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Plummer-Vinson Syndrome (PVS) is a rare disorder characterized by upper esophageal webs and iron deficiency anemia and is even more uncommon among people of African descent. We report a case of this syndrome in a middle-aged black woman, which improved on iron-repletion therapy alone. The patient presented with long-standing dysphagia and symptomatic anemia. Gastrointestinal endoscopy revealed an upper esophageal web arising from the anterior wall. She was started on iron therapy daily and after 2 months both the dysphagia and anemia had improved significantly. Therefore, though this is a relatively rare condition in Africa, it still warrants being part of the differential diagnosis for dysphagia especially in the setting of anemia.

BackgroundThe fossil record reveals surprising crocodile diversity in the Neogene of Africa, but relationships with their living relatives and the biogeographic origins of the modern African crocodylian fauna are poorly understood. A Plio-Pleistocene crocodile from Olduvai Gorge, Tanzania, represents a new extinct species and shows that high crocodylian diversity in Africa persisted after the Miocene. It had prominent triangular "horns" over the ears and a relatively deep snout, these resemble those of the recently extinct Malagasy crocodile Voay robustus, but the new species lacks features found among osteolaemines and shares derived similarities with living species of Crocodylus.Methodology/principal findingsThe holotype consists of a partial skull and skeleton and was collected on the surface between two tuffs dated to approximately 1.84 million years (Ma), in the same interval near the type localities for the hominids Homo habilis and Australopithecus boisei. It was compared with previously-collected material from Olduvai Gorge referable to the same species. Phylogenetic analysis places the new form within or adjacent to crown Crocodylus.Conclusions/significanceThe new crocodile species was the largest predator encountered by our ancestors at Olduvai Gorge, as indicated by hominid specimens preserving crocodile bite marks from these sites. The new species also reinforces the emerging view of high crocodylian diversity throughout the Neogene, and it represents one of the few extinct species referable to crown genus Crocodylus.

Rationale: Tobacco use is a risk factor for COVID-19 adverse outcomes. Despite health implications, data conflict regarding COVID-19 and tobacco consumption. We present results from a survey of health behaviors during the pandemic to identify how COVID-19 influenced tobacco behaviors., Methods: A nationally administered, internet-based survey was deployed between May-September 2020. Of respondents, we analyzed participants who reported current smoking and/or vaping. Our primary outcome of interest was change in tobacco or vape use using measures from the Behavioral Risk Factor Surveillance System, as well as whether participants reported that these changes were related to COVID-19. Our principal exposures were previously psychometrically evaluated measures of anxiety, depression, and novel perceived COVID-19 threat scale with additional adjustment for age. We employed multinomial logistic regression to determine associations between these factors and tobacco consumption., Results: We identified 500 respondents who reported ever smoking in their lifetime, 150 of which reported currently smoking at the time of the survey. Of 220 participants who reported any use of vapes, 110 reported currently vaping. Increased perceived threat of COVID-19 was associated with both increased (aRR increase 1.75, 95% CI [1.07-2.86], P = 0.03) and decreased (aRR decrease 1.72 [1.04-2.85], P = 0.03) tobacco consumption relative to no change. There were no significant relationships found between perceived threat of COVID-19 and vaping behavior., Conclusions: As perceived COVID-19 threat increased, people were more likely to increase or decrease their smoking as opposed to continue at the same amount of use, even after controlling for anxiety and depression, both of which are known to affect smoking in either direction. Further study into motivators of changing tobacco consumption behaviors, and how barriers to care from safer-at-home policies and changes in care delivery moderate change in tobacco use will aid planning tobacco reduction interventions during the ongoing and future respiratory viral pandemics., Trial Registration: This manuscript is derived from baseline survey data obtained in the "Understanding Community Considerations, Opinions, Values, Impacts, and Decisions in COVID-19" study., Clinicaltrials: gov registration NCT04373135, registered 04/30/2020., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: The University of California's Diabetes Prevention Program (UC DPP) Initiative was implemented systemwide to address diabetes and obesity risk on all 10 campuses. As little is known about implementing lifestyle change programs in university settings, we examined implementation partners' (i.e., UC DPP leaders and campus leads) perceptions of factors influencing program success on UC campuses., Methods: We conducted qualitative interviews with UC DPP leaders and campus leads to examine challenges and opportunities with university-based DPP delivery models. Interviews were recorded, professionally transcribed, and reviewed in detail by the research team. Transcripts were analyzed using rapid qualitative analysis (RQA). The study was approved by the UCLA Institutional Review Board. All implementation partners provided verbal informed consent., Results: Twenty-six implementation partners (8 UC DPP leaders and 18 campus leads) completed interviews in 2021. Seven themes were identified as critical for implementation, including (1) marketing and recruitment (i.e., market and recruit broadly through established channels as well as target at-risk populations); (2) enrollment (i.e., offer the program during convenient times and let participants know what to expect); (3) use an adaptable, evidence-based program; (4) secure funding for the program, participants, lifestyle coaches, and space; (5) hire experienced and dedicated staff and lifestyle coaches; (6) ensure leadership support; and (7) utilize campus linkages and resources. Perceptions of challenges faced with respect to these themes are also described., Conclusions: This is one of the first studies to examine the challenges and opportunities of delivering an intensive lifestyle change program across 10 university sites. Understanding factors that enhance success of university-based diabetes prevention programs can facilitate UC DPP efforts and help inform delivery strategies of health and wellness programs across other university settings more broadly., (© 2024. The Author(s).)

Importance: Elevated ambient fine particulate matter (PM2.5) air pollution exposure has been associated with poor health outcomes across several domains, but its associated outcomes among lung transplant recipients are poorly understood., Objective: To investigate whether greater PM2.5 exposure at the zip code of residence is associated with a higher hazard for mortality and graft failure in patients with lung transplants., Design, Setting, and Participants: This retrospective cohort study used panel data provided by the United Network for Organ Sharing, which includes patients receiving transplants across all active US lung transplant programs. Adult patients who received lung transplants between May 2005 and December 2016 were included, with a last follow-up of September 10, 2020. Data were analyzed from September 2022 to May 2023., Exposure: Zip code-level annual PM2.5 exposure was constructed using previously published North American estimates., Main Outcomes and Measures: The primary outcome was time to death or lung allograft failure after lung transplant. A gamma shared frailty Cox proportional hazards model was used to produce unadjusted and adjusted hazard ratios (HRs) to estimate the association of zip code PM2.5 exposure at the time of transplant with graft failure or mortality., Results: Among 18 265 lung transplant recipients (mean [SD] age, 55.3 [13.2] years; 7328 female [40.2%]), the resident zip code's annual PM2.5 exposure level was greater than or equal to the Environmental Protection Agency (EPA) standard of 12μg/m3 for 1790 patients (9.8%) and less than the standard for 16 475 patients (90.2%). In unadjusted analysis, median graft survival was 4.87 years (95% CI, 4.57-5.23 years) for recipients living in high PM2.5 areas and 5.84 years (95% CI, 5.71-5.96 years) for recipients in the low PM2.5 group. Having an annual PM2.5 exposure level greater than or equal to the EPA standard 12 μg/m3 was associated with an increase in the hazard of death or graft failure (HR, 1.11; 95% CI, 1.05-1.18; P < .001) in the unadjusted analysis and after adjusting for covariates (HR, 1.08; 95% CI, 1.01-1.15; P = .02). Each 1 μg/m3 increase in exposure was associated with an increase in the hazard of death or graft failure (adjusted HR, 1.01; 95% CI, 1.00-1.02; P = .004) when treating PM2.5 exposure as a continuous variable., Conclusions and Relevance: In this study, elevated zip code-level ambient PM2.5 exposure was associated with an increased hazard of death or graft failure in lung transplant recipients. Further study is needed to better understand this association, which may help guide risk modification strategies at individual and population levels.

