Search

BACKGROUND: Guidelines recommend measuring blood pressure (BP) in both arms, adopting the higher arm readings for diagnosis and management. Data to support this recommendation are lacking. We evaluated associations of higher and lower arm systolic BPs with diagnostic and treatment thresholds, and prognosis in hypertension, using data from the Inter-arm Blood Pressure Difference—Individual Participant Data Collaboration. METHODS: One-stage multivariable Cox regression models, stratified by study, were used to examine associations of higher or lower reading arm BPs with cardiovascular mortality, all-cause mortality, and cardiovascular events, in individual participant data meta-analyses pooled from 23 cohorts. Cardiovascular events were modelled for Framingham and atherosclerotic cardiovascular disease risk scores. Model fit was compared throughout using Akaike information criteria. Proportions reclassified across guideline recommended intervention thresholds were also compared. RESULTS: We analyzed 53 172 participants: mean age 60 years; 48% female. Higher arm BP, compared with lower arm, reclassified 12% of participants at either 130 or 140 mm Hg systolic BP thresholds (both P< 0.001). Higher arm BP models fitted better for all-cause mortality, cardiovascular mortality, and cardiovascular events (all P P CONCLUSIONS: Using BP from higher instead of lower reading arms reclassified 12% of people over thresholds used to diagnose hypertension. All prediction models performed better when using the higher arm BP. Both arms should be measured for accurate diagnosis and management of hypertension. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: CRD42015031227.

Violence is defined as "the intentional use of physical force or power, threatened or actual, against oneself, another person, or against a group or community, that either results in or has a high likelihood of resulting in injury, death, psychological harm, maldevelopment, or deprivation." Encompassed in this definition are multiple, interrelated forms of violence, including interpersonal firearm death and injury, but also the systems, policies, and practices enacted by those with power to advantage some groups while depriving others of meaningful opportunities for meeting their basic needs-known as "structural violence". Yet dominant violence prevention narratives too often ignore or deemphasize the deeply intertwined threads of structural violence with other forms of violence, leading to policies and practices that are frequently insufficient, and often harmful, for reducing interpersonal firearm violence and building community safety, particularly in minoritized and structurally marginalized communities. We highlight ways in which limited scrutiny of structural violence, the omission of its defining characteristics-power and deprivation-from functional characterizations and frameworks of interpersonal firearm violence, and the inadequate distribution of power and resources to those most impacted by violence to self-determine narratives of and solutions to interpersonal firearm violence grossly impacts how interpersonal firearm violence is collectively conceived, discussed, and addressed. Expanding dominant narratives of interpersonal firearm violence, guided by the wisdom and determination of those most impacted, such that the goal of prevention and intervention efforts is not merely the absence of violence but rather the creation of a community safety and health ecosystem is essential to meet this critical moment in firearm violence research and prevention.

ObjectiveEvaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care.MethodsActive SLE patients (SLE Disease Activity Index 2000 (SLEDAI-2K) ≥6 during screening and SLEDAI-2K ≥4 for clinical features at week 0) despite receiving oral glucocorticoids, antimalarials, or immunomodulatory drugs were randomised (3:2) to receive ustekinumab (intravenous infusion ~6 mg/kg at week 0, followed by subcutaneous injections of ustekinumab 90 mg at week 8 and every 8 weeks) or placebo through week 48. The primary endpoint was SLE Responder Index (SRI)-4 at week 52, and major secondary endpoints included time to flare through week 52 and SRI-4 at week 24.ResultsAt baseline, 516 patients were randomised to placebo (n=208) or ustekinumab (n=308). Following the planned interim analysis, the sponsor discontinued the study due to lack of efficacy but no safety concerns. Efficacy analyses included 289 patients (placebo, n=116; ustekinumab, n=173) who completed or would have had a week 52 visit at study discontinuation. At week 52, 44% of ustekinumab patients and 56% of placebo patients had an SRI-4 response; there were no appreciable differences between the treatment groups in the major secondary endpoints. Through week 52, 28% of ustekinumab patients and 32% of placebo patients had a British Isles Lupus Assessment Group flare, with a mean time to first flare of 204.7 and 200.4 days, respectively. Through week 52, 70% of ustekinumab patients and 74% of placebo patients had ≥1 adverse event.ConclusionsUstekinumab did not demonstrate superiority over placebo in this population of adults with active SLE; adverse events were consistent with the known safety profile of ustekinumab.Trial registration numberNCT03517722.

PURPOSE: To evaluate the association between optical microangiography (OMAG) measurements and progressive ganglion cell-inner plexiform layer (GCIPL) loss in patients with primary open-angle glaucoma (POAG).DESIGN: Prospective case series.METHODS: Sixty-three eyes of 38 patients with POAG were studied for ≥2 years and with ≥ 3 optical coherence tomography examinations. Only those hemifields with mild to moderate functional damage at baseline (106 hemifields) were included in the analysis. OMAG imaging was performed at the baseline visit. The effects of clinical parameters (age, gender, central corneal thickness, presence of disc hemorrhage, and mean and fluctuation of intraocular pressure), baseline mean deviation, retinal nerve fiber layer, and GCIPL thickness and baseline OMAG measurements (peripapillary and macular perfusion density [PD] and vessel density [VD]) on the rate of change of GCIPL thickness were evaluated using linear mixed models.RESULTS: Average (± standard deviation) mean deviation, quadrant retinal nerve fiber layer, and sector GCIPL thickness of the analyzed hemifields respectively at baseline were -5.2 ± 2.8 dB, 94.5 ± 20.0 µm, and 72.4 ± 8.7 µm, respectively. Peripapillary PD and VD in the quadrant were 43.1% ± 7.0% and 17.0 ± 2.6 mm/mm2, respectively. Macular PD and VD in the quadrant were 37.2% ± 6.9% and 15.1 ± 2.6 mm/mm2, respectively. Rate of sector GCIPL change was -0.97 ± 0.15 µm per year. Multivariate mixed models showed that lower peripapillary PD (coefficient 0.04, P = .01) and VD (coefficient 0.09, P = .05) were significantly associated with a faster rate of GCIPL loss.CONCLUSIONS: Lower baseline peripapillary OMAG measurements were significantly associated with a faster rate of GCIPL loss in patients with mild to moderate POAG.

Background: Pediatric studies have shown associations between hepatic steatosis and total body fat, visceral fat, and lean mass. However, these associations have not been assessed simultaneously, leaving their relative importance unknown. Objective: To evaluate associations between hepatic steatosis and total-body adiposity, visceral adiposity, and lean mass in children. Method: In children at risk for fatty liver, hepatic steatosis, adipose, and lean mass were estimated with magnetic resonance imaging and dual-energy X-ray absorptiometry. Results: Two hundred twenty-seven children with mean age 12.1 years had mean percent body fat of 38.9% and mean liver fat of 8.4%. Liver fat was positively associated with total-body adiposity, visceral adiposity, and lean mass (P

Young men in South Africa face the intersecting epidemics of HIV, substance use and endemic poverty. We tested the effectiveness of a behavioral intervention using soccer training to reduce the cluster of risks associated with HIV and substance use. This cluster randomized controlled trial was conducted with men aged 18–29 years old in 27 neighborhoods in the townships of Cape Town, South Africa. Neighborhoods were randomized to receive for 6 months either: (1) Soccer League (SL; n = 18 neighborhoods, n = 778 men) who attended soccer three times weekly (72 sessions; 94% uptake, 45.5% weekly attendance rate), combined with an HIV/substance use, cognitive-behavioral intervention; or (2) a Control Condition (CC; n = 9; 415 men) who received educational materials and referrals at 3 month intervals. The primary outcome was the number of significant changes in a cluster of outcomes including HIV-related risks, substance abuse, employment/income, mental health, violence, and community engagement. There was only one significant difference on the rapid diagnostic tests for mandrax at 6 months, an insufficient number of changes to indicate a successful intervention. A group-based behavioral intervention was ineffective in addressing multiple risk behaviors among at-risk young men, similar to the findings of several recent soccer-related interventions. Early adulthood may be too late to alter well-established patterns of risk behaviors.Clinical Trial Registration This trial was prospectively registered on 24 November 2014 with ClinicalTrials.gov NCT02358226.

Introduction Previous studies show evidence for associations of prenatal exposure to organophosphate (OP) pesticides with poorer childhood neurodevelopment. As children grow older, poorer cognition, executive function, and school performance can give rise to risk-taking behaviors, including substance abuse, delinquency, and violent acts. We investigated whether prenatal OP exposure was associated with these risk-taking behaviors in adolescence and young adulthood in a Mexican American cohort. Methods We measured urinary dialkyl phosphates (DAPs), non-specific metabolites of OPs, twice (13 and 26 weeks gestation) in pregnant women recruited in 1999–2000 in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a birth cohort set in a primarily Latino agricultural community in the Salinas Valley, California. We followed up children throughout their childhood and adolescence; at the 18-year visit, adolescent youth (n = 315) completed a computer-based questionnaire which included questions about substance use, risky sexual activity, risky driving, and delinquency and police encounters. We used multivariable models to estimate associations of prenatal total DAPs with these risk-taking behaviors. Results The prevalence of risk-taking behaviors in CHAMACOS youth ranged from 8.9% for smoking or vaping nicotine to 70.2% for committing a delinquent act. Associations of total prenatal DAPs (geometric mean = 132.4 nmol/L) with risk-taking behavior were generally null and imprecise. Isolated findings included a higher risk for smoking or vaping nicotine within the past 30 days (relative risk [RR] per 10-fold increase in prenatal DAPs = 1.89, 95% CI: 1.00, 3.56) and driving without a license (RR = 1.74, 95% CI: 1.25, 2.42). There were no consistent differences by sex or childhood adversity. Discussion We did not find clear or consistent evidence for associations of prenatal OP exposure with risk-taking behaviors in adolescence/early adulthood in the CHAMACOS population. Our small sample size may have prevented us from detecting potentially subtle associations of early life OP exposure with these risk-taking behaviors.

