National Institutes Of Health Research Articles

Role of Gender in Health and Disease: Methods of Reporting and Interactions with Sex and Other Factors.

Sex and gender are distinct terms that must be used correctly. Data regarding sex and gender may be collected using a 2-step method that separates biological sex and self-reported gender identity. The PhenX Toolkit, funded by the National Institutes of Health (NIH), is one tool that provides investigators with recommended standard data-collection protocols. Another tool is the Diversity Minimal Item Set questionnaire. Importantly, sex and gender interact: for example, pain has both biological aspects (sex differences in electrical, ischemic, thermal, pressure, and muscle pain sensitivity) and cultural aspects (gender factors in how people report pain and how physicians understand and treat pain in patients). Gender norms, identity, and relations all impact patient care. Gender norms, for instance, may influence how a person experiences pain, gender identity may influence a person's willingness to report pain, and gender relations may influence a physician's gendered expectations in relation to a patient's gendered behaviors. Clinicians may perceive women's pain to be psychological; as a result, women may receive more nonspecific diagnoses, wait longer for treatment, and receive more antidepressants and fewer analgesics than men. Research on gender-diverse people and pain is just now emerging. Resources for methods of reporting include The Lancet, Nature, and the Sex and Gender Equity in Research (SAGER) Guidelines. We must consider all relevant factors intersecting with sex and gender, including age, disabilities, educational background, ethnicity, family configuration, geographic location, race, sexuality, social and economic status, sustainability, and more.

Identifying Potentially Undiagnosed Individuals with Hyperimmunoglobulin E Syndrome Utilizing a Scoring System

BackgroundHyperimmunoglobulin E syndrome (HIES) constitutes a group of rare primary immunodeficiency disorders. The diagnosis relies on the National Institutes of Health (NIH) scoring system, incorporating clinical and laboratory data. Scores≥15 raise a strong suspicion of the disease. In an isolated Israeli population, Zinc Finger (ZNF)341 deficiency, a subtype of HIES, has a carrier incidence of 1:20, but the prevalence of the clinical syndrome within this community remains unknown. ObjectiveThis study seeks to estimate the prevalence of potentially undiagnosed HIES cases within this population by utilizing the NIH scoring criteria. MethodsThis retrospective cohort study obtained requisite clinical and laboratory data for NIH score computation from the electronic medical records of Clalit Health Services for the isolated village under scrutiny in comparison to a neighboring village. Subsequently, clinical scores were assigned to each subject, enabling comparative analysis of suspected diagnosis rates between the two populations. ResultsAmong the 29,390 studied subjects, 12 had a documented diagnosis of HIES. All were in the study village, and none were from the control village (0.08% vs. 0%, p<0.01). Within the study village, 235 individuals (1.62%) had an NIH score≥15 and were suspected to suffer from HIES almost doubled compared to the control group 130 (0.87%) (p<0.001). ConclusionThis is the first time the NIH clinical score system has been used for population screening. The significant disparity in the prevalence of suspected, undiagnosed cases between the study village and the control village strongly suggests the potential utility of this tool for preliminary screening.

The role of advocacy in sustaining male contraceptive research and development.

Novel male contraceptives have been in development for well over half a century, and despite a robust predicted global market for new methods, funding for research and development has been extremely limited. While the pharmaceutical industry previously supported male contraceptive research and development, industry partners are only spectators in the current space, awaiting a product that has been de-risked by the public sector before re-entering the field. Current male contraceptive development efforts are thus primarily funded by nonprofit, non-governmental, and government agencies who also act as the primary advocates for the field. Specific organizations include the International Consortium on Male Contraception, the Population Council, the Male Contraceptive Initiative, the World Health Organization, and the US National Institutes of Health. The funding provided by these public agencies, alongside their social and policy-based advocacy efforts such as market research, public education, and calls to action have kept the male contraceptive product development space afloat, resulting in a pipeline of potential products advancing towards market approval. However, as these products mature into more expensive clinical stages of development, they continue to face significant funding challenges, which many programs may not overcome. To fully realize the benefits of novel male contraceptive options, it is incumbent on philanthropic entities, impact investors, venture capital, and/or the pharmaceutical sector to provide significant and timely support for male contraceptive research and development.

Academic and Demographic Profile of Orthopaedic Vice Chairs of Research: Implications for Leadership.

