Disparities in Mortality by Sexual Orientation in a Large, Prospective Cohort of Female Nurses.

Importance: Extensive evidence documents health disparities for lesbian, gay, and bisexual (LGB) women, including worse physical, mental, and behavioral health than heterosexual women. These factors have been linked to premature mortality, yet few studies have investigated premature mortality disparities among LGB women and whether they differ by lesbian or bisexual identity. Objective: To examine differences in mortality by sexual orientation. Design, Setting, and Participants: This prospective cohort study examined differences in time to mortality across sexual orientation, adjusting for birth cohort. Participants were female nurses born between 1945 and 1964, initially recruited in the US in 1989 for the Nurses' Health Study II, and followed up through April 2022. Exposures: Sexual orientation (lesbian, bisexual, or heterosexual) assessed in 1995. Main Outcome and Measure: Time to all-cause mortality from assessment of exposure analyzed using accelerated failure time models. Results: Among 116 149 eligible participants, 90 833 (78%) had valid sexual orientation data. Of these 90 833 participants, 89 821 (98.9%) identified as heterosexual, 694 (0.8%) identified as lesbian, and 318 (0.4%) identified as bisexual. Of the 4227 deaths reported, the majority were among heterosexual participants (n = 4146; cumulative mortality of 4.6%), followed by lesbian participants (n = 49; cumulative mortality of 7.0%) and bisexual participants (n = 32; cumulative mortality of 10.1%). Compared with heterosexual participants, LGB participants had earlier mortality (adjusted acceleration factor, 0.74 [95% CI, 0.64-0.84]). These differences were greatest among bisexual participants (adjusted acceleration factor, 0.63 [95% CI, 0.51-0.78]) followed by lesbian participants (adjusted acceleration factor, 0.80 [95% CI, 0.68-0.95]). Conclusions and Relevance: In an otherwise largely homogeneous sample of female nurses, participants identifying as lesbian or bisexual had markedly earlier mortality during the study period compared with heterosexual women. These differences in mortality timing highlight the urgency of addressing modifiable risks and upstream social forces that propagate and perpetuate disparities.

Evaluation of racial and ethnic heterogeneity in the associations of sleep quality and sleep apnea risk with cognitive function and cognitive decline.

INTRODUCTION: The prevalence of poor sleep quality and sleep apnea differs by race and ethnicity and may contribute to racial disparities in cognitive aging. We investigated whether sleep quality and sleep apnea risk were associated with cognitive function and decline and whether the associations differed by race/ethnicity. METHODS: Participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE; N = 1690; mean age: 75.7 years) study, a cohort of Asian, Black, Latino, and White participants, completed a modified Pittsburgh Sleep Quality Index assessing subjective sleep quality, latency, duration, disturbances, sleep medication use, and daytime dysfunction. Sleep apnea risk was measured by questions about snoring, tiredness, and whether apnea was observed. Executive function and verbal episodic memory were assessed at three time points over an average of 2.7 years with the Spanish and English Neuropsychological Assessment Scale. We fit linear mixed-effect models and stratified analyses by race/ethnicity. RESULTS: Higher sleep apnea risk was associated with faster declines in verbal episodic memory (ß^ sleep apnea = -0.02, 95% confidence interval [CI], -0.04, -0.001) but not in executive function. Poorer sleep quality was associated with lower levels of and faster decline in executive function but not in verbal episodic memory. Race/ethnicity modified these associations: compared to estimated effects among White participants, poorer global sleep quality (ß^ sleep*time = -0.02, 95% CI, -0.02, -0.01) was associated with larger effects on decline in executive function among Black participants. Estimated effects of some individual sleep quality components were also modified by race/ethnicity; for example, sleep medication use was associated with faster declines in executive function (ß^ sleep*time = -0.05, 95% CI, -0.07, -0.03) and verbal episodic memory ß^ sleep*time = -0.04, 95% CI, -0.07, -0.02) among Black participants compared to White participants. DISCUSSION: Observational evidence indicates sleep quality is a promising target for addressing racial/ethnic disparities in cognitive aging, especially among Black older adults. Highlights: Sleep apnea risk was associated with faster declines in verbal episodic memory but not executive function among all participants.Global sleep quality was associated with lower levels of and faster decline in executive function but not verbal episodic memory among all participants.Black older adults were particularly susceptible to the estimated adverse cognitive impacts of global sleep quality, particularly the use of sleep medication.

