregnant women who delivered live-born infants were used. Antipsychotic use at both the class and the individual drug level was defined based on dispensed outpatient prescriptions. Users' characteristics, including mental disorder diagnoses, were described. Temporal trends in use, as well as discontinuation patterns and psychotropic polytherapy, during pregnancy were evaluated.Among 1,522,247 pregnancies, the prevalence of use of second-generation antipsychotics at any time during pregnancy increased threefold, from .4% to 1.3%, over the ten-year period, while the use of first-generation antipsychotics remained stable at around .1%. The increased use of second-generation antipsychotics was largely driven by more frequent use among patients with bipolar disorder. Quetiapine and aripiprazole were the most frequently dispensed drugs, and polytherapy with antipsychotics and antidepressants (65.2%), benzodiazepines (24.9%), and other mood stabilizers (22.0%) was common. More than 50% of women receiving an antipsychotic in the three months prior to pregnancy discontinued the drug during pregnancy.A growing number of pregnant women in Medicaid are exposed to second-generation antipsychotics, frequently in combination with other psychotropic medications. This study highlights the importance of documenting the use and safety of these drugs during pregnancy to inform therapeutic decision making for pregnant women with psychiatric disorders.

  View details for DOI 10.1176/appi.ps.201600408

  View details for PubMedID 28617210

  View details for PubMedCentralID PMC5665733

• Perioperative pain management strategies among women having reproductive surgeries. Fertility and sterility Prabhu, M., Bortoletto, P., Bateman, B. T. 2017; 108 (2): 200-206

  Abstract

  This review presents opioid-sparing strategies for perioperative pain management among women undergoing reproductive surgeries and procedures. Recommendations are provided regarding the use of nonsteroidal anti-inflammatory drugs, acetaminophen, other adjunctive medications, and regional anesthetic blocks. Additional considerations for chronic opioid users or patients using opioid replacement or antagonist therapy are discussed.

  View details for DOI 10.1016/j.fertnstert.2017.06.010

  View details for PubMedID 28697915

  View details for PubMedCentralID PMC5545053

• The Consensus Bundle on Hypertension in Pregnancy and the Anesthesiologist: Doing All the Right Things for All the Patients All of the Time. Anesthesia and analgesia Podovei, M., Bateman, B. T. 2017; 125 (2): 383-385

  View details for DOI 10.1213/ANE.0000000000002296

  View details for PubMedID 28731975

• A prospective study of post-cesarean delivery hypoxia after spinal anesthesia with intrathecal morphine 150μg. International journal of obstetric anesthesia Ladha, K. S., Kato, R., Tsen, L. C., Bateman, B. T., Okutomi, T. 2017; 32: 48-53

  Abstract

  Delayed respiratory depression is a feared complication of intrathecal morphine in patients undergoing cesarean delivery. The incidence, timing and risk factors for hypoxia in this population are not known.Patients undergoing cesarean delivery under spinal anesthesia at a tertiary care center from October 2012 to March 2016 were included in the study. The Berlin sleep apnea Questionnaire was completed before surgery. Oxygen saturation was recorded every second for 24hours after the initiation of spinal anesthesia. Desaturation events were defined as a median saturation of <90% (mild) or <85% (severe) across a 30-s period. Multivariable logistic regression was used to determine predictors of a desaturation event.A total of 721 patients were included in the analysis. Within this cohort, 169 women (23%) experienced at least one mild desaturation event, 91 (13%) experienced two or more mild desaturations, and 26 (4%) suffered a severe desaturation event. After the administration of intrathecal morphine, the median times to first mild or first severe desaturation were 7.4 (IQR 4.1-13.5)h and 12.0 (IQR 5.4-19.6)h, respectively. Patients who screened positive for sleep apnea had increased odds of having a mild desaturation event (OR 2.31, 95% CI 1.40 to 3.79, P=0.001), as did patients who were obese (OR 1.80, 95% CI 1.05 to 3.09, P=0.033).Mild hypoxemia occurred frequently in women receiving intrathecal morphine 150μg for post-cesarean analgesia. Desaturations were observed most frequently 4-8hours after administration of intrathecal morphine. Obesity and a positive Berlin Questionnaire were risk factors for hypoxemic events.

  View details for DOI 10.1016/j.ijoa.2017.06.003

  View details for PubMedID 28964640

  View details for PubMedCentralID PMC5690487

• Placental Complications Associated With Psychostimulant Use in Pregnancy. Obstetrics and gynecology Cohen, J. M., Hernández-Díaz, S., Bateman, B. T., Park, Y., Desai, R. J., Gray, K. J., Patorno, E., Mogun, H., Huybrechts, K. F. 2017; 130 (6): 1192-1201

  Abstract

  To evaluate whether psychostimulants used to treat attention-deficit/hyperactivity disorder (ADHD) are associated with risk of adverse placental-associated pregnancy outcomes including preeclampsia, placental abruption, growth restriction, and preterm birth.We designed a population-based cohort study in which we examined a cohort of pregnant women and their liveborn neonates enrolled in Medicaid from 2000 to 2010. Women who received amphetamine-dextroamphetamine or methylphenidate monotherapy in the first half of pregnancy were compared with unexposed women. We considered atomoxetine, a nonstimulant ADHD medication, as a negative control exposure. To assess whether the risk period extended to the latter half of pregnancy, women who continued stimulant monotherapy after 20 weeks of gestation were compared with those who discontinued. Risk ratios and 95% CIs were estimated with propensity score stratification to control for confounders.Pregnancies exposed to amphetamine-dextroamphetamine (n=3,331), methylphenidate (n=1,515), and atomoxetine (n=453) monotherapy in early pregnancy were compared with 1,461,493 unexposed pregnancies. Among unexposed women, the risks of the outcomes were 3.7% for preeclampsia, 1.4% for placental abruption, 2.9% for small for gestational age, and 11.2% for preterm birth. The adjusted risk ratio for stimulant use was 1.29 for preeclampsia (95% CI 1.11-1.49), 1.13 for placental abruption (0.88-1.44), 0.91 for small for gestational age (0.77-1.07), and 1.06 for preterm birth (0.97-1.16). Compared with discontinuation (n=3,527), the adjusted risk ratio for continuation of stimulant use in the latter half of pregnancy (n=1,319) was 1.26 for preeclampsia (0.94-1.67), 1.08 for placental abruption (0.67-1.74), 1.37 for small for gestational age (0.97-1.93), and 1.30 for preterm birth (1.10-1.55). Atomoxetine was not associated with the outcomes studied.Psychostimulant use during pregnancy was associated with a small increased relative risk of preeclampsia and preterm birth. The absolute increases in risks are small and, thus, women with significant ADHD should not be counseled to suspend their ADHD treatment based on these findings.

  View details for DOI 10.1097/AOG.0000000000002362

  View details for PubMedID 29112657

  View details for PubMedCentralID PMC5709205

• Use of Bypassing Agents and Risk of Thromboembolic Events in Patients with Haemophilia and Inhibitors. Thrombosis and haemostasis Bykov, K., Bohn, R. L., Ewenstein, B. M., Seeger, J. D., Avorn, J., Bateman, B. T. 2017; 117 (12): 2267-2273

  Abstract

  Patients with haemophilia and inhibitors to factors VIII or IX require bypassing therapy. The primary safety concern of bypassing agents is thromboembolism; however, the incidence of thromboembolic adverse events (TAEs) in haemophilia patients with inhibitors remains poorly characterized. The aim of this study was to assess the incidence of TAEs following exposure to bypassing agents in patients with haemophilia. Using U.S. Medicaid database (2000–2010), we identified a cohort of 719 males (mean age: 10 years at cohort entry) with haemophilia A or B and use of either recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrate (aPCC). Patients were followed up until loss of insurance eligibility, end of study period, or the first occurrence of TAE. Exposure was assessed on as-treated basis, and outcomes were adjudicated through review of healthcare claims. During the observation of a total of 2,823 person-years (py; mean follow-up: 3.9 years), 22 TAEs were identified, leading to incidence rates of 4.2 events (95% confidence interval [CI]: 1.8–8.3) per 1,000 unexposed py; 15.4 events (95% CI: 6.7–30.3) per 1,000 aPCC-exposed py; 18.2 events (95% CI: 8.3–34.6) per 1,000 rFVIIa-exposed py; and 29.7 events (95% CI: 6.1–86.7) per 1,000 py of concomitant exposure to both agents. The results were consistent across sensitivity analyses. In conclusion, we found no difference in the rate of TAEs across agents, but the data are compatible with a possibly increased rate associated with a combination therapy, highlighting the need for continuing safety monitoring through prospective registries or observational data.

  View details for DOI 10.1160/TH17-05-0365

  View details for PubMedID 29212114

• Predictors of In-hospital Postoperative Opioid Overdose After Major Elective Operations: A Nationally Representative Cohort Study. Annals of surgery Cauley, C. E., Anderson, G., Haynes, A. B., Menendez, M., Bateman, B. T., Ladha, K. 2017; 265 (4): 702-708

  Abstract

  The aim of this study was to describe national trends and outcomes of in-hospital postoperative opioid overdose (OD) and identify predictors of postoperative OD.In 2000, the Joint Commission recommended making pain the 5th vital sign, increasing the focus on postoperative pain control. However, the benefits of pain management must be weighed against the potentially lethal risk of opioid OD.This is a retrospective multi-institutional cohort study of patients undergoing 1 of 6 major elective inpatient operation from 2002 to 2011 using the Nationwide Inpatient Sample, an approximately 20% representative sample of all United States hospital admissions. Patients with postoperative OD were identified using ICD-9 codes for poisoning from opioids or adverse effects from opioids. Multivariate logistic regression was used to identify independent predictors.Among 11,317,958 patients, 9458 (0.1%) had a postoperative OD; this frequency doubled over the study period from 0.6 to 1.1 overdoses per 1000 cases. Patients with postoperative OD died more frequently during their hospitalization (1.7% vs 0.4%, P < 0.001). Substance abuse history was the strongest predictor of OD (odds ratio = 14.8; 95% confidence interval: 12.7-17.2). Gender, age, income, geographic location, operation type, and certain comorbid diseases also predicted OD (P < 0.05). Hospital variables, including teaching status, size, and urban/rural location, did not predict postoperative OD.Postoperative OD is a rare, but potentially lethal complication, with increasing incidence. Postoperative monitoring and treatment safety interventions should be thoughtfully employed to target high-risk patients and avoid this potentially fatal complication.

  View details for DOI 10.1097/SLA.0000000000001945

  View details for PubMedID 28267693

  View details for PubMedCentralID PMC6153445

• Patterns and predictors of persistent opioid use following hip or knee arthroplasty. Osteoarthritis and cartilage Kim, S. C., Choudhry, N., Franklin, J. M., Bykov, K., Eikermann, M., Lii, J., Fischer, M. A., Bateman, B. T. 2017; 25 (9): 1399-1406

  Abstract

  The relationship between arthroplasty and long-term opioid use in patients with knee or hip osteoarthritis is not well studied. We examined the prevalence, patterns and predictors of persistent opioid use after hip or knee arthroplasty.Using claims data (2004-2013) from a US commercial health plan, we identified adults who underwent hip or knee arthroplasty and filled ≥1 opioid prescription within 30 days after the surgery. We defined persistent opioid users as patients who filled ≥1 opioid prescription every month during the 1-year postoperative period based on group-based trajectory models. Multivariable logistic regression was used to determine preoperative predictors of persistent opioid use after surgery.We identified 57,545 patients who underwent hip or knee arthroplasty. The mean ± SD age was 61.5 ± 7.8 years and 87.1% had any opioid use preoperatively. Overall, 7.6% persistently used opioids after the surgery. Among patients who used opioids in 80% of the time for ≥4 months preoperatively (n = 3023), 72.1% became persistent users. In multivariable analysis, knee arthroplasty vs hip, a longer hospitalization stay, discharge to a rehabilitation facility, preoperative opioid use (e.g., a longer duration and greater dosage and frequency), a higher comorbidity score, back pain, rheumatoid arthritis, fibromyalgia, migraine and smoking, and benzodiazepine use at baseline were strong predictors for persistent opioid use (C-statistic = 0.917).Over 7% of patients persistently used opioids in the year after hip or knee arthroplasty. Given the adverse health effects of persistent opioid use, strategies need to be developed to prevent persistent opioid use after this common surgery.

  View details for DOI 10.1016/j.joca.2017.04.002

  View details for PubMedID 28433815

  View details for PubMedCentralID PMC5565694

• Pregabalin use early in pregnancy and the risk of major congenital malformations. Neurology Patorno, E., Bateman, B. T., Huybrechts, K. F., MacDonald, S. C., Cohen, J. M., Desai, R. J., Panchaud, A., Mogun, H., Pennell, P. B., Hernandez-Diaz, S. 2017; 88 (21): 2020-2025

  Abstract

  To assess whether first-trimester exposure to pregabalin is associated with an increased risk of major congenital malformations, as recently suggested in a pregnancy registry study.We performed a cohort study nested in the US Medicaid Analytic eXtract (MAX). The study population included 1,323,432 pregnancies resulting in a live-born infant between 2000 and 2010. We examined the risk of major congenital malformations among infants born to women exposed to pregabalin during the first trimester compared with women unexposed to anticonvulsants. We used propensity score fine stratification to control for >50 potential confounders, and we estimated relative risks (RRs) and 95% confidence intervals (CIs) in generalized linear models. The analyses were replicated in the Truven Health MarketScan Commercial Database (MarketScan). Pooled estimates based on the adjusted RR produced in MAX, MarketScan, and the previous registry study were calculated.Of 477 infants exposed to pregabalin during the first trimester in MAX, 28 (5.9%) had malformations compared to 3.3% in nonexposed infants. The crude RR of major congenital malformations for pregabalin was 1.80 (95% CI 1.26-2.58). After propensity score adjustment, the RR moved to 1.16 (95% CI 0.81-1.67). Restriction to pregabalin monotherapy and sensitivity analyses produced similar results. The adjusted RR for major congenital malformations for the 174 infants exposed in MarketScan was 1.03 (95% CI 0.56-1.90). The pooled RR was 1.33 (95% CI 0.83-2.15) for pregabalin any use and 1.02 (95% CI 0.69-1.51) for pregabalin monotherapy.Findings did not confirm the suggested teratogenic effects of pregabalin, although they cannot rule out the possibility of a small effect.

  View details for DOI 10.1212/WNL.0000000000003959

  View details for PubMedID 28446648

  View details for PubMedCentralID PMC5440246

• Postpartum anemia: missed opportunities for prevention and recognition. Transfusion Prabhu, M., Bateman, B. T. 2017; 57 (1): 3-5

  View details for DOI 10.1111/trf.13927

  View details for PubMedID 28097696

• Educational Outreach to Opioid Prescribers: The Case for Academic Detailing. Pain physician Trotter Davis, M., Bateman, B., Avorn, J. 2017; 20 (2S): S147-S151

  Abstract

  Nonmedical use of opioid medications constitutes a serious health threat as the rates of addiction, overdoses, and deaths have risen in recent years. Increasingly, inappropriate and excessively liberal prescribing of opioids by physicians is understood to be a central part of the crisis. Public health officials, hospital systems, and legislators are developing programs and regulations to address the problem in sustained and systematic ways that both insures effective treatment of pain and appropriate limits on the availability of opioids. Three approaches have obtained prominence as means of avoiding excessive and inappropriate prescribing, including: providing financial incentives to physicians to change their clinical decision through pay-for-performance contracts, monitoring patient medications through Prescription Drug Monitoring Programs, and educational outreach to physicians. A promising approach to educational outreach to physicians is an intervention known as "academic detailing." It was developed in the 1980s to provide one-on-one educational outreach to physicians using similar methods as the pharmaceutical industry that sends "detailers" to market their products to physician practices. Core to academic detailing, however, is the idea that medical decisions should be based on evidence-based information, including managing conditions with updated assessment measures, behavioral, and nonpharmacological interventions. With the pharmaceutical industry spending billions of dollars to advertise their products, individual practitioners can have difficulty gathering unbiased information, especially as the number of approved medications grows each year. Academic detailing has successfully affected the management of health conditions, such as atrial fibrillation, chronic obstructive pulmonary disease, and recently, has targeted physicians who prescribe opioids. This article discusses the approach as a potentially effective preventative intervention to address the epidemic of opioid overuse.Key words: Opioid abuse, opioid misuse, academic detailing, health policy, interactive education,prevention.

  View details for PubMedID 28226336

• The 2017 Virginia Apgar Collection Part II: Maternal Safety and Abstract Reasoning. Anesthesia and analgesia Bateman, B. T., Smiley, R. 2017; 124 (3): 724-725

  View details for DOI 10.1213/ANE.0000000000001881

  View details for PubMedID 28207443

  View details for PubMedCentralID PMC5325047

• Adverse Events Associated with Antipsychotic Use in Hospitalized Older Adults After Cardiac Surgery. Journal of the American Geriatrics Society Kim, D. H., Huybrechts, K. F., Patorno, E., Marcantonio, E. R., Park, Y., Levin, R., Abdurrob, A., Bateman, B. T. 2017; 65 (6): 1229-1237

  Abstract

  To evaluate in-hospital adverse events associated with typical and atypical antipsychotic medications (APMs) after cardiac surgery.Retrospective cohort study.Nationwide inpatient database, 2003 to 14.Individuals (mean age 70) newly treated with oral atypical (n = 2,580) or typical (n = 1,126 APMs) after coronary artery bypass grafting or valve surgery (N = 3,706).In-hospital mortality, arrhythmia, pneumonia, use of brain imaging (surrogate for oversedation and neurological events), and length of stay after drug initiation RESULTS: In the propensity score-matched cohort, median treatment duration was 3 days (interquartile range (IQR) 1-6 days) for atypical APMs and 2 days (IQR 1-3 days) for typical APMs. There were no large differences in in-hospital mortality (atypical 5.4%, typical 5.3%; risk difference (RD) = 0.1%, 95% confidence interval (CI) = -2.1 to 2.3%), arrhythmia (2.0% vs 2.2%; RD = 0.0%; 95% CI = -1.4 to 1.4%), pneumonia (16.1% vs 14.5%; RD = 1.6%, 95% CI = -1.9 to 5.0%), and length of stay (9.9 days vs 9.3 days; mean difference = 0.5 days, 95% CI = -1.2 to 2.2). Use of brain imaging was more common after initiating atypical APMs (17.3%) than after typical APMs (12.4%; RD = 4.9%, 95% CI = 1.4-8.4).In hospitalized individuals who underwent cardiac surgery, short-term use of typical APMs was associated with risks of adverse events similar to those with atypical APMs. Moreover, greater use of brain imaging associated with atypical APMs suggests that these drugs may cause oversedation or adverse neurological events. Because of the low event rates, the analysis could not exclude modest differences in adverse events between atypical and typical APMs.

  View details for DOI 10.1111/jgs.14768

  View details for PubMedID 28186624

  View details for PubMedCentralID PMC5478449

• Pulmonary Hypertension in Pregnancy: A Report of 49 Cases at Four Tertiary North American Sites. Obstetrics and gynecology Meng, M. L., Landau, R., Viktorsdottir, O., Banayan, J., Grant, T., Bateman, B., Smiley, R., Reitman, E. 2017; 129 (3): 511-520

  Abstract

  To identify whether pregnancy outcomes vary by etiology and severity of pulmonary hypertension and whether contemporary therapies influence outcomes.A retrospective review of medical records at four academic institutions was conducted to identify pregnant women with pulmonary hypertension (2001-2015). International Classification of Diseases, 9th Revision codes for pulmonary hypertension and pregnancy were used to identify potential participants. Medical records were abstracted for demographics, management, and outcomes. Women were classified according to the 2013 World Health Organization (WHO) pulmonary hypertension classification groups 1-5. Mild pulmonary hypertension was defined as a mean pulmonary artery pressure 25-49 mm Hg and severe pulmonary hypertension as mean pulmonary artery pressure 50 mm Hg or greater or systolic pulmonary artery pressure 70 mm Hg or greater. Descriptive statistics were used to compare outcomes.Forty-nine women were identified. Mortality rate was 16% (n=8/49); all deaths occurred postpartum, and seven of eight deaths occurred in women with WHO group 1 pulmonary hypertension (mortality rate 23%, n=7/30). Of the women who had documented live births with known mode of delivery (n=41), mortality was 4 of 22 among women with severe pulmonary hypertension and 1 of 19 among women with mild pulmonary hypertension. Mortality among women who delivered by cesarean was 4 of 22 and was 1 of 19 among women who delivered vaginally. Neuraxial anesthesia was performed in 20 of 22 cesarean and 17 of 19 vaginal deliveries with no anesthesia-related adverse events. Women with severe pulmonary hypertension needed more advanced therapies such as inotropes, pulmonary vasodilators, and extracorporeal membrane oxygenation than did women with mild pulmonary hypertension, 19 of 26 compared with 7 of 22. Preterm delivery was more common in women with severe compared with mild pulmonary hypertension, 19 of 23 compared with 8 of 17. There was one 25-week intrauterine fetal demise, but no neonatal deaths.In this large series of pulmonary hypertension in pregnancy, mortality remained high despite advanced therapies. Maternal mortality was specific to WHO group 1 pulmonary hypertension and possibly associated with severe pulmonary hypertension. In selected patients with a favorable prognosis for vaginal birth, a trial of labor can be considered.

  View details for DOI 10.1097/AOG.0000000000001896

  View details for PubMedID 28178055

• Tipping our CAPS to the UKOSS cardiac arrest in pregnancy study. BJOG : an international journal of obstetrics and gynaecology Mhyre, J. M., Bateman, B. T. 2017; 124 (9): 1382

  View details for DOI 10.1111/1471-0528.14569

  View details for PubMedID 28109048

• Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations. Obstetrics and gynecology Bateman, B. T., Patorno, E., Desai, R. J., Seely, E. W., Mogun, H., Dejene, S. Z., Fischer, M. A., Friedman, A. M., Hernandez-Diaz, S., Huybrechts, K. F. 2017; 129 (1): 174-184

  Abstract

  To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations.We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization.The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations.After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations.

  View details for DOI 10.1097/AOG.0000000000001775

  View details for PubMedID 27926639

  View details for PubMedCentralID PMC5177460

• A Propensity-score-based Fine Stratification Approach for Confounding Adjustment When Exposure Is Infrequent. Epidemiology (Cambridge, Mass.) Desai, R. J., Rothman, K. J., Bateman, B. T., Hernandez-Diaz, S., Huybrechts, K. F. 2017; 28 (2): 249-257

  Abstract

  When exposure is infrequent, propensity-score matching results in reduced precision because it discards a large proportion of unexposed patients. To our knowledge, the relative performance of propensity-score stratification in these circumstances has not been examined.Using an empirical example of the association of first trimester statin exposure (prevalence = 0.04%) with risk of congenital malformations and 1,000 simulated cohorts (n = 20,000) with eight combinations of exposure prevalence (0.5%, 1%, 5%, 10%) and outcome risk (3.5%, 10%), we compared four propensity-score-based approaches to confounding adjustment: (1) matching (1:1, 1:5, full), (2) stratification in 10, 50, and 100 strata by entire cohort propensity-score distribution, (3) stratification in 10, 50, and 100 strata by exposed group propensity-score distribution, (4) standardized mortality ratio (SMR) weighting. Weighted generalized linear models were used to derive effect estimates after weighting unexposed according to the distribution of the exposed in their stratum for the stratification approaches.In the empirical example, propensity-score stratification (cohort) approaches resulted in greater imbalances in covariate distributions between statin-exposed and unexposed compared with propensity-score stratification (exposed) and matching. In simulations, propensity-score stratification (exposed) resulted in smaller relative bias than the cohort approach with 10 and 50 strata, and greater precision than matching and SMR weighting at 0.5% and 1% exposure prevalence, but similar performance at 5% and 10%.For exposures with prevalence under 5%, propensity-score stratification with fine strata, based on the exposed group propensity-score distribution, produced the best results. For more common exposures, all approaches were equivalent.