Background Point-of-care ultrasound (POCUS) is a noninvasive bedside tool with many pediatric applications but is not currently a formal part of pediatric training and practice. Formal surveys of general pediatricians regarding POCUS training are lacking. We aimed to quantify the baseline ultrasound experience and training needs of general pediatricians and pediatric residents across different practice settings. Methods In 2020, we sent an online survey to 485 current faculty, residents, and graduates from an urban pediatric academic medical center in Northern California. Pediatric subspecialists were excluded. Survey questions about baseline experience, comfort, and perceived usefulness of 20 common POCUS applications were developed by two POCUS experts using existing literature. Chi-squared analysis was used to compare residents versus attendings and to compare attendings practicing in inpatient versus outpatient versus mixed settings. Results Response rate was 20% (98/485). Compared to attendings (n = 73), residents (n = 25) endorsed more exposure to POCUS in medical school (32% vs 5%, p = 0.003) and residency (12% vs 5%, p = 0.003). Respondents endorsed low comfort with POCUS (mean 1.3 out of 5 on Likert scale). Of 20 procedural and diagnostic applications, respondents identified abscess drainage, bladder catheterization, soft tissue, neck, advanced abdominal, and constipation as most useful. Overall, 50% of pediatricians (and 70% of pediatric residents) responded that there were opportunities to use POCUS multiple times a week or more in their clinical practice. Conclusions There is an unmet demand for POCUS training among general pediatricians and trainees in our study. Although the majority of respondents were not POCUS users, our results could guide future efforts to study the role of POCUS in general pediatrics and develop pediatric curricula.

Background The relationship between inadequate sleep duration and hypertension risk has been established in the general population, but there is a gap in the literature on predictors of habitual sleep duration in adults with hypertension. This study examined factors associated with habitual sleep duration among adults with hypertension in the United States (US). Methods Data of 5660 adults with hypertension were obtained by combining the 2015–2018 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey weighted multinomial logistic regression models were fit to examine factors associated with short ( 9 h) sleep duration with adequate sleep duration (7–9 h) as the reference. Results The prevalence of self-reported adequate sleep duration was 65.7%, while short sleep duration was 23.6%, and long sleep duration 10.7%. Short sleep duration (compared to adequate sleep duration) was positively associated with history of seeking help for sleeping difficulties (relative risk ratio [RRR], 1.25; 95% confidence interval [CI], 1.02–1.53), Non-Hispanic Black race/ethnicity (RRR, 2.08; 95% CI, 1.61–2.67), working ≥45 h/week (RRR, 1.81; 95% CI, 1.32–2.48), and negatively associated with older age ≥ 65 years (RRR, 0.63; 95% CI, 0.45–0.91) and female gender (RRR, 0.70; 95% CI, 0.56–0.88). Long sleep duration was positively associated with female gender (RRR, 1.24; 95% CI, 1.001–1.54), chronic kidney disease (RRR, 1.48; 95% CI, 1.14–1.92), moderate depressive symptoms (RRR, 1.62; 95% CI, 1.08–2.44), moderately severe to severe depressive symptoms (RRR, 1.89; 95% CI, 1.05–3.43), being in retirement (RRR, 3.46; 95% CI, 2.18–5.49), and not working due to health reasons (RRR, 4.87; 95% CI, 2.89–8.22) or other reasons (RRR, 3.29; 95% CI, 1.84–5.88). Conclusion This population-based study identified factors independently associated with habitual sleep duration in adults with hypertension. These included help-seeking for sleeping difficulty, gender, age, chronic kidney disease, depressive symptoms, race/ethnicity, and employment status. These findings can help in the development of tailored approaches for promoting adequate sleep duration in adults with hypertension.

Background Upcoming alternative payment models Primary Care First (PCF) and Kidney Care Choices (KCC) incorporate capitated payments for chronic disease management. Prior research on the effect of capitated payments on chronic disease management has shown mixed results. We assessed the patient, physician, and practice characteristics of practices with capitation as the majority of revenue, and evaluated the association of capitated reimbursement with quality of chronic disease care. Methods We performed a cross-sectional analysis of visits in the United States’ National Ambulatory Medical Care Survey (NAMCS) for patients with hypertension, diabetes, or chronic kidney disease (CKD). Our predictor was practice reimbursement type, classified as 1) majority capitation, 2) majority FFS, or 3) other reimbursement mix. Outcomes were quality indicators of hypertension control, diabetes control, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (ACEi/ARB) use, and statin use. Results About 9% of visits were to practices with majority capitation revenue. Capitated practices, compared with FFS and other practices, had lower visit frequency (3.7 vs. 5.2 vs. 5.2, p = 0.006), were more likely to be located in the West Census Region (55% vs. 18% vs. 17%, p p = 0.005), more likely to be owned by an insurance company, health plan or HMO (24% vs. 13% vs. 13%, p = 0.033), and more likely to have private insurance (43% vs. 25% vs. 19%, p = 0.004) and managed care payments (69% vs. 23% vs. 26%, p Conclusions Practices with majority capitation revenue differed substantially from FFS and other practices in patient, physician, and practice characteristics, but were not associated with consistent quality differences. Our findings establish baseline estimates of chronic disease quality of care performance by practice reimbursement composition, informing chronic disease care delivery within upcoming payment models.

Background Despite the growing interest in transformational performance improvement among nearly all countries, international benchmarking has rarely been used. Cross-comparative research could allow an appreciation of the extent of Lean’s use in healthcare and a better evaluation of possible cultural influences on Lean implementation. This study provides a comparative international benchmarking of Lean adoption, implementation, and outcomes of hospitals in the US and Italy. Methods The National Survey of Lean, developed in 2017 in the US and adapted in Italy in 2019 was used to compare the two healthcare systems along three dimensions: the maturity of adoption, the implementation approach, identifying both strategic and operational activities and tools, and the Lean performance, investigated through patients, employed, and affiliated staff, costs, and service provision areas. Descriptive statistics including T-tests were used to examine differences between the two countries on the study variables. Results Lean has been adopted less by Italian public hospitals (36%) than US public hospitals (53%). Each country averages 4 years of experience with Lean. Italian hospitals reported being at a higher maturity stage while the US implemented a more system-wide approach, developing Lean in more operational units. The daily management system, leadership commitment, education and training indexes were higher or the same in the US while in Italy, hospitals had a higher self-reported performance index. Conclusion This exploratory work is one of the first international benchmarking studies on Lean implementation in healthcare systems using a standardized survey with a common set of definitions and questions. The study identifies different forms of Lean implementation that can be adopted, both at strategic and operational levels, with related perceived outcomes. Despite the US public hospitals being more likely to report a higher number of units using Lean, a higher daily management system index and use of Lean tools, Italian hospitals report more achievements primarily due to Lean. Further research can build on these findings by examining the relationship between Lean adoption/implementation and independent, objective performance measures.

ObjectivesTo investigate factors associated with severe COVID-19 in people with psoriasis (PsO), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA).MethodsDemographic data, clinical characteristics and COVID-19 outcome severity of adults with PsO, PsA and axSpA were obtained from two international physician-reported registries. A three-point ordinal COVID-19 severity scale was defined: no hospitalisation, hospitalisation (and no death) and death. ORs were estimated using multivariable ordinal logistic regression.ResultsOf 5045 cases, 18.3% had PsO, 45.5% PsA and 36.3% axSpA. Most (83.6%) were not hospitalised, 14.6% were hospitalised and 1.8% died. Older age was non-linearly associated with COVID-19 severity. Male sex (OR 1.54, 95% CI 1.30 to 1.83), cardiovascular, respiratory, renal, metabolic and cancer comorbidities (ORs 1.25–2.89), moderate/high disease activity and/or glucocorticoid use (ORs 1.39–2.23, vs remission/low disease activity and no glucocorticoids) were associated with increased odds of severe COVID-19. Later pandemic time periods (ORs 0.42–0.52, vs until 15 June 2020), PsO (OR 0.49, 95% CI 0.37 to 0.65, vs PsA) and baseline exposure to TNFi, IL17i and IL-23i/IL-12+23i (OR 0.57, 95% CI 0.44 to 0.73; OR 0.62, 95% CI 0.45 to 0.87; OR 0.67, 95% CI 0.45 to 0.98; respectively; vs no disease-modifying antirheumatic drug) were associated with reduced odds of severe COVID-19.ConclusionOlder age, male sex, comorbidity burden, higher disease activity and glucocorticoid intake were associated with more severe COVID-19. Later pandemic time periods, PsO and exposure to TNFi, IL17i and IL-23i/IL-12+23i were associated with less severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with PsO, PsA and axSpA during COVID-19 waves or similar future respiratory pandemics.