Sample size requirements for testing treatment effect heterogeneity in cluster randomized trials with binary outcomes.

Cluster randomized trials (CRTs) refer to a popular class of experiments in which randomization is carried out at the group level. While methods have been developed for planning CRTs to study the average treatment effect, and more recently, to study the heterogeneous treatment effect, the development for the latter objective has currently been limited to a continuous outcome. Despite the prevalence of binary outcomes in CRTs, determining the necessary sample size and statistical power for detecting differential treatment effects in CRTs with a binary outcome remain unclear. To address this methodological gap, we develop sample size procedures for testing treatment effect heterogeneity in two-level CRTs under a generalized linear mixed model. Closed-form sample size expressions are derived for a binary effect modifier, and in addition, a computationally efficient Monte Carlo approach is developed for a continuous effect modifier. Extensions to multiple effect modifiers are also discussed. We conduct simulations to examine the accuracy of the proposed sample size methods. We present several numerical illustrations to elucidate features of the proposed formulas and to compare our method to the approximate sample size calculation under a linear mixed model. Finally, we use data from the Strategies and Opportunities to Stop Colon Cancer in Priority Populations (STOP CRC) CRT to illustrate the proposed sample size procedure for testing treatment effect heterogeneity.

Development of risk prediction models for preterm delivery in a rural setting in Ethiopia.

Background: Preterm birth complications are the leading causes of death among children under five years. However, the inability to accurately identify pregnancies at high risk of preterm delivery is a key practical challenge, especially in resource-constrained settings with limited availability of biomarkers assessment. Methods: We evaluated whether risk of preterm delivery can be predicted using available data from a pregnancy and birth cohort in Amhara region, Ethiopia. All participants were enrolled in the cohort between December 2018 and March 2020. The study outcome was preterm delivery, defined as any delivery occurring before week 37 of gestation regardless of vital status of the foetus or neonate. A range of sociodemographic, clinical, environmental, and pregnancy-related factors were considered as potential inputs. We used Cox and accelerated failure time models, alongside decision tree ensembles to predict risk of preterm delivery. We estimated model discrimination using the area-under-the-curve (AUC) and simulated the conditional distributions of cervical length (CL) and foetal fibronectin (FFN) to ascertain whether they could improve model performance. Results: We included 2493 pregnancies; among them, 138 women were censored due to loss-to-follow-up before delivery. Overall, predictive performance of models was poor. The AUC was highest for the tree ensemble classifier (0.60, 95% confidence interval = 0.57-0.63). When models were calibrated so that 90% of women who experienced a preterm delivery were classified as high risk, at least 75% of those classified as high risk did not experience the outcome. The simulation of CL and FFN distributions did not significantly improve models' performance. Conclusions: Prediction of preterm delivery remains a major challenge. In resource-limited settings, predicting high-risk deliveries would not only save lives, but also inform resource allocation. It may not be possible to accurately predict risk of preterm delivery without investing in novel technologies to identify genetic factors, immunological biomarkers, or the expression of specific proteins.

Affordable Care Act state Medicaid expansion and human papillomavirus vaccination among adolescent and young adult US women: A national study.

OBJECTIVE: To ascertain the impact of Affordable Care Act (ACA) state Medicaid expansion on human papillomavirus (HPV) vaccination among both adolescent and young adult US women. DATA SOURCES: We used state-level data on ACA Medicaid expansion and individual-level data on US women aged 15-25 years living at or below 138% of the Federal Poverty Level (FPL) from the 2011-2017 waves of the National Survey of Family Growth (N = 2408). STUDY DESIGN: We conducted a quasi-experimental study examining the association between ACA state Medicaid expansion and HPV vaccination initiation among eligible adolescent and young adult US women. METHODS: We used linear probability modeling within a difference-in-differences approach, adjusting for individual- and state-level covariates. PRINCIPAL FINDINGS: Adjusting for individual- and state-level covariates, we found a negative association between Medicaid expansion and HPV vaccination among US women aged 15-25 years living in low-income households in the first year post-expansion (coefficient: -15.9 percentage points; 95% confidence interval [CI]: -30.1, -1.6 points). In contrast, we observed a positive association in the third year post-expansion (coefficient: 20.5 percentage points; 95% confidence interval [CI]: -1.8, 42.9 points). CONCLUSIONS: Medicaid expansion may have increased HPV vaccination among adolescent and young adult US women over time. Additional research is needed to identify the mechanisms and differential effects of Medicaid expansion on HPV vaccination among diverse subgroups of US women.

