Recent deb items

Bridging community-engaged research and implementation science methods to advance public health practice

Thu, 7 May 2026 00:00:00 +0000

Addressing public health challenges through equitable, evidence-based strategies remains a pressing global need. Implementation science bridges research and practice, offering methods to improve intervention design, delivery, and evaluation. Concurrently, community-engaged research embeds equity and trust into public health initiatives. This paper introduces selected community engagement methods and related implementation science approaches to address characteristic common constraints in public health practice, illustrated with real-world examples. Adapting the Knowledge to Action framework, we present a discussion of community-engaged methods and accompanying case studies. The discussion follows four phases present in applied public health research: (1) identifying and defining the problem, (2) designing and modifying the intervention, (3) evaluating the intervention, and (4) communicating and disseminating findings. For each phase, we highlight...

Use of Paracervical Blocks for Patients Who Undergo Intrauterine Device Insertion

Thu, 7 May 2026 00:00:00 +0000

Paracervical blocks can reduce pain during intrauterine device (IUD) insertions, but the extent and context in which they are used in practice are unclear. To evaluate paracervical block use during IUD insertions in an academic health system. This retrospective cross-sectional time-series study was performed at the University of California, San Francisco (UCSF), academic health care system using electronic health record data. Participants included individuals who underwent IUD insertions between July 2, 2012, and August 16, 2024. Data were analyzed from October 2023 to April 2025. Clinic-, clinician-, and patient-level variables. Paracervical block receipt was determined from clinical notes. Associations of paracervical block receipt with variables at the clinic, clinician, and patient levels were estimated with multilevel models. The role of clinic specialty (pediatrics or adolescent medicine vs all other specialties) in accounting for the association of age less than 18 years...

Unleashing Diffusion and State Space Models for Medical Image Segmentation

Thu, 7 May 2026 00:00:00 +0000

Existing segmentation models trained on a single medical imaging dataset often lack robustness when encountering unseen organs or tumors. Developing a robust model capable of identifying rare or novel tumor categories not present during training is crucial for advancing medical imaging applications. We propose DSM, a novel framework that leverages diffusion and state space models to segment unseen tumor categories beyond the training data. DSM utilizes two sets of object queries trained within modified attention decoders to enhance classification accuracy. Initially, the model learns organ queries using an object-aware feature grouping strategy to capture organ-level visual features. It then refines tumor queries by focusing on diffusion-based visual prompts, enabling precise segmentation of previously unseen tumors. Furthermore, we incorporate diffusion-guided feature fusion to improve semantic segmentation performance. By integrating CLIP text embeddings, DSM captures category-sensitive...

Integrating Mobile Text Messaging Pre-Exposure Prophylaxis Navigation Services Into a Home HIV and Sexually Transmitted Infection Self-Testing Program in the United States: Formative Work and Pilot Implementation Study.

Fri, 1 May 2026 00:00:00 +0000

Background

HIV testing is the gateway to the HIV prevention continuum and offers an important opportunity to provide HIV prevention services. TakeMeHome.org is an online program that enables state and local health departments to offer free in-home HIV and sexually transmitted infection self-testing. As few TakeMeHome users have used pre-exposure prophylaxis (PrEP), there is an opportunity to link TakeMeHome users to PrEP information and services.

Objective

The aim of this study is to develop an implementation strategy to link HIV or sexually transmitted infection self-testers from online orders to PrEP services via direct digital linkage to a novel SMS text messaging navigation program.

Methods

PrEPmate is an evidence-based bidirectional text-messaging platform that has demonstrated increased PrEP retention and adherence. We developed a novel program to link TakeMeHome testers to mobile SMS text messaging PrEP navigation via PrEPmate. We conducted focus groups...

Muscle mass, function and performance across the adult lifespan: the study of muscle, mobility and ageing

Wed, 22 Apr 2026 00:00:00 +0000

BACKGROUND: D3-creatine (D3Cr) dilution provides an accurate estimate of total body skeletal muscle mass, yet few studies have examined its relationship with function and performance across the lifespan, particularly before age 70. We modelled the association of age with D₃Cr muscle mass across adulthood and compared it with age-related differences in muscle function and performance. METHODS: Adults aged 30-69 years (n = 69; 33 men) and 70+ (n = 826; 344 men) from the Study of Muscle, Mobility and Ageing completed assessments of D3Cr muscle mass, magnetic resonance imaging (MRI) thigh muscle volume, 1-RM leg strength and leg extension power, 4 m walking speed and cardiorespiratory fitness (VO2 peak). Regression models estimated annualised percent differences with age for each outcome. RESULTS: In men, progressively lower D₃Cr muscle mass with advancing age (-0.5%/year in young adults to -1.4%/year in oldest-old) paralleled the pattern observed for leg strength and walking...

Enhanced Prenatal Care Models and Postpartum Depression

Thu, 9 Apr 2026 00:00:00 +0000

Racial, ethnic, and income disparities in perinatal depression prevalence and treatment are partially driven by social determinants of health. Effective treatments addressing these determinants are needed. To determine whether enhanced group prenatal care (eGPC) outperforms enhanced individual prenatal care (eIPC) for reducing perinatal depressive symptoms. This randomized clinical trial was conduced in 10 Medicaid-serving clinics in California’s San Joaquin Valley, enrolling English- or Spanish-speaking Medicaid-eligible pregnant individuals at less than 25 weeks’ gestation, from November 2019 to January 2024, with 2 follow-up surveys through 12 weeks postpartum. Analyses were conducted as intention-to-treat. Data were analyzed from December 2024 to December 2025. Participants were randomized to eIPC or eGPC. eIPC enhancements included assessments tailored to individual psychosocial, clinical, oral health, and substance use needs. eGPC enhancements included childcare, perinatal...

Development of the Preparation for Community‐Based Labor and Birth Instrument Centering Black Perspectives in the United States: A Participatory Adaptation

Wed, 1 Apr 2026 00:00:00 +0000

INTRODUCTION: Community-based birth supported by midwives and nurses is increasing in the United States amid stark racial disparities in maternal outcomes and worsening access to pregnancy care. Although studies examining prenatal confidence have shown that persons with higher confidence are more likely to give birth vaginally, reporting less pain, anxiety, and dissatisfaction, existing measurement tools have focused on hospital births. Accordingly, we adapted the previously validated Preparation for Labor and Birth (P-LAB) instrument, which measures third-trimester confidence for physiologic birth, for community-based births, centering the perspectives of Black populations. METHODS: Expert stakeholders (N = 5) including practicing midwives and maternal health researchers assessed the relevance and completeness of the P-LAB. Following individual reviews, stakeholders adapted the tool during a group review session. Virtual cognitive interviews were then conducted with community...

Long‐term safety of early discontinuation of antiseizure medication after resolution of acute provoked neonatal seizures

Thu, 26 Mar 2026 00:00:00 +0000

OBJECTIVE: To assess long-term safety of antiseizure medication (ASM) discontinuation after resolution of acute provoked neonatal seizures and prior to hospital discharge. METHODS: Prospective, observational, comparative effectiveness cohort study of neonates with acute provoked seizures born from July 2015 to March 2018, and followed until September 2024, at nine U.S. Neonatal Seizure Registry centers with Level IV neonatal intensive care units and Level IV pediatric epilepsy programs. Duration of ASM treatment was quantified as (1) discontinuation before discharge from the neonatal seizure admission or (2) maintenance at the time of hospital discharge. Outcomes were adjusted for propensity to receive ASM at discharge. Propensity for ASM maintenance was defined among enrolled participants by a logistic regression model including seizure etiology, gestational age, therapeutic hypothermia, worst electroencephalography (EEG) background, days of EEG seizures, and discharge neurological...

Behavioral interventions related to plastic waste management in low-and middle-income countries: a systematic review using the behavior change wheel and the theoretical domains framework

Thu, 26 Mar 2026 00:00:00 +0000

Abstract

Addressing the mounting plastic waste problem requires system-level solutions, along with interventions that promote behavioral change. In low-resource countries, inadequate, if not absent, waste management systems lead to unsafe disposal practices, including open burning. While theory-informed approaches are essential for identifying enablers and barriers to target behavior change, their application is limited in these settings. Given the lack of a theory-driven synthesis of behavioral strategies to address plastic waste, this systematic review aimed to: (1) synthesize behavioral interventions related to plastic waste management in low-resource countries; (2) map these interventions to the behavior change wheel (BCW), using the capability-opportunity-motivation-behavior model, and the theoretical domains framework (TDF); and (3) classify implementation strategies to inform theory-driven intervention design. This review is the first to use the BCW to examine behavioral...

Individualized Atrophy‐Based Prediction of Dementia Progression in Familial Frontotemporal Lobar Degeneration With Bayesian Linear Mixed‐Effects Modeling

Tue, 24 Mar 2026 00:00:00 +0000

OBJECTIVE: Age of symptom onset is highly variable in familial frontotemporal lobar degeneration (f-FTLD). Accurate prediction of onset would inform clinical management and trial enrollment. Prior studies indicate that individualized maps of brain atrophy can predict conversion to dementia in f-FTLD. We used a Bayesian linear mixed-effect (BLME) prediction method for identifying accelerated brain volume loss to predict conversion to dementia. METHODS: Participants included 234 asymptomatic or prodromal carriers of C9orf72, GRN, or MAPT mutations (including 21 dementia converters) with ≥3 longitudinal magnetic resonance imaging (MRI) T1-weighted scans. The BLME models established individual voxel-wise gray matter trajectories using the first 2 scans. Person-specific clusters of accelerated volume loss were estimated in subsequent scans and tested as predictors of dementia conversion compared with other approaches in time-varying Cox proportional hazard models covarying for age....

Intensity of Cyclophosphamide-Based Bridging Therapy Before Chimeric Antigen Receptor T Cell Therapy in Myeloma

Fri, 13 Mar 2026 00:00:00 +0000

Patients receiving autologous chimeric antigen receptor T cell (CAR-T) therapy for multiple myeloma (MM) may require bridging therapy (BT) before CAR-T infusion to maintain some level of disease control. Alkylators, such as cyclophosphamide (Cy), are often used in regimens, either in high-intensity regimens, such as modified hyperCVAD (cyclophosphamide, vincristine, doxorubicin, and dexamethasone), or once-weekly regimens, such as KCd (carfilzomib, cyclophosphamide, and dexamethasone). However, there is no consensus regarding the optimal BT alkylator dose intensity in MM. We performed a single-center analysis of all instances of BT before planned autologous CAR-T for MM during a 5-year period ending in April 2022. We classified bridging regimens into 3 cohorts: (1) hyperfractionated Cy (HyperCy) with inpatient Cy every 12 to 24 hours or as a continuous i.v. infusion; (2) less intensive Cy dosing (WeeklyCy), such as KCd; and (3) NonCy, in which no alkylators were used in BT. Demographic,...

