Education & Certifications
PhD, Johns Hopkins School of Public Health, Biostatistics (2011)
BA, St. Olaf College, Mathematics with minors in Statistics and Linguistics (2006)
Intravenous Calcium to Decrease Blood Loss During Intrapartum Cesarean Delivery: A Randomized Controlled Trial.
Obstetrics and gynecology
OBJECTIVE: To evaluate whether prophylactic administration of 1 g of intravenous calcium chloride after cord clamping reduces blood loss from uterine atony during intrapartum cesarean delivery.METHODS: This single-center, block-randomized, placebo-controlled, double-blind superiority trial compared the effects of 1 g intravenous calcium chloride with those of saline placebo control on blood loss at cesarean delivery. Parturients at 34 or more weeks of gestation requiring intrapartum cesarean delivery after oxytocin exposure in labor were enrolled. Calcium or saline placebo was infused over 10 minutes beginning 1minute after umbilical cord clamping in addition to standard care with oxytocin. The primary outcome was quantitative blood loss, analyzed by inverse Gaussian regression. Planned subgroup analysis excluded nonatonic bleeding, such as hysterotomy extension, arterial bleeding, and occult placenta accreta. We planned to enroll 120 patients to show a 200-mL reduction in quantitative blood loss in planned subgroup analysis, assuming up to 40% incidence of nonatonic bleeding (80% power, alpha<0.05).RESULTS: From April 2022 through March 2023, 828 laboring parturients provided consent and 120 participants were enrolled. Median blood loss was 840 mL in patients allocated to calcium chloride (n=60) and 1,051 mL in patients allocated to placebo (n=60), which was not statistically different (mean reduction 211 mL, 95% CI -33 to 410). In the planned subgroup analysis (n=39 calcium and n=40 placebo), excluding cases of surgeon-documented nonatonic bleeding, calcium reduced quantitative blood loss by 356 mL (95% CI 159-515). Rates of reported side effects were similar between the two groups (38% calcium vs 42% placebo).CONCLUSION: Prophylactic intravenous calcium chloride administered during intrapartum cesarean delivery after umbilical cord clamping did not significantly reduce blood loss in the primary analysis. However, in the planned subgroup analysis, calcium infusion significantly reduced blood loss by approximately 350 mL. These data suggest that this inexpensive and shelf-stable medication warrants future study as a novel treatment strategy to decrease postpartum hemorrhage, the leading global cause of maternal morbidity and mortality.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05027048.
View details for DOI 10.1097/AOG.0000000000005441
View details for PubMedID 37917943
The evolving role of data & safety monitoring boards for real-world clinical trials.
Journal of clinical and translational science
2023; 7 (1): e179
Clinical trials provide the "gold standard" evidence for advancing the practice of medicine, even as they evolve to integrate real-world data sources. Modern clinical trials are increasingly incorporating real-world data sources - data not intended for research and often collected in free-living contexts. We refer to trials that incorporate real-world data sources as real-world trials. Such trials may have the potential to enhance the generalizability of findings, facilitate pragmatic study designs, and evaluate real-world effectiveness. However, key differences in the design, conduct, and implementation of real-world vs traditional trials have ramifications in data management that can threaten their desired rigor.Three examples of real-world trials that leverage different types of data sources - wearables, medical devices, and electronic health records are described. Key insights applicable to all three trials in their relationship to Data and Safety Monitoring Boards (DSMBs) are derived.Insight and recommendations are given on four topic areas: A. Charge of the DSMB; B. Composition of the DSMB; C. Pre-launch Activities; and D. Post-launch Activities. We recommend stronger and additional focus on data integrity.Clinical trials can benefit from incorporating real-world data sources, potentially increasing the generalizability of findings and overall trial scale and efficiency. The data, however, present a level of informatic complexity that relies heavily on a robust data science infrastructure. The nature of monitoring the data and safety must evolve to adapt to new trial scenarios to protect the rigor of clinical trials.
View details for DOI 10.1017/cts.2023.582
View details for PubMedID 37745930
View details for PubMedCentralID PMC10514684
- The evolving role of data & amp; safety monitoring boards for real-world clinical trials JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE 2023; 7 (1)
Quantifying structural racism in cohort studies to advance prospective evidence.
SSM - population health
2023; 22: 101417
Calls-to-action in health research have described a need to improve research on race, ethnicity, and structural racism. Well-established cohort studies typically lack access to novel structural and social determinants of health (SSDOH) or precise race and ethnicity categorization, contributing to a loss of rigor to conduct informative analyses and a gap in prospective evidence on the role of structural racism in health outcomes. We propose and implement methods that prospective cohort studies can use to begin to rectify this, using the Women's Health Initiative (WHI) cohort as a case study. To do so, we evaluated the quality, precision, and representativeness of race, ethnicity, and SSDOH data compared with the target US population and operationalized methods to quantify structural determinants in cohort studies. Harmonizing racial and ethnic categorization to the current standards set by the Office of Management and Budget improved measurement precision, aligned with published recommendations, disaggregated groups, decreased missing data, and decreased participants reporting "some other race". Disaggregation revealed sub-group disparities in SSDOH, including a greater proportion of Black-Latina (35.2%) and AIAN-Latina (33.3%) WHI participants with income below the US median compared with White-Latina (42.5%) participants. We found similarities in the racial and ethnic patterning of SSDOH disparities between WHI and US women but less disparity overall in WHI. Despite higher individual-level advantage in WHI, racial disparities in neighborhood resources were similar to the US, reflecting structural racism. Median neighborhood income was comparable between Black WHI ($39,000) and US ($34,700) women. WHI SSDOH-associated outcomes may be generalizable on the basis of comparing across race and ethnicity but may quantitatively (but not qualitatively) underestimate US effect sizes. This paper takes steps towards data justice by implementing methods to make visible hidden health disparity groups and operationalizing structural-level determinants in prospective cohort studies, a first step to establishing causality in health disparities research.
View details for DOI 10.1016/j.ssmph.2023.101417
View details for PubMedID 37207111
View details for PubMedCentralID PMC10189286
Evaluation of acebilustat, a selective inhibitor of leukotriene B4 biosynthesis, for treatment of outpatients with mild-moderate COVID-19 disease: A randomized, double-blind, placebo- controlled Phase 2 trial.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
The vast majority of COVID-19 disease occurs in outpatients where treatment is limited to anti-virals for high-risk subgroups. Acebilustat, a leukotriene B4 (LTB4) inhibitor, has potential to reduce inflammation and symptom duration.In a single-center trial spanning Delta and Omicron variants, outpatients were randomized to 100 mg of oral acebilustat or placebo for 28 days. Patients reported daily symptoms via electronic query through Day 28 with phone follow-up on Day 120 and collected nasal swabs on Days 1-10. The primary outcome was sustained symptom resolution to Day 28. Secondary 28-day outcomes included time to first symptom resolution, area under the curve (AUC) of longitudinal daily symptom scores; duration of viral shedding through Day 10; and symptoms on Day 120.Sixty participants were randomized to each study arm. At enrollment, median duration and number of symptoms were 4 (IQR 3-5) days and 9 (IQR 7-11) symptoms. Most patients (90%) were vaccinated with 73% having neutralizing antibodies. A minority (44%) of participants (35% in the acebilustat arm and 53% in placebo) had sustained symptom resolution at Day 28 (HR 0.6, 95% CI 0.34-1.04, p = 0.07 favoring placebo). There was no difference in mean AUC of symptom scores over 28 days (difference in mean of AUC 9.4, 95% CI -42.1-60.9, p=0.72). Acebilustat did not impact viral shedding or symptoms at Day 120.Sustained symptoms through Day 28 were common in this low-risk population. Despite this, LTB4 antagonism with acebilustat did not shorten symptom duration in outpatients with COVID-19.
View details for DOI 10.1093/cid/ciad187
View details for PubMedID 36996150
The development of a mobile app-focused deduplication strategy for the Apple Heart Study that informs recommendations for future digital trials.
Stat (International Statistical Institute)
2022; 11 (1): e470
An app-based clinical trial enrolment process can contribute to duplicated records, carrying data management implications. Our objective was to identify duplicated records in real time in the Apple Heart Study (AHS). We leveraged personal identifiable information (PII) to develop a dissimilarity score (DS) using the Damerau-Levenshtein distance. For computational efficiency, we focused on four types of records at the highest risk of duplication. We used the receiver operating curve (ROC) and resampling methods to derive and validate a decision rule to classify duplicated records. We identified 16,398 (4%) duplicated participants, resulting in 419,297 unique participants out of a total of 438,435 possible. Our decision rule yielded a high positive predictive value (96%) with negligible impact on the trial's original findings. Our findings provide principled solutions for future digital trials. When establishing deduplication procedures for digital trials, we recommend collecting device identifiers in addition to participant identifiers; collecting and ensuring secure access to PII; conducting a pilot study to identify reasons for duplicated records; establishing an initial deduplication algorithm that can be refined; creating a data quality plan that informs refinement; and embedding the initial deduplication algorithm in the enrolment platform to ensure unique enrolment and linkage to previous records.
View details for DOI 10.1002/sta4.470
View details for PubMedID 36589778
Effectiveness of a Community-Based Structured Physical Activity Program for Adults With Type 2 Diabetes: A Randomized Clinical Trial.
JAMA network open
2022; 5 (12): e2247858
The efficacy of physical activity interventions among individuals with type 2 diabetes has been established; however, practical approaches to translate and extend these findings into community settings have not been well explored.To test the effectiveness of providing varying frequencies of weekly structured exercise sessions to improve diabetes control.The IMPACT (Initiate and Maintain Physical Activity in Communities Trial) study was a controlled randomized clinical trial (randomization occurred from October 2016 to April 2019) that included a 6-month, structured exercise intervention either once or thrice weekly vs usual care (UC; advice only). The exercise intervention was conducted at community-based fitness centers. Follow-up visits were conducted in a university research clinic. Participants included adults with type 2 diabetes (hemoglobin A1c [HbA1c] 6.5%-13.0%, not taking insulin, and no precluding health issues). Data analysis was performed from January to April 2022.A once-weekly structured exercise group, a thrice-weekly structured exercise group, or UC.The primary outcome was HbA1c at 6 months.A total of 357 participants (143 women [40.1%]) with a mean (SD) age of 57.4 (11.1) years were randomized (119 each to the UC, once-weekly exercise, and thrice-weekly exercise groups). There was no significant difference in HbA1c change by study group in the intention-to-treat analysis at 6 months. Specifically, HbA1c changed by -0.23% (95% CI, -0.48% to 0.01%) in the thrice-weekly exercise group and by -0.16% (95% CI, -0.41% to 0.09%) in the once-weekly exercise group. A total of 62 participants (52.1%) in the once-weekly exercise group and 56 participants (47.1%) in the thrice-weekly exercise group were at least 50% adherent to the assigned structured exercise regimen and were included in the per-protocol analysis. Per-protocol analysis showed that HbA1c changed by -0.35% (95% CI, -0.60% to -0.10%; P = .005) at 3 months and by -0.38% (95% CI, -0.65% to -0.12%; P = .005) at 6 months in the thrice-weekly exercise group compared with UC. There was no significant decrease in HbA1c in the once-weekly exercise group. The exercise intervention was effective in improving self-reported minutes of metabolic equivalent tasks per week for participants in the thrice-weekly exercise group (both overall and per protocol).Although the intervention was not effective in the intention-to-treat analysis, participants in the thrice-weekly exercise group who attended at least 50% of the sessions during the 6-month exercise intervention program improved HbA1c levels at 6 months. Future efforts should focus on improving adherence to thrice-weekly structured exercise programs to meet exercise guidelines.ClinicalTrials.gov Identifier: NCT02061579.
View details for DOI 10.1001/jamanetworkopen.2022.47858
View details for PubMedID 36542382
Contemplative Practices Behavior Is Positively Associated with Well-Being in Three Global Multi-Regional Stanford WELL for Life Cohorts.
