Targeting DBS to the centrolateral thalamic nucleus improves movement in a lesion-based model of acquired cerebellar dystonia in mice.

Dystonia is the third most common movement disorder and an incapacitating co-morbidity in a variety of neurologic conditions. Dystonia can be caused by genetic, degenerative, idiopathic, and acquired etiologies, which are hypothesized to converge on a "dystonia network" consisting of the basal ganglia, thalamus, cerebellum, and cerebral cortex. In acquired dystonia, focal lesions to subcortical areas in the network - the basal ganglia, thalamus, and cerebellum - lead to a dystonia that can be difficult to manage with canonical treatments, including deep brain stimulation (DBS). While studies in animal models have begun to parse the contribution of individual nodes in the dystonia network, how acquired injury to the cerebellar outflow tracts instigates dystonia; and how network modulation interacts with symptom latency remain as unexplored questions. Here, we present an electrolytic lesioning paradigm that bilaterally targets the cerebellar outflow tracts. We found that lesioning these tracts, at the junction of the superior cerebellar peduncles and the medial and intermediate cerebellar nuclei, resulted in acute, severe dystonia. We observed that dystonia is reduced with one hour of DBS of the centrolateral thalamic nucleus, a first order node in the network downstream of the cerebellar nuclei. In contrast, one hour of stimulation at a second order node in the short latency, disynaptic projection from the cerebellar nuclei, the striatum, did not modulate the dystonia in the short-term. Our study introduces a robust paradigm for inducing acute, severe dystonia, and demonstrates that targeted modulation based on network principles powerfully rescues motor behavior. These data inspire the identification of therapeutic targets for difficult to manage acquired dystonia.

Health Care Utilization and Care-seeking Behavior Among Vulnerabilized Sexual Minority Women: A Social-ecological Approach.

Sexual minority women (SMW) experience worse health than their heterosexual counterparts but have largely been omitted from health services research. To address this gap, we conducted 25 semi-structured, in-depth interviews with SMW. Transcripts were analyzed using thematic analysis, and findings were organized using a modified socioecological framework. Key themes at each socioecological level include (1) structural: stigma, sociocultural norms, health infrastructure; (2) organizational: stigma, patient-provider relationship, hours and location, linkage to care and co-location of services; (3) interpersonal: stigma and social support; (4) individual: internalized stigma, self-efficacy, socioeconomic status, health literacy, and intersecting identities. Stigma is the central theme affecting vulnerabilized SMW's experiences accessing care. Anti-stigma initiatives and factors that lead to personal resilience and can mitigate care access barriers were identified at each level. Interventions should focus on building inclusive policies/infrastructure and using SMW's unique social networks to empower and improve care access and health outcomes among vulnerabilized SMW.

Frequencies and spectra of aflatoxin B1-induced mutations in liver genomes of NEIL1-deficient mice as revealed by duplex sequencing.

Increased risk for the development of hepatocellular carcinoma (HCC) is driven by a number of etiological factors including hepatitis viral infection and dietary exposures to foods contaminated with aflatoxin-producing molds. Intracellular metabolic activation of aflatoxin B1 (AFB1) to a reactive epoxide generates highly mutagenic AFB1-Fapy-dG adducts. Previously, we demonstrated that repair of AFB1-Fapy-dG adducts can be initiated by the DNA glycosylase NEIL1 and that male Neil1-/- mice were significantly more susceptible to AFB1-induced HCC relative to wild-type mice. To investigate the mechanisms underlying this enhanced carcinogenesis, WT and Neil1-/- mice were challenged with a single, 4 mg/kg dose of AFB1 and frequencies and spectra of mutations were analyzed in liver DNAs 2.5 months post-injection using duplex sequencing. The analyses of DNAs from AFB1-challenged mice revealed highly elevated mutation frequencies in the nuclear genomes of both males and females, but not the mitochondrial genomes. In both WT and Neil1-/- mice, mutation spectra were highly similar to the AFB1-specific COSMIC signature SBS24. Relative to wild-type, the NEIL1 deficiency increased AFB1-induced mutagenesis with concomitant elevated HCCs in male Neil1-/- mice. Our data establish a critical role of NEIL1 in limiting AFB1-induced mutagenesis and ultimately carcinogenesis.

Understanding the role of AMPA receptors in autism: insights from circuit and synapse dysfunction.

