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  Exome-wide association analysis identifies novel risk loci for alcohol-associated hepatitis

  Yuan, Qiaoping; Hodgkinson, Colin; Liu, Xiaochen; Barton, Bruce A; Diazgranados, Nancy; Schwandt, Melanie; Morgan, Timothy; Bataller, Ramon; Liangpunsakul, Suthat; Nagy, Laura E; et al. (2024-07-26)

  Background and aims: Alcohol-associated hepatitis (AH) is a clinically severe, acute disease that afflicts only a fraction of patients with alcohol use disorder (AUD). Genomic studies of alcohol-associated cirrhosis (AC) have identified several genes of large effect, but the genetic and environmental factors that lead to AH and AC, and their degree of genetic overlap, remain largely unknown. This study aims to identify genes and genetic variation that contribute to the development of AH. Approach and results: Exome-sequencing of patients with AH (N=784) and heavy drinking controls (N=951) identified exome-wide significant association for AH at PNPLA3, as previously observed for AC in GWAS, although with a much lower effect-size. SNPs of large effect-size at ICOSLG (Chr 21) and TOX4/RAB2B (Chr 14), were also exome-wide significant. ICOSLG encodes a co-stimulatory signal for T-cell proliferation and cytokine secretion and induces B-cell proliferation and differentiation. TOX4 was previously implicated in diabetes and immune system function. Other genes previously implicated in AC did not strongly contribute to AH, and the only prominently implicated (but not exome wide significant) gene overlapping with AUD was ADH1B. Polygenic signals for AH were observed in both common and rare variant analysis and identified genes with roles associated with inflammation. Conclusions: This study has identified two new genes of high effect size with a previously unknown contribution to ALD, and highlights both the overlap in etiology between liver diseases, and the unique origins of AH.
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  Living a private lie: intersectional stigma, depression and suicidal thoughts for selected young key populations living with HIV in Zambia

  Zulu, Joseph Mumba; Budhwani, Henna; Wang, Bo; Menon, Anitha; Kim, Deogwoon; Zulu, Mirriam; Nyamaruze, Patrick; Govender, Kaymarlin; Armstrong, Russell (2024-07-19)

  Background: Limited research has been conducted on the forms, manifestations and effects of intersectional stigma among young HIV-positive men who have sex with men (MSM) and transgender women (TGW) in Zambia. In this study, we aimed to address this gap by elucidating the experiences of these in a small group of young, HIV + MSM and TGW in Zambia. Methods: We applied a mixed-methods design. Data were collected from January 2022 to May 2022. Qualitative data were collected using in-depth interviews while quantitative data were collected using a questionnaire. Qualitative transcripts were coded using thematic analysis while paper-based questionnaire data were entered into Kobo Connect. Descriptive statistics, using chi-squared tests were calculated using Excel. In this paper, we provide a descriptive profile of the sample and then focus on the qualitative findings on intersectional stigma, depression, and contemplation of suicide. Results: We recruited 56 participants from three sites: Lusaka, Chipata, and Solwezi districts. Participants' mean age was 23 years. The study found that 36% of all participants had moderate to significant symptoms of depression, 7% had major depression, 30% had moderate signs of anxiety, 11% had high signs of anxiety, 4% had very high signs of anxiety and 36% had contemplated suicide at least once. A greater proportion of TGW had moderate to significant symptoms of depression (40%) or major depression (10%) compared to MSM, at 33% and 6%, respectively (X2 = 0.65; p = 0.42). Similarly, more TGW (55%) had contemplated suicide than MSM peers (36%, X2=1.87; p = 0.17). In the qualitative data, four emergent themes about the forms, manifestations, and effects of intersectional stigma were (1) HIV, sexual orientation, and gender identity disclosure; (2) Dual identity; (3) Challenges of finding and maintaining sexual partners; (4) Coping and resilience. Overall, having to hide both one's sexuality and HIV status had a compounding effect and was described as living "a private lie." Conclusion: Effectively addressing stigmas and poor mental health outcomes among young HIV-positive MSM and TGW will require adopting a socio-ecological approach that focuses on structural interventions, more trauma-informed and identity-supportive care for young people with HIV, as well as strengthening of authentic community-informed public health efforts.
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  To treat or not to treat: a comparative effectiveness analysis of oral anticoagulant outcomes among U.S. nursing home residents with atrial fibrillation

  Chen, Qiaoxi; Baek, Jonggyu; Goldberg, Robert J.; Tjia, Jennifer; Lapane, Kate L; Alcusky, Matthew J (2024-07-19)