Machine learning to optimize precision in the analysis of randomized trials: A journey in pre-specified, yet data-adaptive learning.

Thu, 12 Mar 2026 00:00:00 +0000

Covariate adjustment is an approach to improve the precision of trial analyses by adjusting for baseline variables that are prognostic of the primary endpoint. Motivated by the SEARCH Universal HIV Test-and-Treat Trial (2013-2017), we tell our story of developing, evaluating, and implementing a machine learning-based approach for covariate adjustment. We provide the rationale for as well as the practical concerns with such an approach for estimating marginal effects. Using schematics, we illustrate our procedure: targeted machine learning estimation (TMLE) with Adaptive Pre-specification. Briefly, sample-splitting is used to data-adaptively select the combination of estimators of the outcome regression (i.e. the conditional expectation of the outcome given the trial arm and covariates) and known propensity score (i.e. the conditional probability of being randomized to the intervention given the covariates) that minimizes the cross-validated variance estimate and, thereby, maximizes...

Intrauterine SARS-CoV-2 Exposure and Infant Neurodevelopment through 18 Months of Age: Findings from the RECOVER Pregnancy Study

Thu, 12 Mar 2026 00:00:00 +0000

OBJECTIVE: To assess associations between exposure to intrauterine SARS-CoV-2 and subsequent child neurodevelopment in a large, diverse cohort with confirmation of maternal SARS-CoV-2 status. STUDY DESIGN: The Researching COVID to Enhance Recovery (RECOVER) Pregnancy Cohort enrolled adults with and without SARS-CoV-2 during pregnancy and their offspring born January 2020 through December 2023 at 23 sites across the US. Neurodevelopment was assessed at 12 months with the Ages and Stages Questionnaire, 3^rd edition (ASQ-3) and at 18 months with the ASQ Social-Emotional (ASQ-SE) and the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). We compared exposed and unexposed infants' ASQ-3 total and subdomain scores, ASQ-SE and M-CHAT-R scores, and proportions meeting published referral thresholds, using multivariable linear and logistic regression. RESULTS: Among 1179 participants enrolled, 1008 (85.5%) had exposure, with 806 (80.0%) exposed during Omicron predominance....

The accuracy of self-reported height, weight and BMI in a sample of emerging adult college students across California: an observational study

Thu, 26 Feb 2026 00:00:00 +0000

BackgroundSelf-reported height and weight are pragmatic, lower-cost alternatives for objective measurements but are potentially less accurate. This study examines the accuracy of self-reported measurements in a population of emerging adults.MethodsParticipants were 603 emerging adult college students aged 18 to 24 who attend public Hispanic-Serving Institutions of higher education in California, USA. The population was heterogeneous by race/ethnicity, gender, socioeconomic position, and body size. Participants self-reported height and weight; height and weight were then objectively measured during an in-person visit.ResultsRelative to objective measurements, participants, on average, overreported their height by 1.53 cm and underreported their weight by 0.77 kg, leading to an average body mass index (BMI) underestimation of 0.73 kg/m2. The discrepancy between self-report and objective measures significantly differed by gender, race/ethnicity, and weight but not...

Well-being of health workers providing maternal and newborn care: A qualitative evidence synthesis.

Tue, 17 Feb 2026 00:00:00 +0000

Health workers providing maternal and newborn care can experience burnout and emotional distress, which harms their well-being and, consequently, their ability to deliver respectful care. The World Health Organization (WHO) Compendium on respectful maternal and newborn care identifies health workers well-being as a critical area for intervention, but no specific definition or domains of well-being exist for this group. We conducted a qualitative evidence synthesis to synthesise key domains of well-being for health workers providing maternal and newborn care, by exploring health workers perceptions and experiences about their well-being. We searched MEDLINE, CINAHL and MIDIRS from 2010 to 20 August 2025 to identify studies reporting health workers perceptions and experiences of well-being while providing routine maternal and newborn care in any context. Using maximum variation purposive sampling, we sampled papers for data extraction. Thematic synthesis was employed for analysis,...

Effects of an agricultural intervention on psychosocial health among pregnant and non-pregnant women with HIV in Kenya.

Fri, 13 Feb 2026 00:00:00 +0000

OBJECTIVES: We examined whether effects of an agricultural livelihood intervention on food insecurity and psychosocial outcomes remained robust in pregnant compared to non-pregnant women living with HIV, and whether potentially negative associations between pregnancy and these outcomes were alleviated by the intervention. DESIGN: Secondary analysis of the Shamba Maisha cluster-randomized controlled trial (N = 396 women; NCT02815579). The intervention included agribusiness training and supplies. METHODS: Food insecure women with HIV in Kenya were followed for 24 months between 2016 and 2019. Food insecurity, empowerment, social support, depression, HIV stigma, and intimate partner violence were collected at all visits. We estimated (1) the effect of the intervention on trends for each outcome via mixed-effects regression, separately for women who did and did not become pregnant during follow-up, and (2) whether trends differed by pregnancy status, separately by arm and adjusted...

Integrating nonpharmacologic strategies for pain with Inclusion, Respect, and Equity (INSPIRE): a digital health study protocol for a pragmatic multisite randomized controlled trial

Fri, 6 Feb 2026 00:00:00 +0000

BackgroundChronic pain (CP) is among the most common medical conditions, is the leading cause of disability, and is often refractory to medical treatment. The CDC and the American College of Physicians recommend nonopioid and nonpharmacologic treatment as first-line strategies, including cognitive-behavioral therapy (CBT), mindfulness-based interventions (MBI), and movement-focused interventions (MFI); however, only 3% of people with chronic pain (CP) have access to these evidence-based treatments. Patients from historically minoritized populations and those speaking languages other than English are particularly underserved and may go untreated. Stigma regarding CP and interventions to manage it present additional obstacles.MethodsThe Integrating Nonpharmacologic Strategies for Pain with Inclusion, Respect, and Equity (INSPIRE) study evaluates a blend of these non-pharmacologic, evidence-based interventions using a pragmatic, parallel, two-arm RCT comparing intervention participants...

Metabolic response to extended continuous positive airway pressure in premature infants

Thu, 29 Jan 2026 00:00:00 +0000

BackgroundExtending the duration of continuous positive airway pressure (CPAP) in preterm infants with respiratory distress may improve lung function.ObjectiveAssess the impact of extended CPAP (eCPAP) on the metabolomic profile and relationship to lung function.Design/methodsInfants ≤32 weeks’ gestational age were randomized to bubble eCPAP with room air or discontinued CPAP (dCPAP). Functional residual capacity (FRC) was measured at randomization and at 2 weeks. Blood samples obtained during treatment were subjected to UHPLC:MS/MS (Metabolon Inc.) and metabolomic data were analyzed by ANCOVA.ResultseCPAP infants had greater increases in both FRC (2.1-fold, p = 0.005) and weight (1.13-fold, p = 0.03). Of 1230 total metabolites detected, levels of 87 were higher at p < 0.05 and 75 were lower in eCPAP infants. A new plateau level for key metabolites occurred at 5 ± 2 days after discontinuing CPAP. Sub pathway enrichment (p < 0.05) occurred for bilirubin degradation products...

Neuropathological comorbidities in Frontotemporal Lobar Degeneration: Implications for Diagnosis

Thu, 15 Jan 2026 00:00:00 +0000

AbstractBackground

Frontotemporal lobar degeneration (FTLD) is an umbrella term encompassing neurodegenerative diseases that either feature tau, TDP‐43, or FET inclusions. As FTLD is associated with a younger age of onset, there has been less focus on studying age‐related co‐pathologies. The presence of co‐pathology affects clinical manifestations and has implications for diagnosis as well as management. To investigate the frequency and type of co‐pathologies in the FTLD spectrum, we examined a large postmortem clinicopathological cohort.

Method

We included all FTLD cases at the Neurodegenerative Disease Brain Bank (NDBB) at UCSF collected between 2005 and 2024 (Table 1). All brains underwent standardized neuropathological assessment. We investigated the frequency of the most common age‐related neurodegenerative changes in primary neuropathological diseases including FTLD‐TDP43 type A (n = 43), type B (n = 48), type C (n = 43) and unclassifiable...

HPV vaccine awareness and uptake in rural Indigenous communities in Guatemala: a cross-sectional study.

Sat, 10 Jan 2026 00:00:00 +0000

Objectives

To assess human papillomavirus (HPV) vaccine awareness and uptake among caregivers in rural Indigenous communities in Guatemala and to identify sociodemographic predictors of vaccine unawareness and non-uptake.

Methods

This cross-sectional survey was conducted across 12 rural Indigenous communities in Guatemalas Central Highlands. Using a community-engaged research approach, trained multilingual health workers administered surveys in Spanish, Kaqchikel or Kiche. Eligible participants were adults who served as primary caregivers to children. The survey assessed HPV vaccine awareness, vaccine attitudes and uptake among those with daughters aged 8 or older. Logistic regression was used to examine predictors of vaccine unawareness and bivariate analysis explored differences in vaccine uptake.

Results

Among 602 participants (92.5% identified as Indigenous), 95% expressed willingness to vaccinate a child against cervical cancer, yet only 56% had heard...

Beyond pain presence: the impact of multisite pain and pain interference on cognitive functioning among middle-aged and older adults

Fri, 9 Jan 2026 00:00:00 +0000

OBJECTIVES: This study investigates the relationship between chronic pain and cognitive function in the U.S. middle-aged and older population, focusing on the impact of the number of pain sites. It also explores whether pain interference mediates the association between pain sites and cognition. METHODS: Data were drawn from the 2004-2006 and 2013-2017 waves of the Midlife in the United States Study (MIDUS 2 and MIDUS 3, N = 2,219). We fit inverse-probability-weighted models to examine the associations between pain status, number of pain sites (none vs. 1-2 vs. 3+ sites), and cognitive function in MIDUS 3, controlling for confounders from MIDUS 2. The Sobel-Goodman mediation test with Bonferroni-adjusted significance level was applied to assess the mediating role of pain interference in five domains: activities, mood, relationships, sleep, and enjoyment. RESULTS: Among those with chronic pain, 40% report pain in three or more sites. There was no significant difference in cognitive...