International journal of environmental research and public health
2022; 19 (20)
Positive associations between well-being and a single contemplative practice (e.g., mindfulness meditation) are well documented, yet prior work may have underestimated the strength of the association by omitting consideration of multiple and/or alternative contemplative practices. Moreover, little is known about how contemplative practice behavior (CPB) impacts different dimensions of well-being. This study investigates the relationship of CPB, consisting of four discrete practices (embodied somatic-observing, non-reactive mindfulness, self-compassion, and compassion for others), with multiple dimensions of well-being. As with other canonical lifestyle behaviors, multiple contemplative practices can be integrated into one's daily routine. Thus, it is critical to holistically consider these behaviors, extending them beyond a simple uni-dimensional measure (e.g., daily mindfulness meditation practice). We developed an integrative measure of four types of contemplative practice and found it to be significantly associated with a multi-dimensional measure of well-being. Importantly, our findings were from three large global multi-regional cohorts and compared against better-understood lifestyle behaviors (physical activity). Data were drawn from California/San Francisco Bay Area, (n = 6442), Hangzhou City (n = 10,268), and New Taipei City (n = 3033). In all three cohorts, we found statistically significant (p < 0.05) positive associations between CPB and well-being, both overall and with all of the constituent domains of well-being, comparable to or stronger than the relationship with physical activity across most well-being outcomes. These findings provide robust and cross-cultural evidence for a positive association between CPB and well-being, illuminate dimensions of well-being that could be most influenced by CPB, and suggest CPB may be useful to include as part of fundamental lifestyle recommendations for health and well-being.
View details for DOI 10.3390/ijerph192013485
View details for PubMedID 36294068
Early immune markers of clinical, virological, and immunological outcomes in patients with COVID-19: a multi-omics study.
The great majority of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunological outcomes in SARS-CoV-2-infected patients.Leveraging longitudinal samples and data from a clinical trial (N=108) in SARS-CoV-2-infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients. We characterized the association between early immune markers and subsequent disease progression, control of viral shedding, and SARS-CoV-2-specific T cell and antibody responses measured up to 7 months after enrollment. We further compared associations between early immune markers and subsequent T cell and antibody responses following natural infection with those following mRNA vaccination. We developed machine-learning models to predict patient outcomes and validated the predictive model using data from 54 individuals enrolled in an independent clinical trial.We identify early immune signatures, including plasma RIG-I levels, early IFN signaling, and related cytokines (CXCL10, MCP1, MCP-2, and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2-specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizer-BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine-learning models using 2-7 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset.Early immune signatures following infection can accurately predict clinical and immunological outcomes in outpatients with COVID-19 using validated machine-learning models.Support for the study was provided from National Institute of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) (U01 AI150741-01S1 and T32-AI052073), the Stanford's Innovative Medicines Accelerator, National Institutes of Health/National Institute on Drug Abuse (NIH/NIDA) DP1DA046089, and anonymous donors to Stanford University. Peginterferon lambda provided by Eiger BioPharmaceuticals.
View details for DOI 10.7554/eLife.77943
View details for PubMedID 36239699
Lessons learned in the Apple Heart Study and implications for the data management of future digital clinical trials.
Journal of biopharmaceutical statistics
The digital clinical trial is fast emerging as a pragmatic trial that can improve a trial's design including recruitment and retention, data collection and analytics. To that end, digital platforms such as electronic health records or wearable technologies that enable passive data collection can be leveraged, alleviating burden from the participant and study coordinator. However, there are challenges. For example, many of these data sources not originally intended for research may be noisier than traditionally obtained measures. Further, the secure flow of passively collected data and their integration for analysis is non-trivial. The Apple Heart Study was a prospective, single-arm, site-less digital trial designed to evaluate the ability of an app to detect atrial fibrillation. The study was designed with pragmatic features, such as an app for enrollment, a wearable device (the Apple Watch) for data collection, and electronic surveys for participant-reported outcomes that enabled a high volume of patient enrollment and accompanying data. These elements led to challenges including identifying the number of unique participants, maintaining participant-level linkage of multiple complex data streams, and participant adherence and engagement. Novel solutions were derived that inform future designs with an emphasis on data management. We build upon the excellent framework of the Clinical Trials Transformation Initiative to provide a comprehensive set of guidelines for data management of the digital clinical trial that include an increased role of collaborative data scientists in the design and conduct of the modern digital trial.
View details for DOI 10.1080/10543406.2022.2080698
View details for PubMedID 35695137
Modifiable Resources and Resilience in Racially and Ethnically Diverse Older Women: Implications for Health Outcomes and Interventions.
International journal of environmental research and public health
2022; 19 (12)
Introduction: Resilience-which we define as the "ability to bounce back from stress"-can foster successful aging among older, racially and ethnically diverse women. This study investigated the association between psychological resilience in the Women's Health Initiative Extension Study (WHI-ES) and three constructs defined by Staudinger's 2015 model of resilience and aging: (1) perceived stress, (2) non-psychological resources, and (3) psychological resources. We further examined whether the relationship between resilience and key resources differed by race/ethnicity. Methods: We conducted a secondary analysis on 77,395 women aged 62+ (4475 Black or African American; 69,448 non-Hispanic White; 1891 Hispanic/Latina; and 1581 Asian or Pacific Islanders) who enrolled in the WHI-ES, which was conducted in the United States. Participants completed a short version of the Brief Resilience Scale one-time in 2011. Guided by Staudinger's model, we used linear regression analysis to examine the relationships between resilience and resources, adjusting for age, race/ethnicity, and stressful life events. To identify the most significant associations, we applied elastic net regularization to our linear regression models. Findings: On average, women who reported higher resilience were younger, had fewer stressful life events, and reported access to more resources. Black or African American women reported the highest resilience, followed by Hispanic/Latina, non-Hispanic White, and Asian or Pacific Islander women. The most important resilience-related resources were psychological, including control of beliefs, energy, personal growth, mild-to-no forgetfulness, and experiencing a sense of purpose. Race/ethnicity significantly modified the relationship between resilience and energy (overall interaction p = 0.0017). Conclusion: Increasing resilience among older women may require culturally informed stress reduction techniques and resource-building strategies, including empowerment to control the important things in life and exercises to boost energy levels.
View details for DOI 10.3390/ijerph19127089
View details for PubMedID 35742334
Favipiravir for treatment of outpatients with asymptomatic or uncomplicated COVID-19: a double-blind randomized, placebo-controlled, phase 2 trial.
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Favipiravir is an oral, RNA-dependent RNA polymerase inhibitor with in vitro activity against SARS-CoV2. Despite limited data, favipiravir is administered to patients with COVID-19 in several countries.We conducted a phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV2 RT-PCR within 72 hours of enrollment. Participants were randomized 1: 1 to receive placebo or favipiravir (1800mg BID Day 1, 800 mg BID Days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis.From July 8, 2020 - March 23, 2021, we randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (SD 12.5) and 57 (49%) were women. We found no difference in time to shedding cessation by treatment arm overall (HR 0.76 favoring placebo, 95% confidence interval [CI] 0.48-1.20) or in sub-group analyses (age, sex, high-risk comorbidities, seropositivity or symptom duration at enrollment). We observed no difference in time to symptom resolution (initial: HR 0.84, 95% CI 0.54-1.29; sustained: HR 0.87, 95% CI 0.52-1.45). We detected no difference in accumulation of transition mutations in the viral genome during treatment.Our data do not support favipiravir use at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher doses of favipiravir are effective and safe for patients with COVID-19.
View details for DOI 10.1093/cid/ciac312
View details for PubMedID 35446944
Gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA suggest prolonged gastrointestinal infection.
Med (New York, N.Y.)
COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.1,2 SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.3-5 Although much is known about early fecal RNA shedding, little is known about the long term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.6.We analyze the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlate shedding with disease symptoms.Fecal SARS-CoV-2 RNA is detected in 49.2% [95% Confidence interval = 38.2%-60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at and after 4 months, 12.7% [8.5%-18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% [2.0%-7.3%] shed at 7 months. Finally, we find that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA.The extended presence of viral RNA in feces, but not respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract, and that this infection can be prolonged in a subset of individuals with COVID-19.
View details for DOI 10.1016/j.medj.2022.04.001
View details for PubMedID 35434682
View details for PubMedCentralID PMC9005383
Early immune responses have long-term associations with clinical, virologic, and immunologic outcomes in patients with COVID-19.
The great majority of SARS-CoV-2 infections are mild and uncomplicated, but some individuals with initially mild COVID-19 progressively develop more severe symptoms. Furthermore, there is substantial heterogeneity in SARS-CoV-2-specific memory immune responses following infection. There remains a critical need to identify host immune biomarkers predictive of clinical and immunologic outcomes in SARS-CoV-2-infected patients. Leveraging longitudinal samples and data from a clinical trial in SARS-CoV-2 infected outpatients, we used host proteomics and transcriptomics to characterize the trajectory of the immune response in COVID-19 patients within the first 2 weeks of symptom onset. We identify early immune signatures, including plasma RIG-I levels, early interferon signaling, and related cytokines (CXCL10, MCP1, MCP-2 and MCP-3) associated with subsequent disease progression, control of viral shedding, and the SARS-CoV-2 specific T cell and antibody response measured up to 7 months after enrollment. We found that several biomarkers for immunological outcomes are shared between individuals receiving BNT162b2 (Pfizera"BioNTech) vaccine and COVID-19 patients. Finally, we demonstrate that machine learning models using 7-10 plasma protein markers measured early within the course of infection are able to accurately predict disease progression, T cell memory, and the antibody response post-infection in a second, independent dataset.
View details for DOI 10.21203/rs.3.rs-847082/v1
View details for PubMedID 35132407
Low-fat dietary pattern reduces urinary incontinence in postmenopausal women: post hoc analysis of the Women's Health Initiative Diet Modification Trial.
AJOG global reports
2022; 2 (1): 100044
BACKGROUND: Urinary incontinence affects >40% of women in the United States, with an annual societal cost of >$12 billion and demonstrated associations with depressive symptoms, social isolation, and loss of work productivity. Weight has been established as an exposure that increases urinary incontinence risk and certain dietary components have been associated with urinary incontinence symptoms. We hypothesized that diet plays a key role in the association between weight and urinary incontinence in US women.OBJECTIVE: This study aimed to examine the effect of a low-fat diet on urinary incontinence in postmenopausal women as a post hoc analysis of a randomized controlled trial of diet modification.STUDY DESIGN: This was a post hoc analysis of the Women's Health Initiative Dietary Modification randomized controlled trial of 48,835 postmenopausal women from 40 US centers assigned to a dietary intervention (20% energy from fat, 5 fruits or vegetable servings, and 6 whole grain servings daily and an intensive behavioral modification program) or to the usual diet comparison group. The outcome was urinary incontinence at 1 year.RESULTS: Of the participants, 60% were randomized to the usual diet comparison group and 40% to the dietary modification intervention. After adjusting for weight change, women assigned to the dietary modification intervention were less likely to report urinary incontinence (odds ratio, 0.94; 95% confidence interval, 0.90-0.98; P=.003), more likely to report urinary incontinence resolution (odds ratio, 1.11; 95% confidence interval, 1.03-1.19; P=.01), and less likely to develop urinary incontinence (odds ratio, 0.92; 95% confidence interval, 0.87-0.98; P=.01) in adjusted models.CONCLUSION: Dietary modification may be a reasonable treatment for postmenopausal women with incontinence and also a urinary incontinence prevention strategy for continent women. Our results provide evidence to support a randomized clinical trial to determine whether a reduced fat-intake dietary modification is an effective intervention for the prevention and treatment of urinary incontinence. In addition to providing further insights into mechanisms of lower urinary tract symptoms, these findings may have a substantial impact on public health based on the evidence that diet seems to be a modifiable risk factor for urinary incontinence.
View details for DOI 10.1016/j.xagr.2021.100044
View details for PubMedID 36274962
Hispanic Ethnicity and Social Determinants of Health in Pulmonary Arterial Hypertension: The Pulmonary Hypertension Association Registry.
Annals of the American Thoracic Society
Rationale There is a noticeable underrepresentation of minorities in clinical trials and registries in pulmonary arterial hypertension (PAH). Prior studies evaluating the association between Hispanic ethnicity and clinical outcomes in patients with PAH have not assessed the socioeconomic profile of Hispanic individuals or the significance of social determinants of health in clinical outcomes. Objective To determine the association between Hispanic ethnicity, social determinants of health, and clinical outcomes in PAH. Methods Prospective cohort study of adult participants with PAH enrolled in the Pulmonary Hypertension Association Registry, a multicenter US-based registry of patients treated at Pulmonary Hypertension Care Centers. Participants were classified as Hispanics and non-Hispanic Whites, based on self-reported ethnicity. A comparison of baseline clinical and sociodemographic characteristics between groups was performed as well using absolute standardized differences (ASD). The primary outcome of the study was to assess transplant-free survival between Hispanics and non-Hispanic Whites. A Cox proportional hazards model was used for the multivariable analysis after adjusting for age, sex, PAH etiology, annual income, education level and health insurance. Results A total of 683 individuals were included, 98 (14.3%) of Hispanic ethnicity. Hispanic patients had impaired access to health care (31.6% vs. 12.9% Medicaid/uninsured; ASD 0.35), lower education level (72.6% vs. 94.0% high school graduates or higher; ASD 0.60) and lower annual income (32.0% vs. 17.4% with income <20,000 US dollars; ASD 0.47), as compared with non-Hispanic Whites. Hispanic patients had a higher frequency of ER visits and a higher number of hospitalizations, despite having similar disease severity (incidence rate ratio 1.452, 95% CI 1.326 - 1.590 and 1.428, 95% CI 1.292 - 1.577, respectively). While the unadjusted analysis showed a lower transplant/death hazard ratio for Hispanics (HR 0.47, 95% CI 0.24-0.94; p=0.032), there was no association between Hispanic ethnicity and outcome in the multivariable model after adjusting for social determinants of health and other covariates (HR 0.76, 95% CI 0.35-1.62; p=0.474). Conclusions Hispanic ethnicity was not associated with differences in survival after adjusting for social determinants of health and other factors. Social determinants of health are important to consider when assessing the association between ethnicity and outcomes in PAH.
