A comparison of computational algorithms for the Bayesian analysis of clinical trials.

BACKGROUND: Clinical trials are increasingly using Bayesian methods for their design and analysis. Inference in Bayesian trials typically uses simulation-based approaches such as Markov Chain Monte Carlo methods. Markov Chain Monte Carlo has high computational cost and can be complex to implement. The Integrated Nested Laplace Approximations algorithm provides approximate Bayesian inference without the need for computationally complex simulations, making it more efficient than Markov Chain Monte Carlo. The practical properties of Integrated Nested Laplace Approximations compared to Markov Chain Monte Carlo have not been considered for clinical trials. Using data from a published clinical trial, we aim to investigate whether Integrated Nested Laplace Approximations is a feasible and accurate alternative to Markov Chain Monte Carlo and provide practical guidance for trialists interested in Bayesian trial design. METHODS: Data from an international Bayesian multi-platform adaptive trial that compared therapeutic-dose anticoagulation with heparin to usual care in non-critically ill patients hospitalized for COVID-19 were used to fit Bayesian hierarchical generalized mixed models. Integrated Nested Laplace Approximations was compared to two Markov Chain Monte Carlo algorithms, implemented in the software JAGS and stan, using packages available in the statistical software R. Seven outcomes were analysed: organ-support free days (an ordinal outcome), five binary outcomes related to survival and length of hospital stay, and a time-to-event outcome. The posterior distributions for the treatment and sex effects and the variances for the hierarchical effects of age, site and time period were obtained. We summarized these posteriors by calculating the mean, standard deviations and the 95% equitailed credible intervals and presenting the results graphically. The computation time for each algorithm was recorded. RESULTS: The average overlap of the 95% credible interval for the treatment and sex effects estimated using Integrated Nested Laplace Approximations was 96% and 97.6% compared with stan, respectively. The graphical posterior densities for these effects overlapped for all three algorithms. The posterior mean for the variance of the hierarchical effects of age, site and time estimated using Integrated Nested Laplace Approximations are within the 95% credible interval estimated using Markov Chain Monte Carlo but the average overlap of the credible interval is lower, 77%, 85.6% and 91.3%, respectively, for Integrated Nested Laplace Approximations compared to stan. Integrated Nested Laplace Approximations and stan were easily implemented in clear, well-established packages in R, while JAGS required the direct specification of the model. Integrated Nested Laplace Approximations was between 85 and 269 times faster than stan and 26 and 1852 times faster than JAGS. CONCLUSION: Integrated Nested Laplace Approximations could reduce the computational complexity of Bayesian analysis in clinical trials as it is easy to implement in R, substantially faster than Markov Chain Monte Carlo methods implemented in JAGS and stan, and provides near identical approximations to the posterior distributions for the treatment effect. Integrated Nested Laplace Approximations was less accurate when estimating the posterior distribution for the variance of hierarchical effects, particularly for the proportional odds model, and future work should determine if the Integrated Nested Laplace Approximations algorithm can be adjusted to improve this estimation.

The impact of multimorbidity and functional limitation on quality of life in patients with heart failure: A multi-site study.

BACKGROUND: Multimorbidity and functional limitation are associated with poor outcomes in heart failure (HF). However, the individual and combined effect of these on health-related quality of life in patients with HF is not well understood. METHODS: Patients aged ≥30 years with two or more HF diagnostic codes and one or more HF-related prescription drugs from four U.S. institutions were mailed a survey to measure patient-centric factors including functional status (activities of daily living [ADLs]) and health-related quality of life (PROMIS-29 Health Profile). Patients with HF from January 1, 2013 to February 1, 2018 were included. Multimorbidity was defined as ≥2 non-cardiovascular comorbidities; functional limitation as any limitation in at least one of eight ADLs. Patients were categorized into four groups by multimorbidity (Yes/No) and functional limitation (Yes/No). We dichotomized the PROMIS-29 sub-scale scores at the median and calculated odd ratios for the four multimorbidity/functional limitation groups. RESULTS: A total of 3330 patients with HF returned the survey (response rate 31%); 3020 completed the questions of interest and were retained. Among these patients (45% female; mean age 73 [standard deviation: 12] years), 29% had neither multimorbidity nor functional limitation, 24% had multimorbidity only, 22% had functional limitation only, and 25% had both. After adjustment, having functional limitation only was associated with higher anxiety (odds ratio [OR]: 3.44, 95% confidence interval [CI]: 2.66-4.45), depression (OR: 3.11, 95% CI: 2.39-4.06), and fatigue (OR: 4.19, 95% CI: 3.25-5.40); worse sleep (OR: 2.14, 95% CI: 1.69-2.72) and pain (OR: 6.73, 95% CI: 5.15-8.78); and greater difficulty with social activities (OR: 9.40, 95% CI: 7.19-12.28) compared with having neither. Results were similar for having both multimorbidity and functional limitation. CONCLUSION: Patients with only functional limitation have similar poor health-related quality of life scores as those with both multimorbidity and functional limitation, underscoring the important role that physical functioning plays in the well-being of patients with HF.