Evaluating segregated school attendance as a mediator of geographic inequities in late‐life cognitive function: evidence from the Study of Healthy Aging in African Americans (STAR)

Thu, 8 Jan 2026 00:00:00 +0000

INTRODUCTION: Birth in the Southern United States is associated with poorer late-life cognitive health, especially among Black Americans, yet the role of school segregation is unclear. METHODS: Utilizing decomposition methods, we estimated the total effect, natural direct effect (NDE), and natural indirect effect (NIE) of Southern birth on domain-specific cognition among 727 older Black adults, adjusting for early-life covariates. We also estimated the proportion of the total effect mediated by self-reported segregated school attendance. RESULTS: Southern birth was associated with lower late-life executive function and semantic memory; estimates were negative but not significant for verbal episodic memory. The direct effect of Southern birth was negative but not significant for all domains. Attending a segregated school mediated 35% and 49% of the total association between Southern birth and executive function (NIE: -0.07, 95% confidence interval [CI]: [-0.18, 0.02]) and...

Alzheimers Imaging Consortium.

Tue, 6 Jan 2026 00:00:00 +0000

Background

Amyloid PET use has been associated with change in clinical management among cognitively impaired older adults but various ethnoracial groups were underrepresented in prior studies. New IDEAS examined whether this association exists among cognitively impaired ethnoracially diverse Medicare beneficiaries and beneficiaries presenting with clinically atypical (non-memory predominant) presentations of Alzheimers disease (AD).

Methods

New IDEAS was a national, multi-site, prospective, longitudinal study that enrolled Medicare beneficiaries with mild cognitive impairment (MCI) or dementia who underwent amyloid PET scan as recommended by their treating dementia specialists at real-world clinics. The study examined association between amyloid PET and subsequent change in clinical management within 90 days of PET. Primary endpoint was change in management between pre- and post-PET visits defined as a composite inclusive of change in AD and non-AD drugs and change...

Alzheimers Imaging Consortium.

Tue, 6 Jan 2026 00:00:00 +0000

Background

Socioeconomic vulnerabilities and healthcare environment contribute to disparities in dementia assessment. Whether these affect dementia management, however, remains unclear. We used Imaging Dementia - Evidence for Amyloid Scanning (IDEAS) study data to compare the impact of amyloid PET on pharmacological management across social factors, patient comorbidities, and physician practice settings.

Methods

We analyzed rates of pharmacological change in IDEAS participants with visually interpretable amyloid PET, completed pre- and post-PET case reports, social determinants (racioethnic identity of Asian, Black, Hispanic, or White, area deprivation index (ADI), living arrangement, education) and medical history. Outcomes included any change between pre-PET and post-PET visits in prescription of Alzheimers disease (AD) drugs, and of non-AD drugs treating dementia risk factors or affecting cognition/mood/behavior. We used multilevel logistic regression with a...

Hotspot exons are common targets of splicing perturbations

Mon, 22 Dec 2025 00:00:00 +0000

High-throughput splicing assays have demonstrated that many exonic variants can disrupt splicing; however, splice-disrupting variants distribute non-uniformly across genes. We propose the existence of exons that are particularly susceptible to splice-disrupting variants, which we refer to as hotspot exons. Hotspot exons are also more susceptible to splicing perturbation through drug treatment and knock-down of RNA-binding proteins. We develop a classifier for exonic splice-disrupting variants and use it to infer hotspot exons. We estimate that 1400 exons in the human genome are hotspots. Using panels of splicing reporters, we demonstrate how the ability of an exon to tolerate a mutation is inversely proportional to the strength of its neighboring splice sites.

Decreased limb muscle and increased central adiposity are associated with 5-year all-cause mortality in HIV infection

Fri, 5 Dec 2025 00:00:00 +0000

BACKGROUND: Unintentional loss of weight and muscle due to aging and disease has been associated with increased mortality. Wasting and weight loss occur in HIV infection even in the modern era of effective antiretroviral therapy. METHODS: We determined the association of MRI-measured regional and total skeletal muscle and adipose tissue with 5-year, all-cause mortality in 922 HIV-infected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). RESULTS: After 5 years of follow-up, HIV-infected participants with arm skeletal muscle in the lowest tertile had a mortality rate of 23%, compared with 11 and 8% for those in the middle and highest tertiles. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, inflammatory markers, and renal disease, we found that lower arm skeletal muscle, lower leg skeletal muscle and higher visceral adipose tissue (VAT) were each independently associated with increased mortality....

Regional Adipose Tissue and Lipid and Lipoprotein Levels in HIV-Infected Women

Fri, 5 Dec 2025 00:00:00 +0000

BACKGROUND: HIV infection and antiretroviral therapy are associated with dyslipidemia, but the association between regional body fat and lipid levels is not well described. METHODS: Multivariable linear regression analyzed the association between magnetic resonance imaging-measured regional adipose tissue and fasting lipids in 284 HIV-infected and 129 control women. RESULTS: Among African Americans, HIV-infected women had higher triglyceride (116 vs. 83 mg/dL; P < 0.001), similar high-density lipoprotein (HDL; 52 vs. 50 mg/dL; P = 0.60), and lower low-density lipoprotein (LDL; 99 vs. 118 mg/dL; P = 0.008) levels than controls. Among whites, HIV-infected women had higher triglyceride (141 vs. 78 mg/dL; P < 0.001), lower HDL (46 vs. 57 mg/dL; P < 0.001), and slightly lower LDL (100 vs. 107 mg/dL; P = 0.059) levels than controls. After adjustment for demographic and lifestyle factors, the highest tertile of visceral adipose tissue (VAT) was associated with higher triglyceride...

Psychometric Validation of Trust, Commitment, and Satisfaction Scales to Measure Marital Relationship Quality Among Newly Married Women in Nepal

Sun, 30 Nov 2025 00:00:00 +0000

Marital relationship quality significantly influences health outcomes, but validated measurement tools for South Asian populations remain limited. To validate scales measuring trust, commitment, and satisfaction as key components of marital relationship quality among newly married women in Nepal, we conducted a two-wave psychometric validation study in rural Nawalparasi district. The study included 200 newly married women aged 18-25 years, with 192 participants (96% retention) completing 6-month follow-up. We assessed factor structure, internal consistency, test-retest reliability, and criterion validity of trust (eight items), commitment (five items), and satisfaction (seven items) scales using exploratory and confirmatory factor analysis. Exploratory factor analysis identified single-factor solutions for trust and commitment scales and a two-factor model for satisfaction. Confirmatory factor analysis confirmed these structures, with satisfaction comprising marital conflict/dissatisfaction...

Data Resource Profile: Global Trachoma Serology Data Repository

Thu, 20 Nov 2025 00:00:00 +0000

Data Resource Profile: Global Trachoma Serology Data Repository

Pharmacist care for attention-deficit/hyperactivity disorder electronic medication refills: A cluster randomized trial.

Thu, 20 Nov 2025 00:00:00 +0000

BACKGROUND: During the pandemic, the US government loosened restrictions on telemedicine prescribing for controlled substance refills. Parent requests for attention-deficit/hyperactivity disorder (ADHD) medication refills have increased electronic inbox workload for physicians. Pharmacists can now fulfill these requests via collaborative practice agreements, but scant information exists on the effectiveness of this approach. OBJECTIVE: To compare pharmacist with pediatrician management of ADHD medication refill requests regarding quality, timeliness, and parent ratings. METHODS: This cluster randomized clinical trial assigned electronic ADHD medication refill requests from 63 medical facilities in a regional health care system to either Pharmacist Care by a regional team (32 facilities) or local Pediatrician Care (31 facilities) from May 14, 2024, to June 21, 2024. The primary outcome was prespecified in the study protocol as a quality measure to be evaluated among patients without...

Social Media Recruitment in Indigenous and Native American Populations: Challenges in the AI Age

Mon, 17 Nov 2025 00:00:00 +0000

Unlabelled: Using social media recruitment for public health research presents both opportunities and challenges. Despite its increased use, few studies have detailed the practical issues, challenges encountered, and alternative strategies available for social media recruitment. This paper explores strategies for recruiting Indigenous and Native American populations in California for a study on COVID-19 vaccination and social networks. We describe different recruitment approaches, challenges faced, and pros and cons of strategies used to enhance data quality and efficiency, including survey design considerations, Facebook targeting versus use of research panels, quality assurance checks, and decisions around participant incentives. Our local setting involved recruiting Native American and Mesoamerican Indigenous individuals living in California through social media platforms. We highlight key adaptations to survey design, recruitment strategies, and data cleaning processes, noting...

Intergenerational upward educational mobility and cognitive performance: results from the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA)

Fri, 7 Nov 2025 00:00:00 +0000

INTRODUCTION: Upward educational attainment is associated with better cognitive function; differences by Hispanic/Latino heritage are unclear. METHODS: We analyzed data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and its ancillary study SOL-Investigation of Neurocognitive Aging (SOL-INCA; n = 3300) to compare cognitive function and 7-year cognitive change between first-generation and multigenerational high school (HS) graduates (i.e., neither parent vs 1+ parent graduated HS) using survey-linear regression models, and assessing for heterogeneity by heritage and nativity. RESULTS: First-generation Cuban, Mexican, and Puerto Rican HS graduates had significantly lower baseline cognitive scores than multigenerational graduates, while Dominican, Central, and South American graduates had similar cognitive scores. We found some evidence of heterogeneity by nativity. Cognitive change was similar across groups. DISCUSSION: More studies of Latinos across...

The I-ACTED study (investigating action civics training through an experimental design): a cluster randomized controlled trial of a school-based action civics education intervention on adolescent wellbeing

Thu, 6 Nov 2025 00:00:00 +0000

BackgroundObservational studies have found that youth civic engagement is associated with positive mental health, education, and socioeconomic outcomes. However, access to civic opportunities is not evenly distributed. Many classrooms in the United States of America (USA) do not have access to high-quality civics education. Action civics approaches to civic education prepare students for civic engagement by developing the necessary civic skills, knowledge, and character. Through action civics, classes take action on a real-world issue students choose together. Some evidence suggests that action civics may positively affect participants’ wellbeing through the feelings of civic connection and empowerment. The aim of this study is to investigate, through a randomized controlled trial, the impact of a school-based action civics education intervention on civic and wellbeing outcomes, and the mechanisms of any impact observed, among middle and high school students in the USA.MethodsThis...