Autism spectrum disorders represent a diverse etiological spectrum that converge on a syndrome characterized by discrepant deficits in developmental domains often highlighted by concerns in socialization, sensory integration, and autonomic functioning. Importantly, the incidence and prevalence of autism spectrum disorders have seen sharp increases since the syndrome was first described in the 1940s. The wide etiological spectrum and rising number of individuals being diagnosed with the condition lend urgency to capturing a more nuanced understanding of the pathogenic mechanisms underlying the autism spectrum disorders. The current review seeks to understand how the disruption of AMPA receptor (AMPAr)-mediated neurotransmission in the cerebro-cerebellar circuit, particularly in genetic autism related to SHANK3 or SYNGAP1 protein dysfunction function and autism associated with in utero exposure to the anti-seizure medications valproic acid and topiramate, may contribute to the disease presentation. Initially, a discussion contextualizing AMPAr signaling in the cerebro-cerebellar circuitry and microstructural circuit considerations is offered. Subsequently, a detailed review of the literature implicating mutations or deletions of SHANK3 and SYNGAP1 in disrupted AMPAr signaling reveals how bidirectional pathogenic modulation of this key circuit may contribute to autism. Finally, how pharmacological exposure may interact with this pathway, via increased risk of autism diagnosis with valproic acid and topiramate exposure and potential treatment of autism using AMPAr modulator perampanel, is discussed. Through the lens of the review, we will offer speculation on how neuromodulation may be used as a rational adjunct to therapy. Together, the present review seeks to synthesize the disparate considerations of circuit understanding, genetic etiology, and pharmacological modulation to understand the mechanistic interaction of this important and complex disorder.

Patient and Therapist Perceptions of a Publicly Funded Internet-Based Cognitive Behavioral Therapy (iCBT) Program for Ontario Adults During the COVID-19 Pandemic: Qualitative Study.

BACKGROUND: To address the anticipated rise in mental health symptoms experienced at the population level during the COVID-19 pandemic, the Ontario government provided 2 therapist-assisted internet-delivered cognitive behavioral therapy (iCBT) programs to adults free of charge at the point of service. OBJECTIVE: The study aims to explore the facilitators of and barriers to implementing iCBT at the population level in Ontario, Canada, from the perspective of patients and therapists to better understand how therapist-assisted iCBT programs can be effectively implemented at the population level and inform strategies for enhancing service delivery and integration into the health care system. METHODS: Using a convenience sampling methodology, semistructured interviews were conducted with 10 therapists who delivered iCBT and 20 patients who received iCBT through either of the publicly funded programs to explore their perspectives of the program. Interview data were analyzed using inductive thematic analysis to generate themes. RESULTS: Six salient themes were identified. Facilitators included the therapist-assisted nature of the program; the ease of registration and the lack of cost; and the feasibility of completing the psychoeducational modules given the online and self-paced nature of the program. Barriers included challenges with the online remote modality for developing the therapeutic alliance; the program's generalized nature, which limited customization to individual needs; and a lack of formal integration between the iCBT program and the health care system. CONCLUSIONS: Although the program was generally well-received by patients and therapists due to its accessibility and feasibility, the digital format of the program presented both benefits and unique challenges. Strategies for improving the quality of service delivery include opportunities for synchronous communication between therapists and patients, options for increased customization, and the formal integration of iCBT into a broader stepped-care model that centralizes patient referrals between care providers and promotes continuity of care.

Sclerotherapy off the Lower Extremities: A Single-Center Retrospective Study of Veins Treated on the Dorsal Hands and Chest.

BACKGROUND: Few studies have evaluated the safety and efficacy of treatment of cosmetic dorsal hand and chest/breast veins. OBJECTIVE: To retrospectively evaluate results of dorsal hand and chest vein foam sclerotherapy. MATERIALS AND METHODS: A retrospective chart review of dorsal hand and chest vein sclerotherapy patients at a dermatology practice was performed between January 2014 and April 2023. RESULTS: Fifty-five patients (54 female and 1 male patients) with a mean age of 55.8 ± 10.5 (31-83) years underwent treatment. Mean number of sessions for dorsal hand ( n = 41) and chest ( n = 14) patients were 1.5 ± 0.9 (1-5) and 1.6 ± 1.2 (1-5), respectively. Both groups were predominantly treated with 0.2% sodium tetradecyl sulfate or 0.5% polidocanol foam. Rate of coagulum formation across all sessions in the dorsal hands and chest was 15.2% and 3.0%, respectively. Vein induration, edema, postsclerotherapy hyperpigmentation, and persistent erythema were rarely seen. No patients experienced superficial venous thrombophlebitis, erosion/ulceration, telangiectatic matting, or neurologic side effects. Seventy-five percent and 63.2% of chest and hand patients, respectively, demonstrated significant clinical improvement at 3-month follow-up, although not systematically evaluated. CONCLUSION: Foam sclerotherapy of dorsal hand and chest veins with detergent sclerosing agents is safe and effective with mild, self-limited adverse events.