  View details for DOI 10.1097/EDE.0000000000000595

  View details for PubMedID 27922533

  View details for PubMedCentralID PMC5497217

• Trends in Use of Hydroxychloroquine during Pregnancy in SLE Patients from 2001 to 2012 Bermas, B. L., Kim, S., Huybrechts, K., Hernandez-diaz, S., Bateman, B. T., Desai, R. J. WILEY. 2016

  View details for Web of Science ID 000417143404063

• The Death of a Prince: Chronicle of a Death Foretold PAIN PRACTICE Cahana, A., Bateman, B. T., Landau, R. 2016; 16 (7): 788-790

  View details for DOI 10.1111/papr.12487

  View details for Web of Science ID 000383772700006

  View details for PubMedID 27600922

• Opioid Use Following Discharge After Cesarean Delivery Bateman, B. T., Huybrechts, K. F., Booth, J., Briggs, H., Flood, P., Bauer, M., Landau, R. WILEY-BLACKWELL. 2016: 330-331

  View details for Web of Science ID 000385483502199

• Pregnancy Outcomes in Women with Chronic Hypertension Initiated on Labetalol versus Methyldopa Bateman, B. T., Huybrechts, K. F., Cohen, J., Mogun, H., Desai, R. J., Patorno, E., Hernandez-Diaz, S. WILEY-BLACKWELL. 2016: 15-16

  View details for Web of Science ID 000385483501021

• Is There a Dose-Response Relation Between the Use of Lithium in Early Pregnancy and the Risk of Cardiac Malformations? Patorno, E., Huybrechts, K., Bateman, B., Mogun, H., Desai, R., Hernandez-Diaz, S. WILEY-BLACKWELL. 2016: 236

  View details for Web of Science ID 000385483502038

• Continuation of Atypical Antipsychotic Medications During Pregnancy and the Risk of Gestational Diabetes Park, Y., Hernandez-Diaz, S., Bateman, B. T., Cohen, J., Patorno, E., Mogun, H., Huybrechts, K. F. WILEY. 2016: 235-236

  View details for Web of Science ID 000385483502037

• Psychotropic Medications and the Risk of Neonatal Withdrawal Huybrechts, K. F., Bateman, B. T., Hernandez-Diaz, S., Desai, R. J., Rough, K., Mogun, H., Patorno, E. WILEY. 2016: 260

  View details for Web of Science ID 000385483502077

• Comparative Safety of Antipsychotic Medications in Hospitalized Myocardial Infarction Patients Park, Y., Bateman, B. T., Kim, D., Hernandez-Diaz, S., Patorno, E., Glynn, R. J., Mogun, H., Huybrechts, K. F. WILEY. 2016: 262

  View details for Web of Science ID 000385483502080

• Mood Stabilizer Use and Risk of Ischemic Placental Disease Cohen, J. M., Patorno, E., Huybrechts, K. F., Park, Y., Bateman, B. T., Hernandez-Diaz, S. WILEY. 2016: 297

  View details for Web of Science ID 000385483502140

• Increase in Aberrant Prescription Opioid Use by Pregnant Women in a Nationwide Cohort of Medicaid Beneficiaries Rough, K., Hernandez-Diaz, S., Huybrechts, K. F., Desai, R. J., Patorno, E., Bateman, B. T. WILEY. 2016: 331-332

  View details for Web of Science ID 000385483502201

• Comparative Risk of Serious Infections During Pregnancy in Patients Treated with Immunomodulatory Agents Desai, R. J., Bateman, B. T., Huybrechts, K. F., Patorno, E., Hernandez-Diaz, S., Park, Y., Mogun, H., Kim, S. C. WILEY-BLACKWELL. 2016: 461

  View details for Web of Science ID 000385483503059

• Maternal outcomes of term breech presentation delivery: impact of successful external cephalic version in a nationwide sample of delivery admissions in the United States BMC PREGNANCY AND CHILDBIRTH Weiniger, C. F., Lyell, D. J., Tsen, L. C., Butwick, A. J., Shachar, B., Callaghan, W. M., Creanga, A. A., Bateman, B. T. 2016; 16

  Abstract

  We aimed to define the frequency and predictors of successful external cephalic version in a nationally-representative cohort of women with breech presentations and to compare maternal outcomes associated with successful external cephalic version versus persistent breech presentation.Using the Nationwide Inpatient Sample, a United States healthcare utilization database, we identified delivery admissions between 1998 and 2011 for women who had successful external cephalic version or persistent breech presentation (including unsuccessful or no external cephalic version attempt) at term. Multivariable logistic regression identified patient and hospital-level factors associated with successful external cephalic version. Maternal outcomes were compared between women who had successful external cephalic version versus persistent breech.Our study cohort comprised 1,079,576 delivery admissions with breech presentation; 56,409 (5.2 %) women underwent successful external cephalic version and 1,023,167 (94.8 %) women had persistent breech presentation at the time of delivery. The rate of cesarean delivery was lower among women who had successful external cephalic version compared to those with persistent breech (20.2 % vs. 94.9 %; p < 0.001). Compared to women with persistent breech at the time of delivery, women with successful external cephalic version were also less likely to experience several measures of significant maternal morbidity including endometritis (adjusted Odds Ratio (aOR) = 0.36, 95 % Confidence Interval (CI) 0.24-0.52), sepsis (aOR = 0.35, 95 % CI 0.24-0.51) and length of stay > 7 days (aOR = 0.53, 95 % CI 0.40-0.70), but had a higher risk of chorioamnionitis (aOR = 1.83, 95 % CI 1.54-2.17).Overall a low proportion of women with breech presentation undergo successful external cephalic version, and it is associated with significant reduction in the frequency of cesarean delivery and a number of measures of maternal morbidity. Increased external cephalic version use may be an important approach to mitigate the high rate of cesarean delivery observed in the United States.

  View details for DOI 10.1186/s12884-016-0941-9

  View details for Web of Science ID 000379605300001

  View details for PubMedID 27392035

  View details for PubMedCentralID PMC4938982

• Comparative Safety of Antipsychotic Medication in Hospitalized MI Patients Park, Y., Bateman, B., Kim, D., Hernandez-Diaz, S., Patorno, E., Glynn, R., Mogun, H., Huybrechts, K. WILEY. 2016: S237

  View details for Web of Science ID 000374763800660

• Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries. British journal of anaesthesia 2016; 117 (5): 601-609

  Abstract

  As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care.We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries.A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries.Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care.ISRCTN51817007

  View details for DOI 10.1093/bja/aew316

  View details for PubMedID 27799174

  View details for PubMedCentralID PMC5091334

• Impact of Perioperative Epidural Placement on Postdischarge Opioid Use in Patients Undergoing Abdominal Surgery. Anesthesiology Ladha, K. S., Patorno, E., Liu, J., Bateman, B. T. 2016; 124 (2): 396-403

  Abstract

  Opioids play a crucial role in providing analgesia throughout the perioperative period; however, patients may become persistent users of these medications months after surgery. Epidurals have been posited to prevent the development of persistent pain, but there are little data on the effect of epidurals on persistent opioid use.This study was conducted using a claims database of a large, nationwide commercial health insurer. Opioid-naive patients who underwent open abdominal surgery from January 2004 to December 2013 were included in the study. Propensity scores for epidural placement were calculated accounting for demographic characteristics, resource utilization, and comorbid conditions (including medical, psychiatric, and pain conditions). Time-to-event analysis was used with the primary outcome defined as 30 days without filling an opioid prescription after discharge. In addition, total morphine equivalents dispensed within 90 days of discharge were also calculated for each patient.A total of 6,432 patients were included in the final propensity score-matched cohort. The Cox proportional hazards ratio was 0.96 (95% CI, 0.91 to 1.01; P = 0.0910) for the relation between epidural placement and time till a 30-day gap without filling an opioid prescription. There was no difference in the total morphine equivalents dispensed within 90 days of discharge between the groups (P = 0.7670).Epidural placement was not protective against persistent opioid use in a large cohort of opioid-naive patients undergoing abdominal surgery. This finding does not detract from the other potential benefits of epidural placement. More research is needed to understand the mechanism of persistent opioid use after surgery and its prevention.

  View details for DOI 10.1097/ALN.0000000000000952

  View details for PubMedID 26575145

  View details for PubMedCentralID PMC4718880

• Brief Report: Patterns and Secular Trends in Use of Immunomodulatory Agents During Pregnancy in Women With Rheumatic Conditions. Arthritis & rheumatology (Hoboken, N.J.) Desai, R. J., Huybrechts, K. F., Bateman, B. T., Hernandez-Diaz, S., Mogun, H., Gopalakrishnan, C., Patorno, E., Kim, S. C. 2016; 68 (5): 1183-9

  Abstract

  To describe patterns and secular trends in the use of immunomodulatory agents in pregnant women with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS).We identified a cohort of women with SLE, RA, PsA, or AS enrolled in public (Medicaid, 2001-2010) or private (Optum Clinformatics, 2004-2012) health insurance, and we included women filling prescriptions for immunomodulatory agents (including steroids, nonbiologic disease-modifying agents, and biologic agents) in the 3-month period immediately prior to their pregnancies. The proportion of women continuing or discontinuing individual agents during pregnancy was reported. Annual prescription fill rates, estimated after accounting for patient characteristics and random variability from year to year in mixed-effects regression models, were used to conduct time trends analysis.We included 2,645 women being treated with immunomodulatory agents prior to pregnancy. More women with PsA or AS stopped filling prescriptions for immunomodulatory agents during pregnancy (61%) than women with SLE (26%) or women with RA (34.5%). From the first to the third trimester, the proportions of women filling prescriptions for immunomodulatory agents decreased across all indications. Overall, steroids and hydroxychloroquine were the most frequently used agents in pregnancy (48.4% and 27.1%, respectively). The rates (reported per 100 deliveries in our cohort) for steroid prescription fills during pregnancy decreased significantly from 54.4 in 2001 to 42.4 in 2012, while rates for biologic agents increased from 5.1 in 2001 to 16.6 in 2012 (P < 0.001 for both trends).Steroids and hydroxychloroquine remain the most widely prescribed treatment options in pregnancy, but the use of biologic agents is becoming increasingly common.

  View details for DOI 10.1002/art.39521

  View details for PubMedID 26606742

  View details for PubMedCentralID PMC4848128

• Treatment patterns and short-term outcomes in ischemic stroke in pregnancy or postpartum period. American journal of obstetrics and gynecology Leffert, L. R., Clancy, C. R., Bateman, B. T., Cox, M., Schulte, P. J., Smith, E. E., Fonarow, G. C., Kuklina, E. V., George, M. G., Schwamm, L. H. 2016; 214 (6): 723.e1-723.e11

  Abstract

  Stroke, which is a rare but devastating event during pregnancy, occurs in 34 of every 100,000 deliveries; obstetricians are often the first providers to be contacted by symptomatic patients. At least one-half of pregnancy-related strokes are likely to be of the ischemic stroke subtype. Most pregnant or newly postpartum women with ischemic stroke do not receive acute stroke reperfusion therapy, although this is the recommended treatment for adults. Little is known about these therapies in pregnant or postpartum women because pregnancy has been an exclusion criterion for all reperfusion trials. Until recently, pregnancy and obstetric delivery were specifically identified as warnings to intravenous alteplase tissue plasminogen activator in Federal Drug Administration labeling.The primary study objective was to compare the characteristics and outcomes of pregnant or postpartum vs nonpregnant women with ischemic stroke who received acute reperfusion therapy.Pregnant or postpartum (<6 weeks; n = 338) and nonpregnant (n = 24,303) women 18-44 years old with ischemic stroke from 1991 hospitals that participated in the American Heart Association's Get With the Guidelines-Stroke Registry from 2008-2013 were identified by medical history or International Classification of Diseases, Ninth Revision, codes. Acute stroke reperfusion therapy was defined as intravenous tissue plasminogen activator, catheter-based thrombolysis, or thrombectomy or any combination thereof. A sensitivity analysis was done on patients who received intravenous tissue plasminogen activator monotherapy only. Chi-square tests were used for categoric variables, and Wilcoxon Rank-Sum was used for continuous variables. Conditional logistic regression was used to assess the association of pregnancy with short-term outcomes.Baseline characteristics of the pregnant or postpartum vs nonpregnant women with ischemic stroke revealed a younger group who, despite greater stroke severity, were less likely to have a history of hypertension or to arrive via emergency medical services. There were similar rates of acute stroke reperfusion therapy in the pregnant or postpartum vs nonpregnant women (11.8% vs 10.5%; P = .42). Pregnant or postpartum women were less likely to receive intravenous tissue plasminogen activator monotherapy (4.4% vs 7.9%; P = .03), primarily because of pregnancy and recent surgery. There was a trend toward increased symptomatic intracranial hemorrhage in the pregnant or postpartum patients who were treated with tissue plasminogen activator, yet no cases of major systemic bleeding or in-hospital death occurred, and there were similar rates of discharge to home. Data on the timing of pregnancy, which were available in 145 of 338 cases, showed that 44.8% of pregnancy-related strokes were antepartum, that 2.8% occurred during delivery, and that 52.4% were during the postpartum period.Using data from the Get With the Guidelines-Stroke Registry to assemble the largest cohort of pregnant or postpartum ischemic stroke patients who had been treated with reperfusion therapy, we observed that pregnant or postpartum women had similarly favorable short-term outcomes and equal rates of total reperfusion therapy to nonpregnant women, despite lower rates of intravenous tissue plasminogen activator use. Future studies should identify the characteristics of pregnant and postpartum ischemic stroke patients who are most likely to safely benefit from reperfusion therapy.

  View details for DOI 10.1016/j.ajog.2015.12.016

  View details for PubMedID 26709084

• Variations in the Use of Perioperative Multimodal Analgesic Therapy. Anesthesiology Ladha, K. S., Patorno, E., Huybrechts, K. F., Liu, J., Rathmell, J. P., Bateman, B. T. 2016; 124 (4): 837-45

  Abstract

  Practice guidelines for perioperative pain management recommend that multimodal analgesic therapy should be used for all postsurgical patients. However, the proportion of patients who actually receive this evidence-based approach is unknown. The objective of this study was to describe hospital-level patterns in the utilization of perioperative multimodal analgesia.Data for the study were obtained from the Premier Research Database. Patients undergoing below-knee amputation, open lobectomy, total knee arthroplasty, and open colectomy between 2007 and 2014 were included in the analysis. Patients were considered to have multimodal therapy if they received one or more nonopioid analgesic therapies. Mixed-effects logistic regression models were used to estimate the hospital-specific frequency of multimodal therapy use while adjusting for the case mix of patients and hospital characteristics and accounting for random variation.The cohort consisted of 799,449 patients who underwent a procedure at 1 of 315 hospitals. The mean probability of receiving multimodal therapy was 90.4%, with 95% of the hospitals having a predicted probability between 42.6 and 99.2%. A secondary analysis examined whether patients received two or more nonopioid analgesics, which gave an average predicted probability of 54.2%, with 95% of the hospitals having a predicted probability between 9.3 and 93.2%.In this large nationwide sample of surgical admissions in the United States, the authors observed tremendous variation in the utilization of multimodal therapy not accounted for by patient or hospital characteristics. Efforts should be made to identify why there are variations in the use of multimodal analgesic therapy and to promote its adoption in appropriate patients.

  View details for DOI 10.1097/ALN.0000000000001034

  View details for PubMedID 26835644

  View details for PubMedCentralID PMC4792695

• Postpartum Hemorrhage Preparedness Elements Vary Among Hospitals in New Jersey and Georgia. Journal of obstetric, gynecologic, and neonatal nursing : JOGNN Bingham, D., Scheich, B., Byfield, R., Wilson, B., Bateman, B. T. 2016; 45 (2): 227-38

  Abstract

  To identify the presence or absence of 38 postpartum hemorrhage preparedness elements in hospitals in New Jersey and Georgia as a component of the Postpartum Hemorrhage Project of the Association of Women's Health, Obstetric and Neonatal Nurses.Quality improvement baseline assessment survey.Hospitals (N = 95) in New Jersey and Georgia.Key informants were clinicians who were members of their hospitals' obstetric teams and were recognized as knowledgeable about their hospitals' postpartum hemorrhage policies.An electronic survey was sent by e-mail to each identified hospital's key informant.The mean number of elements present was 23.1 (SD = 5.2; range = 12-34). Volume of births, students, magnet status, and other hospital characteristics did not predict preparedness. None of the hospitals had all of the 38 preparedness elements available. Less than 50% of the hospitals had massive hemorrhage protocols, performed risk assessments and drills, or measured blood loss. For every 10% increase in the total percentage of African American women who gave birth, there was a decrease of one preparedness element.Objective measures of preparedness are needed, because perceptions of preparedness were inconsistent with the number of preparedness elements reported.

  View details for DOI 10.1016/j.jogn.2015.12.003

  View details for PubMedID 26852254

• Suppression of Substance Abuse Claims in Medicaid Data and Rates of Diagnoses for Non-Substance Abuse Conditions. JAMA Rough, K., Bateman, B. T., Patorno, E., Desai, R. J., Park, Y., Hernandez-Diaz, S., Huybrechts, K. F. 2016; 315 (11): 1164-6

  View details for DOI 10.1001/jama.2015.18417

  View details for PubMedID 26978213

  View details for PubMedCentralID PMC4794113

• Opioid Prescribing After Surgical Extraction of Teeth in Medicaid Patients, 2000-2010. JAMA Baker, J. A., Avorn, J., Levin, R., Bateman, B. T. 2016; 315 (15): 1653-4

  View details for DOI 10.1001/jama.2015.19058

  View details for PubMedID 26978601

  View details for PubMedCentralID PMC5297370

• Persistent opioid use following cesarean delivery: patterns and predictors among opioid-naïve women. American journal of obstetrics and gynecology Bateman, B. T., Franklin, J. M., Bykov, K., Avorn, J., Shrank, W. H., Brennan, T. A., Landon, J. E., Rathmell, J. P., Huybrechts, K. F., Fischer, M. A., Choudhry, N. K. 2016; 215 (3): 353.e1-353.e18

  Abstract

  The incidence of opioid-related death in women has increased 5-fold over the past decade. For many women, their initial opioid exposure will occur in the setting of routine medical care. Approximately 1 in 3 deliveries in the United States is by cesarean, and opioids are commonly prescribed for postsurgical pain management.The objective of this study was to determine the risk that opioid-naïve women prescribed opioids after cesarean delivery will subsequently become consistent prescription opioid users in the year following delivery and to identify predictors for this behavior.We identified women in a database of commercial insurance beneficiaries who underwent cesarean delivery and who were opioid naïve in the year prior to delivery. To identify persistent users of opioids, we used trajectory models, which group together patients with similar patterns of medication filling during follow-up, based on patterns of opioid dispensing in the year following cesarean delivery. We then constructed a multivariable logistic regression model to identify independent risk factors for membership in the persistent user group.A total of 285 of 80,127 (0.36%, 95% confidence interval, 0.32-0.40), opioid-naïve women became persistent opioid users (identified using trajectory models based on monthly patterns of opioid dispensing) following cesarean delivery. Demographics and baseline comorbidity predicted such use with moderate discrimination (c statistic = 0.73). Significant predictors included a history of cocaine abuse (risk, 7.41%; adjusted odds ratio, 6.11, 95% confidence interval, 1.03-36.31) and other illicit substance abuse (2.36%; adjusted odds ratio, 2.78, 95% confidence interval, 1.12-6.91), tobacco use (1.45%; adjusted odds ratio, 3.04, 95% confidence interval, 2.03-4.55), back pain (0.69%; adjusted odds ratio, 1.74, 95% confidence interval, 1.33-2.29), migraines (0.91%; adjusted odds ratio, 2.14, 95% confidence interval, 1.58-2.90), antidepressant use (1.34%; adjusted odds ratio, 3.19, 95% confidence interval, 2.41-4.23), and benzodiazepine use (1.99%; adjusted odds ratio, 3.72, 95% confidence interval, 2.64-5.26) in the year prior to the cesarean delivery.A very small proportion of opioid-naïve women (approximately 1 in 300) become persistent prescription opioid users following cesarean delivery. Preexisting psychiatric comorbidity, certain pain conditions, and substance use/abuse conditions identifiable at the time of initial opioid prescribing were predictors of persistent use.

  View details for DOI 10.1016/j.ajog.2016.03.016

  View details for PubMedID 26996986

  View details for PubMedCentralID PMC5003640

• Body Mass Index, Smoking and Hypertensive Disorders during Pregnancy: A Population Based Case-Control Study. PloS one Gudnadóttir, T. A., Bateman, B. T., Hernádez-Díaz, S., Luque-Fernandez, M. A., Valdimarsdottir, U., Zoega, H. 2016; 11 (3): e0152187

  Abstract

  While obesity is an indicated risk factor for hypertensive disorders of pregnancy, smoking during pregnancy has been shown to be inversely associated with the development of preeclampsia and gestational hypertension. The purpose of this study was to investigate the combined effects of high body mass index and smoking on hypertensive disorders during pregnancy. This was a case-control study based on national registers, nested within all pregnancies in Iceland 1989-2004, resulting in birth at the Landspitali University Hospital. Cases (n = 500) were matched 1:2 with women without a hypertensive diagnosis who gave birth in the same year. Body mass index (kg/m2) was based on height and weight at 10-15 weeks of pregnancy. We used logistic regression models to calculate odds ratios and corresponding 95% confidence intervals as measures of association, adjusting for potential confounders and tested for additive and multiplicative interactions of body mass index and smoking. Women's body mass index during early pregnancy was positively associated with each hypertensive outcome. Compared with normal weight women, the multivariable adjusted odds ratio for any hypertensive disorder was 1.8 (95% confidence interval, 1.3-2.3) for overweight women and 3.1 (95% confidence interval, 2.2-4.3) for obese women. The odds ratio for any hypertensive disorder with obesity was 3.9 (95% confidence interval 1.8-8.6) among smokers and 3.0 (95% confidence interval 2.1-4.3) among non-smokers. The effect estimates for hypertensive disorders with high body mass index appeared more pronounced among smokers than non-smokers, although the observed difference was not statistically significant. Our findings may help elucidate the complicated interplay of these lifestyle-related factors with the hypertensive disorders during pregnancy.

  View details for DOI 10.1371/journal.pone.0152187

  View details for PubMedID 27010734

  View details for PubMedCentralID PMC4807030

• Limited Hospital Variation in the Use and Yield of CT for Pulmonary Embolism in Patients Undergoing Total Hip or Total Knee Replacement Surgery. Radiology Kumamaru, K. K., Kumamaru, H., Bateman, B. T., Gronsbell, J., Cai, T., Liu, J., Higgins, L. D., Aoki, S., Ohtomo, K., Rybicki, F. J., Patorno, E. 2016; 281 (3): 826-834

  Abstract

  Purpose To evaluate the variation among U.S. hospitals in overall use and yield of in-hospital computed tomographic (CT) pulmonary angiography (PA) in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery. Materials and Methods Patients in the Premier Research Database who underwent elective TKR or THR between 2007 and 2011 were enrolled in this HIPAA-compliant, institutional review board-approved retrospective observational study. The informed consent requirement was waived. Hospitals were categorized into low, medium, and high tertiles of CT PA use to compare baseline patient- and hospital-level characteristics and pulmonary embolism (PE) positivity rates. To further investigate between-hospital variation in CT PA use, a hierarchical logistic regression model that included hospital-specific random effects and fixed patient- and hospital-level effects was used. The intraclass correlation coefficient (ICC) was used to measure the amount of variability in CT PA use attributable to between-hospital variation. Results The cohort included 205 198 patients discharged from 178 hospitals (median of 734.5 patients discharged per hospital; interquartile range, 316-1461 patients) with 3647 CT PA studies (1.8%). The crude frequency of CT PA scans among the hospitals ranged from 0% to 6.2% (median, 1.6%); more than 90% of the hospitals performed CT PA in less than 3% of their patients. The mean hospital-level PE positivity rate was 12.3% (median, 9.1%); there was no significant difference in PE positivity rate across low through high CT PA use tertiles (11.3%, 11.9%, 12.9%, P = .37). After adjustment for hospital- and patient-level factors, the remaining amount of interhospital variation was relatively low (ICC, 9.0%). Conclusion Limited interhospital variation in use and yield of in-hospital CT PA was observed among patients undergoing TKR or THR in the United States. © RSNA, 2016 Online supplemental material is available for this article.

  View details for DOI 10.1148/radiol.2016152765

  View details for PubMedID 27228331

• Variation in Use of Blood Transfusion in Primary Total Hip and Knee Arthroplasties. The Journal of arthroplasty Menendez, M. E., Lu, N., Huybrechts, K. F., Ring, D., Barnes, C. L., Ladha, K., Bateman, B. T. 2016; 31 (12): 2757-2763.e2

  Abstract

  There is growing clinical and policy emphasis on minimizing transfusion use in elective joint arthroplasty, but little is known about the degree to which transfusion rates vary across US hospitals. This study aimed to assess hospital-level variation in use of allogeneic blood transfusion in patients undergoing elective joint arthroplasty and to characterize the extent to which variability is attributable to differences in patient and hospital characteristics.The study population included 228,316 patients undergoing total knee arthroplasty (TKA) at 922 hospitals and 88,081 patients undergoing total hip arthroplasty (THA) at 606 hospitals from January 1, 2009 to December 31, 2011 in the Nationwide Inpatient Sample database, a 20% stratified sample of US community hospitals.The median hospital transfusion rates were 11.0% (interquartile range, 3.5%-18.5%) in TKA and 15.9% (interquartile range, 5.4%-26.2%) in THA. After fully adjusting for patient- and hospital-related factors using mixed-effects logistic regression models, the average predicted probability of blood transfusion use in TKA was 6.3%, with 95% of the hospitals having a predicted probability between 0.37% and 55%. For THA, the average predicted probability of blood transfusion use was 9.5%, with 95% of the hospitals having a predicted probability between 0.57% and 66%. Hospital transfusion rates were inversely associated with hospital procedure volume and directly associated with length of stay.The use of blood transfusion in elective joint arthroplasty varied widely across US hospitals, largely independent of patient case-mix and hospital characteristics.