Objectives: To report lessons from integrating the methods and perspectives of clinical informatics (CI) and implementation science (IS) in the context of Improving the Management of symPtoms during and following Cancer Treatment (IMPACT) Consortium pragmatic trials., Materials and Methods: IMPACT informaticists, trialists, and implementation scientists met to identify challenges and solutions by examining robust case examples from 3 Research Centers that are deploying systematic symptom assessment and management interventions via electronic health records (EHRs). Investigators discussed data collection and CI challenges, implementation strategies, and lessons learned., Results: CI implementation strategies and EHRs systems were utilized to collect and act upon symptoms and impairments in functioning via electronic patient-reported outcomes (ePRO) captured in ambulatory oncology settings. Limited EHR functionality and data collection capabilities constrained the ability to address IS questions. Collecting ePRO data required significant planning and organizational champions adept at navigating ambiguity., Discussion: Bringing together CI and IS perspectives offers critical opportunities for monitoring and managing cancer symptoms via ePROs. Discussions between CI and IS researchers identified and addressed gaps between applied informatics implementation and theory-based IS trial and evaluation methods. The use of common terminology may foster shared mental models between CI and IS communities to enhance EHR design to more effectively facilitate ePRO implementation and clinical responses., Conclusion: Implementation of ePROs in ambulatory oncology clinics benefits from common understanding of the concepts, lexicon, and incentives between CI implementers and IS researchers to facilitate and measure the results of implementation efforts., Competing Interests: The authors have no competing interests to report., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Preclinical studies suggest that simultaneous HER2/VEGF blockade may have cooperative effects in gastroesophageal adenocarcinomas. In a single-arm investigator initiated clinical trial for patients with untreated advanced HER2+ gastroesophageal adenocarcinoma, bevacizumab was added to standard of care capecitabine, oxaliplatin, and trastuzumab in 36 patients (NCT01191697). Primary endpoint was objective response rate and secondary endpoints included safety, duration of response, progression free survival, and overall survival. The study met its primary endpoint with an objective response rate of 81% (95% CI 65-92%). Median progression free and overall survival were 14.0 (95% CI, 11.3-36.4) and 23.2 months (95% CI, 16.6-36.4), respectively. The median duration of response was 14.9 months. The regimen was well tolerated without unexpected or severe toxicities. In post-hoc ctDNA analysis, baseline ctDNA features were prognostic: Higher tumor fraction and alternative MAPK drivers portended worse outcomes. ctDNA at resistance identified oncogenic mutations and these were detectable 2-8 cycles prior to radiographic progression. Capecitabine, oxaliplatin, trastuzumab and bevacizumab shows robust clinical activity in HER2+ gastroesophageal adenocarcinoma. Combination of VEGF inhibitors with chemoimmunotherapy and anti-PD1 regimens is warranted., (© 2024. The Author(s).)

Importance: Gender-affirming hormone treatment (GAHT) is a common therapy for transgender individuals to reduce gender dysphoria and improve quality of life. Clarifying the long-term effects of GAHT remains a priority in transgender health research., Objective: To explore whether sex hormones (estradiol and testosterone) are associated with the development of metabolic syndrome in transgender veterans compared with cisgender veterans., Design, Setting, and Participants: This retrospective, longitudinal cohort study used International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes for gender dysphoria from the Veterans Health Administration national database to identify transfeminine and transmasculine veterans receiving documented feminizing (estradiol) or masculinizing (testosterone) treatment from January 1, 2006, to December 31, 2019, and for whom the GAHT initiation date and metabolic syndrome component-related data were available. Transgender veterans were matched to cisgender referents., Exposure: Gender-affirming hormone treatment., Main Outcomes and Measures: Metabolic syndrome z-scores were calculated based on body mass index, systolic blood pressure, and levels of high-density lipoprotein cholesterol, triglycerides, and blood glucose. Changes in mean z-scores were compared among the transgender and cisgender groups before and after the index date (corresponding to GAHT initiation) using a repeated-measures analysis of variance model., Results: The cohort included 1290 participants: 645 transgender (494 [38.3%] transfeminine, 151 [11.7%] transmasculine) and 645 cisgender (280 [21.7%] female, 365 [28.3%] male). Mean (SD) age at the index date was 41.3 (13.2) years. Metabolic syndrome z-scores changed significantly over time and differed significantly across groups. Overall, transmasculine veterans had the greatest percentage increase in mean (SEM) z-scores after vs before the index date (298.0% [57.0%]; P < .001), followed by cisgender females (108.3% [27.5%]; P < .001), cisgender males (49.3% [27.5%]; P = .02), and transfeminine persons (3.0% [10.7%]; P = .77)., Conclusions and Relevance: In this cohort study, in both cisgender and transgender veterans, estradiol was associated with reduced metabolic syndrome risk, whereas testosterone was associated with increased risk. However, transmasculine individuals had the greatest risk and transfeminine individuals had the lowest risk of metabolic syndrome associated with these hormones. This is relevant for the management of metabolic syndrome risk factors in cisgender and transgender individuals and to potentially predict the risk of atherosclerotic cardiovascular disease, type 2 diabetes, systolic hypertension, insulin resistance, and nonalcoholic fatty liver disease.

Importance: Chronic pain is common and disabling in older adults, and psychological interventions are indicated. However, the gold standard approach, cognitive-behavioral therapy (CBT), produces only modest benefits, and more powerful options are needed., Objectives: To evaluate whether emotional awareness and expression therapy (EAET) is superior to CBT for treatment of chronic pain among predominantly male older veterans and whether higher baseline depression, anxiety, or posttraumatic stress disorder (PTSD) symptoms-key targets of EAET-moderate treatment response., Design, Setting, and Participants: This 2-arm randomized clinical trial was conducted from May 16, 2019, to September 14, 2023, in the US Department of Veterans Affairs Greater Los Angeles Healthcare System. The trial included a racially and ethnically diverse group of veterans aged 60 to 95 years with at least 3 months of musculoskeletal pain., Interventions: Emotional awareness and expression therapy or CBT, conducted concurrently, each presented as one 90-minute individual session followed by eight 90-minute group sessions., Main Outcomes and Measures: The primary outcome was Brief Pain Inventory pain severity (range, 0 to 10) from baseline to posttreatment (week 10, primary end point) and 6-month follow-up. Secondary outcomes included Patient Reported Outcomes Institute Measurement System Anxiety, Depression, Fatigue, General Life Satisfaction (NIH Toolbox), Pain Interference, and Sleep Disturbance Short Forms, Patient Global Impression of Change (PGIC), and Satisfaction with Therapy and Therapist Scale-Revised. A subset of participants completed the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). All analyses were for the intention-to-treat population and included all randomized participants., Results: Among 126 randomized participants (66 in the EAET group and 60 in the CBT group; mean [SD] age, 71.9 [5.9] years; 116 [92%] male), 111 (88%) completed posttreatment, and 104 (82%) completed the 6-month follow-up. The EAET was superior to CBT for the primary outcome of reduction in pain severity at posttreatment (estimate, -1.59 [95% CI, -2.35 to -0.83]; P < .001) and follow-up (estimate, -1.01 [95% CI, -1.78 to -0.24]; P = .01). A greater percentage of participants in EAET vs CBT had clinically significant (at least 30%) pain reduction (63% vs 17%; odds ratio, 21.54 [95% CI, 4.66-99.56]; P < .001) at posttreatment. In addition, EAET was superior to CBT on 50% pain reduction (35% vs 7%; odds ratio, 11.77 [95% CI, 2.38-58.25]; P = .002), anxiety (estimate, -2.49 [95% CI, -4.30 to -0.68]; P = .006), depression (estimate, -3.06 [95% CI, -5.88 to -0.25]; P = .03), general life satisfaction (estimate, 1.23 [95% CI, 0.36-2.10]; P = .005), PTSD symptoms (estimate, -4.39 [95% CI, -8.44 to -0.34]; P = .03), PGIC score (estimate, 1.46 [95% CI, 0.77-2.15]; P < .001), and global treatment satisfaction (estimate, 0.28 [95% CI, 0.12-0.45]; P < .001) at posttreatment. Higher baseline depression (estimate, -1.55 [95% CI, -0.37 to 2.73]; P < .001), anxiety (estimate, -1.53 [95% CI, -2.19 to -0.88]; P < .001), and PTSD symptoms (estimate, -1.69 [95% CI, -2.96 to -0.42]; P = .009) moderated greater reduction in pain severity after EAET but not CBT., Conclusions and Relevance: The results of this randomized clinical trial suggest that EAET may be a preferred intervention for medically and psychiatrically complex patients with pain. The societal burden of chronic pain could be improved by further incorporating the principles of EAET into mainstream clinical pain medicine., Trial Registration: ClinicalTrials.gov Identifier: NCT03918642.