  Background: Nursing home residents with atrial fibrillation are at high risk for ischemic stroke, but most are not treated with anticoagulants. This study compared the effectiveness and safety between oral anticoagulant (OAC) users and non-users. Methods: We conducted a new-user retrospective cohort study by using Minimum Data Set 3.0 assessments linked with Medicare claims. The participants were Medicare fee-for-service beneficiaries with atrial fibrillation residing in US nursing homes between 2011 and 2016, aged ≥ 65 years. The primary outcomes were occurrence of an ischemic stroke or systemic embolism (effectiveness), occurrence of intracranial or extracranial bleeding (safety) and net clinical outcome (effectiveness or safety outcomes). Secondary outcomes included total mortality and a net clinical and mortality outcome. Cox proportional hazards and Fine and Grey models estimated multivariable adjusted hazard ratios (aHRs) and sub-distribution hazard ratios (sHRs). Results: Outcome rates were low (effectiveness: OAC: 0.86; non-users: 1.73; safety: OAC: 2.26; non-users: 1.75 (per 100 person-years)). OAC use was associated with a lower rate of the effectiveness outcome (sHR: 0.69; 95% Confidence Interval (CI): 0.61-0.77), higher rates of the safety (sHR: 1.70; 95% CI: 1.58-1.84) and net clinical outcomes (sHR: 1.20; 95% CI: 1.13-1.28) lower rate of all-cause mortality outcome (sHR: 0.60; 95% CI: 0.59-0.61), and lower rate of the net clinical and mortality outcome (sHR: 0.60; 95% CI: 0.59-0.61). Warfarin users, but not DOAC users, had a higher rate of the net clinical outcome versus OAC non-users. Conclusions: Our results support the benefits of treatment with OACs to prevent ischemic strokes and increase longevity, while highlighting the need to weigh apparent benefits against elevated risk for bleeding. Results were consistent with net favorability of DOACs versus warfarin.
• Comparing the effect of two systems-level interventions on perinatal generalized anxiety disorder and posttraumatic stress disorder symptoms

  Zimmermann, Martha; Merton, Catherine; Flahive, Julie; Robbins, Cheryl L; Ko, Jean Y; Allison, Jeroan J.; Person, Sharina D.; Simas, Tiffany A Moore; Byatt, Nancy (2024-07-09)

  Background: The Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms are designed to help obstetric practices address perinatal depression. The PRogram in Support of Moms includes the statewide Massachusetts Child Psychiatry Access Program for Moms program, plus proactive implementation support. Objective: The goal of this study was to understand the impact of these programs on perinatal generalized anxiety disorder and posttraumatic stress disorder symptoms among individuals screening positive for depression. Study design: We conducted a secondary analysis of 2017-2022 data from a cluster randomized controlled trial of Massachusetts Child Psychiatry Access Program for Moms vs PRogram In Support of Moms. We included participants completing a generalized anxiety disorder or posttraumatic stress disorder screen at baseline (n=254) with antenatal Edinburgh Postnatal Depression Scale scores ≥10. We assessed changes in generalized anxiety disorder and posttraumatic stress disorder symptoms from pregnancy (4-25 weeks of gestational age or 32-40 weeks of gestational age), 4-12 weeks postpartum, and 11-13 months postpartum. We conducted a difference-in-difference analysis to compare symptom change from pregnancy to postpartum. We used adjusted linear mixed models with repeated measures to examine the impact of the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms on changes in the Generalized Anxiety Disorder 7 and the Posttraumatic Stress Disorder Checklist. Results: Mean Generalized Anxiety Disorder 7 scores decreased by 3.6 (Massachusetts Child Psychiatry Access Program for Moms) and 6.3 (PRogram In Support of Moms) points from pregnancy to 4-12 weeks postpartum. Mean Posttraumatic Stress Disorder Checklist scores decreased by 6.2 and 10.0 points, respectively, at 4-12 weeks postpartum among individuals scree ning positive on the Generalized Anxiety Disorder 7 (n=83) or Posttraumatic Stress Disorder Checklist (n=58) in pregnancy. Generalized Anxiety Disorder 7 and Posttraumatic Stress Disorder Checklist scores decreased among both groups at 11-13 months postpartum. These changes were clinically meaningful. PRogram In Support of Moms conferred a statistically significant greater decrease (2.7 points) on the Generalized Anxiety Disorder 7 than the Massachusetts Child Psychiatry Access Program for Moms at 4-12 weeks postpartum. No differences were found between the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms in Posttraumatic Stress Disorder Checklist or Generalized Anxiety Disorder 7 change at 11-13 months, although both were associated with a reduction in generalized anxiety disorder and posttraumatic stress disorder symptoms at 4-12 weeks and 11-13 months postpartum. Conclusion: Both the Massachusetts Child Psychiatry Access Program for Moms and PRogram In Support of Moms could help to improve symptoms for individuals experiencing co-occurring symptoms of depression, generalized anxiety disorder, or posttraumatic stress disorder. PRogram In Support of Moms may confer additional benefits in the early postpartum period, although this difference was not clinically significant.
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  Conquering hypertension in Vietnam: 12- month follow up results from a cluster-randomised controlled trial