  View details for DOI 10.1016/j.arth.2016.05.022

  View details for PubMedID 27325367

• The Validity of Discharge Billing Codes Reflecting Severe Maternal Morbidity. Anesthesia and analgesia Sigakis, M. J., Leffert, L. R., Mirzakhani, H., Sharawi, N., Rajala, B., Callaghan, W. M., Kuklina, E. V., Creanga, A. A., Mhyre, J. M., Bateman, B. T. 2016; 123 (3): 731-8

  Abstract

  Discharge diagnoses are used to track national trends and patterns of maternal morbidity. There are few data regarding the validity of the International Classification of Diseases (ICD) codes used for this purpose. The goal of our study was to try to better understand the validity of administrative data being used to monitor and assess trends in morbidity.Hospital stay billing records were queried to identify all delivery admissions at the Massachusetts General Hospital for the time period 2001 to 2011 and the University of Michigan Health System for the time period 2005 to 2011. From this, we identified patients with ICD-9-Clinical Modification (CM) diagnosis and procedure codes indicative of severe maternal morbidity. Each patient was classified with 1 of 18 different medical/obstetric categories (conditions or procedures) based on the ICD-9-CM code that was recorded. Within each category, 20 patients from each institution were selected at random, and the corresponding medical charts were reviewed to determine whether the ICD-9-CM code was assigned correctly. The percentage of correct codes for each of 18 preselected clinical categories was calculated yielding a positive predictive value (PPV) and 99% confidence interval (CI).The overall number of correctly assigned ICD-9-CM codes, or PPV, was 218 of 255 (86%; CI, 79%-90%) and 154 of 188 (82%; CI, 74%-88%) at Massachusetts General Hospital and University of Michigan Health System, respectively (combined PPV, 372/443 [84%; CI, 79-88%]). Codes within 4 categories (Hysterectomy, Pulmonary edema, Disorders of fluid, electrolyte and acid-base balance, and Sepsis) had a 99% lower confidence limit ≥75%. Codes within 8 additional categories demonstrated a 99% lower confidence limit between 74% and 50% (Acute respiratory distress, Ventilation, Other complications of obstetric surgery, Disorders of coagulation, Cardiomonitoring, Acute renal failure, Thromboembolism, and Shock). Codes within 6 clinical categories demonstrated a 99% lower confidence limit <50% (Puerperal cerebrovascular disorders, Conversion of cardiac rhythm, Acute heart failure [includes arrest and fibrillation], Eclampsia, Neurotrauma, and Severe anesthesia complications).ICD-9-CM codes capturing severe maternal morbidity during delivery hospitalization demonstrate a range of PPVs. The PPV was high when objective supportive evidence, such as laboratory values or procedure documentation supported the ICD-9-CM code. The PPV was low when greater judgment, interpretation, and synthesis of the clinical data (signs and symptoms) was required to support a code, such as with the category Severe anesthesia complications. As a result, these codes should be used for administrative research with more caution compared with codes primarily defined by objective data.

  View details for DOI 10.1213/ANE.0000000000001436

  View details for PubMedID 27387839

  View details for PubMedCentralID PMC7481827

• In Reply. Anesthesiology Ladha, K. S., Bateman, B. T. 2016; 125 (2): 440-1

  View details for DOI 10.1097/ALN.0000000000001192

  View details for PubMedID 27433769

  View details for PubMedCentralID PMC5373081

• Initiation patterns of statin therapy among adult patients undergoing intermediate to high-risk non-cardiac surgery. Pharmacoepidemiology and drug safety Patorno, E., Wang, S. V., Schneeweiss, S., Liu, J., Bateman, B. T. 2016; 25 (1): 64-72

  Abstract

  A growing body of literature has been produced on the potential role of statins in reducing perioperative cardiac events in patients undergoing non-cardiac surgery. However, evidence remains inconsistent, and little is known about the patterns of perioperative statin use in routine care.The objective of this study was to examine patterns of perioperative statin initiation among adults undergoing non-cardiac elective surgery in the USA.Using data from a large US healthcare insurer, we identified patients aged ≥18 years who underwent moderate-risk to high-risk non-cardiac elective surgery between 2003 and 2012 and initiated statins within 30 days before surgery. We evaluated temporal trends of statin initiation and patient characteristics. In a matched analysis, we assessed the effect of temporal proximity to surgery on the likelihood of statin initiation.Of 460,154 patients undergoing surgery, 5628 (12 per 1000 patients) initiated a statin within 30 days before surgery. Statin initiation increased from 8 per 1000 patients in 2003 to 15 in 2012 (p = 0.0022). The increase was more pronounced among patients undergoing vascular surgery (149 initiators per 1000 patients by the end of 2012) and with Revised Cardiac Risk Index (RCRI) score ≥2 (72 per 1000 patients). Proximity to surgery, in particular vascular surgery, was predictive of statin initiation.Despite the lack of robust evidence, perioperative statin initiation progressively increased from 2003 to 2012, particularly among patients undergoing major vascular surgery and with higher RCRI score. These trends were largely attributable to the initiation of statins in anticipation of non-cardiac surgery rather than routine dyslipidemia treatment.

  View details for DOI 10.1002/pds.3892

  View details for PubMedID 26494361

  View details for PubMedCentralID PMC4843110

• Population-based risk for peripartum hysterectomy during low- and moderate-risk delivery hospitalizations. American journal of obstetrics and gynecology Friedman, A. M., Wright, J. D., Ananth, C. V., Siddiq, Z., D'Alton, M. E., Bateman, B. T. 2016; 215 (5): 640.e1-640.e8

  Abstract

  Postpartum hysterectomy is an obstetric procedure that carries significant maternal risk that is not well characterized by hospital volume.The objective of this study was to determine risk for peripartum hysterectomy for women at low and moderate risk for the procedure.This population-based study used data from the Nationwide Inpatient Sample to characterize risk for peripartum hysterectomy. Women with a diagnosis of placenta accreta or prior cesarean and placenta previa were excluded. Obstetrical risk factors along with demographic and hospital factors were evaluated. Multivariable mixed-effects log-linear regression models were developed to determine adjusted risk. Based on these models receiver operating characteristic curves were plotted, and the area under the curve was determined to assess discrimination.Peripartum hysterectomy occurred in 1 in 1913 deliveries. Risk factors associated with significant risk for hysterectomy included mode of delivery, stillbirth, placental abruption, fibroids, and antepartum hemorrhage. These factors retained their significance in adjusted models: the risk ratio for stillbirth was 3.44 (95% confidence interval, 2.94-4.02), abruption 2.98 (95% confidence interval, 2.52-3.20), fibroids 3.63 (95% confidence interval, 3.22-4.08), and antepartum hemorrhage 7.15 (95% confidence interval, 6.16-8.32). The area under the curve for the model was 0.833.Peripartum hysterectomy is a relatively common event that hospitals providing routine obstetric care should be prepared to manage. That specific risk factors are highly associated with risk for hysterectomy supports routine use of hemorrhage risk-assessment tools. However, given that a significant proportion of hysterectomies will be unpredictable, the availability of rapid transfusion protocols may be necessary for hospitals to safely manage these cases.

  View details for DOI 10.1016/j.ajog.2016.06.032

  View details for PubMedID 27349293

  View details for PubMedCentralID PMC5086282

• Oral intake during labor: an alternative interpretation of recent data. American journal of obstetrics and gynecology McQuaid-Hanson, E., Leffert, L. R., Bateman, B. T. 2016; 215 (5): 672

  View details for DOI 10.1016/j.ajog.2016.06.030

  View details for PubMedID 27349292

• Late Pregnancy β Blocker Exposure and Risks of Neonatal Hypoglycemia and Bradycardia. Pediatrics Bateman, B. T., Patorno, E., Desai, R. J., Seely, E. W., Mogun, H., Maeda, A., Fischer, M. A., Hernandez-Diaz, S., Huybrechts, K. F. 2016; 138 (3)

  Abstract

  β blockers are widely used in the treatment of hypertensive disorders during pregnancy. These medications cross the placenta and may cause physiologic changes in neonates exposed in utero. We sought to define the risks of neonatal hypoglycemia and bradycardia associated with maternal exposure to β blockers at the time of delivery in a large, nationwide cohort of Medicaid beneficiaries.We used a cohort of 2 292 116 completed pregnancies linked to liveborn infants of Medicaid-enrolled women from 2003 to 2007. We examined the risks of neonatal hypoglycemia and neonatal bradycardia associated with maternal exposure to β blockers at the time of delivery. Propensity score matching was used to control for potential confounders including maternal demographics, obstetric and medical conditions, and exposure to other medications.There were 10 585 (0.5%) pregnancies exposed to β blockers at the time of delivery. The risk of neonatal hypoglycemia was 4.3% in the β blocker-exposed neonates versus 1.2% in the unexposed; the risk of neonatal bradycardia was 1.6% in the exposed versus 0.5% in the unexposed. After controlling for confounders, risk remained elevated for both neonatal hypoglycemia and bradycardia among exposed pregnancies versus unexposed (adjusted odds ratio, 1.68, 95% confidence interval, 1.50-1.89 and adjusted odds ratio, 1.29, 95% confidence interval, 1.07-1.55, respectively).Our findings suggest that neonates born to mothers exposed to β blockers in late pregnancy, including labetalol, are at elevated risk for neonatal hypoglycemia and bradycardia.

  View details for DOI 10.1542/peds.2016-0731

  View details for PubMedID 27577580

  View details for PubMedCentralID PMC5005024

• In Response. Anesthesia and analgesia Bateman, B. T., Butwick, A. J., Huybrechts, K. F. 2015; 121 (5): 1397-1398

  View details for DOI 10.1213/ANE.0000000000000847

  View details for PubMedID 26484466

• COMPARATIVE SAFETY OF TYPICAL AND ATYPICAL ANTIPSYCHOTICS AFTER CARDIAC SURGERY Kim, D. H., Patorno, E., Park, Y., Huybrechts, K. F., Levin, R., Bateman, B. OXFORD UNIV PRESS INC. 2015: 82

  View details for Web of Science ID 000374222700309

• Patterns and Secular Trends in Use of Immunosuppressive Agents during Pregnancy in Women with Rheumatologic Conditions Desai, R. J., Huybrechts, K., Bateman, B., Hernandez-Diaz, S., Mogun, H., Gopalakrishnan, C., Patorno, E., Kim, S. C. WILEY-BLACKWELL. 2015

  View details for Web of Science ID 000370860204076

• Morbidity associated with cesarean delivery in the United States: is placenta accreta an increasingly important contributor? AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Creanga, A. A., Bateman, B. T., Butwick, A. J., Raleigh, L., Maeda, A., Kuklina, E., Callaghan, W. M. 2015; 213 (3)

  Abstract

  To examine cesarean morbidity and its predictors in the United States.We used 2000-2011 Nationwide Inpatient Sample data to identify cesarean deliveries and records with 12 potential cesarean complications, including placenta accreta. We estimated cesarean morbidity rates and rate changes during 2000-2011, and fitted Poisson regression models to assess the relative incidence of morbidity among repeat versus primary cesareans and explore its predictors.During 2000-2011, 76 in 1,000 cesareans (97 in 1,000 primary and 48 in 1,000 repeat cesareans) were accompanied by ≥1 of 12 complications. The unadjusted composite cesarean morbidity rate increased by 3.6% only among women with a primary cesarean (p<0.001), while the unadjusted rate of placenta accreta increased by 30.8% only among women with a repeat cesarean (p=0.025). The adjusted rate of overall composite cesarean morbidity decreased by 1% annually during 2000-2011 (p<0.001). Compared to women with a primary cesarean, those who underwent a repeat cesarean were half as likely (incidence rate ratio=0.50; 95%CI 0.49-0.50) to develop a complication, but 2.13 (95%CI 1.98-2.29) times more likely to have a placenta accreta diagnosis. Both cesarean morbidity and placenta accreta were positively associated with: age >30 years; non-Hispanic black race-ethnicity; presence of a chronic medical condition; and delivery in urban, teaching, or larger hospitals.Overall, cesarean morbidity declined modestly during 2000-2011, but placenta accreta became an increasingly important contributor to repeat cesarean morbidity. Clinicians should maintain a high index of suspicion for abnormal placentation and make adequate preparations for patients who need cesarean deliveries.

  View details for DOI 10.1016/j.ajog.2015.05.002

  View details for Web of Science ID 000360551700027

  View details for PubMedID 25957019

• Perioperative Beta-Blocker (BB) Therapy in Non-cardiac Surgery and the Risk of In-hospital Myocardial Infarction (MI), Stroke, and Mortality Patorno, E., Glynn, R., Schneeweiss, S., Liu, J., Bateman, B. WILEY. 2015: 4-5

  View details for Web of Science ID 000369980200008

• Validation of the Overutilization Monitoring System to Detect Opioid Misuse Using Claims Data Rough, K., Huybrechts, K. F., Hernandez-Diaz, S., Desai, R. J., Patorno, E., Bateman, B. T. WILEY. 2015: 26

  View details for Web of Science ID 000369980200045

• Patterns and Predictors of Persistent Opioid Use Following Hip or Knee Arthroplasty Kim, S. C., Franklin, J. M., Bykov, K., Lii, H., Fischer, M. A., Choudhry, N. K., Bateman, B. T. WILEY-BLACKWELL. 2015: 85

  View details for Web of Science ID 000369980200147

• Utilization of Antipsychotics and Stimulants during Pregnancy among Publicly Insured Women in the United States Park, Y., Hernandez-Diaz, S., Bateman, B. T., Patorno, E., Desai, R. J., Mogun, H., Huybrechts, K. F. WILEY. 2015: 205-206

  View details for Web of Science ID 000369980200357

• Attention Deficit Hyperactivity Medications during Pregnancy and the Risk of Congenital Cardiac Malformations: A Cohort Study Bateman, B. T., Huybrechts, K. F., Patorno, E., Desai, R., Hernandez-Diaz, S. WILEY. 2015: 206-207

  View details for Web of Science ID 000369980200359

• The Safety of Mood Stabilizers in Pregnant Women with Regard to the Risk of Congenital Cardiac Malformations Patorno, E., Huybrechts, K., Bateman, B., Desai, R., Mogun, H., Hernandez-Diaz, S. WILEY. 2015: 207-208

  View details for Web of Science ID 000369980200360

• Antipsychotic Medication Use during Pregnancy and Risk of Congenital Cardiac Malformations Huybrechts, K. F., Bateman, B. T., Patorno, E., Desai, R., Mogun, H., Hernandez-Diaz, S. WILEY. 2015: 206

  View details for Web of Science ID 000369980200358

• Confounding Control Using Propensity Scores When the Exposure Is Infrequent: Making the Case for a Fine Stratification Approach Desai, R. J., Rothman, K. J., Bateman, B. T., Hernandez-Diaz, S., Huybrechts, K. F. WILEY. 2015: 217

  View details for Web of Science ID 000369980200376

• Labor Induction and Offspring Risk of Autism Spectrum Disorder Oberg, A. S., D'Onofrio, B. M., Rickert, M. E., Hernandez-Diaz, S., Bateman, B. T. WILEY. 2015: 237

  View details for Web of Science ID 000369980200410

• Exposure to Prescription Opioid Analgesics In-Utero and the Risk of Neonatal Abstinence Syndrome: A Population-based Cohort Study Desai, R. J., Huybrechts, K. F., Hernandez-Diaz, S., Patorno, E., Bateman, B. T. WILEY. 2015: 263

  View details for Web of Science ID 000369980200452

• Comparative Safety of Typical and Atypical Antipsychotics after Cardiac Surgery Kim, D., Patorno, E., Park, Y., Huybrechts, K., Levin, R., Bateman, B. WILEY. 2015: 332

  View details for Web of Science ID 000369980200572

• Late Pregnancy Exposure to Beta Blockers and the Risks of Neonatal Hypoglycemia and Bradycardia Bateman, B. T., Huybrechts, K. F., Desai, R., Patorno, E., Hernandez-Diaz, S. WILEY. 2015: 401

  View details for Web of Science ID 000369980200693

• ACE Inhibitors During the First Trimester of Pregnancy and the Risk of Congenital Malformations: A Cohort Study Bateman, B. T., Hernandez-Diaz, S., Patorno, E., Desai, R., Huybrechts, K. F. WILEY. 2015: 400-401

  View details for Web of Science ID 000369980200692

• Second-line uterotonics and the risk of hemorrhage-related morbidity. American journal of obstetrics and gynecology Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5): 642 e1-7

  Abstract

  Uterine atony is a leading cause of postpartum hemorrhage (PPH). Although most cases of PPH respond to first line therapy with uterine massage and oxytocin administration, second line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at Cesarean delivery (CD).We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent CD and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cells (RBC) transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs. carboprost. Propensity-score matching was used to account for potential confounders.The study cohort comprised 1,335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (RR = 1.7; 95% CI = 1.2 - 2.6).In this propensity-score matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during CD compared to carboprost. Based on these results, methylergonovine may be a more effective second line uterotonic.

  View details for DOI 10.1016/j.ajog.2015.01.008

  View details for PubMedID 25582104

• Second-line uterotonics and the risk of hemorrhage-related morbidity AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Butwick, A. J., Carvalho, B., Blumenfeld, Y. J., El-Sayed, Y. Y., Nelson, L. M., Bateman, B. T. 2015; 212 (5)

  Abstract

  Uterine atony is a leading cause of postpartum hemorrhage (PPH). Although most cases of PPH respond to first line therapy with uterine massage and oxytocin administration, second line uterotonics including methylergonovine and carboprost are integral for the management of refractory uterine atony. Despite their ubiquitous use, it is uncertain whether the risk of hemorrhage-related morbidity differs in women exposed to methylergonovine or carboprost at Cesarean delivery (CD).We performed a secondary analysis using the Maternal-Fetal Medicine Units Network Cesarean Registry. We identified women who underwent CD and received either methylergonovine or carboprost for refractory uterine atony. The primary outcome was hemorrhage-related morbidity defined as intraoperative or postoperative red blood cells (RBC) transfusion or the need for additional surgical interventions including uterine artery ligation, hypogastric artery ligation, or peripartum hysterectomy for atony. We compared the risk of hemorrhage-related morbidity in those exposed to methylergonovine vs. carboprost. Propensity-score matching was used to account for potential confounders.The study cohort comprised 1,335 women; 870 (65.2%) women received methylergonovine and 465 (34.8%) women received carboprost. After accounting for potential confounders, the risk of hemorrhage-related morbidity was higher in the carboprost group than the methylergonovine group (RR = 1.7; 95% CI = 1.2 - 2.6).In this propensity-score matched analysis, methylergonovine was associated with reduced risk of hemorrhage-related morbidity during CD compared to carboprost. Based on these results, methylergonovine may be a more effective second line uterotonic.

  View details for DOI 10.1016/j.ajog.2015.01.008

  View details for Web of Science ID 000353598500025

  View details for PubMedID 25582104

• Risk of Preeclampsia in Patients With Genetic Predisposition To Common Medical Conditions Gray, K. J., Kovacheva, V. P., Mirzakhani, H., Bjonnes, A., Keating, B., Bateman, B. T., Saxena, R. SAGE PUBLICATIONS INC. 2015: 200A

  View details for Web of Science ID 000351407202053

• Patient Characteristics and Outcomes After Hemorrhagic Stroke in Pregnancy. Circulation. Cardiovascular quality and outcomes Leffert, L. R., Clancy, C. R., Bateman, B. T., Cox, M., Schulte, P. J., Smith, E. E., Fonarow, G. C., Schwamm, L. H., Kuklina, E. V., George, M. G. 2015; 8 (6 Suppl 3): S170-8

  Abstract

  Hospitalizations for pregnancy-related stroke are rare but increasing. Hemorrhagic stroke (HS), ie, subarachnoid hemorrhage and intracerebral hemorrhage, is more common than ischemic stroke in pregnant versus nonpregnant women, reflecting different phenotypes or risk factors. We compared stroke risk factors and outcomes in pregnant versus nonpregnant HS in the Get With The Guidelines-Stroke Registry.Using medical history or International Classification of Diseases-Ninth Revision codes, we identified 330 pregnant and 10 562 nonpregnant female patients aged 18 to 44 years with HS in Get With The Guidelines-Stroke (2008-2014). Differences in patient and care characteristics were compared by χ(2) or Fisher exact test (categorical variables) or Wilcoxon rank-sum (continuous variables) tests. Conditional logistic regression assessed the association of pregnancy with outcomes conditional on categorical age and further adjusted for patient and hospital characteristics. Pregnant versus nonpregnant HS patients were younger with fewer pre-existing stroke risk factors and medications. Pregnant versus nonpregnant subarachnoid hemorrhage patients were less impaired at arrival, and less than half met blood pressure criteria for severe preeclampsia. In-hospital mortality was lower in pregnant versus nonpregnant HS patients: adjusted odds ratios (95% CI) for subarachnoid hemorrhage 0.17 (0.06-0.45) and intracerebral hemorrhage 0.57 (0.34-0.94). Pregnant subarachnoid hemorrhage patients also had a higher likelihood of home discharge (2.60 [1.67-4.06]) and independent ambulation at discharge (2.40 [1.56-3.70]).Pregnant HS patients are younger and have fewer risk factors than their nonpregnant counterparts, and risk-adjusted in-hospital mortality is lower. Our findings suggest possible differences in underlying disease pathophysiology and challenges to identifying at-risk patients.

  View details for DOI 10.1161/CIRCOUTCOMES.115.002242

  View details for PubMedID 26515206

• Chronic hypertension in pregnancy and the risk of congenital malformations: a cohort study. American journal of obstetrics and gynecology Bateman, B. T., Huybrechts, K. F., Fischer, M. A., Seely, E. W., Ecker, J. L., Oberg, A. S., Franklin, J. M., Mogun, H., Hernandez-Diaz, S. 2015; 212 (3): 337.e1-14

  Abstract

  Chronic hypertension is a common medical condition in pregnancy. The purpose of the study was to examine the association between maternal chronic hypertension and the risk of congenital malformations in the offspring.We defined a cohort of 878,126 completed pregnancies linked to infant medical records using the Medicaid Analytic Extract. The risk of congenital malformations was compared between normotensive controls and those with treated and untreated chronic hypertension. Confounding was addressed using propensity score matching.After matching, compared with normotensive controls, pregnancies complicated by treated chronic hypertension were at increased risk of congenital malformations (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.2-1.5), as were pregnancies with untreated chronic hypertension (OR 1.2; 95% CI, 1.1-1.3). In our analysis of organ-specific malformations, both treated and untreated chronic hypertension was associated with a significant increase in the risk of cardiac malformations (OR, 1.6; 95% CI, 1.4-1.9 and OR, 1.5; 95% CI, 1.3-1.7, respectively). These associations persisted across a range of sensitivity analyses.There is a similar increase in the risk of congenital malformations (particularly cardiac malformations) associated with treated and untreated chronic hypertension that is independent of measured confounders. Studies evaluating the teratogenic potential of antihypertensive medications must control for confounding by indication. Fetuses and neonates of mothers with chronic hypertension should be carefully evaluated for potential malformations, particularly cardiac defects.

  View details for DOI 10.1016/j.ajog.2014.09.031

  View details for PubMedID 25265405

  View details for PubMedCentralID PMC4346443

• Hypertensive disorders and pregnancy-related stroke: frequency, trends, risk factors, and outcomes. Obstetrics and gynecology Leffert, L. R., Clancy, C. R., Bateman, B. T., Bryant, A. S., Kuklina, E. V. 2015; 125 (1): 124-131

  Abstract

  To evaluate trends and associations of hypertensive disorders of pregnancy with stroke risk and test the hypothesis that hypertensive disorders of pregnancy-associated stroke results in higher rates of stroke-related complications than pregnancy-associated stroke without hypertensive disorders.A cross-sectional study was performed using 81,983,216 pregnancy hospitalizations from the 1994-2011 Nationwide Inpatient Sample. Rates of stroke hospitalizations with and without these hypertensive disorders were reported per 10,000 pregnancy hospitalizations. Using logistic regression, adjusted odds ratios (OR) with 95% confidence intervals were obtained.Between 1994-1995 and 2010-2011, the nationwide rate of stroke with hypertensive disorders of pregnancy increased from 0.8 to 1.6 per 10,000 pregnancy hospitalizations (103%), whereas the rate without these disorders increased from 2.2 to 3.2 per 10,000 pregnancy hospitalizations (47%). Women with hypertensive disorders of pregnancy were 5.2 times more likely to have a stroke than those without. Having traditional stroke risk factors (eg, congenital heart disease, atrial fibrillation, sickle cell anemia, congenital coagulation defects) substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations: from adjusted OR 2.68 for congenital coagulation defects to adjusted OR 13.1 for congenital heart disease. Stroke-related complications were increased in stroke with hypertensive disorders of pregnancy compared with without (from adjusted OR 1.23 for nonroutine discharge to adjusted OR 1.93 for mechanical ventilation).Having traditional stroke risk factors substantially increased the stroke risk among hypertensive disorders of pregnancy hospitalizations. Stroke with hypertensive disorders in pregnancy had two distinctive characteristics: a greater increase in frequency since the mid-1990s and significantly higher stroke-related complication rates.III.

  View details for DOI 10.1097/AOG.0000000000000590

  View details for PubMedID 25560114

  View details for PubMedCentralID PMC4445352

• The Obstetric Comorbidity Index predicts severe maternal morbidity. BJOG : an international journal of obstetrics and gynaecology Bateman, B. T., Gagne, J. J. 2015; 122 (13): 1756

  View details for DOI 10.1111/1471-0528.13297

  View details for PubMedID 25639706

• Accuracy of ICD-9-CM coding to identify small for gestational age newborns. Pharmacoepidemiology and drug safety Phiri, K., Hernandez-Diaz, S., Tsen, L. C., Puopolo, K. M., Seeger, J. D., Bateman, B. T. 2015; 24 (4): 381-8

  Abstract

  This study aimed to evaluate the accuracy of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis code for small for gestational age (SGA) recorded in administrative healthcare records using birthweight and gestational age information recorded in electronic medical records.We used billing and medical records from women aged 13-55 years who delivered at a tertiary care center in the USA between 2004 and 2011. Information on birthweight, gestational age at birth, and ICD-9-CM code for SGA, 656.5x, was abstracted from the database. Each infant's birthweight percentile for gestational age was calculated on the basis of published US references; infants below the 10th percentile were classified as SGA. The performance characteristics of SGA ICD-9-CM diagnosis code against SGA classification based on birthweight and gestational age were calculated, for all deliveries and by strata of demographic and delivery characteristics.We identified 51 292 singleton live birth deliveries. The prevalence of SGA infants calculated from birthweight and gestational age at birth was higher (13%) than the prevalence based on ICD-9-CM code (2%). Sensitivity of the SGA ICD-9-CM code was 14.2%, specificity was 99.7%, positive predictive value was 86.8%, and negative predictive value was 88.4%. Stratification by demographic and delivery characteristics yielded similar results.Identification of SGA infants using ICD-9-CM code, 656.5x, from administrative healthcare records has low sensitivity but high specificity; the accuracy did not differ across demographic and delivery characteristics. Thus, although this source of information would underestimate the prevalence of SGA, it could produce valid relative risk estimates.

