Current Role at Stanford

Senior Biostatistician, QSU, BMIR

Education & Certifications

  • MS, University of Minnesota, Biostatistics (2012)
  • BME, University of Minnesota, Mechanical Engineering (2009)
  • AS, Minneapolis Community and Technical College, Mathematics (2006)


  • Benjamin Arcand, Bryan N. Rolfes, Nikhil M. Murdeshwar, Joseph E. Hale, Steven M. Johnson, Luke A. Mitlyng, Joseph Mullenbach, Kristopher I. Kapphahn. "United States Patent US 8402619 B2 System and method for reducing environmental crematorial release of mercury from mercury-containing dental amalgam", Minnesota Funeral Directors Association, Mar 26, 2013

All Publications

  • Performance of a Provider-Assigned Functional Outcome Score in Critically Ill Children. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Wilson, N. E., Su, F., DaCar, A., Chang, N., Kapphahn, K., Schroeder, A. R., Tawfik, D. S., Knight, L., Rasmussen, L. 2023


    OBJECTIVES: Determine agreement between Pediatric Cerebral Performance Category (PCPC) scores integrated into clinical workflow and traditional investigator-assigned scores.DESIGN: Longitudinal study.SETTING: A single-center quaternary-care academic institution.SUBJECTS: Children admitted to the PICU between November 2019 and April 2020.INTERVENTIONS: Providers assigned PCPC scores as part of daily workflow. Investigators assigned scores using retrospective chart review.MEASUREMENTS AND MAIN RESULT: s: Of 803 patients admitted to the PICU, 782 survived and were included. Admission and discharge scores were recorded in 95% and 90% of patients, respectively. Agreement between provider- and investigator-assigned scores was excellent, with a weighted kappa of 0.87 (95% CI, 0.84-0.90) and 0.80 (95% CI, 0.76-0.84) for admission and discharge.CONCLUSIONS: Provider-assigned PCPC scores, documented as standard of care, are largely concordant with retrospective investigator-assigned scores. Measurement of cognitive functional status can be successfully integrated into daily provider workflow for use in the clinical, quality improvement, and research arenas.

    View details for DOI 10.1097/PCC.0000000000003234

    View details for PubMedID 37098780

  • Needles in a Haystack: Finding Qualitative and Quantitative Collaborators in Academic Medical Centers. Academic medicine : journal of the Association of American Medical Colleges Pomann, G. M., Truong, T., Boulos, M., Boulware, L. E., Brouwer, R. N., Curtis, L. H., Kapphahn, K., Khalatbari, S., McKeel, J., Messinger, S., O'Hara, R., Pencina, M. J., Samsa, G. P., Spino, C., Yang, L. Z., Desai, M. 2023


    Translational research is a data-driven process that involves transforming scientific laboratory- and clinic-based discoveries into products and activities with real-world impact to improve individual and population health. Successful execution of translational research requires collaboration between clinical and translational science researchers, who have expertise in a wide variety of domains across the field of medicine, and qualitative and quantitative scientists, who have specialized methodologic expertise across diverse methodologic domains. While many institutions are working to build networks of these specialists, a formalized process is needed to help researchers navigate the network to find the best match and to track the navigation process to evaluate an institution's unmet collaborative needs. In 2018, a novel analytic resource navigation process was developed at Duke University to connect potential collaborators, leverage resources, and foster a community of researchers and scientists. This analytic resource navigation process can be readily adopted by other academic medical centers. The process relies on navigators with broad qualitative and quantitative methodologic knowledge, strong communication and leadership skills, and extensive collaborative experience. The essential elements of the analytic resource navigation process are as follows: (1) strong institutional knowledge of methodologic expertise and access to analytic resources, (2) deep understanding of research needs and methodologic expertise, (3) education of researchers on the role of qualitative and quantitative scientists in the research project, and (4) ongoing evaluation of the analytic resource navigation process to inform improvements. Navigators help researchers determine the type of expertise needed, search the institution to find potential collaborators with that expertise, and document the process to evaluate unmet needs. Although the navigation process can create a basis for an effective solution, some challenges remain, such as having resources to train navigators, comprehensively identifying all potential collaborators, and keeping updated information about resources as methodologists join and leave the institution.

    View details for DOI 10.1097/ACM.0000000000005212

    View details for PubMedID 36940408

  • Integrating Community Health Workers Into Care for Patients With Advanced Stages of Cancer-Fragility Index Analysis-Reply. JAMA oncology Patel, M. I., Kapphahn, K. 2022

    View details for DOI 10.1001/jamaoncol.2022.5084

    View details for PubMedID 36301583

  • Effect of a Community Health Worker Intervention on Acute Care Use, Advance Care Planning, and Patient-Reported Outcomes Among Adults With Advanced Stages of Cancer: A Randomized Clinical Trial. JAMA oncology Patel, M. I., Kapphahn, K., Dewland, M., Aguilar, V., Sanchez, B., Sisay, E., Murillo, A., Smith, K., Park, D. J. 2022


    Deficiencies in advance care planning and symptom management are associated with avoidable acute care use among patients with cancer. Community health worker (CHW)-led approaches may be an approach to reduce acute care use but remain untested in community settings.To determine whether a CHW-led advance care planning and symptom screening intervention can reduce acute care use more than usual care in a community setting.This randomized clinical trial was conducted among patients with newly diagnosed advanced-stage or recurrent solid and hematologic cancers from August 8, 2017, through November 30, 2021. Data analysis was performed November 30, 2021, through January 1, 2022, by intention to treat.Participants were randomized 1:1 to usual care (control group) or usual care with the 6-month CHW-led intervention (intervention group).The primary outcome was acute care use. Secondary outcomes included advance care planning documentation, supportive care use, patient-reported outcomes, survival, and end-of-life care use.Among 128 participants, median (range) age was 67 (19-89) years; 61 (47.7%) were female; and 2 (1.6%) were American Indian or Alaska Native, 11 (8.6%) were Asian, 5 (3.9%) were Black, 23 (18.0%) were Hispanic or Latino, 2 (1.6%) were of mixed race, 2 (1.6%) were Native Hawaiian or other Pacific Islander, 86 (67.2%) were White, and 20 (15.6%) did not report race. Intervention participants had 62% lower risk of acute care use than the control (hazard ratio, 0.38; 95% CI, 0.19-0.76) within 6 months. At 12 months, intervention participants had 17% lower odds of acute care use (odds ratio [OR], 0.83; 95% CI, 0.69-0.98), 8 times the odds of advance care planning documentation (OR, 7.18; 95% CI, 2.85-18.13), 4 times the odds of palliative care (OR, 4.46; 95% CI, 1.88-10.55), nearly double the odds of hospice (OR, 1.83; 95% CI, 1.16-2.88), and nearly double the odds of improved mental and emotional health from enrollment to 6 and 12 months postenrollment (OR, 1.82; 95% CI, 1.03-3.28; and OR, 2.20; 95% CI, 1.04-4.65, respectively) than the control. There were no differences in the death (control, 26 [40.6%] vs intervention, 32 [50.0%]). Fewer intervention participants had acute care use (0 vs 6 [23.1%]) in the month before death than the control.In this randomized clinical trial, integration of a CHW-led intervention into cancer care reduced acute care use and is one approach to improve cancer care delivery for patients with advanced stages of disease in community Identifier: NCT03154190.

    View details for DOI 10.1001/jamaoncol.2022.1997

    View details for PubMedID 35771552

  • Clinical Outcomes of Treated and Untreated C. difficile PCR-Positive/Toxin-Negative Adult Hospitalized Patients: a Quasi-Experimental Noninferiority Study. Journal of clinical microbiology Hogan, C. A., Hitchcock, M. M., Frost, S., Kapphahn, K., Holubar, M., Tompkins, L. S., Banaei, N. 2022: e0218721


    Clostridioides difficile infection (CDI) is routinely diagnosed by PCR, with or without toxin enzyme immunoassay testing. The role of therapy for positive PCR and negative toxin remains unclear. The objective of this study was to determine whether clinical outcomes of PCR+/cycle threshold-based toxin (CT-toxin)- individuals vary by result reporting and treatment strategy. We performed a quasiexperimental noninferiority study comparing clinical outcomes of PCR+/CT-toxin- individuals by reporting PCR result only (most patients treated) with reporting CT-toxin result only (most patients untreated) in a single-center, tertiary academic hospital. The primary outcome was symptomatic PCR+/CT-toxin+ conversion at 8weeks. Secondary outcomes included 7-day diarrhea resolution, hospital length of stay, and 30-day all-cause mortality. A total of 663 PCR+/CT-toxin- test results were analyzed from 632 individuals with a median age of 61years (interquartile range [IQR], 44 to 72) and 50.4% immunocompromised. Individuals in the preintervention group were more likely to have received CDI therapy than those in the intervention group (91.5 versus 15.1%; P < 0.001). Symptomatic toxin conversion at 8weeks and hospital length of stay failed to establish the predefined thresholds for noninferiority. Lack of diarrhea resolution at 7days and 30-day all-cause mortality was similar and established noninferiority (20.0 versus 13.7%; adjusted odds ratio [aOR], 0.57; 90% confidence interval [CI], 0.32 to 1.01; P = 0.1; and 8.6 versus 6.5%; aOR, 0.46; 90% CI, 0.20 to 1.04; P = 0.12). These data support the safety of withholding antibiotics for selected hospitalized individuals with suspected CDI but negative toxin.