A large, multi-center survey assessing health, social support, literacy, and self-management resources in patients with heart failure.

BACKGROUND: Most patients with heart failure (HF) have multimorbidity which may cause difficulties with self-management. Understanding the resources patients draw upon to effectively manage their health is fundamental to designing new practice models to improve outcomes in HF. We describe the rationale, conceptual framework, and implementation of a multi-center survey of HF patients, characterize differences between responders and non-responders, and summarize patient characteristics and responses to the survey constructs among responders. METHODS: This was a multi-center cross-sectional survey study with linked electronic health record (EHR) data. Our survey was guided by the Chronic Care Model to understand the distribution of patient-centric factors, including health literacy, social support, self-management, and functional and mental status in patients with HF. Most questions were from existing validated questionnaires. The survey was administered to HF patients aged ≥ 30 years from 4 health systems in PCORnet® (the National Patient-Centered Clinical Research Network): Essentia Health, Intermountain Health, Mayo Clinic, and The Ohio State University. Each health system mapped their EHR data to a standardized PCORnet Common Data Model, which was used to extract demographic and clinical data on survey responders and non-responders. RESULTS: Across the 4 sites, 10,662 patients with HF were invited to participate, and 3330 completed the survey (response rate: 31%). Responders were older (74 vs. 71 years; standardized difference (95% CI): 0.18 (0.13, 0.22)), less racially diverse (3% vs. 12% non-White; standardized difference (95% CI): -0.32 (-0.36, -0.28)), and had higher prevalence of many chronic conditions than non-responders, and thus may not be representative of all HF patients. The internal reliability of the validated questionnaires in our survey was good (range of Cronbach's alpha: 0.50-0.96). Responders reported their health was generally good or fair, they frequently had cardiovascular comorbidities, > 50% had difficulty climbing stairs, and > 10% reported difficulties with bathing, preparing meals, and using transportation. Nearly 80% of patients had family or friends sit with them during a doctor visit, and 54% managed their health by themselves. Patients reported generally low perceived support for self-management related to exercise and diet. CONCLUSIONS: More than half of patients with HF managed their health by themselves. Increased understanding of self-management resources may guide the development of interventions to improve HF outcomes.

Staffing and Antipsychotic Medication Use in Nursing Homes and Neighborhood Deprivation.

Importance: Inappropriate use of antipsychotic medications in nursing homes is a growing public health concern. Residents exposed to higher levels of socioeconomic deprivation in the area around a nursing home may be currently exposed, or have a long history of exposure, to more noise pollution, higher crime rates, and have less opportunities to safely go outside the facility, which may contribute to psychological stress and increased risk of receiving antipsychotic medications inappropriately. However, it is unclear whether neighborhood deprivation is associated with use of inappropriate antipsychotic medications and whether this outcome is different by facility staffing levels. Objective: To evaluate whether reported inappropriate antipsychotic medication use differs in severely and less severely deprived neighborhoods, and whether these differences are modified by higher levels of total nurse staffing. Design, Setting, and Participants: This was a cross-sectional analysis of a national sample of nursing homes that linked across 3 national large-scale data sets for the year 2019. Analyses were conducted between April and June 2023. Exposure: Neighborhood deprivation status (severe vs less severe) and total staffing hours (registered nurse, licensed practical nurse, certified nursing assistant). Main Outcome and Measures: This study estimated the association between neighborhood deprivation and the percentage of long-stay residents who received an antipsychotic medication inappropriately in the nursing home at least once in the past week and how this varied by nursing home staffing through generalized estimating equations. Analyses were conducted on the facility level and adjusted for state fixed effects. Results: This study included 10 966 nursing homes (1867 [17.0%] in severely deprived neighborhoods and 9099 [83.0%] in less deprived neighborhoods). Unadjusted inappropriate antipsychotic medication use was greater in nursing homes located in severely deprived neighborhoods (mean [SD], 15.9% [10.7%] of residents) than in those in less deprived neighborhoods (mean [SD], 14.2% [8.8%] of residents). In adjusted models, inappropriate antipsychotic medication use was higher in severely deprived neighborhoods vs less deprived neighborhoods (19.2% vs 17.1%; adjusted mean difference, 2.0 [95% CI, 0.35 to 3.71] percentage points) in nursing homes that fell below critical levels of staffing (less than 3 hours of nurse staffing per resident-day). Conclusions and Relevance: These findings suggest that levels of staffing modify disparities seen in inappropriate antipsychotic medication use among nursing homes located in severely deprived neighborhoods compared with nursing homes in less deprived neighborhoods. These findings may have important implications for improving staffing in more severely deprived neighborhoods.

