Virology-The next fifty years.

Virology has made enormous advances in the last 50 years but has never faced such scrutiny as it does today. Herein, we outline some of the major advances made in virology during this period, particularly in light of the COVID-19 pandemic, and suggest some areas that may be of research importance in the next 50 years. We focus on several linked themes: cataloging the genomic and phenotypic diversity of the virosphere; understanding disease emergence; future directions in viral disease therapies, vaccines, and interventions; host-virus interactions; the role of viruses in chronic diseases; and viruses as tools for cell biology. We highlight the challenges that virology will face moving forward-not just the scientific and technical but also the social and political. Although there are inherent limitations in trying to outline the virology of the future, we hope this article will help inspire the next generation of virologists.

Establishing or Exaggerating Causality for the Gut Microbiome: Lessons from Human Microbiota-Associated Rodents.

Human diseases are increasingly linked with an altered or "dysbiotic" gut microbiota, but whether such changes are causal, consequential, or bystanders to disease is, for the most part, unresolved. Human microbiota-associated (HMA) rodents have become a cornerstone of microbiome science for addressing causal relationships between altered microbiomes and host pathology. In a systematic review, we found that 95% of published studies (36/38) on HMA rodents reported a transfer of pathological phenotypes to recipient animals, and many extrapolated the findings to make causal inferences to human diseases. We posit that this exceedingly high rate of inter-species transferable pathologies is implausible and overstates the role of the gut microbiome in human disease. We advocate for a more rigorous and critical approach for inferring causality to avoid false concepts and prevent unrealistic expectations that may undermine the credibility of microbiome science and delay its translation.

Molecular Activation of NLRP3 Inflammasome by Particles and Crystals: A Continuing Challenge of Immunology and Toxicology.

Particles and crystals constitute a unique class of toxic agents that humans are constantly exposed to both endogenously and from the environment. Deposition of particulates in the body is associated with a range of diseases and toxicity. The mechanism by which particulates cause disease remains poorly understood due to the lack of mechanistic insights into particle-biological interactions. Recent research has revealed that many particles and crystals activate the NLRP3 inflammasome, an intracellular pattern-recognition receptor. Activated NLRP3 forms a supramolecular complex with an adaptor protein to activate caspase 1, which in turn activates IL-1ß and IL-18 to instigate inflammation. Genetic ablation and pharmacological inhibition of the NLRP3 inflammasome dampen inflammatory responses to particulates. Nonetheless, how particulates activate NLRP3 remains a challenging question. From this perspective, we discuss our current understanding of and progress on revealing the function and mode of action of the NLRP3 inflammasome in mediating adaptive and pathologic responses to particulates in health and disease.

Accurate estimation of biological age and its application in disease prediction using a multimodal image Transformer system.

Aging in an individual refers to the temporal change, mostly decline, in the body's ability to meet physiological demands. Biological age (BA) is a biomarker of chronological aging and can be used to stratify populations to predict certain age-related chronic diseases. BA can be predicted from biomedical features such as brain MRI, retinal, or facial images, but the inherent heterogeneity in the aging process limits the usefulness of BA predicted from individual body systems. In this paper, we developed a multimodal Transformer-based architecture with cross-attention which was able to combine facial, tongue, and retinal images to estimate BA. We trained our model using facial, tongue, and retinal images from 11,223 healthy subjects and demonstrated that using a fusion of the three image modalities achieved the most accurate BA predictions. We validated our approach on a test population of 2,840 individuals with six chronic diseases and obtained significant difference between chronological age and BA (AgeDiff) than that of healthy subjects. We showed that AgeDiff has the potential to be utilized as a standalone biomarker or conjunctively alongside other known factors for risk stratification and progression prediction of chronic diseases. Our results therefore highlight the feasibility of using multimodal images to estimate and interrogate the aging process.

Monocyte Single-Cell Multimodal Profiling in Cardiovascular Disease Risk States.