    View details for DOI 10.1128/jcm.02187-21

    View details for PubMedID 35611653

  • Cardiovascular and Cerebrovascular Disease Mortality in Asian American Subgroups. Circulation. Cardiovascular quality and outcomes Shah, N. S., Xi, K., Kapphahn, K. I., Srinivasan, M., Au, T., Sathye, V., Vishal, V., Zhang, H., Palaniappan, L. P. 2022: 101161CIRCOUTCOMES121008651


    BACKGROUND: Asian American individuals comprise the fastest-growing race and ethnic group in the United States. Certain subgroups may be at disproportionately high cardiovascular risk. This analysis aimed to identify cardiovascular and cerebrovascular disease mortality trends in Asian American subgroups.METHODS: Age-standardized mortality rates (ASMR), average annual percent change of ASMR calculated by regression, and proportional mortality ratios of ischemic heart disease, heart failure, and cerebrovascular disease were calculated by sex in non-Hispanic Asian American subgroups (Chinese, Filipino, Asian Indian, Japanese, Korean, and Vietnamese), non-Hispanic White, and Hispanic individuals from US death certificates, 2003 to 2017.RESULTS: Among 618 004 non-Hispanic Asian American, 30 267 178 non-Hispanic White, and 2 292 257 Hispanic deaths from all causes, ASMR from ischemic heart disease significantly decreased in all subgroups of Asian American women and in non-Hispanic White and Hispanic women; significantly decreased in Chinese, Filipino, Japanese, and Korean men and non-Hispanic White and Hispanic men and remained stagnant in Asian Indian and Vietnamese men. The highest 2017 ASMR from ischemic heart disease among Asian American decedents was in Asian Indian women (77 per 100 000) and men (133 per 100 000). Heart failure ASMR remained stagnant in Chinese, Korean, and non-Hispanic White women, and Chinese and Vietnamese men. Heart failure ASMR significantly increased in both sexes in Filipino, Asian Indian, and Japanese individuals, Vietnamese women, and Korean men, with highest 2017 ASMR among Asian American subgroups in Asian Indian women (14 per 100 000) and Asian Indian men (15 per 100 000). Cerebrovascular disease ASMR decreased in Chinese, Filipino, and Japanese women and men between 2003 and 2017, and remained stagnant in Asian Indian, Korean, and Vietnamese women and men. The highest cerebrovascular disease ASMR among Asian American subgroups in 2017 was in Vietnamese women (46 per 100 000) and men (47 per 100 000).CONCLUSIONS: There was heterogeneity in cardiovascular and cerebrovascular mortality among Asian American subgroups, with stagnant or increasing mortality trends in several subgroups between 2003 and 2017.

    View details for DOI 10.1161/CIRCOUTCOMES.121.008651

    View details for PubMedID 35535589

  • Small Intestinal Bacterial Overgrowth in Children: Clinical Features and Treatment Response. JPGN reports Peinado Fabregat, M. I., Gardner, R. M., Hassan, M. A., Kapphahn, K., Yeh, A. M. 2022; 3 (2): e185


    To characterize the population of children diagnosed with small intestinal bacterial overgrowth (SIBO) based on breath test (BT), correlate symptomatology, and describe SIBO treatments and treatment efficacy.A retrospective cohort study of pediatric patients seen at Stanford Children's Health Gastroenterology Clinics from 2012 to 2018 who had a positive BT, defined by a rise in hydrogen by ≥20 ppm, a baseline hydrogen level ≥20 ppm, or a methane value ≥10 ppm. The main outcome was symptom resolution, defined as complete or partial improvement after a course of treatment. Absolute standardized differences and Chi-square tests were used to assess associations.From 98 children, 54 met inclusion and did not meet exclusion criteria (53.7% female). Lactulose substrate was used for 41 (75.9%) patients, whereas glucose was used for 13 (24.1%). Complete or partial resolution of symptoms was achieved in 13 of 16 (81.2%) patients who received probiotics with or without antibiotics versus 21 of 31 (67.7%) patients treated with antibiotics alone (P = 0.524). Metronidazole versus rifaximin versus other antibiotics showed no significant difference in symptom resolution (12 (63.2%), 13 (76.5%), 7 (77.8%), respectively, P = 0.601).Seventy-two percent of patients experienced at least partial symptom relief after treatment. We did not find a strong correlation between specific symptoms and analyte elevation. There was no difference in effectiveness between metronidazole and rifaximin to treat SIBO symptoms. Further research needs to be done to determine effective treatments for SIBO in pediatrics.

    View details for DOI 10.1097/PG9.0000000000000185

    View details for PubMedID 37168915

    View details for PubMedCentralID PMC10158461

  • COVIDNearTerm: A simple method to forecast COVID-19 hospitalizations JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE Olshen, A. B., Garcia, A., Kapphahn, K., Weng, Y., Wesson, P. D., Rutherford, G. W., Gonen, M., Desai, M., Vargo, J., Pugliese, J. A., Crow, D. 2022; 6 (1)
  • COVIDNearTerm: A simple method to forecast COVID-19 hospitalizations. Journal of clinical and translational science Olshen, A. B., Garcia, A., Kapphahn, K. I., Weng, Y., Vargo, J., Pugliese, J. A., Crow, D., Wesson, P. D., Rutherford, G. W., Gonen, M., Desai, M. 2022; 6 (1): e59


    COVID-19 has caused tremendous death and suffering since it first emerged in 2019. Soon after its emergence, models were developed to help predict the course of various disease metrics, and these models have been relied upon to help guide public health policy.Here we present a method called COVIDNearTerm to "forecast" hospitalizations in the short term, two to four weeks from the time of prediction. COVIDNearTerm is based on an autoregressive model and utilizes a parametric bootstrap approach to make predictions. It is easy to use as it requires only previous hospitalization data, and there is an open-source R package that implements the algorithm. We evaluated COVIDNearTerm on San Francisco Bay Area hospitalizations and compared it to models from the California COVID Assessment Tool (CalCAT).We found that COVIDNearTerm predictions were more accurate than the CalCAT ensemble predictions for all comparisons and any CalCAT component for a majority of comparisons. For instance, at the county level our 14-day hospitalization median absolute percentage errors ranged from 16 to 36%. For those same comparisons, the CalCAT ensemble errors were between 30 and 59%.COVIDNearTerm is a simple and useful tool for predicting near-term COVID-19 hospitalizations.

    View details for DOI 10.1017/cts.2022.389

    View details for PubMedID 35720970

    View details for PubMedCentralID PMC9161046

  • Parent Preferences for Transparency of Their Child's Hospitalization Costs. JAMA network open Bassett, H. K., Beck, J., Coller, R. J., Flaherty, B., Tiedt, K. A., Hummel, K., Tchou, M. J., Kapphahn, K., Walker, L., Schroeder, A. R. 2021; 4 (9): e2126083


    Importance: Health care in the US is often expensive for families; however, there is little transparency in the cost of medical services. The extent to which parents want cost transparency in their children's care is not well characterized.Objective: To explore the preferences and experiences of parents of hospitalized children regarding the discussion and consideration of health care costs in the inpatient care of their children.Design, Setting, and Participants: This cross-sectional multicenter survey study included 6 geographically diverse university-affiliated US children's hospitals from November 3, 2017, to November 8, 2018. Participants included a convenience sample of English- and Spanish-speaking parents of hospitalized children nearing hospital discharge. Data were analyzed from January 1, 2020, to June 25, 2021.Main Outcomes and Measures: Parents' preferences and experiences regarding transparency of their child's health care costs. Multivariable linear regression examined associations between clinical and sociodemographic variables with parents' preferences for knowing, discussing, and considering costs in the clinical setting. Factors included family financial difficulties, child's level of chronic disease, insurance payer, deductible, family poverty level, race, ethnicity, parental educational level, and study site.Results: Of 644 invited participants, 526 (82%) were enrolled (290 [55%] male), of whom 362 (69%) were White individuals, 400 (76%) were non-Hispanic/Latino individuals, and 274 (52%) had children with private insurance. Overall, 397 families (75%) wanted to discuss their child's medical costs, but only 36 (7%) reported having a cost conversation. If cost discussions were to occur, 294 families (56%) would prefer to speak to a financial counselor. Ninety-eight families (19%) worried discussing costs would hurt the quality of their child's care. Families with a medical financial burden unrelated to their hospitalized child had higher mean agreement that their child's physician should consider the family's costs in medical decision-making than families without a medical financial burden (effect size, 0.55 [95% CI, 0.18-0.92]). No variables were consistently associated with cost transparency preferences.Conclusions and Relevance: Most parents want to discuss their child's costs during an acute hospitalization. Discussions of health care costs may be an important, relatively unexplored component of family-centered care. However, these discussions rarely occur, indicating a tremendous opportunity to engage and support families in this issue.

    View details for DOI 10.1001/jamanetworkopen.2021.26083

    View details for PubMedID 34546372

  • The impact of estradiol on pregnancy outcomes in letrozole-stimulated frozen embryo transfer cycles. F&S reports Zhang, W. Y., Gardner, R. M., Kapphahn, K. I., Ramachandran, M. K., Murugappan, G., Aghajanova, L., Lathi, R. B. 2021; 2 (3): 320-326


    Objective: To assess the impact of low estradiol (E2) levels in letrozole-stimulated frozen embryo transfer (FET) cycles on pregnancy and neonatal outcomes.Design: Retrospective cohort.Setting: University-affiliated fertility center.Patients: All patients who underwent letrozole-stimulated FET cycles from January 2017 to April 2020 (n = 217). The "Low E2" group was defined as those with E2 serum levels on the day of trigger <10th percentile level (E2 <91.16 pg/mL, n = 22) and the "Normal E2" group was defined as those with E2 serum levels ≥10th percentile level (E2 ≥91.16 pg/mL, n = 195).Interventions: None.Main Outcome Measures: Pregnancy outcomes including rates of clinical pregnancy, clinical miscarriage, and live birth. Neonatal outcomes including gestational age at delivery, birth weight, and Apgar score.Results: The mean ± SD estradiol level was 66.8 ± 14.8 pg/mL for the "Low E2" group compared with 366.3 ± 322.1 pg/mL for the "Normal E2" group. There were otherwise no substantial differences in cycle characteristics such as endometrial thickness on the day of ovulation trigger and progesterone levels in early pregnancy. The "Low E2" group had a significantly higher clinical miscarriage rate (36.4% vs. 8.8%, adjusted odds ratio 8.06) and lower live birth rate (31.8% vs. 57.9%, adjusted odds ratio 0.28). Neonatal outcomes such as gestational age at delivery, mean birth weight, Apgar scores, and incidence of newborn complications were not clinically different between the groups.Conclusion: Low E2 levels were associated with a significantly higher miscarriage rate and lower live birth rate, suggesting that E2 levels in the follicular phase may have an effect on cycle outcomes. Given the rise in use of FET, further studies are needed to confirm our findings and understand the mechanisms.

