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Substantial evidence indicates that medical mistrust, resulting from experiences with discrimination and marginalisation, is a determinant of health disparities in minority populations. However, this research is largely limited to the US and other industrialised countries. To broaden our understanding of the role of medical mistrust on health-care decision making, we conducted a study on healthcare experiences and perceptions in a rural, underserved indigenous community in northwest Namibia (n = 86). Mixing semi-structured interview questions with the medical mistrust index (MMI), we aim to determine the relevance of the MMI in a non-industrialised population and compare index scores with reports of healthcare experiences. We find that medical mistrust is a salient concept in this community, mapping onto negative healthcare experiences and perceptions of discrimination. Reported healthcare experiences indicate that perceived incompetence, maltreatment and discrimination drive mistrust of medical personnel. However, reporting of recent healthcare experiences are generally positive. Our results indicate that the concept of medical mistrust can be usefully applied to communities in the Global South. These populations, like minority communities in the US, translate experiences of discrimination and marginalisation into medical mistrust. Understanding these processes can help address health disparities and aid in effective public health outreach in underserved populations.

PurposeThis study sought to understand family functioning surrounding weight in Mexican American women with obesity.MethodsSemi-structured in-depth interviews were conducted with mothers and adult daughters (N = 116).ResultsThematic analysis identified five themes. 1) The communication process drives perception of supportive messages. Messages perceived as non-supportive consist of directives as interventions, confirmation of faults, and critical compliments whereas supportive consist of compliments, encouragement, empathetic listening, and disclosure. 2) Acculturation differences interfere with intergenerational alliance. Differences involve dissonance in communication, behavioural expectations, and weight-related practices. 3) Maladaptive conflict responses contribute to relational strain. These responses include avoidance, withdrawal, and defensiveness. 4) Role transformations alter the generational hierarchical relationship. Daughters serve as role models, caregivers, or collaborators. 5) Low communal coping heightens psychological distress. It does so by challenging family roles, increasing social isolation, and compromising social support.ConclusionObesity interventions for Mexican American women may benefit from targeting relational skills to improve family functioning.

AimTo assess, from a United States (US) payer's perspective, the cost-effectiveness of gels designed to separate the endometrial surfaces (intrauterine spacers) placed following intrauterine surgery.Materials and methodsA decision tree model was developed to estimate the cost-effectiveness of intrauterine spacers used to facilitate endometrial repair and prevent the formation (primary prevention) and reformation (secondary prevention) of intrauterine adhesions (IUAs) and associated pregnancy- and birth-related adverse outcomes. Event rates and costs were extrapolated from data available in the existing literature. Sensitivity analyses were conducted to corroborate the base case results.ResultsIn this model, using intrauterine spacers for adhesion prevention led to net cost savings for US payers of $2,905 per patient over a 3.5-year time horizon. These savings were driven by the direct benefit of preventing procedures associated with IUA formation ($2,162 net savings) and the indirect benefit of preventing pregnancy-related complications often associated with IUA formation ($3,002). These factors offset the incremental cost of intrauterine spacer use of $1,539 based on an assumed price of $1,800 and the related increase in normal deliveries of $931. Model outcomes were sensitive to the probability of preterm and normal deliveries. Budget impact analyses show overall cost savings of $19.96 per initial member within a US healthcare plan, translating to $20 million over a 5-year time horizon for a one-million-member plan.LimitationsThere are no available data on the effects of intrauterine spacers or IUAs on patients' quality of life. Resultingly, the model could not evaluate patients' utility related to treatment with or without intrauterine spacers and instead focused on costs and events avoided.ConclusionThis analysis robustly demonstrated that intrauterine spacers would be cost-saving to healthcare payers, including both per-patient and per-plan member, through a reduction in IUAs and improvements to patients' pregnancy-related outcomes.

IntroductionTuberculosis (TB) preventive treatment (TPT) is recommended for people living with HIV (PLHIV) in high TB burden settings. While 6 months of daily isoniazid remains widely used, shorter regimens are now available. However, little is known about preferences of PLHIV for key features of TPT regimens.MethodsFrom July to November 2022, we conducted a discrete choice experiment among adult PLHIV engaged in care at an urban HIV clinic in Kampala, Uganda. Participants chose between two hypothetical TPT regimens with five different features (pills per dose, frequency, duration, need for adjusted antiretroviral therapy [ART] dosage and side effects), organized across nine random choice tasks. We analysed preferences using hierarchical Bayesian estimation, latent class analysis and willingness-to-trade simulations.ResultsOf 400 PLHIV, 392 (median age 44, 72% female, 91% TPT-experienced) had high-quality choice task responses. Pills per dose was the most important attribute (relative importance 32.4%, 95% confidence interval [CI] 31.6-33.2), followed by frequency (20.5% [95% CI 19.7-21.3]), duration (19.5% [95% CI 18.6-20.5]) and need for ART dosage adjustment (18.2% [95% CI 17.2-19.2]). Latent class analysis identified three preference groups: one prioritized less frequent, weekly dosing (N = 222; 57%); another was averse to ART dosage adjustment (N = 107; 27%); and the last prioritized short regimens with fewer side effects (N = 63; 16%). All groups highly valued fewer pills per dose. Overall, participants were willing to accept a regimen of 2.8 months' additional duration [95% CI: 2.4-3.2] to reduce pills per dose from five to one, 3.6 [95% CI 2.4-4.8] months for weekly rather than daily dosing and 2.2 [95% CI 1.3-3.0] months to avoid ART dosage adjustment.ConclusionsTo align with preferences of PLHIV in Uganda, decision-makers should prioritize the development and implementation of TPT regimens with fewer pills, less frequent dosing and no need for ART dosage adjustment, rather than focus primarily on duration of treatment.

Illness narratives invite practitioners to understand how biomedical and traditional health information is incorporated, integrated, or otherwise internalized into a patient's own sense of self and social identity. Such narratives also reveal cultural values, underlying patterns in society, and the overall life context of the narrator. Most illness narratives have been examined from the perspective of European-derived genres and literary theory, even though theorists from other parts of the globe have developed locally relevant literary theories. Further, illness narratives typically examine only the experience of illness through acute or chronic suffering (and potential recovery). The advent of biomedical disease prevention methods like post- and pre-exposure prophylaxis (PEP and PrEP) for HIV, which require daily pill consumption or regular injections, complicates the notion of an illness narrative by including illness prevention in narrative accounts. This paper has two aims. First, we aim to rectify the Eurocentrism of existing illness narrative theory by incorporating insights from African literary theorists; second, we complicate the category by examining prevention narratives as a subset of illness narratives. We do this by investigating several narratives of HIV prevention from informants enrolled in an HIV prevention trial in Kenya and Uganda in 2022.