BACKGROUND: Monocytes are a critical innate immune system cell type that serves homeostatic and immunoregulatory functions. They have been identified historically by the cell surface expression of CD14 and CD16. However, recent single-cell studies have revealed that they are much more heterogeneous than previously realized. METHODS: We utilized cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing to describe the comprehensive transcriptional and phenotypic landscape of 437 126 monocytes. RESULTS: This high-dimensional multimodal approach identified vast phenotypic diversity and functionally distinct subsets, including IFN-responsive, MHCIIhi (major histocompatibility complex class II), monocyte-platelet aggregates, as well as nonclassical, and several subpopulations of classical monocytes. Using flow cytometry, we validated the existence of MHCII+CD275+ MHCIIhi, CD42b+ monocyte-platelet aggregates, CD16+CD99- nonclassical monocytes, and CD99+ classical monocytes. Each subpopulation exhibited unique characteristics, developmental trajectories, transcriptional regulation, and tissue distribution. In addition, alterations associated with cardiovascular disease risk factors, including race, smoking, and hyperlipidemia were identified. Moreover, the effect of hyperlipidemia was recapitulated in mouse models of elevated cholesterol. CONCLUSIONS: This integrative and cross-species comparative analysis provides a new perspective on the comparison of alterations in monocytes in pathological conditions and offers insights into monocyte-driven mechanisms in cardiovascular disease and the potential for monocyte subpopulation targeted therapies.

Digital Intervention for behaviouR changE and Chronic disease prevenTION (DIRECTION): Study protocol for a randomized controlled trial of a web-based platform integrating nutrition, physical activity, and mindfulness for individuals with obesity.

Excess body weight, suboptimal diet, physical inactivity, alcohol consumption, sleep disruption, and elevated stress are modifiable risk factors associated with the development of chronic diseases. Digital behavioural interventions targeting these factors have shown promise in improving health and reducing chronic disease risk. The Digital Intervention for behaviouR changE and Chronic disease prevenTION (DIRECTION) study is a parallel group, two-arm, randomized controlled trial evaluating the effects of adding healthcare professional guidance and peer support via group-based sessions to a web-based wellness platform (experimental group, n = 90) compared to a self-guided use of the platform (active control group, n = 90) among individuals with a body mass index (BMI) of 30 to <35 kg/m2 and aged 40-65 years. Obesity is defined by a high BMI. The web-based wellness platform employed in this study is My Viva Plan (MVP)®, which holistically integrates nutrition, physical activity, and mindfulness programs. Over 16 weeks, the experimental group uses the web-based wellness platform daily and engages in weekly online support group sessions. The active control group exclusively uses the web-based wellness platform daily. Assessments are conducted at baseline and weeks 8 and 16. The primary outcome is between-group difference in weight loss (kg) at week 16, and secondary outcomes are BMI, percent weight change, proportion of participants achieving 5% or more weight loss, dietary intake, physical activity, alcohol consumption, sleep, and stress across the study. A web-based wellness platform may be a scalable approach to promote behavioural changes that positively impact health. This study will inform the development and implementation of interventions using web-based wellness platforms and personalized digital interventions to improve health outcomes and reduce chronic disease risk among individuals with obesity.

A Multiseason Randomized Controlled Trial of Advax-Adjuvanted Seasonal Influenza Vaccine in Participants With Chronic Disease or Older Age.

BACKGROUND: The aim of the current study was to determine the safety and immunogenicity of trivalent inactivated influenza vaccine (TIV) alone or formulated with Advax delta inulin adjuvant in those who were older (aged >60 years) or had chronic disease. METHODS: Over 4 consecutive years from 2008 through 2011, adult participants with chronic disease or >60 years of age were recruited into a randomized controlled study to assess the safety, tolerability and immunogenicity of Advax-adjuvanted TIV (TIV + Adj) versus standard TIV. The per-protocol population with ≥1 postbaseline measurement of influenza antibodies comprised 1297 participants, 447 in the TIV and 850 in the TIV + Adj) group. RESULTS: No safety issues were identified. Variables negatively affecting vaccine responses included obesity and diabetes mellitus. Advax adjuvant had a positive impact on anti-influenza immunoglobulin M responses and on H3N2 and B strain seropositivity as assessed by hemagglutination inhibition. CONCLUSIONS: TIV + Adj was safe and well tolerated in individuals with chronic disease. There is an ongoing need for research into improved influenza vaccines for high-risk populations. CLINICAL TRIALS REGISTRATION: Australia New Zealand Clinical Trial Registry: ACTRN 12608000364370.

