Implications of Delayed Testosterone Recovery in Patients with Prostate Cancer.

To assess the clinical impact of delayed testosterone recovery (TR) following the discontinuation of medical androgen deprivation therapy (ADT), a retrospective, longitudinal analysis was conducted in adult males with prostate cancer using the Optum® de-identified Electronic Health Record data set and Optum® Enriched Oncology Data (2010-2021). Of 3875 patients who initiated and discontinued ADT, 1553 received one or more testosterone-level tests within the 12 mo following discontinuation and were included in this study. These 1553 patients were categorized into two cohorts: 25% as TR (testosterone levels >280 ng/dl at any test within 12 mo following ADT discontinuation) and 75% as non-TR. At baseline, non-TR patients were older, had lower testosterone levels, and were more likely to have diabetes, hyperlipidemia, and hypertension, but less likely to have sexual dysfunction. After adjustment for baseline characteristics, the TR cohort had a lower risk of new-onset diabetes (hazard ratio [HR] 0.47; 95% confidence interval [CI] 0.27-0.79), trended toward a lower risk of new-onset depression (HR 0.58; 95% CI 0.33-1.02), and had a higher likelihood of seeking treatment for sexual dysfunction (HR 1.33; 95% CI 0.99-1.78) versus the non-TR cohort. These findings support monitoring testosterone levels after ADT discontinuation to manage potential long-term comorbidities in patients with prostate cancer. Patient summary: This real-world analysis of males with prostate cancer who were treated with medical androgen deprivation therapy (ADT) found that most patients did not have their testosterone level checked in the 12 mo after stopping ADT. Of those who did, 75% did not achieve normal testosterone levels (>280 ng/dl), and these patients were more likely to experience new-onset diabetes than those who achieved normal testosterone levels. These results suggest that to ensure effective clinical decision-making, physicians should check patients' testosterone levels after stopping ADT.

Burden of Illness and Treatment Patterns Among Patients With von Willebrand Disease in US Clinical Practice.

In this retrospective cohort study, data from an integrated US healthcare system containing both electronic medical record data and linked claims data (from 01/2004 to 12/2020) were used to evaluate the clinical burden, treatment patterns, and healthcare resource use (HRU) in patients with von Willebrand disease (VWD). Two patient cohorts were analyzed: the overall VWD population (n = 396) and a subset of these patients (n = 75) who were considered potentially eligible for prophylaxis treatment with von Willebrand factor (VWF) based on a history of severe and frequent bleeding. HRU (hospitalizations, outpatient visits, and emergency department visits) were measured in patients with linked claims data (n = 110, overall VWD patients; n = 23 potentially VWF-prophylaxis-eligible VWD patients). In general, patients with VWD experienced a substantial burden of bleeding events, comorbidities, and HRU. Patients with VWD who were considered potentially eligible for prophylaxis owing to severe and frequent bleeds suffered from a higher clinical burden and HRU than the overall VWD population, and thus may benefit from VWF prophylactic treatment. The findings from this study could help improve clinical outcomes and manage HRU for patients with VWD.

Costs of pediatric liver transplantation among commercially insured and Medicaid-insured patients with cholestasis in the US.

Children with rare cholestatic liver diseases, such as Alagille syndrome, progressive familial intrahepatic cholestasis, and biliary atresia typically require liver transplantation (LT). The objective of this analysis was to assess the economic burden of LT on these patients. Health care resource utilization and costs associated with pediatric LT were retrospectively assessed using insurance claims data from the US IBM MarketScan Commercial and Medicaid databases collected between October 2015 and December 2019. Inclusion criteria were as follows: ≥1 procedure code for LT, <18 years old at transplant, and ≥6 months of insurance eligibility at baseline. A cholestatic liver disease population who received LT was selected in the absence of specific diagnosis codes by excluding other severe liver conditions (ie, acute liver failure, malignancy) and by excluding severely decompensated individuals requiring ICU admission before LT. Annualized rates were reported. Over a mean study duration of 1.8 years, 53 commercially insured and 100 Medicaid-insured children received LT, with mean (SD) ages at baseline of 6.9 (6.0) and 5.7 (5.4) years, respectively. During this period, commercially insured and Medicaid-insured patients had annualized means of 65.3 and 52.8 medical visits, respectively. Most were outpatient visits, although the burden of inpatient visits was also high, with mean inpatient stays (inclusive of LT stay) of 37.2 and 31.6 days per year, respectively. Commercially insured and Medicaid-insured patients averaged US$512,124 and $211,863 in medical costs and $26,998 and $15,704 in pharmacy costs, respectively. These costs remained substantial throughout the first year after transplant. Overall, pediatric LT resulted in substantial health care resource utilization and cost burden in both commercially- and Medicaid-insured patients. Novel targeted medications that negate the need for pediatric LT could decrease the associated morbidity and costs.