The Registry-Based Randomized Trial - A Pragmatic Study Design.

Randomized controlled trials are the gold standard of clinical research for comparing therapies in well-defined groups of participants.1 Randomization avoids confounding due to unmeasured variables or to treatment selection and enables a causal interpretation of the estimated treatment effect. It has long been recognized, however, that standard explanatory clinical trials are slow, costly, and subject to participant selection. To preserve the strengths of randomized trials while mitigating their weaknesses, pragmatic randomized clinical trials emerged; these trials aim to facilitate decision-making rather than explicate a mechanism of action and enroll a diverse set of participants using existing structures and data sources.2.

Estimating the effect of diuretics and inhaled corticosteroids for evolving bronchopulmonary dysplasia in preterm infants.

BACKGROUND: Off-label treatment of extremely preterm infants with diuretics and inhaled corticosteroids (ICS) for evolving bronchopulmonary dysplasia (BPD) is common. Their effectiveness in reducing mortality or BPD severity, and optimal treatment timing, are unclear. OBJECTIVES: To determine whether diuretic treatment or ICS administration for infants with early evolving (between 10-27 days postnatal) and progressively evolving (28th-day-36th-week postnatal) BPD are independently associated with reduced mortality and moderate or severe BPD at 36-weeks postmenstrual age (PMA). METHODS: We examined neonates born before 28 weeks' gestation and admitted to neonatal intensive care units on postnatal Day 0 between 2006 and 2016 using data collected during routine care recorded within the Paediatric Health Information System (PHIS). An early evolving BPD cohort consisted of infants treated with oxygen, positive pressure or mechanical ventilation at 10 days postnatal. The progressively evolving BPD cohort consisted of infants treated with these modalities at 28 days. In new users, we evaluated the effect of diuretic and ICS treatment on mortality or BPD severity at 36 weeks PMA, adjusting for time-dependent confounding by respiratory status using marginal structural models. RESULTS: Early evolving BPD was present in 10,135 patients; progressively evolving BPD in 11,728. New diuretic exposure during early evolving BPD (adjusted risk ratio [aRR] 0.77, 95% confidence interval [CI] 0.65, 0.93) was associated with decreased mortality or moderate/severe BPD risk. New diuretics (aRR 0.86, 95% CI 0.75, 0.99) during progressively evolving BPD between 28-days-36-weeks PMA were less strongly associated with mortality or moderate/severe BPD reduction. There was no strong association for ICS in patients with early evolving (aRR: 1.40; 95% CI: 0.79, 2.51) or progressively evolving BPD (aRR 1.16, 95% CI 0.95, 1.49). CONCLUSION: Diuretics, but not ICS, for evolving BPD were associated with mortality and BPD risk reduction.

Assets for integrating task-sharing strategies for hypertension within HIV clinics: Stakeholder's perspectives using the PEN-3 cultural model.