Objective: In support of restarting during the COVID-19 pandemic, some schools partnered with local experts in academia, education, community, and public health to provide decision-support tools for determining what actions to take when presented with students at risk for spreading infection at school. Methods: The Student Symptom Decision Tree, developed in Orange County, California, is a flow chart consisting of branching logic and definitions to assist school personnel in making decisions regarding possible COVID-19 cases in schools, which was repeatedly updated to reflect evolving evidence-based guidelines. A survey of 56 school personnel evaluated the frequency of use, acceptability, feasibility, appropriateness, usability, and helpfulness of the Decision Tree. Results: The tool was used at least 6 times a week by 66% of respondents. The Decision Tree was generally perceived as acceptable (91%), feasible (70%), appropriate (89%), usable (71%), and helpful (95%). Suggestions for improvement included reducing the complexity in content and formatting of the tool. Conclusion: The data suggest that school personnel found value in the Decision Tree, which was intended to assist them with making decisions in a challenging and evolving pandemic.

Background Most medical educational programs emphasize clinical observation or clinical skill acquisition, fewer focus upon research. The Danish-American Research Exchange (DARE) program, sponsored by the Lundbeck Foundation, is unique in that the medical student initiates biomedical research collaboration between Danish and US medical institutions. To achieve this, Danish medical students (DARE students) conduct binational mentored research projects while based in the United States for 10 months. In addition, DARE students are introduced to interdisciplinary thinking about how to develop ultra-low-cost healthcare interventions through the ‘$10 Challenge’. Methods We conducted a cross-sectional study of DARE alumni over five consecutive years (2015–2020, n = 24). Research metrics included completion of a research project, primary authorship, and co-authorship of publications. The number of publications, prior to and after the DARE program were enumerated. For the first four cohorts, graduation from medical school and acceptance or intention to enter a joint MD-PhD program also were assessed. Two focus groups were conducted using constructivist grounded theory. Discussions were transcribed, redacted, and coded using Dedoose software. Results DARE Medical students were 31.2 years (range 24–35), the majority were women (67%;16/24). The majority (17/24;71%) completed a first author publication in a peer-reviewed journal with a median of 3.9 per DARE alumnus. DARE alumnus reported increased proficiency in biostatistics, epidemiology, coding and public speaking as well as stronger research qualities in creativity, critical thinking, comfort in approaching scientist in both the US and Denmark (p Conclusions Preliminarily, this study suggests that medical students can initiate binational collaboration in medicine. Benefits include research productivity, intention to pursue academic medical careers, as well as positive impacts on motivation. This medical student-initiated research model lays the groundwork for using this model across other country pairs to promote binational collaboration.

One Health is a transdisciplinary approach used to address complex concerns related to human, animal, plant, and ecosystem health. One Health frameworks and operational tools are available to support countries and communities, particularly for the prevention and control of zoonotic diseases and antimicrobial resistance and the protection of food safety. However, One Health has yet to be implemented in a manner that fully considers the complexities and interconnectedness of the diverse influences that have impacts at a larger system level. This lack of consideration can undermine the sustainability of any positive outcomes. To ensure the One Health approach can function effectively within the new global context of converging and escalating health, social, economic, and ecological crises, it must evolve and expand in three overlapping dimensions: (1) Scope: the partners, knowledge, and knowledge systems included, (2) Approach: the techniques, methodologies, and scholarship considered, and (3) Worldview inclusivity: the interweaving of other worldviews together with the mainstream scientific worldview that currently predominates. Diverse partners and knowledge from outside the mainstream health and scientific sectors, including Indigenous peoples and representatives of local communities, and traditionally generated knowledge, must be included. These systems of knowledge can then be braided together with mainstream science to comprise a holistic framework for decision-making. Scholarship and methodologies being applied in other fields and contexts to solve complex challenges and manage uncertainty, such as collaborative governance, social-ecologic systems theory, and complexity science, must be recognized and incorporated. The spectrum of considered worldviews must also expand to authentically integrate the expanded scope and approach into action and sustainable impact. By increasing community and social engagement and by recognizing and entwining different worldviews, the plurality of disciplines, and traditional and scientific ways of knowing to address community concerns in the contexts in which they exist, we can ensure that One Health remains effective and true to its paradigm in our rapidly changing and complex world.

The US Congress temporarily expanded the Child Tax Credit (CTC) during the COVID-19 pandemic to provide economic assistance for families with children. Although formerly the CTC provided $2,000 per child for mostly middle-income parents, during July-December 2021 it provided up to $3,600 per child. Eligibility criteria were also expanded to reach more economically disadvantaged families. There has been little research evaluating the effect of the policy expansion on mental health. Using data from the Census Bureau's Household Pulse Survey and a quasi-experimental study design, we examined the effects of the expanded CTC on mental health and related outcomes among low-income adults with children, and by racial and ethnic subgroup. We found fewer depressive and anxiety symptoms among low-income adults. Adults of Black, Hispanic, and other racial and ethnic backgrounds demonstrated greater reductions in anxiety symptoms compared to non-Hispanic White adults with children. There were no changes in mental health care use. These findings are important for Congress and state legislators to weigh as they consider making the expanded CTC and other similar tax credits permanent to support economically disadvantaged families.

ObjectivesThe COVID-19 pandemic accelerated telemedicine use nationally, but differences across health systems are understudied. We examine telemedicine use for adults with diabetes and/or hypertension across 10 health systems and analyze practice and patient characteristics associated with greater use.Study designEncounter-level data from the AMGA Optum Data Warehouse for March 13, 2020, to December 31, 2020, were analyzed, which included 3,016,761 clinical encounters from 764,521 adults with diabetes and/or hypertension attributed to 1 of 1207 practice sites with at least 50 system-attributed patients.MethodsLinear spline regression estimated whether practice size and ownership were associated with telemedicine during the adoption (weeks 0-4), de-adoption (weeks 5-12), and maintenance (weeks 13-42) periods, controlling for patient socioeconomic and clinical characteristics.ResultsTelemedicine use peaked at 11% to 42% of weekly encounters after 4 weeks. In adjusted analyses, small practices had lower telemedicine use for adults with diabetes during the maintenance period compared with larger practices. Practice ownership was not associated with telemedicine use. Practices with higher proportions of Black patients continued to expand telemedicine use during the de-adoption and maintenance periods.ConclusionsPractice ownership was not associated with telemedicine use during first months of the pandemic. Small practices de-adopted telemedicine to a greater degree than medium and large practices. Technical support for small practices, irrespective of their ownership, could enable telemedicine use for adults with diabetes and/or hypertension.

Background Antenatal care and skilled childbirth services are important interventions to improve maternal health and lower the risk of poor pregnancy outcomes and mortality. A growing body of literature has shown that geographic distance to clinics can be a disincentive towards seeking care during pregnancy. On the Thailand-Myanmar border antenatal clinics serving migrant populations have found high rates of loss to follow-up of 17.4%, but decades of civil conflict have made the underlying factors difficult to investigate. Here we perform a comprehensive study examining the geographic, demographic, and health-related factors contributing to loss to follow-up. Methods Using patient records we conducted a spatial and epidemiological analysis looking for predictors of loss to follow-up and pregnancy outcomes between 2007 and 2015. We used multivariable negative binomial regressions to assess for associations between distance travelled to the clinic and birth outcomes (loss to follow-up, pregnancy complications, and time of first presentation for antenatal care.) Results We found distance travelled to clinic strongly predicts loss to follow-up, miscarriage, malaria infections in pregnancy, and presentation for antenatal care after the first trimester. People lost to follow-up travelled 50% farther than people who had a normal singleton childbirth (a ratio of distances (DR) 1.5; 95% confidence interval (CI): 1.4 – 1.5). People with pregnancies complicated by miscarriage travelled 20% farther than those who did not have miscarriages (DR: 1.2; CI 1.1–1.3), and those with Plasmodium falciparum malaria in pregnancy travelled 60% farther than those without P. falciparum (DR: 1.6; CI: 1.6 – 1.8). People who delayed antenatal care until the third trimester travelled 50% farther compared to people who attended in the first trimester (DR: 1.5; CI: 1.4 – 1.5). Conclusions This analysis provides the first evidence of the complex impact of geography on access to antenatal services and pregnancy outcomes in the rural, remote, and politically complex Thailand-Myanmar border region. These findings can be used to help guide evidence-based interventions to increase uptake of maternal healthcare both in the Thailand-Myanmar region and in other rural, remote, and politically complicated environments.

Measures of information processing speed vary between individuals and decline with age. Studies of aging twins suggest heritability may be as high as 67%. The Illumina HumanExome Bead Chip genotyping array was used to examine the association of rare coding variants with performance on the Digit-Symbol Substitution Test (DSST) in community-dwelling adults participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. DSST scores were available for 30,576 individuals of European ancestry from nine cohorts and for 5758 individuals of African ancestry from four cohorts who were older than 45 years and free of dementia and clinical stroke. Linear regression models adjusted for age and gender were used for analysis of single genetic variants, and the T5, T1, and T01 burden tests that aggregate the number of rare alleles by gene were also applied. Secondary analyses included further adjustment for education. Meta-analyses to combine cohort-specific results were carried out separately for each ancestry group. Variants in RNF19A reached the threshold for statistical significance (p = 2.01 × 10−6) using the T01 test in individuals of European descent. RNF19A belongs to the class of E3 ubiquitin ligases that confer substrate specificity when proteins are ubiquitinated and targeted for degradation through the 26S proteasome. Variants in SLC22A7 and OR51A7 were suggestively associated with DSST scores after adjustment for education for African-American participants and in the European cohorts, respectively. Further functional characterization of its substrates will be required to confirm the role of RNF19A in cognitive function.