Food Is Medicine: A Presidential Advisory From the American Heart Association.

Unhealthy diets are a major impediment to achieving a healthier population in the United States. Although there is a relatively clear sense of what constitutes a healthy diet, most of the US population does not eat healthy food at rates consistent with the recommended clinical guidelines. An abundance of barriers, including food and nutrition insecurity, how food is marketed and advertised, access to and affordability of healthy foods, and behavioral challenges such as a focus on immediate versus delayed gratification, stand in the way of healthier dietary patterns for many Americans. Food Is Medicine may be defined as the provision of healthy food resources to prevent, manage, or treat specific clinical conditions in coordination with the health care sector. Although the field has promise, relatively few studies have been conducted with designs that provide strong evidence of associations between Food Is Medicine interventions and health outcomes or health costs. Much work needs to be done to create a stronger body of evidence that convincingly demonstrates the effectiveness and cost-effectiveness of different types of Food Is Medicine interventions. An estimated 90% of the $4.3 trillion annual cost of health care in the United States is spent on medical care for chronic disease. For many of these diseases, diet is a major risk factor, so even modest improvements in diet could have a significant impact. This presidential advisory offers an overview of the state of the field of Food Is Medicine and a road map for a new research initiative that strategically approaches the outstanding questions in the field while prioritizing a human-centered design approach to achieve high rates of patient engagement and sustained behavior change. This will ideally happen in the context of broader efforts to use a health equity-centered approach to enhance the ways in which our food system and related policies support improvements in health.

Cortical Spreading Depolarization in Moyamoya Vasculopathy: A Case Series.

BACKGROUND: Spreading depolarization describes a near-complete electrical discharge with altered local cerebral blood flow. It is described in association with acute and chronic diseases like hemorrhagic stroke or migraine. Moyamoya vasculopathy is a chronic, progressive cerebrovascular disorder leading to cerebral hypoperfusion, hemodynamically insufficient basal collateralization, and increased cortical microvascularization. METHODS: In a prospective case series, we monitored for spontaneous spreading depolarization activity by using intraoperative laser speckle imaging for real-time visualization and measurement of cortical perfusion and cerebrovascular reserve capacity during cerebral revascularization in 4 consecutive patients with moyamoya. RESULTS: Spontaneous spreading depolarization occurrence was documented in a patient with moyamoya before bypass grafting. Interestingly, this patient also exhibited a marked preoperative increase in angiographic collateral vessel formation. CONCLUSIONS: The spontaneous occurrence of SDs in moyamoya vasculopathy could potentially provide an explanation for localized cortical infarction and increased cortical microvascular density in these patients.

A Cross-Sectional Study of Health-Related Quality of Life in Patients with Predominantly Antibody Deficiency.

Health-related quality of life (HRQoL) measures individual well-being across physical, psychological, and social domains. Patients with predominantly antibody deficiency (PAD) are at risk for morbidity and mortality, however, the effect of these complications on HRQoL requires additional study. Patients with PAD were asked to voluntarily complete the Centers for Disease Control (CDC) HRQoL-14 Healthy Days Measure questionnaire. These results were compared to data from the CDC-initiated Behavioral Risk Factor Surveillance System (BRFSS), a cross-sectional questionnaire including questions from CDC-HRQOL-14. Statistical analyses included two-proportion Z-test, t-tests, and analysis of variance. 83 patients with PAD completed the survey. Patients were sub-stratified into mild (23.7%), moderate (35.5%), severe (40.8%), and secondary (8.4%) PAD. "Fair or poor" health status was reported in 52.6% of PAD patients. Mental health challenges ≥ 14 days/month occurred in 25% of patients. Physical health issues ≥ 14 days/month was reported in 44.7% of patients. Activity limitations were noted by 80.3% of patients. There were no statistically significant differences by PAD severity. Patients with autoimmune and inflammatory disease co-morbidities reported more mental health challenges compared to those without (78% vs. 54.3%, p = 0.02). Compared to the CDC-BRFSS data, significantly more patients with PAD reported "fair or poor" health status (53% vs 12.0%; p < 0.0001), mental health challenges (24.1% vs 14.7%; p = 0.02), and poor physical health (44.6% vs 8.0%; p < 0.0001). Patients with PAD had significantly reduced HRQoL compared to CDC-BRFSS respondents from a similar geographical region. Decreased HRQoL was prevalent across all PAD severity levels. Additional research is needed to improve HRQoL for patients with PAD.