BACKGROUND: Access to antiretroviral therapy has increased life expectancy and survival among people living with HIV (PLWH) in African countries like Nigeria. Unfortunately, non-communicable diseases such as cardiovascular diseases are on the rise as important drivers of morbidity and mortality rates among this group. The aim of this study was to explore the perspectives of key stakeholders in Nigeria on the integration of evidence-based task-sharing strategies for hypertension care (TASSH) within existing HIV clinics in Nigeria. METHODS: Stakeholders representing PLWH, patient advocates, health care professionals (i.e. community health nurses, physicians and chief medical officers), as well as policymakers, completed in-depth qualitative interviews. Stakeholders were asked to discuss facilitators and barriers likely to influence the integration of TASSH within HIV clinics in Akwa Ibom, Nigeria. The interviews were transcribed, keywords and phrases were coded using the PEN-3 cultural model as a guide. Framework thematic analysis guided by the PEN-3 cultural model was used to identify emergent themes. RESULTS: Twenty-four stakeholders participated in the interviews. Analysis of the transcribed data using the PEN-3 cultural model as a guide yielded three emergent themes as assets for the integration of TASSH in existing HIV clinics. The themes identified are: 1) extending continuity of care among PLWH; 2) empowering health care professionals and 3) enhancing existing workflow, staff motivation, and stakeholder advocacy to strengthen the capacity of HIV clinics to integrate TASSH. CONCLUSION: These findings advance the field by providing key stakeholders with knowledge of assets within HIV clinics that can be harnessed to enhance the integration of TASSH for PLWH in Nigeria. Future studies should evaluate the effect of these assets on the implementation of TASSH within HIV clinics as well as their effect on patient-level outcomes over time.

Effect of therapeutic-dose heparin on severe acute kidney injury and death in noncritically ill patients hospitalized for COVID-19: a prespecified secondary analysis of the ACTIV4a and ATTACC randomized trial.

Background: Acute kidney injury (AKI) in patients with COVID-19 is partly mediated by thromboinflammation. In noncritically ill patients with COVID-19, therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support. Objectives: We investigated whether therapeutic-dose heparin reduces the incidence of AKI or death in noncritically ill patients hospitalized for COVID-19. Methods: We report a prespecified secondary analysis of the ACTIV4a and ATTACC open-label, multiplatform randomized trial of therapeutic-dose heparin vs usual-care pharmacologic thromboprophylaxis on the incidence of severe AKI (≥2-fold increase in serum creatinine or initiation of kidney replacement therapy (KDIGO stage 2 or 3) or all-cause mortality in noncritically ill patients hospitalized for COVID-19. Bayesian statistical models were adjusted for age, sex, D-dimer, enrollment period, country, site, and platform. Results: Among 1922 enrolled, 23 were excluded due to pre-existing end stage kidney disease and 205 were missing baseline or follow-up creatinine measurements. Severe AKI or death occurred in 4.4% participants assigned to therapeutic-dose heparin and 5.5% assigned to thromboprophylaxis (adjusted relative risk [aRR]: 0.72; 95% credible interval (CrI): 0.47, 1.10); the posterior probability of superiority for therapeutic-dose heparin (relative risk < 1.0) was 93.6%. Therapeutic-dose heparin was associated with a 97.7% probability of superiority to reduce the composite of stage 3 AKI or death (3.1% vs 4.6%; aRR: 0.64; 95% CrI: 0.40, 0.99) compared to thromboprophylaxis. Conclusion: Therapeutic-dose heparin was associated with a high probability of superiority to reduce the incidence of in-hospital severe AKI or death in patients hospitalized for COVID-19.

Building Capacity of Community Nurses to Strengthen the Management of Uncomplicated Hypertension in Persons Living with HIV in Low- and Middle-Income Countries.

Objectives: Poor training of non-physician healthcare workers (especially community nurses) could hinder the successful integration of cardiovascular disease (CVD) management into HIV chronic care in primary healthcare facilities in low- and middle-income countries. To address this limitation, we included a holistic training programme with a robust module for both practice facilitators and community nurses as part of the formative stages of the managing hypertension among people living with HIV: an integrated model (MAP-IT), which is a study that is evaluating the effectiveness of practice facilitation on the integration of a task-strengthening strategy for hypertension control (TASSH) into primary healthcare centres in Akwa Ibom State of Nigeria. Methods: Between June and November 2021, 3 didactic training workshops were conducted using a training module which is based on the simplified Nigerian Hypertension Protocol for primary care and the World Health Organization (WHO) heart package. Knowledge acquired by the participants was assessed using anonymized pre- and post-training assessments in the first two workshops. Participants' view of the training was assessed using a comprehensive course evaluation questionnaire. Results: A total of 92 community nurses and six practice facilitators were trained in the workshops on managing hypertension in persons living with HIV. Mean pre- and post-test scores improved from 11.9(3.4) to 15.9(2.9); p < 0.001 in the first workshop, and from 15.4(0.9) to 16.4 (1.4); p < 0.001 in the second workshop. The methodology used in the training, understanding of the MAP-IT study programme, and the level of engagement was highly rated by the participants with LIKERT scores of 3.2/4.0, 3.2/4.0, and 3.1/4.0 respectively. Conclusion: Our training methodology, which involved the train-the-trainer model to deliver simplified HIV and HTN care guidelines, showed improvement in the knowledge of managing hypertension in persons living with HIV and was highly rated by participants.