BackgroundStudies on cannabis use and adverse cardiovascular outcomes have reported conflicting results. Research on its relationship to calcified arterial plaque remains limited.MethodsCross-sectional data from 2152 participants at Exam 6 (2016-2018) in the Multi-Ethnic Study of Atherosclerosis (MESA) were analyzed, including self-reported cannabis smoking patterns and carotid artery calcification (CAC) as measured via computed tomography. Multivariable relative and absolute risk regression models were used to estimate adjusted prevalence ratios (PRs) and prevalence differences, respectively, for the presence of calcified plaque. Multivariable linear regression was then used to compare group differences in the extent of CAC in those with calcified plaque.ResultsA minority of participants (n = 159, 7.4%) reported a history of regular cannabis smoking. Among all participants, 36.1% (n = 777) had detectable CAC. In models adjusted for demographics, behavioral, and clinical cardiovascular disease factors, a history of regular cannabis smoking was not associated with the prevalence of CAC in either common carotid artery (PR: 1.14, 95% CI: 0.88 to 1.49). In the subset of participants with calcified plaque, and in separate fully adjusted multivariable linear regression models, a history of regular cannabis smoking was not associated with increased calcium volume (difference = 7.7%, 95% CI: -21.8 to 48.5), calcium density (difference = 0.4%, 95% CI: -6.6 to 7.9), or Agatston score (difference = 32.1%, 95% CI: -31.8 to 155.8) in either carotid artery. Models exploring potential effect modification by age, race/ethnicity, and tobacco smoking status showed no significant association, except for higher CAC prevalence in men with a history of regular cannabis smoking.ConclusionsIn a racially and ethnically diverse cohort of older adults with a moderately high prevalence of CAC, no associations were found between a history of regular cannabis smoking, duration, or recency of cannabis smoking, and the prevalence of carotid calcified plaque. These findings were consistent across age, race/ethnicity, and cigarette smoking, except for an increased prevalence in men with a history of regular cannabis smoking. Similarly, in a subgroup with CAC, no association was found between a history of regular cannabis smoking and extent of calcification as measured by volume, density, and Agatston score.

HIV and substance abuse are common among young men, associated with a cluster of risk behaviors. Yet, most services addressing these challenges are delivered in setting underutilized by men and are often inconsistent with male identity. This cluster randomized controlled trial aimed to reduce multiple risk behaviors found among young men township areas on the outskirts of Cape Town, South Africa. Young men aged 18-29 years (N = 1193) across 27 neighborhoods were randomized by area to receive HIV-related skills training during either: (1) a 12-month soccer league (SL) intervention; (2) 6-month SL followed by 6 months of vocational training (VT) intervention (SL/VT, n = 9); or 3) a control condition (CC). Bayesian longitudinal mixture models were used to evaluate behaviors over time. Because we targeted multiple outcomes as our primary outcome, we analyzed if the number of significantly different outcomes between conditions exceeded chance for 13 measures over 18 months (with 83%, 76%, and 61% follow-up). Only if there were three significant benefits favoring the SL/VT over the SL would benefits be significant. Outcome measures included substance use, HIV-testing, protective sexual behaviors, violence, community engagement and mental health. Consistent participation in the SL was typically around 45% over time across conditions, however, only 17% of men completed SL/VT. There were no significant differences between conditions over time based on the number of study outcomes. These structural interventions were ineffective in addressing young men's substance abuse and risk for HIV.Clinical Trial Registration: This trial was prospectively registered on 24 November 2014 with ClinicalTrials.gov (NCT02358226).

Uptake of pre-exposure prophylaxis medication (PrEP) to prevent HIV among people who inject drugs (PWID) remains extremely low in the United States. West Virginia's rising HIV incidence and highest drug overdose rate in the nation makes it an important locus for opioid use and HIV risk interaction. In this pilot study we pioneered the use of Cultural Theory among PWID to understand HIV-related risk perception arising from four contrasting modes of social organization. Carried out during an HIV outbreak, we explored PrEP uptake qualitatively as a window onto risk perception. Of the 26 interviewees, 18 were HIV- and despite the medication's free availability from the health center where recruitment took place, none had taken PrEP, half considering they were not at risk. Intimate couples who showed characteristics of 'enclaves' considered the boundary around themselves protective against HIV, creating a safe space or 'invisible risk group'. Higher HIV risk was perceived among those who were housed compared to those living homeless. Beliefs about the causation of the local HIV outbreak and the validity of scientific research corresponded with characteristics of the contrasting modes of social organization and the approach is promising for informing public health interventions among PWID.

The pursuit of translational biomarkers is complex due to the heterogeneous human pathophysiology, but critical for disease diagnosis, prognosis, monitoring therapeutic efficacy, and for patient stratification. In HIV-associated neurocognitive impairment (NCI), biomarkers that delineate the trajectory of neuropathogenesis and neurocognitive sequelae are critical, particularly considering confounders such as substance use, including Methamphetamine (METH). METH use is a significant health concern among persons living with HIV (PWH), aggravating cognitive deficits and neuroinflammation despite of antiretrovirals, introducing elements in the microenvironment that are fundamentally differerent in relation to non-METH users, such as high levels of dopamine (DA) affecting HIV-innate immune targets. Yet, current biomarkers do not detect these differences. We hypothesized that predefined DA-induced signatures detectable in peripheral blood leukocytes, can distinguish HIV+ METH users compared to HIV-negative or PWH that are non METH users. The elevated expression of CD8A, CREBBP, CCL5, and combinations of dopaminergic pathway transcripts clustered METH users with detectable CSF viral load and major depressive disorder (MDD), indicating neuroimmune-mechanistic links. Cathecol-o-methyltransferase (COMT) gene polymorphisms affecting DA metabolism improved the identification of PWH using METH with biomarkers. The results indicate that underlying immunedopaminergic mechanisms provide signatures and genotypes that can identify PWH that are METH users and their attributes.

BackgroundResearch investigating the association between cigarette smoking and COVID-19 outcomes has yielded mixed results, often overlooking cannabis use. This study examined the association between cigarette smoking and COVID-19 hospitalization with consideration of cannabis use.MethodsWe used electronic health record data from adult patients with COVID-19 (2/1/2020 to 2/3/2022) at a northern California academic medical center. The outcome was COVID-19 hospitalization. We conducted three multivariable logistic models to examine the relationship between cigarette smoking and hospitalization. Model 1 included cigarette smoking status and other covariates; Model 2 added cannabis use status to Model 1; Model 3 added interaction term of cigarette and cannabis use to Model 2, followed by a post-hoc analysis.ResultsOf the 14,440 patients, 8.5 % had COVID-19 hospitalization, 4.9 % and 24.1 % currently and formerly smoked cigarettes, respectively; 7.2 % currently used cannabis, 62.8 % had unknown cannabis use status. Both current and former cigarettes smoking were associated with hospitalization (Models 1-2). In Model 3, the cigarette-cannabis interaction was significant. Former cigarette smoking had higher odds for hospitalization (adjusted odds ratio [AOR] = 1.36; 95 % confidence interval [CI] 1.09-1.70) only among people who did not currently use cannabis. Current cigarette smoking yielded higher odds of hospitalization (AOR = 1.47; 95 % CI 1.02-2.12) among people whose cannabis use was unknown. Cigarette smoking status was not associated with hospitalization among people who currently used cannabis.ConclusionsCigarette smoking's associations with COVID-19 hospitalization varied by cannabis use. Future research should include both cigarette and cannabis use in understanding risk factors for COVID-19 outcomes.

Reducing racial and socioeconomic inequities in smoking has been declared a priority for tobacco control in the USA for several decades. Yet despite the rhetoric, these inequities persist and some have actually worsened over time. Although tobacco companies have targeted racially and ethnically diverse and lower-income tobacco users, which substantially contributes to these disparities, less attention has been given to the role of individuals and organisations within the tobacco control movement who have allowed progress in eliminating disparities to stagnate. We examine the failure of tobacco control professionals to ensure the widespread adoption of equity-focused tobacco control strategies. Review of major US tobacco control reports found that the focus on equity often stops after describing inequities in tobacco use. We suggest ways to advance equity in tobacco control in the USA. These recommendations fall across five categories: surveillance, interventions, funding, accountability and addressing root causes. Policy interventions that will have a pro-equity impact on smoking and related disease should be prioritised. Funding should be designated to tobacco control activities focused on eliminating racial and socioeconomic inequities in smoking, and tobacco control programmes should be held accountable for meeting equity-related goals.