  Nguyen, Hoa L; Ha, Duc A; Tran, Oanh T; Phan, Van H; Nguyen, Cuc T; Nguyen, Giang H; Nguyen, Thang T; Le, Thanh T; Goldberg, Robert J.; Wang, Bo; et al. (2024-07-01)

  Background: Approximately 20% of adults in Vietnam have hypertension, and management of this chronic condition remains challenging. This study aimed to assess the effectiveness of a multicomponent intervention in reducing blood pressure (BP) in adults with uncontrolled hypertension. Methods: This cluster randomised controlled trial was conducted in sixteen communities (8 intervention and 8 comparison) in a rural setting in Vietnam (2017-2022). Consenting adults (aged ≥ 18 years) with uncontrolled hypertension were enrolled. Sixteen communities were equally randomised to an intervention or comparison group stratified by district. Consenting adults were assigned to study groups by community. The comparison arm received training sessions about hypertension prevention and management for health workers, and patient education materials. The intervention arm received training sessions about hypertension prevention and management for health workers, and patient education materials and three enhancement components including a storytelling intervention, home BP self-monitoring, and expanded community health worker services. The primary outcome was the difference in changes in patient's levels of systolic BP between the study groups over a 12-month follow-up period. Patients and outcome assessors were masked. Findings: A total of 671 patients (340: intervention, 331: comparison) were enrolled in the trial. The mean age was 66 years and 45% were men. At the 12-month follow-up, the mean systolic BP declined by 18.4 mmHg in the intervention group and 3.7 mmHg in the comparison group (differential decline of 14.7 mmHg [95% CI: 11.8-17.6]). The intervention group also achieved better BP control and medication adherence than the comparison group. There were no serious adverse events related to study participation. Interpretation: The results of this trial demonstrate that a multicomponent intervention can effectively reduce elevated BP in individuals with uncontrolled hypertension in Vietnam. Trial registration: This trial was registered at ClinicalTrials.gov, NCT03590691. Funding: National Heart, Lung, and Blood Institute.
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  IFNγ-IL12 axis regulates intercellular crosstalk in metabolic dysfunction-associated steatotic liver disease

  Friedline, Randall H; Noh, Hye Lim; Suk, Sujin; Albusharif, Mahaa; Dagdeviren, Sezin; Saengnipanthkul, Suchaorn; Kim, Bukyung; Kim, Allison M; Kim, Lauren H; Tauer, Lauren A; et al. (2024-06-29)

  Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2-/-) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)-12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2-/- mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.
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  Factors Influencing Margin Clearance and the Number of Stages of Mohs Micrographic Surgery in Basal Cell Carcinoma: A Retrospective Chart Review

  Daniel, Vijaya T; Azzolino, Vincent; Abraham, Maria; Leonard, Nicholas; Blankenship, Kaitlin; Lal, Karan; Flahive, Julie; Brown, Regina; Tkachenko, Elizabeth; Teymour, Shereen; et al. (2024-06-28)

  How patient and tumor factors influence clearance margins and the number of Mohs Micrographic Surgery (MMS) stages when treating basal cell carcinoma (BCC) remains widely uncharacterized. It is important to elucidate these relationships, as surgical outcomes may be compared nationally between colleagues. Our objective is to evaluate the relationships between defect size and patient demographics, as well as between BCC subtypes and the number of MMS stages. Our second objective is to compare practice patterns and characteristics of patients requiring MMS at academic centers and private practices. A retrospective chart review was performed using data collected at academic centers (2015-2018) and private practices (2011-2018) of BCC patients older than 18 years old who underwent MMS. In total, 7651 patients with BCC requiring MMS were identified. Academic center adjusted analyses demonstrated clearance margins 0.1 mm higher for every year's increase in age (p < 0.0001) and 0.25 increase in MMS stages for high-risk BCC (p < 0.0001). Private practice adjusted analyses demonstrated clearance margins 0.04 mm higher for every year's increase in age (p < 0.0001). Clearance margins correlate with older age, and additional MMS stages correlate with high-risk BCC, suggesting the role patient and tumor factors may play in predicting tumor clearance and MMS stages.
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  The Puerto Rico Young Adults' Stress, Contextual, Behavioral & Cardiometabolic Risk (PR-OUTLOOK) Study: Design and Methods

  Pérez, C M; Kiefe, Catarina I.; Person, Sharina D.; Tucker, K L; Torres, P; Sandoval, E; Boneu, C; Ramírez, Z; Mattei, J; Rodríguez-Orengo, J; et al. (2024-06-26)