Purpose: Effective visual perceptual processing is one of the many components of surgical competence. Human face identification is most efficient when viewed upright. However, it is not yet clear how this perception sensitivity impacts eyelid symmetry. This study investigates surgeons' and laypeople's accuracy and efficiency in perceiving eyelid asymmetry from different spatial perspectives., Methods: A prospective psychometric experiment was conducted where oculoplastic surgeons were recruited from the American Society of Ophthalmic Plastic and Reconstructive Surgery and the Brazilian Oculoplastic Surgery Society, and control participants were recruited via crowdsourcing (Amazon's Mechanical Turk). Standard illustrations of the human face with varying degrees of eyelid abnormality, laterality, gender and rotation were presented to participants who were asked to judge whether the eyelids were symmetric or asymmetric., Results: The survey was completed by 75 oculoplastic surgeons (49.33% male; mean age of 46.9±10.7) and 192 lay individuals (54.6% male; mean age 34.6±11.3 years). Among oculoplastic surgeons, deviation from upright was significantly associated with increased reaction time and decreased proportion correct (OR per 45° for peak 0.68, 95% CI 0.60 to 0.77, p<0.001; OR per 45° for ptosis 0.52, 95% CI 0.32 to 0.87, p=0.012; OR per 180° for aggregate responses 0.56, 95% CI 0.51 to 0.61, p<0.001). Oculoplastic surgeons demonstrated increasing accuracy and decreasing reaction time with additional trials for both peak and ptosis., Conclusion: Oculoplastic surgeons perceive eyelid asymmetries more accurately and can better compensate for inverted sensory information. However, accuracy increases and reaction time decreases with additional trials, suggesting trainability and potential for improvement in inversion disability., Competing Interests: Competing interests: DBR and SBD have acted as medical consultants for Horizon Therapeutics. All other authors report no conflicts of interest, financial or otherwise. The authors alone are responsible for the content and writing of the paper., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sex and racial disparities in the presentation and management of chest pain persist, however, the impact of coronavirus disease 2019 (COVID-19) on these disparities have not been studied. We sought to determine whether the COVID-19 pandemic contributed to pre-existing sex and racial disparities in the presentation, management, and outcomes of patients presenting to the emergency department (ED) with chest pain., Methods: We conducted an observational cohort study with retrospective data collection of patients between January 1, 2016, and May 1, 2022. This was a single study conducted at a quaternary academic medical center of all patients who presented to the ED with a complaint of chest pain or chest pain equivalent symptoms. Patient were further segregated into different groups based on sex (male, female), race, ethnicity (Asian, Black, Hispanic, White, and other), and age (18 - 40, 41 - 65, > 65). We compared diagnostic evaluations, treatment decisions, and outcomes during prespecified time points before, during, and after the COVID-19 pandemic., Results: This study included 95,764 chest pain encounters. Total chest pain presentations to the ED fell about 38% during the early pandemic months. Females presented significantly less than males during initial COVID-19 (48% vs. 52%, P < 0.001) and Asian females were least likely to present. There was an increase in the total number of troponins and echocardiograms ordered during peak COVID-19 across both sexes, but females were still less likely to have these tests ordered across all timepoints. The number of coronary angiograms did not increase during peak COVID-19, and females were less likely to undergo coronary angiogram during all timepoints. Finally, females with chest pain were less likely to be diagnosed with acute myocardial infarction (AMI) during all timepoints, while in-hospital deaths were similar between males and females during all timepoints., Conclusions: During COVID-19, females, especially Asian females, were less likely to present to the ED for chest pain. Non-White patients were less likely to present to the ED compared to White patients prior to and during the pandemic. Disparities in management and outcomes of chest pain encounters remained similar to pre-COVID-19, with females receiving less cardiac workup and AMI diagnoses than males, but in-hospital mortality remaining similar between groups and timepoints., Competing Interests: None to declare., (Copyright 2024, Hu et al.)

Background: An ongoing important need exists to rapidly develop novel therapeutics for COVID-19 that will retain antiviral efficacy in the setting of rapidly evolving SARS-CoV-2 variants and potential future development of resistance of SARS-COV-2 to remdesivir and protease inhibitors. To date, there is no FDA-approved treatment for post-exposure prophylaxis against SAR-CoV-2. We have shown that the mitochondrial antioxidant mitoquinone/mitoquinol mesylate (Mito-MES), a dietary supplement, has antiviral activity against SARS-CoV-2 in vitro and in SARS-CoV-2 infected K18-hACE2 mice., Methods: In this exploratory, pragmatic open label clinical trial (ClinicalTrials.gov identifier NCT05381454), we studied whether Mito-MES is an effective post-exposure prophylaxis treatment in people who had high-grade unmasked exposures to SARS-CoV-2 within 5 days prior to study entry. Participants were enrolled in real-world setting in Los Angeles, United States between May 1 and December 1, 2022 and were assigned to either mito-MES 20 mg daily for 14 days (n = 40) or no mito-MES (controls) (n = 40). The primary endpoint was development of SARS-CoV-2 infection based on 4 COVID-19 diagnostic tests [rapid antigen tests (RATs) or PCR] performed during the study period (14 days post exposure)., Findings: Out of 40 (23 females; 57.5%) study participants who took Mito-MES, 12 (30%) developed SARS-CoV-2 infection compared to 30 of the 40 controls (75%) (difference -45.0%, 95% confidence intervals (CI): -64.5%, -25.5%). Out of 40 (19 females; 47.5%) study participants in the control group, 30 (75.0%) had at least one positive COVID-19 diagnostic test and 23 (57.5%) were symptomatic. With regards to key secondary outcomes, among symptomatic SARS-CoV-2 infections, the median duration of viral symptoms was lower in the Mito-MES group (median 3.0, 95% CI 2.75, 3.25) compared to the control group (median 5.0, 95% CI 4.0, 7.0). None of the study participants was hospitalized or required oxygen therapy. Mito-MES was well tolerated and no serious side effect was reported in any study participant., Interpretation: This work describes antiviral activity of mito-MES in humans. Mito-MES was well tolerated in our study population and attenuated transmission of SARS-CoV-2 infection. Given established safety of Mito-MES in humans, our results suggest that randomized control clinical trials of Mito-MES as post-exposure prophylaxis against SARS-CoV-2 infection are warranted., Funding: This work was supported in part by National Institutes of Health grant R01AG059501 (TK), National Institutes of Health grant R01AG059502 04S1 (TK), NIH/National Center for Advancing Translational Sciences (NCATS) UCLA CTSI Grant Number UL1TR001881 and California HIV/AIDS Research Program grant OS17-LA-002 (TK)., Competing Interests: Declaration of interests This manuscript is related to patents PCT/US2021/040869, US. Application No 63/166,207., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Non-invasive tests (NITs) can be used to estimate the severity of fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) but their diagnostic accuracy is variable. Hispanic patients are at increased risk of NAFLD and diabetes. We evaluate the diagnostic performance of the fibrosis index based on 4 factors (FIB-4) in a population of Hispanic patients who underwent vibration-controlled transient elastography (VCTE)., Methods: A total of 1,524 patients underwent VCTE at University of California, Los Angeles from July 18, 2019 to June 7, 2022. Ultimately 110 patients were identified as Hispanic, with confirmed NAFLD. Sensitivity, specificity, positive predictive value and negative predictive value of FIB-4 threshold ≥1.3 were calculated. Logistic regression models were used to determine updated thresholds for patients with and without diabetes based on Youden's index., Results: Of the 110 patients, the majority (65%) were female. Prevalence of diabetes was higher in the group with clinically significant fibrosis (76% vs. 36%, P<0.001). Using a FIB-4 threshold ≥1.3 to predict clinically significant fibrosis (F2-F4 on VCTE), area under the receiver operating characteristic (AUROC) was 0.74. By incorporating diabetes status, AUROC was 0.81 when employing a FIB-4 threshold of ≥1.0 in patients with diabetes and ≥1.5 in patients without diabetes., Conclusions: Using a FIB-4 threshold of ≥1.0 in patients with diabetes and ≥1.5 in patients without diabetes improves the diagnostic performance of the test. The new FIB-4 including diabetes status will lead to improved screening in patients who are at risk of clinically significant fibrosis., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-62/coif). S.S. reports receiving consulting fee from Gilead, Madrigal, Mallinckrodt, and speakers bureaus from AbbVie, Gilead, Intercept, Salix, Eisai, Exelisis, Mallinckrodt, Takeda. The other authors have no conflicts of interest to declare., (2024 Translational Gastroenterology and Hepatology. All rights reserved.)