ObjectiveWe examined the acceptability and feasibility of a multi-component digital health outreach intervention to promote uptake of guideline-recommended postpartum screening for type 2 diabetes among patients with gestational diabetes (GDM).MethodsWe conducted a 24 randomized factorial experiment as part of the Multiphase Optimization Strategy (MOST) preparation phase for developing behavioral interventions. Participants with current or recent GDM in an integrated healthcare system were randomized to receive an outreach message with up to four intervention components, designed to be self-administered in about 10 min and efficiently delivered online via REDCap: a streamlined values affirmation, personalized information on diabetes risk, an interactive motivational interviewing-based component, and an interactive action planning component. Patient-reported acceptability and feasibility outcomes were assessed via survey.ResultsAmong 162 participants, 72% self-identified with a racial/ethnic minority group. Across components, acceptability scores averaged 3.9/5; ≥91% of participants read most or all of the outreach message; ≥89% perceived the amount of information as "about right"; and ≥ 87% completed ≥1 interactive prompt.ConclusionEach intervention component was acceptable to diverse patients and feasible to deliver in a brief, self-directed, online format.InnovationThese novel components target unaddressed barriers to patient engagement in guideline-recommended postpartum diabetes screening and adapt theory-based behavior change techniques for large-scale use.

BackgroundOral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings.MethodsHIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies.ResultsAmong 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63-.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of

Background and objectivesPediatric urgent care (PUC) centers may bolster immunization campaigns by offering vaccination during acute care visits, but few such programs have been described.MethodsWe conducted a quality improvement initiative at an academically affiliated federally qualified health center that provides primary, specialty, and PUC services to children. Our PUC began offering routine immunizations in July 2020. The percentage of visits by eligible patients age ≤21 years during which immunization screening (process) and administration (outcome) occurred was measured from March 1, 2021, to February 19, 2023. Administration rates were measured across age, sex, race, language, and medical home groups. Data were analyzed with statistical process control methods. Grievance and adverse event data were monitored (balancing).ResultsWe completed 4 plan-do-study-act cycles. Provider-facing bundles that included training, decision support, electronic health record signaling, and financial incentives were not associated with meaningful changes in screening and administration (cycles 1-3). A dedicated nurse vaccinator (DNV) was added on October 31, 2022 (cycle 4). The mean screening rate increased from 44.7% to 67.4% during the DNV period, and the mean administration rate increased from 26.5% to 50.8%. Lower administration rates were observed during visits by Black and English-speaking patients, and by patients empaneled outside our site.ConclusionsProvider-facing interventions alone were not effective at increasing vaccine screening and administration in our PUC, but marked improvement was observed with the addition of a DNV. Future interventions are needed to address disparities. Additional investigation is needed to determine whether our results are reproducible in other PUCs with access to vaccines.

Human-made chemicals are ubiquitous, leading to chronic exposure to complex mixtures of potentially harmful substances. We investigated chemical exposures in pregnant women in New York City by applying a non-targeted analysis (NTA) workflow to 95 paired prenatal urine and serum samples (35 pairs of preterm birth) collected as part of the New York University Children's Health and Environment Study. We analyzed all samples using liquid chromatography coupled with Orbitrap high-resolution mass spectrometry in both positive and negative electrospray ionization modes, employing full scan and data-dependent MS/MS fragmentation scans. We detected a total of 1524 chemical features for annotation, with 12 chemicals confirmed by authentic standards. Two confirmed chemicals dodecyltrimethylammonium and N,N-dimethyldecylamine N-oxide appear to not have been previously reported in human blood samples. We observed a statistically significant differential enrichment between urine and serum samples, as well as between preterm and term birth (p < 0.0001) in serum samples. When comparing between preterm and term births, an exogenous contaminant, 1,4-cyclohexanedicarboxylic acid (tentative), showed a statistical significance difference (p = 0.003) with more abundance in preterm birth in serum. An example of chemical associations (12 associations in total) observed was between surfactants (tertiary amines) and endogenous metabolites (fatty acid amides).

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide and is the fastest growing cause of cancer death in the United States (U.S.) In the U.S., current national clinical practice guidelines from the 2023 American Association for the Study of Liver Diseases (AASLD) Practice Guidance and the recently updated Liver Imaging Reporting & Data Systems (LI-RADS) Ultrasound (US) Surveillance v2024 core recommend semi-annual serum α-fetoprotein and US screening of patients deemed to be high risk for developing HCC. In this article, we will explore the transition to a patient-centered approach to HCC surveillance, including the role of the new LI-RADS US Surveillance v2024 core and the use of visualization score for determining ultrasound quality, the known risk factors for poor US image quality, and the potential options for alternative surveillance strategies when US may not be a viable option for certain patients, including multiphasic computed tomography (CT), magnetic resonance imaging (MRI), and several abbreviated MRI protocols.

Implementing self-injection (SI) of subcutaneous depot-medroxyprogesterone acetate (DMPA-SC) is a key self-care strategy for sexual and reproductive health, but SI uptake remains low, and assertions about the potential of SI to increase women's control over contraceptive use lack evidence. We sought to qualitatively explore how women with diverse contraceptive experiences-including those with and without experience using SI-view the benefits and challenges of SI as compared to other methods. We conducted 241 in-depth interviews with women across four sub-Saharan African countries and found alignment between the perceived and experienced benefits of SI across our diverse sample. Through the benefits of privacy, easier access, and self-management, we found SI can promote greater control over the contraceptive experience by facilitating a woman's ability to act on her preferences and control who is involved in or aware of her contraceptive use. Interviews revealed SI's potential is, however, constrained by inherent limitations in the method; for example, it is often not private or accessible enough and many fear injecting themselves. SI has the most potential when implemented with programmatic solutions that mitigate challenges women experience or anticipate and allow more women to benefit from the privacy, easier access, and self-management that SI offers.

BackgroundSubstance use is a public crisis in the U.S. Substance use can be understood as a series of events in the life course, from initiation to mortality. Social Determinants of Health (SDoH) have increasingly been recognized as essential contributors to individuals' health. This scoping review aims to examine available evidence of SDoH impact on the life course of substance use disorder (SUD).MethodsThis study identified peer-reviewed articles that reported longitudinal studies with SDoH factors as independent variables and substance use and disorders as dependent variables from PubMed, Embase, and Web of Science. The reported associations between SDoH and substance use stages over the life course were narratively and graphically summarized.ResultsAmong the 50 studies identified, ten revealed parental monitoring/support and early childhood education as protective factors, while negative peer influences and neighborhood instability were risk factors of substance use initiation. Nineteen articles reported factors associated with escalation in substance use, including unemployment, neighborhood vulnerability, negative peer influence, violence/trauma, and criminal justice system (CJS) involvement. Ten articles suggested that employment, social support, urban living, and low-barrier medication treatment facilitated treatment participation, while stigma and CJS involvement had negative impact on treatment trajectory. Social support and employment could foster progress in recovery and CJS involvement and unstable housing deterred recovery. Four studies suggested that unemployment, unstable housing, CJS involvement, and lack of social support were associated with overdose and mortality.ConclusionsThis review underscores the influence of social networks and early life experiences on the life course of SUD. Future SDoH research should investigate overdose and mortality and the impact of broader upstream SDoH on SUD. Interventions addressing these social factors are needed to mitigate their detrimental effects on the trajectories of SUD over the life course.