View details for DOI 10.1513/AnnalsATS.202109-1051OC
View details for PubMedID 35239467
Pregnancy success rates for lesbian women undergoing intrauterine insemination.
2021; 2 (3): 275-281
Objective: To compare the pregnancy outcomes of lesbian women undergoing donor sperm intrauterine insemination (IUI) with that of heterosexual women undergoing IUI using partner or donor sperm.Design: Retrospective cohort analysis.Setting: Two academic fertility practices.Patients: All IUI cycles between 2007 and2016.Interventions: None.Main outcome measures: Primary outcomes included clinical pregnancy (CP) rates and live birth/ongoing pregnancy (LB) rates. The baseline characteristics and cycle characteristics were compared between the two groups using absolute standardized differences (ASDs). To account for the correlation between cycles per patient, a generalized estimating equation method for multivariable logistic regression was used.Results: A total of 11,870 IUI cycles were included, of which 393 were in lesbian women using donor sperm and 11,477 were in heterosexual women with infertility using either partner or donor sperm. The CP rates were similar between the lesbian and heterosexual groups (13.2% vs. 11.1%, respectively, ASD = 0.06). In addition, the LB rates were similar between the two groups (10.4% vs. 8.3%, respectively, ASD = 0.10). After implementing the generalized estimating equation in a multivariable logistic regression, the lesbian group had an overall higher odds of CP (adjusted odds ratio 1.40, 95% confidence interval: [1.04-1.88]) and LB (adjusted odds ratio 1.59, 95% confidence interval [1.15-2.20]) compared with the heterosexual group. The clinical miscarriage rate was higher in the heterosexual group compared with that in the lesbian group (23.8% vs. 15.4%, respectively, ASD = 0.21).Conclusion: Although the unadjusted rates were similar between the two groups, the adjusted CP and LB odds were significantly higher for lesbian women undergoing IUI for procreative management than those for heterosexual women undergoing IUI for infertility.
View details for DOI 10.1016/j.xfre.2021.04.007
View details for PubMedID 34553151
DXA Versus Clinical Measures of Adiposity as Predictors of Cardiometabolic Diseases and All-Cause Mortality in Postmenopausal Women.
Mayo Clinic proceedings
OBJECTIVE: To investigate whether dual-energy x-ray absorptiometry (DXA) estimates of adiposity improve risk prediction for cardiometabolic diseases over traditional surrogates, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in older women.PATIENTS AND METHODS: We analyzed up to 9744 postmenopausal women aged 50 to 79 years participating in the Women's Health Initiative who underwent a DXA scan and were free of cardiovascular disease and diabetes at baseline (October 1993 to December 1998) and followed through September 2015. Baseline BMI, WC, WHR, and DXA-derived percent total-body and trunk fat (%TrF) were incorporated into multivariable Cox proportional hazards models to estimate the risk of incident diabetes, atherosclerosis-related cardiovascular diseases (ASCVDs), heart failure, and death. Concordance probability estimates assessed the relative discriminatory value between pairs of adiposity measures.RESULTS: A total of 1327 diabetes cases, 1266 atherosclerotic cardiovascular disease (ASCVD) cases, 292 heart failure cases, and 1811 deaths from any cause accrued during a median follow-up of up to 17.2 years. The largest hazard ratio observed per 1 standard deviation increase of an adiposity measure was for %TrF and diabetes (1.77; 95% CI, 1.66-1.88) followed by %TrF and broadly defined ASCVD (1.22; 95% CI, 1.15-1.30). These hazard ratios remained significant for both diabetes (1.47; 95% CI, 1.37-1.57) and ASCVD (1.22; 95% CI, 1.14-1.31) even after adjusting for the best traditional surrogate measure of adiposity, WC. Percentage of trunk fat was also the only adiposity measure to demonstrate statistically significant improved concordance probability estimates over BMI, WC, and WHR for diabetes and ASCVD (all P<0.05).CONCLUSION: DXA-derived estimates of abdominal adiposity in postmenopausal women may allow for substantially improved risk prediction of diabetes over standard clinical risk models. Larger DXA studies with complete lipid biomarker profiles and clinical trials are needed before firm conclusions can be made.
View details for DOI 10.1016/j.mayocp.2021.04.027
View details for PubMedID 34479738
The COVID-19 Outpatient Pragmatic Platform Study (COPPS): Study design of a multi-center pragmatic platform trial.
Contemporary clinical trials
More than 3000 clinical trials related to COVID-19 have been registered through clinicaltrials.gov. 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 fructo-oligosaccharide prebiotic is well-tolerated in adults undergoing allogeneic hematopoietic stem cell transplantation: a phase I dose-escalation trial.
Transplantation and cellular therapy
BACKGROUND: Alterations of the gut microbiota after allogeneic hematopoietic cell transplantation (allo-HCT) are a key factor in the development of transplant-related complications such as graft-versus-host disease (GVHD). Interventions that preserve the gut microbiome hold promise to improve HCT-associated morbidity and mortality. Murine models demonstrate that prebiotics such as fructo-oligosaccharides (FOS) may increase gut levels of short-chain fatty acids (SCFAs) such as butyrate, and consequently induce proliferation of immunomodulatory FOXP3+ CD4+ T-regulatory cells (Tregs), that impact GVHD risk.METHODS: We conducted a pilot Phase I trial to assess the investigate the maximum tolerated dose of FOS in patients undergoing reduced-intensity (RIC) allo-HCT (n=15) compared to concurrent controls (n=16). We administered FOS starting at pretransplant conditioning and continuing for a total of 21 days. We characterized the gut microbiome using shotgun metagenomic sequencing, measured stool SCFAs using LC-MS, and determined peripheral T-cell concentrations using CyTOF.RESULTS: We found that FOS was safe and well-tolerated at 10g per day without significant adverse effects in patients undergoing allo-HCT. Community-level gut microbiota composition was significantly different on the day of transplant (day 0) between patients receiving FOS compared to concurrent controls, however FOS-associated alterations of the gut microbiota were not sustained after transplant. Although the impact of FOS was fleeting, transplantation itself impacted a substantial number of taxa over time. In our small pilot trial, no significant differences were observed in gut microbial metabolic pathways, stool SCFAs, or in peripheral Tregs although Tregs trended higher in those patients who received FOS. A marker of CD4+ T-cell activation, namely CTLA4+, was significantly higher in patients receiving FOS, whereas a non-significant trend existed for FOP3+CD4+ T-regulatory cells that were higher in those receiving FOS compared to controls.CONCLUSIONS: FOS is well-tolerated at 10g per day in patients undergoing RIC allo-HCT. While alterations in the gut microbiota and peripheral immune cell composition in those receiving FOS are intriguing, additional studies are required to investigate the use of prebiotics in HCT recipients.
View details for DOI 10.1016/j.jtct.2021.07.009
View details for PubMedID 34274493
The ARREST Pneumonia (Arrest Respiratory Failure due to Pneumonia) Trial: Rationale and Design.
Annals of the American Thoracic Society
Patients hospitalized for pneumonia are at high risk for mortality. Effective therapies are therefore needed. Recent randomized clinical trials suggest that systemic steroids can reduce the length of hospital stay among patients hospitalized for pneumonia. Further, preliminary findings from a feasibility study demonstrated that early treatment with a combination of an inhaled corticosteroid and a bronchodilator can improve oxygenation and reduce risk of respiratory failure in patients at risk of acute respiratory distress syndrome. Whether such a combination administered early is effective in reducing acute respiratory failure among patients hospitalized with pneumonia is unknown. Here we describe the Arrest Respiratory Failure due to Pneumonia (ARREST Pneumonia) trial designed to address this question. ARREST Pneumonia is a two-arm randomized double-blinded placebo-controlled trial designed to test the efficacy of a combination of an inhaled corticosteroid and a beta agonist compared to placebo for the prevention of acute respiratory failure in hospitalized participants with severe pneumonia. The primary outcome is acute respiratory failure within 7 days of randomization, defined as a composite endpoint of intubation and mechanical ventilation, or need for high flow nasal cannula oxygen therapy or non-invasive ventilation for > 36 hours (each alone or combined), or death within 36 hours of being placed on respiratory support. The planned enrollment is 600 adult participants at ten academic medical centers. In addition, we will measure selected plasma biomarkers to better understand mechanisms of action. The trial is funded by the National Heart Lung and Blood Institute and is registered in clinicaltrials.gov (NCT04193878).
View details for DOI 10.1513/AnnalsATS.202009-1115SD
View details for PubMedID 33493423
Clinical trials in a COVID-19 pandemic: Shared infrastructure for continuous learning in a rapidly changing landscape.
Clinical trials (London, England)
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
Design of a population-based longitudinal cohort study of SARS-CoV-2 incidence and prevalence among adults in the San Francisco Bay Area.
Annals of epidemiology
We describe the design of a longitudinal cohort study to determine SARS-CoV-2 incidence and prevalence among a population-based sample of adults living in six San Francisco Bay Area counties.Using an address-based sample, we stratified households by county and by census-tract risk. Risk strata were determined by using regression models to predict infections by geographic area using census-level sociodemographic and health characteristics. We disproportionately sampled high and medium risk strata, which had smaller population sizes, to improve precision of estimates, and calculated a desired sample size of 3400. Participants were primarily recruited by mail and were followed monthly with PCR testing of nasopharyngeal swabs, testing of venous blood samples for antibodies to SARS-CoV-2 spike and nucleocapsid antigens, and testing of the presence of neutralizing antibodies, with completion of questionnaires about socio-demographics and behavior. Estimates of incidence and prevalence will be weighted by county, risk strata and sociodemographic characteristics of non-responders, and will take into account laboratory test performance.We enrolled 3842 adults from August to December, 2020, and completed follow-up March 31, 2021. We reached target sample sizes within most strata.Our stratified random sampling design will allow us to recruit a robust general population cohort of adults to determine the incidence of SARS-CoV-2 infection. Identifying risk strata was unique to the design and will help ensure precise estimates, and high-performance testing for presence of virus and antibodies will enable accurate ascertainment of infections.
View details for DOI 10.1016/j.annepidem.2021.11.001
View details for PubMedID 34800659
Prescription Patterns for Pulmonary Vasodilators in the Treatment of Pulmonary Hypertension Associated With Chronic Lung Diseases: Insights From a Clinician Survey.
Frontiers in medicine
1800; 8: 764815
Background: Pulmonary hypertension is a complication of chronic lung diseases (PH-CLD) associated with significant morbidity and mortality. Management guidelines for PH-CLD emphasize the treatment of the underlying lung disease, but the role of PH-targeted therapy remains controversial. We hypothesized that treatment approaches for PH-CLD would be variable across physicians depending on the type of CLD and the severity of PH. Methods and Results: Between May and July 2020, we conducted an online survey of PH experts asking for their preferred treatment approach in seven hypothetical cases of PH-CLD of varying severity. We assessed agreement amongst clinicians for initial therapy choice using Fleiss' kappa calculations. Over 90% of respondents agreed that they would treat cases of severe PH in the context of mild lung disease with some form of PH-targeted therapy. For cases of severe PH in the context of severe lung disease, over 70% of respondents agreed to use PH-targeted therapy. For mild PH and mild lung disease cases, <50% of respondents chose to start PH-specific therapy. There was overall poor agreement between respondents in the choice to use mono-, double or triple combination therapy with PH-specific agents in all cases. Conclusion: Although management guidelines discourage the routine use of PH-targeted therapies to treat PH-CLD patients, most physicians choose to treat patients with some form of PH-targeted therapy. The choice of therapy and treatment approach are variable and appear to be influenced by the severity of the PH and the underlying lung disease.