  The Puerto Rico (PR) Young Adults' Stress, Contextual, Behavioral & Cardiometabolic Risk Study (PR-OUTLOOK) is investigating overall and component-specific cardiovascular health (CVH) and cardiovascular disease (CVD) risk factors in a sample of young (age 18-29) Puerto Rican adults in PR (target n=3,000) and examining relationships between individual-, family/social- and neighborhood-level stress and resilience factors and CVH and CVD risk factors. The study is conducting standardized measurements of CVH and CVD risk factors and demographic, behavioral, psychosocial, neighborhood, and contextual variables and establishing a biorepository of blood, saliva, urine, stool, and hair samples. The assessment methods are aligned with other National Heart, Lung, and Blood Institute funded studies: the Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT) of adults 30-75 years, the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), the Boston Puerto Rican Health Study (BPRHS), and the Coronary Artery Risk Development in Young Adults (CARDIA). PR-OUTLOOK data and its biorepository will facilitate future longitudinal studies of the temporality of associations between stress and resilient factors and CVH and CVD risk factors among young Puerto Ricans, with remarkable potential for advancing the scientific understanding of these conditions in a high-risk but understudied young population.
• Racial Disparities and Trends in Anticoagulant Use among Ambulatory Care Patients with Atrial Fibrillation and Atrial Flutter in the United States from 2007-2019 [preprint]

  Kan, Vincent; Lapane, Kate L; McManus, David D; Baek, Jonggyu; Darling, Chad E; Alcusky, Matthew J (2024-06-15)

  Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly increasing the risk of stroke. The introduction of direct oral anticoagulants (DOACs) since 2010 has transformed anticoagulation therapy, offering an alternative to warfarin with improved safety profiles. Despite the increased adoption of DOACs, disparities in their use among different racial and ethnic groups in the United States remain understudied. Methods This study utilized a repeated cross-sectional design, analyzing data from the National Ambulatory Medical Care Survey (NAMCS) from 2007 to 2019. The study population included adults diagnosed with AF or atrial flutter (AFL). We analyzed the temporal trends of DOAC and warfarin use from 2007 to 2019. We examined the prevalence of DOAC versus warfarin use and assessed associations between race/ethnicity, patient characteristics, and DOAC utilization from 2011 to 2019. Multivariable modified Poisson regression models were used to calculate adjusted prevalence ratios (aPR) for the associations. Results From 2011 to 2019, NAMCS recorded 3,224 visits involving AF or AFL, representing a weighted estimate of 103.6 million visits. DOAC use increased significantly, with apixaban becoming the predominant anticoagulant by 2016. Non-Hispanic Black patients were less likely to use DOACs compared to non-Hispanic White patients over time (aPR 0.75; 95% CI, 0.63-0.90). Patients with Medicaid insurance were also less likely to use DOACs (aPR 0.14; 95% CI: 0.04-0.46). Conclusion Despite the shift from warfarin to DOACs for AF and AFL treatment, significant racial and socioeconomic disparities persist. Non-Hispanic Black patients and those with Medicaid insurance are less likely to use DOACs. These findings highlight the need for targeted strategies to ensure equitable access to advanced anticoagulant therapies.
• Effectiveness of Short-Acting Opioid Escalation vs Initiation of a Long-Acting Opioid in Nursing Home Residents

  Nunes, Anthony P; Yuan, Yiyang; Baek, Jonggyu; Pawasauskas, Jayne; Hume, Anne L; Liu, Shao-Hsien; Lapane, Kate L (2024-06-08)

  Objectives: Modifications to opioid regimens for persistent pain are typically made after an initial period of short-acting opioid (SAO) use. Regimen changes may include an escalation of the SAO dosage or an initiation of a long-acting opioid (LAO) as a switch or add-on therapy. This study evaluates the comparative effectiveness between these alternative regimens in nursing home residents. Design: A retrospective observational cohort analysis of US long-stay nursing home residents. Setting and participants: Nursing home resident data were obtained from the national Minimum Dataset (MDS) version 3.0 and linked Medicare data, 2011-2016. Methods: Opioid regimen changes were identified using Part D dispensing claims to identify dosage escalation of SAOs, initiation of an LAO, or a switch to an LAO. Outcomes included indices of pain occurrence, frequency, and severity reported on the earliest MDS assessment within 3 months following the opioid regimen change. Resident attributes were described by opioid regimen cohort. Prevalence ratios of pain and depression indices were quantified using doubly robust inverse probability of treatment (IPT)-weighted log-binomial regression. Results: The study cohorts included 2072 SAO dose escalations, 575 LAO add-on initiations, and 247 LAO switch initiations. After IPT weighting, we observed comparable effects on pain and mood across the opioid regimen cohorts. A substantial number of residents continued to report frequent/constant pain (36% in SAO Escalation Cohort, 42% in LAO Add-on Cohort, 42% in the LAO Switch Cohort). The distribution of depressive symptoms was similar regardless of the opioid regimen change. Conclusions and implications: Initiation of an LAO as an add-on to SAO or a switch from SAO had comparable effects on pain and mood to SAO dose escalation without initiation of an LAO. Although fewer residents reported any pain after the regimen change, persistent pain was reported by most residents.
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  Lifestyle practices and associated factors among adults with hypertension: Conquering Hypertension in Vietnam-solutions at the grassroots level study