An integrated assessment of environmental sustainability and nutrient availability of food consumption patterns in Latin America and the Caribbean.

BACKGROUND: In Latin America and the Caribbean (LAC), historical shifts away from traditional, plant-sourced food production and consumption patterns may undermine both nutritional status and environmental sustainability. Although agricultural intensification and increasingly animal-centric dietary preferences in the region are well-documented, their influence on environmental degradation remains unknown. OBJECTIVES: This study aimed to 1) characterize the environmental impacts of current food consumption patterns in South America, Central America, and the Caribbean; and 2) identify food groups that minimize impact while maintaining adequate nutrient availability. METHODS: Apparent regional food consumption was derived using data from the FAO's Food Balance Sheets on per capita food availability and levels of imported and local food production. Region-specific life cycle assessment data on greenhouse gas emissions (GHGEs), land use, and freshwater consumption were leveraged to estimate total, food group-level, and nutrient-specific environmental impacts. RESULTS: Annual overall GHGEs were highest in Caribbean food consumption patterns (2521.2 kg/capita), largely derived from meat (26.7%) and fruit (23.8%) production. Land use (1941.0 m2/capita) and water consumption (2060.8 m3/capita), in contrast, were highest for the South American pattern, owing to high consumption of meat and dairy. Across the regions, meat constituted 7.5%-12.7% of food consumption yet accounted for as much as 73.1% of GHGEs, 56.6% of land use, and 54.2% of water consumption. In contrast, legumes and seeds, cereals, roots, and vegetables demonstrated overall low environmental impacts, particularly relative to their contributions to dietary protein, iron, and zinc availability. CONCLUSIONS: Findings point to the capacity of plant-sourced food consumption to minimize environmental harm without necessarily jeopardizing nutrient availability in LAC. Local agriculture can contribute to food system sustainability by producing diversified plant-sourced foods, cornerstones of many traditional food customs, and mitigating the impacts of industrialized livestock operations and imported, animal-centric dietary habits.

Associations of sleep-related behaviors and the sleep environment at infant age one month with sleep patterns in infants five months later.

OBJECTIVE: To characterize family and environmental correlates of sleep patterns that may contribute to differences in infant sleep. METHODS: We studied 313 infants in the Rise & SHINE (Sleep Health in Infancy & Early Childhood study) cohort. Our main exposures were the parent-reported sleep environment, feeding method and sleep parenting strategies at infant age one month. The main outcomes were nighttime sleep duration, longest nighttime sleep and number of awakenings measured by actigraphy at age six months. We used multivariable linear regression models to examine associations, and secondarily also explored the role of sleep-related environmental exposures in mediating previously observed associations of racial/ethnicity and parental education with infant sleep characteristics. RESULTS: In adjusted models, a non-dark sleep environment (versus an always dark sleep location) and taking the baby to parent's bed when awake at night (versus no co-sleeping) were associated with 28 (95% CI, -45, -11) and 18 (95% CI, -33, -4) minutes less sleep at night, respectively. Bottle feeding at bedtime was associated with 62 (95% CI, 21, 103) minutes additional longest nighttime sleep period. Exploratory mediation analyses suggested a modest mediating role of a non-dark sleep environment on racial/ethnic and educational differences in sleep duration. CONCLUSIONS: Infant sleep duration was positively associated with a dark sleep environment and a focal feed at bedtime while taking the baby to the parent's bed was associated with reduced infant sleep. Modifying the sleep environment and practices may improve infant sleep and reduce sleep health disparities.

Comparison of Mortality Risk With Different Surgeon and Hospital Operative Volumes Among Individuals Undergoing Pancreatectomy by Emulating Target Trials in US Medicare Beneficiaries.