Guidelines for in vivo models of developmental programming of cardiovascular disease risk.

Research using animals depends on the generation of offspring for use in experiments or for the maintenance of animal colonies. Although not considered by all, several different factors preceding and during pregnancy, as well as during lactation, can program various characteristics in the offspring. Here, we present the most common models of developmental programming of cardiovascular outcomes, important considerations for study design, and provide guidelines for producing and reporting rigorous and reproducible cardiovascular studies in offspring exposed to normal conditions or developmental insult. These guidelines provide considerations for the selection of the appropriate animal model and factors that should be reported to increase rigor and reproducibility while ensuring transparent reporting of methods and results.

Co-designing care for multimorbidity: a systematic review.

BACKGROUND: The co-design of health care enables patient-centredness by partnering patients, clinicians and other stakeholders together to create services. METHODS: We conducted a systematic review of co-designed health interventions for people living with multimorbidity and assessed (a) their effectiveness in improving health outcomes, (b) the co-design approaches used and (c) barriers and facilitators to the co-design process with people living with multimorbidity. We searched MEDLINE, EMBASE, CINAHL, Scopus and PsycINFO between 2000 and March 2022. Included experimental studies were quality assessed using the Cochrane risk of bias tool (ROB-2 and ROBINS-I). RESULTS: We screened 14,376 reports, with 13 reports meeting the eligibility criteria. Two reported health and well-being outcomes: one randomised clinical trial (n = 134) and one controlled cohort (n = 1933). Outcome measures included quality of life, self-efficacy, well-being, anxiety, depression, functional status, healthcare utilisation and mortality. Outcomes favouring the co-design interventions compared to control were minimal, with only 4 of 17 outcomes considered beneficial. Co-design approaches included needs assessment/ideation (12 of 13), prototype (11 of 13), pilot testing (5 of 13) (i.e. focus on usability) and health and well-being evaluations (2 of 13). Common challenges to the co-design process include poor stakeholder interest, passive participation, power imbalances and a lack of representativeness in the design group. Enablers include flexibility in approach, smaller group work, advocating for stakeholders' views and commitment to the process or decisions made. CONCLUSIONS: In this systematic review of co-design health interventions, we found that few projects assessed health and well-being outcomes, and the observed health and well-being benefits were minimal. The intensity and variability in the co-design approaches were substantial, and challenges were evident. Co-design aided the design of novel services and interventions for those with multimorbidity, improving their relevance, usability and acceptability. However, the clinical benefits of co-designed interventions for those with multimorbidity are unclear.

Measuring internalized health-related stigma across health conditions: development and validation of the I-HEARTS Scale.

BACKGROUND: Health-related stigma and its internalization among individuals with chronic health conditions contribute to impaired mental and physical health and quality of life. Research on health-related stigma has been siloed, with disease-specific measures that may not capture the experiences of individuals with multiple health conditions and that prevent comparisons across health conditions. The current study aimed to develop and test a transdiagnostic measure of internalized health-related stigma for use among adults with different physical health conditions. METHODS: An existing measure of internalized mental health stigma was adapted to assess stigma due to chronic physical health conditions following COSMIN procedures, with input from advisory boards of community members living with a range of stigmatized health conditions (obesity, type 1 and type 2 diabetes, skin diseases, HIV, chronic pain, and cancers) and of health professionals who specialized in these conditions. The new Internalized Health-Related Stigma (I-HEARTS) Scale was tested in an online sample of 300 adults with these health conditions, recruited from ResearchMatch. Additional psychosocial measures of mental health and quality of life were administered, and participants provided information about their health conditions and demographic characteristics. Exploratory factor analysis and tests of reliability and validity were conducted to determine the psychometric properties of the I-HEARTS Scale, and k-means clustering and receiver of characteristic curve analysis were used to determine a clinically meaningful cutoff score indicating high levels of internalized stigma. RESULTS: Factor analysis results yielded a 25-item scale with a 3-factor solution, with subscales of Perceived and Anticipated Stigma, Stereotype Application and Self-Devaluation, and Stigma Resistance. Psychometric properties for internal consistency, inter-item and item-total correlations, and test-retest reliability were strong. Certain demographics (e.g., younger age) and characteristics related to health conditions (e.g., greater symptom severity) were associated with higher levels of internalized stigma. I-HEARTS Scale scores correlated moderately to strongly with related but distinct psychosocial measures, and a cutoff score of 3.40 or higher on the 1-7 rating scale was determined to indicate clinically meaningful levels of internalized stigma. CONCLUSIONS: The I-HEARTS Scale is a reliable and valid measure for the assessment of internalized health-related stigma among adults with varied stigmatized chronic health conditions. STUDY PRE-REGISTRATION: https://osf.io/84c5d/?view_only=87238512f6d6475c87f8f64280a8a15f .