Background Aedes (Stegomyia) albopictus (Skuse, 1894) is the main vector of dengue virus in China. The resistance to insecticides is a huge obstacle for the control of this species, and determining its resistance status and mechanisms in China is essential for the implementation of vector management strategies. Methods We have investigated the larval and adult resistance status of Ae. albopictus to deltamethrin in eight field populations in China. Mutations at the voltage-gated sodium channel gene, related to the knockdown resistance (kdr) effect, were detected by sequencing of PCR products. The eight field populations were examined for pyrethroid resistance using the World Health Organization standard bioassays, and the association between the mutations and phenotypic resistance was tested. Results The eight field populations of larvae of Ae. albopictus in China exhibited high resistance to deltamethrin; the RR50 values ranged from 12 (ZJ) to 44 (GZ). Adult bioassay revealed that Ae. albopictus populations were resistant to deltamethrin (mortality rate Conclusion There were different degrees of resistance to deltamethrin in field Ae. albopictus populations in China. The longest knockdown time and lowest mortality rate observed in Ae. albopictus population in Guangzhou indicate the severity of high resistance to deltamethrin. The patchy distribution of deltamethrin resistance and kdr mutations in Ae. albopictus mosquitoes suggests the necessity for resistance management and developing counter measures to mitigate the spread of resistance. Graphical Abstract

The volume of subcortical structures represents a reliable, quantitative, and objective phenotype that captures genetic effects, environmental effects such as trauma, and disease effects such as posttraumatic stress disorder (PTSD). Trauma and PTSD represent potent exposures that may interact with genetic markers to influence brain structure and function. Genetic variants, associated with subcortical volumes in two large normative discovery samples, were used to compute polygenic scores (PGS) for the volume of seven subcortical structures. These were applied to a target sample enriched for childhood trauma and PTSD. Subcortical volume PGS from the discovery sample were strongly associated in our trauma/PTSD enriched sample (n = 7580) with respective subcortical volumes of the hippocampus (p = 1.10 × 10−20), thalamus (p = 7.46 × 10−10), caudate (p = 1.97 × 10−18), putamen (p = 1.7 × 10−12), and nucleus accumbens (p = 1.99 × 10−7). We found a significant association between the hippocampal volume PGS and hippocampal volume in control subjects from our sample, but was absent in individuals with PTSD (GxE; (beta = −0.10, p = 0.027)). This significant GxE (PGS × PTSD) relationship persisted (p −19) in four out of five threshold peaks (0.024, 0.133, 0.487, 0.730, and 0.889) used to calculate hippocampal volume PGSs. We detected similar GxE (G × ChildTrauma) relationships in the amygdala for exposure to childhood trauma (rs4702973; p = 2.16 × 10−7) or PTSD (rs10861272; p = 1.78 × 10−6) in the CHST11 gene. The hippocampus and amygdala are pivotal brain structures in mediating PTSD symptomatology. Trauma exposure and PTSD modulate the effect of polygenic markers on hippocampal volume (GxE) and the amygdala volume PGS is associated with PTSD risk, which supports the role of amygdala volume as a risk factor for PTSD.

Background While few countries and healthcare systems are on track to meet the World Health Organization’s hepatitis C virus (HCV) elimination goals, the US Veterans Health Administration (VHA) has been a leader in these efforts. We aimed to determine which implementation strategies were associated with successful national viral elimination implementation within the VHA. Methods We conducted a five-year, longitudinal cohort study of the VHA Hepatic Innovation Team (HIT) Collaborative between October 2015 and September 2019. Participants from 130 VHA medical centers treating HCV were sent annual electronic surveys about their use of 73 implementation strategies, organized into nine clusters as described by the Expert Recommendations for Implementing Change taxonomy. Descriptive and nonparametric analyses assessed strategy use over time, strategy attribution to the HIT, and strategy associations with site HCV treatment volume and rate of adoption, following the Theory of Diffusion of Innovations. Results Between 58 and 109 medical centers provided responses in each year, including 127 (98%) responding at least once, and 54 (42%) responding in all four implementation years. A median of 13–27 strategies were endorsed per year, and 8–36 individual strategies were significantly associated with treatment volume per year. Data warehousing, tailoring, and patient-facing strategies were most commonly endorsed. One strategy—“identify early adopters to learn from their experiences”—was significantly associated with HCV treatment volume in each year. Peak implementation year was associated with revising professional roles, providing local technical assistance, using data warehousing (i.e., dashboard population management), and identifying and preparing champions. Many of the strategies were driven by a national learning collaborative, which was instrumental in successful HCV elimination. Conclusions VHA’s tremendous success in rapidly treating nearly all Veterans with HCV can provide a roadmap for other HCV elimination initiatives.

ObjectiveTo determine predictors of change in neuropsychiatric (NP) event status in a large, prospective, international inception cohort of patients with systemic lupus erythematosus (SLE).MethodsUpon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician-determined resolution were documented. Factors potentially associated with the onset and resolution of NP events were determined by time-to-event analysis using a multistate modeling structure.ResultsNP events occurred in 955 (52.3%) of 1,827 patients, and 593 (31.0%) of 1,910 unique events were attributed to SLE. For SLE-associated NP (SLE NP) events, multivariate analysis revealed a positive association with male sex (P=0.028), concurrent non-SLE NP events excluding headache (P < 0.001), active SLE (P = 0.012), and glucocorticoid use (P = 0.008). There was a negative association with Asian race (P = 0.002), postsecondary education (P = 0.001), and treatment with immunosuppressive drugs (P = 0.019) or antimalarial drugs (P = 0.056). For non-SLE NP events excluding headache, there was a positive association with concurrent SLE NP events (P < 0.001) and a negative association with African race (P = 0.012) and Asian race (P < 0.001). NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache, which had comparable resolution rates. For SLE NP events, multivariate analysis revealed that resolution was more common in patients of Asian race (P = 0.006) and for central/focal NP events (P < 0.001). For non-SLE NP events, resolution was more common in patients of African race (P = 0.017) and less common in patients who were older at SLE diagnosis (P < 0.001).ConclusionIn a large and long-term study of the occurrence and resolution of NP events in SLE, we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.

PurposeTo investigate the association of vision-related quality of life (VRQOL) with the central visual field and macular ganglion cell complex (GCC) thickness in healthy control participants, patients with preperimetric glaucoma, and patients with perimetric glaucoma.DesignRetrospective cross-sectional study.MethodsA total of 39 healthy, 34 preperimetric glaucoma, and 145 perimetric glaucoma patients completed the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). A linear mixed-effect models was used to investigate the association between the glaucoma stage as measured by binocular 10-2 visual field mean sensitivity (VFMS) and GCC thickness with the Rasch-calibrated NEI-VFQ score.ResultsA total of 436 eyes from 218 participants (mean age=67.2 [95% CI=65.1 to 69.2] years) were enrolled. VRQOL calculated by the NEI-VFQ Rasch-calibrated score was worst for patients with perimetric glaucoma (50.7 [95% CI=47.2 to 54.2]), followed by patients with preperimetric glaucoma (41.2 [95% CI=34.5 to 47.9]) and healthy controls (29.3 [95% CI=24.0 to 34.7]. Worse VRQOL had a moderate association with a worse global binocular 10-2 VFMS (-3.4 [95% CI=-5.0 to -1.9] dB per 1 score; P < .001; adjusted R2=0.27), but not with a thinner global GCC in the better eye (-0.1 [95% CI=-0.2 to 0.1] µm per 1 score; P =.0485; adjusted R2=0.17).ConclusionsThese findings suggest that patients with perimetric and preperimetric glaucoma have worse VRQOL than patients with healthy eyes. As compared to macular thickness measurements, the central visual field is more strongly associated with VRQOL and may better help to identify patients in need of intervention.

PurposeWe compared ganglion cell layer (GCL) and inner plexiform layer (IPL) rates of change (RoC) in patients with glaucoma suspect (GS) and established glaucoma (EG) to test the hypothesis that IPL thickness changes would occur earlier than GCL changes in eyes with early damage.DesignProspective, cohort study.MethodsA total of 64 GS eyes (46 patients) and 112 EG eyes (112 patients) with ≥2 years of follow-up and ≥3 macular optical coherence tomography scans were included. GCL and IPL superpixel thickness measurements were exported. A Bayesian hierarchical model with random intercepts/slopes and random residual variances was fitted to estimate RoC in individual superpixels. Normalized RoC and proportions of superpixels with significantly negative and positive GCL and IPL RoC were compared within the groups.ResultsThe average (SD) follow-up time and number of scans were 3.5 (0.7) years and 4.2 (1.0), respectively, in the GS group and 3.6 (0.4) years and 7.3 (1.1) in the EG group. Mean (SD) normalized RoC was faster for GCL than IPL (-0.69 [0.05] vs -0.33 [0.04]) in the GS group, whereas it was faster for IPL (-0.47 [0.03] vs -0.28 [0.02]) in EG eyes. GCL RoC were significantly negative in 24 of 36 superpixels compared with 8 of 36 for IPL (P < .001) in GS eyes. In the EG group, 23 of 36 superpixels had significant negative IPL RoC compared with 13 of 36 superpixels for GCL (P=.006).ConclusionsGCL thickness is more likely to demonstrate change over time compared with IPL in glaucoma suspects. There is no evidence of preferential IPL thinning in eyes with suspected early glaucoma damage.