  View details for DOI 10.1002/pds.3740

  View details for PubMedID 25656656

  View details for PubMedCentralID PMC4533984

• An important step forward in the safe use of epidural steroid injections. Anesthesiology Bateman, B. T., Brenner, G. J. 2015; 122 (5): 964-6

  View details for DOI 10.1097/ALN.0000000000000615

  View details for PubMedID 25668413

  View details for PubMedCentralID PMC4439298

• Pregnancy complications in women with rare tumor suppressor syndromes affecting central and peripheral nervous system. American journal of obstetrics and gynecology Terry, A. R., Merker, V. L., Barker, F. G., Leffert, L., Bateman, B. T., Souter, I., Plotkin, S. R. 2015; 213 (1): 108-109

  View details for DOI 10.1016/j.ajog.2015.02.013

  View details for PubMedID 25687565

• Preoperative Opioid Misuse is Associated With Increased Morbidity and Mortality After Elective Orthopaedic Surgery. Clinical orthopaedics and related research Menendez, M. E., Ring, D., Bateman, B. T. 2015; 473 (7): 2402-12

  Abstract

  Many patients having discretionary orthopaedic surgery take opioids daily, either with a prescription or illicitly, however little is known regarding the prevalence and effect of high-risk opioid use (eg, abuse, dependence) in the perioperative orthopaedic setting.We sought (1) to determine the prevalence of opioid abuse and dependence in patients undergoing major elective orthopaedic surgery; (2) to characterize the relationship of opioid abuse and dependence with in-hospital postoperative mortality and adverse events, failure to rescue, prolonged length of stay, and nonroutine disposition; and (3) to identify factors associated with high-risk opioid use.We used coding data collected in discharge records from the Nationwide Inpatient Sample (2002-2011). We analyzed changes with time in the prevalence of opioid abuse and dependence on admission. Finally, we used multivariate regression modeling to measure the association of opioid abuse and dependence with in-hospital postoperative mortality, morbidity, and resource utilization, and to identify factors associated with high-risk opioid use.The prevalence of opioid abuse and dependence increased from 0.095% in 2002 to 0.24% in 2011, an increase of 152% (p < 0.001). Opioid abuse and dependence were associated with increased inpatient mortality (odds ratio [OR], 3.7; 95% CI, 2.7-5.1) and aggregate morbidity (OR, 2.3 l; 95% CI, 2.2-2.4), including induced mental disorder (OR, 5.9; 95% CI, 5.4-6.3), respiratory failure (OR, 3.1; 95% CI, 2.7-3.6), surgical site infection (OR, 2.5; 95% CI, 2.0-3.0), mechanical ventilation (OR, 2.3; 95% CI, 2.0-2.5), pneumonia (OR, 2.1; 95% CI, 1.8-2.3), myocardial infarction (OR, 1.9; 95% CI, 1.3-2.6), and postoperative ileus or other gastrointestinal events (OR, 1.4; 95% CI, 1.3-1.6) (p < 0.001 for all listed entities). Abuse and dependence also were associated with increased risk for prolonged hospital length of stay (OR, 2.5; 95% CI, 2.4-2.5), nonroutine discharge (OR, 2.2; 95% CI, 2.2-2.3), and failure to rescue (OR, 2.0; 95% CI, 1.4-2.8). High-risk opioid users were more likely to be younger, male, nonwhite, Medicaid-insured patients with mental health and substance use disorders, and to be undergoing spine surgery. Hospital-related characteristics included urban setting, geographic location in the Northeast or West, and serving as a teaching facility.Opioid abuse and dependence are increasing rapidly among orthopaedic surgical inpatients and are associated with considerable postoperative morbidity and mortality and resource utilization. We recommend that orthopaedic surgeons screen patients carefully for opioid misuse preoperatively, help patients who are using opioids inappropriately to discontinue them before scheduling elective surgery, decline to perform elective surgery in patients who misuse opioids, and closely monitor patients who are habituated to opioids at the time they undergo surgery.Level III, prognostic study.

  View details for DOI 10.1007/s11999-015-4173-5

  View details for PubMedID 25694266

  View details for PubMedCentralID PMC4457771

• Elevated upper body position improves pregnancy-related OSA without impairing sleep quality or sleep architecture early after delivery. Chest Zaremba, S., Mueller, N., Heisig, A. M., Shin, C. H., Jung, S., Leffert, L. R., Bateman, B. T., Pugsley, L. J., Nagasaka, Y., Duarte, I. M., Ecker, J. L., Eikermann, M. 2015; 148 (4): 936-944

  Abstract

  During pregnancy, upper airway resistance is increased, predisposing vulnerable women to pregnancy-related OSA. Elevation of the upper body increases upper airway cross-sectional area (CSA) and improves severity of OSA in a subgroup of nonpregnant patients (positional-dependent sleep apnea). We tested the hypothesis that elevated position of the upper body improves OSA early after delivery.Following institutional review board approval, we conducted a randomized, crossover study on two postpartum units of Massachusetts General Hospital. Women during the first 48 h after delivery were included. Polysomnography was performed in nonelevated and 45° elevated upper body position. Upper airway CSA was measured by acoustic pharyngometry in nonelevated, 45° elevated, and sitting body position.Fifty-five patients were enrolled, and measurements of airway CSA obtained. Thirty patients completed polysomnography in both body positions. Elevation of the upper body significantly reduced apnea-hypopnea index (AHI) from 7.7 ± 2.2/h in nonelevated to 4.5 ± 1.4/h in 45° elevated upper body position (P = .031) during sleep. Moderate to severe OSA (AHI > 15/h) was diagnosed in 20% of postpartum patients and successfully treated by elevated body position in one-half of them. Total sleep time and sleep architecture were not affected by upper body elevation. Change from nonelevated to sitting position increased inspiratory upper airway CSA from 1.35 ± 0.1 cm2 to 1.54 ± 0.1 cm2 during wakefulness. Position-dependent increase in CSA and decrease in AHI were correlated (r = 0.42, P = .022).Among early postpartum women, 45° upper body elevation increased upper airway CSA and mitigated sleep apnea. Elevated body position might improve respiratory safety in women early after delivery.ClinicalTrials.gov; No.: NCT01719224; URL: www.clinicaltrials.gov.

  View details for DOI 10.1378/chest.14-2973

  View details for PubMedID 25905714

• Non-steroidal anti-inflammatory drug administration after coronary artery bypass surgery: utilization persists despite the boxed warning. Pharmacoepidemiology and drug safety Kulik, A., Bykov, K., Choudhry, N. K., Bateman, B. T. 2015; 24 (6): 647-53

  Abstract

  In 2005, the US Food and Drug Administration (FDA) issued a boxed warning against the administration of non-steroidal anti-inflammatory drugs (NSAIDs) after coronary artery bypass graft (CABG) surgery because of cardiovascular safety concerns. We assessed utilization rates before and after the advisory and evaluated predictors of NSAID administration following CABG.We assembled a cohort of 277,576 patients who underwent CABG from 2004 to 2010. Temporal trends in NSAID exposure were evaluated, and predictors of postoperative NSAID use were identified using generalized estimating equations.Over the study period, 92,938 CABG patients (33.5%) received NSAIDs following surgery. The frequency of NSAID administration declined steadily over time, from a peak of 38.9% in 2004 to a low of 29.0% in 2010 (p < 0.0007). Ketorolac was the most frequent NSAID prescribed, commonly on the first postoperative day. Surgery performed after the boxed warning was independently associated with a 20% lower odds of NSAID administration [odds ratio (OR): 0.80; p = 0.0003]. Other factors that predicted a lower odds of NSAID use following surgery included a history of renal disease (OR: 0.33; p < 0.0001) and liver disease (OR: 0.66; p < 0.0001), and the need for concurrent valve surgery (OR: 0.78; p < 0.0001). A mammary graft at the time of surgery increased the odds of NSAID administration (OR: 1.23; p < 0.0001).The frequency of NSAID administration after CABG has declined since the FDA advisory, yet many patients continue to receive them in recent years. Our data highlight the need for future research initiatives to further define the risks associated with NSAID use in this population.

  View details for DOI 10.1002/pds.3788

  View details for PubMedID 25907164

• Propofol as a transformative drug in anesthesia: insights from key early investigators. Drug discovery today Bateman, B. T., Kesselheim, A. S. 2015; 20 (8): 1012-7

  View details for DOI 10.1016/j.drudis.2015.04.007

  View details for PubMedID 25936833

• Mortality and Morbidity During Delivery Hospitalization Among Pregnant Women With Epilepsy in the United States. JAMA neurology MacDonald, S. C., Bateman, B. T., McElrath, T. F., Hernández-Díaz, S. 2015; 72 (9): 981-8

  Abstract

  Between 0.3% and 0.5% of all pregnancies occur among women with epilepsy. Evidence suggests an increase in perinatal morbidity and mortality among women with epilepsy. However, these risks have not been quantified in large population-based samples.To report on the risk for death and adverse outcomes at the time of delivery for women with epilepsy in the United States.Retrospective cohort study of pregnant women identified through delivery hospitalization records from the 2007-2011 Nationwide Inpatient Sample. From this representative sample of 20% of all US hospitals, we obtained a weighted sample of delivery hospitalizations from 69 385 women with epilepsy and 20 449 532 women without epilepsy.Obstetrical outcomes including maternal death, cesarean delivery, length of stay, preeclampsia, preterm labor, and stillbirth.Women with epilepsy had a risk of death during delivery hospitalization of 80 deaths per 100 000 pregnancies, significantly higher than the 6 deaths per 100 000 pregnancies found among women without epilepsy (adjusted odds ratio [OR], 11.46 [95% CI, 8.64-15.19]). Women with epilepsy were also at a heightened risk for other adverse outcomes, including preeclampsia (adjusted OR, 1.59 [95% CI, 1.54-1.63]), preterm labor (adjusted OR, 1.54 [95% CI, 1.50-1.57]), and stillbirth (adjusted OR, 1.27 [95% CI, 1.17-1.38]), and had increased health care utilization, including an increased risk of cesarean delivery (adjusted OR, 1.40 [95% CI, 1.38-1.42]) and prolonged length of hospital stay (>6 days) among both women with cesarean deliveries (adjusted OR, 2.13 [95% CI, 2.03-2.23]) and women with vaginal deliveries (adjusted OR, 2.60 [95% CI, 2.41-2.80]).Findings suggest that women with epilepsy are at considerably heightened risk for many adverse outcomes during their delivery hospitalization, including a more than 10-fold increased risk of death, and that increased clinical attention is imperative for these pregnancies.

  View details for DOI 10.1001/jamaneurol.2015.1017

  View details for PubMedID 26147878

  View details for PubMedCentralID PMC4721221

• Stemming the Tide of Obstetric Morbidity: An Opportunity for the Anesthesiologist to Embrace the Role of Peridelivery Physician. Anesthesiology Mhyre, J. M., Bateman, B. T. 2015; 123 (5): 986-9

  View details for DOI 10.1097/ALN.0000000000000847

  View details for PubMedID 26352382

  View details for PubMedCentralID PMC4721222

• Calcium Channel Blocker Exposure in Late Pregnancy and the Risk of Neonatal Seizures. Obstetrics and gynecology Bateman, B. T., Huybrechts, K. F., Maeda, A., Desai, R., Patorno, E., Seely, E. W., Ecker, J. L., Allen-Coleman, C., Mogun, H., Hernandez-Diaz, S., Fischer, M. A. 2015; 126 (2): 271-278

  Abstract

  To assess whether maternal calcium channel blocker exposure during late pregnancy is independently associated with neonatal seizures after carefully controlling for confounding factors.Data were derived from the Medicaid Analytic eXtract for the years 2000-2007 and included 2,529,636 completed pregnancies. We compared the risk of neonatal seizures among neonates who were born to women who took calcium channel blockers in the final month of pregnancy to the risk in neonates born to women who did not use calcium channel blockers. Confounding was addressed through the use of propensity score matching.A total of 22,908 (0.91%) pregnancies included exposure to calcium channel blockers during the final month of pregnancy. Neonatal seizures occurred in 53 (0.23%) neonates born to mothers exposed to calcium channel blockers and in 4,609 (0.18%) neonates of unexposed women (unadjusted odds ratio [OR] 1.26, 95% confidence interval [CI] 0.96-1.65). After accounting for confounders, there was no increase in risk of neonatal seizures associated with calcium channel blocker exposure (OR 0.95, 95% CI 0.70-1.30). This null finding was robust across multiple sensitivity analysis.In this large, carefully controlled, population-based cohort study, there was no significant increase in the risk of neonatal seizures in neonates attributable to maternal calcium channel blocker exposure in late pregnancy. The results suggest that calcium channel blockers can be used by obstetricians in late pregnancy without excess concern about this neonatal complication.II.

  View details for DOI 10.1097/AOG.0000000000000908

  View details for PubMedID 26241414

  View details for PubMedCentralID PMC4526118

• Medical and Obstetric Outcomes Among Pregnant Women With Congenital Heart Disease. Obstetrics and gynecology Thompson, J. L., Kuklina, E. V., Bateman, B. T., Callaghan, W. M., James, A. H., Grotegut, C. A. 2015; 126 (2): 346-354

  Abstract

  To estimate nationwide trends in the prevalence of maternal congenital heart disease (CHD) and determine whether women with CHD are more likely than women without maternal CHD to have medical and obstetric complications.The 2000-2010 Nationwide Inpatient Sample was queried for International Classification of Diseases, 9th Revision, Clinical Modification codes to identify delivery hospitalizations of women with and without CHD. Trends in the prevalence of CHD were determined and then rates of complications were reported for CHD per 10,000 delivery hospitalizations. For Nationwide Inpatient Sample 2008-2010, logistic regression was used to examine associations between CHD and complications.From 2000 to 2010, there was a significant linear increase in the prevalence of CHD from 6.4 to 9.0 per 10,000 delivery hospitalizations (P<.001). Multivariable logistic regression demonstrated that all selected medical complications, including mortality (17.8 compared with 0.7/10,000 deliveries, adjusted odds ratio [OR] 22.10, 95% confidence interval [CI] 13.96-34.97), mechanical ventilation (91.9 compared with 6.9/10,000, adjusted OR 9.94, 95% CI 7.99-12.37), and a composite cardiovascular outcome (614 compared with 34.3/10,000, adjusted OR 10.54, 95% CI 9.55-11.64) were more likely to occur among delivery hospitalizations with maternal CHD than without. Obstetric complications were also common among women with CHD. Delivery hospitalizations with maternal CHD that also included codes for pulmonary circulatory disorders had higher rates of medical complications compared with hospitalizations with maternal CHD without pulmonary circulatory disorders.The number of delivery hospitalizations with maternal CHD in the United States is increasing, and although we were not able to determine whether correction of the cardiac lesion affected outcomes, these hospitalizations have a high burden of medical and obstetric complications.II.

  View details for DOI 10.1097/AOG.0000000000000973

  View details for PubMedID 26241425

  View details for PubMedCentralID PMC4605664

• Patterns of β-blocker initiation in patients undergoing intermediate to high-risk noncardiac surgery. American heart journal Patorno, E., Wang, S. V., Schneeweiss, S., Liu, J., Bateman, B. T. 2015; 170 (4): 812-820.e6

  Abstract

  Based on 2 small randomized controlled trials (RCTs) from the 1990s, β-blockers were promoted to prevent perioperative cardiac events in patients undergoing noncardiac surgery. In 2008, a large RCT (POISE trial) showed an increased mortality risk associated with perioperative β-blockade, raising concerns about an extensive β-Blocker use.The objective of the study is to examine patterns of β-Blocker initiation among patients undergoing noncardiac elective surgery in the US.From a large, nationwide US health care insurer, we identified patients ≥18 years old who underwent moderate- to high-risk noncardiac elective surgery between 2003 and 2012 and initiated a β-Blocker within 30 days before surgery. We evaluated temporal trends and assessed the impact of the POISE trial on perioperative β-Blocker initiation. We also evaluated patient characteristics and examined the effect of temporal proximity to surgery on the likelihood of β-Blocker initiation.Of 499,752 patients undergoing surgery, 9,014 (18 per 1,000 patients) initiated a β-Blocker. β-Blocker initiation increased from 12 per 1,000 patients in 2003 to 23 before POISE, after which it decreased to 14 by December 2012 (P = .0001). β-Blocker initiation remained relatively high among patients undergoing vascular surgery or with Revised Cardiac Risk Index score ≥ 2. Proximity to surgery was highly predictive of β-Blocker initiation (odds ratio 3.34, 95% CI 3.17-3.51).After a period of a rapidly increasing trend, perioperative β-Blocker initiation decreased sharply in the second half of 2008 and continued to decrease afterwards. β-Blocker initiation remained relatively high in patients with Revised Cardiac Risk Index score ≥2 and in those undergoing major vascular surgery.

  View details for DOI 10.1016/j.ahj.2015.06.028

  View details for PubMedID 26386806

  View details for PubMedCentralID PMC7810354

• Maternal Antidepressant Use and Persistent Pulmonary Hypertension of the Newborn--Reply. JAMA Huybrechts, K. F., Bateman, B. T., Hernandez-Diaz, S. 2015; 314 (12): 1294

  View details for DOI 10.1001/jama.2015.10048

  View details for PubMedID 26393857

• Patterns of Second-Line Uterotonic Use in a Large Sample of Hospitalizations for Childbirth in the United States: 2007-2011 ANESTHESIA AND ANALGESIA Bateman, B. T., Tsen, L. C., Liu, J., Butwick, A. J., Huybrechts, K. F. 2014; 119 (6): 1344-1349

  Abstract

  The incidence of postpartum hemorrhage due to uterine atony has increased significantly in the United States during the past decade. For patients with refractory uterine atony after oxytocin administration, second-line uterotonics including methylergonovine maleate, carboprost, and misoprostol are recommended. In this study, we describe hospital-level patterns of second-line uterotonic use in a large, nationwide sample of admissions for childbirth in the United States.The Premier Research Database was used to define a cohort of 2,180,916 patients hospitalized for delivery at 1 of 367 hospitals from 2007 to 2011. Mixed-effects logistic regression models were used to estimate the hospital-specific frequency of second-line uterotonic use adjusting for measured patient-level and hospital-level characteristics that might be risk factors for uterine atony.The median hospital-level frequency of second-line uterotonic use was 7.1% (interquartile range 5.2-% to 10.8%). In the fully adjusted model, the mean (SE) predicted probability of second-line uterotonic use was 7.02% (0.26%), with 95% of the hospitals having a predicted (SE) probability between 1.69% (0.12%) and 24.96% (1.28%).We observed wide interhospital variation in the use of second-line uterotonics that was not explained by patient-level or hospital-level characteristics. Studies aimed at defining the optimal pharmacologic strategies for the management of uterine atony are needed, particularly in light of the increasing incidence of atonic postpartum hemorrhage in the United States and other developed countries.

  View details for DOI 10.1213/ANE.0000000000000398

  View details for Web of Science ID 000345266600021

• Prescription Medication Trends in Medicaid-Enrolled Pregnant Women with Rheumatoid Arthritis, Psoriasis, and Systemic Lupus Erythematosus. Desai, R., Huybrechts, K., Bateman, B., Mogun, H., Hernandez-diaz, S., Kim, S. C. WILEY-BLACKWELL. 2014: S473

  View details for Web of Science ID 000344384902178

• Perioperative Utilization of Statins in Patients Undergoing Intermediate to High Risk Non-Cardiac Surgery Patorno, E., Wang, S., Schneeweiss, S., Liu, J., Bateman, B. WILEY. 2014: 1-2

  View details for Web of Science ID 000342763600003

• Persistent Opioid Use Following Cesarean Delivery: Patterns and Predictors among Opioid Naive Women Bateman, B. T., Franklin, J. M., Bykov, K., Huybrechts, K. F., Fischer, M. A., Choudhry, N. K. WILEY. 2014: 20

  View details for Web of Science ID 000342763600037

• Statins during Pregnancy and the Risk of Congenital Malformations: A Cohort Study Bateman, B. T., Hernandez-Diaz, S., Mogun, H., Fischer, M. A., Huybrechts, K. F. WILEY. 2014: 23-24

  View details for Web of Science ID 000342763600043

• Comparative Safety of Depression Treatments in Late Pregnancy for the Neonate Huybrechts, K., Bateman, B., Levin, R., Mogun, H., Hernandez-Diaz, S. WILEY. 2014: 166

  View details for Web of Science ID 000342763600314

• Impact of Right Truncation in Studies of Drug Safety during Pregnancy Hernandez-Diaz, S., Bateman, B., Huybrechts, K. WILEY. 2014: 165-166

  View details for Web of Science ID 000342763600313

• Patterns of Second-Line Uterotonic Use in a Large Sample of Hospitalizations for Childbirth in the United States: 2007-2011. Anesthesia and analgesia Bateman, B. T., Tsen, L. C., Liu, J., Butwick, A. J., Huybrechts, K. F. 2014

  Abstract

  The incidence of postpartum hemorrhage due to uterine atony has increased significantly in the United States during the past decade. For patients with refractory uterine atony after oxytocin administration, second-line uterotonics including methylergonovine maleate, carboprost, and misoprostol are recommended. In this study, we describe hospital-level patterns of second-line uterotonic use in a large, nationwide sample of admissions for childbirth in the United States.The Premier Research Database was used to define a cohort of 2,180,916 patients hospitalized for delivery at 1 of 367 hospitals from 2007 to 2011. Mixed-effects logistic regression models were used to estimate the hospital-specific frequency of second-line uterotonic use adjusting for measured patient-level and hospital-level characteristics that might be risk factors for uterine atony.The median hospital-level frequency of second-line uterotonic use was 7.1% (interquartile range 5.2-% to 10.8%). In the fully adjusted model, the mean (SE) predicted probability of second-line uterotonic use was 7.02% (0.26%), with 95% of the hospitals having a predicted (SE) probability between 1.69% (0.12%) and 24.96% (1.28%).We observed wide interhospital variation in the use of second-line uterotonics that was not explained by patient-level or hospital-level characteristics. Studies aimed at defining the optimal pharmacologic strategies for the management of uterine atony are needed, particularly in light of the increasing incidence of atonic postpartum hemorrhage in the United States and other developed countries.

  View details for DOI 10.1213/ANE.0000000000000398

  View details for PubMedID 25166464

• In response. Anesthesia and analgesia Bateman, B. T., Sandberg, W. S. 2014; 119 (6): 1452

  View details for DOI 10.1213/ANE.0000000000000432

  View details for PubMedID 25405696

• Authors' reply to Gupta. BMJ (Clinical research ed.) Patorno, E., Bateman, B. T. 2014; 349: g4873

  View details for DOI 10.1136/bmj.g4873

  View details for PubMedID 25078880

• Medical and pregnancy complications among women with congenital heart disease at delivery Thompson, J., Kuklina, E., Bateman, B., Callaghan, W., James, A., Grotegut, C. MOSBY-ELSEVIER. 2014: S28

  View details for DOI 10.1016/j.ajog.2013.10.076

  View details for Web of Science ID 000330322600046

• Racial and ethnic disparities in severe maternal morbidity: a multistate analysis, 2008-2010. American journal of obstetrics and gynecology Creanga, A. A., Bateman, B. T., Kuklina, E. V., Callaghan, W. M. 2014; 210 (5): 435.e1-8

  Abstract

  The purpose of this study was to examine racial and ethnic disparities in severe maternal morbidity during delivery hospitalizations in the United States.We identified delivery hospitalizations from 2008-2010 in State Inpatient Databases from 7 states. We used International Classification of Diseases, 9th Revision, codes to create severe maternal morbidity indicators during delivery hospitalizations. We calculated the rates of severe maternal morbidity that were measured with and without blood transfusion for 5 racial/ethnic groups: non-Hispanic white, non-Hispanic black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native women. Poisson regression models were fitted to explore the associations between race/ethnicity and severe maternal morbidity after we controlled for potential confounders.Overall, severe maternal morbidity rates that were measured with and without blood transfusion were 150.7 and 64.3 per 10,000 delivery hospitalizations, respectively. Non-Hispanic black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native women had 2.1, 1.3, 1.2, and 1.7 times (all P < .05), respectively, higher rates of severe morbidity that were measured with blood transfusion compared with non-Hispanic white women; similar increased rates were observed when severe morbidity was measured without blood transfusion. Other significant positive predictors of severe morbidity were age <20 and ≥30 years, self-pay or Medicaid coverage for delivery, low socioeconomic status, and presence of chronic medical conditions.Severe maternal morbidity disproportionally affects racial/ethnic minority women, especially non-Hispanic black women. There is a need for a systematic review of severe maternal morbidities at the facility, state, and national levels to guide the development of quality improvement interventions to reduce the racial/ethnic disparities in severe maternal morbidity.