The Complex Relationship of Genetic Ancestry With Self‐Reported Race/Ethnicity

Wed, 29 Oct 2025 00:00:00 +0000

Race and ethnicity are demographic constructs used to characterize individuals in biomedical research, and in particular to assess health disparities. Their use in medicine and research has been discussed and challenged, as well as the degree to which they represent strictly social constructs, or ones also with biological meaning. The relationship of race and ethnicity with genetic ancestry has also been described, and how genetic ancestry reflects historical continental isolation, migration, and mating structure. Race and ethnicity are currently most often assessed by self-report in epidemiology and biomedical applications. Here we further interrogate the relationship between how people self-report their race and ethnicity and their genetic ancestry by examining self-report patterns of 97,671 individuals who are participants in the Kaiser Permanente Northern California Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Genetic ancestry was determined from...

The Earth BioGenome Project 2020: Starting the clock

Mon, 20 Oct 2025 00:00:00 +0000

Description

Strategies Facilitating Video Visit Implementation by a Medical Group Serving a Diverse Population.

Sun, 12 Oct 2025 00:00:00 +0000

IntroductionVideo visits have created new opportunities to enhance access to care, but limited information exists on strategies medical groups can employ to facilitate video visit use by higher-risk patients. Our objective was to identify generalizable strategies to facilitate successful delivery of video visits by systems serving highly diverse patient populations. MethodsThe authors conducted a qualitative study of physicians and staff members in a large group practice with 4.5 million patients with diverse race and ethnicity and socioeconomic status. Semi-structured interviews were conducted between January 2021 and April 2021, with key informants identified via purposive and snowball sampling. Video-recorded interviews were transcribed and analyzed using thematic analysis to identify major themes and subthemes. ResultsThe 42 key informants included regional and medical center leaders, primary care physicians, service managers, and medical assistants. Participants described...

Pharmacist vs physician management of e-visit requests for COVID-19 medication: A randomized clinical trial.

Sun, 12 Oct 2025 00:00:00 +0000

BACKGROUND: Electronic visits (e-visits), defined as structured asynchronous electronic messages between patients and clinicians requiring clinical decision-making, are being increasingly used to enhance access to outpatient health care services, but the primary care physicians who typically manage them face work overflow. Pharmacists have been proposed to manage e-visits that lead to prescription requests, but scant evidence exists about the effectiveness of this approach. OBJECTIVE: To compare pharmacist management of structured asynchronous e-visit requests for COVID-19 medication with physician management regarding quality of care, timeliness, and patient care experience. METHODS: This cluster-randomized clinical trial included adults from 17 medical facilities of Kaiser Permanente Northern California who made e-visits requesting COVID-19 medication (nirmatrelvir-ritonavir) from October 9 to December 11, 2023. In the Pharmacist Care group, a regional team of pharmacists managed...

The Integration of Clinical Trials With the Practice of Medicine

Sun, 12 Oct 2025 00:00:00 +0000

Importance: Optimal health care delivery, both now and in the future, requires a continuous loop of knowledge generation, dissemination, and uptake on how best to provide care, not just determining what interventions work but also how best to ensure they are provided to those who need them. The randomized clinical trial (RCT) is the most rigorous instrument to determine what works in health care. However, major issues with both the clinical trials enterprise and the lack of integration of clinical trials with health care delivery compromise medicine's ability to best serve society. Observations: In most resource-rich countries, the clinical trials and health care delivery enterprises function as separate entities, with siloed goals, infrastructure, and incentives. Consequently, RCTs are often poorly relevant and responsive to the needs of patients and those responsible for care delivery. At the same time, health care delivery systems are often disengaged from clinical trials and...

A cross‐sectional study comparing men who have sex with men and inject drugs and people who inject drugs who are men and have sex with men in San Francisco: Implications for HIV and hepatitis C virus prevention

Sun, 12 Oct 2025 00:00:00 +0000

A cross‐sectional study comparing men who have sex with men and inject drugs and people who inject drugs who are men and have sex with men in San Francisco: Implications for HIV and hepatitis C virus prevention

Associations between widowhood status/duration, depression, and cognitive function among community-dwelling Indians age 60 years or older: Exploration of sex and residential factors

Fri, 10 Oct 2025 00:00:00 +0000

BackgroundThe death of a spouse is considered one of the most life challenging stressors. Widowhood has a profound influence on health and may increase the risk of depression and poorer cognitive function. Discriminatory practices in India, such as taboos against remarrying, a lack of occupational opportunities, and social support, may lead to differential widowhood experiences, especially among women. This study examined the associations between widowhood status/duration, depression and cognitive function among community-dwelling men and women in India. Considering the unique cultural and societal context in India, this study also sought to examine differences by sex, rural/urban residence, and multigenerational living status.MethodsWe used baseline data from the Longitudinal Aging Study in India. Data were collected between 2017 and 2019. The study sample consisted of 14,691 men and 15,948 women age ≥ 60 years. Depression was measured using the Short Form Composite International...

Phenotypic pleiotropy of missense variants in human B cell confinement receptor P2RY8

Thu, 9 Oct 2025 00:00:00 +0000

Missense variants can have pleiotropic effects on protein function, and predicting these effects can be difficult. We performed near-saturation deep mutational scanning of P2RY8, a G protein-coupled receptor that promotes germinal center B cell confinement. We assayed the effect of each variant on surface expression, migration, and proliferation. We delineated variants that affected both expression and function, affected function independently of expression, and discrepantly affected migration and proliferation. We also used cryo-electron microscopy to determine the structure of activated, ligand-bound P2RY8, providing structural insights into the effects of variants on ligand binding and signal transmission. We applied the deep mutational scanning results to both improve computational variant effect predictions and to characterize the phenotype of germline variants and lymphoma-associated variants. Together, our results demonstrate the power of integrating deep mutational scanning,...

Identifying the vulnerable among the vulnerable: applying quantitative intersectionality methods to assess potential inequities in the HIV continuum of care for people living with schizophrenia in the united States

Wed, 1 Oct 2025 00:00:00 +0000

BackgroundPeople living with schizophrenia face disproportionate risk of HIV, yet HIV testing remains low. Differential testing rates and engagement in care may be impacted by compounding social marginalization, partly linked to structural barriers. Grounded in intersectionality, we set out to identify the riskiest intersectional positions for HIV testing and engagement in HIV care in the United States.MethodsWe created a retrospective cohort of people living with schizophrenia and matched controls, using 2012 national Medicaid claims data. We coded intersectional positions based on schizophrenia diagnosis, race/ethnicity, sex, and age. We used Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) models to assess intersectional effects for two outcomes, HIV testing and retention in HIV care (RIC) defined as ≥2 CD4 or HIV viral load tests ≥90 days apart.ResultsOf 777,887 patients in the testing cohort, 7.7% tested for HIV; 39% of the 17,913 patients...

Falls Among Individuals With Systemic Lupus Erythematosus: An Observational Study

Fri, 12 Sep 2025 00:00:00 +0000

OBJECTIVE: Systemic lupus erythematosus (SLE) is thought to accelerate the aging process. However, there is limited research on geriatric syndromes, such as falls, in this potentially vulnerable population. This study aimed to describe the prevalence of and contributors to falls in the SLE population. METHODS: Participants were recruited from an ongoing population-based cohort of individuals with validated SLE. Falls (number of falls and fall-related injuries requiring medical attention over the past year) and perceived contributing factors were self-reported. Descriptive statistics were calculated, and age-, sex-, and race-adjusted odds ratios (aORs) of participant characteristics with falls were estimated using multivariable logistic regression. RESULTS: Nearly one-third (30.7%) of participants (overall N = 447; 40.9% aged ≥50 years, 91.7% female, and 82.6% Black) reported falling in the past year; 19.2% fell twice or more. Loss of balance (78.1% of falls), slipping/tripping...

Racial/ethnic and socioeconomic disparities in survival among children with acute lymphoblastic leukemia in California, 1988–2011: A population‐based observational study

Fri, 12 Sep 2025 00:00:00 +0000

BACKGROUND: Despite advances in treatment, survival from acute lymphoblastic leukemia (ALL) remains lower among non-White children than White children in the US. We investigated the association of race/ethnicity and socioeconomic status (SES) with survival. PROCEDURES: We analyzed 9,295 Californian children (3,251 Whites, 4,890 Hispanics, 796 Asians, and 358 Blacks) aged ≤ 19 years diagnosed with a first primary ALL during 1988-2011. We used the Kaplan-Meier method to estimate survival at 1, 5, and 10 years after diagnosis for three calendar periods. Hazard ratios of death for race/ethnicity, SES, and clinical factors were estimated by Cox regression models. RESULTS: Median follow-up time was 7.4 years (range 0-25 years). Over time, survival after ALL improved steadily, but inequalities persisted across races/ethnicities. Five-year survival (95% confidence interval) was 85.0% (83.6-86.2) for White, 81.4% (78.3-84.0) for Asian, 79.0% (77.8-80.2) for Hispanic, and 74.4% (69.4-78.8)...

Efficiency of Evidence Accumulation as a Formal Model-Based Measure of Task-General Executive Functioning in Adolescents

Thu, 11 Sep 2025 00:00:00 +0000

Difficulties with executive functioning are implicated in various forms of psychopathology. However, executive functioning task performance frequently demonstrates poor test-retest reliability, questionable convergent validity, and unstable associations with clinical measures. Model-based approaches may improve measurement by providing richer information about mechanisms underlying performance. The present study systematically compared a model-based measure of task-general executive functioning, efficiency of evidence accumulation (EEA), with traditional summary metrics extracted from the same tasks in a longitudinal study of adolescents (N = 637, age = 7-19). EEA demonstrated reasonable stability across development and strong cross-task reliability. Reflecting traditional metrics, EEA related to self-reported effortful control and parent-reported attention, externalizing and total problems. EEA and one traditional metric (go/no-go standard deviation of reaction time) correlated...