Study design and protocol of a stepped wedge cluster randomized trial using a practical implementation strategy as a model for hypertension-HIV integration - the MAP-IT trial.

BACKGROUND: As people living with HIV (PLWH) experience earlier and more pronounced onset of noncommunicable diseases (NCDs), advancing integrated care networks and models in low-resource-high-need settings is critical. Leveraging current health system initiatives and addressing gaps in treatment for PLWH, we report our approach using a late-stage (T4) implementation research study to test the adoption and sustainability of a proven-effective implementation strategy which has been minimally applied in low-resource settings for the integration of hypertension control into HIV treatment. We detail our protocol for the Managing Hypertension Among People Living with HIV: an Integrated Model (MAP-IT) trial, which uses a stepped wedge cluster randomized trial (SW-CRT) design to evaluate the effectiveness of practice facilitation on the adoption of a hypertension treatment program for PLWH receiving care at primary healthcare centers (PHCs) in Akwa Ibom State, Nigeria. DESIGN: In partnership with the Nigerian Federal Ministry of Health (FMOH) and community organizations, the MAP-IT trial takes place in 30 PHCs. The i-PARiHS framework guided pre-implementation needs assessment. The RE-AIM framework will guide post-implementation activities to evaluate the effect of practice facilitation on the adoption, implementation fidelity, and sustainability of a hypertension program, as well as blood pressure (BP) control. Using a SW-CRT design, PHCs sequentially crossover from the hypertension program only (usual care) to hypertension plus practice facilitation (experimental condition). PHCs will recruit and enroll an average of 28-32 patients to reach a maximum of 960 PLWH participants with uncontrolled hypertension who will be followed longitudinally for BP outcomes. DISCUSSION: Given the need for integrated NCD-HIV care platforms in low-resource settings, MAP-IT will underscore the challenges and opportunities for integrating hypertension treatment into HIV care, particularly concerning adoption and sustainability. The evaluation of our integration approach will also highlight the potential impact of a health systems strengthening approach on BP control among PLWH. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT05031819 ). Registered on 2nd September 2021.

Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial.

Importance: Platelet activation is a potential therapeutic target in patients with COVID-19. Objective: To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients. Intervention: Participants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis. Results: At the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77). Conclusions and Relevance: In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

Organizational readiness to implement task-strengthening strategy for hypertension management among people living with HIV in Nigeria.

BACKGROUND: Hypertension (HTN) is highly prevalent among people living with HIV (PLHIV), but there is limited access to standardized HTN management strategies in public primary healthcare facilities in Nigeria. The shortage of trained healthcare providers in Nigeria is an important contributor to the increased unmet need for HTN management among PLHIV. Evidence-based TAsk-Strengthening Strategies for HTN control (TASSH) have shown promise to address this gap in other resource-constrained settings. However, little is known regarding primary health care facilities' capacity to implement this strategy. The objective of this study was to determine primary healthcare facilities' readiness to implement TASSH among PLHIV in Nigeria. METHODS: This study was conducted with purposively selected healthcare providers at fifty-nine primary healthcare facilities in Akwa-Ibom State, Nigeria. Healthcare facility readiness data were measured using the Organizational Readiness to Change Assessment (ORCA) tool. ORCA is based on the Promoting Action on Research Implementation in Health Services (PARIHS) framework that identifies evidence, context, and facilitation as the key factors for effective knowledge translation. Quantitative data were analyzed using descriptive statistics (including mean ORCA subscales). We focused on the ORCA context domain, and responses were scored on a 5-point Likert scale, with 1 corresponding to disagree strongly. FINDINGS: Fifty-nine healthcare providers (mean age 45; standard deviation [SD]: 7.4, 88% female, 68% with technical training, 56% nurses, 56% with 1-5 years providing HIV care) participated in the study. Most healthcare providers provide care to 11-30 patients living with HIV per month in their health facility, with about 42% of providers reporting that they see between 1 and 10 patients with HTN each month. Overall, staff culture (mean 4.9 [0.4]), leadership support (mean 4.9 [0.4]), and measurement/evidence-assessment (mean 4.6 [0.5]) were the topped-scored ORCA subscales, while scores on facility resources (mean 3.6 [0.8]) were the lowest. CONCLUSION: Findings show organizational support for innovation and the health providers at the participating health facilities. However, a concerted effort is needed to promote training capabilities and resources to deliver services within these primary healthcare facilities. These results are invaluable in developing future strategies to improve the integration, adoption, and sustainability of TASSH in primary healthcare facilities in Nigeria. TRIAL REGISTRATION: NCT05031819.