Vice chairs (VCs) of research play an integral role in orthopaedic departments at academic medical centers; they strategically lead research efforts and support the research careers of faculty and trainees. To our knowledge, no analysis of orthopaedic VCs of research exists in the literature, and no similar analyses have been completed in other medical specialties. We aimed to investigate the academic and demographic characteristics of orthopaedic VCs of research. Doximity was used to identify orthopaedic residencies in the U.S. Personal and program websites were queried to identify VCs of research and collect academic and demographic characteristics. The Scopus database, the National Institutes of Health (NIH) RePORTER, and Google Scholar were used to obtain each investigator's Hirsch index (h-index) and the number and type of NIH grants awarded, respectively. Of the 207 orthopaedic residency programs identified, 71 (34%) had a named VC of research in the orthopaedic department. Of the top 50 medical schools, 42 were affiliated with such programs. Most VCs were men (89%). The racial and/or ethnic background of the majority of VCs was White (85%), followed by Asian (14%), and Black (1%). Most held the rank of professor (78%), followed by associate professor (18%), and assistant professor (4%). Over half were PhDs (55%), followed by MDs (37%) and MD/PhDs (8%). On average, the VCs had an h-index of 40.5. Furthermore, 65% had been awarded at least 1 NIH grant for their research, with 43% awarded at least 1 R01 grant. VCs of research develop research opportunities and shape the brand recognition of academic orthopaedic programs. Most orthopaedic VCs of research are men (89%); 85% each are White and have a rank of professor. Nearly half have been awarded at least 1 R01 grant from the NIH. This study outlines important academic and demographic characteristics among orthopaedic surgery VCs of research. Considering the mentorship aspect of their role, VCs of research have an opportunity to influence the diversity of incoming trainees in the field of academic orthopaedics.

Mortality due to falls by county, age group, race, and ethnicity in the USA, 2000–19: a systematic analysis of health disparities

Fall-related mortality has increased rapidly over the past two decades in the USA, but the extent to which mortality varies across racial and ethnic populations, counties, and age groups is not well understood. The aim of this study was to estimate age-standardised mortality rates due to falls by racial and ethnic population, county, and age group over a 20-year period. Redistribution methods for insufficient cause of death codes and validated small-area estimation methods were applied to death registration data from the US National Vital Statistics System and population data from the US National Center for Health Statistics to estimate annual fall-related mortality. Estimates from 2000 to 2019 were stratified by county (n=3110) and five mutually exclusive racial and ethnic populations: American Indian or Alaska Native (AIAN), Asian or Pacific Islander (Asian), Black, Latino or Hispanic (Latino), and White. Estimates were corrected for misreporting of race and ethnicity on death certificates using published misclassification ratios. We masked (ie, did not display) estimates for county and racial and ethnic population combinations with a mean annual population of less than 1000. Age-standardised mortality is presented for all ages combined and for age groups 20-64 years (younger adults) and 65 years and older (older adults). Nationally, in 2019, the overall age-standardised fall-related mortality rate for the total population was 13·4 deaths per 100 000 population (95% uncertainty interval 13·3-13·6), an increase of 65·3% (61·9-68·8) from 8·1 deaths per 100 000 (8·0-8·3) in 2000, with the largest increases observed in older adults. Fall-related mortality at the national level was highest across all years in the AIAN population (in 2019, 15·9 deaths per 100 000 population [95% uncertainty interval 14·0-18·2]) and White population (14·8 deaths per 100 000 [14·6-15·0]), and was about half as high among the Latino (8·7 deaths per 100 000 [8·3-9·0]), Black (8·1 deaths per 100 000 [7·9-8·4]), and Asian (7·5 deaths per 100 000 [7·1-7·9]) populations. The disparities between racial and ethnic populations varied widely by age group, with mortality among younger adults highest for the AIAN population and mortality among older adults highest for the White population. The national-level patterns were observed broadly at the county level, although there was considerable spatial variation across ages and racial and ethnic populations. For younger adults, among almost all counties with unmasked estimates, there was higher mortality in the AIAN population than in all other racial and ethnic populations, while there were pockets of high mortality in the Latino population, particularly in the Mountain West region. For older adults, mortality was particularly high in the White population within clusters of counties across states including Florida, Minnesota, and Wisconsin. Age-standardised mortality due to falls increased over the study period for each racial and ethnic population and almost every county. Wide variation in mortality across geography, age, and race and ethnicity highlights areas and populations that might benefit most from efficacious fall prevention interventions as well as additional prevention research. US National Institutes of Health (Intramural Research Program, National Institute on Minority Health and Health Disparities; National Heart, Lung, and Blood Institute; Intramural Research Program, National Cancer Institute; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Office of Disease Prevention; and Office of Behavioral and Social Sciences Research).