Background Physical activity may protect the mental health of medical students, yet it is unknown which types and intensities of physical activity have the greatest potential to improve medical student well-being. Objective We characterize the relationship between exercise intensity and stress levels of U.S. medical students, thereby informing the design of future well-being interventions. Design Two cross-sectional validated surveys assessing stress and physical activity were administered one year apart at the David Geffen School of Medicine at UCLA. A total of 1,046 out of 1,392 medical students responded (75%). An ordered logistic regression was used to determine the association between stress and each level of exercise intensity (inactivity, moderate-activity, and health-enhancing physical activity [HEPA]). These exercise intensity groupings were compared to the CDC guidelines for aerobic exercise. Results While achieving either moderate-activity or HEPA is compliant with the CDC guidelines for aerobic exercise, the additional intensity of exercise required to achieve HEPA was associated with a 26% increase in the probability of being in the lowest stress quartile and a 22% decrease in the probability of being in the highest stress quartile. Medical student physical activity levels were on-par with the national average per the CDC exercise guidelines (65% vs. 58%), but medical student HEPA levels were significantly lower than the national average (27% vs. 64%; OR 0.21; 95% CI 0.12–0.37). Conclusions There is a large disparity in rates of the highest intensity physical activity (HEPA) between medical students and the age-adjusted national average, which has previously been overlooked by the binary CDC exercise guidelines. The fact that HEPA levels are not optimized and more strongly associated with lower stress levels relative to less intense forms of exercise makes it a promising new target for future well-being interventions among medical trainees.

ObjectiveTo develop a new caregiver-assisted pain coping skills training protocol specifically tailored for community-dwelling persons with cognitive impairment and pain, and assess its feasibility and acceptability.MethodIn Phase I, we conducted interviews with 10 patient–caregiver dyads to gather feedback about intervention content and delivery. Phase II was a single-arm pilot test to evaluate the intervention's feasibility and acceptability. Dyads in the pilot study (n = 11) completed baseline surveys, received five intervention sessions, and then completed post-intervention surveys. Analyses focused on feasibility and acceptability.ResultsDyads responded positively to the pain coping skills presented in the interviews; their feedback was used to refine the intervention. Findings from the pilot study suggested that the intervention was feasible and acceptable. 69% of eligible dyads consented, 82% completed all five intervention sessions, and 100% completed the post-treatment assessment. Caregivers reported high satisfaction ratings. They also reported using the pain coping skills on a regular basis, and that they found most of the skills helpful and easy to use.Significance of resultsThese preliminary findings suggest that a caregiver-assisted pain coping skills intervention is feasible and acceptable, and that it may be a promising approach to managing pain in patients with cognitive impairment.

Background Clozapine clinics can facilitate greater access to clozapine, but there is a paucity of data on their structure in the US. Methods A 23-item survey was administered to participants recruited from the SMI Adviser Clozapine Center of Excellence listserv to understand characteristics of clozapine clinics. Results Clozapine clinics (N = 32) had a median caseload of 45 (IQR = 21–88) patients and utilized a median of 5 (IQR = 4–6) interdisciplinary roles. The most common roles included psychiatrists (100%), pharmacists (65.6%), nurses (65.6%), psychiatric nurse practitioners (53.1%), and case managers (53.1%). The majority of clinics outreached to patients who were overdue for labs (78.1%) and had access to on-site phlebotomy (62.5%). Less than half had on call services (46.9%). Conclusions In this first systematic description of clozapine clinics in the US, there was variation in the size, staffing, and services offered. These findings may serve as a window into configurations of clozapine teams.

AimTo compare the repeatability of peripapillary perfusion density and flux index measurements on referenced and non-referenced optical microangiography (OMAG) scans in normal, glaucoma suspect and glaucoma eyes.MethodsIn a cross-sectional study, 48 eyes (33 subjects) underwent three repeat, non-referenced peripapillary OMAG scans in the same session and 43 eyes (25 subjects) underwent three referenced peripapillary OMAG scans. In the referenced scan group, repeat scans (second and the third scan) were acquired exactly on the baseline (first) scan using the ‘track to prior scan’ option on the device. Repeatability estimates of the mean and four-sector (temporal, superior, nasal and inferior) OMAG measurements on the non-referenced and referenced scans were assessed using within-subject coefficient of repeatability (CRw) and variation (CVw).ResultsCRw (%) of peripapillary perfusion density measurements (range: 2.0–4.1) on non-referenced scans were significantly higher than that on referenced scans (range: 1.4–2.7). CVw (%) on non-referenced and referenced scans ranged from 1.7 to 3.1 and from 1.2 to 2.1, respectively . CRw of flux index on non-referenced and referenced scans ranged from 4.4 to 5.8 and from 3.6 to 4.8, respectively. CVw on non-referenced and referenced scans ranged from 4.1 to 5.2 and from 3.3 to 4.5, respectively.ConclusionsRepeatability estimates of OMAG measurements were better on referenced scans compared with non-referenced scans. Perfusion density measurements had lower variability than flux index. OCTA-measured perfusion density of referenced scans is preferable for monitoring vascular change in glaucoma.

Background Environmental conditions affect the biology of mosquito vectors. Aedes albopictus is a major vector of many important diseases including dengue, Zika, and chikungunya in China. Understanding the development, fecundity, and survivorship of Ae. albopictus mosquitoes in different environmental conditions is beneficial for the implementation of effective vector control measures. Methods Aedes albopictus larval and adult life-table experiments were conducted under natural conditions in indoor, half-shaded, and fully shaded settings, simulating the three major habitat types in Hainan Province, a tropical island in the South China Sea. Temperature, humidity, and light intensity were recorded daily. Larval rearing used habitat water and tap water, with and without additional artificial food. Development time, survivorship, pupation rate, and adult emergence rates were monitored. Adult mosquito survivorship and fecundity were monitored daily and reproductive rates were determined, and age-dependent survivorship and reproduction were analyzed. Results The pupation time and male and female emergence times were significantly shorter in indoor conditions than in shaded and half-shaded conditions for both tap water with added food and habitat water with added food groups. For habitat water with added food, the shaded environment had the lowest pupation rate among the settings. For tap water with added food group, the shaded environment had the lowest pupation rate. The mean survival time of females was 27.3 ± 0.8 days in the indoor condition, which was significantly longer than that in the half-shaded (18.4 ± 0.6 days) and shaded (13.8 ± 1.2 days) conditions. Adult mortality was age-dependent, and the rate of change in mortality with age was not significantly different among different environmental conditions. The mean net replacement rate (R0) of female mosquitoes showed no significant difference among the three conditions, whereas the per capita intrinsic growth rate (r) in the shaded condition was 42.0% and 20.4% higher than that in the indoor and half-shaded conditions, respectively. Female daily egg mass was also age-dependent in all the settings, decaying exponentially with age. Conclusions Our results imply that half-shaded conditions are likely the best natural condition for adult emergence and female reproduction, and food supply is crucial for larval development and pupation. The results provide new avenues for integrated mosquito management in indoor and outdoor areas, especially in half-shaded areas. Graphical Abstract

Inter-related sustained upward trends in firearm purchasing, violence, and political extremism are converging to put the USA at risk for disaster and threaten our future as a democracy. This narrative review provides a critical assessment and call to action. It explores each trend separately, considers the effects of their likely and imminent convergence, and suggests possibilities for collective and individual action to prevent or at least reduce those effects.

Background In Mozambique, HIV infection disproportionately affects young adults, particularly women. Despite awareness and knowledge of HIV transmission, many university students have not received HIV testing and continue to engage in high-risk sexual behaviors, including inconsistent condom use. Further understanding of patterns of engagement with HIV prevention and testing is key to reducing HIV transmission in this at-risk population. Methods This study used a sequential mixed methods approach to examine patterns of engagement and perceptions of HIV prevention and testing services among higher education students in Mozambique. Survey data were collected from a representative sample of 501 students from Universidade Eduardo Mondlane (UEM) in Maputo, Mozambique to assess the primary outcomes of 1) HIV testing within the last 12 months; and 2) condom use during last sexual encounter. We employed univariate and multivariate regression models. The survey was followed by qualitative interviews with 70 survey participants which were analyzed using an inductive, content-focused analysis to further explain and contextualize survey findings. Results Over 85% of students reported to be sexually active, among these 74% reported condom use during their last sexual encounter, and 64.2% reported an HIV test within the past 12 months. Females were more likely to have had HIV testing in the past 12 months in comparison to their male peers (aOR 1.82, 95% CI 1.11, 2.99), but were half as likely to have used a condom with their last sexual encounter (aOR 0.52, 95% CI 0.33, 0.83), when controlling for other factors. Qualitative data suggests that these discrepancies may be explained by differential perceptions in risk and trust/mistrust, with women being more concerned about infidelity by their male partner(s) and assuming more responsibility for knowing their own serostatus. Women were also subject to negative stereotypes for possessing condoms in comparison to men, which could explain lower propensity for use. Conclusion Given gendered differences in uptake of condom use and HIV testing, and perceived HIV risk, interventions tailored specifically to male and female students may impact engagement with HIV prevention and testing and empower informed choices about sexual behaviors.