    View details for DOI 10.1016/j.xfre.2021.05.007

    View details for PubMedID 34553158

  • The COVID-19 Outpatient Pragmatic Platform Study (COPPS): Study design of a multi-center pragmatic platform trial. Contemporary clinical trials Bunning, B., Hedlin, H., Purington, N., Sundaram, V., Kapphahn, K., Weng, Y., Cunanan, K., Maldonado, Y., Singh, U., Khosla, C., O'Hara, R., Nicolls, M., Springman, E., Parsonnet, J., Rogers, A., Levitt, J., Desai, M. 2021: 106509


    More than 3000 clinical trials related to COVID-19 have been registered through With so many trials, there is a risk that many will be inconclusive due to being underpowered or due to an inability to recruit patients. At academic medical centers, multiple trials are competing for the same resources; the success of one may come at the expense of another. The COVID-19 Outpatient Pragmatic Protocol Study (COPPS) is a flexible phase 2, multi-site, randomized, blinded trial based at Stanford University designed to overcome these issues by simultaneously evaluating multiple COVID-19 treatments in the outpatient setting in one common platform with shared controls. This approach reduces the overall number of patients required for statistical power, while improving the likelihood that any enrolled patient receives active treatment. The platform study has two main domains designed to evaluate COVID-19 treatments by assessing their ability to reduce viral shedding (Viral Domain), measured with self-collected nasal swabs, or improve clinical outcomes (Clinical Domain), measured through self-reported symptomology data. Data are collected on both domains for all participants enrolled. Participants are followed over a 28-day period. COPPS has the advantage of pragmatism created around its workflow that is also appealing to potential participants because of a lower probability of inactive treatment. At the conclusion of this clinical trial we expect to have identified potentially effective therapeutic strategy/ies for treating COVID-19 in the outpatient setting, which will have a transformative impact on medicine and public health.

    View details for DOI 10.1016/j.cct.2021.106509

    View details for PubMedID 34274494

  • A community-based, multi-level, multi-setting, multi-component intervention to reduce weight gain among low socioeconomic status Latinx children with overweight or obesity: The Stanford GOALS randomised controlled trial. The lancet. Diabetes & endocrinology Robinson, T. N., Matheson, D., Wilson, D. M., Weintraub, D. L., Banda, J. A., McClain, A., Sanders, L. M., Haskell, W. L., Haydel, K. F., Kapphahn, K. I., Pratt, C., Truesdale, K. P., Stevens, J., Desai, M. 2021


    BACKGROUND: There are few long-term studies of interventions to reduce in low socioeconomic status children with overweight or obesity. The Stanford GOALS trial evaluated a 3-year, community-based, multi-level, multi-setting, multi-component (MMM) systems intervention, to reduce weight gain among low socioeconomic status, Latinx children with overweight or obesity.METHODS: We did a two-arm, parallel group, randomised, open-label, active placebo-controlled trial with masked assessment over 3 years. Families from low-income, primarily Latinx communities in Northern California, CA, USA, with 7-11-year-old children with overweight or obesity were randomly assigned to a MMM intervention or a Health Education (HE) comparison intervention. The MMM intervention included home environment changes and behavioural counselling, community after school team sports, and reports to primary health-care providers. The primary outcome was child BMI trajectory over three years. Secondary outcomes included one- and two-year changes in BMI. This trial is registered with ClinicalTrials.govNCT01642836.FINDINGS: Between July 13, 2012, and Oct 3, 2013, 241 families were recruited and randomly assigned to MMM (n=120) or HE (n=121). Children's mean age was 9·5 (SD 1·4) years, 134 (56%) were female and 107 (44%) were male, and 236 (98%) were Latinx. 238 (99%) children participated in year 1, 233 (97%) in year 2, and 227 (94%) in year 3 of follow-up assessments. In intention-to-treat analysis, over 3 years, the difference between intervention groups in BMI trajectory was not significant (mean adjusted difference -0·25 [95% CI -0·90 to 0·40] kg/m2; Cohen's d=0.10; p=0·45). Children in the MMM intervention group gained less BMI over 1 year than did children in the HE intervention group (-0·73 [-1·07 to -0·39] kg/m2, d=0.55); the same was true over 2 years (-0·63 [-1·13 to -0·14] kg/m2; d =0.33). No differential adverse events were observed.INTERPRETATION: The MMM intervention did not reduce BMI gain versus HE over 3 years but the effects over 1 and 2 years in this rigorous trial show the promise of this systems intervention approach for reducing weight gain and cardiometabolic risk factors in low socioeconomic status communities.FUNDING: US National Institutes of Health.

    View details for DOI 10.1016/S2213-8587(21)00084-X

    View details for PubMedID 33933181

  • Disaggregated Mortality from Gastrointestinal Cancers in Asian Americans: Analysis of United States Death Records. International journal of cancer Huang, R. J., Sharp, N., Talamoa, R., Kapphahn, K., Sathye, V., Lin, B., Srinivasan, M., Palaniappan, L. P. 2021


    Asian Americans (AAs) are heterogeneous, and aggregation of diverse AA populations in national reporting may mask high-risk groups. Gastrointestinal (GI) cancers constitute one-third of global cancer mortality, and an improved understanding of GI cancer mortality by disaggregated AA subgroups may inform future primary and secondary prevention strategies. Using national mortality records from the United States from 2003-2017, we report age-standardized mortality rates, standardized mortality ratios, and annual percent change trends from GI cancers (esophageal, gastric, colorectal, liver, and pancreatic) for the six largest AA subgroups (Asian Indians, Chinese, Filipinos, Japanese, Koreans and Vietnamese). Non-Hispanic Whites (NHWs) are used as the reference population. We found that mortality from GI cancers demonstrated nearly 3-fold difference between the highest (Koreans, 61 per 100 000 person-years) and lowest (Asian Indians, 21 per 100 000 person-years) subgroups. The distribution of GI cancer mortality demonstrates high variability between subgroups, with Korean Americans demonstrating high mortality from gastric cancer (16 per 100 000), and Vietnamese Americans demonstrating high mortality from liver cancer (19 per 100 000). Divergent temporal trends emerged, such as increasing liver cancer burden in Vietnamese Americans, which exacerbated existing mortality differences. There exist striking differences in the mortality burden of GI cancers by disaggregated AA subgroups. These data highlight the need for disaggregated data reporting, and the importance of race-specific and personalized strategies of screening and prevention. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ijc.33490

    View details for PubMedID 33527405

  • Clinical laboratory tests associated with survival in patients with metastatic renal cell carcinoma: A Laboratory Wide Association Study (LWAS). Urologic oncology Velaer, K., Thomas, I. C., Yang, J., Kapphahn, K., Metzner, T. J., Golla, A., Hoerner, C. R., Fan, A. C., Master, V., Chertow, G. M., Brooks, J. D., Patel, C. J., Desai, M., Leppert, J. T. 2021


    Prognostic models for patients with metastatic renal cell carcinoma (mRCC) include select laboratory values. These models have important limitations, including reliance on a limited array of laboratory tests, and use of dichotomous ("high-low") cutoffs. We applied a Laboratory-Wide Association Study (LWAS) framework to systematically evaluate common clinical laboratory results associated with survival for patients diagnosed with mRCC.We used laboratory data for 3,385 patients diagnosed with mRCC from 2002 to 2017. We developed a LWAS framework, to examine the association with 53 common clinical laboratory tests results (641,712 measurements) and overall survival. We employed false-discovery rate to test the association of multiple laboratory tests with survival, and validated these results using 3 separate cohorts to generate a standardized hazard ratio (sHR), reported for a 1 standard deviation unit change in each laboratory test.The LWAS approach confirmed the association of laboratory values currently used in prognostic models with survival, including calcium (HR 1.35, 95%CI 1.24-1.48), leukocyte count (HR 1.40, 95%CI 1.30-1.51), platelet count (HR 1.36, 95%CI 1.27-1.51), and hemoglobin (HR 0.79, 95%CI 0.72-0.86). Use of these tests as continuous variables improved model performance. LWAS also identified acute phase reactants associated with survival not typically included in prognostic models, including serum albumin (HR 0.66, 95%CI 0.61-0.72), ferritin (HR 1.25, 95%CI 1.08-1.45), alkaline phosphatase (HR 1.31, 95%CI 1.23-1.40), and C-reactive protein (HR 1.70, 95%CI 1.14-2.53).Routinely measured laboratory tests can refine current prognostic models, facilitate comparisons across clinical trial cohorts, and match patients with specific systemic therapies.

    View details for DOI 10.1016/j.urolonc.2021.08.011

    View details for PubMedID 34580027

  • Clinical trials in a COVID-19 pandemic: Shared infrastructure for continuous learning in a rapidly changing landscape. Clinical trials (London, England) Hedlin, H. n., Garcia, A. n., Weng, Y. n., He, Z. n., Sundaram, V. n., Bunning, B. n., Balasubramanian, V. n., Cunanan, K. n., Kapphahn, K. n., Gummidipundi, S. n., Purington, N. n., Boulos, M. n., Desai, M. n. 2021: 1740774520988298


    Clinical trials, conducted efficiently and with the utmost integrity, are a key component in identifying effective vaccines, therapies, and other interventions urgently needed to solve the COVID-19 crisis. Yet launching and implementing trials with the rigor necessary to produce convincing results is a complicated and time-consuming process. Balancing rigor and efficiency involves relying on designs that employ flexible features to respond to a fast-changing landscape, measuring valid endpoints that result in translational actions and disseminating findings in a timely manner. We describe the challenges involved in creating infrastructure with potential utility for shared learning.We have established a shared infrastructure that borrows strength across multiple trials. The infrastructure includes an endpoint registry to aid in selecting appropriate endpoints, a registry to facilitate establishing a Data & Safety Monitoring Board, common data collection instruments, a COVID-19 dedicated design and analysis team, and a pragmatic platform protocol, among other elements.The authors have relied on the shared infrastructure for six clinical trials for which they serve as the Data Coordinating Center and have a design and analysis team comprising 15 members who are dedicated to COVID-19. The authors established a pragmatic platform to simultaneously investigate multiple treatments for the outpatient with adaptive features to add or drop treatment arms.The shared infrastructure provides appealing opportunities to evaluate disease in a more robust manner with fewer resources and is especially valued during a pandemic where efficiency in time and resources is crucial. The most important element of the shared infrastructure is the pragmatic platform. While it may be the most challenging of the elements to establish, it may provide the greatest benefit to both patients and researchers.