View details for DOI 10.3389/fmed.2021.764815
View details for PubMedID 34926507
Arrhythmias Other Than Atrial Fibrillation in Those With an Irregular Pulse Detected With a Smartwatch: Findings From the Apple Heart Study.
Circulation. Arrhythmia and electrophysiology
The Apple watch irregular pulse detection algorithm was found to have a positive predictive value of 0.84 for identification of atrial fibrillation (AF). We sought to describe the prevalence of arrhythmias other than AF in those with an irregular pulse detected on a smartwatch.The Apple Heart Study investigated a smartwatch-based irregular pulse notification algorithm to identify AF. For this secondary analysis, we analyzed participants who received an ambulatory ECG patch after index irregular pulse notification. We excluded participants with AF identified on ECG patch and described the prevalence of other arrhythmias on the remaining participant ECG patches. We also reported the proportion of participants self-reporting subsequent AF diagnosis.Among 419 297 participants enrolled in the Apple Heart Study, 450 participant ECG patches were analyzed, with no AF on 297 ECG patches (66%). Non-AF arrhythmias (excluding supraventricular tachycardias <30 beats and pauses <3 seconds) were detected in 119 participants (40.1%) with ECG patches without AF. The most common arrhythmias were frequent PACs (burden ≥1% to <5%, 15.8%; ≥5% to <15%, 8.8%), atrial tachycardia (≥30 beats, 5.4%), frequent PVCs (burden ≥1% to <5%, 6.1%; ≥5% to <15%, 2.7%), and nonsustained ventricular tachycardia (4-7 beats, 6.4%; ≥8 beats, 3.7%). Of 249 participants with no AF detected on ECG patch and patient-reported data available, 76 participants (30.5%) reported subsequent AF diagnosis.In participants with an irregular pulse notification on the Apple Watch and no AF observed on ECG patch, atrial and ventricular arrhythmias, mostly PACs and PVCs, were detected in 40% of participants. Defining optimal care for patients with detection of incidental arrhythmias other than AF is important as AF detection is further investigated, implemented, and refined.
View details for DOI 10.1161/CIRCEP.121.010063
View details for PubMedID 34565178
Inflammatory but not respiratory symptoms are associated with ongoing upper airway viral shedding in outpatients with uncomplicated COVID-19.
Diagnostic microbiology and infectious disease
2021; 102 (3): 115612
Although the vast majority of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections are uncomplicated, our understanding of predictors of symptom resolution and viral shedding cessation remains limited. We characterized symptom trajectories and oropharyngeal viral shedding among 120 outpatients with uncomplicated Coronavirus Disease of 2019 (COVID-19) enrolled in a clinical trial of Peginterferon Lambda, which demonstrated no clinical or virologic benefit compared with placebo. In the combined trial cohort, objective fever was uncommon, inflammatory symptoms (myalgias, fatigue) peaked at 4 to 5 days postsymptom onset, and cough peaked at 9 days. The median time to symptom resolution from earliest symptom onset was 17 days (95% confidence interval 14-18). SARS-CoV-2 IgG seropositivity at enrollment was associated with hastened resolution of viral shedding (hazard ratio 1.80, 95% confidence interval 1.05-3.1, P = 0.03), but not with symptom resolution. Inflammatory symptoms were associated with a significantly greater odds of oropharyngeal SARS-CoV-2 RNA detection; respiratory symptoms were not. These findings have important implications for COVID-19 screening approaches and trial design.
View details for DOI 10.1016/j.diagmicrobio.2021.115612
View details for PubMedID 34974350
Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial.
2021; 12 (1): 1967
Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.
View details for DOI 10.1038/s41467-021-22177-1
View details for PubMedID 33785743
Resilience and CVD-protective Health Behaviors in Older Women: Examining Racial and Ethnic Differences in a Cross-Sectional Analysis of the Women's Health Initiative.
2020; 12 (7)
Little is known about the relationship between self-reported psychological resilience (resilience) and health behaviors shown to reduce the risk of cardiovascular disease (CVD). This study examines the associations between resilience and CVD-related risk factors, such as diet, smoking, physical activity, sleep, and alcohol consumption among older American women from diverse backgrounds.METHODS: A cross-sectional secondary analysis was conducted on 77,395 women (mean age 77 years, Black (N = 4475, 5.8%), non-Hispanic white (N = 69,448, 89.7%), Latina (N = 1891, 2.4%), and Asian or Pacific Islander (N = 1581, 2.0%)) enrolled in the Women's Health Initiative Extension Study II. Resilience was measured using an abbreviated version of the brief resilience scale. Multivariable logistic regression models were used to evaluate the association between resilience and health behaviors associated with risk for CVD, while adjusting for stressful life events and sociodemographic information. To test whether these associations varied among racial/ethnic groups, an interaction term was added to the fully adjusted models between resilience and race/ethnicity.RESULTS: High levels of resilience were associated with better diet quality (top 2 quintiles of the Healthy Eating Index 2015) (OR = 1.22 (95% Confidence Interval (1.15-1.30)), adhering to recommended physical activity (≥ 150 min per week) (1.56 (1.47, 1.66)), sleeping the recommended hours per night (7-9) (1.36 (1.28-1.44)), and moderate alcohol intake (consuming alcoholic drink(s) 1-7 days per week) (1.28 (1.20-1.37)). The observed association between resilience and sleep is modified by race/ethnicity (p = 0.03).CONCLUSION: Irrespective of race/ethnicity, high resilience was associated with CVD-protective health behaviors. This warrants further investigation into whether interventions aimed at improving resilience could increase the effectiveness of lifestyle interventions.
View details for DOI 10.3390/nu12072107
View details for PubMedID 32708626
Comparing enhanced versus standard Diabetes Prevention Program among indigenous adults in an urban setting: a randomized controlled trial.
BMC public health
2020; 20 (1): 139
Indigenous people in the United States are at high risk for diabetes. Psychosocial stressors like historical trauma may impede success in diabetes prevention programs.A comparative effectiveness trial compared a culturally tailored diabetes prevention program (standard group) with an enhanced one that addressed psychosocial stressors (enhanced group) in 2015 to 2017. Participants were 207 Indigenous adults with a body mass index (BMI) of ≥30 and one additional criterion of metabolic syndrome, and were randomized to the standard or enhanced group. Both groups received a culturally tailored behavioral diabetes prevention program. Strategies to address psychosocial stressors were provided to the enhanced group only. Change in BMI over 12 months was the primary outcome. Secondary outcomes included change in quality of life, and clinical, behavioral, and psychosocial measures at 6 and 12 months.The two groups did not significantly differ in BMI change at 12 months. The two groups also did not differ in any secondary outcomes at 6 or 12 months, with the exception of unhealthy food consumption; the standard group reported a larger mean decrease (95% CI) in consumption of unhealthy food compared with the enhanced group (- 4.6 [- 6.8, - 2.5] vs. -0.7 [- 2.9, 1.4], p = 0.01). At 6 months, significant improvements in weight and the physical component of the quality of life measure were observed for both groups compared with their baseline level. Compared with baseline, at 12 months, the standard group showed significant improvement in BMI (mean [95% CI], - 0.5 [- 1.0, - 0.1]) and the enhanced group showed significant improvement in the physical component of the quality of life (2.9 [0.7, 5.2]).Adding strategies to address psychosocial barriers to a culturally tailored diabetes prevention program was not successful for improving weight loss among urban Indigenous adults.(if applicable): NCT02266576. Registered October 17, 2014 on clinicaltrials.gov. The trial was prospectively registered.
View details for DOI 10.1186/s12889-020-8250-7
View details for PubMedID 32000738
Organizational Characteristics Associated With ICU Liberation (ABCDEF) Bundle Implementation by Adult ICUs in Michigan.
Critical care explorations
2020; 2 (8): e0169
The ICU Liberation (ABCDEF) Bundle can help to improve care and outcomes for ICU patients, but bundle implementation is far from universal. Understanding how ICU organizational characteristics influence bundle implementation could inform quality improvement efforts. We surveyed all hospitals in Michigan with adult ICUs to determine whether organizational characteristics were associated with bundle implementation and to determine the level of agreement between ICU physician and nurse leaders around ICU organizational characteristics and bundle implementation.We surveyed ICU physician and nurse leaders, assessing their safety culture, ICU team collaboration, and work environment. Using logistic and linear regression models, we compared these organizational characteristics to bundle element implementation, and also compared physician and nurse leaders' perceptions about organizational characteristics and bundle implementation.All (n = 72) acute care hospitals with adult ICUs in Michigan.ICU physician and nurse leader pairs from each hospital's main ICU.We developed, pilot-tested, and deployed an electronic survey to all subjects over a 3 month period in 2016.Results from 73 surveys (28 physicians, 45 nurses, 60% hospital response rate) demonstrated significant variation in hospital and ICU size and type, organizational characteristics, and physician/nurse perceptions of ICU organization and bundle implementation. We found that a robust safety culture and collaborative work environment that uses checklists to facilitate team communication are strongly associated with bundle implementation. There is also a significant dose-response effect between safety culture, a collaborative work environment, and overall bundle implementation.We identified several specific ICU practices that can facilitate ABCDEF Bundle implementation. Our results can be used to develop effective bundle implementation strategies that leverage safety culture, interprofessional collaboration, and routine checklist use in ICUs to improve bundle implementation and performance.
View details for DOI 10.1097/CCE.0000000000000169
View details for PubMedID 32885171
View details for PubMedCentralID PMC7437774
The EffectiveNess of LIfestyle with Diet and Physical Activity Education ProGram Among Prehypertensives and Stage 1 HyperTENsives in an Urban Community Setting (ENLIGHTEN) Study.
Journal of community health
This study aimsto determine the effectiveness of a monthly lifestyle education program, which included advice on nutritional changes and physical activity enhancement in the reduction of blood pressure and selected biochemical and anthropometric parameters among pre-hypertensive and stage 1 hypertensive participants in Manila, Philippines. Participants resided in two barangays (districts), in Manila, Philippines, and each barangay was assigned to either the intervention or attention-control group. The intervention group received monthly lectures on cardiovascular disease and organized classes on diet and exercise, while the attention-control group received monthly lectures on non-cardiovascular topics, with verbal advice that healthy diet and exercise are important. The primary outcome was systolic blood pressure, with secondary outcomes of BMI, waist circumference, and laboratory measures. Linear mixed effects models with an interaction between intervention group and time were used to estimate the 6-month change in each group. At 6months, systolic blood pressure was lower in the intervention group compared to the attention-control group (-12.7mmHg (95% CI [-14.5, -10.9]) vs. -0.24mmHg (95% CI [-1.87, 1.43]), p-value<0.001). Waist circumference (p<0.001), BMI (p<0.001), and total cholesterol (p=0.049) were also lower. However, no statistically significant difference in fasting glucose was observed between the two groups (p=0.740). This study showed that participants receiving a non-pharmacological intervention, specifically a low-cost diet and active lifestyle education program, experienced a greater decrease in blood pressure, BMI, waist circumference, and total cholesterol than the attention-control group. Educational programs such as in ENLIGHTEN show promise for a developing country with limited resources to improve hypertension levels, and ultimately cardiovascular health. ENLIGHTEN deserves further study in randomized trials.
View details for DOI 10.1007/s10900-019-00764-0
View details for PubMedID 31677046
CONTAMINATION IN ADULT MIDSTREAM CLEAN-CATCH URINE CULTURES IN THE EMERGENCY DEPARTMENT: A RANDOMIZED CONTROLLED TRIAL
JOURNAL OF EMERGENCY NURSING
2019; 45 (5): 488–501
A midstream clean-catch urine sample is recommended to obtain a urine culture in symptomatic adults with suspected urinary tract infection. The aim of this randomized controlled trial was to determine whether a novel funnel urine-collection system combined with a silver-colloidal cleaning wipe would decrease mixed flora contamination in midstream clean-catch urine cultures from ambulatory adults in the emergency department.In a 2x2 factorial trial, adult participants were randomized to 4 groups: (A) sterile screw-top urine collection container/cup paired with a castile-soap wipe (control group); (B) sterile screw-top urine collection container/cup paired with a colloidal silver-impregnated wipe; (C) sterile urine-collection funnel paired with a castile-soap wipe; (D) sterile urine-collection funnel paired with a colloidal silver-impregnated wipe.The trial was stopped after interim analysis, as the contamination rate in the control group (30%) was markedly lower than the historical ED contamination rate (40%) at the study site. From 1,112 urinalysis results, 223 urine culture results were analyzed (190 female patients and 33 male patients). Urine contamination rates were as follows: Group A, n = 67 (29.9% contaminated); Group B, n = 69 (34.8% contaminated); Group C, n = 51 (23.5% contaminated); Group D, n = 36 (22.2% contaminated). The differences in contamination rates were not statistically different among any of the groups.The use of a funnel urine-collection system and silver-impregnated wipe did not reduce urine-culture contamination in adult midstream clean-catch urine cultures in the emergency department.
