Staff-Facilitated Telemedicine Care Delivery for Treatment of Hepatitis C Infection among People Who Inject Drugs.

BACKGROUND: Telemedicine offers the opportunity to provide clinical services remotely, thereby bridging geographic distances for people engaged in the medical system. Following the COVID-19 pandemic, the widespread adoption of telemedicine in clinical practices has persisted, highlighting its continued relevance for post-pandemic healthcare. Little is known about telemedicine use among people from socially marginalized groups. METHODS: The No One Waits (NOW) Study is a single-arm clinical trial measuring the acceptability, feasibility, and safety of an urban point-of-diagnosis hepatitis C (HCV) treatment initiation model delivered in a non-clinical community setting. Participants enrolled in the NOW Study are recruited via street outreach targeting people experiencing homelessness and injecting drugs. Throughout the NOW Study, clinical care is delivered through a novel staff-facilitated telemedicine model that not only addresses geographic and transportation barriers, but also technology and medical mistrust, barriers often unique to this population. While clinicians provide high-quality specialty practice-based care via telemedicine, on-site staff provide technical support, aid in communication and rapport, and review the clinicians' instructions and next steps with participants following the visits. Research questionnaires collect information on participants' experience with and perceptions of telemedicine (a) prior to treatment initiation and (b) at treatment completion. DISCUSSION: For people from socially marginalized groups with HCV infection, creative person-centered care approaches are necessary to diagnose, treat, and cure HCV. Although non-clinical, community-based staff-facilitated telemedicine requires additional resources compared to standard-of-care telemedicine, it could expand the reach and offer a valuable entrance into technology-delivered care for socially marginalized groups. TRIAL REGISTRATION: NCT03987503.

Screening for social determinants of health among populations at risk for MASLD: a scoping review.

Background: Social determinants of health (SDoH) have been associated with disparate outcomes among those with metabolic dysfunction-associated steatotic liver disease (MASLD) and its risk factors. To address SDoH among this population, real-time SDoH screening in clinical settings is required, yet optimal screening methods are unclear. We performed a scoping review to describe the current literature on SDoH screening conducted in the clinical setting among individuals with MASLD and MASLD risk factors. Methods: Through a systematic literature search of MEDLINE, Embase, and CINAHL Complete databases through 7/2023, we identified studies with clinic-based SDoH screening among individuals with or at risk for MASLD that reported pertinent clinical outcomes including change in MASLD risk factors like diabetes and hypertension. Results: Ten studies (8 manuscripts, 2 abstracts) met inclusion criteria involving 148,151 patients: 89,408 with diabetes and 25,539 with hypertension. Screening was primarily completed in primary care clinics, and a variety of screening tools were used. The most commonly collected SDoH were financial stability, healthcare access, food insecurity and transportation. Associations between clinical outcomes and SDoH varied; overall, higher SDoH burden was associated with poorer outcomes including elevated blood pressure and hemoglobin A1c. Conclusion: Despite numerous epidemiologic studies showing associations between clinical outcomes and SDoH, and guidelines recommending SDoH screening, few studies describe in-clinic SDoH screening among individuals with MASLD risk factors and none among patients with MASLD. Future research should prioritize real-time, comprehensive assessments of SDoH, particularly among patients at risk for and with MASLD, to mitigate disease progression and reduce MASLD health disparities.

Validating Constructs of the Depression, Anxiety, and Stress Scale-21 and Exploring Health Indicators to Predict the Psychological Outcomes of Students Enrolled in the Pacific Islands Cohort of College Students.