    View details for DOI 10.1177/1740774520988298

    View details for PubMedID 33535821

  • Laboratory-wide association study of survival with prostate cancer. Cancer Sohlberg, E. M., Thomas, I., Yang, J., Kapphahn, K., Velaer, K. N., Goldstein, M. K., Wagner, T. H., Chertow, G. M., Brooks, J. D., Patel, C. J., Desai, M., Leppert, J. T. 2020


    BACKGROUND: Estimates of overall patient health are essential to inform treatment decisions for patients diagnosed with cancer. The authors applied XWAS methods, herein referred to as "laboratory-wide association study (LWAS)", to evaluate associations between routinely collected laboratory tests and survival in veterans with prostate cancer.METHODS: The authors identified 133,878 patients who were diagnosed with prostate cancer between 2000 and 2013 in the Veterans Health Administration using any laboratory tests collected within 6 months of diagnosis (3,345,083 results). Using the LWAS framework, the false-discovery rate was used to test the association between multiple laboratory tests and survival, and these results were validated using training, testing, and validation cohorts.RESULTS: A total of 31 laboratory tests associated with survival met stringent LWAS criteria. LWAS confirmed markers of prostate cancer biology (prostate-specific antigen: hazard ratio [HR], 1.07 [95% confidence interval (95% CI), 1.06-1.08]; and alkaline phosphatase: HR, 1.22 [95% CI, 1.20-1.24]) as well laboratory tests of general health (eg, serum albumin: HR, 0.78 [95% CI, 0.76-0.80]; and creatinine: HR, 1.05 [95% CI, 1.03-1.07]) and inflammation (leukocyte count: HR, 1.23 [95% CI, 1.98-1.26]; and erythrocyte sedimentation rate: HR, 1.33 [95% CI, 1.09-1.61]). In addition, the authors derived and validated separate models for patients with localized and advanced disease, identifying 28 laboratory markers and 15 laboratory markers, respectively, in each cohort.CONCLUSIONS: The authors identified routinely collected laboratory data associated with survival for patients with prostate cancer using LWAS methodologies, including markers of prostate cancer biology, overall health, and inflammation. Broadening consideration of determinants of survival beyond those related to cancer itself could help to inform the design of clinical trials and aid in shared decision making.LAY SUMMARY: This article examined routine laboratory tests associated with survival among veterans with prostate cancer. Using laboratory-wide association studies, the authors identified 31 laboratory tests associated with survival that can be used to inform the design of clinical trials and aid patients in shared decision making.

    View details for DOI 10.1002/cncr.33341

    View details for PubMedID 33237577

  • Life expectancy estimates for patients diagnosed with prostate cancer in the Veterans Health Administration. Urologic oncology Sohlberg, E. M., Thomas, I., Yang, J., Kapphahn, K., Daskivich, T. J., Skolarus, T. A., Shelton, J. B., Makarov, D. V., Bergman, J., Bang, C. K., Goldstein, M. K., Wagner, T. H., Brooks, J. D., Desai, M., Leppert, J. T. 2020


    PURPOSE: Accurate life expectancy estimates are required to inform prostate cancer treatment decisions. However, few models are specific to the population served or easily implemented in a clinical setting. We sought to create life expectancy estimates specific to Veterans diagnosed with prostate cancer.MATERIALS AND METHODS: Using national Veterans Health Administration electronic health records, we identified Veterans diagnosed with prostate cancer between 2000 and 2015. We abstracted demographics, comorbidities, oncologic staging, and treatment information. We fit Cox Proportional Hazards models to determine the impact of age, comorbidity, cancer risk, and race on survival. We stratified life expectancy estimates by age, comorbidity and cancer stage.RESULTS: Our analytic cohort included 145,678 patients. Survival modeling demonstrated the importance of age and comorbidity across all cancer risk categories. Life expectancy estimates generated from age and comorbidity data were predictive of overall survival (C-index 0.676, 95% CI 0.674-0.679) and visualized using Kaplan-Meier plots and heatmaps stratified by age and comorbidity. Separate life expectancy estimates were generated for patients with localized or advanced disease. These life expectancy estimates calibrate well across prostate cancer risk categories.CONCLUSIONS: Life expectancy estimates are essential to providing patient-centered prostate cancer care. We developed accessible life expectancy estimation tools for Veterans diagnosed with prostate cancer that can be used in routine clinical practice to inform medical-decision making.

    View details for DOI 10.1016/j.urolonc.2020.05.015

    View details for PubMedID 32674954

  • Impact of Rapid Antimicrobial Susceptibility Testing in Gram-negative Rod Bacteremia: A Quasi-Experimental Study. Journal of clinical microbiology Hogan, C. A., Ebunji, B., Watz, N., Kapphahn, K., Rigdon, J., Mui, E., Meng, L., Alegria, W., Holubar, M., Deresinski, S., Banaei, N. 2020


    Background: Clinical justification for rapid antimicrobial susceptibility testing (AST) in Gram-negative rod (GNR) bacteremia is compelling; however, evidence supporting its value is sparse. We investigated the impact of rapid AST on clinical and antimicrobial stewardship outcomes in real-world practice.Methods: We performed a before and after quasi-experimental study from February 2018 to July 2019 at a tertiary hospital of the 24-hour/day, 7-day/week implementation of the direct VITEK2 AST method from positive blood culture broth for GNR bacteremia with electronic isolate-specific de-escalation comments, and daytime antibiotic stewardship program (ASP) intervention. The primary outcome was time to appropriate antibiotic escalation or de-escalation, and secondary outcomes included time to oral antibiotic step-down, hospital length-of-stay (LOS), all-cause 30-day mortality, 7-day incidence of acute kidney injury (AKI) and 30-day incidence of C. difficile infection (CDI).Results: A total of 671 GNR isolates were included from 643 adult patients. Among patients for whom antibiotic change occurred after rapid AST result, rapid AST was associated with a trend in decreased time to escalation or de-escalation (hazard ratio 1.22, 95% CI 0.99-1.51; p=0.06), with median times of 52.3 vs 42.2 hours. Secondary outcomes were similar in both groups including median time to oral antibiotic step-down, LOS, all-cause mortality, and incidence of AKI and CDI.Conclusion: Rapid AST led to improved stewardship measures but did not impact clinical patient outcomes. These results highlight that multiple variables in addition to timing of AST result contribute to clinical outcome and that further intervention may be required to clinically justify rapid AST implementation.

    View details for DOI 10.1128/JCM.00360-20

    View details for PubMedID 32434782

  • Computing the Cost of Care Per Day for Patients With Metastatic NETs Gupta, D., Kapphahn, K., Qin, F., Hornbacker, K., Henry, S., Wood, D., Blayney, D., Kunz, P. LIPPINCOTT WILLIAMS & WILKINS. 2020: 470
  • Sex differences in symptom presentation and functional outcomes: a pilot study in a matched sample of veterans with mild TBI. Brain injury Gray, M., Adamson, M. M., Thompson, R. C., Kapphahn, K. I., Han, S., Chung, J. S., Harris, O. A. 2020: 1–13


    Primary Objective: Research focused on mild traumatic brain injury in active military and veteran populations details the psychological, neurological and functional outcomes of mTBI, in a primarily male (~95%) cohort. This may misrepresent female symptoms and outcomes. Here we assess for genuine sex differences in symptom presentation and functional outcomes.Research Design: We used matched pairs to preclude potential sex bias in outcome data.Methods and Procedures: We matched 49 female/male pairs on; 1) mechanism of injury, 2) time from injury to assessment and 3) age at assessment. Statistics were t-tests, chi-square, correlations and post hoc linear regression.Main outcomes and results: Outcome assessment revealed four significant (p <.05) sex differences; Living situation, Marital status, Vocation and Branch of service. Only the Neurobehavioral Symptom Inventory (NSI) composite cognitive domain factor was significantly different between females (mean: 10.26) and males (mean: 7.58). Linear regression confirmed a significant effect of sex for the cognitive composite (p =.002).Conclusion: We conclude that sex has a moderate effect on mTBI post-concussive symptom presentation. The significant sex difference in the NSI cognitive domain characterizes sex-related symptomology profiles providers can focus on for better rehabilitation management. Replication in the larger cohort would improve generalizability.Abbreviation: TBI: Traumatic Brain Injuries; mTBI: mild Traumatic Brain Injuries; OIF: Operation Iraqi Freedom; OEF: Operation Enduring Freedom; VA: Veterans Affairs Health Care System; PSC: Polytrauma System of Care; PRC: Polytrauma Rehabilitation Center; PTRP: Polytrauma Transitional Rehabilitation Program; PNS: Polytrauma Network Site; PTSD: Post Traumatic Stress Disorder; DoD: Department of Defense; NSI: Neurobehavioral Symptom Inventory; LOC: loss of consciousness; AOC: alteration of consciousness; PTA: posttraumatic amnesia; CPRS: computerized patient record system; CTBIE: Comprehensive TBI Evaluation; OCD: obsessive compulsive disorder; ETOH: alcohol abuse.

    View details for DOI 10.1080/02699052.2020.1725979

    View details for PubMedID 32064965

  • Safety of Plasma Infusions in Parkinson's Disease. Movement disorders : official journal of the Movement Disorder Society Parker, J. E., Martinez, A. n., Deutsch, G. K., Prabhakar, V. n., Lising, M. n., Kapphahn, K. I., Anidi, C. M., Neuville, R. n., Coburn, M. n., Shah, N. n., Bronte-Stewart, H. M. 2020


    Young plasma infusions have emerged as a potential treatment for neurodegenerative disease, and convalescent plasma therapy has been used safely in the management of viral pandemics. However, the effect of plasma therapy in Parkinson's disease (PD) is unknown.The objective of this study was to determine the safety, tolerability, and feasibility of plasma infusions in people with PD.A total of 15 people with clinically established PD, at least 1 cognitive complaint, and on stable therapy received 1 unit of young fresh frozen plasma twice a week for 4 weeks. Assessments and adverse effects were performed/reported on and off therapy at baseline, immediately after, and 4 weeks after the infusions ended. Adverse effects were also assessed during infusions. The primary outcomes were safety, tolerability, and feasibility. Exploratory outcomes included Unified Parkinson's Disease Rating Scale Part III off medication, neuropsychological battery, Parkinson's Disease Questionnaire-39, inflammatory markers (tumor necrosis factor-α, interleukin-6), uric acid, and quantitative kinematics.Adherence rate was 100% with no serious adverse effects. There was evidence of improvement in phonemic fluency (P = 0.002) and in the Parkinson's Disease Questionnaire-39 stigma subscore (P = 0.013) that were maintained at the delayed evaluation. Elevated baseline tumor necrosis factor-α levels decreased 4 weeks after the infusions ended.Young fresh frozen plasma was safe, feasible, and well tolerated in people with PD, without serious adverse effects and with preliminary evidence for improvements in phonemic fluency and stigma. The results of this study warrant further therapeutic investigations in PD and provide safety and feasibility data for plasma therapy in people with PD who may be at higher risk for severe complications of COVID-19. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC. on behalf of International Parkinson and Movement Disorder Society.