View details for DOI 10.1016/j.jen.2019.06.001
View details for Web of Science ID 000482217800004
View details for PubMedID 31445626
- Multiple listing in lung transplant candidates: A cohort study AMERICAN JOURNAL OF TRANSPLANTATION 2019; 19 (4): 1098–1108
- Discovery of Distinct Immune Phenotypes Using Machine Learning in Pulmonary Arterial Hypertension CIRCULATION RESEARCH 2019; 124 (6): 904–19
Fibrinogen Concentrate as an Alternative to Cryoprecipitate in a Postcardiopulmonary Transfusion Algorithm in Infants Undergoing Cardiac Surgery: A Prospective Randomized Controlled Trial.
Anesthesia and analgesia
Infants undergoing cardiac surgery are at risk for bleeding and massive transfusion due to an immature coagulation system, complex surgeries, and cardiopulmonary bypass (CPB) effects. Hemodilution from CPB promotes an acquired hypofibrinogenemia that results in impaired fibrin formation, inadequate clot formation, and increased bleeding. In North America, the current standard of care to supplement fibrinogen is cryoprecipitate. An alternative option is the off-label use of fibrinogen concentrate (FC; RiaSTAP; CSL Behring, Marburg, Germany), a purified fibrinogen. Because perioperative allogenic transfusions are associated with increased morbidity and mortality, we sought to determine whether FC would be an acceptable alternative to cryoprecipitate in a post-CPB transfusion algorithm in infants undergoing open-heart surgery.We randomized 60 infants (<12 months) undergoing nonemergent cardiac surgery with CPB at 2 tertiary care children's hospitals to receive either cryoprecipitate or FC in a post-CPB transfusion algorithm. Infants underwent a stratified randomization based on institution and surgical complexity. The primary outcome was the difference in number of intraoperative allogenic blood product transfusions. Secondary outcomes included 24-hour chest tube output (CTO), mechanical ventilation time, adverse events (AEs), intensive care unit (ICU) length of stay (LOS), hospital LOS, postoperative thrombosis, and death within 30 days of surgery. The primary analysis followed the intent-to-treat (ITT) principle and was performed using linear regression adjusted for institution and complexity of surgery. A per-protocol (PP) analysis was also performed.Between June 2016 and January 2018, we enrolled 60 patients with complete data available for 25 patients who received cryoprecipitate and 29 patients who received FC. Patients in the cryoprecipitate group (median age: 4 months [2-6 months]) received 5.5 (4.0-7.0) allogeneic blood units in the ITT analysis and 6.0 units (5.0-7.0 units) in the PP analysis. Patients in the FC group (median age: 4 months [2-5]) received 4 units (3.0-5.0 units) in the ITT analysis and 4.0 units (3.0-5.0 units) in the PP analysis. In the adjusted ITT analysis, the FC group received 1.79 units (95% confidence interval [CI], 0.64-2.93; P = .003) less than the cryoprecipitate group. In the adjusted PP analysis, the FC group received 2.67 units (95% CI, 1.75-3.59; P < .001) less than the cryoprecipitate group. There were no significant differences in secondary outcomes or AEs.Our findings suggest that FC may be considered as an alternative to cryoprecipitate for the treatment of hypofibrinogenemia in infants with bleeding after CPB. Although we found no significant differences between secondary outcomes or AEs, further studies are needed to assess safety.
View details for DOI 10.1213/ANE.0000000000004384
View details for PubMedID 31490252
Development of a comprehensive health-risk prediction tool for postmenopausal women.
Menopause (New York, N.Y.)
The aim of the study was to develop a web-based calculator that predicts the likelihood of experiencing multiple, competing outcomes prospectively over 5, 10, and 15 years.Baseline demographic and medical data from a healthy and racially and ethnically diverse cohort of 161,808 postmenopausal women, aged 50 to 79 at study baseline, who participated in the Women's Health Initiative (WHI), were used to develop and evaluate a risk-prediction calculator designed to predict individual risk for morbidity and mortality outcomes. Women were enrolled from 40 sites arranged in four regions of the United States. The calculator predicts all-cause mortality, adjudicated outcomes of health events (ie, myocardial infarction [MI], stroke, and hip fracture), and disease (lung, breast, and colorectal cancer). A proportional subdistribution hazards regression model was used to develop the calculator in a training dataset using data from three regions. The calculator was evaluated using the C-statistic in a test dataset with data from the fourth region.The predictive validity of our calculator measured by the C-statistic in the test dataset for a first event at 5 and 15 years was as follows: MI 0.77, 0.61, stroke 0.77, 0.72, lung cancer 0.82, 0.79, breast cancer 0.60, 0.59, colorectal cancer 0.67, 0.60, hip fracture 0.79, 0.76, and death 0.74, 0.72.This study represents the first large-scale study to develop a risk prediction calculator that yields health risk prediction for several outcomes simultaneously. Development of this tool is a first step toward enabling women to prioritize interventions that may decrease these risks. : Video Summary:http://links.lww.com/MENO/A463.
View details for DOI 10.1097/GME.0000000000001411
View details for PubMedID 31567871
Large-Scale Assessment of a Smartwatch to Identify Atrial Fibrillation.
The New England journal of medicine
2019; 381 (20): 1909–17
BACKGROUND: Optical sensors on wearable devices can detect irregular pulses. The ability of a smartwatch application (app) to identify atrial fibrillation during typical use is unknown.METHODS: Participants without atrial fibrillation (as reported by the participants themselves) used a smartphone (Apple iPhone) app to consent to monitoring. If a smartwatch-based irregular pulse notification algorithm identified possible atrial fibrillation, a telemedicine visit was initiated and an electrocardiography (ECG) patch was mailed to the participant, to be worn for up to 7 days. Surveys were administered 90 days after notification of the irregular pulse and at the end of the study. The main objectives were to estimate the proportion of notified participants with atrial fibrillation shown on an ECG patch and the positive predictive value of irregular pulse intervals with a targeted confidence interval width of 0.10.RESULTS: We recruited 419,297 participants over 8 months. Over a median of 117 days of monitoring, 2161 participants (0.52%) received notifications of irregular pulse. Among the 450 participants who returned ECG patches containing data that could be analyzed - which had been applied, on average, 13 days after notification - atrial fibrillation was present in 34% (97.5% confidence interval [CI], 29 to 39) overall and in 35% (97.5% CI, 27 to 43) of participants 65 years of age or older. Among participants who were notified of an irregular pulse, the positive predictive value was 0.84 (95% CI, 0.76 to 0.92) for observing atrial fibrillation on the ECG simultaneously with a subsequent irregular pulse notification and 0.71 (97.5% CI, 0.69 to 0.74) for observing atrial fibrillation on the ECG simultaneously with a subsequent irregular tachogram. Of 1376 notified participants who returned a 90-day survey, 57% contacted health care providers outside the study. There were no reports of serious app-related adverse events.CONCLUSIONS: The probability of receiving an irregular pulse notification was low. Among participants who received notification of an irregular pulse, 34% had atrial fibrillation on subsequent ECG patch readings and 84% of notifications were concordant with atrial fibrillation. This siteless (no on-site visits were required for the participants), pragmatic study design provides a foundation for large-scale pragmatic studies in which outcomes or adherence can be reliably assessed with user-owned devices. (Funded by Apple; Apple Heart Study ClinicalTrials.gov number, NCT03335800.).
View details for DOI 10.1056/NEJMoa1901183
View details for PubMedID 31722151
Discovery of Distinct Immune Phenotypes Using Machine Learning in Pulmonary Arterial Hypertension.
Accumulating evidence implicates inflammation in pulmonary arterial hypertension (PAH) and therapies targeting immunity are under investigation, though it remains unknown if distinct immune phenotypes exist.Identify PAH immune phenotypes based on unsupervised analysis of blood proteomic profiles.In a prospective observational study of Group 1 PAH patients evaluated at Stanford University (discovery cohort, n=281) and University of Sheffield (validation cohort, n=104) between 2008-2014, we measured a circulating proteomic panel of 48 cytokines, chemokines, and factors using multiplex immunoassay. Unsupervised machine learning (consensus clustering) was applied in both cohorts independently to classify patients into proteomic immune clusters, without guidance from clinical features. To identify central proteins in each cluster, we performed partial correlation network analysis. Clinical characteristics and outcomes were subsequently compared across clusters. Four PAH clusters with distinct proteomic immune profiles were identified in the discovery cohort. Cluster 2 (n=109) had low cytokine levels similar to controls. Other clusters had unique sets of upregulated proteins central to immune networks- cluster 1 (n=58)(TRAIL, CCL5, CCL7, CCL4, MIF), cluster 3 (n=77)(IL-12, IL-17, IL-10, IL-7, VEGF), and cluster 4 (n=37)(IL-8, IL-4, PDGF-β, IL-6, CCL11). Demographics, PAH etiologies, comorbidities, and medications were similar across clusters. Non-invasive and hemodynamic surrogates of clinical risk identified cluster 1 as high-risk and cluster 3 as low-risk groups. Five-year transplant-free survival rates were unfavorable for cluster 1 (47.6%, CI 35.4-64.1%) and favorable for cluster 3 (82.4%, CI 72.0-94.3%)(across-cluster p<0.001). Findings were replicated in the validation cohort, where machine learning classified four immune clusters with comparable proteomic, clinical, and prognostic features.Blood cytokine profiles distinguish PAH immune phenotypes with differing clinical risk that are independent of World Health Organization Group 1 subtypes. These phenotypes could inform mechanistic studies of disease pathobiology and provide a framework to examine patient responses to emerging therapies targeting immunity.
View details for PubMedID 30661465
- Rationale and design of a large-scale, app-based study to identify cardiac arrhythmias using a smartwatch: The Apple Heart Study AMERICAN HEART JOURNAL 2019; 207: 66–75
Validation of a novel automated signal analysis tool for ablation of Wolff-Parkinson-White Syndrome.
2019; 14 (6): e0217282
BACKGROUND: In previous pilot work we demonstrated that a novel automated signal analysis tool could accurately identify successful ablation sites during Wolff-Parkinson-White (WPW) ablation at a single center.OBJECTIVE: We sought to validate and refine this signal analysis tool in a larger multi-center cohort of children with WPW.METHODS: A retrospective review was performed of signal data from children with WPW who underwent ablation at two pediatric arrhythmia centers from 2008-2015. All patients with WPW ≤ 21 years who underwent invasive electrophysiology study and ablation with ablation signals available for review were included. Signals were excluded if temperature or power delivery was inadequate or lesion time was < 5 seconds. Ablation lesions were reviewed for each patient. Signals were classified as successful if there was loss of antegrade and retrograde accessory pathway (AP) conduction or unsuccessful if ablation did not eliminate AP conduction. Custom signal analysis software analyzed intracardiac electrograms for amplitudes, high and low frequency components, integrated area, and signal timing components to create a signal score. We validated the previously published signal score threshold 3.1 in this larger, more diverse cohort and explored additional scoring options. Logistic regression with lasso regularization using Youden's index criterion and a cost-benefit criterion to identify thresholds was considered as a refinement to this score.RESULTS: 347 signals (141 successful, 206 unsuccessful) in 144 pts were analyzed [mean age 13.2 ± 3.9 years, 96 (67%) male, 66 (45%) left sided APs]. The software correctly identified the signals as successful or unsuccessful in 276/347 (80%) at a threshold of 3.1. The performance of other thresholds did not significantly improve the predictive ability. A signal score threshold of 3.1 provided the following diagnostic accuracy for distinguishing a successful from unsuccessful signal: sensitivity 83%, specificity 77%, PPV 71%, NPV 87%.CONCLUSIONS: An automated signal analysis software tool reliably distinguished successful versus unsuccessful ablation electrograms in children with WPW when validated in a large, diverse cohort. Refining the tools using an alternative threshold and statistical method did not improve the original signal score at a threshold of 3.1. This software was effective across two centers and multiple operators and may be an effective tool for ablation of WPW.
View details for DOI 10.1371/journal.pone.0217282
View details for PubMedID 31242221
Methamphetamine use association with pulmonary diseases: a retrospective investigation of hospital discharges in California from 2005 to 2011
European Respiratory Journal Open Research
View details for DOI 10.1183/23120541.00017-2019
Effects of reproductive period duration and number of pregnancies on midlife ECG indices: a secondary analysis from the Women's Health Initiative Clinical Trial
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
Melanoma risk prediction using a multilocus genetic risk score in the Women's Health Initiative cohort.