Background: The University of California's Diabetes Prevention Program (UC DPP) Initiative was implemented across all 10 UC campuses in 2018. The COVID-19 pandemic and accompanying mandates required swift changes to program delivery, including pivoting from in-person to virtual delivery (i.e., Zoom). Our goal was to assess multilevel constituent perceptions of the use of a virtual platform to deliver UC DPP due to COVID-19 mandates., Methods: We conducted qualitative interviews with 68 UC DPP participants, coordinators, and leaders to examine the use of virtual platform delivery on the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) of UC DPP. Transcripts were analyzed using rapid qualitative analysis and emergent themes were categorized using domains corresponding to RE-AIM framework., Results: Among UC DPP participants ( n  = 42), virtual delivery primarily impacted perceptions of UC DPP effectiveness and implementation. Some participants perceived program effectiveness to be negatively impacted, given their preference for in-person sessions, which they felt provided more engagement, peer support, and accountability. Implementation challenges included problems with virtual format (e.g., "Zoom fatigue"); however, several benefits were also noted (e.g., increased flexibility, maintenance of DPP connections during campus closures). UC DPP coordinators ( n  = 18) perceived virtual delivery as positively impacting UC DPP reach, since virtual platforms provided access for some who could not participate in-person, and negatively impacting effectiveness due to reduced engagement and lower peer support. UC leaders ( n  = 8) perceived that use of the virtual format had a positive impact on reach (e.g., increased availability, accessibility) and negatively impacted effectiveness (e.g., less intensive interactions on a virtual platform). Across constituent levels, the use of a virtual platform had little to no impact on perceptions of adoption and maintenance of UC DPP., Conclusion: Perceptions of the reach, effectiveness, and implementation of UC DPP using a virtual platform varied across constituents, although all groups noted a potential negative impact on overall program effectiveness. Unanticipated program adaptations, including virtual delivery, present potential benefits as well as perceived drawbacks, primarily across the effectiveness domain. Understanding differential constituent perceptions of the impact of virtual delivery can help maximize RE-AIM and inform future UC DPP delivery strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Loeb, Gholami, Ramm, Shedd, Soetenga, Jackson, Chung, Duru, Mangione, Hamilton and Moin.)

Objectives: To examine changes in the 30-day surgical mortality rate after common surgical procedures during the COVID-19 pandemic and investigate whether its impact varies by urgency of surgery or patient race, ethnicity and socioeconomic status., Design: We used a quasi-experimental event study design to examine the effect of the COVID-19 pandemic on surgical mortality rate, using patients who received the same procedure in the prepandemic years (2016-2019) as the control, adjusting for patient characteristics and hospital fixed effects (effectively comparing patients treated at the same hospital). We conducted stratified analyses by procedure urgency, patient race, ethnicity and socioeconomic status (dual-Medicaid status and median household income)., Setting: Acute care hospitals in the USA., Participants: Medicare fee-for-service beneficiaries aged 65-99 years who underwent one of 14 common surgical procedures from 1 January 2016 to 31 December 2020., Main Outcome Measures: 30-day postoperative mortality rate., Results: Our sample included 3 620 689 patients. Surgical mortality was higher during the pandemic, with peak mortality observed in April 2020 (adjusted risk difference (aRD) +0.95 percentage points (pp); 95% CI +0.76 to +1.26 pp; p<0.001) and mortality remained elevated through 2020. The effect of the pandemic on mortality was larger for non-elective (vs elective) procedures (April 2020: aRD +0.44 pp (+0.16 to +0.72 pp); p=0.002 for elective; aRD +1.65 pp (+1.00, +2.30 pp); p<0.001 for non-elective). We found no evidence that the pandemic mortality varied by patients' race and ethnicity (p for interaction=0.29), or socioeconomic status (p for interaction=0.49)., Conclusions: 30-day surgical mortality during the COVID-19 pandemic peaked in April 2020 and remained elevated until the end of the year. The influence of the pandemic on surgical mortality did not vary by patient race and ethnicity or socioeconomic status, indicating that once patients were able to access care and undergo surgery, surgical mortality was similar across groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Short interpregnancy intervals (SIPIs) are associated with increased risk of adverse maternal and neonatal outcomes. Disparities exist across socioeconomic status, but there is little information on SIPIs among women experiencing homelessness., Objective: To investigate (1) differences in rates and characteristics of SIPIs between women experiencing homelessness and domiciled women, (2) whether the association of homelessness with SIPIs differs across races and ethnicities, and (3) whether the association between SIPIs of less than 6 months (very short interpregnancy interval [VSIPIs]) and maternal and neonatal outcomes differs between participant groups., Design, Setting, and Participants: This cohort study used a Colorado statewide database linking the Colorado All Payer Claims Database, Homeless Management Information System, death records, and infant birth records. Participants included all women who gave birth between January 1, 2016, and December 31, 2021. Data were analyzed from September 1, 2022, to May 10, 2023., Exposures: Homelessness and race and ethnicity., Main Outcomes and Measures: The primary outcome consisted of SIPI, a binary variable indicating whether the interval between delivery and conception of the subsequent pregnancy was shorter than 18 months. The association of VSIPI with maternal and neonatal outcomes was also tested., Results: A total of 77 494 women (mean [SD] age, 30.7 [5.3] years) were included in the analyses, of whom 636 (0.8%) were women experiencing homelessness. The mean (SD) age was 29.5 (5.4) years for women experiencing homelessness and 30.7 (5.3) years for domiciled women. In terms of race and ethnicity, 39.3% were Hispanic, 7.3% were non-Hispanic Black, and 48.4% were non-Hispanic White. Associations between homelessness and higher odds of SIPI (adjusted odds ratio [AOR], 1.23 [95% CI, 1.04-1.46]) were found. Smaller associations between homelessness and SIPI were found among non-Hispanic Black (AOR, 0.59 [95% CI, 0.37-0.96]) and non-Hispanic White (AOR, 0.57 [95% CI, 0.39-0.84]) women compared with Hispanic women. A greater association of VSIPI with emergency department visits and low birth weight was found among women experiencing homelessness compared with domiciled women, although no significant differences were detected., Conclusions and Relevance: In this cohort study of women who gave birth from 2016 to 2021, an association between homelessness and higher odds of SIPIs was found. These findings highlight the importance of conception management among women experiencing homelessness. Racial and ethnic disparities should be considered when designing interventions.

Aims: In patients with atrial fibrillation (AF) and stroke risk factors, randomized trials have demonstrated that anticoagulation decreases the risk of ischemic stroke. However, all trials to date have excluded patients with significant liver disease, leaving guidelines to extrapolate recommendations. We aim to evaluate the impact of anticoagulation on safety events in patients with AF and cirrhosis., Methods and Results: In this retrospective cohort study, we obtained de-identified health record data to extract anticoagulation strategy, comorbidities, prescriptions, lab values, and procedures for a cohort of patients with cirrhosis who develop AF. After selecting a propensity matched population to match patients with various anticoagulation strategies, we tracked data on outcomes for death, transfusion requirements, hospital and ICU admissions. After propensity score weighting and multivariable adjustment, anticoagulation strategy was associated with increased hospital admission count (OR = 1.74 per admission, P  < .001), binary risk of hospital admission (OR = 1.54, P  = .010) and risk of ICU admission (OR = 1.41, P  = .047). We detected no significant differences in mortality, transfusion of blood products, or average length of stay. Direct oral anticoagulant (DOAC) prescriptions were associated with increased binary risk of hospital admission compared to warfarin prescriptions. In a third comparison, DOAC strategy alone was associated with increased hospital admission count (OR = 1.41 per admission, P  < .001) and binary risk of hospital admission (OR = 1.52, P  = .038) compared to no anticoagulation strategy., Conclusion: Anticoagulation strategy in patients with cirrhosis and AF was associated with increased rate of hospital admission and ICU admission but not associated with increased risk of mortality or transfusion requirement., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Purpose: Clinical documentation of patient acuity is a major determinant of payer reimbursement. This project aimed to improve case mix index (CMI) by incorporating a novel electronic health record (EHR) discharge documentation tool into the inpatient general neurology service at the University of California, Los Angeles (UCLA) Medical Center., Methods: We used data from Vizient AMC Hospital: Risk Model Summary for Clinical Data Base (CBD) 2017 to create a discharge diagnosis documentation tool consisting of dropdown menus to better capture relevant secondary diagnoses and comorbidities. After implementation of this tool, we compared pre- (July 2017-June 2019) and post-intervention (July 2019-June 2021) time periods on mean expected length of stay (LOS) and mean CMI with two sample T-tests and the percentage of encounters classified as having Major Complications/Comorbidities (MCC), with Complication/Comorbidity (CC), and without CC/MCC with tests of proportions., Results: Mean CMI increased significantly from 1.2 pre-intervention to 1.4 post-intervention implementation ( P < .01). There was a pattern of increased MCC percentages for "Bacterial infections," "Other Disorders of Nervous System", "Multiple Sclerosis," and "Nervous System Neoplasms" diagnosis related groups post-intervention., Conclusions: This pilot study describes the creation of an innovative EHR discharge diagnosis documentation tool in collaboration with neurology healthcare providers, the clinical documentation improvement team, and neuro-informaticists. This novel discharge diagnosis documentation tool demonstrates promise in increasing CMI, shifting diagnosis related groups to a greater proportion of those with MCC, and improving the quality of clinical documentation., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

This study describes a novel, distinct phenotype of urinary symptoms named "myofascial urinary frequency syndrome" (MUFS) present in one-third of individuals presenting with urinary frequency. In addition to a characteristic symptom constellation suggestive of myofascial dysfunction, MUFS subjects exhibit "persistency": a persistent feeling of needing to urinate regardless of urine volume. On examination, 97% of MUFS patients demonstrated pelvic floor hypertonicity with either global tenderness or myofascial trigger points, and 92% displayed evidence of impaired muscular relaxation, hallmarks of myofascial dysfunction. To confirm this symptom pattern was attributable to the pelvic floor musculature, we confirmed the presence of "persistency" in 68 patients with pelvic floor myofascial dysfunction established through comprehensive examination and electromyography and corroborated by improvement with pelvic floor myofascial release. These symptoms distinguish subjects with myofascial dysfunction from subjects with OAB, IC/BPS, and asymptomatic controls, confirming MUFS is a distinct LUTS symptom complex., (© 2023. The Author(s).)