The Depression, Anxiety, and Stress Scale-21 (DASS-21) has been used in various countries to assess the mental states of individuals. The objectives of this study were to validate the DASS-21 for use in Guam, an island that endures a high burden of mental health challenges, such as suicide, and examine the predictive impact of selected health indicators on DASS-21 variables. Three years of data (2017-2019) were pooled from the Pacific Islands Cohort of College Students (PICCS) study conducted annually at the University of Guam. In total, 726 students were included in the secondary data analysis. MPlus statistical software was used to perform a confirmatory factor analysis (CFA) for the validation and structural equation modeling (SEM) for the predictive modeling. The results from the CFA suggested an acceptable model fit (RMSEA: 0.073, CFI: 0.901, TLI: 0.889, RMR: 0.044), while SEM suggested that sleep quality and physical activity were significant predictors of DASS-21 variables. Therefore, the DASS-21 is a valid instrument for measuring depression, anxiety, and stress among emerging adults in Guam.

Telehepatology Satisfaction Is Associated with Ethnicity: The Real-World Experience of a Vulnerable Population with Fatty Liver Disease.

BACKGROUND: Since the coronavirus disease 2019 (COVID-19) pandemic began, telemedicine use has transformed healthcare delivery. Yet there is concern that telemedicine may widen care disparities for vulnerable populations, and patient experience data are limited. AIMS: We aimed to assess patient satisfaction with hepatology-related telemedicine (telehepatology) for delivery of fatty liver disease (FLD) care in a safety-net healthcare system. METHODS: Adult patients with FLD were surveyed regarding satisfaction with telehepatology. Clinical, demographic, resources, and social determinants of health (SDoH) data were collected to identify factors associated with satisfaction through multivariable modeling. RESULTS: From June 2020 to March 2022, 220 participants were enrolled: the median age was 52 years, 37% were men, and 68% were Hispanic. One hundred nineteen (54%) had prior telehepatology experience. Overall, satisfaction was high; 70% reported being somewhat or very satisfied. On univariate analysis, Hispanic ethnicity (versus non-Hispanic, OR 0.34, 95% CI 0.1-0.9, p = 0.03) and limited access to personal cellphone/internet (OR 0.16, 95% CI 0.04-0.6, p = 0.01) were associated with lower satisfaction. On multivariable logistic regression modeling adjusted for pandemic duration, age, sex, severity of liver disease, and coexisting liver disease, Hispanic ethnicity and lack of personal cellphone/internet remained independently associated with lower telehepatology satisfaction (OR 0.24, 95% CI 0.07-0.9, p = 0.03 and OR 0.2, 95% CI 0.04-0.9, p = 0.04, respectively). The association remained statistically significant after inclusion of various SDoH in the multivariable model. CONCLUSIONS: Satisfaction with telehepatology among FLD patients in a safety-net clinical setting was high overall. However, Hispanic ethnicity and lack of personal cellphone/internet were independently associated with lower telehepatology satisfaction. A better understanding of patients' experience with telehepatology is needed to identify reasons for dissatisfaction, and in-person visits should remain an option for patients to ensure equitable care.

Community engagement in the development of health-related data visualizations: a scoping review.

OBJECTIVE: This scoping review aims to address a gap in the literature on community engagement in developing data visualizations intended to improve population health. The review objectives are to: (1) synthesize literature on the types of community engagement activities conducted by researchers working with community partners and (2) characterize instances of "creative data literacy" within data visualizations developed in community-researcher partnerships. METHODS: Using the 2018 PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, the review focuses on peer-reviewed journal articles from 2010 to 2022 in PubMed, Web of Science, and Google Scholar. A community engagement tool was applied to the studies by independent reviewers to classify levels of community engagement, social determinants, and vulnerable populations. RESULTS: Twenty-seven articles were included in the scoping review. Twelve articles worked with vulnerable populations. Four articles attempted to alleviate barriers to representation in their respective studies, with addressing language barriers being the most prevalent approach. Thirteen articles considered social determinants of health. Sixteen studies engaged in iterative approaches with intended users when developing the visualization or tool. DISCUSSION: Only a few significant examples of creative data literacy are incorporated in the studies. We recommend a specific focus on engaging intended users at every step of the development process, addressing language and cultural differences, and empowering intended users as data storytellers. CONCLUSIONS: There is room for deeper and more meaningful community involvement in the development of health-related data visualizations geared towards them.