Journal of the American Academy of Dermatology
BACKGROUND: Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk.OBJECTIVE: We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women.METHODS: Genetic risk scores were calculated using 21 genome-wide association study-significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset.RESULTS: Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma.LIMITATIONS: Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort.CONCLUSION: Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available.
View details for PubMedID 29499294
Patterns of Disrespectful Physician Behavior at an Academic Medical Center: Implications for Training, Prevention, and Remediation.
Academic medicine : journal of the Association of American Medical Colleges
PURPOSE: Physician disrespectful behavior affects quality of care, patient safety, and collaborative clinical team function. Evidence defining the demographics, ethnography, and epidemiology of disrespectful behavior is lacking.METHOD: The authors conducted a retrospective analysis of reports of disrespectful physician behavior at Stanford Hospital and Clinics from March 2011 through February 2015. Events were stratified by role, gender, specialty, and location in the hospital or clinics where the event occurred. Event rate ratios were estimated using a multivariable negative binomial regression model. Correlation of rates of faculty and trainees in the same specialty were assessed.RESULTS: One-hundred-ninety-nine events concerned faculty; 160 concerned trainees. Events were concentrated among a small number of physicians in both groups. The rates of faculty and trainee events within the same specialty were highly correlated (Spearman's rho: 0.90; P < .001). Male physicians had an adjusted event rate 1.86 (95% CI = 1.33 - 2.60; P < .001) times that of females. Procedural physicians were 3.67 times (95% CI = 2.63 - 5.13; P < .001) more likely to have a disrespectful behavior event than non-procedural physicians when adjusting for other covariates. Most common location for faculty was the operating rooms (69 events, 34%); for trainees, the medical/surgical units (43 events, 27%).CONCLUSIONS: Patterns of physician disrespectful behavior differed by role, gender, specialty, and location. Rates among faculty and trainees of the same specialty were highly correlated. These patterns can be used to create more focused education and training for specific physician groups and individualized remediation interventions.
View details for DOI 10.1097/ACM.0000000000002126
View details for PubMedID 29319539
Randomised placebo-controlled safety and tolerability trial of FK506 (tacrolimus) for pulmonary arterial hypertension
EUROPEAN RESPIRATORY JOURNAL
2017; 50 (3)
Pulmonary arterial hypertension (PAH) is a devastating disease characterised by occlusive pulmonary vasculopathy. Activation of bone morphogenetic protein receptor 2 (BMPR2) signalling by FK506 (tacrolimus) reverses occlusive vasculopathy in rodent PAH models. Here, we determined the safety and tolerability of low-level FK506 therapy in stable PAH patients.We performed a randomised, double-blind, placebo-controlled, 16-week, single-centre, phase IIa trial in PAH patients with New York Heart Association functional class II/III symptoms using three FK506 target levels (<2, 2-3 and 3-5 ng·mL-1). 23 patients were randomised and 20 patients completed the trial.FK506 was generally well tolerated, with nausea/diarrhoea being the most commonly reported adverse event and no observation of line infections in patients on intravenous prostacyclin therapy. PAH patients had significantly lower BMPR2 expression in peripheral blood mononuclear cells versus healthy controls (n=13; p=0.005), which improved after FK506 treatment. While we observed that some patients responded with a pronounced increase in BMPR2 expression as well as improvement in 6-min walk distance, and serological and echocardiographic parameters of heart failure, these changes were not significant.Low-level FK506 is well tolerated and increases BMPR2 in subsets of PAH patients. These results support the study of FK506 in a phase IIb efficacy trial.
View details for PubMedID 28893866
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
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
Racial and ethnic disparities in lung transplant listing and waitlist outcomes.
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
The United States lung transplant registry data demonstrate differences in adult waitlist mortality by race/ethnicity. It is unknown whether these differences persist after risk adjustment or occur secondary to disparities in disease severity at the time of listing.Adult lung transplant waitlist candidates between May 4, 2005 and March 5, 2015 were identified and compared by non-Hispanic white (NHW), non-Hispanic black (NHB), Hispanic and Asian race/ethnicity. A competing risk proportional hazards model was used to assess the association of race/ethnicity with the unadjusted and adjusted risk of waitlist death or removal for too sick, transplant, or removal for other reason. Disease illness severity at transplant listing was compared by race/ethnicity.There were 20,684 lung transplant candidates identified (82% NHW, 9% NHB, 6% Hispanic, 2% Asian and 1% other). Non-white candidates had higher unadjusted waitlist mortality, which was fully mitigated by adjusting for other risk factors (NHB: hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.93 to 1.18; Hispanic: HR 1.02, 95% CI 0.99 to 1.18; Asian: HR 0.90, 95% CI 0.70 to 1.16). Adjusted waitlist access to transplant was lower in non-white candidates (NHB: HR 0.88, 95% CI 0.83 to 0.94; Hispanic: HR 0.87, 95% CI 0.81 to 0.94; Asian: HR 0.83, 95% CI 0.73 to 0.96). NHW candidates with obstructive lung disease and pulmonary fibrosis were older with less illness severity at listing than non-white candidates.Within the current lung allocation system, there is no difference in risk-adjusted waitlist mortality by race/ethnicity, but non-white waitlist candidates have lower risk-adjusted access to lung transplant. Non-white candidates are generally younger with greater disease-specific illness severity at the time of lung transplant listing.
View details for PubMedID 29129372
Features and Outcomes of Methamphetamine Associated Pulmonary Arterial Hypertension.
American journal of respiratory and critical care medicine
While amphetamines are recognized as "likely" agents to cause drugs and toxins associated pulmonary arterial hypertension (PAH), (meth)amphetamine associated PAH (Meth-APAH) has not been well described.To prospectively characterize the clinical presentation, histopathology, and outcomes of Meth-APAH compared to those of idiopathic PAH (iPAH).We performed a prospective cohort study of Meth-APAH and iPAH patients presenting to the Stanford University Pulmonary Hypertension Program between 2003-2015. Clinical, pulmonary angiography, histopathology, and outcomes data were compared. We used data from the Healthcare Cost and Utilization Project to estimate the epidemiology of PAH in (meth)amphetamine abusers hospitalized in California.The study sample included 90 Meth-APAH and 97 iPAH patients. Meth-APAH patients were less likely to be female, but similar in age, body mass index, and six minute walk distance to iPAH patients. Meth-PAH patients reported more advanced heart failure symptoms, had significantly higher right atrial pressure (12.7±6.8 vs. 9.8±5.1 mmHg, p=0.001), and lower stroke volume index (22.2±7.1 vs 25.5±8.7 mL/m2, p=0.01). Event-free survival in Meth-APAH was 64.2%, 47.2%, and 25% at 2.5, 5, and 10 years respectively, representing more than double the risk of clinical worsening or death compared to iPAH (HR 2.04, 95% CI 1.28-3.25, p=0.003) independent of confounders. California data demonstrated a 2.6 fold increase in risk of PAH diagnosis in hospitalized (meth)amphetamine users.Meth-APAH is a severe and progressive form of PAH with poor outcomes. Future studies should focus on mechanisms of disease and potential therapeutic considerations.
View details for PubMedID 28934596
Breast and Cervical Cancer Screening Literacy Among Korean American Women: A Community Health Worker-Led Intervention.
American journal of public health
2017; 107 (1): 159-165
To test a community health worker (CHW)-led health literacy intervention on mammogram and Papanicolaou test screening among Korean American women.We conducted a cluster-randomized trial at 23 ethnic churches in the Baltimore, Maryland-Washington, DC, metropolitan area between 2010 and 2014. Trained CHWs enrolled 560 women. The intervention group received an individually tailored cancer-screening brochure followed by CHW-led health literacy training and monthly telephone counseling with navigation assistance. Study outcomes included receipt of an age-appropriate cancer screening test, health literacy, cancer knowledge, and perceptions about cancer screening at 6 months.The odds of having received a mammogram were 18.5 (95% confidence interval [CI] = 9.2, 37.4) times higher in the intervention than in the control group, adjusting for covariates. The odds of receiving a Papanicolaou test were 13.3 (95% CI = 7.9, 22.3) times higher; the odds of receiving both tests were 17.4 (95% CI = 7.5, 40.3) times higher. Intervention effects also included increases in health literacy and positive perceptions about cancer screening.A health literacy-focused CHW intervention successfully promoted cancer-screening behaviors and related cognitive and attitudinal outcomes in Korean American women.
View details for PubMedID 27854539
Risk Estimates for Atherosclerotic Cardiovascular Disease in Adults With Congenital Heart Disease
AMERICAN JOURNAL OF CARDIOLOGY
2017; 119 (1): 112-118
The adult with congenital heart disease (CHD) is at risk of developing atherosclerotic cardiovascular disease (ASCVD). We performed a cross-sectional study to describe established ASCVD risk factors and estimate 10-year and lifetime risk of ASCVD in adults over age 18 with CHD of moderate or great complexity using 3 validated risk assessment tools-the Framingham Study Cardiovascular Disease Risk Assessment, the Reynolds Risk Score, and the ASCVD Risk Estimator. We obtained extensive clinical and survey data on 178 enrolled patients, with average age 37.1 ± 12.6 years, 51% men. At least 1 modifiable ASCVD risk factor was present in 70%; the 2 most common were overweight/obesity (53%) and systemic hypertension (24%). Laboratory data were available in 103 of the 178 patients. Abnormal levels of glycated hemoglobin, high-sensitivity C-reactive protein, and high-density lipoprotein were each found in around 30% of patients. The 10-year ASCVD predicted risk using all 3 tools was relatively low (i.e., at least 90% of patients <10% risk), yet the median estimated lifetime risk was 36%. In conclusion, ASCVD risk factors are prevalent in adults with CHD. The risk estimation tools suggest that this population is particularly vulnerable to ASCVD with aging and should undergo guideline-based screening and management of modifiable risk factors.
View details for DOI 10.1016/j.amjcard.2016.09.023
View details for PubMedID 28247847
Physical activity and sedentary behavior in relation to lung cancer incidence and mortality in older women: The Women's Health Initiative.
International journal of cancer
2016; 139 (10): 2178-2192
Physical activity has been associated with lower lung cancer incidence and mortality in several populations. We investigated these relationships in the Women's Health Initiative Observational Study (WHI-OS) and Clinical Trial (WHI-CT) prospective cohort of postmenopausal women. The WHI study enrolled 161,808 women aged 50-79 years between 1993-1998 at 40 U.S. clinical centers; 129,401 were eligible for these analyses. Cox proportional hazards models were used to assess the association of baseline physical activity levels [metabolic equivalent (MET)-minutes/week: none <100 (reference), low 100-<500, medium 500-<1200, high 1200+] and sedentary behavior with total lung cancer incidence and mortality. Over 11.8 mean follow-up years, 2,148 incident lung cancer cases and 1,365 lung cancer deaths were identified. Compared to no activity, higher physical activity levels at study entry were associated with lower lung cancer incidence [p=0.009; hazard ratios (95% confidence intervals) for each physical activity category: low, HR: 0.86 (0.76-0.96); medium, HR: 0.82 (0.73-0.93); and high, HR: 0.90 (0.79-1.03)], and mortality [p<0.0001; low, HR: 0.80 (0.69-0.92); medium, HR: 0.68 (0.59-0.80); and high, HR: 0.78 (0.66-0.93)]. Body mass index (BMI) modified the association with lung cancer incidence (p=0.01), with a stronger association in women with BMI<30 kg/m(2) . Significant associations with sedentary behavior were not observed. In analyses by lung cancer subtype, higher total physical activity levels were associated with lower lung cancer mortality for both overall NSCLC and adenocarcinoma. In conclusion, physical activity may be protective for lung cancer incidence and mortality in postmenopausal women, particularly in non-obese women. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ijc.30281
View details for PubMedID 27439221
Hospitalized Patients with Heart Failure and Common Bacterial Infections: A Nationwide Analysis of Concomitant Clostridium Difficile Infection Rates and In-Hospital Mortality.