Safety and efficacy of a STAT3-targeted cyclic oligonucleotide: From murine models to a phase 1 clinical trial in pet cats with oral cancer

Wed, 10 Sep 2025 00:00:00 +0000

STAT3 is an oncogenic transcription factor that activates cancer cell signaling and induces an immunosuppressive immune environment, making it an attractive therapeutic target. Transcription factors are exceptionally challenging targets and there are no Food and Drug Administration-approved STAT3 inhibitors. We previously reported positive pharmacodynamics of a linear STAT3 decoy oligonucleotide administered intratumorally in a phase 0 trial in patients with head and neck cancer squamous cell carcinoma (HNSCC). Here, we describe the anti-tumor and immune effects of a systemically administered cyclic STAT3 decoy (CS3D) in immunocompetent HNSCC murine models and the safety and efficacy of CS3D in a clinical trial in pet cats with HNSCC. Responders in the clinical trial (35% disease control rate) showed significant differences in selected peripheral blood immune parameters as well as elevated PD-1 expression in the tumors compared with non-responders. These findings support a clinical...

Modeling the importance of life exposure factors on memory performance in diverse older adults: A machine learning approach

Sat, 23 Aug 2025 00:00:00 +0000

INTRODUCTION: Many health life exposure factors (LEFs) influence cognitive decline and dementia incidence, but their relative importance to episodic memory (an early indicator of cognitive decline) among diverse older adults is unclear. We used machine learning to rank LEFs for memory performance in a large and diverse US cohort. METHODS: Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR), participants underwent neuropsychological testing and answered questionnaires about multiple LEFs. XGBoost and Shapley Additive exPlanation values ranked the importance of factors influencing cross-sectional episodic memory in the full sample and by sex and ethnic group. RESULTS: Among 2245 adults (mean age: 74 years; range 54-90), age, sex, education, volunteering, income, vision, hearing, sleep, and exercise contributed to memory performance regardless of group stratification. DISCUSSION: This innovative methodology can help identify...

Perceptions of pharmacist-furnished nicotine replacement therapy among participants who smoke in California

Tue, 19 Aug 2025 00:00:00 +0000

BACKGROUND AND OBJECTIVE: California's Central Valley has high rates of tobacco product use and low rates of access to primary care providers. In 2016, California sought to increase access to cessation treatment by allowing pharmacists to prescribe nicotine replacement therapy (NRT). We sought to identify the extent to which this prescribing authority has been integrated into practice. METHODS: From December 2023 to May 2024, we surveyed adult California participants (n = 271) who smoke about their smoking patterns, perceptions towards NRT, experiences with receiving tobacco cessation resources in pharmacies. Participants were recruited via email and in person. We analyzed participants' smoking and quitting history, perceptions of NRT, and experiences with tobacco cessation, comparing residents of California's Central Valley (n = 52) to other regions of the state (n = 219). RESULTS: Smoking rates were comparable for respondents in the Central Valley and those residing in other...

Improved detection of microbiome-disease associations via population structure-aware generalized linear mixed effects models (microSLAM)

Thu, 14 Aug 2025 00:00:00 +0000

Microbiome association studies typically link host disease or other traits to summary statistics measured in metagenomics data, such as diversity or taxonomic composition. But identifying disease-associated species based on their relative abundance does not provide insight into why these microbes act as disease markers, and it overlooks cases where disease risk is related to specific strains with unique biological functions. To bridge this knowledge gap, we developed microSLAM, a mixed-effects model and an R package that performs association tests that connect host traits to the presence/absence of genes within each microbiome species, while accounting for strain genetic relatedness across hosts. Traits can be quantitative or binary (such as case/control). MicroSLAM is fit in three steps for each species. The first step estimates population structure across hosts. Step two calculates the association between population structure and the trait, enabling detection of species for...

Improved prediction and flagging of extreme random effects for non-Gaussian outcomes using weighted methods

Mon, 4 Aug 2025 00:00:00 +0000

Investigators often focus on predicting extreme random effects from mixed effects models fitted to longitudinal or clustered data, and on identifying or "flagging" outliers such as poorly performing hospitals or rapidly deteriorating patients. Our recent work with Gaussian outcomes showed that weighted prediction methods can substantially reduce mean square error of prediction for extremes and substantially increase correct flagging rates compared to previous methods, while controlling the incorrect flagging rates. This paper extends the weighted prediction methods to non-Gaussian outcomes such as binary and count data. Closed-form expressions for predicted random effects and probabilities of correct and incorrect flagging are not available for the usual non-Gaussian outcomes, and the computational challenges are substantial. Therefore, our results include the development of theory to support algorithms that tune predictors that we call "self-calibrated" (which control the incorrect...

Characterisation of between-cluster heterogeneity in malaria cluster randomised trials to inform future sample size calculations

Sun, 3 Aug 2025 00:00:00 +0000

Cluster randomised trials (CRTs) are important tools for evaluating the community-wide effect of malaria interventions. During the design stage, CRT sample sizes need to be inflated to account for the cluster heterogeneity in measured outcomes. The coefficient of variation (k), a measure of such heterogeneity, is typically used in malaria CRTs yet is often predicted without prior data. Underestimation of k decreases study power, thus increases the probability of generating null results. In this meta-analysis of cluster-summary data from 24 malaria CRTs, we calculate true prevalence and incidence k values using methods-of-moments and regression modelling approaches. Using random effects regression modelling, we investigate the impact of empirical k values on original trial power and explore factors associated with elevated k. Results show empirical estimates of k often exceed those used in sample size calculations, which reduces study power and effect size precision. Elevated...

Cluster randomised controlled trial of a household-level, group preconception nutrition awareness and norm intervention (SUMADHUR) combined with multiple micronutrient supplements (MMS) for newly married households: a protocol

Sat, 2 Aug 2025 00:00:00 +0000

INTRODUCTION: Micronutrient deficiencies remain prominent drivers of adverse maternal and child health outcomes in Nepal. Gender-based inequalities and norms around women's status and access to nutrition exacerbate poor nutritional status. Many newly married, preconception women lack adequate nutrition due to delayed engagement with the health system and limited autonomy to prioritise their own health. To address this gap, the Sumadhur trial provides multiple micronutrient supplements (MMS) alongside a household-level behavioural intervention targeting newly married women, their husbands and mothers-in-law. METHODS AND ANALYSIS: This will be a village-cluster randomised controlled trial across three districts in Nepal, enrolling 700 households, each comprising a triad of newly married woman, husband and mother-in-law. Villages will be randomised to receive either Sumadhur behavioural intervention+MMS (intervention) or standard of care (control). In intervention villages, participants...

Development of a machine learning algorithm to predict the residual cognitive reserve index

Wed, 30 Jul 2025 00:00:00 +0000

Elucidating the mechanisms by which late-life neurodegeneration causes cognitive decline requires understanding why some individuals are more resilient than others to the effects of brain change on cognition (cognitive reserve). Currently, there is no way of measuring cognitive reserve that is valid (e.g. capable of moderating brain-cognition associations), widely accessible (e.g. does not require neuroimaging and large sample sizes), and able to provide insight into resilience-promoting mechanisms. To address these limitations, this study sought to determine whether a machine learning approach to combining standard clinical variables could (i) predict a residual-based cognitive reserve criterion standard and (ii) prospectively moderate brain-cognition associations. In a training sample combining data from the University of California (UC) Davis and the Alzheimer's Disease Neuroimaging Initiative-2 (ADNI-2) cohort (N = 1665), we operationalized cognitive reserve using an...

Overheated and Understudied: A Scoping Review of Heat‐Related Health Impacts in the Arabian Peninsula

Wed, 16 Jul 2025 00:00:00 +0000

Extreme heat is worsening due to climate change, and, in combination with increasing urban growth, is an escalating public health concern. In the Arabian Peninsula, the wet-bulb temperature is projected to surpass theoretical human tolerance limits during the 21st century. Yet, heat research in the region has generally not focused on health impacts, and it is unclear how epidemiologic literature has investigated this. We performed a scoping review to examine the existing literature that assessed the relationship between extreme heat and health outcomes in the Arabian Peninsula, collecting papers published from 2010 to 2024 from three databases. We identified and extracted detailed information from a limited number of studies (n = 12). The greatest number of studies were conducted in Kuwait (n = 8), with others in Saudi Arabia (n = 4), and Qatar, Oman, Yemen, and the United Arab Emirates (n = 1 each). Average temperature...

Development of chronic pain and high‐impact chronic pain across the US rural–urban continuum, 2019–2020

Mon, 7 Jul 2025 00:00:00 +0000

PURPOSE: Rural health disadvantages are well documented in previous literature; however, research on rural-urban disparities in chronic pain outcomes is scarce. This paper fills this gap by examining pain prevalences and longitudinal transitions across the rural-urban continuum (i.e., large central metro, large fringe metro, medium and small metro, and nonmetropolitan). METHODS: Based on the 2019-2020 National Health Interview Survey Longitudinal Cohort (NHIS-LC) data, we examined the disparities in pain prevalences and transitions among different pain statuses, including no pain, nonchronic pain, chronic pain, and high-impact chronic pain (HICP), across the rural-urban continuum and by age, sex, race/ethnicity, and region. A test for linear trend was conducted to examine the significance of linear changes across the rural-urban continuum. FINDINGS: The findings reveal significant linear increases in the prevalence of chronic pain and HICP, as well as transitions from no pain...

Adult child educational attainment and older parents’ psychosocial outcomes during the COVID-19 pandemic

Mon, 7 Jul 2025 00:00:00 +0000

BackgroundOlder adults’ psychosocial outcomes during the COVID-19 pandemic have been inequitable by socio-economic status (SES). However, studies have focused solely on own SES, ignoring emerging evidence of the relationship between adult child SES and late-life health. We evaluated whether adult child educational attainment – a core marker of SES – is associated with older parents’ psychosocial outcomes during the pandemic.MethodsWe used data from the Survey of Health, Aging, and Retirement in Europe (SHARE) 2004–2018 and the SHARE Corona Surveys (SCS) 2020 and 2021. We included 40,392 respondents ≥ 65 years who had pre-pandemic information on adult child educational attainment and self-reported psychosocial outcomes during the pandemic, including self-assessments of worsened psychosocial outcomes compared to the pre-pandemic period. We used generalized estimating equations with a Poisson distribution and a log link, adjusted for respondent and family-level characteristics,...