Background: Adolescent and young adult cancer patients (AYAs) who are sexual and gender minorities (SGM) are a rapidly increasing population that experiences unmet cancer-related needs. Despite emerging awareness, little is known about cancer care and outcomes for this vulnerable population. The purpose of this scoping review was to explore current knowledge and gaps in the literature on cancer care and outcomes for AYAs who identify as SGM., Methods: We reviewed empirical knowledge on SGM AYAs by identifying, describing, and critically appraising the literature to date. We conducted a comprehensive search on OVID MEDLINE, PsycINFO, and CINAHL in February 2022. Additionally, we developed and piloted a conceptual framework for appraising SGM AYA research., Results: A total of 37 articles were included in the final review. Most studies focused exclusively on SGM-related outcomes as the primary aim of the study (81.1%, n = 30), whereas others included some focus on SGM-related outcomes (18.9%, n = 7). The majority of studies included AYAs as part of a broader age range (86.0%, n = 32), and only a few studies examined exclusively AYA samples (14.0%, n = 5). Gaps in scientific evidence on SGM AYAs were seen across the cancer care continuum., Conclusion: Numerous gaps in knowledge of cancer care and outcomes exist for SGM AYAs diagnosed with cancer. Future efforts should fill this void with high-quality empirical studies that reveal unknown disparities in care and outcomes and are inclusive of the intersectionality of SGM AYAs with other minoritized experiences, thereby advancing health equity in meaningful ways., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Whether greater leisure time physical activity (LTPA) is associated with less bone mineral density (BMD) loss during the menopause transition (MT) remains an open question. We hypothesized that: 1) larger increases in LTPA from pre-/early perimenopause (period 1) to late perimenopause/postmenopause (period 2) would be associated with a slower period 2 BMD loss rate; and 2) greater entire-study LTPA levels would be associated with better final absolute BMD (g/cm 2 )., Methods: Data were from of the Study of Women's Health Across the Nation (1996-2017). Exclusions were: bone beneficial medications, inability to identify start of the MT, and extreme BMD change rates. LTPA measures were a validated ordinal scale and number of metabolic equivalents per hour per week (MET hr wk -1 ) from sport/exercise. Multiply adjusted, linear regression models estimated: 1) BMD decline rate (annualized %) as a function of LTPA change; and 2) final BMD as a function of entire-study LTPA., Findings: Median [p25, p75] MET hr wk -1 were 4.2 [0.9, 10.1] and 4.9 [1.4, 11.2] in periods 1 and 2, respectively; walking was the commonest activity. In adjusted models (N = 875), greater increases in LTPA ordinal score and MET hr wk -1 were statistically significantly associated with a slower decline in femoral neck (FN) BMD. Larger entire-study averages of each LTPA measure were statistically significantly related to better final FN and lumbar spine BMD levels., Interpretation: Findings suggest that LTPA, at modest levels, mitigate MT-related BMD decline and even small increases in intensity, duration or frequency of common activities may lessen bone loss at the population level., Funding: US-NIH., Competing Interests: All authors declare that they have no financial relationships with any organisation that might have an interest in the submitted work and have no other relationships or activities that could appear to have influenced the submitted work., (© 2023 The Authors.)

Importance: Telemedicine can increase access to care, but uptake has been low among people living in rural areas. The Veterans Health Administration initially encouraged telemedicine uptake in rural areas, but telemedicine expansion efforts have broadened since the COVID-19 pandemic., Objective: To examine changes over time in rural-urban differences in telemedicine use for primary care and for mental health integration services among Veterans Affairs (VA) beneficiaries., Design, Setting, and Participants: This cohort study examined 63.5 million primary care and 3.6 million mental health integration visits across 138 VA health care systems nationally from March 16, 2019, to December 15, 2021. Statistical analysis took place from December 2021 to January 2023., Exposures: Health care systems with most clinic locations designated as rural., Main Outcomes and Measures: For every system, monthly visit counts for primary care and mental health integration specialties were aggregated from 12 months before to 21 months after pandemic onset. Visits were categorized as in person or telemedicine, including video. A difference-in-difference approach was used to examine associations in visit modality by health care system rurality and pandemic onset. Regression models also adjusted for health care system size as well as relevant patient characteristics (eg, demographic characteristics, comorbidities, broadband internet access, and tablet access)., Results: The study included 63 541 577 primary care visits (6 313 349 unique patients) and 3 621 653 mental health integration visits (972 578 unique patients) (6 329 124 unique patients among the cohort; mean [SD] age, 61.4 [17.1] years; 5 730 747 men [90.5%]; 1 091 241 non-Hispanic Black patients [17.2%]; and 4 198 777 non-Hispanic White patients [66.3%]). In fully adjusted models for primary care services before the pandemic, rural VA health care systems had higher proportions of telemedicine use than urban ones (34% [95% CI, 30%-38%] vs 29% [95% CI, 27%-32%]) but lower proportions of telemedicine use than urban health care systems after pandemic onset (55% [95% CI, 50%-59%] vs 60% [95% CI, 58%-62%]), signifying a 36% reduction in the odds of telemedicine use (odds ratio [OR], 0.64; 95% CI, 0.54-0.76). The rural-urban telemedicine gap was even larger for mental health integration (OR, 0.49; 95% CI, 0.35-0.67) than for primary care services. Few video visits occurred across rural and urban health care systems (unadjusted percentages: before the pandemic, 2% vs 1%; after the pandemic, 4% vs 8%). Nonetheless, there were rural-urban divides for video visits in both primary care (OR, 0.28; 95% CI, 0.19-0.40) and mental health integration services (OR, 0.34; 95% CI, 0.21-0.56)., Conclusions and Relevance: This study suggests that, despite initial telemedicine gains at rural VA health care sites, the pandemic was associated with an increase in the rural-urban telemedicine divide across the VA health care system. To ensure equitable access to care, the VA health care system's coordinated telemedicine response may benefit from addressing rural disparities in structural capacity (eg, internet bandwidth) and from tailoring technology to encourage adoption among rural users.

Background and Objective: Nodding syndrome (NS) is a unique childhood-onset epileptic disorder that occurs predominantly in several regions of sub-Saharan Africa. The disease has been associated with Onchocerca volvulus (Ov) -induced immune responses and possible cross-reactivity with host proteins. The aim of this study was to compare structural changes in the brain on MRI between NS and other forms of onchocerciasis-associated epilepsies (OAEs) and to relate structural changes to the Ov-induced immune responses and level of disability., Methods: Thirty-nine children with NS and 14 age-matched participants with other forms of OAE from an endemic region in Uganda underwent detailed clinical examination, serologic evaluation (including Ov-associated antibodies to Ov-16 and Hu-leiomodin-1) and quantitative volumetric analysis of brain MRIs (1.5 T scanner) using Neuroreader, a cloud-based software., Results: Cerebral and cerebellar atrophy were the predominant features in both NS and OAE. On quantitative volumetric analysis, participants with NS had larger ventricular volumes compared with participants with OAE, indicative of increased global cortical atrophy (p corr = 0.036). Among children with NS, severe disability correlated with higher degree of atrophy in the gray matter volume (p corr = 0.009) and cerebellar volume (p corr = 0.009). NS cases had lower anti-Ov-16 IgG signal-to-noise ratios than the OAE cases ( p < 0.01), but no difference in the levels of the Hu-leiomodin-1 antibodies ( p = 0.64). The levels of Ov-associated antibodies did not relate to the degree of cerebral or cerebellar atrophy in either NS or OAE cases., Discussion: This is the first study to show that cerebral and cerebellar atrophy correlated with the severity of NS disability, providing an imaging marker for these endemic epileptic disorders that until now have remained poorly characterized. Both NS and OAE have cerebral and cerebellar atrophy, and the levels of Ov-associated antibodies do not seem to be related to the structural changes on MRI., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