Disease progression rates in ambulatory Duchenne muscular dystrophy by steroid type, patient age and functional status.

Aim: To examine benefits of corticosteroids for Duchenne muscular dystrophy (DMD) by age and disease progression. Methods: Data from daily steroid users (placebo-treated) were pooled from four phase 2b/3 trials in DMD. Outcomes assessed overall and among subgroups included changes from baseline to 48 weeks in six-minute walk distance (6MWD), timed function tests and North Star Ambulatory Assessment total score. Results: Among 231 patients receiving deflazacort (n = 127) or prednisone (n = 104), observed differences in 6MWD favoring deflazacort over prednisone were significant for patients with relatively older age (≥8-years-old), greater disease progression (baseline timed stand from supine ≥5 s), or longer corticosteroid use (>3 years). Conclusion: Daily deflazacort had greater benefits than daily prednisone particularly among older/more progressed patients.

Functional and Clinical Outcomes Associated with Steroid Treatment among Non-ambulatory Patients with Duchenne Muscular Dystrophy1.

BACKGROUND: Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited. OBJECTIVE: Characterize and compare disease progression by steroid treatment (prednisone, deflazacort, or no steroids) among non-ambulatory boys with DMD. METHODS: Disease progression was measured by functional status (Performance of Upper Limb Module for DMD 1.2 [PUL] and Egen Klassifikation Scale Version 2 [EK] scale) and by cardiac and pulmonary function (left ventricular ejection fraction [LVEF], forced vital capacity [FVC] % -predicted, cough peak flow [CPF]). Longitudinal changes in outcomes, progression to key disease milestones, and dosing and body composition metrics were analyzed descriptively and in multivariate models. RESULTS: This longitudinal cohort study included 86 non-ambulatory patients with DMD (mean age 13.4 years; n = 40 [deflazacort], n = 29 [prednisone], n = 17 [no steroids]). Deflazacort use resulted in slower average declines in FVC % -predicted vs. no steroids (+3.73 percentage points/year, p < 0.05). Both steroids were associated with significantly slower average declines in LVEF, improvement in CPF, and slower declines in total PUL score and EK total score vs. no steroids; deflazacort was associated with slower declines in total PUL score vs. prednisone (all p < 0.05). Both steroids also preserved functional abilities considered especially important to quality of life, including the abilities to perform hand-to-mouth function and to turn in bed at night unaided (all p < 0.05 vs. no steroids). CONCLUSIONS: Steroid use after loss of ambulation in DMD was associated with delayed progression of important pulmonary, cardiac, and upper extremity functional deficits, suggesting some benefits of deflazacort over prednisone.

Maralixibat Treatment Response in Alagille Syndrome is Associated with Improved Health-Related Quality of Life.

OBJECTIVE: The objective of this study was to assess the impact of treatment response to the ileal bile acid transporter inhibitor maralixibat on health-related quality of life (HRQoL) in children with Alagille syndrome. STUDY DESIGN: This analysis used data from the ICONIC trial, a phase 2 study with a 4-week double-blind, placebo-controlled, randomized drug withdrawal period in children with Alagille syndrome with moderate-to-severe pruritus. Clinically meaningful treatment response to maralixibat was defined a priori as a ≥1-point reduction in the Itch-Reported Outcome (Observer) score, from baseline to week 48. HRQoL was assessed using the Pediatric Quality of Life Inventory Generic Core, Family Impact, and Multidimensional Fatigue scale scores, which were collected via the caregiver. The minimal clinically important difference for HRQoL ranged from 4 to 5 points, depending on the scale. RESULTS: Twenty of the 27 patients (74%) included in this analysis achieved an Itch-Reported Outcome (Observer) treatment response at week 48. The mean (SD) change in Multidimensional Fatigue score was +25.8 (23.0) for responders vs -3.1 (19.8) for nonresponders (P = .03). Smaller and non-statistically significant mean changes were observed for the Pediatric Quality of Life Inventory Generic Core and Family Impact scores. Controlling for baseline Family Impact score, responders' Family Impact scores increased an average of 16.9 points over 48 weeks compared with non-responders (P = .05). Smaller and non-statistically significant point estimates were observed for the Pediatric Quality of Life Inventory Generic Core and Multidimensional Fatigue scores. CONCLUSION: The significant improvements in pruritus seen with maralixibat at week 48 of the ICONIC study are clinically meaningful and are associated with improved HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160782.