Neonatal Seizures and Associated Neurobehavioral Profiles in Preschool Age Children

Fri, 27 Jun 2025 00:00:00 +0000

BACKGROUND: Neonatal seizures are common with acute brain injury. Up to 25% of survivors develop postneonatal epilepsy. We hypothesized postneonatal epilepsy diagnosed by age 24 months would increase risk for early markers of neurobehavioral disorders than acute provoked neonatal seizures alone. METHODS: Neonates with acute provoked seizures born from July 2015 to March 2018 were enrolled at nine Neonatal Seizure Registry sites. Composite scores from parent-completed standardized ratings assessed Adaptive, Social, Externalizing, Internalizing, Self-Regulation, and Sensory Seeking domains. Linear regression demonstrated relationships between composite scores for children who developed postneonatal epilepsy compared with those who did not. Results were adjusted for seizure etiology, sex, gestational age, and cerebral palsy (CP) severity. RESULTS: A total of 151 children (n = 20, 13% with postneonatal epilepsy), 4.1 years median age, participated. Children with epilepsy...

Preferred Parental Language and Neurodevelopmental Outcomes Among Infants With Acute Provoked Neonatal Seizures in the United States

Fri, 27 Jun 2025 00:00:00 +0000

BACKGROUND: Parental non-English language preference (NELP) is associated with worse pediatric health outcomes. However, little is known about its relationship with developmental outcomes in infants with neonatal seizures. This study evaluated the relationship between parental NELP and neurodevelopment in a multicenter cohort of infants with neonatal seizures. METHODS: Infants in the Neonatal Seizure Registry-II were included. Parental NELP was defined by the use of a professional interpreter for research consent and survey completion. The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) assessment was conducted at age 24 months. Multivariate regression was used to examine the association between parental NELP and WIDEA-FS. Functional developmental impairment was defined as a WIDEA-FS score 2 S.D.s below the normative mean. RESULTS: Among 270 infants with neonatal seizures, 15 (6%) had parental NELP. Children with parental NELP had a WIDEA-FS...

Effect of mass drug administration on malaria incidence in southeast Senegal during 2020–22: a two-arm, open-label, cluster-randomised controlled trial

Sat, 21 Jun 2025 00:00:00 +0000

BACKGROUND: In Africa, the scale-up of malaria-control interventions has reduced malaria burden, but progress towards elimination has stalled. Mass drug administration (MDA) is promising as a transmission-reducing strategy, but evidence from low-to-moderate transmission settings is needed. We aimed to assess the safety, coverage, and effect of three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine on Plasmodium falciparum incidence and prevalence in southeast Senegal. METHODS: We conducted a two-arm, open-label, cluster-randomised controlled trial in villages in the Tambacounda health district of southeast Senegal. Eligible villages had a population size of 200-800, were within a health-post catchment area with an annual malaria incidence of 60-160 cases per 1000 people, and had an established or planned Prise en Charge à Domicile Plus model. We randomly assigned villages (1:1) using a stratified, constrained randomisation approach to receive...

Integration of MRI radiomics and germline genetics to predict the IDH mutation status of gliomas

Fri, 20 Jun 2025 00:00:00 +0000

The molecular profiling of gliomas for isocitrate dehydrogenase (IDH) mutations currently relies on resected tumor samples, highlighting the need for non-invasive, preoperative biomarkers. We investigated the integration of glioma polygenic risk scores (PRS) and radiographic features for prediction of IDH mutation status. We used 256 radiomic features, a glioma PRS and demographic information in 158 glioma cases within elastic net and neural network models. The integration of glioma PRS with radiomics increased the area under the receiver operating characteristic curve (AUC) for distinguishing IDH-wildtype vs. IDH-mutant glioma from 0.83 to 0.88 (PΔAUC = 6.9 × 10−5) in the elastic net model and from 0.91 to 0.92 (PΔAUC = 0.32) in the neural network model. Incorporating age at diagnosis and sex further improved the classifiers (elastic net: AUC = 0.93, neural network: AUC = 0.93). Patients predicted to have IDH-mutant vs. IDH-wildtype tumors had significantly lower mortality risk...

Adapting and Validating the G‐NORM (Gender Norms Scale) in Nepal: An Examination of How Gender Norms Are Associated with Agency and Reproductive Health Outcomes

Fri, 20 Jun 2025 00:00:00 +0000

Research calls for the sexual and reproductive rights field to prioritize gender norms to ensure that women can act on their reproductive rights. However, there is a gap in accepted measures. We addressed this by including important theoretical components of gender norms: differentiating between descriptive and injunctive norms and adding a referent group. Our team originally developed and validated the G-NORM, a gender norms scale, in India. In this paper, we describe how we subsequently adapted and validated it in Nepal. We administered items to women of reproductive age, conducted exploratory and confirmatory factor analysis, and examined associations between the subscales and reproductive health outcomes. Like the original G-NORM, our factor analyses showed that descriptive norms and injunctive norms comprise two distinct scales which fit the data well and had Cronbach alphas of 0.92 and 0.89. More equitable descriptive gender norms were associated with higher decision-making...

Characterising acute and chronic care needs: insights from the Global Burden of Disease Study 2019

Wed, 18 Jun 2025 00:00:00 +0000

Chronic care manages long-term, progressive conditions, while acute care addresses short-term conditions. Chronic conditions increasingly strain health systems, which are often unprepared for these demands. This study examines the burden of conditions requiring acute versus chronic care, including sequelae. Conditions and sequelae from the Global Burden of Diseases Study 2019 were classified into acute or chronic care categories. Data were analysed by age, sex, and socio-demographic index, presenting total numbers and contributions to burden metrics such as Disability-Adjusted Life Years (DALYs), Years Lived with Disability (YLD), and Years of Life Lost (YLL). Approximately 68% of DALYs were attributed to chronic care, while 27% were due to acute care. Chronic care needs increased with age, representing 86% of YLDs and 71% of YLLs, and accounting for 93% of YLDs from sequelae. These findings highlight that chronic care needs far exceed acute care needs globally, necessitating...

The epidemiologic case for urban health: conceptualizing and measuring the magnitude of challenges and potential benefits

Thu, 22 May 2025 00:00:00 +0000

We discuss how epidemiology has been and can continue to be used to advance understanding of the links between urban areas and health informed by an existing urban-health conceptual framework. This framework considers urban areas as contexts for health, determinants of health and modifiers of health pathways, and part of a complex system that affects health. We highlight opportunities for descriptive epidemiology to inform the context of urban health, for example, by characterizing the social and physical environments that give rise to health and the actions that change those conditions. We then describe inferential tools for evaluating the impact of group-level actions (e.g., interventions, policies) on urban health, providing some examples, and describing assumptions and challenges. Finally, we discuss opportunities and challenges of applying systems thinking and methods to advance urban health. While different conceptual frames lead to different insights, each perspective demonstrates...

Increased vulnerability to psychological distress and suicidal ideation among transgender women with self-reported disabilities in San Francisco, California

Thu, 22 May 2025 00:00:00 +0000

OBJECTIVE: Research among transgender women has found health, but especially mental health, to be shaped by social inequities and multiple, intersectional, structural vulnerabilities. While some studies have shown that transgender adults are also more likely to have a disability than cisgender adults, few studies have explored this intersection. We assess possible associations between disability status and psychological stress and suicidal ideation among transgender women. METHODS: We analyzed data from the San Francisco site of the National HIV Behavioral Surveillance Transgender (NHBS-Trans) Study (2019-2020) to explore how disability status among transgender women influences mental health. Chi-squared and Fisher's exact tests to assess associations between disability status and psychological distress. Multivariable logistic regression models assessed the magnitude of these associations adjusted for potential confounders. RESULTS: 71.14 % of the sample (N = 201)...

Intersectional forces of urban inequality and the global HIV pandemic: a retrospective analysis

Fri, 9 May 2025 00:00:00 +0000

To determine how the intersection of increased urban growth and poverty has impacted HIV incidence and prevalence, given growing HIV inequalities globally. Retrospective analysis using combined data from five publicly available, population-level datasets to determine city- and within-urban countrywide estimates of 95-95-95 treatment targets, prevalence and incidence rates from 2015 to 2019. For city-level estimates, we analysed combined data from: Fast-Track City (FTC), SINAN from Brazil and UNAIDS Naomi-Spectrum. Countrywide estimates of HIV prevalence in the urban slum versus non-slum since 2012 were compiled from Population-Based HIV Impact Assessment (PHIA) surveys in 12 countries and Demographic Health Surveys (DHS) in 28 countries. HIV prevalence is generally higher among the urban slum, compared to their non-slum counterparts, thus resulting in national HIV estimates masking nuances in HIV inequalities between the urban slum and non-slum. Specifically, national and city-level...

Defining and Characterizing Temporary Childbirth Migration in India

Thu, 8 May 2025 00:00:00 +0000

Women returning to their natal homes for pregnancy, delivery, and postpartum is common and understudied in South Asia, with important implications for maternal and newborn health policies, as well as data quality and interpretation. Using data from 1252 women residing in a Health and Demographic Surveillance Site in Maharashtra, India we explore timing, duration and associated socio-economic factors with Temporary Childbirth Migration (TCM). Our overall goal is to develop a definition of temporary childbirth migration and situate it within demographic migration theory. Most (80%) of women migrated for over 1 month in the last trimester of pregnancy, with a sizeable proportion (22%) departing immediately after delivery. Socio-demographic factors were not associated with migrating during pregnancy; migrating postpartum was associated with younger age and higher education. Based on these findings, we propose a definition of Temporary childbirth Migration as a form of migration...

Temporary childbirth migration and perinatal healthcare in rural Maharashtra, India

Sat, 26 Apr 2025 00:00:00 +0000

Introduction: Maternal health in rural India has improved due to national initiatives, but inadequate healthcare provision persists across most sociodemographic groups. The connection between perinatal care and the widespread practice of Temporary Childbirth Migration (TCM)-returning to one's natal home for delivery and the postpartum period-remains unexplored. Methods: Cross-sectional data on migration and health visits were collected from a sample of 1288 women in the Vadu Health and Demographic Surveillance Site (HDSS) (Western Maharashtra) who gave birth in 2018-2022. Childbirth migration (exposure) was analyzed in three ways: binary (any migration), continuous (duration of stay), and multidimensional (duration of stay and change of provider). Outcomes included number of health visits - both facility check-ups and home visits by community health workers - and early antenatal care initiation. Multivariate poisson, negative binomial and logistic regressions were used. Sensitivity...