Journal of cardiac failure
2016; 22 (11): 891-900
Patients with heart failure (HF) are frequently hospitalized with common bacterial infections. It is unknown whether they experience concomitant Clostridium difficile infection (CDI) more frequently than patients without HF, and whether CDI affects their mortality.We used 2012 National Inpatient Sample data to determine the rate of CDI and associated in-hospital mortality for hospitalized patients with comorbid HF and urinary tract infection (UTI), pneumonia (PNA), or sepsis. Univariate and multivariate analyses were performed. Weighted data are presented.There were an estimated 5,851,582 patient hospitalizations with discharge diagnosis of UTI, PNA, or sepsis in 2012 in the United States. Of these, 23.4% had discharge diagnosis of HF. Patients with HF were on average older and had more comorbidities. CDI rates were higher in hospitalizations with discharge diagnosis of HF compared with those without HF (odds ratio 1.13, 95% confidence interval 1.10-1.16) after controlling for patient demographics and comorbidities and hospital characteristics. Among HF hospitalizations with UTI, PNA, or sepsis, those with concomitant CDI had a higher in-hospital mortality than those without concomitant CDI (odds ratio 1.81, 95% confidence interval 1.71-1.92) after controlling for the covariates outlined previously.HF is associated with higher CDI rates among hospitalized patients with other common bacterial infections, even when adjusting for other known risk factors for CDI. Among these patients with comorbid HF, CDI is associated with markedly higher in-hospital mortality. These findings may suggest an opportunity to improve outcomes for hospitalized patients with HF and common bacterial infections, possibly through improved Clostridium difficile screening and prophylaxis protocols.
View details for DOI 10.1016/j.cardfail.2016.06.005
View details for PubMedID 27317844
Development and evaluation of an enhanced diabetes prevention program with psychosocial support for urban American Indians and Alaska natives: A randomized controlled trial
CONTEMPORARY CLINICAL TRIALS
2016; 50: 28-36
Diabetes is highly prevalent, affecting over 25 million adults in the US, yet it can be effectively prevented through lifestyle interventions, including the well-tested Diabetes Prevention Program (DPP). American Indian/Alaska Native (AIAN) adults, the majority of whom live in urban settings, are more than twice as likely to develop diabetes as non-Hispanic whites. Additionally, prevalent mental health issues and psychosocial stressors may facilitate progression to diabetes and hinder successful implementation of lifestyle interventions for AIAN adults. This 2-phased study first engaged community stakeholders to develop culturally-tailored strategies to address mental health concerns and psychosocial stressors. Pilot testing (completed) refined those strategies that increase engagement in an enhanced DPP for urban AIAN adults. Second, the enhanced DPP will be compared to a standard DPP in a randomized controlled trial (ongoing) with a primary outcome of body mass index (BMI) and a secondary outcome of quality of life (QoL) over 12months. Obese self-identified AIAN adults residing in an urban setting with one or more components of the metabolic syndrome (excluding waist circumference) will be randomized to the enhanced or standard DPP (n=204). We hypothesize that addressing psychosocial barriers within a culturally-tailored DPP will result in clinical (BMI) and superior patient-centered (QoL) outcomes as compared to a standard DPP. Exploratory outcomes will include cardiometabolic risk factors (e.g., waist circumference, blood pressure, fasting glucose) and health behaviors (e.g., diet, physical activity). Results of this trial may be applicable to other urban AIAN or minority communities or even diabetes prevention in general.
View details for DOI 10.1016/j.cct.2016.06.015
View details for Web of Science ID 000385321600005
View details for PubMedID 27381232
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
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
Lung Quality and Utilization in Controlled Donation After Circulatory Determination of Death Within the United States
AMERICAN JOURNAL OF TRANSPLANTATION
2016; 16 (4): 1207-1215
Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization.
View details for DOI 10.1111/ajt.13599
View details for Web of Science ID 000373075400021
Relation of statin use with non-melanoma skin cancer: prospective results from the Women's Health Initiative.
British journal of cancer
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
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
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
Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.
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
Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma.
2016; 7: 12510-?
Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC.
View details for DOI 10.1038/ncomms12510
View details for PubMedID 27539887
View details for PubMedCentralID PMC4992160
Coffee and caffeine consumption and the risk of hypertension in postmenopausal women
AMERICAN JOURNAL OF CLINICAL NUTRITION
2016; 103 (1): 210-217
The associations of coffee and caffeine intakes with the risk of incident hypertension remain controversial.We sought to assess longitudinal relations of caffeinated coffee, decaffeinated coffee, and total caffeine intakes with mean blood pressure and incident hypertension in postmenopausal women in the Women's Health Initiative Observational Study.In a large prospective study, type and amount of coffee and total caffeine intakes were assessed by using self-reported questionnaires. Hypertension status was ascertained by using measured blood pressure and self-reported drug-treated hypertension. The mean intakes of caffeinated coffee, decaffeinated coffee, and caffeine were 2-3 cups/d, 1 cup/d, and 196 mg/d, respectively. Using multivariable linear regression, we examined the associations of baseline intakes of caffeinated coffee, decaffeinated coffee, and caffeine with measured systolic and diastolic blood pressures at annual visit 3 in 29,985 postmenopausal women who were not hypertensive at baseline. We used Cox proportional hazards models to estimate HRs and their 95% CIs for time to incident hypertension.During 112,935 person-years of follow-up, 5566 cases of incident hypertension were reported. Neither caffeinated coffee nor caffeine intake was associated with mean systolic or diastolic blood pressure, but decaffeinated coffee intake was associated with a small but clinically irrelevant decrease in mean diastolic blood pressure. Decaffeinated coffee intake was not associated with mean systolic blood pressure. Intakes of caffeinated coffee, decaffeinated coffee, and caffeine were not associated with the risk of incident hypertension (P-trend > 0.05 for all).In summary, these findings suggest that caffeinated coffee, decaffeinated coffee, and caffeine are not risk factors for hypertension in postmenopausal women.
View details for DOI 10.3945/ajcn.115.120147
View details for Web of Science ID 000367869500025
View details for PubMedCentralID PMC4691674
Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity.
Breast cancer research and treatment
2015; 154 (3): 609-616
In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.
View details for DOI 10.1007/s10549-015-3647-1
View details for PubMedID 26602222
Factors Associated with Nursing Home Admission after Stroke in Older Women.
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
2015; 24 (10): 2329-2337
We examined the social and economic factors associated with nursing home (NH) admission in older women, overall and poststroke.The Women's Health Initiative (WHI) included women aged 50-79 years at enrollment (1993-1998). In the WHI Extension Study (2005-2010), participants annually reported any NH admission in the preceding year. Separate multivariate logistic regression models analyzed social and economic factors associated with long-term NH admission, defined as an admission on 2 or more questionnaires, overall and poststroke.Of 103,237 participants, 8904 (8.6%) reported NH admission (2005-2010); 534 of 2225 (24.0%) women with incident stroke reported poststroke NH admission. Decreased likelihoods of NH admission overall were demonstrated for Asian, Black, and Hispanic women (versus whites, adjusted odds ratio [aOR] = .35-.44, P < .001) and women with higher income (aOR = .75, 95% confidence interval [CI] = .63-.90), whereas increased likelihoods of NH admission overall were seen for women with lower social support (aOR = 1.34, 95% CI = 1.16-1.54) and with incident stroke (aOR = 2.59, 95% CI = 2.15-3.12). Increased odds of NH admission after stroke were demonstrated for women with moderate disability after stroke (aOR = 2.76, 95% CI = 1.73-4.42). Further adjustment for stroke severity eliminated the association found for race/ethnicity, income, and social support.The level of care needed after a disabling stroke may overwhelm social and economic structures in place that might otherwise enable avoidance of NH admission. We need to identify ways to provide care consistent with patients' preferences, even after a disabling stroke.
View details for DOI 10.1016/j.jstrokecerebrovasdis.2015.06.013
View details for PubMedID 26169547
View details for PubMedCentralID PMC4592792
Calcium and vitamin D supplementation do not influence menopause-related symptoms: Results of the Women's Health Initiative Trial
2015; 81 (3): 377-383
It is unknown whether supplementation with calcium and vitamin D has an impact on menopause-related symptoms.As part of the Women's Health Initiative Calcium/Vitamin D Supplementation Trial (CaD), women were randomized at 40 clinical sites to elemental calcium carbonate 1000 mg with vitamin D 400 IU daily or placebo. At the CaD baseline visit (year 1 or year 2) and during a mean follow-up of 5.7 years, participants provided data on menopause-related symptoms via questionnaires. Generalized linear mixed effects techniques were used to address research questions.After excluding participants with missing data (N=2125), we compared menopause-related symptoms at follow-up visits of 17,101 women randomized to CaD with those of 17,056 women given the placebo. Women in the CaD arm did not have a different number of symptoms at follow-up compared to women taking the placebo (p=0.702). Similarly, there was no difference between sleep disturbance, emotional well-being, or energy/fatigue at follow-up in those who were randomized to CaD supplementation compared to those taking the placebo.Our data suggest that supplementation with 1000 mg of calcium plus 400 IU of vitamin D does not influence menopause-related symptoms over an average of 5.7 years of follow-up among postmenopausal women with an average age of 64 at the WHI baseline visit.
View details for DOI 10.1016/j.maturitas.2015.04.007
View details for Web of Science ID 000357229600009
View details for PubMedID 26044075
View details for PubMedCentralID PMC4469550
Recreational activity and sedentary behavior in relation to lung cancer incidence and mortality in the Women's Health Initiative
AMER SOC CLINICAL ONCOLOGY. 2015
View details for Web of Science ID 000358036900386
Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women: A Cohort Study From the Women's Health Initiative.
Circulation. Cardiovascular quality and outcomes
2015; 8 (3): 309-316
Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors.We identified 15,288 women from the Women's Health Initiative Biomarkers studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993-1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol ratio TG/HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which occurred in 894 (5.8%) women. Insulin resistance was associated with CVD risk after adjusting for age and race/ethnicity with hazard ratios (95% confidence interval [CI]) per doubling in insulin of 1.21 (CI, 1.12-1.31), in HOMA-IR of 1.19 (CI, 1.11-1.28), in TG/HDL-C of 1.35 (CI, 1.26-1.45), and for impaired fasting glucose of 1.31 (CI, 1.05-1.64). Although insulin, HOMA-IR, and TG/HDL-C remained associated with increased CVD risk after adjusting for most CVD risk factors, none remained significant after adjusting for HDL-C: hazard ratios for insulin, 1.06 (CI, 0.98-1.16); for HOMA-IR, 1.06 (CI, 0.98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD risk discrimination and reclassification.Measures of insulin resistance were no longer associated with CVD risk after adjustment for high-density lipoprotein-cholesterol and did not provide independent prognostic information in postmenopausal women without diabetes mellitus.URL: http://www.clinicaltrial.gov. Unique identifier: NCT00000611.
View details for DOI 10.1161/CIRCOUTCOMES.114.001563
View details for PubMedID 25944628
Race and ethnicity, obesity, metabolic health, and risk of cardiovascular disease in postmenopausal women.
Journal of the American Heart Association
2015; 4 (5)
It is unclear whether obesity unaccompanied by metabolic abnormalities is associated with increased cardiovascular disease risk across racial and ethnic subgroups.We identified 14 364 postmenopausal women from the Women's Health Initiative who had data on fasting serum lipids and serum glucose and no history of cardiovascular disease or diabetes at baseline. We categorized women by body mass index (in kg/m(2)) as normal weight (body mass index 18.5 to <25), overweight (body mass index 25 to <30), or obese (body mass index ≥30) and by metabolic health, defined first as the metabolic syndrome (metabolically unhealthy: ≥3 metabolic abnormalities) and second as the number of metabolic abnormalities. We used Cox proportional hazards regression to assess associations between baseline characteristics and cardiovascular risk. Over 13 years of follow-up, 1101 women had a first cardiovascular disease event (coronary heart disease or ischemic stroke). Among black women without metabolic syndrome, overweight women had higher adjusted cardiovascular risk than normal weight women (hazard ratio [HR] 1.49), whereas among white women without metabolic syndrome, overweight women had similar risk to normal weight women (HR 0.92, interaction P=0.05). Obese black women without metabolic syndrome had higher adjusted risk (HR 1.95) than obese white women (HR 1.07; interaction P=0.02). Among women with only 2 metabolic abnormalities, cardiovascular risk was increased in black women who were overweight (HR 1.77) or obese (HR 2.17) but not in white women who were overweight (HR 0.98) or obese (HR 1.06). Overweight and obese women with ≤1 metabolic abnormality did not have increased cardiovascular risk, regardless of race or ethnicity.Metabolic abnormalities appeared to convey more cardiovascular risk among black women.
View details for DOI 10.1161/JAHA.114.001695
View details for PubMedID 25994446
Active and passive smoking in relation to lung cancer incidence in the Women's Health Initiative Observational Study prospective cohort†.