Importance: The association of surgeons' and hospitals' operative volumes with postoperative patient outcomes has been studied for decades and holds important policy implications; however, in many volume-outcome analyses, this association is described without the envisioning of a clear intervention, which often introduces unintentional bias. Acting on such results may lead to unintended consequences from policy interventions or patient recommendations. Objective: To specify how (hypothetical) target trials would be designed to estimate the association between postoperative mortality of patients undergoing operations and a range of surgeon and hospital volume conditions and then to emulate these trials by using observational data. Design, Setting, and Participants: This observational data analysis emulated 4 hypothetical target trials of increasing complexity, ranging from a poorly defined trial that would randomly assign participants only to surgeon volume to one that would randomly assign participants to surgeon volume, hospital volume, and specific surgeon and hospital. This population-based cohort study included 9136 Medicare beneficiaries with a first diagnosis of pancreatic malignant neoplasm who did not require neoadjuvant therapy and underwent pancreatectomy between January 1, 2012, and September 30, 2016. Data analysis was performed between September 1, 2019, and October 8, 2021. Exposures: Number of pancreatectomies performed by surgeon and hospital during the prior year. Main Outcomes and Measures: Ninety-day mortality. Results: The analyses included 9136 Medicare beneficiaries treated by 1358 surgeons at 697 hospitals; median age was 73.3 years (IQR, 69.1-78.1 years), and 4642 were men (51%). When trials with poorly defined interventions on surgeon volume were emulated, the estimated 90-day mortality was 7.9% (95% CI, 6.4%-9.4%) for lower-volume surgeons and 5.2% (95% CI, 2.7%-10.9%) for higher-volume surgeons. When trials with better-defined interventions were emulated, the difference was reduced: 7.8% (95% CI, 6.3%-9.3%) for lower-volume surgeons and 7.2% (95% CI, 6.0%-8.7%) for higher-volume surgeons. Conclusions and Relevance: In this cohort study that emulated 4 different target trials with data from Medicare beneficiaries undergoing pancreatectomy, mortality differences across surgical volume levels were attenuated when the interventions were well defined. The application of the hypothetical target trial framework to this specific volume-outcomes scenario revealed the complexities of this research question and the unintentional biases introduced in prior studies, which emulated poorly defined trials whose results are therefore difficult to interpret. The target trial framework may be of value to outcomes researchers asking questions that correspond to well-defined interventions for the real world.

Exploring a theory of change: Are increases in parental empowerment associated with healthier weight-related parenting practices?

INTRODUCTION: Parent health-related empowerment is defined as the process by which parents realize control over their life situation and take action to promote a healthier lifestyle. For decades, researchers have described the theoretical potential of empowerment in health promotion efforts, though few have empirically examined this hypothesized relationship. This study is one of the first to examine the relationship between parental empowerment and healthy weight parenting practices (i.e., food, physical activity, sleep, and media parenting), as a mechanism for early childhood health promotion in community settings. METHODS: Low-income parents of preschool-aged children attending Head Start in Greater Boston between fall 2017 and spring 2019 were invited to complete a survey in the fall and spring of each academic school year (n = 578 with two surveys and n = 45 with four). Parental empowerment and healthy weight parenting practices were assessed using validated surveys. We used a multilevel difference-in-difference approach to estimate changes in healthy weight parenting practices score by changes in parental empowerment score. RESULTS: Out of a possible score of four, the unadjusted mean (SD) score in fall was 3.20 (0.40) for empowerment and 3.01 (0.40) for parenting. An increase in parental empowerment was associated with an increase in healthier parenting practices (b = 0.14; 95% CI = 0.08, 0.20; p < 0.0001). CONCLUSIONS: Parent empowerment may be an important target in interventions to prevent obesity in low-income children.

Sexual and reproductive health information: Disparities across sexual orientation groups in two cohorts of U.S. women.

INTRODUCTION: Limited research exists about how receiving/seeking sexual and reproductive health (SRH) information differs by sexual orientation. Our goal was to identify how sources and topics of SRH information differed by sexual orientation during adolescence in a sample of U.S. women. METHODS: A sample of 8,541 U.S. women ages 22-35 years from two cohorts of the Growing Up Today Study completed a 2016 questionnaire measure about receiving/seeking SRH information before age 18 years. Adjusted log-linear models assessed differences in SRH information topics and sources by reported sexual orientation (completely heterosexual with no same-sex partners [reference]; completely heterosexual with same-sex partners; mostly heterosexual; bisexual; lesbian). RESULTS: Compared to the referent, most sexual minority subgroups were more likely to receive/seek information from peers, media, and other sources (e.g., community centers). With the exception of lesbians, sexual minority subgroups were more likely to receive/seek information about contraception, and mostly heterosexual and bisexual women were more likely to receive information about sexually transmitted infections. Conclusions: Findings indicate women of diverse sexual orientations need access to SRH information from sources like schools, peers, and media. Sexual minority women receive/seek information about many SRH topics, which indicates that opportunities to tailor educational resources within and outside of schools are needed so SRH benefits to these populations are maximized. POLICY IMPLICATIONS: Specifying sexual minority-sensitive educational materials in sex education policy can meet information needs and aid sexual minority women in making informed sexual health decisions.