Health Care Resource Utilization by Patients with Alagille Syndrome.

OBJECTIVE: To assess and characterize health care resource utilization (HRU) in children with the rare, genetic, multisystem disorder, Alagille syndrome. STUDY DESIGN: This retrospective analysis reviewed commercially insured and Medicaid-insured claims from October 1, 2015 to December 31, 2019 to assess HRU in patients with Alagille syndrome. As there is no specific International Classification ofDiseases-10 code for Alagille syndrome, patients were identified using the following algorithm: ≥1 claim with diagnosis code Q44.7 (other congenital malformations of the liver); <18 years of age, with no history of biliary atresia (International Classification ofDiseases-10 code: Q44.2); and ≥6 months of insurance eligibility prior to diagnosis. HRU was summarized per patient per year over all available claims postdiagnosis. RESULTS: A total of 171 commercially insured and 215 Medicaid-insured patients with Alagille syndrome were available for analysis. Annually, commercially insured and Medicaid-insured patients averaged 31 medical visits (range, 1.5-237) and 48 medical visits (range, 0.7-690), respectively. The most common visits were outpatient with the majority encompassing lab/imaging and primary care visits (commercially insured: 21 [range, 0.0-183]; Medicaid-insured: 26 [range, 0.0-609]). Inpatient visits were the highest driver of costs in both the commercial and Medicaid populations. CONCLUSIONS: Patients with Alagille syndrome have a substantial HRU burden driven largely by numerous outpatient visits and costly inpatient stays. Given the complexity and variability of Alagille syndrome presentation, patients may benefit from multidisciplinary and subspecialized care.

The Economic Burden of Schizophrenia in the United States.

Aim: The economic burden of schizophrenia in the United States (US) was estimated at $155.7 billion in 2013. Since 2013, the US experienced significant health care reforms and treatment advances. This study analyzed recent data and literature to update the US economic burden estimate for schizophrenia.Methods: Direct and indirect costs associated with schizophrenia were estimated using a prevalence-based approach. Direct health care costs were assessed retrospectively using an exact matched cohort design in the IBM Watson Health MarketScan databases from October 1, 2015, through December 31, 2019. Patients with schizophrenia (identified using ICD-10-CM codes F20 and F25) were exactly matched to controls on demographics, insurance type, and index year. Direct non-health care costs were estimated using published literature and government data. Indirect costs were estimated using a human capital approach and the value of quality-adjusted life-years lost. Cost offsets were estimated to account for basic living costs avoided. Excess costs, comparing costs for individuals with and without schizophrenia, were reported in 2019 USD.Results: The estimated excess economic burden of schizophrenia in the US in 2019 was $343.2 billion, including $251.9 billion in indirect costs (73.4%), $62.3 billion in direct health care costs (18.2%), and $35.0 billion in direct non-health care costs (10.2%). The largest drivers of indirect costs were caregiving ($112.3 billion), premature mortality ($77.9 billion), and unemployment ($54.2 billion). Cost offsets, representing $6.0 billion (1.7%), were subtracted from direct non-health care costs.Conclusions: The estimated burden of schizophrenia in the US doubled between 2013 and 2019 and was $343.2 billion in 2019, highlighting the importance of effective strategies and treatment options to improve the management of this difficult-to-treat patient population.

Impact of the COVID-19 pandemic on adolescent vaccinations: projected time to reverse deficits in routine adolescent vaccination in the United States.