Chikungunya virus is an emerging mosquito-borne alphavirus that causes febrile illness and arthritic disease. Chikungunya virus is endemic in 110 countries and the World Health Organization estimates that it has caused more than 2 million cases of crippling acute and chronic arthritis globally since it re-emerged in 2005. Chikungunya virus outbreaks have occurred in Africa, Asia, Indian Ocean islands, South Pacific islands, Europe, and the Americas. Until recently, no specific countermeasures to prevent or treat chikungunya disease were available. To address this need, multiple vaccines are in human trials. These vaccines use messenger RNA-lipid nanoparticles, inactivated virus, and viral vector approaches, with a live-attenuated vaccine VLA1553 and a virus-like particle PXVX0317 in phase III testing. In November 2023, the US Food and Drug Administration (FDA) approved the VLA1553 live-attenuated vaccine, which is marketed as IXCHIQ. In June 2024, Health Canada approved IXCHIQ, and in July 2024, IXCHIQ was approved by the European Commission. On August 13, 2024, the US FDA granted priority review for PXVX0317. The European Medicine Agency is considering accelerated assessment review of PXVX0317, with potential for approval by both agencies in 2025. In this review, we summarize published data from pre-clinical and clinical trials for the IXCHIQ and PXVX0317 vaccines. We also discuss unanswered questions including potential impacts of pre-existing chikungunya virus immunity on vaccine safety and immunogenicity, whether long-term immunity can be achieved, safety in children, pregnant, and immunocompromised individuals, and vaccine efficacy in people with previous exposure to other emerging alphaviruses in addition to chikungunya virus.

BackgroundBreast arterial calcification (BAC) on mammograms has emerged as a biomarker of women's cardiovascular disease (CVD) risk, but there is a lack of quantification tools and clinical outcomes studies.ObjectivesThis study assessed the association of BAC (both presence and quantity) with CVD outcomes.MethodsThis single-center, retrospective study included women with a screening mammogram from 2007 to 2016. BAC was quantified using an artificial intelligence-generated score, which was assessed as both a binary and continuous variable. Regression analyses evaluated the association between BAC and mortality and a composite of acute myocardial infarction, heart failure, stroke, and mortality. Analyses were adjusted for age, race, diabetes, smoking, blood pressure, cholesterol, and history of CVD and chronic kidney disease.ResultsA total of 18,092 women were included in this study (mean age 56.8 ± 11.0 years; diabetes [13%], hypertension [36%], hyperlipidemia [40%], and smoking [5%]). BAC was present in 4,223 (23%). Over a median follow-up of 6 years, death occurred in 7.8% and 2.3% of women with and without BAC, respectively. The composite occurred in 12.4% and 4.3% of women with and without BAC, respectively. Compared to those without, women with BAC had adjusted HRs of 1.49 (95% CI: 1.33-1.67) for mortality and 1.56 (95% CI: 1.41-1.72) for the composite. Each 10-point increase in the BAC score was associated with higher risk of mortality (HR: 1.08 [95% CI: 1.06-1.11]) and the composite (HR: 1.08 [95% CI: 1.06-1.10]). BAC was especially predictive of future events among younger women.ConclusionsBAC is independently associated with mortality and CVD, especially among younger women. Measurement of BAC beyond presence adds incremental risk stratification. Quantifying BAC using an artificial intelligence algorithm is feasible, clinically relevant, and may improve personalized CVD risk stratification.

BackgroundThere are no clinical practice guidelines addressing the treatment of tobacco-cannabis co-use and a dearth of studies to inform treatment for co-use. This narrative review aims to (1) summarize promising intervention components used in published co-use treatment studies, (2) describe key gaps and emerging issues in co-use, and (3) provide recommendations and considerations in the development and evaluation of co-use interventions.MethodsWe conducted a literature search in June 2024 across several databases to update previous reviews on tobacco-cannabis co-use treatment. We found 9 published intervention studies that specifically addressed treatment for both substances. Data from these studies were manually extracted and summarized.ResultsMost of the 9 included studies (1) focused on acceptability and/or feasibility, (2) provided both psychosocial/behavioral and pharmacotherapy intervention components, (3) were conducted in adults, and (4) were delivered in-person, with some having digital asynchronous components, for a 5-to-12-week duration. The most common psychosocial/behavioral strategies used were Cognitive Behavioral Therapy, Motivational Interviewing, and Contingency Management; while the most common pharmacotherapy was Nicotine Replacement Therapy. There was no evidence of compensatory use of tobacco or cannabis when providing simultaneous treatment for both substances.ConclusionsThe literature to date provides support for well-integrated multi-component interventions of psychosocial/behavioral and pharmacotherapy strategies for co-use treatment. This review reinforces an urgent need for treatments targeting tobacco and cannabis co-use. Future interventions should address key gaps, including co-use of vaporized products among youth and young adults, tailored interventions for priority populations, and digital applications to increase reach and advance health equity.

ABSTRACTJustice-impacted persons may inconsistently access HIV testing. This cross-sectional secondary analysis investigates lifetime HIV testing prevalence among adults with prior histories of incarceration in Southern California, United States, participating in health-focused programming (n = 3 studies). Self-reported demographic and lifetime HIV testing data were collected between 2017-2023; descriptive analyses were conducted. Across the three samples, at least 74% of participants were male; Latino and African American individuals accounted for nearly two-thirds of participants. Lifetime HIV testing ranged from 72.8% to 84.2%. Males were significantly more likely than females to report never being tested in two samples and accounted for >95% of those never tested. No statistically significant differences in testing were observed by race/ethnicity. Single young adults (ages 18-26) were less likely than their partnered peers to report testing. HIV testing is critical for ensuring that individuals access prevention and treatment. HIV testing among justice-impacted adults in this study was higher than in the general population, potentially due to opt-out testing in correctional settings. Nevertheless, these findings underscore the importance of implementing targeted interventions to reduce structural (e.g., health insurance, access to self-testing kits) and social barriers (e.g., HIV stigma) to increase HIV testing among justice-impacted males and single young adults.

BackgroundLifestyle changes have been demonstrated to impact pathophysiology in Multiple Sclerosis (MS). Various diet and exercise protocols have been reported to improve symptoms and function in persons with MS. Evidence is accumulating that interventions as early as possible in the disease course are warranted. The objective of this study was to investigate the effect of a remotely delivered lifestyle program focusing on specific diet and exercise recommendations in persons with early MS.MethodsMS patients, with disease diagnosis no more than 2 years prior, were recruited from the patient population of the MS clinic of the Pacific Neuroscience Institute. Participants followed recommendations for diet and exercise delivered via remote heath coaching. Each participant received 6 sessions with a health coach over a 12-week period. They were given parameters of a Mediterranean-type diet to follow, and specific and individualized recommendations about duration, intensity and type of exercise and physical activity. Outcome measures included Quality of Life (QOL), cognition (Symbol Digit Modalities Test, SDMT), fatigue (Multiple Sclerosis Fatigue Impact Scale, MFIS), fitness (estimated with Metabolic equivalents, METS) and other objective and patient reported outcomes (PRO). Changes in outcomes were analyzed using mixed effects general linear models and standardized pre-post differences.(Cohen's d) RESULTS: Fifteen persons with early (≤ 2 years) MS enrolled in the study, 14 of whom completed the study. We observed significant improvements in QOL (p = 0.02), SDMT (p = 0.006), fatigue(p = 0.005), fitness (p = 0.04), and other PRO and objective metrics at the end of the protocol compared to baseline. Adherence and patient satisfaction measures were high.ConclusionsSpecific and individualized lifestyle recommendations can be effectively delivered remotely, and may produce improvement in symptoms and function in persons with early MS. Larger controlled trials of these interventions are warranted.