Impact of financial incentives on viral suppression among adults initiating HIV treatment in Tanzania: a hybrid effectiveness–implementation trial

Small incentives could improve engagement in HIV care. We evaluated the short-term and longer-term effects of financial incentives for visit attendance on viral suppression among adults initiating antiretroviral therapy (ART) in Tanzania. In a type 1 hybrid effectiveness-implementation study, we randomised (1:1) 32 primary care HIV clinics in four Tanzanian regions to usual care (control group) or the intervention (usual care plus ≤6 monthly incentives [22 500 Tanzanian Shillings, about US$10, each], conditional on visit attendance). Adults (aged ≥18 years) initiating ART (<30 days) who owned a mobile phone and had no plans to transfer to another facility were eligible. The primary outcome was retention on ART with viral suppression (<1000 copies per mL) at 12 months. Secondary outcomes included retention on ART with viral suppression at 6 months and viral suppression at 6 months and 12 months using a lower threshold (<50 copies per mL). Intent-to-treat analysis and a cluster-based permutation test were used to evaluate the effect of financial incentives on outcomes. This trial is registered with ClinicalTrials.gov, NCT04201353, and is completed. Between May 28, 2021, and March 8, 2022, 1990 participants (805 male and 1185 female) were enrolled in the study. 1059 participants were assigned to the intervention group and 931 participants were assigned to the control group. Overall, 1536 (88%) participants at 6 months and 1575 (83%) at 12 months were on ART with viral suppression. At 12 months, 6 months after the intervention ended, 866 (85%) participants in the intervention group compared with 709 (81%) in the control group had viral loads less than 1000 copies per mL (adjusted risk difference [aRD] 4·4 percentage points, 95% CI -1·4 to 10·1, permutation test p=0·35). At 6 months, 858 participants (90%) in the intervention group were on ART with viral loads less than 1000 copies per mL compared with 678 (86%) in the control group (aRD 5·1 percentage points, 95% CI 1·1 to 9·1, permutation test p=0·06). Effects were larger at 6 months and 12 months with the lower threshold for viral suppression, and there was significant effect heterogeneity by region. Adverse events included 106 deaths (56 in the control group and 50 in the intervention group), none related to study participation. Short-term incentives for visit attendance had modest, short term benefits on viral suppression and did not harm retention or viral suppression after discontinuation. These findings suggest the need to understand subgroups who would most benefit from incentives to support HIV care. National Institute of Mental Health. For the Swahili translation of the abstract see Supplementary Materials section.

Multidisciplinary lifestyle interventions for neurological disorders during the Silent phase (MINDS) study: a multi-omics randomized controlled trial protocol

IntroductionGiven the prevalence and staggering cost of neurological disorders, there is dire need for effective early detection and intervention tools. Emerging evidence suggests that multidisciplinary lifestyle interventions (MLI) may mitigate the risk and progression of neurological disorders. The objectives of this protocol are (1) to test the impact of MLI on the progression of neurological disorders and (2) to identify multi-omic biomarkers for early stages of neurological disease and the impact of MLIs on these biomarkers.Methods and analysisWe present the Multidisciplinary lifestyle Interventions for Neurological Disorders during the Silent phase (MINDS) protocol, a randomized controlled trial of MLI in neurologically healthy older adults (≥ 50 years old) exhibiting elevated risk for common neurological disorders: stroke, epilepsy, Parkinson’s Disease, or Alzheimer’s disease and related dementias. Participants will be randomly assigned to intervention (n = 100) or control (n = 100) groups. The intervention group will receive 3 months of weekly 2-hour sessions on diet education, yoga, music therapy, and cognitive skills training. The participants’ neurological health and engagement in relevant lifestyle practices will be assessed at regular intervals for 12 months. Neuroimaging and samples for multi-omic analyses will be collected at baseline, and at 3 months and 12 months after enrollment. Primary outcomes will be signs of progression of the neurological disorder risk that qualified them for study enrollment or a clinical diagnosis of the disorder. Secondary and exploratory outcomes will be based on self-reported health and multi-omic data. Data analysis will include between-group and longitudinal within-group analyses.PerspectivesThe MINDS protocol and trial aims to clarify the impact of MLI on the progression of neurological disorder risk or diagnosis in older adults and to identify biomarkers that can be used to confirm MLI efficacy. The ability to validate the impact of MLI on neurological disorder progression based on biomarker data allows the identification of individuals most likely to benefit from such therapies in the early stages of neurological disease.Trial registrationThe trial is registered on the National Institutes of Health (NIH) ClinicalTrials.gov (NCT05984056) site. It was registered on August 2nd, 2023. The trial has full approval of the Cleveland Clinic Internal Review Board.