The impact of adverse childhood experiences on multimorbidity: a systematic review and meta-analysis.

BACKGROUND: Adverse childhood experiences (ACEs) have been implicated in the aetiology of a range of health outcomes, including multimorbidity. In this systematic review and meta-analysis, we aimed to identify, synthesise, and quantify the current evidence linking ACEs and multimorbidity. METHODS: We searched seven databases from inception to 20 July 2023: APA PsycNET, CINAHL Plus, Cochrane CENTRAL, Embase, MEDLINE, Scopus, and Web of Science. We selected studies investigating adverse events occurring during childhood (< 18 years) and an assessment of multimorbidity in adulthood (≥ 18 years). Studies that only assessed adverse events in adulthood or health outcomes in children were excluded. Risk of bias was assessed using the ROBINS-E tool. Meta-analysis of prevalence and dose-response meta-analysis methods were used for quantitative data synthesis. This review was pre-registered with PROSPERO (CRD42023389528). RESULTS: From 15,586 records, 25 studies were eligible for inclusion (total participants = 372,162). The prevalence of exposure to ≥ 1 ACEs was 48.1% (95% CI 33.4 to 63.1%). The prevalence of multimorbidity was 34.5% (95% CI 23.4 to 47.5%). Eight studies provided sufficient data for dose-response meta-analysis (total participants = 197,981). There was a significant dose-dependent relationship between ACE exposure and multimorbidity (p < 0.001), with every additional ACE exposure contributing to a 12.9% (95% CI 7.9 to 17.9%) increase in the odds for multimorbidity. However, there was heterogeneity among the included studies (I2 = 76.9%, Cochran Q = 102, p < 0.001). CONCLUSIONS: This is the first systematic review and meta-analysis to synthesise the literature on ACEs and multimorbidity, showing a dose-dependent relationship across a large number of participants. It consolidates and enhances an extensive body of literature that shows an association between ACEs and individual long-term health conditions, risky health behaviours, and other poor health outcomes.

The relationship of cancer history and chronic disease status to colorectal cancer screening: A cross-sectional analysis of 2020-2021 Behavioral Risk Factor Surveillance System.

PURPOSE: We examined whether having a history of cancer and chronic diseases was associated with guideline-concordant colorectal cancer (CRC) screening utilization. METHODS: Self-reported data from the 2020 and 2021 Behavioral Risk Factor Surveillance System in Oregon and West Virginia were used. Guideline-concordant CRC screening was the outcome of interest. The exposure was having a personal history of cancer, chronic diseases, or both. Multivariable logistic regressions were applied to assess the abovementioned association. RESULTS: Among 10,373 respondents aged 45-75 years, 75.5% of those with a history of cancer and chronic diseases had guideline-concordant CRC screening use versus 52.8% of those without any history (p-value < 0.05). In multivariable analysis, having a history of cancer (OR 1.74; 95% CI 1.11-2.71), chronic diseases (OR 1.35; 95% CI 1.14-1.59), and both cancer and chronic diseases (OR 2.14; 95% CI 1.62-2.82) were positively associated with screening uptake compared to respondents without any history. Regardless of disease history, older age was associated with greater CRC screening uptake (p-value < 0.05). Among respondents with chronic diseases only or without any condition, those with a health care provider had 1.7-fold and 2.7-fold increased odds of receiving CRC screening, respectively. However, current smokers were 28% and 34% less likely to be screened for CRC among those with chronic diseases only and without any conditions, respectively. CONCLUSION: Having a personal history of cancer and chronic diseases appears to be positively associated with guideline-concordant CRC screening use. Effective implementation of patient-centered communication through primary care initiatives may increase adherence to CRC screening recommendations.