  View details for DOI 10.1016/j.ajog.2013.11.039

  View details for PubMedID 24295922

• Patterns of recurrence of postpartum hemorrhage in a large population-based cohort. American journal of obstetrics and gynecology Oberg, A. S., Hernandez-Diaz, S., Palmsten, K., Almqvist, C., Bateman, B. T. 2014; 210 (3): 229.e1-8

  Abstract

  Although a history of postpartum hemorrhage (PPH) is a recognized risk factor for PPH in subsequent pregnancies, little is known about how the risk accumulates over multiple pregnancies, how recurrence varies by PPH subtype, and whether recurrence can be explained by chronic maternal conditions.Risks of PPH were assessed according to a history of PPH, severity, and subtype (atony, retained placenta, or lacerations) in 538,332 primiparous women whose data were included in the Swedish Medical Birth Register from 1997-2009. The role of stable maternal risk factors was evaluated in regression models that predicted probability of recurrent PPH in second and third pregnancy.Women with a history of PPH had a 3-fold increased risk of PPH in their second pregnancy compared with unaffected women (15.0% vs 5.0%, respectively). Adjustment for stable maternal risk factors did not attenuate this risk significantly (adjusted relative risk, 3.0; 95% confidence interval, 2.9-3.1). In a third pregnancy, the risk of PPH was 26.6% after 2 previously affected pregnancies, compared with 4.4% in women with no previous PPH. A history of a specific type of PPH predicted recurrence of PPH in the second pregnancy, not only of the same type but other causes as well.PPH risk is highest among women with >1 previously affected delivery and in those with a previous severe PPH. Chronic conditions that are known to be risk factors for PPH do not explain the recurrence risks. The recurrence patterns across PPH subtypes may point to shared pathologic mechanisms underlying the varying PPH causes.

  View details for DOI 10.1016/j.ajog.2013.10.872

  View details for PubMedID 24351791

  View details for PubMedCentralID PMC3943527

• Triggers of spontaneous preterm delivery--why today? Paediatric and perinatal epidemiology Hernández-Díaz, S., Boeke, C. E., Romans, A. T., Young, B., Margulis, A. V., McElrath, T. F., Ecker, J. L., Bateman, B. T. 2014; 28 (2): 79-87

  Abstract

  Our goal is to study the triggers of spontaneous preterm delivery using a case-crossover design.In a pilot study, we enrolled 50 women with spontaneous preterm labour (PTL) and 50 with preterm premature rupture of membranes (PPROM) between 2011 and 2012. To assess non-transient risk factors, we also enrolled a control group of 158 pregnant women at their regular prenatal care visits matched to cases by gestational age and calendar time. The index time was defined as the onset of PTL/PPROM (for cases) or interview (for controls). Detailed data were collected through structured interviews regarding factors of interest during the 72 h that preceded the index time. Within case subjects, we compared the frequency of transient factors from 0 to 24 h before index time with that from 48 to 72 h before index time, and estimated matched odds ratios (OR) and 95% confidence intervals (CI).Previously hypothesised chronic risk factors for spontaneous preterm delivery, including mood disorders and stressful events, were more common among cases than among controls. Within cases, skipped meals [OR 4.3, 95% CI 1.2, 15.2], disturbed sleep [OR 4.5, 95% CI 1.5, 13.3], sexual activity [OR 6.0, 95% CI 0.7, 69.8], and intake of spicy foods [OR 7.0, 95% CI 1.6, 30.8] were associated with an increased risk for PTL/PPROM within the subsequent 24 h. For physical exertion and other potential risk factors evaluated, the OR was close to the null.Skipping meals and disturbed sleep may be associated with imminent PTL/PPROM; sexual activity and spicy food may trigger PTL/PPROM in susceptible women. Larger case-crossover studies will be able to evaluate the impact of modifiable risk factors and acute predictors of PTL/PPROM, and might help guide obstetrical management.

  View details for DOI 10.1111/ppe.12105

  View details for PubMedID 24384058

  View details for PubMedCentralID PMC4106670

• Patterns of opioid utilization in pregnancy in a large cohort of commercial insurance beneficiaries in the United States. Anesthesiology Bateman, B. T., Hernandez-Diaz, S., Rathmell, J. P., Seeger, J. D., Doherty, M., Fischer, M. A., Huybrechts, K. F. 2014; 120 (5): 1216-24

  Abstract

  There are few data regarding the utilization of opioids during pregnancy. The objective of this study was to define the prevalence and patterns of opioid use in a large cohort of pregnant women who were commercial insurance beneficiaries.Data for the study were derived from a deidentified research database of women from across the United States who had both medical and prescription benefits. By using diagnostic codes, the authors defined a cohort of 534,500 women with completed pregnancies who were enrolled in a commercial insurance plan from 6 months before pregnancy through delivery.Overall, 76,742 women (14.4%) were dispensed an opioid at some point during pregnancy. There were 30,566 women (5.7%) dispensed an opioid during the first trimester, 30,434 women (5.7%) during the second trimester, and 34,906 women (6.5%) during the third trimester. Of these, 11,747 women (2.2%) were dispensed opioids three or more times during pregnancy. The most commonly dispensed opioids during pregnancy were hydrocodone (6.8%), codeine (6.1%), and oxycodone (2.0%). The prevalence of exposure at anytime during pregnancy decreased slightly during the study period from 14.9% for pregnancies that delivered in 2005 to 12.9% in 2011. The prevalence of exposure varied significantly by region and was lowest in the Northeast and highest in the South.This study demonstrates that opioids are very common exposures during pregnancy. Given the small and inconsistent body of literature on their safety in pregnancy, these findings suggest a need for research in this area.

  View details for DOI 10.1097/ALN.0000000000000172

  View details for PubMedID 24525628

  View details for PubMedCentralID PMC3999216

• Cardiac arrest during hospitalization for delivery in the United States, 1998-2011. Anesthesiology Mhyre, J. M., Tsen, L. C., Einav, S., Kuklina, E. V., Leffert, L. R., Bateman, B. T. 2014; 120 (4): 810-8

  Abstract

  The objective of this analysis was to evaluate the frequency, distribution of potential etiologies, and survival rates of maternal cardiopulmonary arrest during the hospitalization for delivery in the United States.By using data from the Nationwide Inpatient Sample during the years 1998 through 2011, the authors obtained weighted estimates of the number of U.S. hospitalizations for delivery complicated by maternal cardiac arrest. Clinical and demographic risk factors, potential etiologies, and outcomes were identified and compared in women with and without cardiac arrest. The authors tested for temporal trends in the occurrence and survival associated with maternal arrest.Cardiac arrest complicated 1 in 12,000 or 8.5 per 100,000 hospitalizations for delivery (99% CI, 7.7 to 9.3 per 100,000). The most common potential etiologies of arrest included hemorrhage, heart failure, amniotic fluid embolism, and sepsis. Among patients with cardiac arrest, 58.9% of patients (99% CI, 54.8 to 63.0%) survived to hospital discharge.Approximately 1 in 12,000 hospitalizations for delivery is complicated by cardiac arrest, most frequently due to hemorrhage, heart failure, amniotic fluid embolism, or sepsis. Survival depends on the underlying etiology of arrest.

  View details for DOI 10.1097/ALN.0000000000000159

  View details for PubMedID 24694844

  View details for PubMedCentralID PMC4445354

• Increase in prescription opioid use during pregnancy among Medicaid-enrolled women. Obstetrics and gynecology Desai, R. J., Hernandez-Diaz, S., Bateman, B. T., Huybrechts, K. F. 2014; 123 (5): 997-1002

  Abstract

  To report the prevalence of prescription opioid use and evaluate the trends in a large cohort of Medicaid-enrolled pregnant women.A cohort of pregnancies was identified using data from the Medicaid Analytical eXtract for the period of 2000-2007. Dispensing of opioids, as a class and separately for individual agents, was evaluated using claims from filled prescriptions. Variations in patterns of prescription opioid fills were examined by demographic characteristics, by geographic region, and over time. Median number of opioid prescriptions dispensed and cumulative days of availability for prescription opioids during pregnancy were reported.The study population consisted of more than 1.1 million women with completed pregnancies from 46 U.S. states and Washington, DC. One of five women from our cohort (21.6%) filled a prescription for an opioid during pregnancy; this proportion increased from 18.5% in 2000 to 22.8% in 2007. Substantial regional variation was seen with the proportion of women who filled a prescription during pregnancy, ranging between 9.5% and 41.6% across the states. Codeine and hydrocodone were the most commonly prescribed opioids. Among women filling at least one opioid prescription, the median (interquartile range) number of prescriptions filled was 1 (1-2) and the median (interquartile range) cumulative days of opioid availability during pregnancy were 5 (3-13) days.We observed high and increasing number of filled prescriptions for opioids during pregnancy among Medicaid-enrolled women. These findings call for further safety evaluations of these drugs and their effects on the developing fetus to inform clinical practice.II.

  View details for DOI 10.1097/AOG.0000000000000208

  View details for PubMedID 24785852

  View details for PubMedCentralID PMC4020039

• Prescription of antihypertensive medications during pregnancy in the UK. Pharmacoepidemiology and drug safety Cea Soriano, L., Bateman, B. T., García Rodríguez, L. A., Hernández-Díaz, S. 2014; 23 (10): 1051-8

  Abstract

  This study aimed to describe the management of antihypertensive medications in pregnancy by general practitioners in the UK and compare it with current guidelines.We used electronic medical records from The Health Improvement Network database from 1996 to 2010 to identify completed pregnancies. The study cohort included the first pregnancy identified during the study period in women aged 13-49 years. Information on both hypertension diagnoses and prescription of specific antihypertensive medications within the 90 days before the last menstrual period (LMP) and during pregnancy was ascertained from electronic medical records.Among 148,544 eligible pregnancies, we identified 1995 (1.3%) during which the women had pre-existing hypertension diagnosed by the LMP date. Overall, the prevalence of antihypertensive medications during the first trimester was 1.5%; beta-blockers were the most commonly prescribed antihypertensive. Among women with pre-existing hypertension, 36% were prescribed an antihypertensive medication during the 90 days before the LMP. Among those, 9.6% and 22.2% had discontinued their medication by the first and second trimesters, respectively. For contraindicated drugs such as angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, the corresponding discontinuation rates were around 25% and 70%. Women who switched therapy received preferably either methyldopa or an alpha/beta-blocker.In this population of UK pregnant women, prescription patterns of antihypertensive medications were dominated by recommended treatments, although some patients continued on contraindicated drugs throughout pregnancy or switched to preferred agents in a delayed fashion.

  View details for DOI 10.1002/pds.3641

  View details for PubMedID 24797728

  View details for PubMedCentralID PMC4198617

• Anesthesiologist as epidemiologist: insights from registry studies of obstetric anesthesia-related complications. Anesthesiology Bateman, B. T., Tsen, L. C. 2014; 120 (6): 1311-2

  View details for DOI 10.1097/ALN.0000000000000252

  View details for PubMedID 24845916

• Performance of racial and ethnic minority-serving hospitals on delivery-related indicators. American journal of obstetrics and gynecology Creanga, A. A., Bateman, B. T., Mhyre, J. M., Kuklina, E., Shilkrut, A., Callaghan, W. M. 2014; 211 (6): 647.e1-16

  Abstract

  We sought to explore how racial/ethnic minority-serving hospitals perform on 15 delivery-related indicators, and examine whether indicators vary by race/ethnicity within the same type of hospitals.We used 2008 through 2011 linked State Inpatient Database and American Hospital Association data from 7 states, and designated hospitals with >50% of deliveries to non-Hispanic white, non-Hispanic black, and Hispanic women as white-, black-, and Hispanic-serving, respectively. We calculated indicator rates per 1000 deliveries by hospital type and, separately, for non-Hispanic white, non-Hispanic black, and Hispanic women within each hospital type. We fitted multivariate Poisson regression models to examine associations between delivery-related indicators and patient and hospital characteristics by hospital type.White-serving hospitals offer obstetric care to an older and wealthier population than black- or Hispanic-serving hospitals. Rates of the most prevalent indicators examined (complicated vaginal delivery, complicated cesarean delivery, obstetric trauma) were lowest in Hispanic-serving hospitals. Generally, indicator rates were similar in Hispanic- and white-serving hospitals. Black-serving hospitals performed worse than other hospitals on 12 of 15 indicators. Indicator rates varied greatly by race/ethnicity in white- and Hispanic-serving hospitals, with non-Hispanic blacks having 1.19-3.27 and 1.15-2.68 times higher rates than non-Hispanic whites, respectively, for 11 of 15 indicators. Conversely, there were few indicator rate differences by race/ethnicity in black-serving hospitals, suggesting an overall lower performance of these hospitals compared to white- and Hispanic-serving hospitals.We found considerable differences in delivery-related indicators by hospital type and patients' race/ethnicity. Obstetric care quality measures are needed to track racial/ethnic disparities at the facility and population levels.

  View details for DOI 10.1016/j.ajog.2014.06.006

  View details for PubMedID 24909341

• In Reply: Cho et al. Obstetrics and gynecology Desai, R. J., Hernandez-Diaz, S., Bateman, B. T., Huybrechts, K. F. 2014; 124 (3): 638

  View details for DOI 10.1097/AOG.0000000000000445

  View details for PubMedID 25162278

• Authors' reply to Sholapurkar. BMJ (Clinical research ed.) Oberg, A. S., Bateman, B. T. 2014; 349: g6210

  View details for DOI 10.1136/bmj.g6210

  View details for PubMedID 25316117

• Opioid abuse and dependence during pregnancy: temporal trends and obstetrical outcomes. Anesthesiology Maeda, A., Bateman, B. T., Clancy, C. R., Creanga, A. A., Leffert, L. R. 2014; 121 (6): 1158-65

  Abstract

  The authors investigated nationwide trends in opioid abuse or dependence during pregnancy and assessed the impact on maternal and obstetrical outcomes in the United States.Hospitalizations for delivery were extracted from the Nationwide Inpatient Sample from 1998 to 2011. Temporal trends were assessed and logistic regression was used to examine the associations between maternal opioid abuse or dependence and obstetrical outcomes adjusting for relevant confounders.The prevalence of opioid abuse or dependence during pregnancy increased from 0.17% (1998) to 0.39% (2011) for an increase of 127%. Deliveries associated with maternal opioid abuse or dependence compared with those without opioid abuse or dependence were associated with an increased odds of maternal death during hospitalization (adjusted odds ratio [aOR], 4.6; 95% CI, 1.8 to 12.1, crude incidence 0.03 vs. 0.006%), cardiac arrest (aOR, 3.6; 95% CI, 1.4 to 9.1; 0.04 vs. 0.01%), intrauterine growth restriction (aOR, 2.7; 95% CI, 2.4 to 2.9; 6.8 vs. 2.1%), placental abruption (aOR, 2.4; 95% CI, 2.1 to 2.6; 3.8 vs. 1.1%), length of stay more than 7 days (aOR, 2.2; 95% CI, 2.0 to 2.5; 3.0 vs. 1.2%), preterm labor (aOR, 2.1; 95% CI, 2.0 to 2.3; 17.3 vs. 7.4%), oligohydramnios (aOR, 1.7; 95% CI, 1.6 to 1.9; 4.5 vs. 2.8%), transfusion (aOR, 1.7; 95% CI, 1.5 to 1.9; 2.0 vs. 1.0%), stillbirth (aOR, 1.5; 95% CI, 1.3 to 1.8; 1.2 vs. 0.6%), premature rupture of membranes (aOR, 1.4; 95% CI, 1.3 to 1.6; 5.7 vs. 3.8%), and cesarean delivery (aOR, 1.2; 95% CI, 1.1 to 1.3; 36.3 vs. 33.1%).Opioid abuse or dependence during pregnancy is associated with considerable obstetrical morbidity and mortality, and its prevalence is dramatically increasing in the United States. Identifying preventive strategies and therapeutic interventions in pregnant women who abuse drugs are important priorities for clinicians and scientists.

  View details for DOI 10.1097/ALN.0000000000000472

  View details for PubMedID 25405293

• Opioid use is rising. Anesthesiology Wanderer, J. P., Bateman, B. T., Rathmell, J. P. 2014; 121 (6): A23

  View details for DOI 10.1097/01.anes.0000456214.34289.aa

  View details for PubMedID 25405312

• Medical and Mechanical Prophylaxis for Venous Thromboembolism after Total Hip and Knee Replacement Patorno, E., Bateman, B., Choudhry, N., Landon, J., Schneeweiss, S. WILEY. 2013: 486

  View details for Web of Science ID 000334876102083

• Type of Stress Ulcer Prophylaxis and the Risk of Nosocomial Pneumonia in Cardiac Surgical Patients Bateman, B. T., Bykov, K., Schneeweiss, S., Gagne, J., Polinski, J. M., Franklin, J. M., Fischer, M. A., Choudhry, N. K., Rassen, J. A. WILEY. 2013: 35-36

  View details for Web of Science ID 000334876100067

• Hypertension and Patterns of Prescription of Antihypertensive Medications during Pregnancy Using THIN Database Cea Soriano, L., Bateman, B. T., Garcia Rodriguez, L. A., Hernandez-Diaz, S. WILEY-BLACKWELL. 2013: 145-146

  View details for Web of Science ID 000334876100280

• Methylergonovine Maleate and the Risk of Myocardial Ischemia and Infarction Bateman, B. T., Huybrechts, K. F., Hernandez-Diaz, S., Liu, J., Avorn, J. WILEY. 2013: 195

  View details for Web of Science ID 000334876100376

• TRIGGERS OF SPONTANEOUS PRETERM DELIVERY: WHY DID IT HAPPEN TODAY? Boeke, C. E., Bateman, B. T., Thornton, A., Young, B., Margulis, A. V., McElrath, T. F., Ecker, J. L., Hernandez-Diaz, S. OXFORD UNIV PRESS INC. 2013: S143

  View details for Web of Science ID 000319870300564

• FAMILIAL CLUSTERING OF POSTPARTUM HEMORRHAGE IN THE SWEDISH POPULATION. Oberg, A., Frisell, T., Hernandez-Diaz, S., Almqvist, C., Bateman, B. T. OXFORD UNIV PRESS INC. 2013: S80

  View details for Web of Science ID 000319870300312

• Massive blood transfusion during hospitalization for delivery in New York State, 1998-2007. Obstetrics and gynecology Mhyre, J. M., Shilkrut, A., Kuklina, E. V., Callaghan, W. M., Creanga, A. A., Kaminsky, S., Bateman, B. T. 2013; 122 (6): 1288-94

  Abstract

  To define the frequency, risk factors, and outcomes of massive transfusion in obstetrics.The State Inpatient Dataset for New York (1998-2007) was used to identify all delivery hospitalizations for hospitals that reported at least one delivery-related transfusion per year. Multivariable logistic regression analysis was performed to examine the relationship between maternal age, race, and relevant clinical variables and the risk of massive blood transfusion defined as 10 or more units of blood recorded.Massive blood transfusion complicated 6 of every 10,000 deliveries with cases observed even in the smallest facilities. Risk factors with the strongest independent associations with massive blood transfusion included abnormal placentation (1.6/10,000 deliveries, adjusted odds ratio [OR] 18.5, 95% confidence interval [CI] 14.7-23.3), placental abruption (1.0/10,000, adjusted OR 14.6, 95% CI 11.2-19.0), severe preeclampsia (0.8/10,000, adjusted OR 10.4, 95% CI 7.7-14.2), and intrauterine fetal demise (0.7/10,000, adjusted OR 5.5, 95% CI 3.9-7.8). The most common etiologies of massive blood transfusion were abnormal placentation (26.6% of cases), uterine atony (21.2%), placental abruption (16.7%), and postpartum hemorrhage associated with coagulopathy (15.0%). A disproportionate number of women who received a massive blood transfusion experienced severe morbidity including renal failure, acute respiratory distress syndrome, sepsis, and in-hospital death.Massive blood transfusion was infrequent, regardless of facility size. In the presence of known risk for receipt of massive blood transfusion, women should be informed of this possibility, should deliver in a well-resourced facility if possible, and should receive appropriate blood product preparation and venous access in advance of delivery.: II.

  View details for DOI 10.1097/AOG.0000000000000021

  View details for PubMedID 24201690

  View details for PubMedCentralID PMC4547558

• Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study. BMJ (Clinical research ed.) Bateman, B. T., Bykov, K., Choudhry, N. K., Schneeweiss, S., Gagne, J. J., Polinski, J. M., Franklin, J. M., Doherty, M., Fischer, M. A., Rassen, J. A. 2013; 347: f5416

  Abstract

  To examine the relation between the type of stress ulcer prophylaxis administered and the risk of postoperative pneumonia in patients undergoing coronary artery bypass grafting.Retrospective cohort study.Premier Research Database.21,214 patients undergoing coronary artery bypass graft surgery between 2004 and 2010; 9830 (46.3%) started proton pump inhibitors and 11,384 (53.7%) started H2 receptor antagonists in the immediate postoperative period.Occurrence of postoperative pneumonia, assessed using appropriate diagnostic codes.Overall, 492 (5.0%) of the 9830 patients receiving a proton pump inhibitor and 487 (4.3%) of the 11,384 patients receiving an H2 receptor antagonist developed postoperative pneumonia during the index hospital admission. After propensity score adjustment, an elevated risk of pneumonia associated with treatment with proton pump inhibitors compared with H2 receptor antagonists remained (relative risk 1.19, 95% confidence interval 1.03 to 1.38). In the instrumental variable analysis, use of a proton pump inhibitor (compared with an H2 receptor antagonist) was associated with an increased risk of pneumonia of 8.2 (95% confidence interval 0.5 to 15.9) cases per 1000 patients.Patients treated with proton pump inhibitors for stress ulcer had a small increase in the risk of postoperative pneumonia compared with patients treated with H2 receptor antagonists; this risk remained after confounding was accounted for using multiple analytic approaches.

  View details for DOI 10.1136/bmj.f5416

  View details for PubMedID 24052582

  View details for PubMedCentralID PMC3777797

• Spinal Anesthesia in Severe Preeclampsia. Anesthesia and analgesia Henke, V. G., Bateman, B. T., Leffert, L. R. 2013

  Abstract

  Spinal anesthesia is widely regarded as a reasonable anesthetic option for cesarean delivery in severe preeclampsia, provided there is no indwelling epidural catheter or contraindication to neuraxial anesthesia. Compared with healthy parturients, those with severe preeclampsia experience less frequent, less severe spinal-induced hypotension. In severe preeclampsia, spinal anesthesia may cause a higher incidence of hypotension than epidural anesthesia; however, this hypotension is typically easily treated and short lived and has not been linked to clinically significant differences in outcomes. In this review, we describe the advantages and limitations of spinal anesthesia in the setting of severe preeclampsia and the evidence guiding intraoperative hemodynamic management.

  View details for DOI 10.1213/ANE.0b013e31829eeef5

  View details for PubMedID 23868886

• The risk and outcomes of epidural hematomas after perioperative and obstetric epidural catheterization: a report from the Multicenter Perioperative Outcomes Group Research Consortium. Anesthesia and analgesia Bateman, B. T., Mhyre, J. M., Ehrenfeld, J., Kheterpal, S., Abbey, K. R., Argalious, M., Berman, M. F., Jacques, P. S., Levy, W., Loeb, R. G., Paganelli, W., Smith, K. W., Wethington, K. L., Wax, D., Pace, N. L., Tremper, K., Sandberg, W. S. 2013; 116 (6): 1380-5

  Abstract

  In this study, we sought to determine the frequency and outcomes of epidural hematomas after epidural catheterization.Eleven centers participating in the Multicenter Perioperative Outcomes Group used electronic anesthesia information systems and quality assurance databases to identify patients who had epidural catheters inserted for either obstetrical or surgical indications. From this cohort, patients undergoing laminectomy for the evacuation of hematoma within 6 weeks of epidural placement were identified.Seven of 62,450 patients undergoing perioperative epidural catheterizations developed hematoma requiring surgical evacuation. The event rate was 11.2 × 10(-5) (95% confidence interval [CI], 4.5 × 10(-5) to 23.1 × 10(-5)). Four of the 7 had anticoagulation/antiplatelet therapy that deviated from American Society of Regional Anesthesia guidelines. None of 79,837 obstetric patients with epidural catheterizations developed hematoma (upper limit of the 95% CI, 4.6 × 10(-5)). The hematoma rate in obstetric epidural catheterizations was significantly lower than in perioperative epidural catheterizations (P = 0.003).In this series, the 95% CI for the frequency of epidural hematoma requiring laminectomy after epidural catheter placement for perioperative anesthesia/analgesia was 1 event per 22,189 placements to 1 event per 4330 placements. Risk was significantly lower in obstetric epidurals.

  View details for DOI 10.1213/ANE.0b013e318251daed

  View details for PubMedID 22504213

• Assessing cardiovascular disease risk among young women with a history of delivering a low-birth-weight infant. American journal of perinatology Dietz, P. M., Kuklina, E. V., Bateman, B. T., Callaghan, W. M. 2013; 30 (4): 267-73

  Abstract

  To assess the prevalence and risk factors of cardiovascular disease (CVD) among younger women by pregnancy history.Cross-sectional study using 1999 to 2006 National Health and Nutrition Examination Survey including women aged 20 to 64 years who had delivered at least one infant (n = 4820). Women self-reported pregnancy history and a clinician diagnosed CVD; CVD risk factors included hypertension (mean systolic blood pressure [BP] ≥140 mm Hg or mean diastolic BP ≥90 mm Hg, or currently treated), high cholesterol (total cholesterol ≥240 mg/dL or currently treated), diabetes (self-report or hemoglobin A1c ≥6.5), and smoking (self-report or cotinine-verified). Multivariable logistic regression was used to assess the association between pregnancy history and CVD.Of the women we studied, 4.6% had CVD; 3.1% had delivered a term low-birth-weight infant (TLBWI). Women with a history of TLBWI had an adjusted odds ratio (AOR) of 2.07 (95% confidence intervals [CI] 1.08 to 3.99) for CVD compared with women without a history of LBWI. Adjustment for hypertension and high cholesterol mildly attenuated the association (AOR 1.85, 95% CI 0.89 to 3.83). Among women without CVD (n = 4555), 23.1% with a history of TLBWI had two risk factors compared with 14.0% of those without a history of LBWI (p = 0.0016).Women with a history of TLBWI should be informed of a possible increased risk of CVD and encouraged to receive screenings as recommended.