OBJECTIVE: The COVID-19 pandemic has led to significant reductions in the administration of routinely recommended vaccines among adolescents in the US including tetanus, diphtheria, and acellular pertussis (Tdap); meningococcal (ACWY); and human papillomavirus (HPV) vaccines. The extent to which these deficits could persist in 2021 and beyond is unclear. To address this knowledge gap, this study estimated the cumulative deficits of routine vaccine doses among US adolescents during the COVID-19 pandemic and estimated the time and effort needed to recover from those deficits. METHODS: Monthly reductions in Tdap, meningococcal, and HPV doses administered to US adolescents during the COVID-19 pandemic were quantified using MarketScan Commercial Claims and Encounters data. The time and effort required to reverse the vaccination deficit under various catch-up scenarios were estimated. RESULTS: Annual doses administered of Tdap, meningococcus, and HPV vaccines decreased by 21.2%, 20.8%, and 24.0%, respectively, in 2020 compared to 2019. For 2021, the reduction in doses administered is projected to be 6%-21% compared to 2019 under different scenarios. The projected deficit of missed doses is expected to be cleared between winter 2023 and fall 2031. CONCLUSIONS: Administration rates of routine vaccines decreased significantly among US adolescents during COVID-19. Reversing these deficits to mitigate long-term health and economic consequences will require a sustained increase in vaccination rates over multiple years.

Steroid switching in dystrophinopathy treatment: a US chart review of patient characteristics and clinical outcomes.

Aim: To describe reasons for switching from prednisone/prednisolone to deflazacort and associated clinical outcomes among patients with Duchenne and Becker muscular dystrophy (DMD and BMD, respectively) in the USA. Methods: A chart review of patients with DMD (n = 62) or BMD (n = 30) who switched from prednisone to deflazacort (02/2017-12/2018) collected demographic/clinical characteristics, reasons for switching, outcomes and common adverse events. Results: The mean ages at switch were 20.1 (DMD) and 9.2 (BMD) years. The primary physician-reported reasons for switching were 'to slow disease progression' (DMD: 83%, BMD: 79%) and 'tolerability' (67 and 47%). Switching was 'very' or 'somewhat' effective at addressing the primary reasons in 90-95% of patients. Conclusion: Physician-reported outcomes were consistent with deflazacort addressing patients' primary reasons for switching.

Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: experience at a single, large care center.

Aim: To assess outcomes among patients with Duchenne muscular dystrophy receiving deflazacort or prednisone in real-world practice. Methods: Clinical data for 435 boys with Duchenne muscular dystrophy from Cincinnati Children's Hospital Medical Center were studied retrospectively using time-to-event and regression analyses. Results: Median ages at loss of ambulation were 15.6 and 13.5 years among deflazacort- and prednisone-initiated patients, respectively. Deflazacort was also associated with a lower risk of scoliosis and better ambulatory function, greater % lean body mass, shorter stature and lower weight, after adjusting for age and steroid duration. No differences were observed in whole body bone mineral density or left ventricular ejection fraction. Conclusion: This single center study adds to the real-world evidence associating deflazacort with improved clinical outcomes.

Mother's education and late-life disparities in memory and dementia risk among US military veterans and non-veterans.

BACKGROUND: Adverse childhood socioeconomic status (cSES) predicts higher late-life risk of memory loss and dementia. Veterans of U.S. wars are eligible for educational and economic benefits that may offset cSES disadvantage. We test whether cSES disparities in late-life memory and dementia are smaller among veterans than non-veterans. METHODS: Data came from US-born men in the 1995-2014 biennial surveys of the Health and Retirement Study (n=7916 born 1928-1956, contributing n=38 381 cognitive assessments). Childhood SES was represented by maternal education. Memory and dementia risk were assessed with brief neuropsychological assessments and proxy reports. Military service (veteran/non-veteran) was evaluated as a modifier of the effect of maternal education on memory and dementia risk. We employed linear or logistic regression models to test whether military service modified the effect of maternal education on memory or dementia risk, adjusted for age, race, birthplace and childhood health. RESULTS: Low maternal education was associated with worse memory than high maternal education (ß = -0.07 SD, 95% CI -0.08 to -0.05), while veterans had better memory than non-veterans (ß = 0.03 SD, 95% CI 0.02 to 0.04). In interaction analyses, maternal education disparities in memory were smaller among veterans than non-veterans (difference in disparities = 0.04 SD, 95% CI 0.01 to 0.08, p = 0.006). Patterns were similar for dementia risk. CONCLUSIONS: Disparities in memory by maternal education were smaller among veterans than non-veterans, suggesting military service and benefits partially offset the deleterious effects of low maternal education on late-life cognitive outcomes.

Can Survival Bias Explain the Age Attenuation of Racial Inequalities in Stroke Incidence?: A Simulation Study.