  Nguyen, Phuong H; Goldberg, Robert J.; Allison, Jeroan J.; Nguyen, Diep B; Tran, Ha T; Tran, Oanh M; Ha, Duc A; Nguyen, Hieu L; Tran, Brittany A; Wang, Bo; et al. (2024-06-06)

  Background: Vietnam is experiencing an increasing prevalence of hypertension in its adult population. In addition to medical therapy, modifying adverse lifestyle practices is important for effective blood pressure control. There are limited data on unhealthy lifestyle practices in patients with chronic diseases, however, particularly among hypertensive patients living in rural Vietnam. Our study objectives were to examine the prevalence of unhealthy lifestyle practices and associated factors among rural Vietnamese adults with uncontrolled hypertension. Methods: Data from the baseline survey of a cluster randomized trial among hypertensive Vietnamese adults (2017-2022) were utilized. Information on unhealthy lifestyle practices including smoking, excessive alcohol consumption, physical inactivity, and inadequate fruit and vegetable intake was collected from study participants. The primary study outcome was having ≥2 unhealthy lifestyle practices. A multivariable logistic regression model was used to examine factors associated with the primary study outcome. Results: The mean age of the 671 patients was 67 years and 45.0% were men. Nearly three out of every four participants had one or fewer unhealthy practices, 24.0% had two, and 3.3% had three or all four unhealthy lifestyle practices. Men, individuals who did unpaid work or were unemployed, and individuals with hypertension level III were more likely to have ≥2 unhealthy lifestyle practices, whereas individuals with higher education were less likely to have ≥2 unhealthy lifestyle practices compared with respective comparison groups. Conclusions: We observed a high prevalence of unhealthy lifestyle practices among rural Vietnamese patients with uncontrolled hypertension. Several demographic factors were associated with a greater number of unhealthy lifestyle practices. Newer interventions and educational programs encouraging lifestyle modification practices are needed to control hypertension among adults living in rural settings of Vietnam.
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  Health Insurance Type and Outpatient Specialist Care Among Children With Asthma

  Geissler, Kimberley H; Shieh, Meng-Shiou; Krishnan, Jerry A; Lindenauer, Peter K; Ash, Arlene S.; Goff, Sarah L (2024-06-03)

  Importance: Although children with asthma are often successfully treated by primary care clinicians, outpatient specialist care is recommended for those with poorly controlled disease. Little is known about differences in specialist use for asthma among children with Medicaid vs private insurance. Objective: To examine differences among children with asthma regarding receipt of asthma specialist care by insurance type. Design, setting, and participants: In this cross-sectional study using data from the Massachusetts All Payer Claims Database (APCD) between 2014 to 2020, children with asthma were identified and differences in receipt of outpatient specialist care by whether their insurance was public (Medicaid and the Children's Health Insurance Program) or private were examined. Eligible participants included children with asthma in 2015 to 2020 aged 2 to 17 years. Data analysis was conducted from January 2023 to April 2024. Exposure: Medicaid vs private insurance. Main outcomes and measures: The primary outcome was receipt of specialist care (any outpatient visit with a pulmonology, allergy and immunology, or otolaryngology physician). Multivariable logistic regression models estimated differences in receipt of specialist care by insurance type accounting for child and area characteristics including demographics, health status, persistent asthma, calendar year, and zip code characteristics. Additional analyses examined if the associations of specialist care with insurance type varied by asthma persistence and severity, and whether associations varied over time. Results: Among 198 101 unique children, there were 432 455 child-year observations (186 296 female [43.1%] and 246 159 male [56.9%]; 211 269 aged 5 to 11 years [48.9%]; 82 108 [19.0%] with persistent asthma) including 286 408 (66.2%) that were Medicaid insured and 146 047 (33.8%) that were privately insured. Although persistent asthma was more common among child-year observations with Medicaid vs private insurance (57 381 [20.0%] vs 24 727 [16.9%]), children with Medicaid were less likely to receive specialist care. Overall, 64 239 child-year observations (14.9%) received specialist care, with substantially lower rates for children with Medicaid vs private insurance (34 093 child-year observations [11.9%] vs 30 146 child-year observations [20.6%]). Regression-based estimates confirmed these disparities; children with Medicaid had 55% lower odds of receiving specialist care (adjusted odds ratio, 0.45; 95% CI, 0.43 to 0.47) and a regression-adjusted 9.7 percentage point (95% CI, -10.4 percentage points to -9.1 percentage points) lower rate of receipt of specialist care. Compared with children with private insurance, there was an additional 3.2 percentage point (95% CI, 2.0 percentage points to 4.4 percentage points) deficit for children with Medicaid with persistent asthma. Conclusions and relevance: In this cross-sectional study, children with Medicaid were less likely to receive specialist care, with the largest gaps among those with persistent asthma. These findings suggest that closing this care gap may be one approach to addressing ongoing disparities in asthma outcomes.
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  Performance of and Severe Acute Respiratory Syndrome Coronavirus 2 Diagnostics Based on Symptom Onset and Close Contact Exposure: An Analysis From the Test Us at Home Prospective Cohort Study