Quantitative estimation of intracellular oxidative stress in human tissues.

Oxidative stress is known to be involved in and possibly a key driver of the development of numerous chronic diseases, including cancer. It is highly desired to have a capability to reliably estimate the level of intracellular oxidative stress as it can help to identify functional changes and disease phenotypes associated with such a stress, but the problem proves to be very challenging. We present a novel computational model for quantitatively estimating the level of oxidative stress in tissues and cells based on their transcriptomic data. The model consists of (i) three sets of marker genes found to be associated with the production of oxidizing molecules, the activated antioxidation programs and the intracellular stress attributed to oxidation, respectively; (ii) three polynomial functions defined over the expression levels of the three gene sets are developed aimed to capture the total oxidizing power, the activated antioxidation capacity and the oxidative stress level, respectively, with their detailed parameters estimated by solving an optimization problem and (iii) the optimization problem is so formulated to capture the relevant known insights such as the oxidative stress level generally goes up from normal to chronic diseases and then to cancer tissues. Systematic assessments on independent datasets indicate that the trained predictor is highly reliable and numerous insights are made based on its application results to samples in the TCGA, GTEx and GEO databases.

Exercise intensity- and body region-specific differences in sweating in middle-aged to older men with and without type 2 diabetes.

Type 2 diabetes (T2D) is associated with reduced whole body sweating during exercise-heat stress. However, it is unclear if this impairment is related to exercise intensity and whether it occurs uniformly across body regions. We evaluated whole body (direct calorimetry) and local (ventilated-capsule technique; chest, back, forearm, thigh) sweat rates in physically active men with type 2 diabetes [T2D; aged 59 (7) yr; V̇o2peak 32.3 (7.6) mL·kg-1·min-1; n = 26; HbA1c 5.1%-9.1%] and without diabetes [Control; aged 61 (5) yr; V̇o2peak 37.5 (5.4) mL·kg-1·min-1; n = 26] during light- (∼40% V̇o2peak), moderate- (∼50% V̇o2peak), and vigorous- (∼65% V̇o2peak) intensity exercise (elicited by fixing metabolic heat production at ∼150, 200, 250 W·m-2, respectively) in 40°C, ∼17% relative humidity. Whole body sweating was ∼11% (T2D: Control mean difference [95% confidence interval]: -37 [-63, -12] g·m-2·h-1) and ∼13% (-50 [-76, -25] g·m-2·h-1) lower in the T2D compared with the Control group during moderate- and vigorous- (P ≤ 0.001) but not light-intensity exercise (-21 [-47, 4] g·m-2·h-1; P = 0.128). Consequently, the diabetes-related reductions in whole body sweat rate were 2.3 [1.6, 3.1] times greater during vigorous relative to light exercise (P < 0.001). Furthermore, these diabetes-related impairments in local sweating were region-specific during vigorous-intensity exercise (group × region interaction: P = 0.024), such that the diabetes-related reduction in local sweat rate at the trunk (chest, back) was 2.4 [1.2, 3.7] times greater than that at the limbs (thigh, arm). In summary, when assessed under hot, dry conditions, diabetes-related impairments in sweating are exercise intensity-dependent and greater at the trunk compared with the limbs.NEW & NOTEWORTHY This study evaluates the influence of exercise intensity on decrements in whole body sweating associated with type 2 diabetes. Furthermore, it investigates whether diabetes-related sweating impairments were exhibited uniformly or heterogeneously across body regions. We found that whole body sweating was attenuated in the type 2 diabetes group relative to control participants during moderate- and vigorous-intensity exercise but not light-intensity exercise; impairments were largely mediated by reduced sweating at the trunk rather than the limbs.

A contactless cure: Leveraging telehealth to improve hepatitis C treatment at a safety-net hospital.