ObjectivesTo evaluate the prevalence of weight discrimination (the perception of being treated unfairly based on weight) and its sociodemographic associations among early adolescents aged 10 to 13 in the United States.MethodsWe analyzed cross-sectional data from the Adolescent Brain Cognitive Development (ABCD) Study in Year Two (2018-2020). Multivariable logistic regression analyses were conducted, with perceived weight discrimination as the dependent variable and age, sex, sexual orientation, race and ethnicity, body mass index (BMI) category, household income, and highest parental education level as adjusted independent variables. Interaction with BMI category and weight discrimination by sex, sexual orientation, race and ethnicity, and household income was tested for.ResultsIn our analytical sample (N = 7129), we found that 5.46 % of early adolescents reported experiencing weight discrimination. Adolescents with BMI percentile ≥95th (adjusted odds ratio [AOR], 6.41; 95 % confidence interval [CI], 4.71-8.70),

Despite established efficacy for oral pre-exposure prophylaxis (PrEP) in reducing HIV incidence, multi-level barriers within the health system, clinics, and the processes that shape practice have hindered service delivery and subsequent population-level effects. We applied the Consolidated Framework for Implementation Research (CFIR) to assess the context of PrEP delivery for adolescent girls and young women (AGYW) in rural South Africa and identify the factors supporting and impeding PrEP implementation to develop strategies to improve PrEP delivery. Between 2021 and 2022, we conducted in-depth interviews with five young women with PrEP use experience and 11 healthcare providers as well as four key informant stakeholder interviews. Tailored interviews organized around the CFIR domains provided multiple perspectives on the inter-connected processes, gaps, and opportunities between health systems, clinics, communities, and PrEP services. Shifts in PrEP policies, funding pressures, and inconsistent communications from the National Department of Health spurred fragmented planning, engagement, execution, and monitoring of PrEP delivery processes within clinics already struggling to address multiple population health needs. Resulting challenges included: conflicting priorities within clinics and across NGO partners, unclear goals and targets, staffing and space constraints, and insufficient community engagement. Individual clinics' implementation climate and readiness to deliver PrEP varied in terms of operational plans and delivery models. Interviewees reported complexity of initiation procedures and support for PrEP maintenance, with opportunities to improve systems communications and processes to facilitate integrated services and more user-friendly experiences. Applying CFIR identified opportunities to strengthen PrEP delivery across levels within this complex service delivery setting.

ObjectiveSexual and gender minority individuals are more likely to use tobacco and cannabis and have lower cigarette cessation. This study examined cannabis use associations with daily cigarettes smoked in sexual and gender minority individuals before and during a quit attempt.MethodParticipants included dual smoking same-sex/gender couples from California that were willing to make a quit attempt (individual n = 205, 68.3% female sex). Participants reported baseline past 30-day cannabis use and number of cigarettes smoked and cannabis use (yes/no) during 35 nightly surveys. Individuals with current cannabis use reported baseline cannabis use and/or nightly survey cannabis use. Multilevel linear models predicted number of cigarettes smoked by cannabis use.ResultsNumber of cigarettes decreased from before to during a quit attempt, but this decrease was smaller in individuals with current cannabis use compared to no current cannabis use (p < .001). In individuals with current cannabis use, number of cigarettes smoked was greater on days with cannabis use (p < .001). Furthermore, cannabis use that day increased overall number of cigarettes in those with relatively high overall cannabis use but only during a quit attempt in those with relatively low cannabis use (Within-Subject Cannabis Use × Between-Subject Cannabis Use × Quit Attempt interaction; p < .001).ConclusionsSexual and gender minority individuals with cannabis and cigarette use may have a harder time quitting smoking than those who do not use cannabis. For those with cannabis use, guidance on not using cannabis during a quit attempt may improve cigarette cessation outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand smoke exposure: persistent pollutant reservoirs, pollutant transport, routes of exposure, the time gap between initial cause and effect, and remediation and disposal. We examine four policy considerations to better protect the public from involuntary exposure to tobacco smoke pollutants from all sources. We call for (a) redefining smokefree as free of tobacco smoke pollutants from secondhand and thirdhand smoke; (b) eliminating exemptions to comprehensive smoking bans; (c) identifying indoor environments with significant thirdhand smoke reservoirs; and (d) remediating thirdhand smoke. We use the case of California as an example of how secondhand smoke-protective laws may be strengthened to encompass thirdhand smoke protections. The health risks and economic costs of thirdhand smoke require that smokefree policies, environmental protections, real estate and rental disclosure policies, tenant protections, and consumer protection laws be strengthened to ensure that the public is fully protected from and informed about the risks of thirdhand smoke exposure.

BackgroundShort-course tuberculosis (TB) prevention regimens, including 12 weeks of isoniazid and rifapentine (3HP), are increasingly used in high-TB-burden countries. Despite established safety and tolerability in efficacy trials, 3HP-related adverse events (AEs) could differ in routine settings. Real-world data on AE type, frequency, and timing are crucial for health systems considering 3HP programmatic scale-up.MethodsWe reviewed AEs among people with human immunodeficiency virus (HIV) participating in a pragmatic implementation trial of facilitated 3HP taken by directly observed therapy (DOT) or self-administered therapy (SAT) in Kampala, Uganda, and classified them using the Common Terminology Criteria for Adverse Events. We assessed AE timing and summarized related clinical actions including laboratory tests, diagnoses made, medications prescribed, and treatment interruptions.ResultsAmong 1655 people with HIV treated between July 2020 and September 2022, 270 (16.3%) reported 451 events; main issues included general (7%), nervous system (6%), musculoskeletal (5%), gastrointestinal (5%), and dermatologic (3%) disorders. Most (61%) occurred within 6 weeks of initiating 3HP. Among those with events, 211 (78%) required further clinician evaluation, 202 (75%) required laboratory testing, 102 (38%) had medications prescribed, 40 (15%) had treatment paused, and 14 (5%) discontinued 3HP. Women, those multidimensionally impoverished, and DOT recipients were more likely to report an AE. SAT users and later enrollees were more likely to have 3HP interrupted or stopped due to an AE.ConclusionsIn a routine setting, 3HP was safe, with 16% of people with HIV reporting AEs and only 3% requiring temporary or permanent treatment interruption. These findings support 3HP expansion in routine HIV/AIDS care settings for TB prevention. Clinical Trials Registration. NCT03934931.

Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to live a lifespan approaching that of people without HIV, without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing emphasis on maintaining health throughout the lifespan. To receive optimal medical care and achieve desired outcomes, persons with HIV must be consistently engaged in care and able to access uninterrupted treatment, including ART. Comprehensive evidence-based HIV primary care guidance is, therefore, more important than ever. Creating a patient-centered, stigma-free care environment is essential for care engagement. Barriers to care must be decreased at the societal, health system, clinic, and individual levels. As the population ages and noncommunicable diseases arise, providing comprehensive health care for persons with HIV becomes increasingly complex, including management of multiple comorbidities and the associated challenges of polypharmacy, while also attending to HIV-specific health concerns. Clinicians must address issues specific to preventive health, including cancer screening, providing recommended vaccinations, as well as promoting sexual health, including sexually transmitted infection diagnosis, treatment, and prevention. Clinicians also must address issues for specific populations, including persons of childbearing potential, including during preconception and pregnancy; children; adolescents; and transgender and gender-diverse individuals. This guidance from an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America updates the previous 2020 HIV Primary Care Guidance.