  Herbert, Carly; Wang, Biqi; Lin, Honghuang; Yan, Yi; Hafer, Nathaniel; Pretz, Caitlin; Stamegna, Pamela; Wright, Colton; Suvarna, Thejas; Harman, Emma; et al. (2024-05-31)

  Background: Understanding changes in diagnostic performance after symptom onset and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure within different populations is crucial to guide the use of diagnostics for SARS-CoV-2. Methods: The Test Us at Home study was a longitudinal cohort study that enrolled individuals across the United States between October 2021 and February 2022. Participants performed paired antigen-detection rapid diagnostic tests (Ag-RDTs) and reverse-transcriptase polymerase chain reaction (RT-PCR) tests at home every 48 hours for 15 days and self-reported symptoms and known coronavirus disease 2019 exposures immediately before testing. The percent positivity for Ag-RDTs and RT-PCR tests was calculated each day after symptom onset and exposure and stratified by vaccination status, variant, age category, and sex. Results: The highest percent positivity occurred 2 days after symptom onset (RT-PCR, 91.2%; Ag-RDT, 71.1%) and 6 days after exposure (RT-PCR, 91.8%; Ag-RDT, 86.2%). RT-PCR and Ag-RDT performance did not differ by vaccination status, variant, age category, or sex. The percent positivity for Ag-RDTs was lower among exposed, asymptomatic than among symptomatic individuals (37.5% (95% confidence interval [CI], 13.7%-69.4%) vs 90.3% (75.1%-96.7%). Cumulatively, Ag-RDTs detected 84.9% (95% CI, 78.2%-89.8%) of infections within 4 days of symptom onset. For exposed participants, Ag-RDTs detected 94.0% (95% CI, 86.7%-97.4%) of RT-PCR-confirmed infections within 6 days of exposure. Conclusions: The percent positivity for Ag-RDTs and RT-PCR tests was highest 2 days after symptom onset and 6 days after exposure, and performance increased with serial testing. The percent positivity of Ag-RDTs was lowest among asymptomatic individuals but did not differ by sex, variant, vaccination status, or age category.
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  Methods for structural sexism and population health research: Introducing a novel analytic framework to capture life-course and intersectional effects

  Beccia, Ariel L; Agénor, Madina; Baek, Jonggyu; Ding, Eric Y; Lapane, Kate L; Austin, S Bryn (2024-05-31)

  Accumulating evidence links structural sexism to gendered health inequities, yet methodological challenges have precluded comprehensive examinations into life-course and/or intersectional effects. To help address this gap, we introduce an analytic framework that uses sequential conditional mean models (SCMMs) to jointly account for longitudinal exposure trajectories and moderation by multiple dimensions of social identity/position, which we then apply to study how early life-course exposure to U.S. state-level structural sexism shapes mental health outcomes within and between gender groups. Data came from the Growing Up Today Study, a cohort of 16,875 children aged 9-14 years in 1996 who we followed through 2016. Using a composite index of relevant public policies and societal conditions (e.g., abortion bans, wage gaps), we assigned each U.S. state a year-specific structural sexism score and calculated participants' cumulative exposure by averaging the scores associated with states they had lived in during the study period, weighted according to duration of time spent in each. We then fit a series of SCMMs to estimate overall and group-specific associations between cumulative exposure from baseline through a given study wave and subsequent depressive symptomology; we also fit models using simplified (i.e., non-cumulative) exposure variables for comparison purposes. Analyses revealed that cumulative exposure to structural sexism: (1) was associated with significantly increased odds of experiencing depressive symptoms by the subsequent wave; (2) disproportionately impacted multiply marginalized groups (e.g., sexual minority girls/women); and (3) was more strongly associated with depressive symptomology compared to static or point-in-time exposure operationalizations (e.g., exposure in a single year). Substantively, these findings suggest that long-term exposure to structural sexism may contribute to the inequitable social patterning of mental distress among young people living in the U.S. More broadly, the proposed analytic framework represents a promising approach to examining the complex links between structural sexism and health across the life course and for diverse social groups.
• Geographic Variation of Antidementia and Antipsychotic Medication Use Among US Nursing Home Residents With Dementia

  Rataj, Alison; Alcusky, Matthew J; Baek, Jonggyu; Ott, Brian; Lapane, Kate L (2024-05-29)