    View details for DOI 10.1002/mds.28198

    View details for PubMedID 32633860

  • Financial Difficulties in Families of Hospitalized Children. Journal of hospital medicine Bassett, H. K., Coller, R. J., Beck, J. n., Hummel, K. n., Tiedt, K. A., Flaherty, B. n., Tchou, M. J., Kapphahn, K. n., Walker, L. n., Schroeder, A. R. 2020


    High costs of hospitalization may contribute to financial difficulties for some families.To examine the prevalence of financial distress and medical financial burden in families of hospitalized children and identify factors that can predict financial difficulties.Cross-sectional survey of parents of hospitalized children at six children's hospitals between October 2017 and November 2018.The outcomes were high financial distress and medical financial burden. Multivariable logistic regression identified predictors of each outcome. The primary predictor variable was level of chronic disease (complex chronic disease, C-CD; noncomplex chronic disease, NC-CD; no chronic disease, no-CD).Of 644 invited participants, 526 (82%) were enrolled, with 125 (24%) experiencing high financial distress, and 160 (30%) reporting medical financial burden. Of those, 86 (54%) indicated their medical financial burden was caused by costs associated with their hospitalized child. Neither C-CD nor NC-CD were associated with high financial distress. Child-related medical financial burden was associated with both C-CD and NC-CD (adjusted odds ratio [AOR], 4.98; 95% CI, 2.41-10.29; and AOR, 2.57; 95% CI, 1.11-5.93), compared to no-CD. Although household poverty level was associated with both measures, financial difficulties occurred in all family income brackets.Financial difficulties are common in families of hospitalized children. Low-income families and those who have children with chronic conditions are at particular risk; however, financial difficulties affect all subsets of the pediatric population. Hospitalization may be a prime opportunity to identify and engage families at risk for financial distress and medical financial burden.

    View details for DOI 10.12788/jhm.3500

    View details for PubMedID 33147127

  • QTc Prolongation and Risk of Torsades de Pointes in Hospitalized Pediatric Oncology Patients. The Journal of pediatrics Lim, T. R., Rangaswami, A. A., Dubin, A. M., Kapphahn, K. I., Sakarovitch, C., Long, J., Motonaga, K. S., Trela, T., Ceresnak, S. R. 2019


    OBJECTIVE: To evaluate the prevalence of torsades de pointes and to identify risk factors associated with QTc prolongation of ≥500milliseconds in hospitalized pediatric oncology patients. A QTc prolongation of ≥500milliseconds is associated with higher mortality in hospitalized adults but has not been demonstrated in pediatrics.STUDY DESIGN: A single-center, retrospective review of all hospitalized oncology patients ≤21years of age was performed from 2014 to 2016. Patients with long/short QT syndrome or a QRS interval of ≥120ms were excluded. Rapid response events were reviewed to determine the prevalence of torsades. In patients with ECGs for review, data were compared between patients with a QTc of <500 and≥500ms via logistic regression.RESULTS: There were 1934 hospitalized patients included. Rapid response events occurred in 90 patients (4.7%) with 2 torsades events (0.1%). There were 1412 electrocardiograms performed in 287 unique patients (10.6±6.3years of age; 43% female). The mean QTc was 448±31ms; 25 patients (8.7%) had ≥1 ECG with a QTc of ≥500ms. The prevalence of torsades was greater in patients with a QTc of ≥500ms (8% vs 0%; P<.01). In multivariate analysis, factors associated with a QTc of ≥500ms included female sex, (OR 2.95) and ≥2 QT-prolonging medications (OR, 2.95).CONCLUSIONS: The prevalence of torsades in hospitalized pediatric oncology patients was low (0.1%), although the risk was significantly greater in patients with a QTc of ≥500ms. Routine monitoring of electrocardiograms and electrolytes is essential in patients with risk factors predisposing to QTc prolongation.

    View details for DOI 10.1016/j.jpeds.2019.10.018

    View details for PubMedID 31761428

  • Missing data strategies for time-varying confounders in comparative effectiveness studies of non-missing time-varying exposures and right-censored outcomes. Statistics in medicine Desai, M. n., Montez-Rath, M. E., Kapphahn, K. n., Joyce, V. R., Mathur, M. B., Garcia, A. n., Purington, N. n., Owens, D. K. 2019


    The treatment of missing data in comparative effectiveness studies with right-censored outcomes and time-varying covariates is challenging because of the multilevel structure of the data. In particular, the performance of an accessible method like multiple imputation (MI) under an imputation model that ignores the multilevel structure is unknown and has not been compared to complete-case (CC) and single imputation methods that are most commonly applied in this context. Through an extensive simulation study, we compared statistical properties among CC analysis, last value carried forward, mean imputation, the use of missing indicators, and MI-based approaches with and without auxiliary variables under an extended Cox model when the interest lies in characterizing relationships between non-missing time-varying exposures and right-censored outcomes. MI demonstrated favorable properties under a moderate missing-at-random condition (absolute bias <0.1) and outperformed CC and single imputation methods, even when the MI method did not account for correlated observations in the imputation model. The performance of MI decreased with increasing complexity such as when the missing data mechanism involved the exposure of interest, but was still preferred over other methods considered and performed well in the presence of strong auxiliary variables. We recommend considering MI that ignores the multilevel structure in the imputation model when data are missing in a time-varying confounder, incorporating variables associated with missingness in the MI models as well as conducting sensitivity analyses across plausible assumptions.

    View details for DOI 10.1002/sim.8174

    View details for PubMedID 31099433

  • Transition From Heart Disease to Cancer as the Leading Cause of Death in the United States. Annals of internal medicine Hastings, K. G., Kapphahn, K. n., Boothroyd, D. B., Rehkopf, D. H., Cullen, M. R., Palaniappan, L. n. 2019; 171 (3): 225

    View details for DOI 10.7326/L19-0203

    View details for PubMedID 31382280

  • Maternal and neonatal outcomes associated with trophectoderm biopsy. Fertility and sterility Zhang, W. Y., von Versen-Höynck, F. n., Kapphahn, K. I., Fleischmann, R. R., Zhao, Q. n., Baker, V. L. 2019


    To assess whether pregnancies achieved with trophectoderm biopsy for preimplantation genetic testing (PGT) have different risks of adverse obstetric and neonatal outcomes compared with pregnancies achieved with IVF without biopsy.Observational cohort.University-affiliated fertility center.Pregnancies achieved via IVF with PGT (n = 177) and IVF without PGT (n = 180) that resulted in a live birth.None.Maternal outcomes including preeclampsia and placenta previa and neonatal outcomes including birth weight and birth defects.There was a statistically significant increase in the risk of preeclampsia among IVF+PGT pregnancies compared with IVF without PGT pregnancies, with an incidence of 10.5% versus 4.1% (adjusted odds ratio [aOR] = 3.02; 95% confidence interval [95% CI], 1.10, 8.29). The incidence of placenta previa was 5.8% in IVF+PGT pregnancies versus 1.4% in IVF without PGT pregnancies (aOR = 4.56; 95% CI, 0.93, 22.44). Similar incidences of gestational diabetes, preterm premature rupture of membranes, and postpartum hemorrhage were observed. IVF+PGT and IVF without PGT neonates did not have a significantly different gestational age at delivery or rate of preterm birth, low birth weight, neonatal intensive care unit admission, neonatal morbidities, or birth defects. All trends, including the significantly increased risk of preeclampsia in IVF+PGT pregnancies, persisted upon stratification of analysis to only singleton live births.To date, this is the largest and most extensively controlled study examining maternal and neonatal outcomes after trophectoderm biopsy. There was a statistically significant three-fold increase in the odds of preeclampsia associated with trophectoderm biopsy. Given the rise in PGT use, further investigation is warranted.

    View details for DOI 10.1016/j.fertnstert.2019.03.033

    View details for PubMedID 31103283

    View details for PubMedCentralID PMC6527329

  • Socioeconomic Differences in the Epidemiologic Transition From Heart Disease to Cancer as the Leading Cause of Death in the United States, 2003 to 2015: An Observational Study. Annals of internal medicine Hastings, K. G., Boothroyd, D. B., Kapphahn, K., Hu, J., Rehkopf, D. H., Cullen, M. R., Palaniappan, L. 2018


    Background: Recent data suggest that the United States is in the midst of an epidemiologic transition in the leading cause of death.Objective: To examine county-level sociodemographic differences in the transition from heart disease to cancer as the leading cause of death in the United States.Design: Observational study.Setting: U.S. death records, 2003 to 2015.Participants: Decedents aged 25 years or older, classified by racial/ethnic group.Measurements: All-cause, heart disease, and cancer mortality stratified by quintiles of county median household income. Age- and sex-adjusted mortality rates and average annual percentage of change were calculated.Results: Heart disease was the leading cause of death in 79% of counties in 2003 and 59% in 2015. Cancer was the leading cause of death in 21% of counties in 2003 and 41% in 2015. The shift to cancer as the leading cause of death was greatest in the highest-income counties. Overall, heart disease mortality rates decreased by 28% (30% in high-income counties vs. 22% in low-income counties) from 2003 to 2015, and cancer mortality rates decreased by 16% (18% in high-income counties vs. 11% in low-income counties). In the lowest-income counties, heart disease remained the leading cause of death among all racial/ethnic groups, and improvements were smaller for both heart disease and cancer.Limitation: Use of county median household income as a proxy for socioeconomic status.Conclusion: Data show that heart disease is more likely to be the leading cause of death in low-income counties. Low-income counties have not experienced the same decrease in mortality rates as high-income counties, which suggests a later transition to cancer as the leading cause of death in low-income counties.Primary Funding Source: National Institute on Minority Health and Health Disparities.

    View details for PubMedID 30422275

  • Effects of reproductive period duration and number of pregnancies on midlife ECG indices: a secondary analysis from the Women's Health Initiative Clinical Trial BMJ OPEN Parikh, N. I., Kapphahn, K., Hedlin, H., Olgin, J. E., Allison, M. A., Magnani, J. W., Ryckman, K. R., Waring, M. E., Perez, M., Howard, B. V. 2018; 8 (8): e019129


    Pregnancy, menses and menopause are related to fluctuations in endogenous sex hormones in women, which cumulatively may alter cardiac electrical conduction. Therefore, we sought to study the association between number of pregnancies and reproductive period duration (RD, time from menarche to menopause) with ECG intervals in the Women's Health Initiative Clinical Trials.Secondary analysis of multicentre clinical trial.USA.ECGintervals: PR interval, P-wave duration, P-wave dispersion, QTc interval.n=40 687 women (mean age=62 years) participating in the Women's Health Initiative Clinical Trials. 82.5% were white, 9.3% black, 4% Hispanic and 2.7% Asian.In primary analysis, we employed multivariable linear regression models relating number of pregnancies and RD with millisecond changes in intervals from enrolment ECG. We studied effect modification by hormone therapy use.Among participants, 5+ live births versus 0 prior pregnancies was associated with a 1.32 ms increase in PR interval (95% CI 0.25 to 2.38), with a graded association with longer QTc interval (ms) (none (prior pregnancy, no live births)=0.66 (-0.56 to 1.88), 1=0.15 (-0.71 to 1.02), 2-4=0.25 (-0.43 to 0.94) and 5+ live births=1.15 (0.33 to 1.98), p=0.008). RD was associated with longer PR interval and maximum P-wave duration (but not P-wave dispersion) among never users of hormone therapy: (PR (ms) per additional RD year: 0.10 (0.04 to 0.16); higher P-wave duration (ms): 0.09 (0.06 to 0.12)). For every year increase in reproductive period, QTc decreased by 0.04 ms (-0.07 to -0.01).An increasing number of live births is related to increased and RD to decreased ventricular repolarisation time. Both grand multiparity and longer RD are related to increased atrial conduction time. Reproductive factors that alter midlife cardiac electrical conduction system remodelling in women may modestly influence cardiovascular disease risk in later life.NCT00000611; Post-results.