Individuals with end-stage kidney disease (ESKD) on dialysis experience high mortality and excessive burden of hospitalizations over time relative to comparable Medicare patient cohorts without kidney failure. A key interest in this population is to understand the time-dynamic effects of multilevel risk factors that contribute to the correlated outcomes of longitudinal hospitalization and mortality. For this we utilize multilevel data from the United States Renal Data System (USRDS), a national database that includes nearly all patients with ESKD, where repeated measurements/hospitalizations over time are nested in patients and patients are nested within (health service) regions across the contiguous U.S. We develop a novel spatiotemporal multilevel joint model (STM-JM) that accounts for the aforementioned hierarchical structure of the data while considering the spatiotemporal variations in both outcomes across regions. The proposed STM-JM includes time-varying effects of multilevel (patient- and region-level) risk factors on hospitalization trajectories and mortality and incorporates spatial correlations across the spatial regions via a multivariate conditional autoregressive correlation structure. Efficient estimation and inference are performed via a Bayesian framework, where multilevel varying coefficient functions are targeted via thin-plate splines. The finite sample performance of the proposed method is assessed through simulation studies. An application of the proposed method to the USRDS data highlights significant time-varying effects of patient- and region-level risk factors on hospitalization and mortality and identifies specific time periods on dialysis and spatial locations across the U.S. with elevated hospitalization and mortality risks.

Background: Black adults have higher incidence of all-cause mortality and worse cardiovascular disease (CVD) outcomes when compared to other U.S. populations. The Duffy chemokine receptor is not expressed on erythrocytes in a large majority of Black adults, but the clinical implications of this are unclear. Methods: Here, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and mortality and incident CVD events (coronary heart disease, stroke, and heart failure) in self-identified Black members of three contemporary, longitudinal cohort studies (the Women's Health Initiative, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis). Data on 14,358 Black participants (9023 Duffy-null and 5335 Duffy-receptor-positive, as defined using single-nucleotide polymorphism (SNP) rs2814778) were included in this analysis. Results: Duffy null was strongly associated with higher hs-CRP (meta-analysis p = 2.62 × 10-9), but the association was largely attenuated, though still marginally significant (p = 0.005), after conditioning on known CRP locus alleles in linkage disequilibrium with the Duffy gene. In our discovery cohorts, Duffy-null status appeared to be associated with a higher risk of all-cause mortality and incident stroke, though these associations were attenuated and non-significant following adjustment for traditional risk factors including hs-CRP. Moreover, the association of Duffy-null status with mortality could not be replicated in an independent sample of Black adults from the UK Biobank. Conclusions: These findings suggest that the higher levels of hs-CRP found in Duffy-null individuals may be in part independent of CRP alleles known to influence circulating levels of hs-CRP. During the follow-up of this community-based sample of Black participants, Duffy-null status was not associated with mortality or incident CVD events independently of traditional risk factors including hs-CRP.

BackgroundThe prevalence of toxic chemicals in US commerce has prompted some states to adopt laws to reduce exposure. One with broad reach is California's Proposition 65 (Prop 65), which established a list of chemicals that cause cancer, developmental harm, or reproductive toxicity. The law is intended to discourage businesses from using these chemicals and to minimize consumer exposure. However, a key question remains unanswered: Has Prop 65 reduced population-level exposure to the listed chemicals?ObjectiveWe used national biomonitoring data from the Centers for Disease Control and Prevention (CDC) to evaluate the impact of Prop 65 on population-level exposures.MethodsWe evaluated changes in blood and urine concentrations of 37 chemicals (including phthalates, phenols, VOCs, metals, PAHs, and PFAS), among US National Health and Nutrition Examination Survey (NHANES) participants in relation to the time of chemicals' Prop 65 listing. Of these, 11 were listed prior to, 11 during, and 4 after the biomonitoring period. The remaining 11 were not listed but were closely related to a Prop 65-listed chemical. Where biomonitoring data were available from before and after the date of Prop 65 listing, we estimated the change in concentrations over time for Californians compared with non-Californians, using a difference-in-differences model. We used quantile regression to estimate changes in exposure over time, as well as differences between Californians and non-Californians at the 25th, 75th, and 95th percentiles.ResultsWe found that concentrations of biomonitored chemicals generally declined nationwide over time irrespective of their inclusion on the Prop 65 list. Median bisphenol A (BPA) concentrations decreased 15% after BPA's listing on Prop 65, whereas concentrations of the nonlisted but closely related bisphenol S (BPS) increased 20% over this same period, suggesting chemical substitution. Californians generally had lower levels of biomonitored chemicals than the rest of the US population.DiscussionOur findings suggest that increased scientific and regulatory attention, as well as public awareness of the harms of Prop 65-listed chemicals, prompted changes in product formulations that reduced exposure to those chemicals nationwide. Trends in bisphenols and several phthalates suggest that manufacturers replaced some listed chemicals with closely related but unlisted chemicals, increasing exposure to the substitutes. Our findings have implications for the design of policies to reduce toxic exposures, biomonitoring programs to inform policy interventions, and future research into the regulatory and market forces that affect chemical exposure. https://doi.org/10.1289/EHP13956.

Women living with HIV/AIDS (WLHA) encounter numerous challenges, such as stigma and gender disparities, that hinder their access to care, especially in patriarchal societies like Vietnam. We developed a hybrid intervention with online and offline (in-person) components to empower WLHA in Vietnam. The intervention was pilot tested with 91 WLHA in Hanoi. During baseline and 4-month, study investigators delivered two in-person sessions, one Zoom session, and 15 weeks of Zalo (social media platform) discussions to enhance positive coping strategies, treatment utilization and adherence, and engagement of support from family and peers. The participants continued their Zalo discussions from 4-month to 6-month without investigators' involvement. Intervention outcomes, including active coping and perceived barriers to care, were evaluated at baseline, 4-, and 6-month surveys. Mixed-effects regression models showed that the participants' active coping significantly increased from baseline (50.5 ± 9.4) to 4-month (53.8 ± 6.2; p = 0.0001), although there was a slight decrease at 6-month (52.8 ± 7.2), the change from 4-month to 6-month was not significantly significant (p = 0.3256). There was a significant reduction in participants' perceived barriers to care, from 19.8 ± 5.2 at baseline to 17.4 ± 5.2 at 4-month (p

IntroductionCardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms of dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and clinical trajectories in individuals with autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsTwo hundred forty-seven adults carrying FTLD pathogenic genetic variants (53% asymptomatic) and 189 non-carrier controls completed baseline LS7, and longitudinal neuroimaging and neuropsychological testing.ResultsAmong variant carriers, higher baseline LS7 is associated with slower accumulation of frontal white matter hyperintensities (WMHs), as well as slower memory and language declines. Higher baseline LS7 associated with larger baseline frontotemporal volume, but not frontotemporal volume trajectories.DiscussionBetter baseline cardiovascular health related to slower cognitive decline and accumulation of frontal WMHs in autosomal dominant FTLD. Optimizing cardiovascular health may be an important modifiable approach to bolster cognitive health and brain integrity in FTLD.HighlightsBetter cardiovascular health associates with slower cognitive decline in frontotemporal lobar degeneration (FTLD). Lifestyle relates to the accumulation of frontal white matter hyperintensities in FTLD. More optimal cardiovascular health associates with greater baseline frontotemporal lobe volume. Optimized cardiovascular health relates to more favorable outcomes in genetic dementia.