The behavioral mechanisms by which predators encounter prey are poorly resolved. In particular, the extent to which predators engage in active search for prey versus incidentally encountering them has not been well studied in many systems and particularly not for neonate prey during the birth pulse. Parturition of many large herbivores occurs during a short and predictable temporal window in which young are highly vulnerable to predation. Our study aims to determine how a suite of carnivores responds to the seasonal pulse of newborn ungulates using contemporaneous global positioning system (GPS) locations of four species of predators and two species of prey. We used step-selection functions to assess whether coyotes, cougars, black bears, and bobcats encountered parturient adult female ungulates more often than expected by chance in a low-density population of mule deer and a high-density population of elk. We then assessed whether the carnivore species that encountered parturient prey more often than expected by chance did so by shifting their habitat use toward areas with a high probability of encountering neonates. None of the four carnivore species encountered GPS-collared parturient mule deer more often than expected by chance. By contrast, we determined that cougar and male bear movements positioned them in the proximity of GPS-collared parturient elk more often than expected by chance which may provide evidence of searching behavior. Although both male bears and cougars exhibited behavior consistent with active search for neonates, only male bears used elk parturition habitat in a way that dynamically tracked the phenology of the elk birth pulse suggesting that maximizing encounters with juvenile elk was a motivation when selecting resources. Our results suggest that there is high interspecific and intersexual variability in foraging strategies among large mammalian predators and their prey., Competing Interests: We declare no conflict of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Importance: Interventions directly targeting social factors, such as education, may have the potential to greatly improve health., Objective: To examine the association of attending a high-performing public charter high school with rates of substance use disorder and physical and mental health., Design, Setting, and Participants: This cohort study used the random school admissions lottery system of high-performing public charter high schools in low-income neighborhoods of Los Angeles, California, to examine the health outcomes of students who applied to at least 1 of 5 of these high schools. Participants attended 147 different high schools and were randomly selected from those who won the admissions lottery (intervention group) and those who were placed on a waiting list (control group). Participants were surveyed at the end of grade 8 through transition into grade 9 and then from grade 10 through 3 years after high school completion (at age 21 years). Surveys were conducted from March 2013 through November 2021., Intervention: Attendance at a high-performing public charter high school., Main Outcomes and Measures: Self-reported alcohol use disorder and cannabis misuse, delinquent behaviors, physical and mental health, and body mass index., Results: Of the 1270 participants at baseline (mean [SD] age, 14.2 [0.47] years; 668 female individuals [52.6%]). The control group included 576 individuals (45.4%), and 694 individuals (54.6%) were in the intervention group. Both groups were similar in almost all characteristics at baseline, and the median (IQR) follow-up was 6.4 (6.0-6.7) years. Participants attending a high-performing public charter high school had a 53.33% lower rate of hazardous or dependent alcohol use disorder compared with those in the control group (5.43% vs 11.64%; difference, -6.21% [95% CI, -11.87% to -0.55%]; P = .03). Among male participants, the intervention group had a 42.05% lower rate of self-reported fair or poor physical health (13.33% vs 23.01%; difference, -9.67% [95% CI, -18.30% to -1.05%]; P = .03) and a 32.94% lower rate of obesity or overweight (29.28% vs 43.67%; difference, -14.38% [95% CI, -25.74% to -3.02%]; P = .02) compared with the control group. Among female participants, attending a high-performing public charter high school was associated with worse physical health outcomes (30.29% vs 13.47% reporting fair or poor health; difference, 16.82% [95% CI, 0.36% to 33.28%]; P = .045) and higher rates of overweight or obesity (52.20% vs 32.91%; difference, 19.30% [95% CI, 3.37% to 35.22%]; P = .02) at age 21 years. Few differences in mental health outcomes were observed. Adjusting for educational outcomes did not significantly change these findings., Conclusions and Relevance: Results of this study suggest that attending a high-performing public charter high school was associated with lower rates of substance use disorder independent of academic achievement. Physical health and obesity outcomes were also better but only for young men; the intervention group had worse physical health outcomes among young women for unclear reasons. Schools are a potent social determinant of health and an important target for future health interventions.

Background: The Veterans Health Administration (VA) Grant and Per Diem case management "aftercare" program provides 6 months of case management for homeless-experienced veterans (HEVs) undergoing housing transitions. To standardize and improve aftercare services, we will implement critical time intervention (CTI), an evidence-based, structured, and time-limited case management practice. We will use two strategies to support the implementation and sustainment of CTI at 32 aftercare sites, conduct a mixed-methods evaluation of this implementation initiative, and generate a business case analysis and implementation playbook to support the continued spread and sustainment of CTI in aftercare., Methods: We will use the Replicating Effective Programs (REP) implementation strategy to support CTI implementation at 32 sites selected by our partners. Half (n=16) of these sites will also receive 9 months of external facilitation (EF, enhanced REP). We will conduct a type 3 hybrid cluster-randomized trial to compare the impacts of REP versus enhanced REP. We will cluster potential sites into three implementation cohorts staggered in 9-month intervals. Within each cohort, we will use permuted block randomization to balance key site characteristics among sites receiving REP versus enhanced REP; sites will not be blinded to their assigned strategy. We will use mixed methods to assess the impacts of the implementation strategies. As fidelity to CTI influences its effectiveness, fidelity to CTI is our primary outcome, followed by sustainment, quality metrics, and costs. We hypothesize that enhanced REP will have higher costs than REP alone, but will result in stronger CTI fidelity, sustainment, and quality metrics, leading to a business case for enhanced REP. This work will lead to products that will support our partners in spreading and sustaining CTI in aftercare., Discussion: Implementing CTI within aftercare holds the potential to enhance HEVs' housing and health outcomes. Understanding effective strategies to support CTI implementation could assist with a larger CTI roll-out within aftercare and support the implementation of other case management practices within and outside VA., Trial Registration: This project was registered with ClinicalTrials.gov as "Implementing and sustaining Critical Time Intervention in case management programs for homeless-experienced Veterans." Trial registration NCT05312229 , registered April 4, 2022., (© 2022. The Author(s).)

Context: Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are culture-independent molecular methods available for commercial use to diagnose UTI., Objective: To systematically evaluate the evidence comparing the diagnostic and therapeutic values of molecular diagnostic methods to urine culture in the management of UTI in adults., Evidence Acquisition: We performed a critical review of Embase, Ovid, and PubMed in February 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Studies involving pregnant women, ureteral stones, ureteral stents, and percutaneous nephrostomy tubes were excluded. Risk of bias and methodological quality were assessed using the Cochrane risk of bias tool and Newcastle Ottawa Scale. Fifteen publications were selected for inclusion., Evidence Synthesis: Included reports compared NGS (nine studies) and PCR (six studies) to urine culture. A meta-analysis of seven similar studies utilizing NGS demonstrates that NGS is more sensitive in the identification of urinary bacteria and detects greater species diversity per urine sample than culture. PCR protocols designed to detect a diverse range of microbes had increased sensitivity and species diversity compared with culture. Phenotypic and genotypic resistomes are concordant in approximately 85% of cases. There is insufficient evidence to compare patient symptomatic responses to antibiotic therapy guided by molecular testing versus standard susceptibility testing., Conclusions: Moderately strong evidence exists that molecular diagnostics demonstrate increased sensitivity in detecting urinary bacteria at the expense of poor specificity in controls. Additional data comparing patient symptoms and cure rates following antibiotic selection directed by molecular methods compared with culture are needed to elucidate their place in UTI care., Patient Summary: We compare culture-independent molecular methods with urine culture in the management of urinary tract infection. We found good evidence that molecular methods detect more bacteria than culture; however, the clinical implications to support their routine use are unclear., (© 2022 The Authors.)

