Real-World Effectiveness of a Third Dose of mRNA-1273 Versus BNT162b2 on Inpatient and Medically Attended COVID-19 Among Immunocompromised US Adults.

INTRODUCTION: Recent data have shown elevated infection rates in several subpopulations at risk of SARS-CoV-2 infection and COVID-19, including immunocompromised (IC) individuals. Previous research suggests that IC persons have reduced risks of hospitalization and medically attended COVID-19 with two doses of mRNA-1273 (SpikeVax; Moderna) compared to two doses of BNT162b2 (Comirnaty; Pfizer/BioNTech). The main objective of this retrospective cohort study was to compare real-world effectiveness of third doses of mRNA-1273 versus BNT162b2 at multiple time points on occurrence of COVID-19 hospitalization and medically attended COVID-19 among IC adults in the United States (US). METHODS: This retrospective, observational comparative effectiveness study identified patients from the US HealthVerity database from December 11, 2020, through August 31, 2022. Medically attended SARS-CoV-2 infections and hospitalizations were assessed following a three-dose mRNA-1273 versus BNT162b2 regimen. Inverse probability weighting was applied to balance baseline confounders between vaccine groups. Relative risk (RR) and risk difference were calculated for subgroup and sensitivity analyses using a non-parametric method. RESULTS: In propensity score-adjusted analyses, receiving mRNA-1273 vs. BNT162b2 as third dose was associated with 32.4% (relative risk 0.676; 95% confidence interval 0.506-0.887), 29.3% (0.707; 0.573-0.858), and 23.4% (0.766; 0.626-0.927) lower risk of COVID-19 hospitalization after 90, 180, and 270 days, respectively. Corresponding reductions in medically attended COVID-19 were 8.4% (0.916; 0.860-0.976), 6.4% (0.936; 0.895-0.978), and 2.4% (0.976; 0.935-1.017), respectively. CONCLUSIONS: Our findings suggest a third dose of mRNA-1273 is more effective than a third dose of BNT162b2 in preventing COVID-19 hospitalization and breakthrough medically attended COVID-19 among IC adults in the US.

Cannabis use among adolescents and young adults during the COVID-19 pandemic: A systematic review.

Background: A systematic review of the literature was performed to summarize cannabis use among adolescents and young adults during the COVID-19 pandemic. Special focus was given to the prevalence of cannabis use during COVID-19, as well as factors that may explain changes in cannabis consumption patterns. Methods: The protocol of this systematic review was registered. Articles from seven publication databases were searched in January 2022. The inclusion criteria for studies were as follows: 1) published in English; 2) study instruments needed to include items on COVID-19; 3) conducted after January 1st, 2020; 4) published in a peer-reviewed journal, dissertation, or thesis; 5) study population ≤25 years of age; 6) study designs were limited to observational analytical studies; 7) measured cannabis use. This review excluded other reviews, editorials, and conference abstracts that were not available as full text manuscripts. Independent review, risk of bias assessment, and data abstraction were performed by two authors. Results: Fifteen articles from the United States (n=11) and Canada (n=4) were included in this review. The findings of this review showed that the prevalence of cannabis use during the pandemic among adolescents and young adults were mixed. Some mental health symptoms, including depression and anxiety, were identified as the most commonly reported reasons for increased cannabis use during the pandemic. Conclusions: This review highlights the inconsistencies in the prevalence of cannabis use among adolescents and young adults during the pandemic. Therapeutic interventions for mental health and continued public health surveillance should be conducted to understand the long-term effects of cannabis use among adolescents and young adults.

Educational Intervention to Increase COVID-19 Vaccine Uptake in Rural Patients with Chronic Diseases: Lessons Learned from An Innovative Academic-Community Partnership.