Strengthening Health Services Research Using Target Trial Emulation: An Application to Volume-Outcomes Studies.

The number of operations that surgeons have previously performed is associated with their patients' outcomes. However, this association may not be causal, because previous studies have often been cross-sectional and their analyses have not considered time-varying confounding or positivity violations. In this paper, using the example of surgeons who perform coronary artery bypass grafting, we describe (hypothetical) target trials for estimation of the causal effect of the surgeons' operative volumes on patient mortality. We then demonstrate how to emulate these target trials using data from US Medicare claims and provide effect estimates. Our target trial emulations suggest that interventions on physicians' volume of coronary artery bypass grafting operations have little effect on patient mortality. The target trial framework highlights key assumptions and draws attention to areas of bias in previous observational analyses that deviated from their implicit target trials. The principles of the presented methodology may be adapted to other scenarios of substantive interest in health services research.

Emergence of racial/ethnic and socioeconomic differences in objectively measured sleep-wake patterns in early infancy: results of the Rise & SHINE study.

STUDY OBJECTIVES: To characterize objectively assessed sleep-wake patterns in infants at approximately 1 month and 6 months and examine the differences among infants with different racial/ethnic backgrounds and household socioeconomic status (SES). METHODS: Full-term healthy singletons wore an ankle-placed actigraph at approximately 1 month and 6 months and parents completed sleep diaries. Associations of racial/ethnic and socioeconomic indices with sleep outcomes were examined using multivariable analyses. Covariates included sex, birth weight for gestational age z-score, age at assessment, maternal education, household income, bed-sharing, and breastfeeding. RESULTS: The sample included 306 infants, of whom 51% were female, 42.5% non-Hispanic white, 32.7% Hispanic, 17.3% Asian, and 7.5% black. Between 1 month and 6 months, night sleep duration increased by 65.7 minutes (95% CI: 55.4, 76.0), night awakenings decreased by 2.2 episodes (2.0, 2.4), and daytime sleep duration decreased by 73.3 minutes (66.4, 80.2). Compared to change in night sleep duration over this development period for white infants (82.3 minutes [66.5, 98.0]), night sleep increased less for Hispanic (48.9 minutes [30.8, 66.9]) and black infants (31.6 minutes [-5.9, 69.1]). Night sleep duration also increased less for infants with lower maternal education and household income. Asian infants had more frequent night awakenings. Adjustment for maternal education and household income attenuated all observed day and night sleep duration differences other than in Asians, where persistently reduced nighttime sleep at 6 months was observed. CONCLUSIONS: Racial/ethnic differences in sleep emerge in early infancy. Night and 24-hour sleep durations increase less in Hispanic and black infants compared to white infants, with differences largely explained by SES.

Association of Selective Serotonin Reuptake Inhibitors With the Risk of Type 2 Diabetes in Children and Adolescents.

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

Contextual and Parenting Factors Contribute to Shorter Sleep Among Hispanic/Latinx Compared to Non-Hispanic White Infants.

BACKGROUND: Sleep is an important aspect of child development and health. Disparities in childhood sleep have been observed as early as infancy, but little is known about the factors contributing to them. PURPOSE: The objective of this study was to examine whether intrinsic, contextual, and parenting factors contribute to differences in sleep duration between Hispanic/Latinx and non-Hispanic white infants at 6 months of age. METHODS: We analyzed data of 119 Hispanic/Latinx and 146 non-Hispanic white infants in Rise & SHINE, a prospective birth cohort study of mother-infant dyads. Mothers reported their infant's sleep patterns using the Brief Infant Sleep Questionnaire at 6 months. Mothers also completed surveys measuring intrinsic (sex, gestational length, and birth weight), contextual (cultural, environmental, and familial), and parenting (behaviors and practices) factors. We used multivariable linear and logistic regression analyses to examine the contributing effects of these clusters of variables on the association between racial/ethnic background and infant sleep duration. RESULTS: Hispanic/Latinx infants slept 38 min less than white infants at 6 months (ß: -0.63 [95% confidence interval: -1.07, -0.19]) and were nearly three times more likely to not meet the minimum sleep recommendation. The differences persisted after adjustment for intrinsic factors but were attenuated after additional adjustment for contextual and parenting factors, especially having a foreign-born mother and later bedtime. CONCLUSIONS: The results of this study demonstrate that differences in sleep duration among Hispanic/Latinx infants compared to their white counterparts are present as early as 6 months of age and that context and parenting matter.