Barriers and facilitators to COVID-19 testing among staff and parents from San Diego schools.

COVID-19 testing is an important risk mitigation strategy for COVID-19 prevention in school settings, where the virus continues to pose a public health challenge for in-person learning. Socially vulnerable school communities with the highest proportion of low-income, minority, and non-English speaking families have the least testing access despite shouldering a disproportionate burden of COVID-19 morbidity and mortality. Through the Safer at School Early Alert (SASEA) program, we investigated community perceptions of testing in San Diego County schools, with a focus on barriers and facilitators from the perspective of socially vulnerable parents and school staff. Using a mixed-methods approach, we administered a community survey and conducted focus group discussions (FGDs) with staff and parents from SASEA-affiliated schools and childcares. We recruited 299 survey respondents and 42 FGD participants. Protecting one's family (96.6%) and protecting one's community (96.6%) were marked as key motivators to testing uptake. School staff in particular reported that the reassurance of a negative status mitigated concerns about COVID-19 infection in schools. Participants expressed that COVID-19-related stigma, loss of income as a result of isolation/quarantine requirements, and lack of multilingual materials were the most significant barriers to testing. Our findings suggest that the testing barriers faced by school community members are predominantly structural. Testing uptake efforts must provide support and resources to manage the social and financial consequences of testing while continuously communicating its benefits. There is a clear need to continue to incorporate testing as a strategy to maintain school safety and facilitate access for vulnerable community members.

Using machine learning to develop a clinical prediction model for SSRI-associated bleeding: a feasibility study.

INTRODUCTION: Adverse drug events (ADEs) are associated with poor outcomes and increased costs but may be prevented with prediction tools. With the National Institute of Health All of Us (AoU) database, we employed machine learning (ML) to predict selective serotonin reuptake inhibitor (SSRI)-associated bleeding. METHODS: The AoU program, beginning in 05/2018, continues to recruit ≥ 18 years old individuals across the United States. Participants completed surveys and consented to contribute electronic health record (EHR) for research. Using the EHR, we determined participants who were exposed to SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine). Features (n = 88) were selected with clinicians' input and comprised sociodemographic, lifestyle, comorbidities, and medication use information. We identified bleeding events with validated EHR algorithms and applied logistic regression, decision tree, random forest, and extreme gradient boost to predict bleeding during SSRI exposure. We assessed model performance with area under the receiver operating characteristic curve statistic (AUC) and defined clinically significant features as resulting in > 0.01 decline in AUC after removal from the model, in three of four ML models. RESULTS: There were 10,362 participants exposed to SSRIs, with 9.6% experiencing a bleeding event during SSRI exposure. For each SSRI, performance across all four ML models was relatively consistent. AUCs from the best models ranged 0.632-0.698. Clinically significant features included health literacy for escitalopram, and bleeding history and socioeconomic status for all SSRIs. CONCLUSIONS: We demonstrated feasibility of predicting ADEs using ML. Incorporating genomic features and drug interactions with deep learning models may improve ADE prediction.

Impact of virtual visits on primary care physician work flows.