  Background: Several antidementia medications have been approved for symptomatic treatment of cognitive and functional impairment due to Alzheimer disease. Antipsychotics are often prescribed off-label for behavioral symptoms. Objective: The aim of this study was to describe the basis for regional variation in antidementia and antipsychotic medication use. Setting: US nursing homes (n=9735), hospital referral regions (HRR; n=289). Subjects: Long-stay residents with dementia (n=273,004). Methods: Using 2018 Minimum Data Set 3.0 linked to Medicare data, facility information, and Dartmouth Atlas files, we calculated prevalence of use and separate multilevel logistic models [outcomes: memantine, cholinesterase inhibitor (ChEI), antipsychotic use] estimated adjusted odds ratios (aOR) and 95% CIs for resident, facility, and HRR characteristics. We then fit a series of cross-classified multilevel logistic models to estimate the proportional change in cluster variance (PCV). Results: Overall, 20.9% used antipsychotics, 16.1% used memantine, and 23.3% used ChEIs. For antipsychotics, facility factors [eg, use of physical restraints (aOR: 1.08; 95% CI: 1.05-1.11) or poor staffing ratings (aOR: 1.10; 95% CI: 1.06-1.14)] were associated with more antipsychotic use. Nursing homes in HRRs with the highest health care utilization had greater antidementia drug use (aOR memantine: 1.68; 95% CI: 1.44-1.96). Resident/facility factors accounted for much regional variation in antipsychotics (PCV STATE : 27.80%; PCV HRR : 39.54%). For antidementia medications, HRR-level factors accounted for most regional variation (memantine PCV STATE : 37.44%; ChEI PCV STATE : 39.02%). Conclusion: Regional variations exist in antipsychotic and antidementia medication use among nursing home residents with dementia suggesting the need for evidence-based protocols to guide the use of these medications.
• Disparities in Palliative Care Use for Patients With Blood Cancer Who Died in the Hospital

  Hsieh, Tien-Chan; Yeo, Yee Hui; Zou, Guangchen; Zhou, Chan; Ash, Arlene S. (2024-05-27)

  Background: Palliative care can enhance quality of life during a terminal hospitalization. Despite advances in diagnostic and treatment tools, blood cancers lag behind solid malignancies in palliative use. It is not clear what factors affect palliative care use in blood cancer. Methods: We used the 2016 to 2019 National Inpatient Sample to identify demographic and socioeconomic factors associated with receiving palliative care among patients over age 18 with any malignant hematological diagnosis during a terminal hospitalization lasting at least 3 days, excluding those receiving a stem cell transplant. Results: Palliative care use was documented 54% of the time among 49,720 weighted cases (9944 distinct individual hospitalizations), approximately evenly distributed across the years 2016-2019. Palliative care use was lowest in 2016 (51%) and highest in 2018 (58%), and increased with age, reaching 58% for those 80 years and older. Men and women were similarly likely to receive care. Patients of Hispanic ethnicity and African Americans received less palliative care (47% and 49%, respectively), as did those insured by Medicaid (48%), and those admitted to small or rural hospitals (52% and 47%, respectively). Charges for hospitalizations with palliative care were 19% lower than for those without it. Conclusions: This study highlights disparities in palliative care use among blood-cancer patients who died in the hospital. It seems likely that many of the 46% who did not receive palliative care could have benefitted from it. Interventions are likely needed to achieve equitable access to ideal levels of palliative care services in late-stage blood cancer.
• Cognitive impairment and treatment strategy for atrial fibrillation in older adults: The SAGE-AF study

  Athreya, Deepti S; Saczynski, Jane S; Gurwitz, Jerry H; Monahan, Kevin M; Bamgbade, Benita A; Paul, Tenes J; Sogade, Felix; Lessard, Darleen M; McManus, David D; Helm, Robert H (2024-05-14)

  Background: Cognitive impairment is strongly associated with atrial fibrillation (AF). Rate and rhythm control are the two treatment strategies for AF and the effect of treatment strategy on risk of cognitive decline and frailty is not well established. We sought to determine how treatment strategy affects geriatric-centered outcomes. Methods: The Systematic Assessment of Geriatric Elements-AF (SAGE-AF) was a prospective, observational, cohort study. Older adults with AF were prospectively enrolled between 2016 and 2018 and followed longitudinally for 2 years. In a non-randomized fashion, participants were grouped by rate or rhythm control treatment strategy based on clinical treatment at enrollment. Baseline characteristics were compared. Longitudinal binary mixed models were used to compare treatment strategy with respect to change in cognitive function and frailty status. Cognitive function and frailty status were assessed with the Montreal Cognitive Assessment Battery and Fried frailty phenotype tools. Results: 972 participants (mean age = 75, SD = 6.8; 49% female, 87% non-Hispanic white) completed baseline examination and 2-year follow-up. 408 (42%) were treated with rate control and 564 (58%) with rhythm control. The patient characteristics of the two groups were different at baseline. Participants in the rate control group were older, more likely to have persistent AF, prior stroke, be treated with warfarin and have baseline cognitive impairment. After adjusting for baseline differences, participants treated with rate control were 1.5 times more likely to be cognitively impaired over 2 years (adjusted OR: 1.47, 95% CI:1.12, 1.98) and had a greater decline in cognitive function (adjusted estimate: -0.59 (0.23), p < 0.01) in comparison to rhythm control. Frailty did not vary between the treatment strategies. Conclusions: Among those who had 2-year follow-up in non-randomized observational cohort, the decision to rate control AF in older adults was associated with increased odds of decline in cognitive function but not frailty.
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  Teachers' Perceptions of the Impact of the COVID-19 Pandemic and Their Implementation of an Evidence-based HIV Prevention Program in the Bahamas