BACKGROUND: The pandemic has disproportionately impacted rural communities with a higher burden of chronic disease and COVID-19 infection. West Virginia is a rural state with a high rate of diabetes, hypertension, and COPD, which are known risk factors for severe COVID-19 and long COVID. Yet, there is a significant hesitancy regarding COVID-19 vaccination uptake in the state. The purpose of this study was to use an educational intervention to increase vaccine knowledge and vaccine acceptance in rural patients with chronic disease(s) in West Virginia. This project used an academic-community partnership comprised of researchers, practitioners, community organizations, community-engaged partners, and patient stakeholders to increase COVID-19 health literacy and increase vaccine acceptance among rural West Virginians with chronic conditions. MATERIALS AND METHODS: A quasi-experimental study design was used to deliver an educational intervention by trained Health Navigators using short videos to increase COVID-19 health literacy and address participants' vaccine concerns. Eligibility included adults (18 years and older) who have at least one chronic condition. A statewide community advisory board (CAB) guided the development of the educational training curriculum and implementation strategies. An adapted version of the Exploration, Preparation, Implementation, Sustainment (EPIS) framework guided the development of the intervention. Health Navigators (n = 45) delivered the educational intervention in their local communities between November 2022 and October 2023 (project implementation is still ongoing). Intervention fidelity checks, an adaptable script, and a flow chart allowed tailoring of brief videos to address participants' specific COVID-19 questions and vaccine concerns. A validated online survey, monitored by an online Research Electronic Data Capture (REDCap) database, assessed participants' knowledge, perceived susceptibility, and vaccine intention. RESULTS: Health Navigators delivered the intervention to 1368 West Virginians in 52 counties (59.2% women; 61.8% without a college degree). Participants reported living with an average of 2.1 ± 1.4 chronic conditions. The mean age was 43.5 ± 18.8 years. The majority of participants (81.2%) had received the primary vaccination series, and 63.1% had at least one booster. However, 18% were unvaccinated or did not complete the primary COVID-19 vaccine series. Discussions to improve vaccine literacy focused on how the vaccine was so quickly developed and protects against variants, addressing concerns related to the safety, short- and long-term side effects, and importance of vaccine uptake for immunocompromised individuals. Participants with higher concerns were more likely to be unvaccinated and to have not completed their primary series or boosters (p < 0.001). However, the educational intervention improved the willingness of individuals who were either unvaccinated or did not complete their primary vaccine series to get vaccinated (11.4%). DISCUSSION: Our findings highlight the importance of vaccine literacy in increasing vaccination rates among rural patients with chronic diseases. Using the EPIS framework allowed us to reflect upon the challenges, ensure resilience during changing local contexts, and plan and implement a promising, cost-effective intervention in rural areas. CONCLUSIONS: This study provides insights into the need for tailored educational interventions based on disease status, which has implications for public health and patient care in rural and underserved communities. Academic-community partnerships can be useful for successful knowledge transfer for vaccine acceptance to reduce rural health disparities.

Exploring facilitators and barriers to patient-provider communication regarding diabetes self-management.

Objective: Long-term type 2 diabetes management requires open communication between a patient and their provider for self-care adherence. This study explored facilitators and barriers to diabetes-specific communication in West Virginia, a medically underserved state with the highest prevalence of diabetes (16.2%) in the U.S. Methods: A secondary qualitative analysis was conducted using data from semi-structured interviews (n = 34) and 4 focus groups (n = 23) with participants of a diabetes education program. Transcripts were analyzed using thematic analysis. Results: Three facilitators to patient-provider communication emerged: "Patient-Provider Partnership", "Provider Accessibility", and "Empowerment Through Education". Partnership with providers, especially those who were accessible outside of scheduled appointments, and empowerment obtained through diabetes education facilitated diabetes-specific patient-provider communication. However, barriers included "Providers' Focus on 'Numbers' Rather than Patient Concerns", "Patient Lack of Preparation for Appointments", and "Providers 'Talking Down to' Patients". Conclusion: The findings highlight patient- and provider-related factors that impact diabetes-specific communication. Innovation: Previous interventions have trained providers in communication skills. Despite some success, challenges in implementation remain considering providers' limited time and overwhelming demands. This study suggests that diabetes education programs incorporating communication and self-advocacy skills could be a promising alternative as they can empower patients to communicate their diabetes-specific needs/preferences with providers.

Impact of Season and Other Factors on Initiation, Discontinuation, and Switching of Systemic Drug Therapy in Patients with Psoriasis: A Retrospective Study.

This study investigated whether systemic drug prescribing for psoriasis varies by season and other exacerbating factors. Eligible patients with psoriasis were assessed for each season for initiation, discontinuation, and switching of systemic drugs. A total of 360,787 patients were at risk of initiating any systemic drugs in 2016‒2019; 39,572 patients and 35,388 patients were at risk of drug discontinuation or switching to a biologic and a nonbiologic systemic drug, respectively. The initiation of biologic therapy in 2016‒2019 peaked in spring (1.28%), followed by summer (1.11%), fall (1.08%), and winter (1.01%). Nonbiologic systemic drugs followed a similar pattern. Those aged 30‒39 years, male, those with psoriatic arthritis, those who live in the South region, those who live in areas with lower altitudes, and those who live in areas with lower humidity had higher initiation with the same seasonality pattern. Discontinuation of biologic drugs peaked in summer, and switching of biologics was highest in spring. Season is associated with initiation, discontinuation, and switching, although seasonality pattern is less clear for nonbiologic systemic drugs. Approximately 14,280 more patients with psoriasis in the United States are estimated to initiate a biologic in spring than in other seasons, and over 840 more biologic users switched in spring than in winter. The findings may provide evidence for healthcare resource planning in psoriasis management.