    View details for PubMedID 30121588

  • Dialysis versus Medical Management at Different Ages and Levels of Kidney Function in Veterans with Advanced CKD. Journal of the American Society of Nephrology : JASN Kurella Tamura, M., Desai, M., Kapphahn, K. I., Thomas, I., Asch, S. M., Chertow, G. M. 2018


    Background Appropriate patient selection and optimal timing of dialysis initiation among older adults with advanced CKD are uncertain. We determined the association between dialysis versus medical management and survival at different ages and levels of kidney function.Methods We assembled a nationally representative 20% sample of United States veterans with eGFR<30 ml/min per 1.73 m2 between 2005 and 2010 (n=73,349), with follow-up through 2012. We used an extended Cox model to determine associations among the time-varying exposures, age (<65, 65-74, 75-84, and ≥85 years), eGFR (<6, 6-<9, 9-<12, 12-<15, and 15-<29 ml/min per 1.73 m2), and provision of dialysis, and survival.Result Over the mean±SEM follow-up of 3.4±2.2 years, 15% of patients started dialysis and 52% died. The eGFR at which dialysis, compared with medical management, associated with lower mortality varied by age (P<0.001). For patients aged <65, 65-74, 75-84, and ≥85 years, dialysis associated with lower mortality for those with eGFR not exceeding 6-<9, <6, 9-<12, and 9-<12 ml/min per 1.73 m2, respectively. Dialysis initiation at eGFR<6 ml/min per 1.73 m2 associated with a higher median life expectancy of 26, 25, and 19 months for patients aged 65, 75, and 85 years, respectively. When dialysis was initiated at eGFR 9-<12 ml/min per 1.73 m2, the estimated difference in median life expectancy was <1 year for these patients.Conclusions Provision of dialysis at higher levels of kidney function may extend survival for some older patients.

    View details for PubMedID 29789430

  • Dialysis Initiation and Mortality Among Older Veterans With Kidney Failure Treated in Medicare vs the Department of Veterans Affairs JAMA INTERNAL MEDICINE Tamura, M., Thomas, I., Montez-Rath, M. E., Kapphahn, K., Desai, M., Gale, R. C., Asch, S. M. 2018; 178 (5): 657–64


    The benefits of maintenance dialysis for older adults with end-stage renal disease (ESRD) are uncertain. Whether the setting of pre-ESRD nephrology care influences initiation of dialysis and mortality is not known.To compare initiation of dialysis and mortality among older veterans with incident kidney failure who received pre-ESRD nephrology care in fee-for-service Medicare vs the Department of Veterans Affairs (VA).Retrospective cohort study of patients from the US Medicare and VA health care systems evaluated 11 215 veterans aged 67 years or older with incident kidney failure between January 1, 2008, and December 31, 2011. Data analysis was performed March 15, 2016, through September 20, 2017.Pre-ESRD nephrology care in Medicare vs VA health care systems.Dialysis treatment and death within 2 years.Of the 11 215 patients included in the study, 11 085 (98.8%) were men; mean (SD) age was 79.1 (6.9) years. Within 2 years of incident kidney failure, 7071 (63.0%) of the patients started dialysis and 5280 (47.1%) died. Patients who received pre-ESRD nephrology care in Medicare were more likely to undergo dialysis compared with patients who received pre-ESRD nephrology care in VA (82% vs 53%; adjusted risk difference, 28 percentage points; 95% CI, 26-30 percentage points). Differences in dialysis initiation between Medicare and VA were more pronounced among patients aged 80 years or older and patients with dementia or metastatic cancer, and less pronounced among patients with paralysis (P < .05 for interaction). Two-year mortality was higher for patients who received pre-ESRD care in Medicare compared with VA (53% vs 44%; adjusted risk difference, 5 percentage points; 95% CI, 3-7 percentage points). The findings were similar in a propensity-matched analysis.Veterans who receive pre-ESRD nephrology care in Medicare receive dialysis more often yet are also more likely to die within 2 years compared with those in VA. The VA's integrated health care system and financing appear to favor lower-intensity treatment for kidney failure in older patients without a concomitant increase in mortality.

    View details for PubMedID 29630695

  • Reproductive history and risk of type 2 diabetes mellitus in postmenopausal women: findings from the Women's Health Initiative MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LeBlanc, E. S., Kapphahn, K., Hedlin, H., Desai, M., Parikh, N. I., Liu, S., Parker, D. R., Anderson, M., Aroda, V., Sullivan, S., Woods, N. F., Waring, M. E., Lewis, C. E., Stefanick, M. 2017; 24 (1): 64-72


    The aim of the study was to understand the association between women's reproductive history and their risk of developing type 2 diabetes. We hypothesized that characteristics signifying lower cumulative endogenous estrogen exposure would be associated with increased risk.Prospective cohort analysis of 124,379 postmenopausal women aged 50 to 79 years from the Women's Health Initiative (WHI). We determined age of menarche and final menstrual period, and history of irregular menses from questionnaires at baseline, and calculated reproductive length from age of menarche and final menstrual period. Presence of new onset type 2 diabetes was from self-report. Using multivariable Cox proportional hazards models, we assessed associations between reproductive variables and incidence of type 2 diabetes.In age-adjusted models, women with the shortest (<30 y) reproductive periods had a 37% (95% CI, 30-45) greater risk of developing type 2 diabetes than women with medium-length reproductive periods (36-40 y). Women with the longest (45+ y) reproductive periods had a 23% (95% CI, 12-37) higher risk than women with medium-length periods. These associations were attenuated after full adjustment (HR 1.07 [1.01, 1.14] for shortest and HR 1.09 [0.99, 1.22] for longest, compared with medium duration). Those with a final menstrual period before age 45 and after age 55 had an increased risk of diabetes (HR 1.04; 95% CI, 0.99-1.09 and HR 1.08; 95% CI, 1.01-1.14, respectively) compared to those with age of final menstrual period between 46 and 55 years. Timing of menarche and cycle regularity was not associated with risk after full adjustment.Reproductive history may be associated with type 2 diabetes risk. Women with shorter and longer reproductive periods may benefit from lifestyle counseling to prevent type 2 diabetes.

    View details for DOI 10.1097/GME.0000000000000714

    View details for Web of Science ID 000391845600010

    View details for PubMedID 27465714

  • Cross-national comparisons of increasing suicidal mortality rates for Koreans in the Republic of Korea and Korean Americans in the USA, 2003-2012. Epidemiology and psychiatric sciences Kung, A., Hastings, K. G., Kapphahn, K. I., Wang, E. J., Cullen, M. R., Ivey, S. L., Palaniappan, L. P., Chung, S. 2016: 1-12


    Korea has the highest suicide rate of developed countries, two times higher than the USA. Suicide trends among Koreans Americans living in the USA during the same period have not yet been described. We report suicide mortality rates and trends for four groups: (1) Korean Americans, (2) non-Hispanic White (NHW) Americans, (3) selected Asian American subgroups and (4) Koreans living in the Republic of Korea.We used US national (n = 18 113 585) and World Health Organization (WHO) (n = 232 919 253) mortality records for Korea from 2003 to 2012 to calculate suicide rates, all expressed per 100 000 persons. We assessed temporal trends and differences in age, gender and race/ethnicity using binomial regression.Suicide rates are highest in Koreans living in the Republic of Korea (32.4 for men and 14.8 for women). Suicide rates in Korean Americans (13.9 for men and 6.5 for women) have nearly doubled from 2003 to 2012 and exceed rates for all other Asian American subgroups (5.4-10.7 for men and 1.6-4.2 for women). Suicide rates among NHWs (21.0 for men and 5.6 for women) remain high. Among elders, suicide in Korean Americans (32.9 for men and 15.4 for women) is the highest of all examined racial/ethnic groups in the USA.Suicide in Korean Americans is higher than for other Asian Americans and follows temporal patterns more similar to Korea than the USA. Interventions to prevent suicide in Korean American populations, particularly among the elderly, are needed.

    View details for PubMedID 27830639

  • Mortality outcomes for Chinese and Japanese immigrants in the USA and countries of origin (Hong Kong, Japan): a comparative analysis using national mortality records from 2003 to 2011. BMJ open Hastings, K. G., Eggleston, K., Boothroyd, D., Kapphahn, K. I., Cullen, M. R., Barry, M., Palaniappan, L. P. 2016; 6 (10)


    With immigration and minority populations rapidly growing in the USA, it is critical to assess how these populations fare after immigration, and in subsequent generations. Our aim is to compare death rates and cause of death across foreign-born, US-born and country of origin Chinese and Japanese populations.We analysed all-cause and cause-specific age-standardised mortality rates and trends using 2003-2011 US death record data for Chinese and Japanese decedents aged 25 or older by nativity status and sex, and used the WHO Mortality Database for Hong Kong and Japan decedents in the same years. Characteristics such as age at death, absolute number of deaths by cause and educational attainment were also reported.We examined a total of 10 458 849 deaths. All-cause mortality was highest in Hong Kong and Japan, intermediate for foreign-born, and lowest for US-born decedents. Improved mortality outcomes and higher educational attainment among foreign-born were observed compared with developed Asia counterparts. Lower rates in US-born decedents were due to decreased cancer and communicable disease mortality rates in the US heart disease mortality was either similar or slightly higher among Chinese-Americans and Japanese-Americans compared with those in developed Asia counterparts.Mortality advantages in the USA were largely due to improvements in cancer and communicable disease mortality outcomes. Mortality advantages and higher educational attainments for foreign-born populations compared with developed Asia counterparts may suggest selective migration. Findings add to our limited understanding of the racial and environmental contributions to immigrant health disparities.