  View details for DOI 10.1055/s-0032-1323589

  View details for PubMedID 22875656

• Neostigmine reversal doesn't improve postoperative respiratory safety. BMJ (Clinical research ed.) Meyer, M. J., Bateman, B. T., Kurth, T., Eikermann, M. 2013; 346: f1460

  View details for DOI 10.1136/bmj.f1460

  View details for PubMedID 23512446

  View details for PubMedCentralID PMC4688546

• Neurofibromatosis type 1 and pregnancy complications: a population-based study. American journal of obstetrics and gynecology Terry, A. R., Barker, F. G., Leffert, L., Bateman, B. T., Souter, I., Plotkin, S. R. 2013; 209 (1): 46.e1-8

  Abstract

  The objective of the study was to determine whether vascular and other complications are more common in pregnant women with neurofibromatosis type 1 (NF1).We performed a population-based retrospective cohort study using the US Nationwide Inpatient Sample, 1988-2009, defining a cohort of pregnancy-related hospitalizations with an associated diagnosis of NF1 and comparing it with the control group not associated with NF1. Multivariable logistic regression was used to adjust for suspected confounders.Among 19 million pregnancy-related admissions between 1988 and 2009, we identified 1553 associated with NF1 (prevalence 0.008%). A diagnosis of NF1 in delivering mothers was associated with gestational hypertension (adjusted odds ratio [AOR], 1.6, 95% confidence interval [CI], 1.2-2.0), preeclampsia (AOR, 2.8, 95% CI, 2.3-3.4), intrauterine growth restriction (AOR, 4.6, 95% CI, 3.7-5.6), cerebrovascular disease (OR, 8.1, 95% CI, 2.6-25.4), preterm labor (AOR, 1.6, 95% CI, 1.4-1.9), and cesarean delivery (AOR, 2.0, 95% CI, 1.8-2.3). Women with NF1 were not significantly more likely to have deep venous thrombosis/pulmonary embolism, acute cardiac events, or stillbirth or to die during their hospitalizations compared with the general obstetric population.NF1 was associated with increased maternal morbidity in pregnancy (including hypertensive and cerebrovascular complications) but not increased maternal mortality. Obstetricians should be aware of the potential for increased antenatal and peripartum complications among women with NF1.

  View details for DOI 10.1016/j.ajog.2013.03.029

  View details for PubMedID 23535241

• Adjuvant vancomycin for antibiotic prophylaxis and risk of Clostridium difficile infection after coronary artery bypass graft surgery. The Journal of thoracic and cardiovascular surgery Bateman, B. T., Rassen, J. A., Schneeweiss, S., Bykov, K., Franklin, J. M., Gagne, J. J., Polinski, J. M., Liu, J., Kulik, A., Fischer, M. A., Choudhry, N. K. 2013; 146 (2): 472-8

  Abstract

  The incidence of hospital-acquired Clostridium difficile infection (CDI) has increased rapidly over the past decade; patients undergoing major surgery, including coronary artery bypass grafting (CABG), are at particular risk. Intravenous vancomycin exposure has been identified as an independent risk factor for CDI, but this is controversial. It is not known whether vancomycin administered for surgical site infection prophylaxis increases the risk of CDI.Using data from the Premier Perspective Comparative Database, we assembled a cohort of 69,807 patients undergoing CABG surgery between 2004 and 2010 who received either a cephalosporin alone (65.1%) or a cephalosporin plus vancomycin (34.9%) on the day of surgery. Patients were observed for CDI until discharge from the index hospitalization. In these groups, we evaluated the comparative rate of postoperative CDI with Cox models; confounding was addressed using propensity scores.In all, 77 (0.32%) of the 24,393 patients receiving a cephalosporin plus vancomycin and 179 (0.39%) of the 45,414 patients receiving a cephalosporin alone had postoperative CDI (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.56-0.95). After adjusting for confounding variables with either propensity score matching or stratification, there was no meaningful association between adjuvant vancomycin exposure and postoperative CDI (HR, 0.85; 95% CI, 0.61-1.19; and HR, 0.85; 95% CI, 0.63-1.15, respectively). Results of multiple sensitivity analyses were similar to the main findings.After adjustment for patient and surgical characteristics, a short course of prophylactic vancomycin was not associated with an increased risk of CDI among patients undergoing CABG surgery.

  View details for DOI 10.1016/j.jtcvs.2013.02.075

  View details for PubMedID 23541855

  View details for PubMedCentralID PMC3720831

• Development and validation of a score for prediction of postoperative respiratory complications. Anesthesiology Brueckmann, B., Villa-Uribe, J. L., Bateman, B. T., Grosse-Sundrup, M., Hess, D. R., Schlett, C. L., Eikermann, M. 2013; 118 (6): 1276-85

  Abstract

  Postoperative respiratory failure is associated with increased morbidity and mortality, as well as high costs of hospital care.Using electronic anesthesia records, billing data, and chart review, the authors developed and validated a score predicting reintubation in the hospital after primary extubation in the operating room, leading to unplanned mechanical ventilation within the first 3 postoperative days. Using multivariable logistic regression analysis, independent predictors were determined and a score postulated and validated.In the entire cohort (n = 33,769 surgical cases within 29,924 patients), reintubation occurred in 137 cases (0.41%). Of those, 16%, (n = 22) died subsequently, whereas the mortality in patients who were not reintubated was 0.26% (P < 0.0001). Independent predictors for reintubation were: American Society of Anesthesiologist Score 3 or more, emergency surgery, high-risk surgical service, history of congestive heart failure, and chronic pulmonary disease. A point value of 3, 3, 2, 2, and 1 were assigned to these predictors, respectively, based on their β coefficient in the predictive model. The score yielded a calculated area under the curve of 0.81, whereas each point increment was associated with a 1.7-fold (odds ratio: 1.72 [95% CI, 1.55-1.91]) increase in the odds for reintubation in the training dataset. Using the validation dataset (n = 16,884), the score had an area under the curve of 0.80 and similar estimated probabilities for reintubation.The authors developed and validated a score for the prediction of postoperative respiratory complications, a simple, 11-point score that can be used preoperatively by anesthesiologists to predict severe postoperative respiratory complications.

  View details for DOI 10.1097/ALN.0b013e318293065c

  View details for PubMedID 23571640

• Epidemiology of obstetric-related ICU admissions in Maryland: 1999-2008*. Critical care medicine Wanderer, J. P., Leffert, L. R., Mhyre, J. M., Kuklina, E. V., Callaghan, W. M., Bateman, B. T. 2013; 41 (8): 1844-52

  Abstract

  To define the prevalence, indications, and temporal trends in obstetric-related ICU admissions.Descriptive analysis of utilization patterns.All hospitals within the state of Maryland.All antepartum, delivery, and postpartum patients who were hospitalized between 1999 and 2008.None.We identified 2,927 ICU admissions from 765,598 admissions for antepartum, delivery, or postpartum conditions using appropriate International Classification of Diseases, 9th Revision, Clinical Modification codes. The overall rate of ICU utilization was 419.1 per 100,000 deliveries, with rates of 162.5, 202.6, and 54.0 per 100,000 deliveries for the antepartum, delivery, and postpartum periods, respectively. The leading diagnoses associated with ICU admission were pregnancy-related hypertensive disease (present in 29.9% of admissions), hemorrhage (18.8%), cardiomyopathy or other cardiac disease (18.3%), genitourinary infection (11.5%), complications from ectopic pregnancies and abortions (10.3%), nongenitourinary infection (10.1%), sepsis (7.1%), cerebrovascular disease (5.8%), and pulmonary embolism (3.7%). We assessed for changes in the most common diagnoses in the ICU population over time and found rising rates of sepsis (10.1 per 100,000 deliveries to 16.6 per 100,000 deliveries, p = 0.003) and trauma (9.2 per 100,000 deliveries to 13.6 per 100,000 deliveries, p = 0.026) with decreasing rates of anesthetic complications (11.3 per 100,000 to 4.7 per 100,000, p = 0.006). The overall frequency of obstetric-related ICU admission and the rates for other indications remained relatively stable.Between 1999 and 2008, 419.1 per 100,000 deliveries in Maryland were complicated by ICU admission. Hospitals providing obstetric services should plan for appropriate critical care management and/or transfer of women with severe morbidities during pregnancy.

  View details for DOI 10.1097/CCM.0b013e31828a3e24

  View details for PubMedID 23648568

  View details for PubMedCentralID PMC3716838

• The risk of congenital malformations associated with exposure to β-blockers early in pregnancy: a meta-analysis. Hypertension (Dallas, Tex. : 1979) Yakoob, M. Y., Bateman, B. T., Ho, E., Hernandez-Diaz, S., Franklin, J. M., Goodman, J. E., Hoban, R. A. 2013; 62 (2): 375-81

  Abstract

  β-blockers are commonly used during the first trimester of pregnancy. Data about risks of congenital anomalies in offspring have not been summarized. We performed a meta-analysis to determine teratogenicity of β-blockers in early pregnancy. A systematic literature search was performed using PubMed, EMBASE, Cochrane Clinical Trials, and hand search. Meta-analyses were performed using random-effects models based on odds ratios (ORs). Prespecified subgroup analyses were performed to explore heterogeneity. Randomized controlled trials or observational studies examining risks of congenital malformations associated with first trimester β-blocker exposure compared with no exposure were included. Thirteen population-based case-control or cohort studies were identified. Based on meta-analyses, first-trimester oral β-blocker use showed no increased odds of all or major congenital anomalies (OR=1.00; 95% confidence interval, 0.91-1.10; 5 studies). However, in analyses examining organ-specific malformations, increased odds of cardiovascular defects (OR=2.01; 95% confidence interval, 1.18-3.42; 4 studies), cleft lip/palate (OR=3.11; 95% confidence interval, 1.79-5.43; 2 studies), and neural tube defects (OR=3.56; 95% confidence interval, 1.19-10.67; 2 studies) were observed. The effects on severe hypospadias were nonsignificant (1 study). Causality is difficult to interpret given the small number of heterogeneous studies and possibility of biases. Given the frequency of this exposure in pregnancy, further research is needed.

  View details for DOI 10.1161/HYPERTENSIONAHA.111.00833

  View details for PubMedID 23753416

  View details for PubMedCentralID PMC4086784

• Methylergonovine maleate and the risk of myocardial ischemia and infarction. American journal of obstetrics and gynecology Bateman, B. T., Huybrechts, K. F., Hernandez-Diaz, S., Liu, J., Ecker, J. L., Avorn, J. 2013; 209 (5): 459.e1-459.e13

  Abstract

  The purpose of this study was to examine the risks of acute coronary syndrome (ACS) and acute myocardial infarction (AMI) that are associated with methylergonovine maleate (Methergine; Novartis Pharmaceuticals Corporation, Plantation, FL) use in a large database of inpatient delivery admissions in the United States.We conducted a retrospective cohort study using data from the Premier Perspective Database and identified 2,233,630 women who were hospitalized for delivery between 2007 and 2011 (approximately one-seventh of all US deliveries during this period). Exposure was defined by a charge code for methylergonovine during the delivery hospitalization. Study outcomes included ACS and AMI. Propensity score matching was used to address potential confounding.Methylergonovine was administered to 139,617 patients (6.3%). Overall, 6 patients (0.004%) who were exposed to methylergonovine and 52 patients (0.002%) who were not exposed to methylergonovine had an ACS. Four patients (0.003%) who were exposed to methylergonovine and 44 patients (0.002%) in the not-exposed group had an AMI. After propensity score matching, the relative risk for ACS that was associated with methylergonovine exposure was 1.67 (95% confidence interval [CI], 0.40-6.97), and the risk difference was 1.44 per 100,000 patients (95% CI, -2.56 to 5.45); the relative risk for AMI that was associated with methylergonovine exposure was 1.00 (95% CI, 0.20-4.95), and the risk difference was 0.00 per 100,000 patients (95% CI, -3.47 to 3.47).Despite studying a very large proportion of US deliveries, we did not find a significant increase in the risk of ACS or AMI in women who received methylergonovine compared with those who did not; estimates were increased only modestly or not at all. The upper limit of the 95% CI of our analysis suggests that treatment with methylergonovine would result in no more than 5 additional cases of ACS and 3 additional cases of AMI per 100,000 exposed patients.

  View details for DOI 10.1016/j.ajog.2013.07.001

  View details for PubMedID 23850529

  View details for PubMedCentralID PMC4103983

• Outpatient calcium-channel blockers and the risk of postpartum haemorrhage: a cohort study. BJOG : an international journal of obstetrics and gynaecology Bateman, B. T., Hernandez-Diaz, S., Huybrechts, K. F., Palmsten, K., Mogun, H., Ecker, J. L., Seely, E. W., Fischer, M. A. 2013; 120 (13): 1668-76; dicussion 1676-7

  Abstract

  To determine whether outpatient exposure to calcium-channel blockers (CCBs) at the time of delivery is associated with an increased risk for postpartum haemorrhage (PPH).Cohort study.United States of America.Medicaid beneficiaries.We identified a cohort of 9750 patients with outpatient prescriptions for CCBs, methyldopa, or labetalol for pre-existing or gestational hypertension whose days of supply overlapped with delivery; 1226 were exposed to CCBs. The risk of PPH was compared in those exposed to CCBs to those exposed to methyldopa or labetalol. Propensity score matching and stratification were used to address potential confounding.The occurrence of PPH during the delivery hospitalisation.There were 27 patients exposed to CCBs (2.2%) and 232 patients exposed to methyldopa or labetalol (2.7%) who experienced PPH. After accounting for confounders, there was no meaningful association between CCB exposure and PPH in the propensity score matched (odds ratio 0.77, 95% CI 0.50-1.18) or stratified (odds ratio 0.79, 95% CI 0.53-1.19) analyses. Similar results were obtained across multiple sensitivity analyses.The outpatient use of CCBs in late pregnancy for the treatment of hypertension does not increase the risk of PPH.

  View details for DOI 10.1111/1471-0528.12428

  View details for PubMedID 24020971

  View details for PubMedCentralID PMC3866215

• Maternal sepsis mortality and morbidity during hospitalization for delivery: temporal trends and independent associations for severe sepsis. Anesthesia and analgesia Bauer, M. E., Bateman, B. T., Bauer, S. T., Shanks, A. M., Mhyre, J. M. 2013; 117 (4): 944-950

  Abstract

  Sepsis is currently the leading cause of direct maternal death in the United Kingdom. In this study, we aimed to determine frequency, temporal trends, and independent associations for severe sepsis during hospitalization for delivery in the United States.Data were obtained from the Nationwide Inpatient Sample for the years 1998 through 2008. The presence of severe sepsis was identified by the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes. Logistic regression analysis was used to assess temporal trends for sepsis, severe sepsis, and sepsis-related death and also to identify independent associations of severe sepsis.Of an estimated 44,999,260 hospitalizations for delivery, sepsis complicated 1:3333 (95% confidence interval [CI], 1:3151-1:3540) deliveries, severe sepsis complicated 1:10,823 (95% CI, 1:10,000-1:11,792) deliveries, and sepsis-related death complicated 1:105,263 (95% CI, 1:83,333-1:131,579) deliveries. While the overall frequency of sepsis was stable(P = 0.95), the risk of severe sepsis and sepsis-related death increased during the study period, (P < 0.001) and (P = 0.02), respectively. Independent associations for severe sepsis, with an adjusted odds ratio and lower bound 95% CI higher than 3, include congestive heart failure, chronic liver disease, chronic renal disease, systemic lupus erythematous, and rescue cerclage placement.Maternal severe sepsis and sepsis-related deaths are increasing in the United States. Severe sepsis often occurs in the absence of a recognized risk factor and underscores the need for developing systems of care that increase sensitivity for disease detection across the entire population. Physicians should enhance surveillance in patients with congestive heart failure, chronic liver disease, chronic renal disease, and systemic lupus erythematous and institute early treatment when signs of sepsis are emerging.

  View details for DOI 10.1213/ANE.0b013e3182a009c3

  View details for PubMedID 24023020

• Development of a comorbidity index for use in obstetric patients. Obstetrics and gynecology Bateman, B. T., Mhyre, J. M., Hernandez-Diaz, S., Huybrechts, K. F., Fischer, M. A., Creanga, A. A., Callaghan, W. M., Gagne, J. J. 2013; 122 (5): 957-965

  Abstract

  To develop and validate a maternal comorbidity index to predict severe maternal morbidity, defined as the occurrence of acute maternal end-organ injury, or mortality.Data were derived from the Medicaid Analytic eXtract for the years 2000-2007. The primary outcome was defined as the occurrence of maternal end-organ injury or death during the delivery hospitalization through 30 days postpartum. The data set was randomly divided into a two-thirds development cohort and a one-third validation cohort. Using the development cohort, a logistic regression model predicting the primary outcome was created using a stepwise selection algorithm that included 24-candidate comorbid conditions and maternal age. Each of the conditions included in the final model was assigned a weight based on its beta coefficient, and these were used to calculate a maternal comorbidity index.The cohort included 854,823 completed pregnancies, of which 9,901 (1.2%) were complicated by the primary study outcome. The derived score included 20 maternal conditions and maternal age. For each point increase in the score, the odds ratio for the primary outcome was 1.37 (95% confidence interval [CI] 1.35-1.39). The c-statistic for this model was 0.657 (95% CI 0.647-0.666). The derived score performed significantly better than available comorbidity indices in predicting maternal morbidity and mortality.This new maternal comorbidity index provides a simple measure for summarizing the burden of maternal illness for use in the conduct of epidemiologic, health services, and comparative effectiveness research.II.

  View details for DOI 10.1097/AOG.0b013e3182a603bb

  View details for PubMedID 24104771

  View details for PubMedCentralID PMC3829199

• Surgical procedures and outcomes among children with sickle cell disease. Anesthesia and analgesia Hyder, O., Yaster, M., Bateman, B. T., Firth, P. G. 2013; 117 (5): 1192-6

  Abstract

  Although children with sickle cell disease often undergo surgery, there are limited current epidemiological data for this pediatric population. We performed a database analysis to estimate population characteristics, surgical procedures, and perioperative outcomes in this population.We queried the Nationwide Inpatient Sample Database from 2000 to 2010 for discharges pertaining to patients <18 years of age having a diagnosis of sickle cell disease who underwent 1 or more surgical procedures during that admission. We abstracted surgical procedures using the Clinical Classifications Software procedure codes and the ICD-9-CM procedure codes. We described characteristics of patients undergoing the 6 most common procedures.During 2000 to 2010, 3.6 % (SE 0.12) of individual hospital discharges were of children with sickle cell disease who had undergone surgical procedures. The most frequent surgical procedures were cholecystectomy (1.47% [0.08]), tonsillectomy/adenoidectomy (0.81% [0.06]), splenectomy (0.62% [0.06]), repair of umbilical hernia (0.19% [0.02]), and appendectomy (0.17% [0.02]). Acute chest syndrome was recorded among 3.08% (0.60) of patients undergoing elective surgery. The incidence of stroke was 0.20% (0.11); death was reported in <11 patients (<0.20%).Surgical procedures such as cholecystectomy, tonsillectomy, splenectomy, hernia repair, and appendectomy account for a small but significant proportion of hospital admissions in children with sickle cell disease. Acute chest syndrome is among the most common complications of elective surgery, while stroke and death are rare.

  View details for DOI 10.1213/ANE.0b013e3182a44d74

  View details for PubMedID 24108258

• Preoperative Statin Use and Postoperative Acute Kidney Injury AMERICAN JOURNAL OF MEDICINE Brunelli, S. M., Waikar, S. S., Bateman, B. T., Chang, T. I., Lii, J., Garg, A. X., Winkelmayer, W. C., Choudhry, N. K. 2012; 125 (12): 1195-?

  Abstract

  Acute kidney injury is a frequent postoperative complication that confers increased mortality, morbidity, and costs. The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury.We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal, cardiac, thoracic, or vascular procedure between 2000 and 2010. Statin users were pair-matched to nonusers on the basis of surgery type, baseline kidney function, days from admission until surgery, and propensity score based on demographics, comorbid conditions, and concomitant medications. Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems, and on the need for renal replacement therapy. Associations between statin use and acute kidney injury were estimated by conditional logistic regression.Across various acute kidney injury definitions, statin use was consistently associated with a decreased risk: adjusted odds ratios (95% confidence intervals) varied from 0.74 (0.58-0.95) to 0.80 (0.71-0.90). Associations were similar among diabetics and nondiabetics, and across strata of baseline kidney function. The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery.Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. Future randomized clinical trials are needed to determine causality.

  View details for DOI 10.1016/j.amjmed.2012.06.021

  View details for Web of Science ID 000311217600020

  View details for PubMedID 23062398

  View details for PubMedCentralID PMC3597342

• Patterns of antihypertensive medication use in medicaid-eligible pregnant women Bateman, B. T., Hernandez-Diaz, S., Huybrechts, K., Palmsten, K., Fischer, M. A. WILEY. 2012: 170

  View details for Web of Science ID 000308131701350

• RECURRENCE OF POSTPARTUM HEMORRHAGE - A STUDY OF 538, 244 SWEDISH WOMEN Oberg, A. S., Palmsten, K., Bateman, B., Frisell, T., Langstrom, N., Hernandez-Diaz, S. OXFORD UNIV PRESS INC. 2012: S81

  View details for Web of Science ID 000322831400318

• Outcomes of Hospitalization in Pregnant Women with Brain Tumors: A Population-Based Study Terry, A., Barker, F., Leffert, L., Bateman, B., Souter, I., Plotkin, S. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000303204804098

• Reply: To PMID 22405526. American journal of obstetrics and gynecology Bateman, B. T., Callaghan, W. M., Kuklina, E. V. 2012; 206 (5): e5-6

  View details for DOI 10.1016/j.ajog.2012.02.039

  View details for PubMedID 22459344

  View details for PubMedCentralID PMC4576917

• Outcomes of hospitalization in pregnant women with CNS neoplasms: a population-based study. Neuro-oncology Terry, A. R., Barker, F. G., Leffert, L., Bateman, B. T., Souter, I., Plotkin, S. R. 2012; 14 (6): 768-76

  Abstract

  Managing a CNS neoplasm during pregnancy presents complex challenges, and population-based studies are lacking. We designed a retrospective cohort study using the Nationwide Inpatient Sample (NIS) to investigate pregnancy outcomes in women with CNS neoplasms. We constructed a logistic regression model for maternal mortality, preterm labor, intrauterine growth restriction (IUGR), and Caesarean delivery, controlling for age, comorbidities, and demographic characteristics. We identified 379 malignant brain tumors, 437 benign brain tumors, and 44 spine tumors among 19 million pregnancy-related admissions from 1988 through 2009. Malignant brain tumors were associated with maternal mortality (odds ratio [OR], 143), preterm labor (OR, 3.4), and IUGR (OR, 2.9). Benign brain tumors were associated with preterm labor (OR, 2.3). A diagnosis of hyperemesis gravidarum was more common in malignant (OR, 2.2) and benign (OR, 2.8) brain tumors. Compared with the general population, Caesarean delivery was more frequent for malignant (OR, 6.4) and benign (OR, 2.8) brain tumors and spine tumors (OR, 3.9). Admission without delivery was more common for malignant (OR, 8.6) and benign (OR, 4.3) brain tumors and spine tumors (OR, 3.8; P < .05 for all outcomes). Thirty-three percent of all hospitalizations involved neurosurgical procedures, but pregnancy complications were not significantly more likely to occur in surgical patients. In conclusion, malignant brain tumors were associated with adverse pregnancy outcomes, and CNS neoplasms were associated with higher rates of Caesarean delivery. Additional research is needed to improve understanding of obstetric risk in these patients and to assist with treatment, counseling, and monitoring during delivery.

  View details for DOI 10.1093/neuonc/nos078

  View details for PubMedID 22513749

  View details for PubMedCentralID PMC3367848

• Hypertension in women of reproductive age in the United States: NHANES 1999-2008. PloS one Bateman, B. T., Shaw, K. M., Kuklina, E. V., Callaghan, W. M., Seely, E. W., Hernández-Díaz, S. 2012; 7 (4): e36171

  Abstract

  To examine the epidemiology of hypertension in women of reproductive age.Using NHANES from 1999-2008, we identified 5,521 women age 20-44 years old. Hypertension status was determined using blood pressure measurements and/or self-reported medication use.The estimated prevalence of hypertension in women of reproductive age was 7.7% (95% confidence interval (CI): 6.9%-8.5%). The prevalence of anti-hypertensive pharmacologic therapy was 4.2% (95% CI 3.5%-4.9%). The prevalence of hypertension was relatively stable across the study period; the age and race adjusted odds of hypertension in 2007-2008 did not differ significantly from 1999-2000 (odds ratio 1.2, CI 0.8 to 1.7, p = 0.45). Significant independent risk factors associated with hypertension included older age, non-Hispanic black race (compared to non-Hispanic whites), diabetes mellitus, chronic kidney disease, and higher body mass index. The most commonly used antihypertensive medications included diuretics, angiotensin-converting enzyme inhibitors (ACE), and beta blockers.Hypertension occurs in about 8% of women of reproductive age. There are remarkable differences in the prevalence of hypertension between racial/ethnic groups. Obesity is a risk factor of particular importance in this population because it affects over 30% of young women in the U.S., is associated with more than 4 fold increased risk of hypertension, and is potentially modifiable.