Relationship Among Diabetes Distress, Health Literacy, Diabetes Education, Patient-Provider Communication and Diabetes Self-Care.

OBJECTIVES: Mechanisms underlying relationships among patients' health literacy, diabetes distress, diabetes education, and provider counseling for self-care of chronic conditions are unclear. This study tested these relationships using SEM with adult patients with comorbid diabetes and hypertension in rural WV. METHODS: Ninety-one participants of a 12-week self-management program reported on diabetes self-care (diet, exercise, blood glucose (BG) monitoring) and related provider counseling. RESULTS: Based on patient report, providers' recommendations included following a low-fat diet, eating fruits/ vegetables, limiting sweets, a daily low-level of exercise and/or exercise ≥20 minutes three times/week, and BG monitoring. Provider recommendations were shown to be associated with patients' self-care behaviors (r=0.22, p<0.05). Multiple factors directly influenced provider recommendations: diabetes distress, health literacy, and family history of diabetes. A positive association was also noted between prior diabetes education and provider recommendations and diabetes self-care (r=0.44, p<0.001). A negative association was noted between diabetes distress and self-care, but a positive effect on provider recommendations was found. The model demonstrated good fit [CFI=0.94, and Root Mean Square Error of Approximation (RMSEA) =0.05]. CONCLUSIONS: To enhance diabetes self-care, providers should consistently provide education on self-care behaviors as well as partner with them to address diabetes distress.

Real-world comparative effectiveness of mRNA-1273 and BNT162b2 vaccines among immunocompromised adults identified in administrative claims data in the United States.

INTRODUCTION: Head-to-head studies comparing COVID-19 mRNA vaccine effectiveness in immunocompromised individuals, who are vulnerable to severe disease are lacking, as large sample sizes are required to make meaningful inferences. METHODS: This observational comparative effectiveness study was conducted in closed administrative claims data from the US HealthVerity database (December 11, 2020-January 10, 2022, before omicron). A 2-dose mRNA-1273 versus BNT162b2 regimen was assessed for preventing medically-attended breakthrough COVID-19 diagnosis and hospitalizations among immunocompromised adults. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) using weighted Cox proportional hazards models were calculated. RESULTS: Overall, 57,898 and 66,981 individuals received a 2-dose regimen of mRNA-1273 or BNT161b2, respectively. Among the weighted population, mean age was 51 years, 53 % were female, and baseline immunodeficiencies included prior blood transplant (8%-9%), prior organ transplant (7%), active cancer (12%-13%), primary immunodeficiency (5-6%), HIV (20%-21%), and immunosuppressive therapy use (60%-61%). Rates per 1,000 person-years (PYs; 95% confidence intervals [CI]s) of breakthrough medically-attended COVID-19 were 25.82 (23.83-27.97) with mRNA-1273 and 30.98 (28.93, 33.18) with BNT162b2 (HR, 0.83; 95% CI, 0.75-0.93). When requiring evidence of an antigen or polymerase chain reaction test before COVID-19 diagnosis, the HR for medically-attended COVID-19 was 0.78 (0.67-0.92). Breakthrough COVID-19 hospitalization rates per 1,000 PYs (95% CI) were 3.66 (2.96-4.51) for mRNA-1273 and 4.68 (3.91-5.59) for BNT162b2 (HR, 0.78; 0.59-1.03). Utilizing open and closed claims for outcome capture only, or both cohort entry/outcome capture, produced HRs (95% CIs) for COVID-19 hospitalization of 0.72 (0.57-0.92) and 0.66 (0.58-0.76), respectively. CONCLUSIONS: Among immunocompromised adults, a 2-dose mRNA-1273 regimen was more effective in preventing medically-attended COVID-19 in any setting (inpatient and outpatient) than 2-dose BNT162b2. Results were similar for COVID-19 hospitalization, although statistical power was limited when using closed claims only. STUDY REGISTRATION: NCT05366322.

Addressing Uncertainty in Informal Familial Caregivers of Stroke Survivors: A Systematic Meta-Ethnography.