  Schieber, Elizabeth; Cottrell, Lesley; Deveaux, Lynette; Li, Xiaoming; Taylor, Marcellus; Adderley, Richard; Marshall, Sharon; Forbes, Nikkiah; Wang, Bo (2024-04-20)

  Information on how school-based programs is implemented and sustained during crises is limited. In this study, we assessed the impact of the COVID-19 pandemic on the implementation of a HIV prevention intervention in The Bahamas. Data were collected from 139 Grade 6 teachers in 2021-2022. Teachers attended virtual training and received implementation monitoring from coordinators. On average, teachers taught 26.4 (SD = 9.2) of the 35 core activities, and 7.4 (SD = 2.4) out of 9 sessions. More than half (58.3%) of teachers completed 28 or more core activities; 69.1% covered eight or all nine sessions, which is equivalent to 80% of the HIV intervention curriculum. Almost half of the teachers (43%) reported that the pandemic negatively impacted their ability to teach the program; 72% of teachers maintained that the program remained "very important" during times of crisis. Greater self-efficacy and supports increased implementation fidelity.
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  A Comparison of 5 Measures of Accelerated Biological Aging and Their Association With Incident Cardiovascular Disease: The CARDIA Study

  Forrester, Sarah N; Baek, Jonggyu; Hou, Lifang; Roger, Veronique; Kiefe, Catarina I (2024-04-12)

  Background: Accelerated biological aging is an increasingly popular way to track the acceleration of biology over time that may not be captured by calendar time. Biological aging has been linked to external and internal chronic stressors and has the potential to be used clinically to understand a person's personalized functioning and predict future disease. We compared the association of different measures of biological aging and incident cardiovascular disease (CVD) overall and by race. Methods and results: We used multiple informants models to compare the strength of clinical marker-derived age acceleration, 5 measures of epigenetic age acceleration (intrinsic and extrinsic epigenetic age acceleration, GrimAge acceleration, and PhenoAge acceleration), and 1 established clinical predictor of future CVD, Framingham 10-year risk score, with incident CVD over an 11-year period (2007-2018). Participants were 913 self-identified Black or White (41% and 59%, respectively) female or male (51% and 49%, respectively) individuals enrolled in the US-based CARDIA (Coronary Artery Risk Development in Young Adults) cohort study. The analytic baseline for this study was the 20-year follow-up examination (2005-2006; median age 45 years). We also included race-specific analysis. We found that all measures were modestly correlated with one another. However, clinical marker-derived age acceleration and Framingham 10-year risk score were more strongly associated with incident CVD than all the epigenetic measures. Clinical marker-derived age acceleration and Framingham 10-year risk score were not significantly different than one another in their association with incident CVD. Conclusions: The type of accelerated aging measure should be taken into consideration when comparing their association with clinical outcomes. A multisystem clinical composite shows associations with incident CVD equally to a well-known clinical predictor.
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  Peer Texting to Promote Quitline Use and Smoking Cessation Among Rural Participants in Vietnam: Randomized Clinical Trial

  Sadasivam, Rajani S; Nagawa, Catherine S; Wijesundara, Jessica G; Flahive, Julie; Nguyen, Hoa L; Larkin, Celine; Faro, Jamie M; Balakrishnan, Kavitha; Ha, Duc Anh; Nguyen, Cuong Kieu; et al. (2024-04-08)

  Objectives: We tested an adapted version of an effective U.S.-based peer-texting intervention to promote Quitline use and smoking cessation among rural participants in Vietnam. Methods: We conducted a two-arm randomized trial with participants recruited at four rural community centers. The intervention included peer messages sent for six months that promoted Quitline use and smoking cessation. Additionally, biweekly two-way text messages assessed participants' interest in Quitline referral and current smoking status. Comparison participants received only the bi-weekly text message assessment of their current smoking status. At six months, we assessed Quitline use and smoking cessation. Smoking cessation was assessed using the 7-day point prevalence question and verified with a carbon monoxide breath monitor (<=6 ppm). Results: Among 750 participants, the intervention had higher Quitline verified use (18%, 95% CI 0.14, 0.22) than comparison (1%, 95% CI .2, 2, p < 0.0001). Carbon-monoxide-verified smoking cessation did not differ between the two groups. However, intervention (28.3%, 95% CI) and comparison (28.1%, 95% CI) participants had substantial rates of carbon monoxide cessation at 6 months (both 28%). Conclusion: Our study highlighted the promise of texting interventions to extend tobacco control efforts in Vietnam.

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