BACKGROUND: In middle age, stroke incidence is higher among black than white Americans. For unknown reasons, this inequality decreases and reverses with age. We conducted simulations to evaluate whether selective survival could account for observed age patterning of black-white stroke inequalities. METHODS: We simulated birth cohorts of 20,000 blacks and 20,000 whites with survival distributions based on US life tables for the 1919-1921 birth cohort. We generated stroke incidence rates for ages 45-94 years using Reasons for Geographic and Racial Disparities in Stroke (REGARDS) study rates for whites and setting the effect of black race on stroke to incidence rate difference (IRD) = 20/10,000 person-years at all ages, the inequality observed at younger ages in REGARDS. We compared observed age-specific stroke incidence across scenarios, varying effects of U, representing unobserved factors influencing mortality and stroke risk. RESULTS: Despite a constant adverse effect of black race on stroke risk, the observed black-white inequality in stroke incidence attenuated at older age. When the hazard ratio for U on stroke was 1.5 for both blacks and whites, but U only directly influenced mortality for blacks (hazard ratio for U on mortality =1.5 for blacks; 1.0 for whites), stroke incidence rates in late life were lower among blacks (average observed IRD = -43/10,000 person-years at ages 85-94 years versus causal IRD = 20/10,000 person-years) and mirrored patterns observed in REGARDS. CONCLUSIONS: A relatively moderate unmeasured common cause of stroke and survival could fully account for observed age attenuation of racial inequalities in stroke.

Implementation of Instrumental Variable Bounds for Data Missing Not at Random.

Instrumental variables are routinely used to recover a consistent estimator of an exposure causal effect in the presence of unmeasured confounding. Instrumental variable approaches to account for nonignorable missing data also exist but are less familiar to epidemiologists. Like instrumental variables for exposure causal effects, instrumental variables for missing data rely on exclusion restriction and instrumental variable relevance assumptions. Yet these two conditions alone are insufficient for point identification. For estimation, researchers have invoked a third assumption, typically involving fairly restrictive parametric constraints. Inferences can be sensitive to these parametric assumptions, which are typically not empirically testable. The purpose of our article is to discuss another approach for leveraging a valid instrumental variable. Although the approach is insufficient for nonparametric identification, it can nonetheless provide informative inferences about the presence, direction, and magnitude of selection bias, without invoking a third untestable parametric assumption. An important contribution of this article is an Excel spreadsheet tool that can be used to obtain empirical evidence of selection bias and calculate bounds and corresponding Bayesian 95% credible intervals for a nonidentifiable population proportion. For illustrative purposes, we used the spreadsheet tool to analyze HIV prevalence data collected by the 2007 Zambia Demographic and Health Survey (DHS).

Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality.

INTRODUCTION: We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality. METHODS: We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years. RESULTS: Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00-1.10, P = .04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41-1.00, P = .05). DISCUSSION: Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.

Contribution of Socioeconomic Status at 3 Life-Course Periods to Late-Life Memory Function and Decline: Early and Late Predictors of Dementia Risk.

Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998-2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (ß = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, ß = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline.

High Hemoglobin A1c and Diabetes Predict Memory Decline in the Health and Retirement Study.

BACKGROUND: Type 2 diabetes (T2D) is an established risk factor for dementia, but evidence for T2D and memory decline is less consistent. Understanding how T2D and blood glucose relate to memory decline is crucial to elucidating the mechanisms linking T2D and dementia. MATERIALS AND METHODS: For 8888 Health and Retirement Study participants aged 50+, glycosylated hemoglobin (HbA1c) was measured in either 2006 or 2008 and physician's diagnosis of diabetes was self-reported in the same year. Composite memory (z scored) was assessed biennially through 2012 using immediate and delayed word list recall or the Informant Questionnaire for Cognitive Decline. Marginal mean regression models for repeated outcomes were specified to predict memory decline as a function of diabetes or HbA1c, using age as the timescale and adjusting for health and social confounders. RESULTS: Diabetes was associated with a 10% faster rate of memory decline [ß=-0.04 per decade; 95% confidence interval (CI), -0.06 to -0.01). A 1 U increase in HbA1c corresponded with a 0.05 SD decrease in memory score per decade (95% CI, -0.08 to -0.03). Even among individuals with HbA1c<6.5% (threshold for diabetes), higher HbA1c was associated with memory decline (ß=-0.05 per decade; 95% CI, -0.08 to -0.03). DISCUSSION: Diabetes accelerated memory loss and higher HbA1c predicted memory decline even in nondiabetics.