    View details for DOI 10.1136/bmjopen-2016-012201

    View details for PubMedID 27793837

    View details for PubMedCentralID PMC5093623

  • The Burden of Cancer in Asian Americans: A Report of National Mortality Trends by Asian Ethnicity CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Thompson, C. A., Gomez, S. L., Hastings, K. G., Kapphahn, K., Yu, P., Shariff-Marco, S., Bhatt, A. S., Wakelee, H. A., Patel, M. I., Cullen, M. R., Palaniappan, L. P. 2016; 25 (10): 1371-1382


    Asian Americans (AA) are the fastest growing U.S. population, and when properly distinguished by their ethnic origins, exhibit substantial heterogeneity in socioeconomic status, health behaviors, and health outcomes. Cancer is the second leading cause of death in the United States, yet trends and current patterns in the mortality burden of cancer among AA ethnic groups have not been documented.We report age-adjusted rates, standardized mortality ratios, and modeled trends in cancer-related mortality in the following AA ethnicities: Asian Indians, Chinese, Filipinos, Japanese, Koreans, and Vietnamese, from 2003 to 2011, with non-Hispanic whites (NHW) as the reference population.For most cancer sites, AAs had lower cancer mortality than NHWs; however, mortality patterns were heterogeneous across AA ethnicities. Stomach and liver cancer mortality was very high, particularly among Chinese, Koreans, and Vietnamese, for whom these two cancer types combined accounted for 15% to 25% of cancer deaths, but less than 5% of cancer deaths in NHWs. In AA women, lung cancer was a leading cause of death, but (unlike males and NHW females) rates did not decline over the study period.Ethnicity-specific analyses are critical to understanding the national burden of cancer among the heterogeneous AA population.Our findings highlight the need for disaggregated reporting of cancer statistics in AAs and warrant consideration of tailored screening programs for liver and gastric cancers. Cancer Epidemiol Biomarkers Prev; 25(10); 1371-82. ©2016 AACR.

    View details for DOI 10.1158/1055-9965.EPI-16-0167

    View details for PubMedID 27694108

  • Alcohol Use and Breast Cancer Survival among Participants in the Women's Health Initiative. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology Lowry, S. J., Kapphahn, K., Chlebowski, R., Li, C. I. 2016; 25 (8): 1268-1273


    Alcohol increases the risk of breast cancer even at moderate levels of intake. However, the relationship between alcohol consumption and mortality among breast cancer patients is less clear.This study included women from the Women's Health Initiative observational study and randomized trial diagnosed with breast cancer (n = 7,835). Cox proportional hazards regression was used to estimate adjusted HRs and 95% confidence intervals (CI) for overall and breast cancer-specific (BCS) mortality associated with drinking alcohol before or after a breast cancer diagnosis. We also assessed whether changes in drinking habits after diagnosis are related to mortality.Women who were consuming alcohol prior to their breast cancer diagnosis had a nonstatistically significant 24% (95% CI, 0.56-1.04) reduced risk of BCS mortality and a 26% (95% CI, 0.61-0.89) reduced risk of all-cause mortality. Some variation was observed by estrogen receptor (ER) status as alcohol consumption was associated with a 49% (95% CI, 0.31-0.83) reduced risk of BCS mortality among ER(-) patients with no change in risk observed among ER(+) patients (HR = 0.97; 95% CI, 0.31-1.54), though the difference between these risks was not statistically significant (P for interaction = 0.39). Postdiagnosis alcohol consumption, and change in consumption patterns after diagnosis, did not appear to be associated with all-cause or BCS mortality.In this large study, consumption of alcohol before or after breast cancer diagnosis did not increase risks of overall or cause-specific mortality.Coupled with existing evidence, alcohol consumption is unlikely to have a substantial impact on mortality among breast cancer patients. Cancer Epidemiol Biomarkers Prev; 25(8); 1268-73. ©2016 AACR.

    View details for DOI 10.1158/1055-9965.EPI-16-0151

    View details for PubMedID 27197280

    View details for PubMedCentralID PMC4970888

  • Association of Leptin with Body Pain in Women. Journal of women's health (2002) Younger, J., Kapphahn, K., Brennan, K., Sullivan, S. D., Stefanick, M. L. 2016; 25 (7): 752-760


    Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia.

    View details for DOI 10.1089/jwh.2015.5509

    View details for PubMedID 27028709

    View details for PubMedCentralID PMC4939369

  • Impact of residential UV exposure in childhood versus adulthood on skin cancer risk in Caucasian, postmenopausal women in the Women's Health Initiative CANCER CAUSES & CONTROL Ransohoff, K. J., Ally, M. S., Stefanick, M. L., Keiser, E., Spaunhurst, K., Kapphahn, K., Pagoto, S., Messina, C., Hedlin, H., Manson, J. E., Tang, J. Y. 2016; 27 (6): 817-823


    Sun exposure is a major risk factor for skin cancer; however, the relative contribution of ultraviolet (UV) exposure during childhood versus adulthood on skin cancer risk remains unclear.Our goal was to determine the impact of residential UV, measured by AVerage daily total GLObal solar radiation (AVGLO), exposure during childhood (birth, 15 years) versus adulthood (35, 50 years, and present) on incident non-melanoma skin cancer (NMSC) and malignant melanoma (MM) in postmenopausal women.Women were followed with yearly surveys throughout the duration of their participation in the Women's Health Initiative Observational study, a multicenter study from 1993 to 2005. A total of 56,557 women had data on all observations and were included in the baseline characteristics. The main exposure, residential UV (as measured by AVGLO), was measured by geographic residence during childhood and adulthood. Outcome was risk of incident NMSC and MM.Over 11.9 years (median follow-up), there were 9,195 (16.3 %) cases of NMSC and 518 (0.92 %) cases of MM. Compared with the reference group (women with low childhood and low adulthood UV), women with low childhood and high adulthood UV had a 21 % increased risk of NMSC (odds ratio 1.21, 95 % confidence interval 1.12, 1.31). Women with high childhood and high adulthood UV had a 19 % increased risk of NMSC (odds ratio 1.19, 95 % confidence interval 1.11, 1.27). Surprisingly, women with high childhood UV and low adulthood UV did not have a significant increase in NMSC risk compared with the reference group (odds ratio 1.08, 95 % confidence interval 0.91, 1.28) in multivariable models. Residential UV exposure in childhood or adulthood was not associated with increased melanoma risk.This study reveals an increase in NMSC risk associated with adulthood residential UV exposure, with no effect for childhood UV exposure.

    View details for DOI 10.1007/s10552-016-0730-9

    View details for Web of Science ID 000376619500011

    View details for PubMedID 27153844

  • Relation of statin use with non-melanoma skin cancer: prospective results from the Women's Health Initiative. British journal of cancer Wang, A., Stefanick, M. L., Kapphahn, K., Hedlin, H., Desai, M., Manson, J. A., Strickler, H., Martin, L., Wactawski-Wende, J., Simon, M., Tang, J. Y. 2016; 114 (3): 314-320


    The relationship between statin use and non-melanoma skin cancer (NMSC) is unclear with conflicting findings in literature. Data from the Women's Health Initiative (WHI) Observational Study and WHI Clinical Trial were used to investigate the prospective relationship between statin use and NMSC in non-Hispanic white (NHW) postmenopausal women.The WHI study enrolled women aged 50-79 years at 40 US centres. Among 133 541 NHW participants, 118 357 with no cancer history at baseline and complete medication/covariate data comprised the analytic cohort. The association of statin use (baseline, overall as a time-varying variable, duration, type, potency, lipophilicity) and NMSC incidence was determined using random-effects logistic regression models.Over a mean of 10.5 years of follow-up, we identified 11 555 NMSC cases. Compared with participants with no statin use, use of any statin at baseline was associated with significantly increased NMSC incidence (adjusted odds ratio (ORadj) 1.21; 95% confidence interval (CI): 1.07-1.35)). In particular, lovastatin (OR 1.52; 95% CI: 1.08-2.16), simvastatin (OR 1.38; 95% CI: 1.12-1.69), and lipophilic statins (OR 1.39; 95% CI: 1.18-1.64) were associated with higher NMSC risk. Low and high, but not medium, potency statins were associated with higher NMSC risk. No significant effect modification of the statin-NMSC relationship was found for age, BMI, smoking, solar irradiation, vitamin D use, and skin cancer history.Use of statins, particularly lipophilic statins, was associated with increased NMSC risk in postmenopausal white women in the WHI cohort. The lack of duration-effect relationship points to possible residual confounding. Additional prospective research should further investigate this relationship.

    View details for DOI 10.1038/bjc.2015.376

    View details for PubMedID 26742009

    View details for PubMedCentralID PMC4742576

  • Racial and Ethnic Variations in Lung Cancer Incidence and Mortality: Results From the Women's Health Initiative. Journal of clinical oncology Patel, M. I., Wang, A., Kapphahn, K., Desai, M., Chlebowski, R. T., Simon, M. S., Bird, C. E., Corbie-Smith, G., Gomez, S. L., Adams-Campbell, L. L., Cote, M. L., Stefanick, M. L., Wakelee, H. A. 2016; 34 (4): 360-368


    This study aimed to evaluate racial/ethnic differences in lung cancer incidence and mortality in the Women's Health Initiative Study, a longitudinal prospective cohort evaluation of postmenopausal women recruited from 40 clinical centers.Lung cancer diagnoses were centrally adjudicated by pathology review. Baseline survey questionnaires collected sociodemographic and health information. Logistic regression models estimated incidence and mortality odds by race/ethnicity adjusted for age, education, calcium/vitamin D, body mass index, smoking (status, age at start, duration, and pack-years), alcohol, family history, oral contraceptive, hormones, physical activity, and diet.The cohort included 129,951 women--108,487 (83%) non-Hispanic white (NHW); 10,892 (8%) non-Hispanic black (NHB); 4,882 (4%) Hispanic; 3,696 (3%) Asian/Pacific Islander (API); 534 (< 1%) American Indian/Alaskan Native; and 1,994 (1%) other. In unadjusted models, Hispanics had 66% lower odds of lung cancer compared with NHW (odds ratio [OR], 0.34; 95% CI, 0.2 to 0.5), followed by API (OR, 0.45; 95% CI, 0.27 to 0.75) and NHB (OR, 0.75; 95% CI, 0.59 to 0.95). In fully adjusted multivariable models, the decreased lung cancer risk for Hispanic compared with NHW women attenuated to the null (OR, 0.59; 95% CI, 0.35 to 0.99). In unadjusted models Hispanic and API women had decreased risk of death compared with NHW women (OR, 0.30 [95% CI, 0.15 to 0.62] and 0.34 [95% CI, 0.16 to 0.75, respectively); however, no racial/ethnic differences were found in risk of lung cancer death in fully adjusted models.Differences in lung cancer incidence and mortality are associated with sociodemographic, clinical, and behavioral factors. These findings suggest modifiable exposures and behaviors may contribute to differences in incidence of and mortality by race/ethnicity for postmenopausal women. Interventions focused on these factors may reduce racial/ethnic differences in lung cancer incidence and mortality.