OBJECTIVE: To understand the impact of virtual visits on primary care physician (PCP) work flows. DESIGN: Qualitative semistructured interviews. SETTING: Primary care practices within 5 regions in southern Ontario. PARTICIPANTS: Physicians representing primary care practices of various sizes and remuneration models (eg, capitation and fee-for-service models). METHODS: Interviews were conducted with PCPs involved in a large-scale pilot project implementing virtual visits (via a Web-based application) into clinical practices. Convenience and purposive sampling were used to recruit PCPs between January 2018 and March 2019. To obtain a representative sample, participants were sought from a variety of practice types and geographic regions. High and low users of virtual visits were included. Interviews were audiorecorded and transcribed. An inductive thematic analysis was used to identify prominent themes and subthemes. MAIN FINDINGS: Twenty-six physicians were interviewed (n=15 using convenience sampling and n=11 through purposive sampling). Four themes were identified: PCPs employ diverse approaches to integrate virtual care into their work flow; PCPs recognize that implementing virtual visits requires upfront time and effort but have variable perceptions regarding long-term impact of virtual care on processes; asynchronous messaging is preferable to synchronous audio or video visits; and strategies were identified to improve the integration of virtual visits. CONCLUSION: The potential of virtual care to improve work flow is dependent on the way these visits are implemented and used. Dedicated time for implementation, emphasis on using asynchronous secure messaging, and access to clinical champions and structured change management support were associated with more seamless integration of virtual visits.

Redesigning primary care: Provider perspectives on the clinical utility of virtual visits.

OBJECTIVE: To explore primary care physician (PCP) perspectives on the clinical utility of virtual visits. DESIGN: Qualitative design involving semistructured interviews. SETTING: Primary care practices within 5 regions in southern Ontario. PARTICIPANTS: Primary care physicians representing different practice sizes and remuneration models. METHODS: Interviews were conducted with PCPs who were involved in a large-scale pilot implementation of virtual visits (patient-provider asynchronous messaging, or synchronous audio or video communication). The first phase involved a convenience sample of users in the first 2 regions where the pilot was initiated; after implementation in all 5 regions, purposive sampling was used to ensure diversity within the sample (eg, physicians representing different use frequencies of virtual visits, regions, and remuneration models). Interviews were audiorecorded and transcribed. An inductive thematic analysis was used to identify prominent themes and subthemes. MAIN FINDINGS: Twenty-six physicians were interviewed. Fifteen were recruited using convenience sampling and 11 through purposive sampling. Four themes regarding the clinical utility of virtual visits were identified: virtual visits can effectively resolve many patient concerns, with some variation in PCP comfort using virtual visits for specific conditions; virtual visits are beneficial for a range of patients but some patients might overuse or inappropriately use them; PCPs prefer to use asynchronous messaging (eg, text or online messaging) because of its convenience and flexibility; and virtual visits can provide value at the patient, provider, and health system levels. CONCLUSION: While participants believed that virtual visits can be appropriately used to resolve a variety of clinical concerns, they found in practice that virtual visits are fundamentally different from face-to-face encounters. Professional guidelines on appropriate use cases should be established to develop a standard framework for virtual care.

Characterization of COVID-19 Vaccine Hesitancy Among Essential Workforce Members of a Large Safety Net Urban Medical Center.

OBJECTIVES: Vaccine hesitancy among essential workers remains a significant public health challenge. We examined psychological constructs of perceived susceptibility, threat, and self-efficacy and their associations with COVID-19 vaccine hesitancy among a racially and ethnically diverse essential workforce population. METHODS: We performed a cross-sectional survey of essential workers from September-December 2020 at a large Los Angeles safety-net medical center as part of a program offering free COVID-19 serology testing. Program participants completed a standardized survey at the time of phlebotomy. Hierarchical logistic regression was utilized to determine factors independently associated with vaccine hesitancy. RESULTS: Among 1327 persons who had serology testing, 1235 (93%) completed the survey. Of these, 958 (78%) were healthcare workers. Based on expressed intent, 22% were vaccine-hesitant 78% were vaccine acceptors. In our multivariate model, vaccine hesitancy was associated with female gender [aOR = 2.09; 95% CI (1.44-3.05)], African American race [aOR = 4.32; (2.16-8.62)], LatinX ethnicity [aOR = 2.47; 95% CI (1.51-4.05)] and history of not/sometimes receiving influenza vaccination [aOR = 4.39; 95% CI (2.98-6.48)]. Compared to nurses, vaccine hesitancy was lower among physicians [aOR = 0.09; 95% CI (0.04-0.23)], non-nursing/non-physician healthcare workers [aOR = 0.55; 95% CI (0.33-0.92)], and non-healthcare care workers [aOR = 0.53; 95% CI (0.36-0.78)]. CONCLUSIONS: Among a racially/ethnically diverse group of safety net medical center essential workers, COVID-19 vaccine hesitancy was associated with racial/ethnic minority groups, employment type, and prior influenza vaccination hesitancy. Interestingly, we found no association with the Health Belief Model construct measures of perceived susceptibility, threat, and self-efficacy. Psychological constructs not assessed may be drivers of vaccine hesitancy in our population.

