Demographic and geographic distribution of diabetes and pre-diabetes risk in rural settings: results from a cross-sectional, countywide rural health survey in Sullivan County, New York.

OBJECTIVE: To perform a detailed characterisation of diabetes burden and pre-diabetes risk in a rural county with previously documented poor health outcomes in order to understand the local within-county distribution of diabetes in rural areas of America. DESIGN, SETTING, AND PARTICIPANTS: In 2021, we prospectively mailed health surveys to all households in Sullivan County, a rural county with the second-worst health outcomes of all counties in New York State. Our survey included questions on demographics, medical history and the American Diabetes Association's Pre-diabetes Risk Test. PRIMARY OUTCOME AND METHODS: Our primary outcome was an assessment of diabetes burden within this rural county. To help mitigate non-response bias in our survey, raking adjustments were performed across strata of age, sex, race/ethnicity and health insurance. We analysed diabetes prevalence by demographic characteristics and used geospatial analysis to assess for clustering of diagnosed diabetes cases. RESULTS: After applying raking procedures for the 4725 survey responses, our adjusted diagnosed diabetes prevalence for Sullivan County was 12.9% compared with the 2019 Behavioural Risk Factor Surveillance System (BRFSS) estimate of 8.6%. In this rural area, diagnosed diabetes prevalence was notably higher among non-Hispanic Black (21%) and Hispanic (15%) residents compared with non-Hispanic White (12%) residents. 53% of respondents without a known history of pre-diabetes or diabetes scored as high risk for pre-diabetes. Nearest neighbour analyses revealed that hotspots of diagnosed diabetes were primarily located in the more densely populated areas of this rural county. CONCLUSIONS: Our mailed health survey to all residents in Sullivan County demonstrated higher diabetes prevalence compared with modelled BRFSS estimates that were based on small telephone samples. Our results suggest the need for better diabetes surveillance in rural communities, which may benefit from interventions specifically tailored for improving glycaemic control among rural residents.

Food insecurity in high-risk rural communities before and during the COVID-19 pandemic.

Objective: To perform a geospatial analysis of food insecurity in a rural county known to have poor health outcomes and assess the effect of the COVID-19 pandemic. Methods: In 2020, we mailed a comprehensive cross-sectional survey to all households in Sullivan County, a rural county with the second-worst health outcomes among all counties in New York State. Surveys of households included validated food insecurity screening questions. Questions were asked in reference to 2019, prior to the pandemic, and for 2020, in the first year of the pandemic. Respondents also responded to demographic questions. Raking adjustments were performed using age, sex, race/ethnicity, and health insurance strata to mitigate non-response bias. To identify significant hotspots of food insecurity within the county, we also performed geospatial analysis. Findings: From the 28,284 households surveyed, 20% of households responded. Of 4725 survey respondents, 26% of households reported experiencing food insecurity in 2019, and in 2020, this proportion increased to 35%. In 2020, 58% of Black and Hispanic households reported experiencing food insecurity. Food insecurity in 2020 was also present in 58% of unmarried households with children and in 64% of households insured by Medicaid. The geospatial analyses revealed that hotspots of food insecurity were primarily located in or near more urban areas of the rural county. Conclusions: Our countywide health survey in a high-risk rural county identified significant increases of food insecurity in the first year of the COVID-19 pandemic, despite national statistics reporting a stable rate. Responses to future crises should include targeted interventions to bolster food security among vulnerable rural populations.

The ASTCT-NMDP ACCESS Initiative: A Collaboration to Address and Sustain Equal Outcomes for All across the Hematopoietic Cell Transplantation and Cellular Therapy Ecosystem.

The American Society for Transplantation and Cellular Therapy (ASTCT) and the National Marrow Donor Program (NMDP) have formed the ACCESS Initiative to address and reduce barriers to hematopoietic cell transplantation (HCT) and cellular therapy (CT) in an effort to ensure equal access and outcomes for all patients in need. In addition to cellular therapy physicians, the initiative includes program administrators, health policy and health equity experts, health service researchers, participants from commercial payer organizations, and federal stakeholders. The inaugural ASTCT-NMDP ACCESS Workshop was held in Washington, DC on July 28 and 29, 2022, wherein committee members met to discuss and to define goals for 3 focus areas: awareness, poverty, and racial and ethnic inequity. This position paper reviews the mission, vision, and structure of the ACCESS Initiative and the proceedings from the inaugural workshop and provides an initial roadmap for the group's efforts at reducing access barriers and outcome disparities in HCT/CT.

Distinct predictors of short- versus long-term depression outcomes following electroconvulsive therapy.