The rising tide of HIV among young men who have sex with men in Brazil: insights from the Conectad@s study

Young gay, bisexual, and other men who have sex with men (YMSM) in Latin America experience disproportionately high rates of HIV. While new case numbers have stabilised in other demographics, the incidence of HIV in this particular group continues to rise. We estimated the prevalence of HIV and sexually transmitted infections (STI) and identified correlates of new HIV diagnoses among YMSM in Brazil. Conectad@s was a respondent-driven sampling-based study to recruit and engage YMSM in HIV prevention and treatment services in Rio de Janeiro, Brazil (November 2021-October 2022). Eligibility criteria were age 18-24 years and self-identification as MSM (cis/trans) or non-binary person who have sex with men. Participants underwent HIV/STI testing and completed a socio-behavioural questionnaire. We described baseline characteristics by HIV status and used logistic regression models to identify correlates of new HIV diagnoses. Trial ID: DERR1-10.2196/34885. Among 409 participants, 370 (90.5%) self-identified as cisgender men, nine (2.2%) transgender men, and 30 (7.3%) non-binary. Median age was 21 years (IQR: 20-23), with 80 (19.6%) aged 18-19 years. Most self-identified as Black or Pardo (70.6%); 109 (26.7%) never tested for HIV. HIV prevalence was 9.8%; 50% (n=20/40) were newly diagnosed with HIV. Only nine participants ever used PrEP and three were currently using it. Overall, 133 (32.5%) reported sexual violence in their lifetime and 102 (24.9%) reported a suicide attempt. Prevalence of active syphilis, chlamydia, and gonorrhoea were 14.4%, 15.9%, and 14.7%, respectively. New HIV diagnoses were positively associated with engaging in high-risk behaviour (aOR 4.88 [95% CI: 1.88-13.40]) and anxiety (aOR 2.67 [95% CI: 1.01-7.70]), and negatively associated with ever disclosing sexual orientation (aOR 0.19 [95% CI: 0.04-0.92]) and HIV knowledge (aOR 0.77 [95% CI: 0.59-1.01]). High prevalence of HIV coupled with a high proportion of new HIV diagnoses underscore a potentially growing HIV epidemic among YMSM in Brazil. National Institutes of Health (NIH), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Ministry of Health of Brazil.

Surgical approaches for pudendal nerve entrapment: insights from a systematic review and meta-analysis.

Pudendal nerve entrapment (PNE) is an underdiagnosed condition affecting a spectrum of pelvic functions, primarily pain, as outlined by Nantes diagnostic criteria. Although numerous surgical decompression techniques are available for its management, consensus on efficacy and safety is lacking. This study conducts a systematic review and meta-analysis to assess the efficacy and complication rates of the main surgical decompression techniques. A comprehensive literature search was conducted in PubMed®, Embase®, Web of Science®, and ClinicalTrails.gov® on 19th of April 2023. Initial screening involved title and abstract evaluation, with subsequent retrieval and assessment of abstracts and full-text articles. Studies assessing pain outcomes before and after surgical release of the pudendal nerve were included. Studies without full-text, focusing on diagnostic methods or with outcomes relating solely to LUTS, digestive symptoms, or sexual dysfunction, were excluded. Risk of bias assessement was conducted using the National Institute of Health (NIH) Study Quality Assessment tool. Studies were categorized based on three surgical techniques: perineal, transgluteal, and laparoscopic transperitoneal. Random-effects meta-analysis with subgroup analysis were used. Meta-regression analyses were conducted to investigate the influence of covariates on the observed outcomes. Nineteen studies, comprising 810 patients, were included. The overall significant pain relief rate across all techniques was estimated at 0.67 (95% CI 0.54 to 0.78) with considerable heterogeneity (I2 = 80.4%). Subgroup analysis revealed success rate for different techniques: laparoscopic (0.91, 95% CI 0.64 to 0.98), perineal (0.69, 95% CI 0.52 to 0.82), and transgluteal (0.50, 95% CI 0.37 to 0.63). The laparoscopic technique exhibited a complication rate of 16.0%. Meta-regression indicated that patient age and median follow-up significantly influenced outcomes. While comparing surgical techniques is challenging, this meta-analysis highlights important outcome differences. The laparoscopic technique appears most promising for pain improvement. However, the study also emphasizes the need for further robust, long-term research due to significant heterogeneity across studies and prevelent risk of bias. PROSPERO database: CRD42023496564.

Clinical spectrum of acute poisoning among children visiting emergency at national institute of child health.

Objective: To determine the clinical spectrum of acute poisoning among children visiting emergency department. Study Design: Cross-sectional study. Setting: Department of Emergency, National Institute of Child Health, Karachi, Pakistan. Period: July 2023 to December 2023. Methods: Children of either gender, aged below 12 years and presenting with acute poisoning were analyzed. Demographic, clinical characteristics and final outcomes of children were reported. Results: In a total of 264 children, 139 (52.7%) were boys. The mean age was 4.79±2.02 years. Mode of poisoning was intentional in 31 (11.7%) children. Non-pharmaceutical exposure was reported in 183 (69.3%) children. Route of poisoning was through oral route in 178 (67.4%) children. The mean time to reach hospital was 80.95±77.77 minutes. Respiratory distress, drowsiness, vomiting, and cough were the most frequent presenting complaints, noted in 111 (42.0%), 43 (16.3%), 38 (14.4%), and 32 (12.1%) children, respectively. Type of poisoning substance were found to have significant association with age (p&lt;0.001), time of presentation (p&lt;0.001), mode of poisoning (p=0.011), place of poisoning (p&lt;0.001), route of poisoning (p&lt;0.001), first aid given (p&lt;0.001), ambulance carrying the child to hospital (p&lt;0.001), and final outcome (p&lt;0.001). No mortality was reported. Conclusion: Acute poisoning most commonly affects children up to 5 years of age. Non-pharmaceutical exposure was reported in majority of acute poisoning cases. Respiratory distress, drowsiness, vomiting, and cough were the most frequent presenting complaints.