Safer at school early alert: an observational study of wastewater and surface monitoring to detect COVID-19 in elementary schools.

Background: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown. Methods: The objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 to March 2021. Findings: In 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88%-98%); 67% were associated with a positive wastewater sample (95% CI: 57%-77%), and 40% were associated with a positive surface sample (95% CI: 29%-52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples. Interpretation: Passive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy. Funding: County of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control.

The multi-tissue landscape of somatic mtDNA mutations indicates tissue-specific accumulation and removal in aging.

Accumulation of somatic mutations in the mitochondrial genome (mtDNA) has long been proposed as a possible mechanism of mitochondrial and tissue dysfunction that occurs during aging. A thorough characterization of age-associated mtDNA somatic mutations has been hampered by the limited ability to detect low-frequency mutations. Here, we used Duplex Sequencing on eight tissues of an aged mouse cohort to detect >89,000 independent somatic mtDNA mutations and show significant tissue-specific increases during aging across all tissues examined which did not correlate with mitochondrial content and tissue function. G→A/C→T substitutions, indicative of replication errors and/or cytidine deamination, were the predominant mutation type across all tissues and increased with age, whereas G→T/C→A substitutions, indicative of oxidative damage, were the second most common mutation type, but did not increase with age regardless of tissue. We also show that clonal expansions of mtDNA mutations with age is tissue- and mutation type-dependent. Unexpectedly, mutations associated with oxidative damage rarely formed clones in any tissue and were significantly reduced in the hearts and kidneys of aged mice treated at late age with elamipretide or nicotinamide mononucleotide. Thus, the lack of accumulation of oxidative damage-linked mutations with age suggests a life-long dynamic clearance of either the oxidative lesions or mtDNA genomes harboring oxidative damage.

Minding the gap and the value of metrics: Count of working pharmacists in the United States.

BACKGROUND: The Bureau of Labor Statistics (BLS) uses a single Standard Occupational Classification (SOC) code (29-1051) that reflects a traditional definition of pharmacist job functions. Pharmacists working in nontraditional roles would be categorized under other SOC codes and not included in the BLS pharmacist count. Knowing the magnitude of how many working pharmacists may not be included in the BLS pharmacist count would help determine whether the gap is a minor margin of error or a significant problem affecting pharmacist workforce projections. OBJECTIVES: The primary objective of this paper was to estimate the gap between the number of possibly working pharmacists and the BLS pharmacist count in 2019. A secondary objective was to examine BLS pharmacist counts in nontraditional roles and compare with published industry data. METHODS: The annual number of individuals receiving their first professional pharmacy degree from 1965 to 2019 (55 graduation cohorts) was adjusted using the expected survival rate to 2019 by age and gender and workforce participation rate in 2019 for pharmacists for each cohort and then summed across cohorts. Data sources included Accreditation Council for Pharmacy Education, U.S. Vital Statistics reports, and American Consumer Survey. One-way and scenario-based sensitivity analyses were conducted to vary professional occupation mortality advantage and pharmacist workforce participation rate assumptions. RESULTS: Based on the number of individuals receiving their first professional pharmacy degree between 1965 and 2019 (442,409), there were 356,998 possibly working pharmacists in 2019. This value indicates 45,798 more pharmacists (15%) may have been working in 2019 than the 311,200 employee pharmacists reported by BLS for 2019. A gap of 8000 to 46,000 more working pharmacists (3%-15%) versus BLS persisted after sensitivity analyses. CONCLUSION: The magnitude of possibly working pharmacists not included in BLS counts warrants further consideration of current pharmacist job projections, methods, and metrics to improve future projections and monitoring of the pharmacist labor force.

Mailed Letter Versus Phone Call to Increase Diabetic-Related Retinopathy Screening Engagement by Patients in a Team-Based Primary Care Practice: Prospective, Single-Masked, Randomized Trial.