Background: Informal familial caregivers of stroke survivors experience uncertainty that begins at the time of the stroke event and continues into home-based care. The uncertainty faced by caregivers contributes to poor mental and physical health outcomes. Objective: This review details the factors associated with, impacts of, and coping skills used to manage uncertainty across the caregiving trajectory. By defining uncertainty reduction and tolerance recommendations, this review also builds upon the Stroke Caregiver Readiness Model to improve preparedness following the stroke event. Methods: A meta-ethnographic review was systematically conducted on thirteen qualitative studies with 218 participants from four countries. The Critical Appraisal Skills Programme (CASP) was used to assess study quality. Results: Following the stroke event, caregivers reported a lack of knowing (e.g., about the cause of the stroke event and survivor prognoses) as contributing to post-stroke uncertainty. As a result of this uncertainty, caregivers expressed concerns about their abilities to navigate caregiving responsibilities and how to plan for the future. Longer-term concerns (e.g., managing finances) and feelings of hopelessness occurred after discharge. Still, caregivers identified strategies to manage uncertainty. Caregiver coping skills included present-focused thinking, gratitude, faith, humor, and social support. Conclusions: The uncertainty faced by informal familial caregivers of stroke survivors is pervasive and changes across time. Uncertainty reduction and tolerance interventions can be used to build upon caregiver strengths and promote preparedness across the caregiving trajectory.

Provider Perspectives on Sleep Apnea from Appalachia: A Mixed Methods Study.

West Virginia (WV) has the highest rates of obesity and cardiopulmonary disease in the United States (U.S.). Recent work has identified a significant care gap in WV for obstructive sleep apnea (OSA). This OSA care gap likely has significant health implications for the region given the high rates of obesity and cardiopulmonary disease. The purpose of this mix methods study was to identify barriers that contribute to the rural OSA care disparity previously identified in WV. Methods: This study used mixed methods to evaluate the barriers and facilitators to management of OSA at Federally Qualified Health Centers serving communities in southern WV. Focus groups were conducted at federally qualified health centers with providers serving Appalachian communities. Participants also completed the validated Obstructive Sleep Apnea Knowledge and Attitudes (OSAKA) questionnaire to gain insight into provider knowledge and beliefs regarding OSA. EMR analysis using diagnostic codes was completed at the sites to assess OSA prevalence rates. The same individual served as the interviewer in all focus group sessions to minimize interviewer variability/bias. Our team checked to ensure that the professional transcriptions were correct and matched the audio via spot checks. Results: Themes identified from the focus groups fell into three broad categories: (1) barriers to OSA care delivery, (2) facilitators to OSA care delivery, and (3) community-based care needs to optimize management of OSA in the targeted rural areas. Questionnaire data demonstrated rural providers feel OSA is an important condition to identify but lack confidence to identify and treat OSA. Evaluation of the electronic medical record demonstrates an even larger OSA care gap in these rural communities than previously described. Conclusion: This study found a lack of provider confidence in the ability to diagnose and treat OSA effectively and identified specific themes that limit OSA care in the communities studied. Training directed toward the identified knowledge gaps and on new technologies would likely give rural primary care providers the confidence to take a more active role in OSA diagnosis and management. An integrated model of care that incorporates primary care providers, specialists and effective use of modern technologies will be essential to address the identified OSA care disparities in rural WV and similar communities across the U.S. Community engaged research such as the current study will be essential to the creation of feasible, practical, relevant and culturally competent care pathways for providers serving rural communities with OSA and other respiratory disease to achieve health equity.

Effects of the Selective Serotonin Reuptake Inhibitor Fluoxetine on Developing Neural Circuits in a Model of the Human Fetal Cortex.

The developing prenatal brain is particularly susceptible to environmental disturbances. During prenatal brain development, synapses form between neurons, resulting in neural circuits that support complex cognitive functions. In utero exposure to environmental factors such as pharmaceuticals that alter the process of synapse formation increases the risk of neurodevelopmental abnormalities. However, there is a lack of research into how specific environmental factors directly impact the developing neural circuitry of the human brain. For example, selective serotonin reuptake inhibitors are commonly used throughout pregnancy to treat depression, yet their impact on the developing fetal brain remains unclear. Recently, human brain models have provided unprecedented access to the critical window of prenatal brain development. In the present study, we used human neurons and cortical spheroids to determine whether the selective serotonin reuptake inhibitor fluoxetine alters neurite and synapse formation and the development of spontaneous activity within neural circuits. We demonstrate that cortical spheroids express serotonin transporter, thus recapitulating the early developmental expression of serotonin transporter associated with cortical pyramidal neurons. Cortical spheroids also appropriately express serotonin receptors, such as synaptic 5-HT2A and glial 5-HT5A. To determine whether fluoxetine can affect developing neural circuits independent of serotonergic innervation from the dorsal and medial raphe nuclei, we treated cortical neurons and spheroids with fluoxetine. Fluoxetine alters neurite formation in a dose-dependent fashion. Intriguingly, in cortical spheroids, neither acute nor chronic fluoxetine significantly altered excitatory synapse formation. However, only acute, but not chronic fluoxetine exposure altered inhibitory synaptogenesis. Finally, fluoxetine reversibly suppresses neuronal activity in a dose-dependent manner. These results demonstrate that fluoxetine can acutely alter synaptic function in developing neural circuits, but the effects were not long-lasting. This work provides a foundation for future studies to combine serotonergic innervation with cortical spheroids and assess the contributions of fluoxetine-induced alterations in serotonin levels to brain development.