Negligence in biomedical research: an anti-racist approach for substance use researchers

Racism is embedded in the fabric of society at structural, disciplinary, hegemonic, and interpersonal levels, working as a mechanism that drives health disparities. In particular, stigmatized views of substance use get entangled with racialization, serving as a tool to uphold oppressive systems. While national health institutions have made commitments to dismantle these systems in the United States, anti-racism has not been integrated into biomedical research practice. The ways in which substance use researchers use and interpret race data—without engaging in structural racism as a mechanism of health inequity—can only be described as inadequate. Drawing upon concepts from the Public Health Critical Race praxis, QuantCrit, and an anti-racism research framework, we recommend a set of guidelines to help biomedical researchers conceptualize and engage with race more responsibly in substance use research.

The Association between Obesity and Polycystic Ovary Syndrome: An Epidemiologic Study of Observational Data.

Polycystic Ovary Syndrome (PCOS) is a common female cardio-metabolic-reproductive disorder. It is unclear whether the global obesity epidemic is impacting the high PCOS prevalence. To determine the extent to which obesity contributes to the PCOS development globally. A systematic review was conducted to identify population studies on PCOS prevalence globally, through July 2023. Linear regression and random-effect models were applied to examine the association of mean body mass index (BMI) or obesity prevalence with the prevalence of PCOS diagnosed by 1990 National Institute of Health (NIH), 2003 Rotterdam (Rotterdam), and 2006 Androgen Excess-PCOS (AE-PCOS) criteria. Subgroup analyses were also conducted for recruitment methods and study quality. Fifty-eight studies with 85,956 adults from 24 countries were included. Considering all available data, a borderline association was observed between PCOS and obesity prevalence when using the AE-PCOS, but not the NIH or Rotterdam criteria. Alternatively, subgroup analysis of studies with better recruitment methods demonstrated a significant positive association of population mean BMI or obesity prevalence with PCOS prevalence when using the Rotterdam or AE-PCOS criteria, while using only high-quality studies revealed an association using NIH as well as Rotterdam and AE-PCOS criteria. Overall, we observed that a 1% increase in obesity prevalence resulted in an approximately 0.4% increase in PCOS prevalence by the Rotterdam criteria. These data indicate that obesity increases the development of PCOS, although the effect is modest. Our data also emphasizes the need to undertake only high-quality studies in assessing PCOS epidemiology.

Microbiota composition effect on immunotherapy outcomes in colorectal cancer patients: A systematic review.

Immune checkpoint inhibitors (ICIs) have emerged as an effective treatment for colorectal cancer (CRC). Studies indicate that the composition of gut microbiota could potentially serve as a biomarker for predicting the clinical effectiveness of immune checkpoint inhibitors. Following PRISMA guidelines, the review was conducted after registering the protocol with PROSPERO. A comprehensive literature search was carried out across five databases: PubMed, Scopus, Web of Science, Embase, and Cochrane Library. Assessment tools from the National Institutes of Health (NIH) were used to gauge the quality of the studies. A total of 5,132 papers were identified, and three studies and one conference abstract published between 2017-2022 met the inclusion criteria and were summarized in a descriptive synthesis table. These four studies were in accord with the following findings, four main phyla, Firmicutes, Bacteroidata, Actinobacteria, and Verrucomicrobiota were associated with CRC patients' clinical response toward ICIs treatment. Ruminococcaceae was predominantly related to CRC patients responding to therapy, while the Micrococcaceae family was more common among the non-responders. Bacterial taxa such as Faecalibacterium and Prevotellaceae were associated with better responses to ICIs and could be predictive biomarkers. The signature of fecal microbiota with Akkermansia muciniphila and Eubacterium rectale enrichment, and Rothia mucilaginosa depletion could independently predict better response to ICIs in patients with CRC. The findings have brought attention to the notable differences in terms of richness and composition of microbiota between patients who responded positively to the treatment and those who did not. Bacterial species and families, such as Faecalibacterium, Bifidobacterium, Lachnospiraceae, Akkermansia sp., Ruminococcaceae, and Prevotellaceae, have consistently surfaced as potential indicators of immunotherapeutic responses. Furthermore, this review also emphasizes the need for additional comprehensive, multi-center studies with larger sample sizes to validate reported microbiota and expand our understanding of the role of gut microbiota in CRC ICIs therapy. PROSPERO ID: CRD42021277691.