Cross-sectional study on stigma and motivation to adhere to lifestyle modification among vulnerable populations with fatty liver disease.

Objectives: Adherence to lifestyle modification (diet, exercise, and alcohol cessation) for fatty liver disease (FLD) management remains challenging. The study examined stigma, barriers, and factors associated with motivation to adhere to lifestyle modification in a diverse and vulnerable population with FLD. Methods: From 2/19/2020 to 2/28/2022, 249 FLD patients within San Francisco safety-net hepatology clinics were surveyed along with clinical data taken from medical records. Multivariable modeling assessed factors associated with motivation to adhere to lifestyle modification in a cross-sectional study. Results: Median age was 53 years, 59% female, 59% Hispanic, 25% Asian/Pacific Islander, 9% White, and 2% Black, 79% were non-English speakers, 64% had ≤ high school education, and 82% reported <$30,000 annual income. Common comorbidities included hyperlipidemia (47%), hypertension (42%), diabetes (39%), and heavy alcohol use (22%). Majority (78%) reported experiencing stigma, 41% reported extreme motivation, and 58% reported ≥ two barriers. When controlling for age, sex, Hispanic ethnicity, alcohol consumption, BMI, >high school (coef 1.41, 95% CI 0.34-2.48), stigma (coef 0.34, 95% CI 0.07-0.62), and depression (coef -1.52, 95% CI -2.79 to -0.26) were associated with motivation. Conclusions: Stigma is commonly reported among FLD patients. Interventions to enhance patient education and mental health support are critical to FLD management, especially in vulnerable populations.

Structure of phosphorylated-like RssB, the adaptor delivering σs to the ClpXP proteolytic machinery, reveals an interface switch for activation.

In enterobacteria such as Escherichia coli, the general stress response is mediated by σs, the stationary phase dissociable promoter specificity subunit of RNA polymerase. σs is degraded by ClpXP during active growth in a process dependent on the RssB adaptor, which is thought to be stimulated by the phosphorylation of a conserved aspartate in its N-terminal receiver domain. Here we present the crystal structure of full-length RssB bound to a beryllofluoride phosphomimic. Compared to the structure of RssB bound to the IraD anti-adaptor, our new RssB structure with bound beryllofluoride reveals conformational differences and coil-to-helix transitions in the C-terminal region of the RssB receiver domain and in the interdomain segmented helical linker. These are accompanied by masking of the α4-ß5-α5 (4-5-5) "signaling" face of the RssB receiver domain by its C-terminal domain. Critically, using hydrogen-deuterium exchange mass spectrometry, we identify σs-binding determinants on the 4-5-5 face, implying that this surface needs to be unmasked to effect an interdomain interface switch and enable full σs engagement and hand-off to ClpXP. In activated receiver domains, the 4-5-5 face is often the locus of intermolecular interactions, but its masking by intramolecular contacts upon phosphorylation is unusual, emphasizing that RssB is a response regulator that undergoes atypical regulation.

A pilot study to understand and respond to loss, theft, and misplacement of hepatitis C treatment medication for people who inject drugs.

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Undiagnosed abnormal alanine transaminase levels in vulnerable populations: Impact of sex, race/ethnicity, and body mass.