Sociodemographic modifiers of effects of statin initiation on dementia incidence: An emulated trial design in a large health care member population with 10+ years of follow‐up

Wed, 23 Apr 2025 00:00:00 +0000

INTRODUCTION: Mixed evidence on how statin use affects risk of Alzheimer's disease and related dementias (ADRD) may reflect heterogeneity across sociodemographic factors. Few studies have sufficient power to evaluate effect modifiers. METHODS: Kaiser Permanente Northern California (KPNC) members (n = 705,061; n = 202,937 with sociodemographic surveys) who initiated statins from 2001 to 2010 were matched on age and low-density lipoprotein cholesterol (LDL-C) with non-initiators and followed through 2020 for incident ADRD. Inverse probability-weighted Cox proportional hazards models were used to evaluate effect modification by age, gender, race/ethnicity, education, marital status, income, and immigrant generation. RESULTS: Statin initiation (vs non-initiation) was not associated with ADRD incidence in any of the 32 subgroups (p > .05). Hazard ratios ranged from 0.964 (95% CI: 0.923 to 1.006) among Asian-identified participants to 1.122 (95% CI:...

Methamphetamine use and associated factors among people who inject drugs in Iran 2020

Mon, 21 Apr 2025 00:00:00 +0000

BackgroundMethamphetamine use is a pressing public health concern among people who inject drugs (PWID) worldwide. This study aimed to estimate the prevalence of methamphetamine use and its correlates in a nationwide survey among PWID in Iran in 2020.Methods We recruited 2,684 PWID in 11 major cities from July 2019 to March 2020 using respondent-driven sampling (RDS). Participants were eligible if they were ≥ 18 years old, self-reported drug injection in the last 12 months, resided in the city of the study, and provided a valid RDS coupon. Behavioral data was collected using a standard questionnaire via face-to-face interviews. 2,259 PWID (84.2%) with valid responses to the primary outcome (i.e., methamphetamine use (either injecting or non-injection use) in the last three months) were included in the analysis. We used RDS-Gile's SS weighted analysis for descriptive statistics and a survey package (svy) using linearized variance estimations and stratification by cities for...

Assessment of the person-centered maternity care scale: a global systematic review

Mon, 21 Apr 2025 00:00:00 +0000

Background: Person-centered maternity care (PCMC) refers to respectful, responsive, and compassionate childbirth care. The PCMC scale enables quantitative measurement of PCMC. Despite the widespread use of the PCMC scale, no global synthesis exists. We, therefore, conducted a global systematic review of studies using the PCMC scale to quantitatively assess women's childbirth experiences, evaluate the scale's psychometric properties, and identify predictors of PCMC. Methods: We searched PubMed, Web of Science, and Embase from inception to September 3, 2024. Included studies used the PCMC scale by Afulani et al. to examine the facility-based childbirth experiences of women in any setting, with no time or language restrictions. Three reviewers independently assessed titles, abstracts, and full texts. We assessed study quality using Joanna Briggs Institute critical appraisal tools. We utilized a standardized extraction template to extract full PCMC and sub-scale scores (standardizing...

Misreporting of Product Adherence in the MTN-003/VOICE Trial for HIV Prevention in Africa: Participants’ Explanations for Dishonesty

Thu, 17 Apr 2025 00:00:00 +0000

Consistent over-reporting of product use limits researchers’ ability to accurately measure adherence and estimate product efficacy in HIV prevention trials. While lying is a universal characteristic of the human condition, growing evidence of a stark discrepancy between self-reported product use and biologic or pharmacokinetic evidence demands examination of the reasons research participants frequently misrepresent product use in order to mitigate this challenge in future research. This study (VOICE-D) was an ancillary post-trial study of the vaginal and oral interventions to control the epidemic (VOICE) phase IIb trial (MTN 003). It was conducted in three African countries to elicit candid accounts from former VOICE trial participants about why actual product use was lower than reported. In total 171 participants were enrolled between December 2012 and March 2014 in South Africa (n = 47), Uganda (n = 59) and Zimbabwe (n = 65). Data suggested that...

Pre- and Postnatal Exposures to Residential Pesticides and Survival of Childhood Acute Lymphoblastic Leukemia

Mon, 14 Apr 2025 00:00:00 +0000

Background: Exposure to pesticides has been associated with an increased risk of developing childhood leukemia. However, the impact of pesticides on childhood leukemia survival has not been examined. We investigated the associations between residential pesticide use during key developmental periods and 5-year survival in children treated for acute lymphoblastic leukemia (ALL). Methods: Residential use of insecticides, herbicides, rodenticides, and flea control products from preconception up to 12 months prior to diagnosis and sociodemographic characteristics were collected via parental interview among 837 children diagnosed with ALL between 1995 and 2008 in California, USA. Data on clinical features were abstracted from medical records. Vital status was obtained through linkage to the National Death Index (NDI) up to 2020. Cox proportional hazards regression models were used to estimate hazard ratios (HRs), adjusting for sociodemographic factors and clinical risk...

Impact of BRCA mutations, age, surgical indication, and hormone status on the molecular phenotype of the human Fallopian tube

Mon, 14 Apr 2025 00:00:00 +0000

The human Fallopian tube (FT) is an important organ in the female reproductive system and has been implicated as a site of origin for pelvic serous cancers, including high-grade serous tubo-ovarian carcinoma (HGSC). We have generated comprehensive whole-genome bisulfite sequencing, RNA-seq, and proteomic data of over 100 human FTs, with detailed clinical covariate annotations. Our results challenge existing paradigms that extensive epigenetic, transcriptomic and proteomic alterations exist in the FTs from women carrying heterozygous germline BRCA1/2 pathogenic variants. We find minimal differences between BRCA1/2 carriers and non-carriers prior to loss of heterozygosity. Covariates such as age and surgical indication can confound BRCA1/2-related differences reported in the literature, mainly through their impact on cell composition. We systematically document and highlight the degree of variations across normal human FT, defining five groups capturing major cellular and molecular...

Exposure to autoimmune disorders is associated with increased Alzheimer’s disease risk in a multi-site electronic health record analysis

Mon, 14 Apr 2025 00:00:00 +0000

Autoimmunity has been proposed to increase Alzheimer's disease (AD) risk, but evaluating the clinical connection between autoimmune disorders and AD has been difficult in diverse populations. We investigate risk relationships between 26 autoimmune disorders and AD using retrospective observational case-control and cohort study designs based on electronic health records for >300,000 individuals at the University of California, San Francisco (UCSF) and Stanford University. We discover that autoimmune disorders are associated with increased AD risk (odds ratios [ORs] 1.4-1.7) across study designs, primarily driven by endocrine, gastrointestinal, dermatologic, and musculoskeletal disorders. We also find that autoimmune disorders associate with increased AD risk in both sexes, but the AD sex disparity remains in those with autoimmune disorders: women exhibit higher AD prevalence than men. This study identifies consistent associations between autoimmune disorders and AD across study...

Clinical, Functional, and Hemodynamic Profile of Schistosomiasis-Associated Pulmonary Arterial Hypertension Patients in Brazil: Systematic Review and Meta-Analysis

Sat, 12 Apr 2025 00:00:00 +0000

BACKGROUND: Schistosoma-associated pulmonary arterial hypertension (Sch-PAH), a complication of hepatosplenic schistosomiasis, is still underdiagnosed and undertreated. Sch-PAH is the third-most common cause of pulmonary arterial hypertension (PAH) in Brazil, and it is estimated that there are around 60,000 afflicted individuals. However, there is a lack of data on these patients, especially in endemic areas. Therefore, this study aimed to describe baseline demographic data, hemodynamic severity of disease, and functional impairment of Sch-PAH patients at diagnosis. METHODS: For this systematic review, five databases (Embase, PubMed, SciELO, LILACS, and Cochrane) were searched to identify candidate publications reporting clinical, hemodynamic, and functional data at diagnosis of Sch-PAH patients referred to a PAH reference center in Brazil. Studies were excluded if they enrolled patients under the age of 18, the diagnosis was not confirmed by right heart catheterization (RHC),...

Acute Declines in Estimated Glomerular Filtration Rate in Patients Treated With Benazepril and Hydrochlorothiazide Versus Amlodipine and Risk of Cardiovascular Outcomes

Sat, 12 Apr 2025 00:00:00 +0000

BACKGROUND: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear. METHODS AND RESULTS: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age...

The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults

Sat, 12 Apr 2025 00:00:00 +0000

OBJECTIVE: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution. METHODS: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores. RESULTS: Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b...

Prevalence and correlates of restricted community mobility in a population-based cohort of adults with systemic lupus erythematosus

Sat, 12 Apr 2025 00:00:00 +0000

OBJECTIVE: Restrictions in community mobility, defined as the frequency of and help required to travel to 'life-spaces' (bedroom, home, yard, neighbourhood and town), are associated with poor outcomes among older adults. We aimed to describe and explore factors associated with community mobility among adults with SLE. METHODS: We assessed community mobility cross-sectionally in a population-based SLE cohort (October 2019 to May 2022), using the University of Alabama Birmingham Study of Aging Life-Space Assessment (UAB LSA) (score range, 0-120; higher scores=greater community mobility). Community mobility was considered to be restricted if the individual reported not reaching the neighbourhood life-space or beyond at least weekly and without help. Estimated percentages (95% CIs) with restricted community mobility were assessed with multivariable logistic regression adjusting for demographics and disease activity and damage. RESULTS: Among 447 participants (91.7% women; 82.6% Black;...

Correlates of duration between initial drug use and first drug injection among people who inject drugs in Iran, 2020

Sat, 12 Apr 2025 00:00:00 +0000

BackgroundPeople who use non-injection drug use are at risk of transitioning to injecting drugs, which increases their vulnerability to HIV and other blood-borne infections. This study aimed to investigate the correlates of the duration between the first drug use and the first drug injection among people who inject drugs (PWID) in Iran, as well as the reasons for injection initiation.MethodsWe analyzed data from the fourth national bio-behavioral surveillance survey among PWID in Iran, conducted in 2020 across 11 cities using respondent-driven sampling (n = 2,684). A generalized linear mixed model with a gamma-distributed dependent variable and log link function was used to investigate the correlates of transition time from non-injection to injection drug use.ResultsAmong 2,356 participants included in the analysis, the mean ± SD of the duration between the first drug use and the first drug injection was 9.37 ± 6.8 years. Factors associated with earlier injection initiation included:...