Background Irrigation schemes may result in subsequent changes in malaria disease dynamics. Understanding the mechanisms and effects of irrigation on malaria vector bionomics and transmission intensity is essential to develop new or alternative surveillance and control strategies to reduce or control malaria risk. This study was designed to assess the effect of rice irrigation on malaria vector bionomics and transmission intensity in the Gambella Region, Ethiopia. Methods Comparative cross-sectional study was conducted in Abobo District of the Gambella Region, Ethiopia. Accordingly, clusters (kebeles) were classified into nearby and faraway clusters depending on their proximity to the irrigation scheme. Adult mosquito survey was conducted in February, August and November 2018 from three nearby and three faraway clusters using Centers for Disease Control and Prevention (CDC) light traps (LTs). During the November survey, human landing catch (HLC) and pyrethrum spray catch (PSC) were also conducted. The collected mosquitoes were morphologically identified to species and tested for Plasmodium infection using circumsporozoite protein enzyme-linked immunosorbent assay (CSP-ELISA). Furthermore, species-specific polymerase chain reaction (PCR) was performed to identify member species of the Anopheles gambiae complex. Chi-square and t-tests were used to analyze the data using the SPSS version 20 software package. Results A total of 4319 female anopheline mosquitoes comprising An. gambiae sensu lato, An. funestus group, An. pharoensis, An. coustani complex and An. squamosus were collected. Overall, 84.5% and 15.5% of the anopheline mosquitoes were collected from the nearby and faraway clusters, respectively. Anopheles gambiae s.l. was the predominant (56.2%) anopheline species in the area followed by An. pharoensis (15.7%). The density of anopheline mosquitoes was significantly higher in the nearby clusters in both HLCs [t(3) = 5.14, P = 0.0143] and CDC LT catches [t(271.97) = 7.446, P Conclusions Significantly higher mosquito population density was observed in areas close to the irrigation sites. Sporozoite infection rate in the mosquito population was also markedly higher from the nearby clusters. Therefore, the irrigation scheme could increase the risk of malaria in the area. Graphical abstract

Abstract Solitary confinement is a widespread practice in US correctional facilities. Long-standing concerns about the physical and mental health effects of solitary confinement have led to litigation, legislation, and community activism resulting in many prison systems introducing policies or implementing legal mandates to reduce or eliminate its use. Yet little is known about the nature and effectiveness of policies that states have adopted to reduce their use of solitary confinement and exactly how various reforms have actually impacted the lives of people living and working in the prisons where these reforms have taken place. Methods We conducted an embedded case study, analyzing changes in policies and procedures, administrative data, and focus groups and interviews with incarcerated persons and staff, to describe the circumstances that led to changes in solitary confinement policies and practices in the North Dakota Department of Corrections and Rehabilitation (ND DOCR) and the perceived impact of these changes on incarcerated persons and prison staff. Results North Dakota’s correctional officials and staff members attributed the impetus to change their solitary confinement policies to their participation in a program that directly exposed them to the Norwegian Correctional Service’s philosophy, policies, and practices in 2015. The ensuing policy changes made by North Dakota officials were swift and resulted in a 74.28% reduction in the use of solitary confinement between 2016 and 2020. Additionally, placements in any form of restrictive housing decreased markedly for incarcerated persons with serious mental illness. In the two prisons that had solitary confinement units, rule infractions involving violence decreased at one prison overall and it decreased within the units at both prisons that were previously used for solitary confinement. Although fights and assaults between incarcerated people increased in one of the prison’s general population units, during the initial months of reforms, these events continued to decline compared to years before reform. Moreover, incarcerated people and staff attributed the rise to a concomitant worsening of conditions in the general population due to overcrowding, idleness, and double bunking. Both incarcerated persons and staff members reported improvements in their health and well-being, enhanced interactions with one another, and less exposure to violence following the reforms. Conclusions Immersing correctional leaders in the Norwegian Correctional Service’s public health and human rights principles motivated and guided the ND DOCR to pursue policy changes to decrease the use of solitary confinement in their prisons. Ensuing reductions in solitary confinement were experienced as beneficial to the health and wellness of incarcerated persons and staff alike. This case-study describes these policy changes and the perspectives of staff and incarcerated persons about the reforms that were undertaken. Findings have implications for stakeholders seeking to reduce their use of solitary confinement and limit its harmful consequences and underscore the need for research to describe and assess the impact of solitary confinement reforms.

Early exposure to psychosocial adversity is among the most potent predictors of depression. Because depression commonly emerges prior to adulthood, we must consider the fundamental principles of developmental neuroscience when examining how experiences of childhood adversity, including abuse and neglect, can lead to depression. Considering that both the environment and the brain are highly dynamic across the period spanning gestation through adolescence, the purpose of this review is to discuss and integrate stress-based models of depression that center developmental processes. We offer a general framework for understanding how psychosocial adversity in early life disrupts or calibrates the biobehavioral systems implicated in depression. Specifically, we propose that the sources and nature of the environmental input shaping the brain, and the mechanisms of neuroplasticity involved, change across development. We contend that the effects of adversity largely depend on the developmental stage of the organism. First, we summarize leading neurobiological models that focus on the effects of adversity on risk for mental disorders, including depression. In particular, we highlight models of allostatic load, acceleration maturation, dimensions of adversity, and sensitive or critical periods. Second, we expound on and review evidence for the formulation that distinct mechanisms of neuroplasticity are implicated depending on the timing of adverse experiences, and that inherent within certain windows of development are constraints on the sources and nature of these experiences. Finally, we consider other important facets of adverse experiences (e.g., environmental unpredictability, perceptions of one’s experiences) before discussing promising research directions for the future of the field.

Inhaled bronchodilators are central for the treatment of chronic obstructive pulmonary disease (COPD), as they can provide symptom relief and reduce the frequency and severity of exacerbations while improving health status and exercise tolerance. In 2017, glycopyrrolate (GLY) delivered via the eFlow® closed system (CS) nebulizer (nebulized GLY; 25 µg twice daily), was approved by the US Food and Drug Administration for maintenance treatment of moderate-to-very-severe COPD. This approval was based largely on results from the replicate, placebo-controlled, Phase III clinical trials- GOLDEN 3 and 4. In this review, we summarize key findings from secondary analyses of the GOLDEN 3 and 4 studies, and provide a comprehensive overview that may assist both pulmonologists and primary-care providers in their treatment decisions. Comorbidities are common among patients with COPD in clinical practice and may impact bronchodilator efficacy. This review highlights outcomes among subpopulations of patients with comorbidities (e.g., anxiety/depression, cardiovascular disease), and their impact on the efficacy of nebulized GLY. In addition, the efficacy and safety of nebulized GLY across various demographics (e.g., age, gender) and baseline disease characteristics (e.g., disease severity, rescue medication use) are discussed. Real-world outcomes with nebulized GLY, including device satisfaction, healthcare resource utilization, and exacerbations, are also presented. These secondary analyses and real-world data complement the primary results with nebulized GLY from Phase III studies and support the need for the inclusion of patients representative of real-world clinical practice in RCTs. In addition, these data suggest that RCTs for COPD therapies should be complemented with real-world observational studies.

Human cytomegalovirus (HCMV) is a neurotropic herpes virus known to cause neuropathology in patients with impaired immunity. Previously, we reported a reduction in the gray matter volume (GMV) of several brain regions in two independent samples of participants who were seropositive for HCMV (HCMV+) compared to matched participants who were seronegative for HCMV (HCMV−). In addition to an independent replication of the GMV findings, this study aimed to examine whether HCMV+ was associated with differences in resting-state functional connectivity (rsfMRI-FC). After balancing on 11 clinical/demographic variables using inverse probability of treatment weighting (IPTW), GMV and rsfMRI-FC were obtained from 99 participants with major depressive disorder (MDD) who were classified into 42 HCMV+ and 57 HCMV− individuals. Relative to the HCMV− group, the HCMV+ group showed a significant reduction of GMV in nine cortical regions. Volume reduction in the right lateral orbitofrontal cortex (standardized beta coefficient (SBC) = −0.32, [95%CI, −0.62 to −0.02]) and the left pars orbitalis (SBC = −0.34, [95%CI, −0.63 to −0.05]) in the HCMV+ group was also observed in the previous study. Regardless of the parcellation method or analytical approach, relative to the HCMV− group, the HCMV+ group showed hypoconnectivity between the hubs of the sensorimotor network (bilateral postcentral gyrus) and the hubs of the salience network (bilateral insula) with effect sizes ranging from SBC = −0.57 to −0.99. These findings support the hypothesis that a positive HCMV serostatus is associated with altered connectivity of regions that are important for stress and affective processing and further supports a possible etiological role of HCMV in depression.