Hepatitis C virus (HCV) causes significant mortality worldwide. HCV is highly curable but access to care is limited for many patients. The Grady Liver Clinic (GLC), a primary care-based HCV clinic, utilizes a multidisciplinary team to provide comprehensive care for a medically underserved patient population in Atlanta, Georgia. The GLC added a telehealth option for HCV treatment at the start of the COVID-19 pandemic. We describe the outcomes of utilizing telehealth in this population. We performed a retrospective chart review of patients who initiated HCV treatment from March 2019 to February 2020 (pre-pandemic) and March 2020 to February 2021 (pandemic). Charts were abstracted for patient demographics and characteristics, treatment regimen, and treatment outcomes. Our primary outcome was HCV cure rate of the pre-pandemic compared to the pandemic cohorts and within the different pandemic cohort visit types. We performed an intention-to-treat (ITT) analysis for all patients who took at least one dose of a direct-acting antiviral (DAA) regardless of therapy completion, and a per-protocol (PP) analysis of those who completed treatment and were tested for HCV cure. SVR12 rates were >95% on ITT analysis, with no significant difference between pre-pandemic and pandemic cohorts. There was also no significant difference within the pandemic group when treatment was provided traditionally, via telehealth, or via a hybrid of these. Our findings support the use of telehealth as a tool to expand access to HCV treatment in a medically underserved patient population.

Addressing the unmet needs of transitional care in juvenile idiopathic arthritis.

OBJECTIVES: We aimed to comprehensively analyse the available literature to identify the unmet requirements in transitional programs tailored specifically for patients diagnosed with JIA. METHODS: According to published guidance on narrative reviews, a systematic review of the literature on transitional care in rheumatology was conducted. Pertinent documents were collected from reputable databases, such as Web of Science, Scopus, and MEDLINE/PubMed. The search encompassed literature published from the inception of each database until January 2023. RESULTS: In this study, a comprehensive analysis of the findings of 34 studies was conducted. Among these, 12 studies focused on assessing the readiness of adolescents and young adults diagnosed with JIA. Additionally, 18 studies examined the effectiveness of structured transition programs in terms of adherence and satisfaction. Finally, 4 studies investigated disease-related outcomes in this population. CONCLUSION: The need for transitioning children with rheumatic diseases to adult rheumatology services for continued care is clearly evident. However, the absence of established best practice guidelines presents a challenge in facilitating this transition effectively. Although several scoring systems have been proposed to ensure organized and seamless transfers, a consensus has not yet been reached. Furthermore, the socio-economic and cultural variations across countries further complicate the development of universal guidelines for transitioning children with rheumatic diseases. To address these concerns, our objective in conducting this literature review was to emphasize the significance of this issue and identify the specific requirements based on the unmet needs in the transition process.

Intensity and Variation of Health Navigator Support: Addressing Medical and Social Needs of Diabetes Patients in East Oakland.

BACKGROUND: Healthcare systems are increasingly screening and referring patients for unmet social needs (e.g., food insecurity). Little is known about the intensity of support necessary to address unmet needs, how this support may vary by circumstance or time (duration), or the factors that may contribute to this variation. OBJECTIVE: Describe health navigator services and the effort required to support patients with complex needs at a community health center in East Oakland, CA. DESIGN: Retrospective analysis of de-identified patient contact notes (e.g., progress notes). PARTICIPANTS: Convenience sample of patients (n = 27) enrolled in diabetes education and referred to health navigators. INTERVENTIONS: Navigators provide education on managing conditions (e.g., diabetes), initiate and track medical and social needs referrals, and navigate patients to medical and social care organizations. MAIN MEASURES: Descriptive statistics for prevalence, mean, median, and range values of patient contacts and navigation services. We described patterns and variation in navigation utilization (both contacts and navigation services) based on types of need. KEY RESULTS: We identified 811 unmet social and medical needs that occurred over 710 contacts with health navigators; 722 navigation services were used to address these needs. Patients were supported by navigators for a median of 9 months; approximately 25% of patients received support for > 1 year. We categorized patients into 3 different levels of social risk, accounting for patient complexity and resource needs. The top tertile (n = 9; 33%) accounted for the majority of resource utilization, based on health navigator contacts (68%) and navigation services (75%). CONCLUSIONS: The required intensity and support given to meet patients' medical and social needs is substantial and has significant variation. Meeting the needs of complex patients will require considerable investments in human capital, and a risk stratification system to help identify those most in need of services.