BACKGROUND: Vision loss from diabetic-related retinopathy (DR) is preventable through regular screening. OBJECTIVE: The purpose of this study was to test different patient engagement approaches to expand a teleophthalmology program at a primary care clinic in the city of Toronto, Canada. METHODS: A teleophthalmology program was set up in a large, urban, academic, team-based primary care practice. Patients older than 18 years with type 1 or type 2 diabetes were randomized to one of the following 4 engagement strategies: phone call, mail, mail plus phone call, or usual care. Outreach was conducted by administrative staff within the clinic. The primary outcome was booking an appointment for DR screening. RESULTS: A total of 23 patients in the phone, 28 in the mail, 32 in the mail plus phone call, and 27 in the control (usual care) group were included in the analysis. After the intervention and after excluding patients who said they were screened, 88% (15/17) of patients in the phone, 11% (2/18) in the mail, and 100% (21/21) in the mail and phone group booked an appointment with the teleophthalmology program compared to 0% (0/12) in the control group. Phoning patients positively predicted patients booking a teleophthalmology appointment (P<.001), whereas mailing a letter had no effect. CONCLUSIONS: Patient engagement to book DR screening via teleophthalmology in an urban, academic, team-based primary care practice using telephone calls was much more effective than patient engagement using letters or usual care. Practices that have access to a local DR screening program and have resources for such engagement strategies should consider using them as a means to improve their DR screening rates. TRIAL REGISTRATION: ClinicalTrials.gov NCT03927859; https://clinicaltrials.gov/ct2/show/NCT03927859.

Wastewater and surface monitoring to detect COVID-19 in elementary school settings: The Safer at School Early Alert project.

Background: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown. Methods: The objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 - March 2021. Findings: In 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88% - 98%); 67% were associated with a positive wastewater sample (95% CI: 57% - 77%), and 40% were associated with a positive surface sample (95% CI: 29% - 52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples. Interpretation: Passive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy. Funding: County of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control.

Sociodemographic characteristics differ across routine adult vaccine cohorts: An All of Us descriptive study.

BACKGROUND: The National Institutes of Health All of Us (AoU) Research Program is currently building a database of 1million+ adult subjects. With it, we describe the characteristics of those with documented vaccinations. OBJECTIVES: To describe the sociodemographic, health status, and lifestyle factors associated with vaccinations. METHODS: This is a retrospective study involving data from the AoU program (R2020Q4R2, N = 315,297). Five vaccine cohorts [influenza, hepatitis B (HBV), pneumococcal <65 years old, pneumococcal ≥65 years old, and human papillomavirus (HPV)] were generated based on vaccination history. The influenza cohort comprised participants with documented influenza vaccinations in electronic health records (EHRs) from September 2017 to May 2018. Other vaccine cohorts comprised participants with ≥1 lifetime record(s) of vaccination documented in the EHR by December 2018. The vaccine cohorts were compared to the overall AoU cohort. Descriptive statistics were generated using EHR- and survey-based sociodemographic, health, and lifestyle information. The SAMBA (0.9.0) R package was utilized to adjust for EHR selection and outcome misclassification biases to infer sources of disparity for pneumococcal vaccinations in older adults. RESULTS: Cohort counts were as follows: influenza (n = 15,346), HBV (n = 6323), pneumococcal <65 (n = 15,217), pneumococcal ≥65 (n = 15,100), and HPV (n = 2125). All vaccine cohorts had higher proportions of White and non-Hispanic/Latino participants compared to the overall AoU cohort. The largest differences were found in pneumococcal age ≥65, with 80.2% White participants compared to 52.9% in the overall study population. Multivariable analysis revealed that race/ethnic disparities in pneumococcal vaccination among older adults were explained by biological sex, income, health insurance, and education-related variables. CONCLUSION: Racial, ethnic, education, and income characteristics differ across the vaccine cohorts among AoU participants. These findings inform future utilization of large health databases in vaccine epidemiology research and emphasize the need for more targeted interventions that address differences in vaccine uptake.

"It's hard for everyone" systemic barriers to home confinement to prevent community spread of COVID-19.