Background: Liver disease is a leading cause of death in the United States and is often initially detected incidentally on lab tests ordered by general practitioners. Alanine transaminase (ALT), a marker of liver inflammation, is commonly ordered and may be abnormal in the setting of elevated body mass index, diabetes and dyslipidemia. Data regarding ALT testing within vulnerable populations are limited. Therefore, the prevalence of ALT testing and abnormal ALT in the absence of known chronic liver disease (CLD) among a safety-net population were assessed and factors associated with these outcomes were identified. Methods: In this retrospective longitudinal study of 92,997 patients seen between 01/2017-01/2019 within San Francisco's Safety-Net Healthcare System, electronic medical records were used to abstract data back to 04/1997. Descriptive analyses and multivariable modeling were performed. Results: Overall, 59,323 (69%) without known CLD received an ALT test. Age, Black race, Latinx ethnicity, and metabolic factors were associated with higher odds of ALT testing, (p < 0.01). Among those with an abnormal ALT (44%) without known CLD: median age 53 years, 41% male, 19% White, 11% Black, 40% Latinx, 29% Asian/Pacific Islander (API), and 84% overweight/obese. On multivariable analysis, female sex (OR 2.7), Latinx ethnicity (OR 2.6), API race (OR 1.3), overweight/obesity (OR 1.8, OR 2.6), and dyslipidemia (OR 1.3) were associated with abnormal ALT, (p ≤ 0.001). Conclusions: In the absence of known CLD, women, Latinx, API and persons with excess body weight were associated with greater odds of abnormal ALT. Future longitudinal studies are needed to confirm these differences and to determine if adequate work up for CLD is performed for abnormal ALT levels among at-risk populations.

The Implications of Treatment Delays in Adjuvant Therapy for Resected Cholangiocarcinoma Patients.

PURPOSE: The purpose of this study is to understand factors associated with timing of adjuvant therapy for cholangiocarcinoma and the impact of delays on overall survival (OS). METHODS: Data from the National Cancer Database (NCDB) for patients with non-metastatic bile duct cancer from 2004 to 2015 were analyzed. Patients were included only if they underwent surgery and adjuvant chemotherapy and/or radiotherapy (RT). Patients who underwent neoadjuvant or palliative treatments were excluded. Pearson's chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity score matching with inverse probability of treatment weighting, OS was compared between patients initiating therapy past various time points using Kaplan Meier analyses and doubly robust estimation with multivariate Cox proportional hazards modeling. RESULTS: In total, 7,733 of 17,363 (45%) patients underwent adjuvant treatment. The median time to adjuvant therapy initiation was 59 days (interquartile range 45-78 days). Age over 65, black and Hispanic race, and treatment with RT alone were associated with later initiation of adjuvant treatment. Patients with larger tumors and high-grade disease were more likely to initiate treatment early. After propensity score weighting, there was an OS decrement to initiation of treatment beyond the median of 59 days after surgery. CONCLUSIONS: We identified characteristics that are related to the timing of adjuvant therapy in patients with biliary cancers. There was an OS decrement associated with delays beyond the median time point of 59 days. This finding may be especially relevant given the treatment delays seen as a result of COVID-19.

Evaluation of a pilot, community-led mental illness de-stigmatization theater intervention in rural uganda.

BACKGROUND: In rural areas of low- and middle- income countries, mental health care is often unavailable and inaccessible, and stigma is a major barrier to treatment. Destigmatization can increase treatment-seeking attitudes, community support, and acceptance of individuals suffering from mental illness. This study's primary objective was to evaluate the impact of a community-led, theater-based destigmatization campaign for mental illness conducted in the Busoga region of Eastern Uganda. METHODS: One hundred residents of the Busoga region were randomly selected via cluster sampling to complete a structured questionnaire assessing mental health stigma. Four focus groups were conducted for qualitative data on mental health stigma. Common misconceptions and specific points of stigma were identified from these responses, and local village health team personnel developed and performed a culturally-adapted theatrical performance addressing these points. Changes in perceptions of mental illness were measured among 57 attendees using two measures, the Broad Acceptance Scale (designed to reflect factors that contribute to structural stigma) and Personal Acceptance Scale (designed to reflect factors that contribute to interpersonal, or public stigma), before and after the performance. RESULTS: There was a significant increase in acceptance according to the Broad Acceptance Scale (p < .001) and Personal Acceptance Scale (p < .001). Qualitative responses from play attendees also indicated a decrease in stigma and an increased sense of the importance of seeking treatment for mentally ill patients. CONCLUSION: This study shows community-led, theater intervention may be an effective tool for the destigmatization of mental illness in rural areas of Uganda. Larger studies are needed to further test the efficacy of this approach and potential for longer-term scalabilityand sustainability.