NIH funding and journal selection: trends in dermatology publication models across tiers from 2021 to 2023.

This study examines the influence of National Institutes of Health (NIH) funding on the publication choices of dermatologists, particularly in terms of journal tiers and pay-to-publish (P2P) versus free-to-publish (F2P) models. Utilizing k-means clustering for journal ranking based on SCImago Journal Rank, h-index, and Impact Factor, journals were categorized into three tiers and 54,530 dermatology publications from 2021 to 2023 were analyzed. Authors were classified as Top NIH Funded or Non-Top NIH Funded according to Blue Ridge Institute for Medical Research rankings. The study finds significant differences in publication patterns, with Top NIH Funded researchers in Tier I journals demonstrating a balanced use of P2P and F2P models, while they preferred F2P models in Tier II and III journals. Non-Top NIH Funded authors, however, opted for P2P models more frequently across all tiers. These data suggest NIH funding allows researchers greater flexibility to publish in higher-tier journals despite publication fees, while prioritizing F2P models in lower-tier journals. Such a pattern indicates that funding status plays a critical role in strategic publication decisions, potentially impacting research visibility and subsequent funding. The study's dermatology focus limits broader applicability, warranting further research to explore additional factors like geographic location, author gender, and research design.

An Introduction to the Human Connectome Project for Early Psychosis.

The time following a recent onset of psychosis is a critical period during which intervention may be maximally effective. Studying individuals in this period also offers an opportunity to investigate putative brain biomarkers of illness prior to the long-term effects of chronicity and medication. The Human Connectome Project for Early Psychosis (HCP-EP) was funded by the National Institutes of Mental Health (NIMH) as an extension of the original Human Connectome Project's approach to understanding the human brain and its structural and functional connections. The HCP-EP data were collected at 3 sites in Massachusetts (Beth Israel Deaconess Medical Center, McLean Hospital, and Massachusetts General Hospital), and one site in Indiana (Indiana University). Brigham and Women's Hospital served as the data coordination center and as an imaging site. The HCP-EP dataset includes high-quality clinical, cognitive, functional, neuroimaging, and blood specimen data acquired from 303 individuals between the ages of 16-35 years old with affective psychosis (n = 75), non-affective psychosis (n = 148), and healthy controls (n = 80). Participants with early psychosis were within 5 years of illness onset (mean duration = 1.9 years, standard deviation = 1.4 years). All data and novel or modified analytic tools developed as part of the study are publicly available to the research community through the NIMH Data Archive (NDA) or GitHub (https://github.com/pnlbwh). This paper provides an overview of the specific HCP-EP procedures, assessments, and protocols, as well as a brief characterization of the study participants to make it easier for researchers to use this rich dataset. Although we focus here on discussing and comparing affective and non-affective psychosis groups, the HCP-EP dataset also provides sufficient information for investigators to group participants differently.

Temporal changes in cause of death among adolescents and adults in six countries in eastern and southern Africa in 1995–2019: a multi-country surveillance study of verbal autopsy data

The absence of high-quality comprehensive civil registration and vital statistics systems across many settings in Africa has led to little empirical data on causes of death in the region. We aimed to use verbal autopsy data to provide comparative, population-based estimates of cause-specific mortality among adolescents and adults in eastern and southern Africa. In this surveillance study, we harmonised verbal autopsy and residency data from nine health and demographic surveillance system (HDSS) sites in Kenya, Malawi, Tanzania, South Africa, Uganda, and Zimbabwe, each with variable coverage from Jan 1, 1995, to Dec 31, 2019. We included all deaths to adolescents and adults aged 12 or over that were residents of the study sites and had a verbal autopsy conducted. InSilicoVA, a probabilistic model, was used to assign cause of death on the basis of the signs and symptoms reported in the verbal autopsy. Levels and trends in all-cause and cause-specific mortality rates and cause-specific mortality fractions were calculated, stratified by HDSS site, sex, age, and calendar periods. 52 484 deaths and 5 157 802 person-years were reported among 1 071 913 individuals across the nine sites during the study period. 47 961 (91·4%) deaths had a verbal autopsy, of which 46 570 (97·1%) were assigned a cause of death. All-cause mortality generally decreased across the HDSS sites during this period, particularly for adults aged 20-59 years. In many of the HDSS sites, these decreases were driven by reductions in HIV and tuberculosis-related deaths. In 2010-14, the top causes of death were: road traffic accidents, HIV or tuberculosis, and meningitis or sepsis in adolescents (12-19 years); HIV or tuberculosis in adults aged 20-59 years; and neoplasms and cardiovascular disease in adults aged 60 years and older. There was greater between-HDSS and between-sex variation in causes of death for adolescents compared with adults. This study shows progress in reducing mortality across eastern and southern Africa but also highlights age, sex, within-HDSS, and between-HDSS differences in causes of adolescent and adult deaths. These findings highlight the importance of detailed local data to inform health needs to ensure continued improvements in survival. National Institute of Child Health and Human Development of the US National Institutes of Health.