In the United States, immigrant Latino men who have sex with men (ILMSM) are, compared to white MSM, disproportionately burdened by HIV and lack access to highly effective HIV prevention strategies, such as pre-exposure prophylaxis (PrEP). Qualitative research centered on exploring barriers that ILMSM experience in accessing PrEP and other sexual services is extremely limited, despite a high prevalence of HIV in this population. In this study, a purposive sample of ILMSM (n = 25) was recruited to participate in a semi-structured in-depth interview to identify the distinct barriers and facilitators ILMSM experience in accessing sexual health services given their complex intersectional identities of being an immigrant, Latino, and a sexual minority man. Using a thematic analysis approach, nine themes were generated from the data representing barriers and facilitators. Barriers included: (1) cost and a lack of health insurance, (2) complexity of PrEP assistance programs; (3) challenges related to the immigrant experience; (4) impact of gay stigma; and (5) communication challenges. Facilitators included: (1) improving affordability and accessibility of PrEP services; (2) receiving services from LGBT- or Latine LGBT-centered clinics; (3) receiving services from medical providers who are gay and/or Latino; and (4) providing targeted community outreach, education, and promotion of PrEP to ILMSM. While many of the barriers illuminated in the study were structural (e.g., cost and lack of health insurance), and not easy to overcome, the findings highlight a range of facilitators that can support access to PrEP and other sexual health services for ILMSM. Considering these findings, we suggest strategies that may enhance access to needed sexual health services among ILMSM.

BackgroundDespite elevated rates of trauma exposure, substance misuse, mental health problems, and suicide, systems-impacted teens and their caregivers have limited access to empirically supported behavioral health services. Family-based interventions are the most effective for improving mental health, education, substance use, and delinquency outcomes, yet the familial and placement disruption that occurs during child welfare involvement can interfere with the delivery of family-based interventions.ObjectiveTo address this gap in access to services, we adapted an in-person, empirically supported, family-based affect management intervention using a trauma-informed lens to be delivered via telehealth to families impacted by the child welfare system (Family Telehealth Project). We describe the intervention adaptation process and an open trial to evaluate its feasibility, acceptability, and impact.MethodsAdaptations to the in-person, family-based affect management intervention were conducted iteratively with input from youth, caregivers, and systems partners. Through focus groups and collaborative meetings with systems partners, a caregiver-only version of the intervention was also developed. An open trial of the intervention was conducted to assess family perspectives of its acceptability and feasibility and inform further refinements prior to a larger-scale evaluation. Participants included English-speaking families involved in the child welfare system in the past 12 months with teens (aged 12-18 years). Caregivers were eligible to participate either individually (caregivers of origin, kinship caregivers, or foster parents; n=7) or with their teen (caregiver of origin only; n=6 dyads). Participants completed session feedback forms and surveys at pretreatment, posttreatment, and 3-month posttreatment time points. Qualitative exit interviews were conducted with a subset of participants (12/19, 63%) to further understand their experiences with the intervention.ResultsSession attendance was high, and both caregivers and teens reported high acceptability of clinicians and sessions on feedback forms. Families were comfortable with video technology, with very few (

There is a clinical need for a simple test implementable at the primary point of care to identify individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) in the population. Blood plasma samples from adult patients with varying phenotypes of MASLD were used to identify a minimal set of lipid analytes reflective of underlying histologically confirmed MASLD. Samples were obtained from the NIDDK Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) NAFLD Database prospective cohort study (MASLD group; N = 301). Samples of control subjects were obtained from cohort studies at the University of California San Diego (control group; N = 48). Plasma samples were utilized for targeted quantitation of circulating eicosanoids, related bioactive metabolites, and polyunsaturated fatty acids by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) lipidomics analysis. Bioinformatic approaches were used to discover a panel of bioactive lipids that can be used as a diagnostic tool to identify MASLD. The final panel of fifteen lipid metabolites consists of 12 eicosanoid metabolites and 3 free fatty acids that were identified to be predictive for MASLD by multivariate area under the receiver operating characteristics curve (AUROC) analysis. The panel was highly predictive for MASLD with an AUROC of 0.999 (95% CI = 0.986-1.0) with only one control misclassified. A validation study confirmed the resulting MASLD LIPIDOMICS SCORE, which may require a larger-scale prospective study to optimize. This predictive model should guide the development of a non-invasive "point-of-care" test to identify MASLD patients requiring further evaluation for the presence of metabolic dysfunction-associated steatohepatitis.

BackgroundDual use of both e-cigarettes and cigarettes is popular among young adults and may lead to greater nicotine dependence and additive adverse health effects than single-product use. However, existing cessation programs target quitting either e-cigarettes or cigarettes, highlighting a need for interventions to help young adults quit both products (ie, dual tobacco cessation).ObjectiveThis formative study is part of a larger project to develop a smartphone intervention for dual tobacco cessation among young adults. This study aimed to (1) explore desires for and experiences with quitting both e-cigarettes and cigarettes and (2) identify needs and preferences for dual tobacco cessation intervention programming.MethodsSemistructured interviews were conducted to elicit the need for and experience with dual tobacco cessation among 14 young adults (18-29 years old) recruited through Instagram (Meta) advertisements in 2023. We conducted a thematic analysis to identify common themes related to quitting experiences and cessation needs.ResultsParticipants expressed a strong desire for dual tobacco cessation and had attempted to quit both tobacco products, mostly "cold turkey." The priority product for quitting first varied by the individual's perceived harm or level of consumption. Targets for dual tobacco cessation interventions included (1) highlighting the health effects of dual tobacco use compared with single product use, (2) providing cessation support to quit one prioritized product while cutting down the other product with the explicit goal to quit both, (3) emphasizing unique facilitators and barriers to quitting each product (eg, unpleasant smell of cigarettes facilitating smoking cessation and accessibility and flavors of e-cigarettes hindering vaping cessation), and (4) addressing co-use of tobacco with alcohol or cannabis. Participants wanted personalized interventions through smartphone apps that would tailor support to their tobacco use patterns and unique quitting goals and needs. They also suggested presenting intervention content in multimedia (eg, videos, graphic pictures, quizzes, and games) to increase engagement.ConclusionsThis study provides important insights into young adults' experiences, needs, and preferences for dual tobacco product cessation. We highlight important targets for future smartphone apps to deliver personalized and tailored support to meet the heterogeneous needs and preferences of young people who want to quit using both e-cigarettes and cigarettes.

BackgroundCompared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging.ObjectivesAmong persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD.MethodsThe primary analysis was completed among 446 participants from the Cedars-Sinai Medical Center of the CAC Consortium with very high HDL cholesterol (≥77 mg/dL in men, ≥97 mg/dL in women). Cox proportional hazards regression assessed the association of CAC and traditional risk factors with all-cause mortality during a median follow-up of 10.7 years. Replication and validation analyses were performed for all-cause mortality among 119 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) with very high HDL cholesterol, who also had information on incident ASCVD.ResultsThe mean age was 57.9 years old, 49% were women, and the median HDL cholesterol was 98 mg/dL. One-half of participants (50%) had prevalent CAC, in whom the median CAC score was 118. Prevalent CAC conferred a 3.6-fold higher risk of all-cause mortality (HR: 3.64; 95% CI: 1.21-11.01), which appeared to be a more robust predictor than individual traditional risk factors beyond age. In the validation sample, prevalent CAC but not individual traditional risk factors were associated with all-cause mortality (HR: 2.39; 95% CI: 1.07-5.34) and a 4.0-fold higher risk of ASCVD (HR: 4.06; 95% CI: 1.11-14.84).ConclusionsMeasurement of CAC may facilitate clinical risk assessment among individuals with very high HDL cholesterol.