Animal and human laboratory paradigms offer invaluable approaches to study the complex etiologies and mechanisms of alcohol use disorder (AUD). We contend that human laboratory models provide a “bridge” between preclinical and clinical studies of AUD by allowing for well-controlled experimental manipulations in humans with AUD. As such, examining the consilience between experimental models in animals and humans in the laboratory provides unique opportunities to refine the translational utility of such models. The overall goal of the present review is to provide a systematic description and contrast of commonly used animal paradigms for the study of AUD, as well as their human laboratory analogs if applicable. While there is a wide breadth of animal species in AUD research, the paradigms discussed in this review rely predominately on rodent research. The overarching goal of this effort is to provide critical analysis of these animal models and to link them to human laboratory models of AUD. By systematically contrasting preclinical and controlled human laboratory models, we seek to identify opportunities to enhance their translational value through forward and reverse translation. We provide future directions to reconcile differences between animal and human work and to improve translational research for AUD.

Background Utilization of basic public health services (BPHS) allows for disease prevention and management and is an essential component for protecting health. Disparities in utilization exist between rural-to-urban migrants and their local counterparts in China. This study sought to determine the frequency of BPHS utilization and whether social support, discrimination, and sociodemographic features were risk factors for low BPHS utilization by Chinese female migrants. Methods Data were derived from a survey of female rural-to-urban migrants at nine work sites in Changsha, China. The association between social support, discrimination, sociodemographic factors and BPHS utilization was obtained using Chi-square and logistic regression analysis. Results Between December 2017 and April 2018, 307 female participants completed the survey. A total of 24.7% reported having had health education, 26.1% had breast and cervical cancer screening, 27.2% had established a health care record, and 40.9% had received basic contraceptive services. Two factors were associated with the reduced likelihood of BPHS utilization: Length of migration and health record establishment (OR = 0.53; 95% CI = 0.31, 0.92) and years of education and basic contraceptive service use (OR = 0.36; 95% CI = 0.20, 0.67). The remaining six factors were associated with an increased likelihood of BPHS utilization: Living circumstances and health record establishment (OR = 2.11; 95% CI = 1.17, 3.80), health education (OR = 2.71; 95% CI = 1.51, 4.87) and cancer screening (OR = 2.38; 95% CI = 1.30, 4.36). Utilization of social support was associated with health record establishment (OR = 1.24; 95% CI = 1.06, 1.44), basic contraceptive service use (OR = 1.21; 95% CI = 1.04, 1.42) and cancer screening (OR = 1.29; 95% CI = 1.10, 1.51). Objective social support was associated with health education utilization (OR = 1.15; 95% CI = 1.04, 1.26), while subjective social support was associated with basic contraceptive service use (OR = 1.11; 95% CI = 1.05, 1.18) and cancer screening (OR = 1.10; 95% CI = 1.02, 1.17). Family location was associated with basic contraceptive service use (OR = 1.96; 95% CI = 1.12, 3.44) and migration time in Changsha was associated with basic contraceptive service use (OR = 2.24; 95% CI = 1.18, 4.27). Conclusions Overall, there was low utilization rate for four BPHS by Chinese female migrants, and social support appears to be an important factor in this setting. Government, community, and workplace education efforts for enhancing BPHS utilization among female rural-to-urban migrants are recommended.

Aims/hypothesis Type 2 diabetes is characterised by islet amyloid and toxic oligomers of islet amyloid polypeptide (IAPP). We posed the questions, (1) does IAPP toxicity induce an islet response comparable to that in humans with type 2 diabetes, and if so, (2) what are the key transcriptional drivers of this response? Methods The islet transcriptome was evaluated in five groups of mice: beta cell specific transgenic for (1) human IAPP, (2) rodent IAPP, (3) human calpastatin, (4) human calpastatin and human IAPP, and (5) wild-type mice. RNA sequencing data was analysed by differential expression analysis and gene co-expression network analysis to establish the islet response to adaptation to an increased beta cell workload of soluble rodent IAPP, the islet response to increased expression of oligomeric human IAPP, and the extent to which the latter was rescued by suppression of calpain hyperactivation by calpastatin. Rank-rank hypergeometric overlap analysis was used to compare the transcriptome of islets from human or rodent IAPP transgenic mice vs humans with prediabetes or type 2 diabetes. Results The islet transcriptomes in humans with prediabetes and type 2 diabetes are remarkably similar. Beta cell overexpression of soluble rodent or oligomer-prone human IAPP induced changes in islet transcriptome present in prediabetes and type 2 diabetes, including decreased expression of genes that confer beta cell identity. Increased expression of human IAPP, but not rodent IAPP, induced islet inflammation present in prediabetes and type 2 diabetes in humans. Key mediators of the injury responses in islets transgenic for human IAPP or those from individuals with type 2 diabetes include STAT3, NF-κB, ESR1 and CTNNB1 by transcription factor analysis and COL3A1, NID1 and ZNF800 by gene regulatory network analysis. Conclusions/interpretation Beta cell injury mediated by IAPP is a plausible mechanism to contribute to islet inflammation and dedifferentiation in type 2 diabetes. Inhibition of IAPP toxicity is a potential therapeutic target in type 2 diabetes. Graphical abstract

Background Health workforce planning is critical for health systems to safeguard the ability to afford, train, recruit, and retain the appropriate number and mix of health workers. This balance is especially important when macroeconomic structures are also reforming. The Kingdom of Saudi Arabia is moving toward greater diversification, privatization, and resiliency; health sector reform is a key pillar of this transition. Methods We used the Ministry of Health Yearbook data on the number of workers and health expenditures from 2007 to 2018 and projected health labor market supply and demand of workers through 2030, evaluated the potential shortages and surpluses, and simulated different policy scenarios to identify relevant interventions. We further focused on projections for health workers who are Saudi nationals and health worker demand within the public sector (versus the private sector) to inform national objectives of reducing dependency on foreign workers and better deploying public sector resources. Results We projected the overall health labor market to demand 9.07 physicians and nurses per 1,000 population (356,514) in 2030; the public sector will account for approximately 67% of this overall demand. Compared to a projected supply of 10.16 physicians and nurses per 1,000 population (399,354), we estimated an overall modest surplus of about 42,840 physicians and nurses in 2030. However, only about 17% of these workers are estimated to be Saudi nationals, for whom there will be a demand shortage of 287,895 workers. Among policy scenarios considered, increasing work hours had the largest effect on reducing shortages of Saudi workers, followed by bridge programs for training more nurses. Government resources can also be redirected to supporting more Saudi nurses while still ensuring adequate numbers of physicians to meet service delivery goals in 2030. Conclusion Despite projected overall balance in the labor market for health workers in 2030, without policy interventions, severe gaps in the Saudi workforce will persist and limit progress toward health system resiliency in Saudi Arabia. Both supply- and demand-side policy interventions should be considered, prioritizing those that increase productivity among Saudi health workers, enhance training for nurses, and strategically redeploy financial resources toward employing these workers.

Background The COVID-19 pandemic fundamentally changed every aspect of healthcare delivery and training. Few studies have reported on the impact of these changes on the experiences, skill development, and career expectations of medical students. Method Using 59 responses to a short reflection essay prompt, 3rd year medical students in Philadelphia described how the COVID-19 pandemic affected their education in mid-2020. Using conventional content analysis, six main themes were identified across 14 codes. Results Students reported concerns regarding their decreased clinical skill training and specialty exposure on their career development due to the loss of in-person experience during their family medicine clerkship. A small number felt very let down and exploited by the continued high cost of tuition while missing clinical interactions. However, many students also expressed professional pride and derived meaning from limited patient and mentorship opportunities. Many students developed a new sense of purpose and a call to become stronger public health and patient advocates. Conclusions The medical field will need to adapt to support medical students adversely impacted by the COVID-19 pandemic, from an educational and mental health standpoint. However, there are encouraging signs that this may also galvanize many students to engage in leadership roles in their communities, to become more empathetic and thoughtful physicians, and to redesign healthcare in the future to better meet the needs of their most vulnerable patients.

Background Primary small cell carcinoma of the pancreas (SCCP) is a rare malignant neuroendocrine carcinoma (NEC). Typically, it presents with lymphovascular invasion as well as metastasis at the time of diagnosis which portends a dismal prognosis. Treatment is typically based on therapy used for other aggressive NECs such as small cell lung cancer. Although multimodal surgery, radiation and chemotherapy may improve prognosis, the outcome generally remains poor. Case presentation Here we present a primary SCCP managed with neoadjuvant multi-agent chemotherapy combined with radiotherapy and surgery Conclusions Multi-disciplinary therapy resulted in an ongoing 28 + month radiographic complete response and overall survival.

Background: Despite the widespread knowledge about social support and health, there is little information about the association between social support and HIV risk behaviors such as condom use among female sex workers (FSWs) in Iran. This study aimed to determine the association between social support and frequency of condom use among FSWs in Tehran, Iran. Methods: Using mixed sampling methods, we recruited 170 FSWs in Tehran in 2017. We measured self-reported social support by face-to-face interviews using a standardized questionnaire. Linear regression was used to assess the association between socio-demographic characteristics (age, education level, marital status, and place of living), transactional sex characteristics (age at first transactional sex and frequency of transactional sex in the last month), HIV knowledge, social support network characteristics (social network size, duration of tie, intimacy, social support), and condom use behavior. Results: Of the total of 1193 persons in FSW’s social networks, 615 (51%) were sexual partners, 529 (44%) were peer sex workers, and 36 (5%) were family members. The participants perceived moderate social support from sexual partners, low from peer sex workers, and very low from family members. Adjusted for individual and other network characteristics, peer sex worker social support (b = 0.28, 95%CI 0.06, 0.50), and family support (b = 1.12, 95%CI 0.028, 2.23) were significantly associated with condom use. Conclusion: Family and peer sex worker social support are associated with condom use, but less strongly than HIV knowledge or place of living. However, very few FSWs are socially connected with families. Interventions to promote condom use among this vulnerable population should also consider social and familial support.