Rapid identification and isolation/quarantine of COVID-19 cases or close contacts, respectively, is a vital tool to support safe, in-person learning. However, safe isolation or quarantine for a young child also necessitates home confinement for at least one adult caregiver, as well as rapid learning material development by the teacher to minimize learning loss. The purpose of this study is to better understand barriers and supports to student home confinement. We conducted a mixed-methods study using focus group discussions and a self-administered online survey with parents and staff members from 12 elementary schools and childcare sites across San Diego County serving low-income and socially vulnerable families. Focus group participants reported that mental distress and loneliness, learning loss, childcare, food, income loss, and overcrowded housing were major barriers related to home confinement. The experiences described by FGD participants were prevalent in a concurrent community survey: 25% of participants reported that isolation would be extremely difficult for a household member who tested positive or was exposed to COVID-19, and 20% were extremely concerned about learning loss while in isolation or quarantine. Our findings suggest that there are serious structural impediments to safely completing the entire recommended course of isolation or quarantine, and that the potential for isolation or quarantine may also lead to increased hesitancy to access diagnostic testing.

BACKGROUND: During the COVID-19 pandemic, home confinement (isolation and quarantine) are important public health tools to keep children learning in-person at schools. However, isolation or quarantine for young children also means that often their caregivers must also go into home confinement, as well as forcing teachers to adapt their lessons to online teaching. PURPOSE: The purpose of this study is to better understand what makes home confinement comfortable or difficult for students and their families. METHODS: We did focus group discussions and shared an online survey with parents and staff members from 12 elementary schools and childcare centers across San Diego County vulnerable families. RESULTS: Focus group participants said that mental distress and loneliness, learning loss, childcare, food, income loss, and overcrowded housing made home confinement hard to do. Also 25% of survey participants said that isolation would be difficult for a household member who tested positive or was exposed to COVID-19, and 20% were really concerned about their child's learning loss if the family had to isolate or do quarantine. CONCLUSIONS: Our study's results suggest that there are serious structural issues for school families to safely go into isolation or quarantine, and because of this may make families more hesitant to get tested for COVID-19.

Function and dysfunction of the dystonia network: an exploration of neural circuits that underlie the acquired and isolated dystonias.

Dystonia is a highly prevalent movement disorder that can manifest at any time across the lifespan. An increasing number of investigations have tied this disorder to dysfunction of a broad "dystonia network" encompassing the cerebellum, thalamus, basal ganglia, and cortex. However, pinpointing how dysfunction of the various anatomic components of the network produces the wide variety of dystonia presentations across etiologies remains a difficult problem. In this review, a discussion of functional network findings in non-mendelian etiologies of dystonia is undertaken. Initially acquired etiologies of dystonia and how lesion location leads to alterations in network function are explored, first through an examination of cerebral palsy, in which early brain injury may lead to dystonic/dyskinetic forms of the movement disorder. The discussion of acquired etiologies then continues with an evaluation of the literature covering dystonia resulting from focal lesions followed by the isolated focal dystonias, both idiopathic and task dependent. Next, how the dystonia network responds to therapeutic interventions, from the "geste antagoniste" or "sensory trick" to botulinum toxin and deep brain stimulation, is covered with an eye towards finding similarities in network responses with effective treatment. Finally, an examination of how focal network disruptions in mouse models has informed our understanding of the circuits involved in dystonia is provided. Together, this article aims to offer a synthesis of the literature examining dystonia from the perspective of brain networks and it provides grounding for the perspective of dystonia as disorder of network function.

Perceptions of a Teleophthalmology Screening Program for Diabetic Retinopathy in Adults With Type 1 and Type 2 Diabetes in Urban Primary Care Settings.

OBJECTIVES: Teleophthalmology has improved diabetic retinopathy screening, and should be expanded in urban areas, where most unscreened individuals reside. In this study we explored facilitators and barriers of teleophthalmology in primary care settings in Toronto, Canada. METHODS: Semistructured interviews were conducted with 7 health-care providers and 7 individuals with diabetes to explore their perspectives of teleophthalmology in urban primary care settings. Interview data were analyzed using interpretive thematic analysis to generate themes. RESULTS: Six themes were identified. Facilitators included patient-centred implementation, access to teleophthalmology at primary care sites and patients' trust in their providers' recommendations. Barriers included patients' lack of understanding of diabetic retinopathy and the health-care system, providers' lack of interest and the need to streamline administrative processes. CONCLUSIONS: Although teleophthalmology was well-received by patients, there was limited interest from primary care providers. Strategies for increasing uptake include increasing primary care providers' awareness of teleophthalmology's value in urban centres, improving administrative processes and centralizing patient recruitment.