Purpose  This study characterizes the current landscape of uveitis specialists and their practice settings in the United States. Methods  An anonymous Internet-based survey with questions pertaining to training history and practice characteristics was distributed via REDCap to the American Uveitis Society and Young Uveitis Specialists listservs. Results  Forty-eight uveitis specialists in the United States responded to the survey out of 174 uveitis specialists that identify as practicing in the United States. Twenty-five of 48 respondents (52%) completed an additional fellowship. These additional fellowships ranged from surgical retina (12/25, 48%), cornea (8/25, 32%), and medical retina (4/25, 16%). Two-thirds of uveitis specialists managed their own immunosuppression, while one-third comanaged immunosuppression with rheumatologists. Thirty-three of 48 (69%) maintained a surgical practice. Conclusion  This is the first survey of uveitis specialists across the United States to provide understanding into training and practice characteristics. These data will provide insight into career planning, practice building, and assist in resource allocation., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Background: While cannabis is known to have immunomodulatory properties, the clinical consequences of its use on outcomes in COVID-19 have not been extensively evaluated. We aimed to assess whether cannabis users hospitalized for COVID-19 had improved outcomes compared to non-users., Methods: We conducted a retrospective analysis of 1831 patients admitted to two medical centers in Southern California with a diagnosis of COVID-19. We evaluated outcomes including NIH COVID-19 Severity Score, need for supplemental oxygen, ICU (intensive care unit) admission, mechanical ventilation, length of hospitalization, and in-hospital death for cannabis users and non-users. Cannabis use was reported in the patient's social history. Propensity matching was used to account for differences in age, body-mass index, sex, race, tobacco smoking history, and comorbidities known to be risk factors for COVID-19 mortality between cannabis users and non-users., Results: Of 1831 patients admitted with COVID-19, 69 patients reported active cannabis use (4% of the cohort). Active users were younger (44 years vs. 62 years, p < 0.001), less often diabetic (23.2% vs 37.2%, p < 0.021), and more frequently active tobacco smokers (20.3% vs. 4.1%, p < 0.001) compared to non-users. Notably, active users had lower levels of inflammatory markers upon admission than non-users-CRP (C-reactive protein) (3.7 mg/L vs 7.6 mg/L, p < 0.001), ferritin (282 μg/L vs 622 μg/L, p < 0.001), D-dimer (468 ng/mL vs 1140 ng/mL, p = 0.017), and procalcitonin (0.10 ng/mL vs 0.15 ng/mL, p = 0.001). Based on univariate analysis, cannabis users had significantly better outcomes compared to non-users as reflected in lower NIH scores (5.1 vs 6.0, p < 0.001), shorter hospitalization (4 days vs 6 days, p < 0.001), lower ICU admission rates (12% vs 31%, p < 0.001), and less need for mechanical ventilation (6% vs 17%, p = 0.027). Using propensity matching, differences in overall survival were not statistically significant between cannabis users and non-users, nevertheless ICU admission was 12 percentage points lower (p = 0.018) and intubation rates were 6 percentage points lower (p = 0.017) in cannabis users., Conclusions: This retrospective cohort study suggests that active cannabis users hospitalized with COVID-19 had better clinical outcomes compared with non-users, including decreased need for ICU admission or mechanical ventilation. However, our results need to be interpreted with caution given the limitations of a retrospective analysis. Prospective and observational studies will better elucidate the effects cannabis use in COVID-19 patients., (© 2022. The Author(s).)

Objective: The importance of nontechnical skills in surgery is widely recognized. We demonstrate the feasibility of administering and assessing the results of a formal Non-Technical Skills in Surgery (NOTSS) curriculum to cardiothoracic surgery residents., Methods: Eight cardiothoracic surgery residents participated in the NOTSS curriculum. They were assessed on their cognitive (situation awareness, decision-making) and social (communication and teamwork, leadership) skills based on simulated vignettes. The residents underwent pretraining NOTSS assessments followed by self-administered confidence ratings regarding the 4 skills. Subsequently, a formal NOTSS lecture was delivered and additional readings from the NOTSS textbook was assigned. A month later, the residents returned for post-training NOTSS assessments and self-administered confidence ratings. Changes across days (or within-day before vs after curriculum) were assessed using Wilcoxon signed rank test., Results: There was a significant improvement in the overall NOTSS assessment score (P = .01) as well as in the individual categories (situation awareness, P = .02; decision-making, P = .02; communication and teamwork, P = .01; leadership, P = .02). There was also an increase in resident self-perception of improvement on the post-training day (P = .01)., Conclusions: We have developed a simulation-based NOTSS curriculum in cardiothoracic surgery that can be formally integrated into the current residency education. This pilot study indicates the feasibility of reproducible assessments by course educators and self-assessments by participating residents in nontechnical skills competencies., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: The incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC)., Methods: We studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided., Results: Of 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93)., Conclusion: In this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Infertility clinics and providers in the United States have made efforts to become LGBTQ-inclusive, yet patients in same-sex partnerships continue to face disproportionate barriers to accessing fertility services when pursuing parenthood. This narrative case study of a same-sex couple's "labor to conceive" illustrates some of the structural barriers to family building that lesbian mothers face when seeking fertility care, including insurance coverage of fertility treatments, federal regulations for sperm donation, and legal definitions of parenthood. Exclusionary medical and legal systems are discussed, as are the informal strategies that this samesex couple utilized to negotiate and circumvent these barriers. A patient-centered model of advocacy that facilitates access to and protection of same-sex partners seeking (in)fertility services is presented. Intervention points at the (1) Logistical and (2) Societal levels are considered with respect to three domains of same-sex reproduction: (A) insurance;(B) sperm donation; (C) legal adoption., Competing Interests: Conflicts of Interest: The authors declare no conflict of interest.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as an unpleasant sensation perceived to be related to the bladder with associated urinary symptoms. Due to difficulties discriminating pelvic visceral sensation, IC/BPS likely represents multiple phenotypes with different etiologies that present with overlapping symptomatic manifestations, which complicates clinical management. We hypothesized that unique bladder pain phenotypes or "symptomatic clusters" would be identifiable using machine learning analysis (unsupervised clustering) of validated patient-reported urinary and pain measures. Patients ( n = 145) with pelvic pain/discomfort perceived to originate in the bladder and lower urinary tract symptoms answered validated questionnaires [OAB Questionnaire (OAB-q), O'Leary-Sant Indices (ICSI/ICPI), female Genitourinary Pain Index (fGUPI), and Pelvic Floor Disability Index (PFDI)]. In comparison to asymptomatic controls ( n = 69), machine learning revealed three bladder pain phenotypes with unique, salient features. The first group chiefly describes urinary frequency and pain with the voiding cycle, in which bladder filling causes pain relieved by bladder emptying. The second group has fluctuating pelvic discomfort and straining to void, urinary frequency and urgency without incontinence, and a sensation of incomplete emptying without urinary retention. Pain in the third group was not associated with voiding, instead being more constant and focused on the urethra and vagina. While not utilized as a feature for clustering, subjects in the second and third groups were significantly younger than subjects in the first group and controls without pain. These phenotypes defined more homogeneous patient subgroups which responded to different therapies on chart review. Current approaches to the management of heterogenous populations of bladder pain patients are often ineffective, discouraging both patients and providers. The granularity of individual phenotypes provided by unsupervised clustering approaches can be exploited to help objectively define more homogeneous patient subgroups. Better differentiation of unique phenotypes within the larger group of pelvic pain patients is needed to move toward improvements in care and a better understanding of the etiologies of these painful symptoms., Competing Interests: Conflict of Interest: ALA is an expert witness for Cynosure and a consultant for Watershed Medical. KE is a consultant for Allergan and Coloplast. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Type 2 diabetes can negatively impact long term health outcomes, healthcare costs and quality of life. However, intensive lifestyle interventions, including the Diabetes Prevention Program (DPP), can significantly lower risk of incident type 2 diabetes among overweight adults with prediabetes. Unfortunately, the majority of adults in the US who are at risk of developing diabetes do not engage in DPP-based lifestyle change programs. Increased adoption of evidence-based obesity and diabetes prevention interventions, such as the DPP, may help large employers reduce health risks and improve health outcomes among employees. In 2018, the University of California Office of thePresident (UCOP) implemented the UC DPP Initiative, a novel, multi-component program to address diabetes and obesity prevention across the UC system., Methods: The goal of our study is to conduct a multifaceted evaluation of the UC DPP Initiative using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Our evaluation will integrate unique and diverse UC data sources, including electronic health record (EHR) data, administrative claims, campus-based DPP cohort data, qualitative interviews and site visits. Our primary outcome of interest is the mean percent weight change among three groups of overweight/obese UC beneficiaries at risk for diabetes at 12-month follow-up. Secondary outcomes include mean percent weight change at 24-month follow-up, barriers and facilitators associated with implementatio, as well as  the degree of program adoption and maintenance., Discussion: Our study will help inform diabetes and obesity prevention efforts across the UC system. Findings from this evaluation will also be highly applicable to universities and large employers, as well as community organizers, healthcare organizations and insurers implementing the DPP and/or other health promotion interventions., (© 2021. The Author(s).)