    View details for DOI 10.1200/JCO.2015.63.5789

    View details for PubMedID 26700122

  • Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative. American journal of kidney diseases : the official journal of the National Kidney Foundation Arce, C. M., Rhee, J. J., Cheung, K. L., Hedlin, H., Kapphahn, K., Franceschini, N., Kalil, R. S., Martin, L. W., Qi, L., Shara, N. M., Desai, M., Stefanick, M. L., Winkelmayer, W. C. 2016; 67 (2): 198-208


    Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative.Prospective cohort study.Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs).Categories of eGFR (exposure); race/ethnicity (effect modifier).The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death.We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity.During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories.Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics.In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

    View details for DOI 10.1053/j.ajkd.2015.07.020

    View details for PubMedID 26337132

    View details for PubMedCentralID PMC4724531

  • Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans. EBioMedicine David, S. P., Wang, A., Kapphahn, K., Hedlin, H., Desai, M., Henderson, M., Yang, L., Walsh, K. M., Schwartz, A. G., Wiencke, J. K., Spitz, M. R., Wenzlaff, A. S., Wrensch, M. R., Eaton, C. B., Furberg, H., Mark Brown, W., Goldstein, B. A., Assimes, T., Tang, H., Kooperberg, C. L., Quesenberry, C. P., Tindle, H., Patel, M. I., Amos, C. I., Bergen, A. W., Swan, G. E., Stefanick, M. L. 2016; 4: 153-161


    Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood.We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case-control study of African-American females and males (1078 lung cancer cases and 822 controls).Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10(- 5)). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = - 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans.These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.

    View details for DOI 10.1016/j.ebiom.2016.01.002

    View details for PubMedID 26981579

  • Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women's Health Initiative AMERICAN JOURNAL OF KIDNEY DISEASES Arce, C. M., Rhee, J. J., Cheung, K. L., Hedlin, H., Kapphahn, K., Franceschini, N., Kalil, R. S., Martin, L. W., Qi, L., Shara, N. M., Desai, M., Stefanick, M. L., Winkelmayer, W. C. 2016; 67 (2): 198-208


    Kidney disease disproportionately affects minority populations, including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women's Health Initiative.Prospective cohort study.Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50 to 79 years who self-identified as either non-Hispanic white (n=8,921), African American (n=7,436), or Hispanic (n=3,054) were used to calculate estimated glomerular filtration rates (eGFRs).Categories of eGFR (exposure); race/ethnicity (effect modifier).The primary outcome was the composite of 3 physician-adjudicated CV events: myocardial infarction, stroke, or CV-related death.We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity.During a mean follow-up of 7.6 years, 1,424 CV events (653 myocardial infarctions, 627 strokes, and 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship, with lower eGFR being associated with higher CV risk, and higher eGFR, with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFRs and very few events occurring in these categories.Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics.In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women.

    View details for DOI 10.1053/j.ajkd.2015.07.020

    View details for Web of Science ID 000368418800011

    View details for PubMedCentralID PMC4724531

  • Weight loss on low-fat vs. low-carbohydrate diets by insulin resistance status among overweight adults and adults with obesity: A randomized pilot trial OBESITY Gardner, C. D., Offringa, L. C., Hartle, J. C., Kapphahn, K., Cherin, R. 2016; 24 (1): 79-86


    To test for differential weight loss response to low-fat (LF) vs. low-carbohydrate (LC) diets by insulin resistance status with emphasis on overall quality of both diets.Sixty-one adults, BMI 28-40 kg/m(2) , were randomized in a 2 × 2 design to LF or LC by insulin resistance status in this pilot study. Primary outcome was 6-month weight change. Participants were characterized as more insulin resistant (IR) or more insulin sensitive (IS) by median split of baseline insulin-area-under-the-curve from an oral glucose tolerance test. Intervention consisted of 14 one-hour class-based educational sessions.Baseline % carbohydrate:% fat:% protein was 44:38:18. At 6 months, the LF group reported 57:21:22 and the LC group reported 22:53:25 (IR and IS combined). Six-month weight loss (kg) was 7.4 ± 6.0 (LF-IR), 10.4 ± 7.8 (LF-IS), 9.6 ± 6.6 (LC-IR), and 8.6 ± 5.6 (LC-IS). No significant main effects were detected for weight loss by diet group or IR status; there was no significant diet × IR interaction. Significant differences in several secondary outcomes were observed.Substantial weight loss was achieved overall, but a significant diet × IR status interaction was not observed. Opportunity to detect differential response may have been limited by the focus on high diet quality for both diet groups and sample size.

    View details for DOI 10.1002/oby.21331

    View details for PubMedID 26638192

    View details for PubMedCentralID PMC5898445

  • Leading Causes of Death among Asian American Subgroups (2003-2011) PLOS ONE Hastings, K. G., Jose, P. O., Kapphahn, K. I., Frank, A. T., Goldstein, B. A., Thompson, C. A., Eggleston, K., Cullen, M. R., Palaniappan, L. P. 2015; 10 (4)


    Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups.We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

    View details for DOI 10.1371/journal.pone.0124341

    View details for Web of Science ID 000353659100048

    View details for PubMedID 25915940

    View details for PubMedCentralID PMC4411112

  • Cardiovascular Disease Mortality in Asian Americans JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Jose, P. O., Frank, A. T., Kapphahn, K. I., Goldstein, B. A., Eggleston, K., Hastings, K. G., Cullen, M. R., Palaniappan, L. P. 2014; 64 (23): 2486-2494


    Asian Americans are a rapidly growing racial/ethnic group in the United States. Our current understanding of Asian-American cardiovascular disease mortality patterns is distorted by the aggregation of distinct subgroups.The purpose of the study was to examine heart disease and stroke mortality rates in Asian-American subgroups to determine racial/ethnic differences in cardiovascular disease mortality within the United States.We examined heart disease and stroke mortality rates for the 6 largest Asian-American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) from 2003 to 2010. U.S. death records were used to identify race/ethnicity and cause of death by International Classification of Diseases-10th revision coding. Using both U.S. Census data and death record data, standardized mortality ratios (SMRs), relative SMRs (rSMRs), and proportional mortality ratios were calculated for each sex and ethnic group relative to non-Hispanic whites (NHWs).In this study, 10,442,034 death records were examined. Whereas NHW men and women had the highest overall mortality rates, Asian Indian men and women and Filipino men had greater proportionate mortality burden from ischemic heart disease. The proportionate mortality burden of hypertensive heart disease and cerebrovascular disease, especially hemorrhagic stroke, was higher in every Asian-American subgroup compared with NHWs.The heterogeneity in cardiovascular disease mortality patterns among diverse Asian-American subgroups calls attention to the need for more research to help direct more specific treatment and prevention efforts, in particular with hypertension and stroke, to reduce health disparities for this growing population.

    View details for DOI 10.1016/j.jacc.2014.08.048

    View details for Web of Science ID 000345962400007

    View details for PubMedID 25500233

    View details for PubMedCentralID PMC4274749

  • Impact of San Francisco's toy ordinance on restaurants and children's food purchases, 2011-2012. Preventing chronic disease Otten, J. J., Saelens, B. E., Kapphahn, K. I., Hekler, E. B., Buman, M. P., Goldstein, B. A., Krukowski, R. A., O'Donohue, L. S., Gardner, C. D., King, A. C. 2014; 11: E122-?


    In 2011, San Francisco passed the first citywide ordinance to improve the nutritional standards of children's meals sold at restaurants by preventing the giving away of free toys or other incentives with meals unless nutritional criteria were met. This study examined the impact of the Healthy Food Incentives Ordinance at ordinance-affected restaurants on restaurant response (eg, toy-distribution practices, change in children's menus), and the energy and nutrient content of all orders and children's-meal-only orders purchased for children aged 0 through 12 years.Restaurant responses were examined from January 2010 through March 2012. Parent-caregiver/child dyads (n = 762) who were restaurant customers were surveyed at 2 points before and 1 seasonally matched point after ordinance enactment at Chain A and B restaurants (n = 30) in 2011 and 2012.Both restaurant chains responded to the ordinance by selling toys separately from children's meals, but neither changed their menus to meet ordinance-specified nutrition criteria. Among children for whom children's meals were purchased, significant decreases in kilocalories, sodium, and fat per order were likely due to changes in children's side dishes and beverages at Chain A.Although the changes at Chain A did not appear to be directly in response to the ordinance, the transition to a more healthful beverage and default side dish was consistent with the intent of the ordinance. Study results underscore the importance of policy wording, support the concept that more healthful defaults may be a powerful approach for improving dietary intake, and suggest that public policies may contribute to positive restaurant changes.

    View details for DOI 10.5888/pcd11.140026

    View details for PubMedID 25032837

    View details for PubMedCentralID PMC4110247

  • Relation between self-recalled childhood physical activity and adult physical activity: The women's health initiative. Open journal of epidemiology Goodman, D., Park, H. L., Stefanick, M., Leblanc, E., Bea, J., Qi, L., Kapphahn, K., LaMonte, M., Manini, T., Desai, M., Anton-Culver, H. 2013; 3 (4): 224-231


    Evidence suggests that childhood physical activity may play a role in the etiology and prevention of adult chronic diseases. Because researchers must often depend on self-recalled physical activity data many years after the exposure, it is important to understand factors which may influence adult recall of childhood physical activity. This study evaluated the influence of adult characteristics on reported childhood physical activity and the association between adult physical activity and self-recalled childhood physical activity.48,066 post-menopausal women from the Women's Health Initiative Observational Study reported their physical activity level during ages 5 - 9, 10 - 14, and 15 - 19.In this cohort, over 65% of the population reported the same category of physical activity over the three childhood age groups. While higher levels of childhood physical activity were significantly associated with higher adult physical activity, this association varied by race/ethnicity, education, smoking, body mass index, history of diabetes or cardiovascular disease, social support and physical functional status. Women who were consistently highly active reported adult physical activity levels that were 2.82 MET-hr/week (95% C.I. = 2.43, 3.20) higher compared to women who were always physically inactive during childhood.It is important for researchers to understand the influence of adult characteristics on reported childhood physical activity.

    View details for PubMedID 26877895