Severe neighborhood deprivation and nursing home staffing in the United States.

BACKGROUND: Low nursing home staffing in the United States is a growing safety concern. Socioeconomic deprivation in the local areas surrounding a nursing home may be a barrier to improving staffing rates but has been poorly studied. Thus, the objective of this paper was to assess the relationship between neighborhood deprivation and nursing home staffing in the United States. METHODS: This cross-sectional study used 2018 daily payroll-based staffing records and address data for 12,609 nursing homes in the United States linked with resident assessment data. Our primary exposure of interest was severe economic deprivation at the census block group (neighborhood) level, defined as an area deprivation index score ≥85/100. The primary outcome was hours worked per resident-day among nursing home employees providing direct resident care. Marginal linear regression models and generalized estimating equations with robust sandwich-type standard errors were used to estimate associations between severe neighborhood deprivation and staffing rates. RESULTS: Compared to less deprived neighborhoods, unadjusted staffing rates in facilities located within severely deprived neighborhoods were 38% lower for physical and occupational therapists, 30% lower for registered nurses (RNs), and 5% lower for certified nursing assistants. No disparities in licensed practical nurse (LPN) staffing were observed. In models with state-level and rurality fixed effects and clustered on the county, a similar pattern of disparities was observed. Specifically, RN staffing per 100 resident-days was significantly lower in facilities located within severely deprived neighborhoods as compared to those in less deprived areas (mean difference: 5.6 fewer hours, 95% confidence interval [CI] 4.2-6.9). Disparities of lower magnitude were observed for other clinical disciplines except for LPNs. CONCLUSIONS: Significant staffing disparities were observed within facilities located in severely deprived neighborhoods. Targeted interventions, including workforce recruitment and retention efforts, may be needed to improve staffing levels for nursing homes in deprived neighborhoods.

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis.

BACKGROUND: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology. MATERIALS AND METHODS: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk. RESULTS: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade. CONCLUSION: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Interpregnancy interval and preterm delivery: An empirical comparison of between-persons and within-sibship designs.

BACKGROUND: Short interpregnancy interval has been associated with increased risk of preterm delivery; recent studies employing within-sibship designs suggest that this risk may be exaggerated. There are unresolved issues regarding properties of this design. OBJECTIVES: To compare directly the results, for short intervals, of between-person and within-sibship analyses when applied to the same target population. METHODS: Cross-sectional data are from the National Survey of Family Growth, a statistically representative survey of women and men in the USA, 2006-2015. Participants provided a complete pregnancy history including outcome, duration and ending date, enabling calculation of interval. Conventional analysis employed log-linear regression, controlling survey design, early life events, demographic variables, pregnancy intendedness, breastfeeding of the previous birth and obstetric history. Within-sibship analyses, utilising conditional log-linear regression, controlled the same variables, except those remaining static within each participant. RESULTS: Among participants with at least three live- or stillbirths, the percentage of pregnancies in each interval, and the percent of deliveries that were preterm following that interval were 9.2%, 14.6% for <6, and 14.7%, 15.4% for 6-11, versus 12.2%, 14.7% for 18-23 months. Among participants with at least three live- or stillborn infants, those in the within-sibship analysis had a higher risk profile than comparably parous, ineligible participants. In a between-participant analysis, among those included in within-sibship models, the adjusted risk ratios (vs 18-23 months) for preterm delivery for intervals <6 and 6-11 months were 0.74 (95% CI 0.63, 0.88) and 0.85 (95% CI 0.74, 0.98). The corresponding risk ratios were 0.56 (95% CI 0.14, 2.30) and 0.49 (95% CI 0.13, 1.80) for those ineligible for the within-sibship models. CONCLUSIONS: When comparable analyses were employed, the association between interval and preterm delivery was similar between participants included in the within-sibship analysis and those ineligible for the within-sibship analysis, but differed from those in the full cohort, perhaps due to different target populations.