  View details for DOI 10.1371/journal.pone.0036171

  View details for PubMedID 22558371

  View details for PubMedCentralID PMC3340351

• The association of maternal race and ethnicity and the risk of postpartum hemorrhage. Anesthesia and analgesia Bryant, A., Mhyre, J. M., Leffert, L. R., Hoban, R. A., Yakoob, M. Y., Bateman, B. T. 2012; 115 (5): 1127-36

  Abstract

  There are profound racial and ethnic disparities in obstetric outcomes in the United States, but little is known about disparities in risk of postpartum hemorrhage (PPH). We explored the association of race and ethnicity on the risk of PPH due to uterine atony with sequential adjustment for possible mediating factors.This analysis was based on the Nationwide Inpatient Sample, from between 2005 and 2008. The frequencies of atonic PPH and atonic PPH resulting in transfusion or hysterectomy were estimated. We developed multivariable logistic regression models to estimate the odds of these outcomes in maternal racial/ethnic groups by sequentially adding potential mediators.Hispanic ethnicity and Asian/Pacific Islander race were associated with a statistically significant increased odds of atonic PPH in comparison with Caucasians, despite adjustment for potential mediators (adjusted odds ratio [OR] for Hispanics: 1.21, 99% confidence interval [1.18, 1.25]; for Asians/Pacific Islanders: 1.31 [1.25, 1.38], with Caucasians as reference). Similar results were observed for these racial/ethnic groups for atonic PPH resulting in transfusion or hysterectomy.Hispanic ethnicity and Asian/Pacific Islander race are significant risk factors for atonic PPH independent of measured potential mediators; biological differences may play a role.

  View details for DOI 10.1213/ANE.0b013e3182691e62

  View details for PubMedID 22886840

• Patterns of outpatient antihypertensive medication use during pregnancy in a Medicaid population. Hypertension (Dallas, Tex. : 1979) Bateman, B. T., Hernandez-Diaz, S., Huybrechts, K. F., Palmsten, K., Mogun, H., Ecker, J. L., Fischer, M. A. 2012; 60 (4): 913-20

  Abstract

  Hypertensive disorders occur in approximately 6% to 8% of all pregnancies and are a significant source of maternal and fetal morbidity. Little is known about the range of agents routinely used in practice. We used Medicaid claims from 2000 to 2007 to identify completed pregnancies. We included women who were Medicaid beneficiaries from at least 3 months prior to last menstrual period to 1 month postdelivery, and were successfully linked to infant records. Maternal exposure to antihypertensive medications was derived from Medicaid pharmacy claim files, and duration of exposure was assigned based on the days' supply dispensed. We identified 1,106,757 Medicaid patients in our cohort, of whom 48,453 (4.4%) were exposed to antihypertensive medications during pregnancy. The prevalence of antihypertensive use increased from 3.5% to 4.9% during the study period. Antihypertensive medication users were older than nonusers, more likely to be white or black, and more likely to have comorbid diabetes mellitus and renal disease. Overall, 1.9% of pregnant women were exposed during the first trimester, 1.7% during the second trimester, and 3.2% during the third trimester. The range of antihypertensive medications to which patients were exposed was highly heterogeneous and frequently included agents other than methyldopa or labetalol. Angiotensin-converting enzyme inhibitor exposure, which is contraindicated in late pregnancy, occurred in 928 (4.9%) antihypertensive medication users in the second trimester and 383 (1.1%) in the third trimester. Antihypertensive use during pregnancy is relatively common and increasing. The wide range of agents used during pregnancy includes medications considered contraindicated during pregnancy.

  View details for DOI 10.1161/HYPERTENSIONAHA.112.197095

  View details for PubMedID 22966012

  View details for PubMedCentralID PMC3501756

• Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study. BMJ (Clinical research ed.) Grosse-Sundrup, M., Henneman, J. P., Sandberg, W. S., Bateman, B. T., Uribe, J. V., Nguyen, N. T., Ehrenfeld, J. M., Martinez, E. A., Kurth, T., Eikermann, M. 2012; 345: e6329

  Abstract

  To determine whether use of intermediate acting neuromuscular blocking agents during general anesthesia increases the incidence of postoperative respiratory complications.Prospective, propensity score matched cohort study.General teaching hospital in Boston, Massachusetts, United States, 2006-10.18,579 surgical patients who received intermediate acting neuromuscular blocking agents during surgery were matched by propensity score to 18,579 reference patients who did not receive such agents.The main outcome measures were oxygen desaturation after extubation (hemoglobin oxygen saturation <90% with a decrease in oxygen saturation after extubation of >3%) and reintubations requiring unplanned admission to an intensive care unit within seven days of surgery. We also evaluated effects on these outcome variables of qualitative monitoring of neuromuscular transmission (train-of-four ratio) and reversal of neuromuscular blockade with neostigmine to prevent residual postoperative neuromuscular blockade.The use of intermediate acting neuromuscular blocking agents was associated with an increased risk of postoperative desaturation less than 90% after extubation (odds ratio 1.36, 95% confidence interval 1.23 to 1.51) and reintubation requiring unplanned admission to an intensive care unit (1.40, 1.09 to 1.80). Qualitative monitoring of neuromuscular transmission did not decrease this risk and neostigmine reversal increased the risk of postoperative desaturation less than 90% (1.32, 1.20 to 1.46) and reintubation (1.76, 1.38 to 2.26).The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications. Our data suggest that the strategies used in our trial to prevent residual postoperative neuromuscular blockade should be revisited.

  View details for DOI 10.1136/bmj.e6329

  View details for PubMedID 23077290

  View details for PubMedCentralID PMC3473088

• Obstructive sleep apnea predicts adverse perioperative outcome: evidence for an association between obstructive sleep apnea and delirium. Anesthesiology Bateman, B. T., Eikermann, M. 2012; 116 (4): 753-5

  View details for DOI 10.1097/ALN.0b013e31824b96e1

  View details for PubMedID 22337163

• Peripartum hysterectomy in the United States: nationwide 14 year experience. American journal of obstetrics and gynecology Bateman, B. T., Mhyre, J. M., Callaghan, W. M., Kuklina, E. V. 2012; 206 (1): 63.e1-8

  Abstract

  The objective of the study was to examine the trends in the rate of peripartum hysterectomy and the contribution of changes in maternal characteristics to these trends.This was a cross-sectional study of peripartum hysterectomy identified from hospitalizations for delivery recorded in the 1994-2007 Nationwide Inpatient Sample.The overall rate of peripartum hysterectomy increased by 15% during the study period. The rate of hysterectomy for abnormal placentation increased by 1.2-fold; adjustment for previous cesarean delivery explained nearly all of this increase. The rate of hysterectomy for uterine atony following repeat cesarean delivery increased nearly 4-fold, following primary cesarean delivery approximately 2.5-fold, and following vaginal delivery about 1.5-fold. This fast growing trend in peripartum hysterectomy secondary to uterine atony was also largely explained by increasing rates of primary and repeat cesareans.Rates of peripartum hysterectomy increased substantially in the United States from 1994 to 2007; much of this increase was due to rising rates of cesarean delivery.

  View details for DOI 10.1016/j.ajog.2011.07.030

  View details for PubMedID 21982025

• Trends in the hospitalization of ischemic stroke in the United States, 1998-2007. International journal of stroke : official journal of the International Stroke Society Lee, L. K., Bateman, B. T., Wang, S., Schumacher, H. C., Pile-Spellman, J., Saposnik, G. 2012; 7 (3): 195-201

  Abstract

  The late 1990s/early 2000s was a time of change in both the prevention and acute care of ischemic stroke, with primary prevention driven by increased utilization of antihypertensive, antiplatelet, anticoagulation, and lipid-lowering agents.To examine whether ischemic stroke hospitalization rates and outcomes in the United States have changed.We retrospectively identified 894 169 hospitalizations with a primary diagnosis of ischemic stroke from 1 January 1998 through to 31 December 2007 in the Nationwide Inpatient Sample, the largest all-payer healthcare database in the United States. Annual, national case estimates were combined with US Census data to derive age-adjusted and age-specific population hospitalization rates. Temporal trends were tested using linear regression.From 1998 through 2007, there were an estimated 4 382 336 ischemic stroke hospitalizations in the United States. Overall, the age-adjusted rate of ischemic stroke hospitalization decreased from 184 to 128 per 100 000 (P < 0·0001). Age-specific rates decreased among those 55+ years old (P < 0·0001), but increased among those 25-34 and 35-44 years old (P < 0·001 and P < 0·0001, respectively). Rates among those <25 and 45-54 years old were unchanged. In-hospital mortality decreased from 7·0% (standard error 0·1) to 5·4% (standard error 0·1) (P < 0·0001). Case proportion at the highest quintile of hospitals by annual caseload increased from 54·0% (standard error 2·1) to 61·8% (standard error 2·0) (P < 0·0001). Mean adjusted hospitalization costs increased from $9273 (standard deviation 199) to $10 524 (standard deviation 77) (P < 0·0001).In 1998 through to 2007, the overall rate of ischemic stroke hospitalization in the United States decreased. However, rates among young adults increased. In-hospital mortality rates decreased over the study period.

  View details for DOI 10.1111/j.1747-4949.2011.00700.x

  View details for PubMedID 22151527

• Peripartum subarachnoid hemorrhage: nationwide data and institutional experience. Anesthesiology Bateman, B. T., Olbrecht, V. A., Berman, M. F., Minehart, R. D., Schwamm, L. H., Leffert, L. R. 2012; 116 (2): 324-33

  Abstract

  Subarachnoid hemorrhage (SAH) in pregnancy occurs because of a variety of etiologies, which range from ruptured aneurysms to benign venous bleeding. The more malignant etiologies represent an important cause of maternal morbidity and mortality. We sought to investigate the epidemiology and mechanisms of pregnancy-related SAH.Using the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, we extracted pregnancy-related admissions for women ages 15-44 from 1995-2008 and identified admissions complicated by SAH. Logistic regression identified independent predictors of SAH. Outcomes and risk factors were then compared with age-matched, nonpregnant women with SAH. We also analyzed our institution's experience with pregnancy-related SAH.There were 639 cases (5.8 per 100,000 deliveries) of pregnancy-related SAH in the cohort during the study period; SAH was associated with 4.1% of all pregnancy-related in-hospital deaths. More than half of the SAH cases occurred postpartum. Advancing age, African-American race, Hispanic ethnicity, hypertensive disorders, coagulopathy, tobacco, drug or alcohol abuse, intracranial venous thrombosis, sickle cell disease, and hypercoagulability were independent risk factors for pregnancy-related SAH. Compared with SAH in nonpregnant controls, pregnancy-related SAH had lower clipping/coiling rates (12.7% vs. 44.5%, P < 0.001). We identified 12 cases of pregnancy-related SAH in our hospital, the majority of which presented postpartum and with severe headache.SAH during pregnancy results from a range of etiologies, and is less likely to be because of a cerebral aneurysm than SAH occurring in the nonpregnant patient. Peripartum SAH frequently occurs in the setting of hypertensive disorders.

  View details for DOI 10.1097/ALN.0b013e3182410b22

  View details for PubMedID 22166951

• Prevalence, trends, and outcomes of chronic hypertension: a nationwide sample of delivery admissions. American journal of obstetrics and gynecology Bateman, B. T., Bansil, P., Hernandez-Diaz, S., Mhyre, J. M., Callaghan, W. M., Kuklina, E. V. 2012; 206 (2): 134.e1-8

  Abstract

  We sought to define the prevalence, trends, and outcomes of primary and secondary chronic hypertension in a population-based sample of deliveries.An estimated 56,494,634 deliveries were identified from the 1995 through 2008 Nationwide Inpatient Sample. The association of primary and secondary chronic hypertension with adverse fetal and maternal outcomes was evaluated using regression modeling and adjusted population-attributable fractions were calculated.During the study period, the prevalence of primary and secondary hypertension increased from 0.90% in 1995 through 1996 to 1.52% in 2007 through 2008 (P for trend < .001) and from 0.07% to 0.24% (P for trend < .001), respectively. The population-attributable fraction for chronic hypertension was considerable for many maternal adverse outcomes, including acute renal failure (21%), pulmonary edema (14%), preeclampsia (11%), and in-hospital mortality (10%).Primary and secondary chronic hypertension were both strongly associated with adverse pregnancy outcomes and accounted for a substantial fraction of maternal morbidity. Prioritizing research efforts in this area is needed.

  View details for DOI 10.1016/j.ajog.2011.10.878

  View details for PubMedID 22177190

  View details for PubMedCentralID PMC4103984

• OUTCOMES OF HOSPITALIZATION AMONG PREGNANT WOMEN WITH CNS NEOPLASMS: A POPULATION-BASED STUDY Terry, A. R., Barker, F. G., Leffert, L. R., Bateman, B., Souter, I., Plotkin, S. R. OXFORD UNIV PRESS INC. 2011: 28

  View details for Web of Science ID 000297026600119

• Influence of patient comorbidities on the risk of near-miss maternal morbidity or mortality. Anesthesiology Mhyre, J. M., Bateman, B. T., Leffert, L. R. 2011; 115 (5): 963-72

  Abstract

  Maternal morbidity and mortality are increased in the United States compared with that of other developed countries. The objective of this investigation is to determine the extent to which it is possible to predict which patients will experience near-miss morbidity or mortality.The authors defined near-miss morbidity as end-organ injury associated with length of stay greater than the 99 percentile or discharge to a second medical facility, and identified all cases of near-miss morbidity or death from admissions for delivery in the 2003-2006 Nationwide Inpatient Sample. Logistic regression was used to examine the effect of maternal characteristics on rates of near-miss morbidity/mortality.Approximately 1.3 per 1,000 hospitalizations for delivery was complicated by near-miss morbidity/mortality as defined in this study (95% CI 1.3-1.4). Most of these events (58.3%) occurred in 11.8% of the delivering population-in those women with important medical comorbidities or obstetric complications identified before admission for delivery. The highest rates were noted among women with pulmonary hypertension (98.0 cases per 1,000 deliveries), malignancy (23.4 per 1,000), and systemic lupus erythematosus (21.1 per 1,000).Risk for near-miss morbidity or mortality is substantially increased among an identifiable subset of pregnant women. To the extent that antepartum multidisciplinary coordination and high-quality intrapartum care improve delivery outcomes for women with significant antepartum medical and obstetric disease, then public health investments to reduce the national burden of delivery-related near-miss morbidity and mortality will have the greatest effect by focusing resources on identifying and serving these high-risk groups.

  View details for DOI 10.1097/ALN.0b013e318233042d

  View details for PubMedID 21934482

• Pregnancy complications and prevention of cardiovascular disease in women: stay tuned. Journal of women's health (2002) Kuklina, E. V., Bateman, B. T. 2011; 20 (5): 657-9

  View details for DOI 10.1089/jwh.2011.2827

  View details for PubMedID 21599426

• Pus in the ventricles of a patient with a lumbar cerebrospinal fluid drain for a thoracoabdominal aneurysm repair. Anesthesiology Charnin, J. E., Bateman, B. T., Bittner, E. A. 2011; 115 (6): 1302

  View details for DOI 10.1097/ALN.0b013e3182267c30

  View details for PubMedID 21709541

• Perioperative ischemic stroke in non-cardiovascular surgery patients. Journal of anesthesia Kikura, M., Bateman, B. T., Tanaka, K. A. 2010; 24 (5): 733-8

  Abstract

  Perioperative ischemic stroke occurs in approximately 0.08-0.7% of patients after non-cardiovascular surgery and confers a significant risk of morbidity and mortality. The mortality rate of this major complication is similar in non-cardiovascular and cardiovascular surgery. Its incidence appears to be similar in Japan, Europe, and the United States. Perioperative physicians should be aware of the pathophysiology and predictors of ischemic stroke, and the anti-thrombotic strategies to prevent it. The main causes of perioperative ischemic stroke include cerebral atherothrombosis; lacuna stroke; cardiac thrombi due to atrial fibrillation; dehydration; hypotension; and perioperative systemic hypercoagulability. Perioperative management includes detailed informed consent regarding potential stroke risks, counseling, careful surgical treatment decisions, and identification of the high-risk patient for perioperative antithrombotic strategies. The 2009 Japanese guidelines for the management of stroke recommend using the appropriate intravenous infusions to avoid dehydration and consideration of anticoagulation in the patients who are at high risk for thrombosis and embolism while antithrombotic agents are discontinued. Understanding how to prevent perioperative ischemic stroke remains a challenge. In this article, we review the incidence, timing of the occurrence, mortality, risk factors, and pathophysiology of perioperative ischemic stroke in the non-cardiovascular surgery patient.

  View details for DOI 10.1007/s00540-010-0969-3

  View details for PubMedID 20549522

• The epidemiology of postpartum hemorrhage in a large, nationwide sample of deliveries. Anesthesia and analgesia Bateman, B. T., Berman, M. F., Riley, L. E., Leffert, L. R. 2010; 110 (5): 1368-73

  Abstract

  In this study, we sought to (1) define trends in the incidence of postpartum hemorrhage (PPH), and (2) elucidate the contemporary epidemiology of PPH focusing on risk factors and maternal outcomes related to this delivery complication.Hospital admissions for delivery were extracted from the Nationwide Inpatient Sample, the largest discharge dataset in the United States. Using International Classification of Diseases, Clinical Modification (ninth revision) codes, deliveries complicated by PPH were identified, as were comorbid conditions that may be risk factors for PPH. Temporal trends in the incidence of PPH from 1995 to 2004 were assessed. Logistic regression was used to identify risk factors for the most common etiology of PPH-uterine atony.In 2004, PPH complicated 2.9% of all deliveries; uterine atony accounted for 79% of the cases of PPH. PPH was associated with 19.1% of all in-hospital deaths after delivery. The overall rate of PPH increased 27.5% from 1995 to 2004, primarily because of an increase in the incidence of uterine atony; the rates of PPH from other causes including retained placenta and coagulopathy remained relatively stable during the study period. Logistic regression modeling identified age <20 or > or =40 years, cesarean delivery, hypertensive diseases of pregnancy, polyhydramnios, chorioamnionitis, multiple gestation, retained placenta, and antepartum hemorrhage as independent risk factors for PPH from uterine atony that resulted in transfusion. Excluding maternal age and cesarean delivery, one or more of these risk factors were present in only 38.8% of these patients.PPH is a relatively common complication of delivery and is associated with substantial maternal morbidity and mortality. It is increasing in frequency in the United States. PPH caused by uterine atony resulting in transfusion often occurs in the absence of recognized risk factors.

  View details for DOI 10.1213/ANE.0b013e3181d74898

  View details for PubMedID 20237047

• Temporal trends in the epidemiology of severe postoperative sepsis after elective surgery: a large, nationwide sample. Anesthesiology Bateman, B. T., Schmidt, U., Berman, M. F., Bittner, E. A. 2010; 112 (4): 917-25

  Abstract

  Multiple studies have used administrative datasets to examine the epidemiology of sepsis in general, but the entity of postoperative sepsis has been studied less intensively. Therefore, we undertook an analysis of the epidemiology of postoperative sepsis using the Nationwide Inpatient Sample, the largest in-patient dataset available in the United States.Elective admissions of patients aged 18 yr or older with a length of stay more than 3 days for any 1 of the 20 most common elective operative procedures were extracted from the dataset for the years 1997-2006. Postoperative sepsis was defined using the appropriate International Classification of Diseases, Ninth Revision, Clinical Modification codes; severe sepsis was defined as sepsis along with organ dysfunction. Logistic regression was used to assess the significance of temporal trends after adjusting for relevant demographic characteristics, operative procedure, and comorbid conditions.We identified 2,039,776 admissions for analysis. The rate of severe sepsis increased from 0.3% in 1997 to 0.9% in 2006. This trend persisted after adjusting for relevant covariables-the adjusted odds ratio of severe sepsis per year increase in the study period was 1.12 (95% CI, 1.11-1.13; P < 0.001). The in-hospital mortality rate for patients with severe postoperative sepsis declined from 44.4% in 1997 to 34.0% in 2006; this trend also persisted after adjustment for relevant covariables-the adjusted odds ratio per year was 0.94 (95% CI, 0.93-0.95; P < 0.001).During the 10-yr period that we studied, there was a marked increase in the rate of severe postoperative sepsis but a concomitant decrease in the in-hospital mortality rate in severe sepsis.

  View details for DOI 10.1097/ALN.0b013e3181cea3d0

  View details for PubMedID 20357565

• Commonly used eponyms in anesthesia. Journal of clinical anesthesia Bateman, B. T., Alston, T. A. 2009; 21 (1): 67-71

  Abstract

  Names with eponym status in present-day anesthesia include Apgar, Bier, Bovie, Esmarch, Fick, Foley, Ganz, Hofmann, Huber, Joule, Luer, Macintosh, Magill, Mallampati, Miller, Ovassapian, Pascal, Ringer, Seldinger, Sellick, Swan, Trendelenburg, Tuohy, Valsalva, and Yankauer. A discussion of the people behind the eponyms, which may make these commonly used terms more interesting and provides a sense of the history of the specialty of anesthesia, is presented.

  View details for DOI 10.1016/j.jclinane.2008.05.027

  View details for PubMedID 19232946

• Perioperative acute ischemic stroke in noncardiac and nonvascular surgery: incidence, risk factors, and outcomes. Anesthesiology Bateman, B. T., Schumacher, H. C., Wang, S., Shaefi, S., Berman, M. F. 2009; 110 (2): 231-8

  Abstract

  Perioperative acute ischemic stroke (AIS) is a recognized complication of noncardiac, nonvascular surgery, but few data are available regarding incidence and effect on outcome. This study examines the epidemiology of perioperative AIS in three common surgeries: hemicolectomy, total hip replacement, and lobectomy/segmental lung resection.Discharges for patients aged 18 yr or older who underwent any of the surgical procedures listed above were extracted from the Nationwide Inpatient Sample, an administrative database that contains 20% of all discharges from non-Federal hospitals each year, for years 2000 to 2004. Using appropriate International Classification of Diseases, 9th revision, Clinical Modification codes, patients with perioperative AIS were identified, as were comorbid conditions that may be risk factors for perioperative AIS. Multivariate logistic regression was performed to identify independent predictors of perioperative AIS and to ascertain the effect of AIS on outcome.A total of 0.7% of 131,067 hemicolectomy patients, 0.2% of 201,235 total hip replacement patients, and 0.6% of 39,339 lobectomy/segmental lung resection patients developed perioperative AIS. For patients older than 65 yr, AIS rose to 1.0% for hemicolectomy, 0.3% for hip replacement, and 0.8% for pulmonary resection. Multivariate logistic regression analysis revealed renal disease (odds ratio, 3.0), atrial fibrillation (odds ratio, 2.0), history of stroke (odds ratio, 1.6), and cardiac valvular disease (odds ratio, 1.5) to be the most significant risk factors for perioperative AIS.Perioperative AIS is an important source of morbidity and mortality associated with noncardiac, nonvascular surgery, particularly in elderly patients and patients with atrial fibrillation, valvular disease, renal disease, or previous stroke.

  View details for DOI 10.1097/ALN.0b013e318194b5ff

  View details for PubMedID 19194149

• Young-onset Parkinson's disease: hospital utilization and medical comorbidity in a nationwide survey. Neuroepidemiology Louis, E. D., Henchcliffe, C., Bateman, B. T., Schumacher, C. 2007; 29 (1-2): 39-43

  Abstract

  10% of Parkinson's disease (PD) patients have young-onset PD (YOPD). We compared YOPD patients to control patients in terms of hospital utilization and outcomes and medical comorbidities during hospitalization.The Nationwide Inpatient Sample (NIS) provides yearly data on hospital admissions and discharges from approximately 1,000 hospitals. NIS data sets (1998-2003) were used to identify persons aged 18-40 years, including 714 PD patients and 2,007 randomly selected control patients (1:3 matching).Hospital length of stay (p < 0.001) and number of discharge diagnoses (p < 0.001) were higher in PD patients than controls. PD patients were more likely than controls to be discharged to a short-term hospital (odds ratio, OR, 2.23, 95% confidence interval, CI, 1.30-3.84, p = 0.004) or a skilled nursing facility (OR 4.14, 95% CI 3.06-5.61, p < 0.001); 20.4% required transfer to a short-term hospital or another facility. The most common discharge Diagnosis-Related Group code in PD patients was psychosis (23% of patients) whereas pneumonia and hip or pelvic fractures were not associated with PD.YOPD patients had greater healthcare utilization and hospital morbidity than controls. Upon discharge, 1 in 5 required transfer to a short-term hospital or another facility. Psychosis was the most common comorbidity whereas several comorbidities associated with older PD patients were not common.

  View details for DOI 10.1159/000108916

  View details for PubMedID 17898522

• Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies. Neuroradiology Pan, J., Konstas, A. A., Bateman, B., Ortolano, G. A., Pile-Spellman, J. 2007; 49 (2): 93-102

  Abstract

  Restoration of blood flow following ischemic stroke can be achieved by means of thrombolysis or mechanical recanalization. However, for some patients, reperfusion may exacerbate the injury initially caused by ischemia, producing a so-called "cerebral reperfusion injury". Multiple pathological processes are involved in this injury, including leukocyte infiltration, platelet and complement activation, postischemic hyperperfusion, and breakdown of the blood-brain barrier.Magnetic resonance imaging (MRI) can provide extensive information on this process of injury, and may have a role in the future in stratifying patients' risk for reperfusion injury following recanalization. Moreover, different MRI modalities can be used to investigate the various mechanisms of reperfusion injury. Antileukocyte antibodies, brain cooling and conditioned blood reperfusion are potential therapeutic strategies for lessening or eliminating reperfusion injury, and interventionalists may play a role in the future in using some of these therapies in combination with thrombolysis or embolectomy. The present review summarizes the mechanisms of reperfusion injury and focuses on the way each of those mechanisms can be evaluated by different MRI modalities. The potential therapeutic strategies are also discussed.