Addressing Diabetes Distress in Self-Management Programs: Results of a Randomized Feasibility Study.

Background: West Virginia ranks 1st nationally in the prevalence of hypertension (HTN; 43.8%) and diabetes (16.2%). Patients with type 2 diabetes mellitus (T2DM) are distressed over physical and psychological burden of disease self-management. Methods: This study investigated the effectiveness of an intervention to reduce diabetes distress and outcomes [glycemic control, blood pressure (BP)] among T2DM adults with comorbid HTN. Participants were randomized to a 12-week diabetes and hypertension self-management program versus a 3-month wait-listed control group. Trained health coaches and experts implemented the lifestyle program in a faith-based setting using an adapted evidence-based curriculum. Twenty adults with T2DM and HTN (n=10 per group) completed baseline and 12-week assessments. Diabetes distress was measured by using a validated Diabetes Distress Survey (17-item Likert scale; four sub-scales of emotional burden, physician related burden, regimen related burden, and interpersonal distress). Baseline and post-intervention changes in diabetes distress were compared for both groups; reduction in distress in the intervention groups are depicted using waterfall plots. The mean age, HbA1c and BMI were 55 ± 9.6 years, 7.8 ± 2.24 and 36.4 ± 8.8, respectively. Diabetes distress (total; mean) was 1.84±0.71. Results: Participants reported higher diabetes distress related to emotional burden (2.1±0.94) and regimen-related distress (2.0 ± 0.74); physician-related distress was the lowest (1.18±0.64). In general, diabetes distress reduced among intervention participants and was especially significant among those with HbA1c ≤ 8% (r=0.28, p=0.4), and systolic/diastolic BP ≤140/80 mm Hg (r=0.045, P=0.18). Implications: Findings suggest that lifestyle self-management programs have the potential to reduce diabetes distress.

Cytoskeletal regulation of synaptogenesis in a model of human fetal brain development.

Excitatory synapse formation begins in mid-fetal gestation. However, due to our inability to image fetal synaptogenesis, the initial formation of synapses remains understudied. The recent development of human fetal brain spheroids provides access to this critical period of synapse formation. Using human neurons and brain spheroids, we address how altered actin regulation impacts the formation of excitatory synapses during fetal brain development. Prior to synapse formation, inhibition of RhoA kinase (ROCK) signaling promotes neurite elongation and branching. In addition to increasing neural complexity, ROCK inhibition increases the length of protrusions along the neurite, ultimately promoting excitatory synapse formation in human cortical brain spheroids. A corresponding increase in Rac1-driven actin polymerization drives this increase in excitatory synaptogenesis. Using STORM super-resolution microscopy, we demonstrate that actomyosin regulators, including the Rac1 regulator, α-PIX, and the RhoA regulator, p115-RhoGEF, localize to nascent excitatory synapses, where they preferentially localize to postsynaptic compartments. These results demonstrate that coordinated RhoGTPase activities underlie the initial formation of excitatory synapses and identify critical cytoskeletal regulators of early synaptogenic events.

Variety, Price, and Consumer Desirability of Fresh Fruits and Vegetables in 7 Cities around the World.

Few studies have attempted to quantify the variety, price, and consumer desirability of fruits and vegetables (F&Vs) across a diversity of cities. We implemented a market basket survey of F&Vs from December 2018 to February 2019 in middle-income neighborhoods of the following cities: Visakhapatnam, India; Kathmandu, Nepal; Addis Ababa, Ethiopia; Dar es Salaam, Tanzania; Mexico City, Mexico; Bangkok, Thailand; and Brookline, United States. The total variety of fruits ranged from 4.1 in Visakhapatnam to 17.3 in Brookline, and of vegetables from 6.1 in Dar es Salaam to 20.3 in Brookline. Of the 3 fruits for which price data were collected, apples tended to be the most expensive, and bananas the least expensive. For vegetables, capsicum tended to be the most expensive and eggplants the least expensive. Tablet-based market basket surveys are a useful tool for evaluating food environments. These pilot data provide further evidence of the homogenization of global diets.