Cost-effectiveness of group medical visits and microfinance interventions versus usual care to manage hypertension in Kenya: a secondary modelling analysis of data from the Bridging Income Generation with Group Integrated Care (BIGPIC) trial

The Bridging Income Generation with Group Integrated Care (BIGPIC) trial in rural Kenya showed that integrating usual care with group medical visits or microfinance interventions reduced systolic blood pressure and cardiovascular risk in participants. We aimed to estimate the incremental cost-effectiveness of three BIGPIC interventions for a modelled cohort and by sex, as well as the cost of implementing these interventions. For this analysis, we used data collected during the BIGPIC trial, a four-group, cluster-randomised trial conducted in the western Kenyan catchment area of the Academic Model Providing Access to Healthcare. BIGPIC enrolled participants from 24 rural health facilities in rural western Kenya aged 35 years or older with either increased blood pressure or diabetes. Participants were assigned to receive either usual care, group medical visits, microfinance, or a combination of group medical visits and microfinance (GMV-MF). Our model estimated the incremental cost-effectiveness of the three BIGPIC interventions via seven health states (ie, a hypertensive state, five chronic cardiovascular-disease states, and a death state) by simulating transitions between health states for a hypothetical cohort of individuals with hypertension on the basis of QRISK3 scores. In every cycle, participants accrued costs and disability-adjusted life-years (DALYs) associated with their health state. Incremental cost-effectiveness ratios (ICERs) were calculated for the entire modelled cohort and by sex by dividing the incremental cost by the incremental effectiveness of the next most expensive intervention. The main outcome of this analysis was ICERs for each intervention evaluated. This analysis is registered at ClinicalTrials.gov (NCT02501746). Between Feb 6, 2017, and Dec 29, 2019, 2890 people were recruited to the BIGPIC trial. 2020 (69·9%) of 2890 participants were female and 870 (30·1%) were male. At baseline, mean QRISK3 score was 11·5 (95% CI 11·1-11·9) for the trial population, 11·9 (11·5-12·2) for male participants, and 11·3 (11·0-11·6) for female participants. For the population of Kenya, group medical visits were estimated to cost US$7 more per individual than usual care and result in 0·005 more DALYs averted (ICER $1455 per DALY averted). Microfinance was estimated to cost $19 more than group medical visits but was only estimated to avert 0·001 more DALYs. Relative to group medical visits, GMV-MF was estimated to cost $29 more and avert 0·009 more DALYs ($3235 per DALY averted). Relative to usual care, GMV-MF was estimated to cost $37 more and avert 0·014 more DALYs ($2601 per DALY averted). In the first year of the intervention, usual care was estimated to be the least expensive intervention to implement ($87 per participant; $10 238 per health-facility catchment area [HFCA]), then group medical visits ($99 per participant; $12 268 per HFCA), then microfinance ($120 per participant; $14 172 per HFCA), with GMV-MF estimated to be the most expensive intervention to implement ($139 per participant; $16 913 per HFCA). Group medical visits and GMV-MF were estimated to be cost-effective strategies to improve blood-pressure control in rural Kenya. However, which intervention to pursue depends on resource availability. Policy makers should consider these factors, in addition to sex differences in programme effectiveness, when selecting optimal implementation strategies. US National Institutes of Health.

Diet-induced obesity mediated through Estrogen-Related Receptor α is independent of intestinal function.

ChIP-seq and RNA-seq data from this publication have been deposited to GEO accession numbers GSE269824 and GSE269825, respectively. Any additional information required to reanalyze the data reported in this paper is available from the corresponding author upon request. This research was funded by grants from the National Institutes of Health (NIH) to M.P.V. (R01DK121915 and R01DK126446). K.V. was supported by an American Heart Association pre-doctoral fellowship (906006). S.K. was supported by a Rutgers DLS Summer Undergraduate Research Fellowship. A.L. was supported by grants from the NIH grant F31DK137596 and the NIH T32 Biotechnology Training Program (GM135141). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no competing interests.