Deciphering the mechanism and function of Hsp100 unfoldases from protein structure.

Hsp100 chaperones, also known as Clp proteins, constitute a family of ring-forming ATPases that differ in 3D structure and cellular function from other stress-inducible molecular chaperones. While the vast majority of ATP-dependent molecular chaperones promote the folding of either the nascent chain or a newly imported polypeptide to reach its native conformation, Hsp100 chaperones harness metabolic energy to perform the reverse and facilitate the unfolding of a misfolded polypeptide or protein aggregate. It is now known that inside cells and organelles, different Hsp100 members are involved in rescuing stress-damaged proteins from a previously aggregated state or in recycling polypeptides marked for degradation. Protein degradation is mediated by a barrel-shaped peptidase that physically associates with the Hsp100 hexamer to form a two-component system. Notable examples include the ClpA:ClpP (ClpAP) and ClpX:ClpP (ClpXP) proteases that resemble the ring-forming FtsH and Lon proteases, which unlike ClpAP and ClpXP, feature the ATP-binding and proteolytic domains in a single polypeptide chain. Recent advances in electron cryomicroscopy (cryoEM) together with single-molecule biophysical studies have now provided new mechanistic insight into the structure and function of this remarkable group of macromolecular machines.

Racial/ethnic differences in fibrosis prevalence and progression in biopsy-proven steatosis: A focus on the Asian American population.

Fatty liver disease (FLD) is a leading cause of chronic liver disease (CLD) globally, and vulnerable populations are disproportionately affected. Prior studies have suggested racial/ethnic differences in FLD prevalence and severity; however, these studies often excluded Asian Americans. This study aims to evaluate racial/ethnic differences in the prevalence of, and predictors associated with steatohepatitis, advanced fibrosis, and fibrosis progression over time within a diverse population. Using descriptive analyses and multivariable modeling, we performed a longitudinal evaluation of 648 patients with histologic evidence of FLD (steatosis or steatohepatitis) from August 2009 to February 2020 within San Francisco's safety-net health care system. Overall demographics were median age of 53 years, 54% male, and 38% Asian (40% Hispanic, 14% White). On histology, 61% had steatohepatitis and 30% had advanced fibrosis (≥F3). The comparison between steatosis and steatohepatitis groups showed differences in sex, race/ethnicity, metabolic risk factors, and co-existing CLD (predominantly viral hepatitis); patients with steatosis were more likely to be Asian (50%), and those with steatohepatitis were more likely to be Hispanic (51%). On multivariable modeling, while Asian race (vs. non-Asian) was not associated with steatohepatitis or advanced fibrosis when models included all relevant clinical predictors, Asian race was associated with higher relative risk of fibrosis progression as defined by change in Fibrosis-4 category over time (relative risk ratio = 1.9; p = 0.047). Conclusion: In this vulnerable population with a large proportion of Asian Americans, Asian race was associated with progression of fibrosis. Given the relative paucity of data in this high-risk group, future studies should confirm these findings.

Noninvasive Fibrosis Screening in Fatty Liver Disease Among Vulnerable Populations: Impact of Diabetes and Obesity on FIB-4 Score Accuracy.

OBJECTIVE: Fatty liver disease (FLD) is prevalent in diabetes, and both disproportionately affect vulnerable populations. The FIB-4 index is recommended to screen for advanced liver fibrosis. Limited data have suggested that diabetes may impact FIB-4. RESEARCH DESIGN AND METHODS: We evaluated FIB-4 accuracy for advanced fibrosis compared with liver biopsy in the presence of diabetes and obesity. RESULTS: Among 363 FLD patients receiving care in San Francisco's safety net health care system from August 2009 to February 2020, characteristics were as follows: median age 51 years, 46% male, 59% Hispanic, 68% obese, 33% with diabetes, and 31% with advanced fibrosis on histology. Overall, the c-statistic for FIB-4 was 0.79, but was worse in patients with diabetes, 0.68, than without, 0.85 (P = 0.003). Accuracy also varied by weight, at 0.65, 0.85, and 0.75 for normal weight, overweight, and obese, respectively, although not significantly (P = 0.24). CONCLUSIONS: The findings highlight limitations of FIB-4 in screening for advanced liver fibrosis, particularly in individuals with diabetes.