Outcome-dependent sampling in cluster-correlated data settings with application to hospital profiling.

Hospital readmission is a key marker of quality of healthcare and an important policy measure, used by the Centers for Medicare and Medicaid Services to determine, in part, reimbursement rates. Currently, analyses of readmissions are based on a logistic-normal generalized linear mixed model that permits estimation of hospital-specific measures while adjusting for case mix differences. Recent moves to identify and address healthcare disparities call for expanding case mix adjustment to include measures of socio-economic status while minimizing additional burden to hospitals associated with collecting data on such measures. Towards resolving this dilemma, we propose that detailed socio-economic data be collected on a subsample of patients via an outcome-dependent sampling scheme, specifically the cluster-stratified case-control design. Estimation and inference, for both the fixed and the random-effects components, are performed via pseudo-maximum-likelihood wherein inverse probability weights are incorporated in the usual integrated likelihood to account for the design. In comprehensive simulations, cluster-stratified case-control sampling proves to be an efficient design whenever interest lies in fixed or random effects of a generalized linear mixed model and covariates are unobserved or expensive to collect. The methods are motivated by and illustrated with an analysis of N = 889661 Medicare beneficiaries hospitalized between 2011 and 2013 with congestive heart failure at one of K = 3116 hospitals. Results highlight that the framework proposed provides a means of mitigating disparities in terms of which hospitals are indicated as being poor performers, relative to a naive analysis that fails to adjust for missing case mix variables.

Impact of the Affordable Care Act on human papillomavirus vaccination initiation among lesbian, bisexual, and heterosexual U.S. women.

OBJECTIVE: To examine the effect of the 2010 Affordable Care Act (ACA) extended dependent coverage and no cost-sharing provisions on human papillomavirus (HPV) vaccination in relation to sexual orientation identity among U.S. women. DATA SOURCES: 2006-2010 and 2011-2015 National Survey of Family Growth. STUDY DESIGN: We used an interrupted time series design and multivariable Poisson regression to assess differences in HPV vaccination initiation before (2007-2010) and after (2011-2015) the 2010 ACA provisions among heterosexual, bisexual, and lesbian U.S. women aged 15-25 years (N = 7033), adjusting for temporal trends and demographic factors. DATA COLLECTION: Computer-assisted personal interview and audio computer-assisted self-interview questionnaires. PRINCIPAL FINDINGS: The adjusted prevalence of HPV vaccination initiation was significantly higher among lesbian and bisexual women after compared to before the 2010 ACA-at 19.1 (95% confidence interval [CI]: 5.4, 32.9) and 15.7 (95% CI: 4.4, 27.1) percentage points in 2015 compared to 2007-2010, respectively. We observed no association between the 2010 ACA provisions and HPV vaccination initiation among heterosexual women after adjusting for temporal trends and demographic factors. CONCLUSIONS: The 2010 ACA provisions may have improved HPV vaccination initiation among lesbian and bisexual women. Policies and programs that increase access to health insurance and provide HPV vaccines at no cost to patients may facilitate HPV vaccine uptake in these marginalized populations.

Health system modelling research: towards a whole-health-system perspective for identifying good value for money investments in health system strengthening.

Global health research has typically focused on single diseases, and most economic evaluation research to date has analysed technical health interventions to identify 'best buys'. New approaches in the conduct of economic evaluations are needed to help policymakers in choosing what may be good value (ie, greater health, distribution of health, or financial risk protection) for money (ie, per budget expenditure) investments for health system strengthening (HSS) that tend to be programmatic. We posit that these economic evaluations of HSS interventions will require developing new analytic models of health systems which recognise the dynamic connections between the different components of the health system, characterise the type and interlinks of the system's delivery platforms; and acknowledge the multiple constraints both within and outside the health sector which limit the system's capacity to efficiently attain its objectives. We describe priority health system modelling research areas to conduct economic evaluation of HSS interventions and ultimately identify good value for money investments in HSS.

A tool for empirical equipoise assessment in multigroup comparative effectiveness research.