There has been a fundamental failure to translate preclinically supported research into clinically efficacious treatments for psychiatric disorders. One of the greatest impediments toward improving this species gap has been the difficulty of identifying translatable neurophysiological signals that are related to specific behavioral constructs. Here, we present evidence from three paradigms that were completed by humans and mice using analogous procedures, with each task eliciting candidate a priori defined electrophysiological signals underlying effortful motivation, reinforcement learning, and cognitive control. The effortful motivation was assessed using a progressive ratio breakpoint task, yielding a similar decrease in alpha-band activity over time in both species. Reinforcement learning was assessed via feedback in a probabilistic learning task with delta power significantly modulated by reward surprise in both species. Additionally, cognitive control was assessed in the five-choice continuous performance task, yielding response-locked theta power seen across species, and modulated by difficulty in humans. Together, these successes, and also the teachings from these failures, provide a roadmap towards the use of electrophysiology as a method for translating findings from the preclinical assays to the clinical settings.

International audience; Scope While cocoa flavanol (CF) consumption improves cardiovascular risk biomarkers, molecular mechanisms underlying their protective effects are not understood. Objective To investigate nutri(epi)genomic effects of CF and identify regulatory networks potential mediating vascular health benefits. Methods and Results Twenty healthy middle-aged men consume CF (bi-daily 450 mg) or control drinks for 1 month. Microarray analysis identifies 2235 differentially expressed genes (DEG) involved in processes regulating immune response, cell adhesion, or cytoskeleton organization. Distinct patterns of DEG correlate with CF-related changes in endothelial function, arterial stiffness, and blood pressure. DEG profile negatively correlates with expression profiles of cardiovascular disease patients. CF modulated DNA methylation profile of genes implicates in cell adhesion, actin cytoskeleton organization, or cell signaling. In silico docking analyses indicate that CF metabolites have the potential of binding to cell signaling proteins and transcription factors. Incubation of plasma obtained after CF consumption decrease monocyte to endothelial adhesion and dose-dependently increase nitric oxide-dependent chemotaxis of circulating angiogenic cells further validating the biological functions of CF metabolites. Conclusion In healthy humans, CF consumption may mediate vascular protective effects by modulating gene expression and DNA methylation towards a cardiovascular protective effect, in agreement with clinical results, by preserving integrity of immunological-endothelial barrier functions.

Background Women with prior severe preeclampsia are at an increased risk for cardiovascular diseases later in life compared to women who had a normotensive pregnancy. The objective of this study was to assess their needs and preferences regarding app-based cardiovascular health promotion. Methods Patients (n = 35) of the Follow-Up PreEClampsia Outpatient Clinic (FUPEC), Erasmus MC, the Netherlands, participated in an anonymous online survey. The main outcomes under study were women’s needs for health behavior promotion, and their preferences with respect to intervention delivery. Descriptive statistics were used to evaluate needs, and thematic analysis was used to analyze preferences. Results Women’s primary need for health behavior promotion pertained to their fat and sugar intake and physical activity; for some, to their mental health (practices), fruit and vegetable intake, salt intake, and water intake; and for a few, to their alcohol and tobacco use. Most women preferred an app-based intervention to include, in descending order: the tracking of health-related metrics, an interactive platform, the use of behavior change strategies, the provision of information, and personalization. Conclusion Cardiovascular health promotion targeting women with prior severe preeclampsia should feel relevant to its audience. App-based interventions are likely to be well received if they target fat and sugar intake and physical activity. These interventions should preferably track health-related metrics, be interactive, contain behavior change strategies, provide information, and be personalized. Adopting these findings during intervention design could potentially increase uptake, behavior change, and behavior change maintenance in this population.

Objective: To explore factors influencing COVID-19 vaccine decision-making among Black adults at high-risk for COVID-19 infection. Despite effective treatment and vaccination availability, Black Americans continue to be disproportionately impacted by COVID-19.Design, Setting, and Participants: Using community-engaged qualitative methods, we conducted virtual, semi-structured focus groups with Black residents in Los Angeles County before widespread vaccine rollout. Recruitment occurred through local com­munity partners.Methods: As part of a larger study exploring COVID-19 vaccine decision-making factors among multiethnic groups, two-hour virtual focus groups were conducted between December 15, 2020 and January 27, 2021. Transcripts were analyzed using reflexive thematic analysis.Main Outcome Measures: Themes and subthemes on factors for vaccine confi­dence and accessibility.Results: Three focus groups were con­ducted with 17 Black participants, who were primarily female (n=15), residents of high-poverty zip codes (n=11) and employed full-time (n=6). Black-specific considerations for vaccine confidence and accessibility include: 1) reduced confidence in COVID-19 vaccines due to historical gov­ernment inaction and racism (existing health inequities and disparities are rooted in rac­ism; historical unethical research practices); 2) misunderstanding of Black communities’ vaccine concerns (“vaccine hesitancy” as an inaccurate label to describe vaccine skepti­cism; ignorance to root causes of vaccine skepticism); and 3) recognizing and building on resources (community agency to address COVID-19 vaccine needs adequately).Conclusions: Vaccination campaigns should improve understanding of underlying vac­cination concerns to improve vaccine out­reach effectiveness and should partner with, provide resources to, and invest in local, trusted Black community entities to improve COVID-19 vaccination disparities.Ethn Dis. 2022;32(4):341-350; doi:10.18865/ed.32.4.341

Background: Though critical to primary care, continuity of care has rarely been examined in China. This study aims to assess the relationship between continuity of care and healthcare costs among patients with chronic diseases within primary care settings in China.Methods: In this cross-sectional study, we used a social health insurance claims dataset of 1406 patients with hypertension and/or diabetes in Yuhuan City, Zhejiang Province collected in 2017-2019. We measured continuity of care using the Bice-Boxerman Continuity of Care (COC) Index, Herfindahl Index (HI), Sequential Continuity of Care (SECON) Index, Usual Provider of Care (UPC), and a binary variable indicating whether a patient's UPC was a primary care provider. We examined the associations between continuity of care and healthcare costs in the same period and the subsequent year, using ordinary least squares regression for the outpatient costs and two-part regression for the inpatient costs. Based on the regression coefficients, we predicted costs saved if each continuity measure was set to 1 from the status quo.Results: When optimum continuity were to be achieved, 7.12-27.29% of total outpatient costs and 55.38-73.35% of total inpatient costs could be saved compared to the status quo during the two-year study period. If optimum continuity were to be achieved in the first year, 7.47%-21.78% of total outpatient costs and 8.84-40.22% of total inpatient costs could be saved in the second-year.Conclusions: Care continuity indicators were consistently associated with reduced outpatient costs and hospitalization risks. Future health reform in China should further enhance continuity of care in primary care.

ImportanceMost healthcare institutions require employees to be vaccinated against SARS-CoV-2 and many also require at least one booster.ObjectiveWe determine the impact of vaccine type, demographics, and health conditions on COVID-19 vaccine side effects in healthcare professionals.DesignA COVID-19 immunity study was performed at the 2021 American Association for Clinical Chemistry Annual Scientific meeting. As part of this study, a REDCap survey with cascading questions was administered from September 9, 2021 to October 20, 2021. General questions included participant demographics, past and present health conditions, smoking, exercise, and medications. COVID-19 specific questions asked about SARS-CoV-2 vaccine status and type, vaccine-associated side effects after each dose including any boosters, previous infection with COVID-19, diagnostic testing performed, and type and severity symptoms of COVID-19.ResultsThere were 975 participants (47.1% male, median age of 50 years) who completed the survey. Pfizer was the most commonly administered vaccine (56.4%) followed by Moderna (32.0%) and Johnson & Johnson (7.1%). There were no significant differences in vaccine type received by age, health conditions, smoking, exercise, or type or number of prescription medications. Side effects were reported more frequently after second dose (e.g., Moderna or Pfizer) (54.1%) or single/only dose of Johnson & Johnson (47.8%). Males were significantly more likely to report no side effects (p < 0.001), while females were significantly more likely to report injection site reactions (p < 0.001), fatigue (p < 0.001), headache (p < 0.001), muscle pain (p < 0.001), chills (p = 0.001), fever (p = 0.007), and nausea (p < 0.001). There was a significant upward trend in participants reporting no side effects with increasing age (p < 0.001). There were no significant trends in side effects among different races, ethnicities, health conditions, medications, smoking status or exercise. In multivariate logistic regressions analyses, the second dose of Moderna was associated with a significantly higher risk of side effects than both the second dose of Pfizer and the single dose of Johnson & Johnson.Conclusions and relevanceYounger people, females, and those receiving the second dose of Moderna had more COVID-19 vaccine side effects that per self-report led to moderate to severe limitations. As reported in other studies, the increase in side effects from Moderna may be explained by higher viral mRNA concentrations but be associated with additional protective immunity.