Burden of Allergic Disease in Racial and Ethnic Structurally Oppressed Communities Within Canada and the United States: A Scoping Review.

BACKGROUND: The social determinants of health have been extensively studied as potential mediating variables in the development and/or progression of many chronic illnesses, including allergic diseases, and may contribute to social inequities as barriers in accessing health care. OBJECTIVE: We aimed to perform a scoping literature review to describe the burden of disease and access to health care for treatment of allergic disease within literature specific to structurally oppressed racial and ethnic populations. METHODS: We performed a scoping review, guided by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines for Scoping Reviews, of 3 scientific databases and 5 relevant gray literature sites. Search strategy including keywords describing race and ethnicity were selected based on the acceptable nomenclature in Canada and the United States. We imposed no restrictions on date or country of publication, study design, or age of participants. RESULTS: Our literature search yielded 1,198 potentially relevant articles following deduplication. After title and abstract, and subsequently full-text screening, a total of 12 (1.08% of all articles) were included. These 12 included studies pointed toward a higher burden of allergic and atopic disease, including increased presentations to emergency departments, hospitalizations, mortality, younger age of diagnosis, and/or greater severity of disease, among Black or African American individuals, than the general population. Allergies beyond the top 9 food allergens, eosinophilic esophagitis, and asthma appeared to be more prevalent and more severe in this population than in the general population. There appears to be an increased burden of allergic and atopic disease among the Indigenous Peoples of Canada, whereas this was not noted for Latinx or Hispanic populations, in part due to a paucity of studies involving these populations. Owing to a lack of published literature, no conclusions could be drawn regarding allergy and atopy in Native American populations. CONCLUSIONS: Structurally oppressed racial and ethnic communities may face an increased burden of allergic and atopic disease-but that this may be magnified by issues regarding oppression, access, and social environment that warrant further investigation.

Social support, exhaled nitric oxide, and upper respiratory symptoms in health and asthma.

Accumulating research identifies a role of psychological process, particularly negative affect, in the expression of airway nitric oxide (NO), yet directional associations tend to vary across methodologies and samples. Recent findings indicate higher social support to be associated with higher airway NO; however, consequences for respiratory infection remain unexplored. NO has a key role in the first line of epithelial defense against pathogens, thus, social support could unfold airway protective effects through enhanced production of NO. We therefore examined the associations among social support, negative affect, airway NO, and cold symptoms in a sample of undergraduate students. In this cross-sectional study, 637 participants completed questionnaires of social support, negative affect, medical history, and current cold symptoms followed by measurements of fractional exhaled NO (FENO) to study airway NO during a semester period of relative low stress. Findings showed that greater social support was associated with higher FENO and fewer cold symptoms, controlling for key covariates. Further analysis suggested an additional indirect effect of social support on FENO through cold symptoms such that higher social support was related to lower cold symptoms, which were related to lower FENO. These results, coupled with longitudinal findings in the previous research, suggest that social support can affect FENO and cold symptoms through a complex pattern of direct and indirect effects. Overall, findings support the role of psychological processes - particularly social support - as relevant to FENO and cold symptoms in young adults.

Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies Against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We have previously developed highly thermo-tolerant monomeric and trimeric receptor binding domain derivatives that can withstand 100{degrees}C for 90 minutes and 37{degrees}C for four weeks, and help eliminate cold chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations, and 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for the upcoming Phase I human clinical trials, and that there is potential for increasing efficacy with vaccine matching to improve responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions which show that while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible, and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.