Comparing Variability, Severity, and Persistence of Depressive Symptoms as Predictors of Future Stroke Risk.

OBJECTIVE: Numerous studies show that depressive symptoms measured at a single assessment predict greater future stroke risk. Longer-term symptom patterns, such as variability across repeated measures or worst symptom level, might better reflect adverse aspects of depression than a single measurement. This prospective study compared five approaches to operationalizing depressive symptoms at annual assessments as predictors of stroke incidence. DESIGN: Cohort followed for incident stroke over an average of 6.4 years. SETTING: The Adult Changes in Thought cohort follows initially cognitively intact, community- dwelling older adults from a population base defined by membership in Group Health, a Seattle-based nonprofit healthcare organization. PARTICIPANTS: 3,524 individuals aged 65 years and older. MEASUREMENTS: We identified 665 incident strokes using ICD codes. We considered both baseline Center for Epidemiologic Studies-Depression scale (CES-D) score and, using a moving window of three most recent annual CES-D measurements, we compared most recent, maximum, average, and intra-individual variability of CES-D scores as predictors of subsequent stroke using Cox proportional hazards models. RESULTS: Greater maximum (hazard ratio [HR]: 1.18; 95% CI: 1.07-1.30), average (HR: 1.20; 95% CI: 1.05-1.36) and intra-individual variability (HR: 1.15; 95% CI: 1.06-1.24) in CES-D were each associated with elevated stroke risk, independent of sociodemographics, cardiovascular risks, cognition, and daily functioning. Neither baseline nor most recent CES-D was associated with stroke. In a combined model, intra-individual variability in CES-D predicted stroke, but average CES-D did not. CONCLUSIONS: Capturing the dynamic nature of depression is relevant in assessing stroke risk. Fluctuating depressive symptoms may reflect a prodrome of reduced cerebrovascular integrity.

A Simulation Platform for Quantifying Survival Bias: An Application to Research on Determinants of Cognitive Decline.

Bias due to selective mortality is a potential concern in many studies and is especially relevant in cognitive aging research because cognitive impairment strongly predicts subsequent mortality. Biased estimation of the effect of an exposure on rate of cognitive decline can occur when mortality is a common effect of exposure and an unmeasured determinant of cognitive decline and in similar settings. This potential is often represented as collider-stratification bias in directed acyclic graphs, but it is difficult to anticipate the magnitude of bias. In this paper, we present a flexible simulation platform with which to quantify the expected bias in longitudinal studies of determinants of cognitive decline. We evaluated potential survival bias in naive analyses under several selective survival scenarios, assuming that exposure had no effect on cognitive decline for anyone in the population. Compared with the situation with no collider bias, the magnitude of bias was higher when exposure and an unmeasured determinant of cognitive decline interacted on the hazard ratio scale to influence mortality or when both exposure and rate of cognitive decline influenced mortality. Bias was, as expected, larger in high-mortality situations. This simulation platform provides a flexible tool for evaluating biases in studies with high mortality, as is common in cognitive aging research.

African Ancestry, Social Factors, and Hypertension Among Non-Hispanic Blacks in the Health and Retirement Study.

The biomedical literature contains much speculation about possible genetic explanations for the large and persistent black-white disparities in hypertension, but profound social inequalities are also hypothesized to contribute to this outcome. Our goal is to evaluate whether socioeconomic status (SES) differences provide a plausible mechanism for associations between African ancestry and hypertension in a U.S. cohort of older non-Hispanic blacks. We included only non-Hispanic black participants (N = 998) from the Health and Retirement Study who provided genetic data. We estimated percent African ancestry based on 84,075 independent single nucleotide polymorphisms using ADMIXTURE V1.23, imposing K = 4 ancestral populations, and categorized into quartiles. Hypertension status was self-reported in the year 2000. We used linear probability models (adjusted for age, sex, and southern birth) to predict prevalent hypertension with African ancestry quartile, before and after accounting for a small set of SES measures. Respondents with the highest quartile of African ancestry had 8 percentage points' (RD = 0.081; 95% CI: -0.001, 0.164) higher prevalence of hypertension compared to the lowest quartile. Adjustment for childhood disadvantage, education, income, and wealth explained over one-third (RD = 0.050; 95% CI: -0.034, 0.135) of the disparity. Explanations for the residual disparity remain unspecified and may include other indicators of SES or diet, lifestyle, and psychosocial mechanisms.