Access to rideshare and satisfaction, prenatal healthcare utilisation, and preterm delivery among pregnant Medicaid recipients: A randomised controlled trial.

BACKGROUND: Lack of access to reliable transportation is a barrier to timely receipt of prenatal care. OBJECTIVES: We aimed to assess the impact of modernisation of non-emergency medical transportation services on patient satisfaction, prenatal care utilisation, and preterm delivery. METHODS: We conducted a randomised controlled pilot trial among pregnant Medicaid recipients in Franklin County, Ohio, a county with high rates of infant mortality. Individuals were randomly assigned to usual non-emergency medical transportation services or enhanced smart transportation (EST) services (i.e. on-demand transportation with access to a mobile application and trips to the grocery store, food bank or pharmacy). The primary outcome was satisfaction with transportation services. Secondary outcomes included adequacy of prenatal care utilisation (APNCU) and preterm delivery <37 weeks. RESULTS: Women were screened between 31 May 2019 and 30 June 2020, with 143 being eligible and enrolling. Evidence of increased satisfaction with transportation was observed in the intervention group compared to usual transportation, with 83.8% and 68.8% reporting being somewhat satisfied or very satisfied respectively (risk difference [RD] 14.8%, 95% confidence interval [CI] 0.5, 29.1). There were no meaningful differences in APNCU or preterm delivery between groups (APNCU: RD 2.1%, 95% CI -14.0, 18.2 and preterm delivery: RD -3.9%, 95% CI -17.0, 9.3). CONCLUSIONS: We found evidence of increased transportation satisfaction among pregnant women randomly assigned to EST versus usual transportation. It remains unclear whether the provision of EST increases prenatal care utilisation or decreases preterm delivery.

A Comparison of Vaginal and Intramuscular Progesterone for the Prevention of Recurrent Preterm Birth.

OBJECTIVE: This study aimed to examine whether vaginal progesterone is noninferior to 17-α hydroxyprogesterone caproate (17OHP-C) in the prevention of recurrent preterm birth (PTB). STUDY DESIGN: This retrospective cohort study included singleton pregnancies among women with a history of spontaneous PTB who received prenatal care at a single tertiary center from 2011 to 2016. Pregnancies were excluded if progesterone was not initiated prior to 24 weeks or the fetus had a major congenital anomaly. The primary outcome was PTB <37 weeks. A priori, noninferiority was to be established if the upper bound of the adjusted two-sided 90% confidence interval (CI) for the difference in PTB fell below 9%. Inverse probability of treatment weighting (IPTW) was used to carefully control for confounding associated with choice of treatment and PTB. Adjusted differences in PTB proportions were estimated via IPTW regression, with standard errors adjustment for multiple pregnancies per woman. Secondary outcomes included PTB <34 and <28 weeks, spontaneous PTB, neonatal intensive care unit admission, and gestational age at delivery. RESULTS: Among 858 pregnancies, 41% (n = 353) received vaginal progesterone and 59% (n = 505) were given 17OHP-C. Vaginal progesterone use was more common later in the study period, and among women who established prenatal care later, had prior PTBs at later gestational ages, and whose race/ethnicity was neither non-Hispanic white nor non-Hispanic Black. Vaginal progesterone did not meet noninferiority criteria compared with 17-OHPC in examining PTB <37 weeks, with an IPTW adjusted difference of 3.4% (90% CI: -3.5, 10.3). For secondary outcomes, IPTW adjusted differences between treatment groups were generally small and CIs were wide. CONCLUSION: We could not conclude noninferiority of vaginal progesterone to 17OHP-C; however, women and providers may be willing to accept a larger difference (>9%) when considering the cost and availability of vaginal progesterone versus 17OHP-C. A well-designed randomized trial is needed. KEY POINTS: · Vaginal progesterone is not noninferior to 17OHP-C.. · PTB risk may be 10% higher with vaginal progesterone.. · Associations did not differ based on obesity status..

Demographic and Clinical Characteristics Associated With the Failure of Nonoperative Management of Uncomplicated Appendicitis in Children: Secondary Analysis of a Nonrandomized Clinical Trial.