Subtypes A1 and D, and recombinant HIV-1 natural polymorphisms associated with lenacapavir drug resistance in Uganda

Fri, 11 Apr 2025 00:00:00 +0000

BACKGROUND: Lenacapavir, a novel HIV-1 capsid inhibitor, shows promise for treating MDR HIV-1, as well as for pre-exposure prophylaxis (PrEP) in prevention of HIV infection. Its unique mechanism and lack of cross-resistance with other antiretroviral classes make lenacapavir a significant addition to HIV therapy. The clinical trials CALIBRATE and CAPELLA have demonstrated high viral suppression rates in both ART-naive individuals and individuals with MDR HIV-1. Lenacapavir-associated resistance mutations, such as M66I and Q67H, rarely seen as natural polymorphisms in lenacapavir-naive populations, are predominantly studied in subtype B HIV-1. OBJECTIVES: Our study aimed to investigate the prevalence of lenacapavir resistance-associated mutations in HIV-1 subtypes A1 and D in a cohort of individuals living with HIV-1 from southwestern Uganda. METHODS: Utilizing plasma samples from ART-naive adults living in Uganda, HIV-1 Gag p24 (capsid) sequences were analysed for lenacapavir resistance...

A large genome-wide association study of QT interval length utilizing electronic health records.

Fri, 11 Apr 2025 00:00:00 +0000

QT interval length is an important risk factor for adverse cardiovascular outcomes; however, the genetic architecture of QT interval remains incompletely understood. We conducted a genome-wide association study of 76,995 ancestrally diverse Kaiser Permanente Northern California members enrolled in the Genetic Epidemiology Research on Adult Health and Aging cohort using 448,517 longitudinal QT interval measurements, uncovering 9 novel variants, most replicating in 40,537 individuals in the UK Biobank and Population Architecture using Genomics and Epidemiology studies. A meta-analysis of all 3 cohorts (n = 117,532) uncovered an additional 19 novel variants. Conditional analysis identified 15 additional variants, 3 of which were novel. Little, if any, difference was seen when adjusting for putative QT interval lengthening medications genome-wide. Using multiple measurements in Genetic Epidemiology Research on Adult Health and Aging increased variance explained by 163%, and we show...

Disturbed sleep after lung transplantation is associated with worse patient-reported outcomes and chronic lung allograft dysfunction

Fri, 11 Apr 2025 00:00:00 +0000

Background: Many lung transplant recipients fail to derive the expected improvements in health-related quality of life (HRQL) and survival. Sleep may represent an important, albeit rarely examined, factor associated with lung transplant outcomes. Methods: Within a larger cohort study, 141 lung transplant recipients completed the Medical Outcomes Study Sleep Problems Index (SPI) Revised scale along with a broader survey of patient-reported outcome (PRO) measures and frailty assessment. From the SPI, we also derived an insomnia-specific subscale. Potential perioperative risk factors for disturbed sleep were derived from medical records. We investigated associations between perioperative predictors on SPI and insomnia and associations between SPI and insomnia on PROs and frailty by linear regressions, adjusting for age, sex, and lung function. We evaluated the associations between SPI and insomnia on time to chronic lung allograft dysfunction (CLAD) and death using Cox models, adjusting...

Understanding Onset, Dynamic Transitions, and Associated Inequality Risk Factors for Adverse Posttraumatic Neuropsychiatric Sequelae After Trauma Exposure

Fri, 11 Apr 2025 00:00:00 +0000

Objective: Several gaps remain in the understanding of the onset, dynamic transitions, and associated risk factors of adverse posttraumatic neuropsychiatric sequelae (APNS) in the acute post-trauma window. Based on serial assessments of symptoms from a large cohort study, we identified homogeneous statuses across multiple APNS symptom domains and investigated the dynamic transitions among these statuses during the first 2 months after trauma exposure. Furthermore, we studied how symptom onset and transitions are affected by equity-relevant characteristics. Methods: The analysis was based on 2557 participants enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA). APNS symptoms comprised pain, depression, sleep discontinuity, nightmares, avoidance, re-experience, anxiety, hyperarousal, somatic symptoms, and mental fatigue. We identified the homogeneous status of APNS symptoms at baseline, 1 month, and 2 months, and explored transition probabilities...

ChromaFactor: Deconvolution of single-molecule chromatin organization with non-negative matrix factorization

Thu, 10 Apr 2025 00:00:00 +0000

The investigation of chromatin organization in single cells holds great promise for identifying causal relationships between genome structure and function. However, analysis of single-molecule data is hampered by extreme yet inherent heterogeneity, making it challenging to determine the contributions of individual chromatin fibers to bulk trends. To address this challenge, we propose ChromaFactor, a novel computational approach based on non-negative matrix factorization that deconvolves single-molecule chromatin organization datasets into their most salient primary components. ChromaFactor provides the ability to identify trends accounting for the maximum variance in the dataset while simultaneously describing the contribution of individual molecules to each component. Applying our approach to two single-molecule imaging datasets across different genomic scales, we find that these primary components demonstrate significant correlation with key functional phenotypes, including...

Comparative characterization of human accelerated regions in neurons

Thu, 10 Apr 2025 00:00:00 +0000

Human accelerated regions (HARs) are conserved genomic loci that have experienced rapid nucleotide substitutions following the divergence from chimpanzees1,2. HARs are enriched in candidate regulatory regions near neurodevelopmental genes, suggesting their roles in gene regulation3. However, their target genes and functional contributions to human brain development remain largely uncharacterized. Here we elucidate the cis-regulatory functions of HARs in human and chimpanzee induced pluripotent stem (iPS) cell-induced excitatory neurons. Using genomic4 and chromatin looping information, we prioritized 20 HARs and their chimpanzee orthologues for functional characterization via single-cell CRISPR interference, and demonstrated their species-specific gene regulatory functions. Our findings reveal diverse functional outcomes of HAR-mediated cis-regulation in human neurons, including attenuated NPAS3 expression by altering the binding affinities of multiple transcription factors in...

Unveiling the Genetic Landscape of Coronary Artery Disease Through Common and Rare Structural Variants

Thu, 10 Apr 2025 00:00:00 +0000

BACKGROUND: Genome-wide association studies have identified several hundred susceptibility single nucleotide variants for coronary artery disease (CAD). Despite single nucleotide variant-based genome-wide association studies improving our understanding of the genetics of CAD, the contribution of structural variants (SVs) to the risk of CAD remains largely unclear. METHOD AND RESULTS: We leveraged SVs detected from high-coverage whole genome sequencing data in a diverse group of participants from the National Heart Lung and Blood Institute's Trans-Omics for Precision Medicine program. Single variant tests were performed on 58 706 SVs in a study sample of 11 556 CAD cases and 42 907 controls. Additionally, aggregate tests using sliding windows were performed to examine rare SVs. One genome-wide significant association was identified for a common biallelic intergenic duplication on chromosome 6q21 (P=1.54E-09, odds ratio=1.34). The sliding window-based aggregate tests found...

State home and community‐based services expenditures and unmet care needs in the United States: Has everyone benefitted equally?

Wed, 9 Apr 2025 00:00:00 +0000

OBJECTIVE: To test whether the impacts of Medicaid's Home and Community-Based Services (HCBS) expenditures have been equitable. DATA SOURCES AND STUDY SETTING: This is a secondary data analysis. We linked annual data on state-level Medicaid HCBS expenditures with individual data from U.S. Health and Retirement Study (HRS; 2006-2016). STUDY DESIGN: We evaluated the association between state-level HCBS expenditure quartiles and the risk of experiencing challenges in basic or instrumental activities of daily living (I/ADLs) without assistance (unmet needs for care). We fitted generalized estimating equations (GEE) with a Poisson distribution, log link function, and an unstructured covariance matrix. We controlled demographics, time, and place-based fixed effects and estimated models stratified by race and ethnicity, gender, and urbanicity. We tested the robustness of results with negative controls. DATA COLLECTION/EXTRACTION METHODS: Our analytic sample included HRS Medicaid beneficiaries,...

Added Value of Whole-Body Diffusion-Weighted Imaging in Patients Undergoing Prostate-Specific Membrane Antigen Positron Emission Tomography

Mon, 7 Apr 2025 00:00:00 +0000

Background/Objectives: Patients with metastatic castration-resistant prostate cancer (mCRPC) who have Prostate-Specific Membrane Antigen (PSMA)-negative disease have inferior outcomes with radioligand therapy (RLT). The objective of this study is to assess the added value of whole-body (WB) diffusion-weighted imaging (DWI) to PSMA PET for identifying PSMA-negative disease, which is important for risk stratification. Methods: Consecutive PSMA PET/MRI exams at our institution, which included WB DWI in patients with mCRPC, were retrospectively reviewed. For both WB DWI and PSMA PET, two independent readers scored 14 anatomic locations, which were considered positive only if both readers identified lesions. The proportion of patients with mismatched disease was summarized descriptively for each anatomic location and overall. The inter-reader agreement was computed with intra-class correlation coefficients (ICCs). Results: The study included 41 patients (with a...

Leukocyte telomere length change in children with obesity in the context of an isocaloric fructose restriction intervention

Sat, 5 Apr 2025 00:00:00 +0000

BackgroundFew studies have evaluated changes in leukocyte telomere length (LTL) over a short time period (e.g. 1 week). LTL shortening is accelerated by exposure to inflammation and reactive oxygen species (ROS) damage.MethodsIn the context of an isocaloric fructose restriction study that was conducted with 43 Black and Latinx children over a 9-day period, we evaluated the relationship between metabolic health at baseline and metabolic changes and LTL at baseline and %LTL change over the follow-up period. Linear regression models were used to assess associations between metabolic correlates and LTL at baseline and LTL changes over 9 days.ResultsOverall children lost − 0.05 ± 0.14 T/S units or − 2.98 ± 8.74% total change over the follow-up period. Higher concentrations of HDL-C, APO-AI and a greater % of large HDL-C at baseline were associated with reduced LTL attrition rates at day 10 (p < 0.01; p < 0.01 and p = 0.02 respectively). Increases in APO-AI over the...

Electroacupuncture Plus Auricular Acupressure on Chemotherapy-Related Insomnia in Patients With Breast Cancer (EACRI): Study Protocol for a Randomized, Sham-Controlled Trial