This longitudinal cohort study's aim was to detect whether larger increases in C-reactive protein (CRP) predict greater amounts of subsequent bone loss in women transitioning from premenopause to postmenopause. Participants were initially 42 to 52 years of age and premenopausal or early perimenopausal. The sample included 1431 women who were not using hormone therapy and whose CRP values were not consistent with acute inflammation. Individual fixed effects (IFE) models estimated the association of log 2 CRP with subsequent bone mineral density (BMD) decline rate, adjusted for menopause transition (MT) stage (1: premenopausal or early perimenopausal; 2: late perimenopausal or early postmenopausal; or 3: late postmenopausal), body mass index, diabetes, smoking, alcohol, bone active medications, and anti-inflammatory medications. BMD decline at both the lumbar spine (LS) and femoral neck (FN) was faster for observations made in MT stage 2 than that during other stages (all p  < .001). In adjusted IFE models, MT stage modified the relation between increase in CRP and BMD decline rate (interaction p values <.05). Each within-woman doubling of CRP was associated with a 0.09% faster yearly decline in FN BMD in MT stages 1 ( p = .006) and 3 ( p = .03), and 0.10% faster decline in LS BMD in MT stage 3 only ( p = .007). Within-woman increases in CRP in premenopause and early perimenopause and in late postmenopause predict faster BMD decline in the next ~2 years, but the magnitude of CRP's effect is small. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors declare that no conflict of interest exists., (© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Background: Schools and school climate are thought to influence academic outcomes as well as child and adolescent development, health and well-being. We sought to examine the relationship between several aspects of the school climate with adolescent social-emotional health outcomes., Methods: We analysed data from the Reducing Inequities through Social and Educational change Follow-up (RISE UP) Study, a longitudinal natural experimental study of Los Angeles high school students collected from 2013 to 2018. We analysed data on the portion of the sample that completed the baseline, 10th grade and 11th grade surveys (n=1114). Students reported their perceptions of school climate at 10th grade and social-emotional outcomes including grit, self-efficacy, depression, hopelessness, and stress at baseline (9th grade) and at 11th grade. Multivariable regressions adjusted for student and parental demographics and baseline social-emotional states tested associations between school climate and each outcome., Results: Students who reported being in authoritative school environments in 10th grade, one that is highly supportive and highly structured, had subsequently higher levels of self-efficacy (p< 0.001) and grit (p=0.01). They also had fewer depressive symptoms (p=0.008), and less hopelessness (p = 0.01), stress at school (p=0.002) and stress about the future (p=0.03) reported in 11th grade., Conclusions: School climate, and particularly an authoritative school environment, is strongly associated with better social-emotional health among adolescents. Relationship with teachers and their disciplinary style may be a focus for future interventions to improve the social-emotional health of children.

Background: Hospital readmission rates decreased for myocardial infarction (AMI), heart failure (CHF), and pneumonia with implementation of the first phase of the Hospital Readmissions Reduction Program (HRRP). It is not established whether readmissions fell for chronic obstructive pulmonary disease (COPD), an HRRP condition added in 2014., Objective: We sought to determine whether HRRP penalties influenced COPD readmissions among Medicare, Medicaid, or privately insured patients., Design: We analyzed a retrospective cohort, evaluating readmissions across implementation periods for HRRP penalties ("pre-HRRP" January 2010-April 2011, "implementation" May 2011-September 2012, "partial penalty" October 2012-September 2014, and "full penalty" October 2014-December 2016)., Patients: We assessed discharged patients ≥ 40 years old with COPD versus those with HRRP Phase 1 conditions (AMI, CHF, and pneumonia) or non-HRRP residual diagnoses in the Nationwide Readmissions Database., Interventions: HRRP was announced and implemented during this period, forming a natural experiment., Measurements: We calculated differences-in-differences (DID) for 30-day COPD versus HRRP Phase 1 and non-HRRP readmissions., Key Results: COPD discharges for 1.2 million Medicare enrollees were compared with 22 million non-HRRP and 3.4 million HRRP Phase 1 discharges. COPD readmissions decreased from 19 to 17% over the study. This reduction was significantly greater than non-HRRP conditions (DID - 0.41%), but not HRRP Phase 1 (DID + 0.02%). A parallel trend was observed in the privately insured, with significant reduction compared with non-HRRP (DID - 0.83%), but not HRRP Phase 1 conditions (DID - 0.45%). Non-significant reductions occurred in Medicaid (DID - 0.52% vs. non-HRRP and - 0.21% vs. Phase 1 conditions)., Conclusions: In Medicare, HRRP implementation was associated with reductions in COPD readmissions compared with non-HRRP controls but not versus other HRRP conditions. Parallel findings were observed in commercial insurance, but not in Medicaid. Condition-specific penalties may not reduce readmissions further than existing HRRP trends.

The use of upfront chemotherapy for primary localized soft tissue sarcoma (STS) of the extremity and trunk is debated. It remains unclear if chemotherapy adds clinical benefit, which patients are likely to benefit, and whether the timing of therapy affects outcomes. We used the National Cancer Database (NCDB) to examine the association between overall survival (OS) and chemotherapy in 5436 patients with the five most common subtypes of STS with primary disease localized to the extremity or trunk, mirroring the patient population of a modern phase 3 clinical trial of neoadjuvant chemotherapy. We then examined associations between timing of multi-agent chemotherapy (neoadjuvant or adjuvant) and OS. We used a Cox proportional hazards model and propensity score matching (PSM) to account for covariates including demographic, patient, clinical, treatment, and facility factors. In the overall cohort, we observed no association between multi-agent chemotherapy or its timing and improved OS. Multi-agent chemotherapy was associated with improved OS in several subgroups, including patients with larger tumors (>5 cm), those treated at high-volume centers, or those who received radiation. We also identified an OS benefit to multi-agent chemotherapy among the elderly (>70 years) and African American patients. Multi-agent chemotherapy was associated with improved survival for patients with tumors >5 cm, who receive radiation, or who receive care at high-volume centers. Neither younger age nor chemotherapy timing was associated with better outcomes. These 'real-world' findings align with recent randomized trial data supporting the use of multi-agent chemotherapy in high-risk patients with localized STS.

This article was migrated. The article was marked as recommended. Introduction: Despite the increasing popularity of high-fidelity simulation (SIM), few studies compare the effectiveness of SIM with established small-group modalities such as problem-based learning (PBL) for factual learning among pre-clinical medical undergraduates. Methods: 162 second-year medical students were randomized to two groups. The first group encountered teaching points related to the management of hypertensive emergency during a traditional PBL session, while the second group covered the same teaching points through SIM. Both groups then completed a post-test. The students were subsequently crossed-over to the opposite modality and assessed on teaching points related to the management of chronic obstructive pulmonary disease exacerbations. Results: A total of 162 students participated in the study. For the hypertension case, the average proportion of correct questions for the SIM intervention was 83% compared to 70% for the PBL intervention (OR = 3.1, 95% CI [1.3, 7.2], p =0.009). For the COPD case, the average proportion of correct questions for the SIM intervention was 73% compared to 51% for the PBL intervention (OR = 2.6, 95% CI [1.8, 3.8], p < 0.001). Conclusion: Students scored significantly higher with SIM in both cases, indicating that SIM may be superior to PBL for factual learning among students with limited clinical exposure., (Copyright: © 2020 Larsen T et al.)

Background and Purpose- Lowering blood pressure and cholesterol, antiplatelet/antithrombotic use, and smoking cessation reduce risk of recurrent stroke. However, gaps in risk factor control among stroke survivors warrant development and evaluation of alternative care delivery models that aim to simultaneously improve multiple risk factors. Randomized trials of care delivery models are rarely of sufficient duration or size to be powered for low-frequency outcomes such as observed recurrent stroke. This creates a need for tools to estimate how changes across multiple stroke risk factors reduce risk of recurrent stroke. Methods- We reviewed existing evidence of the efficacy of interventions addressing blood pressure reduction, cholesterol lowering, antiplatelet/antithrombotic use, and smoking cessation and extracted relative risks for each intervention. From this, we developed a tool to estimate reductions in recurrent stroke risk, using bootstrapping and simulation methods. We also calculated a modified Global Outcome Score representing the proportion of potential benefit (relative risk reduction) achieved if all 4 individual risk factors were optimally controlled. We applied the tool to estimate stroke risk reduction among 275 participants with complete 12-month follow-up data from a recently published randomized trial of a healthcare delivery model that targeted multiple stroke risk factors. Results- The recurrent stroke risk tool was feasible to apply, yielding an estimated reduction in the relative risk of ischemic stroke of 0.36 in both the experimental and usual care trial arms. Global Outcome Score results suggest that participants in both arms likely averted, on average, 45% of recurrent stroke events that could possibly have been prevented through maximal implementation of interventions for all 4 individual risk factors. Conclusions- A stroke risk reduction tool facilitates estimation of the combined impact on vascular risk of improvements in multiple stroke risk factors and provides a summary outcome for studies testing alternative care models to prevent recurrent stroke. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT00861081.