The burden of cirrhosis mortality by county, race, and ethnicity in the USA, 2000–19: a systematic analysis of health disparities

Cirrhosis is responsible for substantial health and economic burden in the USA. Reducing this burden requires better understanding of how rates of cirrhosis mortality vary by race and ethnicity and by geographical location. This study describes rates and trends in cirrhosis mortality for five racial and ethnic populations in 3110 US counties from 2000 to 2019. We estimated cirrhosis mortality rates by county, race and ethnicity, and year (2000-19) using previously validated small-area estimation methods, death registration data from the US National Vital Statistics System, and population data from the US National Center for Health Statistics. Five racial and ethnic populations were considered: American Indian or Alaska Native (AIAN), Asian or Pacific Islander (Asian), Black, Latino or Hispanic (Latino), and White. Cirrhosis mortality rate estimates were age-standardised using the age distribution from the 2010 US census as the standard. For each racial and ethnic population, estimates are presented for all counties with a mean annual population greater than 1000. From 2000 to 2019, national-level age-standardised cirrhosis mortality rates decreased in the Asian (23·8% [95% uncertainty interval 19·6-27·8], from 9·4 deaths per 100 000 population [8·9-9·9] to 7·1 per 100 000 [6·8-7·5]), Black (22·8% [20·6-24·8], from 19·8 per 100 000 [19·4-20·3] to 15·3 per 100 000 [15·0-15·6]), and Latino (15·3% [13·3-17·3], from 26·3 per 100 000 [25·6-27·0] to 22·3 per 100 000 [21·8-22·8]) populations and increased in the AIAN (39·3% [32·3-46·4], from 45·6 per 100 000 [40·6-50·6] to 63·5 per 100 000 [57·2-70·2] in 2000 and 2019, respectively) and White (25·8% [24·2-27·3], from 14·7 deaths per 100 000 [14·6-14·9] to 18·5 per 100 000 [18·4-18·7]) populations. In all years, cirrhosis mortality rates were lowest among the Asian population, highest among the AIAN population, and higher in males than females for each racial and ethnic population. The degree of heterogeneity in county-level cirrhosis mortality rates varied by racial and ethnic population, with the narrowest IQR in the Asian population (median 8·0 deaths per 100 000, IQR 6·4-10·4) and the widest in the AIAN population (55·1, 30·3-78·8). Cirrhosis mortality increased over the study period in almost all counties for the White (2957 [96·9%] of 3051 counties) and AIAN (421 [88·8%] of 474) populations, but in a smaller proportion of counties for the Asian, Black, and Latino populations. For all racial and ethnic populations, cirrhosis mortality rates increased in more counties between 2000 and 2015 than between 2015 and 2019. Cirrhosis mortality increased nationally and in many counties from 2000 to 2019. Although the magnitude of racial and ethnic disparities decreased in some places, disparities nonetheless persisted, and mortality remained high in many locations and communities. Our findings underscore the need to implement targeted and locally tailored programmes and policies to reduce the burden of cirrhosis at both the national and local level. US National Institutes of Health (Intramural Research Program, National Institute on Minority Health and Health Disparities; National Heart, Lung, and Blood Institute; Intramural Research Program, National Cancer Institute; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Office of Disease Prevention; and Office of Behavioral and Social Sciences Research).

Using a mixed-reality headset to elicit and track clinically relevant movement in the clinic.

21st century neurology will require scalable and quantitative tools that can improve neurologic evaluations over telehealth and expand access to care. Commercially available mixed-reality headsets allow for simultaneous presentation of stimuli via holograms projected into the real world and objective and quantitative measurement of hand movement, eye movement, and phonation. We created 6 tasks designed to mimic standard neurologic assessments and administered them to a single participant via the Microsoft HoloLens 2 mixed-reality headset. The tasks assessed postural hand tremor, finger tapping, pronation and supination of hands, hand and eye tracking of a center-out task, hand and eye tracking of a random motion task, and vocal assessment. We show the utility of the HoloLens for commonly used neurological exams. First, we demonstrate that headset-derived holograms can project hand movements and objects in 3D space, providing a method to accurately and reproducibly present test stimuli to reduce test-test variability. Second, we found that participant hand movements closely matched holographic stimuli using a variety of metrics calculated on recorded movement data. Third, we showed that the HoloLens can record and playback exam tasks for visual inspection, sharing with other medical providers, and future analysis. Fourth, we showed that vocal recordings and analysis could be used to profile vocal characteristics over time. Together, this demonstrates the versatility of mixed reality headsets and possible applications for neurological assessment. Administering components of the neurologic exam via a self-contained and commercially available mixed-reality headset has numerous benefits including detailed kinematic quantification, reproducible stimuli presentation from test to test, and can be self-administered expanding access to neurological care and saving hospital time and money. This work was supported by grants from the National Institutes of Health (NIH) (F30AG063468) (E.L.), (F31NS113395) (D.J.C), and the Pilot Grant Award from the University of Colorado Movement Disorders Center (D.J.C).