The fundamental organization of the human brain is established before birth, with rapid growth continuing over the first postnatal years. Children exposed before or after birth to various biological (e.g., substance exposure) or psychosocial hazards (e.g., maltreatment) are at elevated likelihood of deviating from a typical developmental trajectory, which in turn can be associated with psychological, behavioral, and physical health sequelae. In the HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, brain, physical, biological, cognitive, behavioral, social, and emotional development is being examined starting in pregnancy and planned through age 10 (data are sampled at varying degrees of granularity depending on age, with more dense sampling earlier in life). HBCD aims to determine the short- and long-term impacts of a variety of both harmful and protective factors, including prenatal substance use, on developmental trajectories through early childhood. Organized as a nationwide consortium across 27 sites, the HBCD Study will collect multimodal data that will be made publicly available on a yearly basis, through a data use application and approval process. Here we provide an overview of the HBCD Study design, sampling, protocol development, and data management. Data collected through HBCD will be fundamental to informing future prenatal and early childhood interventions and policies to promote wellbeing and resilience in all children.

The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54-0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07-1.91; extensive disease: HR 2.02, 95%CI 1.07-3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

BackgroundAlthough vaccines are largely effective and safe, there is variability in post-vaccination experience regarding antibody response, side effects, and affective outcomes. Vaccine mindsets, specific beliefs about the vaccine, may be associated with post-vaccination experience. This is important since mindsets are malleable and may help decrease vaccine hesitancy and improve post-vaccination experience.MethodsIn a prospective study, we measured overall positive vaccine mindset and specific mindsets regarding efficacy, body response, and side effects. We tested whether vaccine mindsets before vaccination predicted neutralizing antibody response, side effects, vaccine-related stress, and affective outcomes (general stress, sadness, and happiness). Antibody response was assessed one month and six months after participants completed a SARS-CoV-2 vaccination series. Side effect experience and affective reactions were assessed daily on the vaccination day and the subsequent five days.ResultsThere was no significant association between the aggregate vaccine mindset score and neutralizing antibody response; however, people with a more positive vaccine mindset reported fewer side effects, less same-day vaccine-related anxiety, and improved affective outcomes after vaccination. In secondary analyses, when specific mindsets were explored, the mindset that vaccine side effects are a sign of treatment efficacy predicted higher antibodies, but not side effects experience and vaccine-related anxiety. Vaccine efficacy and body-response mindsets predicted fewer side effects, vaccine-related anxiety, and improved affective outcomes after vaccination.ConclusionThese findings underscore the potential of vaccine mindsets in enhancing the overall post-vaccination experience and, in some cases, increasing antibody response.

Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (βs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset.

PurposeLong COVID-19 syndrome occurs in 10-20 % of people after a confirmed/probable SARS-COV-2 infection; new symptoms begin within three months of COVID-19 diagnosis and last > 8 weeks. Little is known about risk factors for long COVID, particularly in older people who are at greater risk of COVID complications.MethodsData are from Women's Health Initiative (WHI) postmenopausal women who completed COVID surveys that included questions on whether they had ever been diagnosed with COVID and length and nature of symptoms. Long COVID was classified using standard consensus criteria. Using WHI demographic and health data collected at study enrollment (1993-98) through the present day, machine learning identified the top 20 risk factors for long COVID. These variables were tested in logistic regression models.ResultsOf n = 37,280 survey respondents, 1237 (mean age = 83 years) reported a positive COVID-19 test and 425 (30 %) reported long COVID. Symptoms included an array of neurological, cardio-pulmonary, musculoskeletal, and general fatigue, and malaise symptoms. Long COVID risk factors included weight loss, physical and mobility limitations, and specific heath conditions (e.g., history of heart valve procedure, rheumatoid arthritis).ConclusionsKnowledge of risk factors for long COVID may be the first step in understanding the etiology of this complex disease.

The COVID-19 pandemic has uniquely impacted people living with HIV (PLWH) worldwide. The negative impacts on PLWH's mental health from fear of COVID-19 are labeled as "a double stress." The association between fear of COVID-19 and HIV (internalized) stigma has been found among PLWH. Studies that explore the relationships between fear of COVID-19 and physical health outcomes are few, especially among PLWH. In this study, we explored the relationship between fear of COVID-19 and physical health among PLWH and the mediated effects of HIV stigma, social support, and substance use. A cross-sectional online survey of PLWH (n = 201) from November 2021 to May 2022 was carried out in Shanghai, China. The data on socio-demographics, fear of COVID-19, physical health, HIV-related perceived stigma, social support, and substance use were gathered and analyzed by structure equation modeling (SEM). In SEM analysis, fear of COVID-19 showed a significant and indirect effect on physical health (β=-0.085) which was primarily mediated by HIV stigma. In SEM analysis, the final model had a good fit. Fear of COVID-19 showed a significant effect on HIV stigma (β = 0.223) with the majority being direct effects (β = 0.262) and a small indirect effect via substance use (β=-0.039). Furthermore, HIV stigma showed a significant effect on physical health (β=-0.382), the majority of which was direct (β=-0.340), and a small indirect effect via social support (β=-0.042). This is one of the first studies to explore how fear of contracting COVID-19 can affect PLWH's coping behaviors (e.g., using substances and obtaining social support) used to combat HIV stigma as well as to achieve better physical health in China.

BackgroundTobacco smoke may affect atopic dermatitis (AD) because of its known effects on humoral and cellular immunity, but prior studies lack data on disease severity and biomarkers over time.ObjectiveWe investigated the association between passive and active tobacco smoke exposure (TSE) during childhood and adolescence and the activity and severity of AD.MethodsA birth cohort of 10,521 individuals was followed through adolescence as part of the Avon Longitudinal Study of Parents and Children. We used mixed-effect models to determine the risk of AD (based on repeated assessments) with passive smoke exposure during childhood, active TSE during adolescence, and using a serum biomarker of tobacco exposure (cotinine) at 3 time points.ResultsAfter adjusting for confounding factors, there was no evidence of a relationship between passive TSE and concurrent AD activity in childhood (adjusted odds ratio, 0.95; 95% confidence interval, 0.83, 1.07) or of an increased risk between active smoking and AD activity in adolescence (adjusted odds ratio, 0.57; 95% confidence interval, 0.44, 0.75). Secondary analyses demonstrated no dose-response relationship and no increased severity of AD with passive or active TSE. Furthermore, we found no increased risk of AD with a cumulative measure of passive TSE across childhood (adjusted relative risk ratio, 0.98; 95% confidence interval, 0.96, 1.00).ConclusionNeither active nor passive TSE was associated with AD during childhood and adolescence.

Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1-4. Despite the clinical evidence1,5-7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8-10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.

Objective: Circulating microRNAs show cross-sectional associations with overweight and obesity. Few studies provided data to differentiate between a snapshot perspective on these associations versus how microRNAs characterize prodromal risk from disease pathology and complications. This study assessed longitudinal relationships between circulating microRNAs and weight at multiple time-points in the Diabetes Prevention Program trial. Research design and methods: A subset of participants (n=150) from the Diabetes Prevention Program were included. MicroRNAs were measured from banked plasma using a Fireplex Assay. We used generalized linear mixed models to evaluate relationships between microRNAs and changes in weight at baseline, year-1, and year-2. Logistic regression was used to evaluate whether microRNAs at baseline were associated with weight change after 2 years. Results: In fully adjusted models that included relevant covariates, seven miRs (i.e., miR-126, miR-15a, miR-192, miR-23a, and miR-27a) were statistically associated with weight over 2 years. MiR-197 and miR-320a remained significant after adjustment for multiple comparisons. Baseline levels of let-7f, miR-17, and miR-320c were significantly associated with 3% weight loss after 2 years in fully adjusted models. Discussion: This study provided evidence for longitudinal relationships between circulating microRNAs and weight. Because microRNAs characterize the combined effects of genetic determinants and responses to behavioral determinants, they may provide insights about the etiology of overweight and obesity in the context or risk for common, complex diseases. Additional studies are needed to validate the potential genes and biological pathways that might be targeted by these microRNA biomarkers and have mechanistic implications for weight loss and disease prevention.