PURPOSE: In observational research, equipoise concerns whether groups being compared are similar enough for valid inference. Empirical equipoise was previously proposed as a tool to assess patient similarity based on propensity scores (PS). We extended this work for multigroup observational studies. METHODS: We modified the tool to allow for multinomial exposures such that the proposed definition reduces to the original when there are only two groups. We illustrated how the tool can be used as a method to assess study design within three-group clinical examples. We then conducted three-group simulations to assess how the tool performed in a setting with residual confounding after PS weighting. RESULTS: In a clinical example based on rheumatoid arthritis, 44.5% of the sample fell within the region of empirical equipoise when considering first-line biologics, whereas 57.7% did so for second-line biologics, consistent with the expectation that a second-line design results in better equipoise. In a simulation where the unmeasured confounder had the same magnitude of association with the treatment as the measured confounders and a 25% greater association with the outcome, the tool crossed the proposed threshold for empirical equipoise at a residual confounding of 20% on the ratio scale. When the unmeasured variable had a twice larger association with treatment, the tool became less sensitive and crossed the threshold at a residual confounding of 30%. CONCLUSION: Our proposed tool may be useful in guiding cohort identification in multigroup observational studies, particularly with similar effects of unmeasured and measured covariates on treatment and outcome.

Association of the Hospital Readmissions Reduction Program With Mortality Among Medicare Beneficiaries Hospitalized for Heart Failure, Acute Myocardial Infarction, and Pneumonia.

Importance: The Hospital Readmissions Reduction Program (HRRP) has been associated with a reduction in readmission rates for heart failure (HF), acute myocardial infarction (AMI), and pneumonia. It is unclear whether the HRRP has been associated with change in patient mortality. Objective: To determine whether the HRRP was associated with a change in patient mortality. Design, Setting, and Participants: Retrospective cohort study of hospitalizations for HF, AMI, and pneumonia among Medicare fee-for-service beneficiaries aged at least 65 years across 4 periods from April 1, 2005, to March 31, 2015. Period 1 and period 2 occurred before the HRRP to establish baseline trends (April 2005-September 2007 and October 2007-March 2010). Period 3 and period 4 were after HRRP announcement (April 2010 to September 2012) and HRRP implementation (October 2012 to March 2015). Exposures: Announcement and implementation of the HRRP. Main Outcomes and Measures: Inverse probability-weighted mortality within 30 days of discharge following hospitalization for HF, AMI, and pneumonia, and stratified by whether there was an associated readmission. An additional end point was mortality within 45 days of initial hospital admission for target conditions. Results: The study cohort included 8.3 million hospitalizations for HF, AMI, and pneumonia, among which 7.9 million (mean age, 79.6 [8.7] years; 53.4% women) were alive at discharge. There were 3.2 million hospitalizations for HF, 1.8 million for AMI, and 3.0 million for pneumonia. There were 270 517 deaths within 30 days of discharge for HF, 128 088 for AMI, and 246 154 for pneumonia. Among patients with HF, 30-day postdischarge mortality increased before the announcement of the HRRP (0.27% increase from period 1 to period 2). Compared with this baseline trend, HRRP announcement (0.49% increase from period 2 to period 3; difference in change, 0.22%, P = .01) and implementation (0.52% increase from period 3 to period 4; difference in change, 0.25%, P = .001) were significantly associated with an increase in postdischarge mortality. Among patients with AMI, HRRP announcement was associated with a decline in postdischarge mortality (0.18% pre-HRRP increase vs 0.08% post-HRRP announcement decrease; difference in change, -0.26%; P = .01) and did not significantly change after HRRP implementation. Among patients with pneumonia, postdischarge mortality was stable before HRRP (0.04% increase from period 1 to period 2), but significantly increased after HRRP announcement (0.26% post-HRRP announcement increase; difference in change, 0.22%, P = .01) and implementation (0.44% post-HPPR implementation increase; difference in change, 0.40%, P < .001). The overall increase in mortality among patients with HF and pneumonia was mainly related to outcomes among patients who were not readmitted but died within 30 days of discharge. For all 3 conditions, HRRP implementation was not significantly associated with an increase in mortality within 45 days of admission, relative to pre-HRRP trends. Conclusions and Relevance: Among Medicare beneficiaries, the HRRP was significantly associated with an increase in 30-day postdischarge mortality after hospitalization for HF and pneumonia, but not for AMI. Given the study design and the lack of significant association of the HRRP with mortality within 45 days of admission, further research is needed to understand whether the increase in 30-day postdischarge mortality is a result of the policy.