Importance: The factors associated with the failure of nonoperative management of appendicitis and the differences in patient-reported outcomes between successful and unsuccessful nonoperative management remain unknown. Objectives: To investigate factors associated with the failure of nonoperative management of appendicitis and compare patient-reported outcomes between patients whose treatment succeeded and those whose treatment failed. Design, Setting, and Participants: This study was a planned subgroup secondary analysis conducted in 10 children's hospitals that included 370 children aged 7 to 17 years with uncomplicated appendicitis enrolled in a prospective, nonrandomized clinical trial between May 1, 2015, and October 31, 2018, with 1-year follow-up comparing nonoperative management with antibiotics vs surgery for uncomplicated appendicitis. Statistical analysis was performed from November 1, 2019, to February 12, 2022. Interventions: Nonoperative management with antibiotics vs surgery. Main Outcomes and Measures: Failure of nonoperative management and patient-reported outcomes. The relative risk (RR) of failure based on sociodemographic and clinical characteristics was calculated. Patient-reported outcomes were compared based on the success or failure of nonoperative management. Results: Of 370 patients (34.6% of 1068 total patients; 229 boys [61.9%]; median age, 12.3 years [IQR, 10.0-14.6 years]) enrolled in the nonoperative group, treatment failure occurred for 125 patients (33.8%) at 1 year, with 53 patients (14.3%) undergoing appendectomy during initial hospitalization and 72 patients (19.5%) experiencing delayed treatment failure after hospital discharge. Higher patient-reported pain at presentation was associated with increased risk of in-hospital treatment failure (RR, 2.1 [95% CI, 1.0-4.4]) but not delayed treatment failure (RR, 1.3 [95% CI, 0.7-2.3]) or overall treatment failure at 1 year (RR, 1.5 [95% CI, 1.0-2.2]). Pain duration greater than 24 hours was associated with decreased risk of delayed treatment failure (RR, 0.3 [95% CI, 0.1-1.0]) but not in-hospital treatment failure (RR, 1.2 [95% CI, 0.5-2.7]) or treatment failure at 1 year (RR, 0.7 [95% CI, 0.4-1.2]). There was no increased risk of treatment failure associated with age, white blood cell count, sex, race, ethnicity, primary language, insurance status, transfer status, symptoms at presentation, or imaging results. Health care satisfaction at 30 days and patient-reported, health-related quality of life at 30 days and 1 year were not different. Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs 27.0; difference, 1.0 [95% CI, 0.01-2.0]) and 1 year (28.1 vs 27.0; difference, 1.1 [95% CI, 0.2-2.0]). Conclusions and Relevance: This analysis suggests that a higher pain level at presentation was associated with a higher risk of initial failure of nonoperative management and that a longer duration of pain was associated with lower risk of delayed treatment failure. Although satisfaction was high in both groups, satisfaction with the treatment decision was higher among patients with successful nonoperative management at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT02271932.

A pilot randomized controlled trial of vaginal estrogen on postpartum atrophy, perineal pain, and sexual function.

INTRODUCTION AND HYPOTHESIS: Vulvovaginal symptoms following perineal laceration may be worsened by atrophy related to decreased estrogen. Our objective was to evaluate the effect of local estrogen therapy in this setting. METHODS: We conducted a single-center, pilot, randomized, placebo-controlled trial of local estradiol in primiparous women with a second-degree or greater perineal laceration following a term vaginal delivery. Participants were randomized to twice weekly estradiol or placebo cream from delivery through 3 months postpartum. The primary outcome was a validated measure of vulvovaginal symptoms at 12 weeks postpartum. Secondary outcomes included measures of perineal pain, quality of life, sexual function, ease of use, likelihood of continued use, and adverse events. RESULTS: We planned to enroll 70 women; however, due to human subjects research restrictions related to the COVID-19 pandemic, enrollment was stopped early. A total of 59 women were randomized, 31 to the estradiol group and 28 to the placebo group. Nearly all participants (95%) were followed through 12 weeks with suggestion of marginal improvement in Vulvar Assessment Scale scores [-0.10; 90% CI = (-0.20, 0.01)] in those randomized to estradiol compared to placebo. Local estradiol was not associated with improvement in other measures, and only one non-serious adverse event was observed. CONCLUSIONS: In primiparous women with a perineal laceration, use of local estradiol showed minimal clinical benefit in vulvovaginal atrophy and related symptoms but appears to be acceptable and safe for postpartum use. Larger adequately powered trials enrolling a diverse group of postpartum women are needed to affirm these findings.