  View details for DOI 10.1007/s00234-006-0183-z

  View details for PubMedID 17177065

  View details for PubMedCentralID PMC1786189

• Nationwide data confirms absence of 'July phenomenon' in obstetrics: it's safe to deliver in July. Journal of perinatology : official journal of the California Perinatal Association Ford, A. A., Bateman, B. T., Simpson, L. L., Ratan, R. B. 2007; 27 (2): 73-6

  Abstract

  To determine whether operator-dependent obstetric complications occur at higher rates in July at teaching hospitals using a large, nationwide sample of deliveries.Data for this study were obtained from an administrative dataset, the Nationwide Inpatient Sample, for the years 1998 to 2002. Singleton deliveries and singleton livebirth admissions among Medicaid patients at teaching hospitals with OB/GYN residents working on the Labor and Delivery ward were identified. Outcomes for various complications for these patients in the month of July were compared to those occurring in the months from August to June.The 26,546 women in our cohort who delivered in July were compared to the 272,584 women delivering during August to June. There were no statistically significant differences in the rates of cesarean delivery, urethral/bladder injury, third or fourth degree lacerations, wound complications, postpartum hemorrhage, transfusion, shoulder dystocia, chorioamnionitis or anesthesia-related complications. The 26,175 singleton livebirth admissions in July were compared to 266,158 such admissions in August to June. There were no statistically significant differences in the rates of brachial plexus injury (0.2 vs 0.2%, P=0.824) or birth asphyxia (0.1 vs 0.1%, P=0.643).This study shows no increased rate of operator-dependent complications of delivery at teaching hospitals nationwide in the month of July.

  View details for DOI 10.1038/sj.jp.7211635

  View details for PubMedID 17262037

• Use of thrombolysis in acute ischemic stroke: analysis of the Nationwide Inpatient Sample 1999 to 2004. Annals of emergency medicine Schumacher, H. C., Bateman, B. T., Boden-Albala, B., Berman, M. F., Mohr, J. P., Sacco, R. L., Pile-Spellman, J. 2007; 50 (2): 99-107

  Abstract

  The aim of this study is to characterize hospital and patient characteristics associated with administration of thrombolysis in acute ischemic stroke patients in the United States.This retrospective, observational, cohort study used data from the Nationwide Inpatient Sample, an administrative discharge database. A total of 366,194 hospitalizations admitted through the emergency department with a primary diagnosis of acute ischemic stroke were selected for analysis. The primary outcome considered in this study is whether the patient received thrombolytic therapy on hospital day 0 or 1.Thrombolysis was used in 1.12% (95% confidence interval [CI] 0.95% to 1.32%) of ischemic stroke hospitalizations. Most hospitals (69.5%; 95% CI 68.4% to 70.6%) treating ischemic stroke patients did not use thrombolysis during the study period. For the hospitals that used thrombolysis, the mean annual number of patients treated with thrombolysis per hospital was 3.06 (95% CI 2.68 to 3.44). In the binary logistic regression analysis, hospital characteristics associated with high use of thrombolysis were teaching hospital status and increasing number of stroke patients treated annually. Patient characteristics associated with higher use of thrombolysis were age younger than 55 years, male sex, and low comorbidity as measured by the modified Charlson Index; white race; and private self-pay health insurance.Use of thrombolysis for ischemic stroke in the United States from 1999 to 2004 was infrequent and showed significant differences, depending on hospital and patient demographic characteristics.

  View details for DOI 10.1016/j.annemergmed.2007.01.021

  View details for PubMedID 17478010

• Convulsive status epilepticus after ischemic stroke and intracerebral hemorrhage: frequency, predictors, and impact on outcome in a large administrative dataset. Neurocritical care Bateman, B. T., Claassen, J., Willey, J. Z., Hirsch, L. J., Mayer, S. A., Sacco, R. L., Schumacher, H. C. 2007; 7 (3): 187-93

  Abstract

  Relatively little is known about the epidemiology of generalized convulsive status epilepticus (GCSE) in acute ischemic and hemorrhagic stroke. We examined the occurrence of GCSE in acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) using a large discharge database.Data were derived from the Nationwide Inpatient Sample for the years 1994-2002. Using the appropriate ICD-9-CM codes, patients admitted through the emergency room with a diagnosis of AIS or ICH were selected for analysis. From these patients, those coded as having GCSE were identified. Multivariate logistic regression was performed using clinical elements available in the database to identify independent predictors of GCSE. The association between GCSE and various outcome measures was also assessed.The cohort included 718,531 hospitalizations with AIS and 102,763 with ICH. GCSE developed in 1,415 (0.2%) of the AIS cohort and 266 (0.3%) of the ICH cohort. For the AIS cohort, female sex, African American race, renal disease, alcohol abuse, sodium imbalance, and hemorrhagic transformation were associated with higher rates, while increasing age, hypertension, and diabetes mellitus were associated with lower rates of GCSE. For the ICH cohort, African American and Hispanic race, renal disease, coagulopathy, brain tumor, alcohol abuse, and sodium imbalance were associated with higher rates, while increasing age and hypertension were associated with lower rates of GCSE. GCSE was associated with higher rates of adverse outcomes.GCSE is a rare but serious complication in the setting of acute ischemic stroke and intracerebral hemorrhage.

  View details for DOI 10.1007/s12028-007-0056-2

  View details for PubMedID 17503112

• Generalized convulsive status epilepticus after nontraumatic subarachnoid hemorrhage: the nationwide inpatient sample. Neurosurgery Claassen, J., Bateman, B. T., Willey, J. Z., Inati, S., Hirsch, L. J., Mayer, S. A., Sacco, R. L., Schumacher, H. C. 2007; 61 (1): 60-4; discussion 64-5

  Abstract

  To identify the frequency of and impact on outcome of generalized convulsive status epilepticus (GCSE) among patients with nontraumatic subarachnoid hemorrhage (SAH).We used the Nationwide Inpatient Sample, a database of admissions to nonfederal United States hospitals between 1994 and 2002, for this study. From this database, we identified all adult patients with nontraumatic SAH who were admitted through the emergency department. Independent predictors of GCSE and mortality were identified using multivariate logistic regression. Multivariate linear regression analysis was used to determine whether GCSE was independently associated with increased cost and/or duration of hospitalization.Among the 29,998 patients hospitalized with nontraumatic SAH, GCSE was reported to occur in 0.2% of patients (N = 73 patients). GCSE occurred more frequently among those in the youngest tertiale (49 years old or younger; odds ratio, 3.2; 95% confidence interval, 2.0-5.1), those with renal disease (odds ratio, 4.8; 95% confidence interval, 2.6-8.8), and those who did not undergo a neurosurgical procedure involving a craniotomy (odds ratio, 2.2; 95% confidence interval, 1.3-3.8). GCSE was independently associated with higher in-hospital mortality (48% versus 33% of patients; odds ratio, 2.1; 95% confidence interval, 1.3-3.4; P = 0.002) and longer (9 versus 7 days; P = 0.016) and more expensive (US $39,677 versus US $26,686; P = 0.007) hospitalizations.GCSE rarely complicates SAH; however, it is associated with increased patient mortality, length of hospital stay, and cost. GCSE occurs more frequently in young patients, those with a history of renal disease, and patients who do not undergo a craniotomy.

  View details for DOI 10.1227/01.neu.0000279724.05898.e7

  View details for PubMedID 17621019

• Vaginal birth after cesarean delivery in twin gestations: a large, nationwide sample of deliveries. American journal of obstetrics and gynecology Ford, A. A., Bateman, B. T., Simpson, L. L. 2006; 195 (4): 1138-42

  Abstract

  The purpose of this study was to assess the maternal morbidity associated with attempted vaginal birth after cesarean (VBAC) in twin gestations using a large, nationwide sample of deliveries.Data for this study were obtained from an administrative dataset, the Nationwide Inpatient Sample, a representative sample of discharges from non-Federal hospitals, for the years 1993 to 2002. Patients admitted nonemergently for the delivery of twin gestations who had a history of previous cesarean delivery were selected. Patients that either delivered vaginally or who had discharge codes that indicated labor before cesarean delivery were defined as the trial of labor group, while patients who had a cesarean delivery without discharge codes that indicated labor were defined as the elective cesarean group. Various complications of delivery were analyzed for each group.We identified 4705 women who underwent an elective cesarean delivery and 1850 women who underwent a trial of labor. For women who had a trial of labor, 836 (45.2%) delivered vaginally. The rate of uterine rupture was higher in the trial of labor group than in the elective cesarean group (0.9% vs 0.1%, P < .001), and the rate of wound complications was lower (0.6% vs 1.3%, P < .02). The rates of other complications including hysterectomy, transfusion, major postpartum infection, thromboembolism, uterine dehiscence, and pelvic hematoma were not significantly different between the 2 groups.Our study showed a significantly higher rate of uterine rupture in the trial of labor group that is similar to the rates reported for trial of labor after cesarean in singleton pregnancies.

  View details for DOI 10.1016/j.ajog.2006.06.036

  View details for PubMedID 17000246

• Intracerebral hemorrhage in pregnancy: frequency, risk factors, and outcome. Neurology Bateman, B. T., Schumacher, H. C., Bushnell, C. D., Pile-Spellman, J., Simpson, L. L., Sacco, R. L., Berman, M. F. 2006; 67 (3): 424-9

  Abstract

  To describe the frequency, risk factors, and outcome of intracerebral hemorrhage (ICH) in pregnancy and the postpartum period using a large database of US inpatient hospitalizations.The authors obtained data from an administrative dataset, the Nationwide Inpatient Sample, which includes approximately 20% of all discharges from non-Federal hospitals, for the years 1993 through 2002. Women aged 15 to 44 years with a diagnosis of ICH were selected from the database for analysis, and within this group patients coded as pregnant or postpartum were identified. Using US Census data, estimates were made of the rates of ICH in pregnant/postpartum and non-pregnant women. Rates of various comorbidities in patients with pregnancy-related ICH were compared to the rates found in the general population of delivering patients using multivariate logistic regression to identify independent risk factors for pregnancy-related ICH.The authors identified 423 patients with pregnancy-related ICH, which corresponded to 6.1 pregnancy-related ICH per 100,000 deliveries and 7.1 pregnancy-related ICH per 100,000 at-risk person-years (compared to 5.0 per 100,000 person-years for non-pregnant women in the age range considered). The increased risk of ICH associated with pregnancy was largely attributable to ICH occurring in the postpartum period. The in-hospital mortality rate for pregnancy-related ICH was 20.3%. ICH accounted for 7.1% of all pregnancy-related mortality recorded in this database. Significant independent risk factors for pregnancy-related ICH included advanced maternal age (OR 2.11, 95% CI 1.69 to 2.64), African American race (OR 1.83, 95% CI 1.39 to 2.41), preexisting hypertension (OR 2.61, 95% CI 1.34 to 5.07), gestational hypertension (OR 2.41, 95% CI 1.62 to 3.59), preeclampsia/eclampsia (OR 10.39, 95% CI 8.32 to 12.98), preexisting hypertension with superimposed preeclampsia/eclampsia (OR 9.23, 95% CI 5.26 to 16.19), coagulopathy (OR 20.66, 95% CI 13.67 to 31.23), and tobacco abuse (OR 1.95, 95% CI 1.11 to 3.42).Intracerebral hemorrhage (ICH) accounts for a substantial portion of pregnancy-related mortality. The risk of ICH associated with pregnancy is greatest in the postpartum period. Advanced maternal age, African American race, hypertensive diseases, coagulopathy, and tobacco abuse were all independent risk factors for pregnancy-related ICH.

  View details for DOI 10.1212/01.wnl.0000228277.84760.a2

  View details for PubMedID 16894102

• Endovascular recanalization therapy in acute ischemic stroke. Stroke Choi, J. H., Bateman, B. T., Mangla, S., Marshall, R. S., Prabhakaran, S., Chong, J., Mohr, J. P., Mast, H., Pile-Spellman, J. 2006; 37 (2): 419-24

  Abstract

  To assess the outcome in acute ischemic stroke patients not eligible for systemic thrombolysis (outside the 3-hour time window, after surgery, or on anticoagulant) undergoing endovascular recanalization therapy (ERT) at the Columbia University Medical Center (CUMC) and to determine US nationwide usage and outcome of ERT in acute ischemic stroke.Patients treated at CUMC from 2001 to 2004 and the Nationwide Inpatient Sample (NIS) comprising 20% of all admissions in the United States from 1999 to 2002 were analyzed retrospectively.Thirty-one patients underwent ERT. Mean age was 68+/-14 years, 68% were female, and 45% nonwhite (occlusion sites: internal carotid artery 29%; middle cerebral artery 39%; posterior circulation 32%). Pharmacological or mechanical ERT was initiated beyond 3 hours after symptom onset (median time 4.4 hours) in 61%, 29% had surgery, and 39% were on anticoagulant medication. At discharge, 32% had modified Rankin Scale scores of 0 to 2 (52% discharged home or to rehabilitation facilities); overall mortality was 29%, of which 19% were fatal intracerebral hemorrhages. From the NIS cohort, 477 patients (0.17% of all strokes and 14% of all thrombolysis cases) underwent ERT. Fifteen percent died, and approximately 50% were discharged home or to rehabilitation facilities. Intracerebral hemorrhage occurred in 6%. Fewer good outcomes of the CUMC cohort may be explained by more unfavorable premorbid patient characteristics compared with the NIS cohort.Despite significant variability in patient characteristics and treatment methods among 2 sources of data analyzed, ERT in stroke patients not eligible for intravenous thrombolysis appears to be a relatively safe and effective treatment alternative that is being used increasingly nationwide.

  View details for DOI 10.1161/01.STR.0000198808.90579.65

  View details for PubMedID 16373652

• Factors associated with in-hospital mortality after administration of thrombolysis in acute ischemic stroke patients: an analysis of the nationwide inpatient sample 1999 to 2002. Stroke Bateman, B. T., Schumacher, H. C., Boden-Albala, B., Berman, M. F., Mohr, J. P., Sacco, R. L., Pile-Spellman, J. 2006; 37 (2): 440-6

  Abstract

  The prospective trials evaluating the safety and efficacy of intravenous tissue plasminogen activator have generally been conducted at academic medical centers and community hospitals with an institutional commitment to stroke care. Relatively little is known about the safety of this therapy as it is used in the community. We therefore examined outcomes in acute stroke patients treated with thrombolysis using the largest discharge database available in the United States for the years 1999 to 2002.Data were derived from the Nationwide Inpatient Sample for the years 1999 to 2002. Using the appropriate International Classification of Disease-Clinical Modification, 9th revision, codes, patients admitted through the emergency room with a primary diagnosis of acute ischemic stroke were selected for analysis. From these patients, those coded as receiving thrombolysis were identified. Multivariate logistic regression was performed on the thrombolysis and nonthrombolysis cohorts to identify independent predictors of in-hospital mortality from among those clinical elements available in the database.We identified 2594 patients treated with thrombolysis from a group of 248,964 patients admitted through the emergency room with a primary diagnosis of acute ischemic stroke. The thrombolysis cohort had a higher in-hospital mortality rate compared with the nonthrombolysis patients (11.4% versus 6.8%). The rate of intracerebral hemorrhage was 4.4% for the thrombolysis cohort and 0.4% for nonthrombolysis patients. Multivariate logistic regression showed advanced age, Asian/Pacific Islander race, congestive heart failure, and atrial fibrillation/flutter to be independent predictors of in-hospital mortality after thrombolysis. Thrombolysis volume, overall ischemic stroke volume, and teaching status were not significant predictors of in-hospital mortality after thrombolysis.Thrombolysis, as it is used in the community, has a safety profile that is similar to that observed in the large, prospective clinical trials.

  View details for DOI 10.1161/01.STR.0000199851.24668.f1

  View details for PubMedID 16397164

• Higher rate of stillbirth at the extremes of reproductive age: a large nationwide sample of deliveries in the United States. American journal of obstetrics and gynecology Bateman, B. T., Simpson, L. L. 2006; 194 (3): 840-5

  Abstract

  The purpose of this study was to assess the effect of maternal age on the rate of stillbirth in a large, nationwide sample of deliveries in the United States.Data were derived from the Nationwide Inpatient Sample for the years 1995 through 2002. With the use of ICD-9 codes, the rate of stillbirth was determined as a function of maternal age. Multivariate regression analysis was used to assess the effect of maternal age on the odds of stillbirth, with adjustment for multiple known risk factors for stillbirth.There were 5,874,203 deliveries that were identified for analysis. The unadjusted rate of stillbirth was elevated for teenagers and for women aged > or =35 years. In the multivariate analysis, compared with women 20 to 34 years old, women who were < or =19 years old were more likely to have a pregnancy outcome of stillbirth (odds ratio, 1.11; 95% CI, 1.08-1.14), as were women who were 35 to 39 years old (odds ratio, 1.28; 95% CI, 1.24-1.32) and women who were > or =40 years old (odds ratio, 1.72; 95% CI, 1.63-1.81).The extremes of maternal age are associated with an increased risk for stillbirth, even after adjustment for a large number of known predisposing conditions.

  View details for DOI 10.1016/j.ajog.2005.08.038

  View details for PubMedID 16522422

• Vaginal birth after cesarean (VBAC) in twin gestations: A large, nationwide sample of deliveries Bateman, B. T., Simpson, L. L. MOSBY, INC. 2005: S105

  View details for DOI 10.1016/j.ajog.2005.10.363

  View details for Web of Science ID 000233947800344

• Intracerebral hemorrhage in pregnancy: Incidence, risk factors, and outcome in a nationwide sample of deliveries Bateman, B. T., Schumacher, H. C., Pile-Spellman, J., Simpson, L. L., Berman, M. F. MOSBY, INC. 2005: S80

  View details for DOI 10.1016/j.ajog.2005.10.549

  View details for Web of Science ID 000233947800252

• Meningioma resection in the elderly: nationwide inpatient sample, 1998-2002. Neurosurgery Bateman, B. T., Pile-Spellman, J., Gutin, P. H., Berman, M. F. 2005; 57 (5): 866-72; discussion 866-72

  Abstract

  Morbidity and mortality rates reported for meningioma resection in the elderly vary widely. Thus, it is difficult for neurosurgeons to compare the risks and benefits of operating on elderly patients against opting for radiosurgery or watchful waiting. To address this issue, we studied the effect of advanced age on outcome after meningioma resection using the Nationwide Inpatient Sample.We identified all patients over the age of 20 in the Nationwide Inpatient Sample database who underwent surgical resection of a meningioma between 1998 and 2002 and were admitted from home. Primary outcomes were in-hospital mortality, adverse outcome (defined as death or discharge to a facility other than home), and length of hospitalization. Multivariate models were constructed to assess the effect of elderly age on the primary outcomes, adjusting for patient demographics, comorbid medical conditions, and hospital surgical volume.There were 8861 patients in the Nationwide Inpatient Sample database who underwent resection of meningioma during the study period; 26.0% were age 70 or older. Each of the primary outcomes demonstrated a marked effect of advancing age. The in-hospital mortality rate was higher in the elderly than in the nonelderly (4.0% versus 1.1%, P < 0.001), as was the rate of discharge to a facility other than home (53.2% versus 16.6%, P < 0.001). Elderly patients also had a longer mean length of stay (7.2 versus 5.1 d P < 0.001).The association between elderly age and adverse outcome after meningioma resection suggests a note of caution before proceeding to surgery with these patients.

  View details for DOI 10.1227/01.neu.0000179923.66729.87

  View details for PubMedID 16284557

• Definitive embolization of meningiomas. A review. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences Bateman, B. T., Lin, E., Pile-Spellman, J. 2005; 11 (2): 179-88

  Abstract

  This review examines the possible role for definitive embolization as a primary therapy for intracranial meningiomas. Surgery or radiosurgery are currently considered the standard of care for most benign meningiomas. However, each of these carries substantial risks. The perioperative mortality for surgical resection, as reported in large series, is between 3.7-9.4%; these studies report a similarly high rate of new neurological deficits following surgery. The rate of complications from radiosurgery is reported between 2-16% and it may take months to years before improvement in symptoms occurs following this therapy. There are a few reports of treating meningiomas by embolization without subsequent surgery. While these studies include small numbers of patients and have limited follow-up, the initial results are very promising. Given the risks and limitations of surgery and radiosurgery, prospective trials are now needed to determine the safety and efficacy of definitive embolization.

  View details for DOI 10.1177/159101990501100210

  View details for PubMedID 20584499

  View details for PubMedCentralID PMC3399720

• Conducting stroke research with an exception from the requirement for informed consent. Stroke Bateman, B. T., Meyers, P. M., Schumacher, H. C., Mangla, S., Pile-Spellman, J. 2003; 34 (5): 1317-23

  Abstract

  Obtaining viable informed consent from stroke patients for participation in clinical trials of acute stroke therapies is often problematic because of patients' neurological deficits. Furthermore, obtaining permission from surrogates is often not possible or not legally permissible.In 1996 the Food and Drug Administration and Department of Health and Human Services published regulations that allow investigators to conduct emergency research without patient consent under a narrowly defined set of circumstances. We review requirements of these regulations, paying particular attention to how they may be applied in a clinical trial of an acute stroke therapy.Acute stroke researchers should consider conducting clinical trials with an exception from the informed consent requirement permitted by this law.

  View details for DOI 10.1161/01.STR.0000065230.00053.B4

  View details for PubMedID 12663878

• Protection of research subjects. The New England journal of medicine Bateman, B. T., Meyers, P. M. 2003; 349 (2): 188-92; author reply 188-92

  View details for PubMedID 12856646

• Evaluation of a tetracycline-inducible promoter in Staphylococcus aureus in vitro and in vivo and its application in demonstrating the role of sigB in microcolony formation. Infection and immunity Bateman, B. T., Donegan, N. P., Jarry, T. M., Palma, M., Cheung, A. L. 2001; 69 (12): 7851-7

  Abstract

  An inducible promoter system provides a powerful tool for studying the genetic basis for virulence. A variety of inducible systems have been used in other organisms, including pXyl-xylR-inducible promoter, the pSpac-lacI system, and the arabinose-inducible P(BAD) promoter, but each of these systems has limitations in its application to Staphylococcus aureus. In this study, we demonstrated the efficacy of a tetracycline-inducible promoter system in inducing gene expression in S. aureus in vitro and inside epithelial cells as well as in an animal model of infection. Using the xyl/tetO promoter::gfp(uvr) fusion carried on a shuttle plasmid, we demonstrated that dose-dependent tetracycline induction, as measured by bacterial fluorescence, occurred in each of the above environments while basal activation under noninduced conditions remained low. To ascertain how the system can be used to elucidate the genetic basis of a pathogenic phenotype, we cloned the sigB gene downstream of the inducible promoter. Induction of SigB expression led to dose-dependent attachment of the tested strain to polystyrene microtiter wells. Additionally, bacterial microcolony formation, an event preceding mature biofilm formation, also increased with tetracycline induction of SigB.

  View details for DOI 10.1128/IAI.69.12.7851-7857.2001

  View details for PubMedID 11705967

  View details for PubMedCentralID PMC98881

• SarS, a SarA homolog repressible by agr, is an activator of protein A synthesis in Staphylococcus aureus. Infection and immunity Cheung, A. L., Schmidt, K., Bateman, B., Manna, A. C. 2001; 69 (4): 2448-55

  Abstract

  The expression of protein A (spa) is repressed by global regulatory loci sarA and agr. Although SarA may directly bind to the spa promoter to downregulate spa expression, the mechanism by which agr represses spa expression is not clearly understood. In searching for SarA homologs in the partially released genome, we found a SarA homolog, encoding a 250-amino-acid protein designated SarS, upstream of the spa gene. The expression of sarS was almost undetectable in parental strain RN6390 but was highly expressed in agr and sarA mutants, strains normally expressing high level of protein A. Interestingly, protein A expression was decreased in a sarS mutant as detected in an immunoblot but returned to near-parental levels in a complemented sarS mutant. Transcriptional fusion studies with a 158- and a 491-bp spa promoter fragment linked to the xylE reporter gene disclosed that the transcription of the spa promoter was also downregulated in the sarS mutant compared with the parental strain. Interestingly, the enhancement in spa expression in an agr mutant returned to a near-parental level in the agr sarS double mutant but not in the sarA sarS double mutant. Correlating with this divergent finding is the observation that enhanced sarS expression in an agr mutant was repressed by the sarA locus supplied in trans but not in a sarA mutant expressing RNAIII from a plasmid. Gel shift studies also revealed the specific binding of SarS to the 158-bp spa promoter. Taken together, these data indicated that the agr locus probably mediates spa repression by suppressing the transcription of sarS, an activator of spa expression. However, the pathway by which the sarA locus downregulates spa expression is sarS independent.

  View details for DOI 10.1128/IAI.69.4.2448-2455.2001

  View details for PubMedID 11254606

  View details for PubMedCentralID PMC98178

• Our experience in the surgical treatment of congenital club foot in infancy and childhood: (equino-varus-supinated type). Italian journal of orthopaedics and traumatology. Supplementum Marchetti, P. G., Diara, A., Belaise, C., Marcacci, M., Marchetti, N. 1976: 165-76

  View details for PubMedID 1074570