Annals of oncology
2015; 26 (1): 221-230
Lung cancer is the leading cause of worldwide cancer deaths. While smoking is its leading risk factor, few prospective cohort studies have reported on the association of lung cancer with both active and passive smoking. This study aimed to determine the relationship between lung cancer incidence with both active and passive smoking (childhood, adult at home, and at work).The Women's Health Initiative Observational Study (WHI-OS) was a prospective cohort study conducted at 40 US centers that enrolled postmenopausal women from 1993 to 1999. Among 93 676 multiethnic participants aged 50-79, 76 304 women with complete smoking and covariate data comprised the analytic cohort. Lung cancer incidence was calculated by Cox proportional hazards models, stratified by smoking status.Over 10.5 mean follow-up years, 901 lung cancer cases were identified. Compared with never smokers (NS), lung cancer incidence was much higher in current [hazard ratio (HR) 13.44, 95% confidence interval (CI) 10.80-16.75] and former smokers (FS; HR 4.20, 95% CI 3.48-5.08) in a dose-dependent manner. Current and FS had significantly increased risk for all lung cancer subtypes, particularly small-cell and squamous cell carcinoma. Among NS, any passive smoking exposure did not significantly increase lung cancer risk (HR 0.88, 95% CI 0.52-1.49). However, risk tended to be increased in NS with adult home passive smoking exposure ≥30 years, compared with NS with no adult home exposure (HR 1.61, 95% CI 1.00-2.58).In this prospective cohort of postmenopausal women, active smoking significantly increased risk of all lung cancer subtypes; current smokers had significantly increased risk compared with FS. Among NS, prolonged passive adult home exposure tended to increase lung cancer risk. These data support continued need for smoking prevention and cessation interventions, passive smoking research, and further study of lung cancer risk factors in addition to smoking.NCT00000611.
View details for DOI 10.1093/annonc/mdu470
View details for PubMedID 25316260
Public health-specific personal disaster preparedness training: an academic-practice collaboration.
Journal of emergency management (Weston, Mass.)
2014; 12 (1): 55-73
To measure the following three relevant outcomes of a personal preparedness curriculum for public health workers: 1) the extent of change (increase) in knowledge about personal preparedness activities and knowledge about tools for conducting personal preparedness activities; 2) the extent of change (increase) in preparedness activities performed post-training and/or confidence in conducting these tasks; and 3) an understanding of how to improve levels of personal preparedness using the Extended Parallel Process Model (EPPM) framework.Cross-sectional preinterventional and postinterventional survey using a convenience sample.During 2010, three face-to-face workshops were conducted in three locations in West Virginia.One hundred thirty-one participants (baseline survey); 69 participants (1-year resurvey)-representing West Virginia local health department (LHD) and State Health Department employees.A 3-hour interactive, public health-specific, face-to-face workshop on personal disaster preparedness.Change in 1) knowledge about, and tools for, personal preparedness activities; 2) preparedness activities performed post-training and/or confidence in conducting these activities; and 3) the relationship of EPPM categories to personal preparedness activities.One year postworkshop, 77 percent of respondents reported having personal emergency kits (40 percent at baseline) and 67 percent reported having preparedness plans (38 percent at baseline) suggesting some participants assembled supply kits and plans postworkshop. Within the context of EPPM, respondents in high-threat categories agreed more often than respondents in low-threat categories that severe personal impacts were likely to result from a moderate flood. Compared to respondents categorized as low efficacy, respondents in high-efficacy categories perceived confidence in their knowledge and an impact of their response on their job success at higher rates.Personal disaster preparedness trainings for the LHD workforce can yield gains in relevant preparedness behaviors and attitudes but may require longitudinal reinforcement. The EPPM can offer a useful threat and efficacy-based lens to understand relevant perceptions surrounding personal disaster preparedness behaviors among LHD employees.
View details for DOI 10.5055/jem.2014.0162
View details for PubMedID 24691916
Impact of a Home-Based Walking Intervention on Outcomes of Sleep Quality, Emotional Distress, and Fatigue in Patients Undergoing Treatment for Solid Tumors
2013; 18 (4): 476-484
Exercise use among patients with cancer has been shown to have many benefits and few notable risks. The purpose of this study was to evaluate the impact of a home-based walking intervention during cancer treatment on sleep quality, emotional distress, and fatigue. Methods. A total of 138 patients with prostate (55.6%), breast (32.5%), and other solid tumors (11.9%) were randomized to a home-based walking intervention or usual care. Exercise dose was assessed using a five-item subscale of the Cooper Aerobics Center Longitudinal Study Physical Activity Questionnaire. Primary outcomes of sleep quality, distress, and fatigue were compared between the two study arms. Results. The exercise group (n = 68) reported more vigor (p = .03) than control group participants (n = 58). In dose response models, greater participation in aerobic exercise was associated with 11% less fatigue (p < .001), 7.5% more vigor (p = .001), and 3% less emotional distress (p = .03), after controlling for intervention group assignment, age, and baseline exercise and fatigue levels. Conclusion. Patients who exercised during cancer treatment experienced less emotional distress than those who were less active. Increasing exercise was also associated with less fatigue and more vigor. Home-based walking is a simple, sustainable strategy that may be helpful in improving a number of symptoms encountered by patients undergoing active treatment for cancer.
View details for DOI 10.1634/theoncologist.2012-0278
View details for Web of Science ID 000318336200024
View details for PubMedID 23568000
View details for PubMedCentralID PMC3639536
Modern Statistical Modeling Approaches for Analyzing Repeated-Measures Data
2012; 61 (3): 188-194
Researchers often describe the collection of repeated measurements on each individual in a study design. Advanced statistical methods, namely, mixed and marginal models, are the preferred analytic choices for analyzing this type of data.The aim was to provide a conceptual understanding of these modeling techniques.An understanding of mixed models and marginal models is provided via a thorough exploration of the methods that have been used historically in the biomedical literature to summarize and make inferences about this type of data. The limitations are discussed, as is work done on expanding the classic linear regression model to account for repeated measurements taken on an individual, leading to the broader mixed-model framework.A description is provided of a variety of common types of study designs and data structures that can be analyzed using a mixed model and a marginal model.This work provides an overview of advanced statistical modeling techniques used for analyzing the many types of correlated .data collected in a research study.
View details for DOI 10.1097/NNR.0b013e31824f5f58
View details for Web of Science ID 000303604500006
View details for PubMedID 22551993
Teletransmitted Monitoring of Blood Pressure and Bilingual Nurse Counseling-Sustained Improvements in Blood Pressure Control During 12 Months in Hypertensive Korean Americans
JOURNAL OF CLINICAL HYPERTENSION
2011; 13 (8): 605-612
This paper reports the results of a clinical investigation to determine the sustainability of intervention effects to lower blood pressure (BP) that were obtained through a short-term education via home telemonitoring of BP and regular counseling by bilingual nurses during 1 year. A total of 359 middle-aged (40-64 years) Korean immigrants completed a 15-month intervention that consisted of 6-week behavioral education followed by home telemonitoring of BP and bilingual nurse telephone counseling for 12 months. The final analysis revealed a sharp increase in BP control rates sustained for more than 12 months. At baseline, only 30% of the sample achieved BP control (<140/90 mm Hg). After the initial education period (approximately 3 months), 73.3% of the participants had controlled BP levels. The levels of control were maintained and continuously improved during a 12-month follow-up period (83.2%, P<.001). These findings suggest that home telemonitoring of BP and tailored counseling are both useful tools to sustain or improve short-term education effects.
View details for DOI 10.1111/j.1751-7176.2011.00479.x
View details for Web of Science ID 000293349600010
View details for PubMedID 21806771
View details for PubMedCentralID PMC3149834
Interventions that increase use of Pap tests among ethnic minority women: a meta-analysis
2011; 20 (4): 341-351
Although a variety of intervention methods have been used to promote Pap test screening among ethnic minority women in the US, the effectiveness of such interventions is unclear. We performed a meta-analysis to examine the overall effectiveness of these interventions in increasing Pap test use by ethnic minority women in the US.A search of databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and Science Citation Index-Expanded) and review articles for articles published between 1984 and April 2009 identified 18 randomized and non-randomized controlled trials. The primary study outcome was the difference in the proportion of Pap tests between the treatment and comparison groups.The pooled mean weighted effect size (d) for the 18 studies was 0.158 (95% confidence interval [CI]=0.100, 0.215), indicating that the interventions were effective in improving Pap test use among ethnic minority women. Among the intervention types, access enhancement yielded the largest effect size (0.253 [95% CI=0.110, 0.397]), followed by community education (0.167 [95% CI=0.057, 0.278]) and individual counseling or letters (0.132 [95% CI=0.069, 0.195]). Combined intervention effects were significant for studies targeting Asian (0.177 [95% CI=0.098, 0.256]) and African American women (0.146 [95% CI=0.028, 0.265]), but not Hispanic women (0.116 [95% CI=-0.008, 0.240]).Pap test use among ethnic minority women is most likely to increase when access-enhancing strategies are combined. Further research is needed to determine whether more tightly controlled trials of such interventions might reveal an improved rate of cervical cancer screening in Hispanic women as well.
View details for DOI 10.1002/pon.1754
View details for Web of Science ID 000288860400001
View details for PubMedID 20878847
View details for PubMedCentralID PMC3741532
Evaluation of Cumulative Lead Dose and Longitudinal Changes in Structural Magnetic Resonance Imaging in Former Organolead Workers
JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
2010; 52 (4): 407-414
: We evaluated whether tibia lead was associated with longitudinal change in brain volumes and white matter lesions in male former lead workers and population-based controls in whom we have previously reported on the cognitive and structural consequences of cumulative lead dose.: We used linear regression to identify predictors of change in brain volumes and white matter lesion grade scores, using two magnetic resonance imaging scans an average of 5 years apart.: On average, total brain volume declined almost 30 cm, predominantly in gray matter. Increasing age at the first magnetic resonance imaging was strongly associated with larger declines in volumes and greater increases in white matter lesion scores. Tibia lead was not associated with change in brain volumes or white matter lesion scores.: In former lead workers in whom cumulative lead dose was associated with progressive declines in cognitive function decades after occupational exposure had ended, cumulative lead dose was associated with earlier persistent effects on brain structure but not with additional worsening during 5 years.
View details for DOI 10.1097/JOM.0b013e3181d5e386
View details for Web of Science ID 000276668300006
View details for PubMedID 20357679
View details for PubMedCentralID PMC2869464
Covariate-adjusted nonparametric analysis of magnetic resonance images using Markov chain Monte Carlo
STATISTICS AND ITS INTERFACE
2010; 3 (1): 113-123
Permutation tests are useful for drawing inferences from imaging data because of their flexibility and ability to capture features of the brain under minimal assumptions. However, most implementations of permutation tests ignore important confounding covariates. To employ covariate control in a nonparametric setting we have developed a Markov chain Monte Carlo (MCMC) algorithm for conditional permutation testing using propensity scores. We present the first use of this methodology for imaging data. Our MCMC algorithm is an extension of algorithms developed to approximate exact conditional probabilities in contingency tables, logit, and log-linear models. An application of our nonparametric method to remove potential bias due to the observed covariates is presented.
View details for Web of Science ID 000282840000011
View details for PubMedCentralID PMC3232683
A Meta-Analysis of Interventions to Promote Mammography Among Ethnic Minority Women
2009; 58 (4): 246-254
Although many studies have been focused on interventions designed to promote mammography screening among ethnic minority women, few summaries of the effectiveness of the interventions are available.The aim of this study was to determine the effectiveness of the interventions for improving mammography screening among asymptomatic ethnic minority women.A meta-analysis was performed on intervention studies designed to promote mammography use in samples of ethnic minority women. Random-effects estimates were calculated for interventions by measuring differences in intervention and control group screening rates postintervention.The overall mean weighted effect size for the 23 studies was 0.078 (Z = 4.414, p < .001), indicating that the interventions were effective in improving mammography use among ethnic minority women. For mammography intervention types, access-enhancing strategies had the biggest mean weighted effect size of 0.155 (Z = 4.488, p < .001), followed by 0.099 (Z = 6.552, p < .001) for individually directed approaches such as individual counseling or education. Tailored, theory-based interventions resulted in a bigger effect size compared with nontailored interventions (effect sizes = 0.101 vs. 0.076, respectively; p < .05 for all models). Of cultural strategies, ethnically matched intervention deliveries and offering culturally matched intervention materials had effect sizes of 0.067 (Z = 2.516, p = .012) and 0.051 (Z = 2.365, p = .018), respectively.Uniform improvement in mammography screening is a goal to address breast cancer disparities in ethnic minority communities in this country. The results of this meta-analysis suggest a need for increased use of a theory-based, tailored approach with enhancement of access.
View details for Web of Science ID 000268162700004
View details for PubMedID 19609176
View details for PubMedCentralID PMC2862462