Patients and clinicians considering electroconvulsive therapy (ECT) for treatment-resistant depression are faced with limited information about the likely long-term outcomes, and the individual characteristics that predict those outcomes. We aimed to identify sociodemographic and clinical predictors of acute ECT response and subsequent long-term depression severity. This prospective longitudinal study followed adult patients at a single academic ECT center. Among 114 participants, 105 completed an index ECT series and 70 were classified as acute ECT responders. Over a 2-year follow-up period, 82 subjects provided data on depression severity (Patient Health Questionnaire; PHQ-9). Better acute ECT response was predicted by less medication resistance, shorter index episode, and psychotic features (p < 0.05). PHQ-9 scores during the two-year follow-up period improved from baseline at all time points (p < 0.000001) but individual scores varied widely. Lower long-term PHQ-9 scores were predicted by better acute therapeutic response to ECT (p = 0.004) but not by ECT adverse effects (p > 0.05). Married status and greater baseline clinician-rated severity were not associated with acute ECT response but those variables did predict lower PHQ-9 scores longitudinally (p < 0.001), independent of other baseline features, initial ECT response, or intensity of ongoing treatment. These findings confirm previously identified predictors of short-term ECT response and demonstrate that distinct individual characteristics predict long-term depression outcomes. An individual's social context appears to strongly influence long-term but not short-term outcomes, suggesting a potential target for post-ECT therapeutic interventions.

Long-term quality of life in treatment-resistant depression after electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression (TRD), and previous studies have demonstrated short-term improvements in quality of life (QoL) after ECT.  However, long-term QoL after ECT has not been studied, and the baseline patient characteristics that predict long-term QoL remain unknown. METHODS: Seventy-nine subjects with unipolar or bipolar TRD were enrolled in this prospective longitudinal observational study. Physical, psychological, social, and environmental QoL domains were measured with the abbreviated World Health Organization Quality of Life scale (WHOQOL-BREF) at baseline and every 6 months for up to 2 years after ECT.  Baseline sociodemographic and clinical features were tested for association with long-term QoL. RESULTS: Long-term follow-up data were available from 49 participants.  Relative to baseline, average psychological and physical QoL improved during the follow-up period (Hedges' effect size: 0.27-0.83).  About 40-50% of individuals experienced clinically meaningful improvement.  Subjects with better initial antidepressant response with ECT reported better QoL over the subsequent two years.  Long-term QoL improved most among individuals who were married, those without disability status, and those with psychotic features or shorter depressive episodes at baseline. LIMITATIONS: Participants were from a single US academic center and mainly of European ancestry, so findings may not generalize to other settings or ethnicities.  The observational design does not allow causal inferences. CONCLUSIONS: Long-term psychological and physical QoL outcomes vary widely after ECT. Individuals with the best outcomes are those who respond well to ECT initially, married people, and those with a less chronic course of illness.

Methodological advantages and disadvantages of parallel and crossover randomised clinical trials on methylphenidate for attention deficit hyperactivity disorder: a systematic review and meta-analyses.

OBJECTIVE: To assess the methodological advantages and disadvantages of parallel and crossover designs in randomised clinical trials on methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). DESIGN: Secondary analyses of a Cochrane systematic review. SETTING AND PARTICIPANTS: We searched relevant databases up to March 2015 and included data from parallel and crossover randomised trials assessing children and adolescents up to 18 years with ADHD. INTERVENTIONS: Methylphenidate compared with placebo or no-treatment interventions. PRIMARY AND SECONDARY OUTCOMES: The primary outcomes were teacher-rated ADHD symptoms and serious adverse events. The secondary outcomes were non-serious adverse events. RESULTS: We included 38 parallel trials (n=5111) and 147 crossover trials (n=7134). When comparing methylphenidate with placebo or no-treatment on ADHD symptoms, we found no differences between the end of parallel trials and the first-period from crossover trials (Χ²=1.06, df=1, p=0.30, I²=5.5%). We also found no differences when combining the end of first-period crossover trials with the end of parallel trials and comparing them to the end of last-period crossover trials (Χ²=3.25, df=1, p=0.07, I²=69.2%). We found no differences in serious and non-serious adverse events, and no risk of period and carryover effects. However, only two trials contributed data to the latter analyses. CONCLUSIONS: Both parallel and crossover trials seem suitable for investigating methylphenidate in children and adolescents with ADHD, with comparable estimates on ADHD symptom severity and adverse events. However, parallel trials might still offer ethical and statistical advantages over crossover trials.

Kinesin-1 regulates synaptic strength by mediating the delivery, removal, and redistribution of AMPA receptors.

A primary determinant of the strength of neurotransmission is the number of AMPA-type glutamate receptors (AMPARs) at synapses. However, we still lack a mechanistic understanding of how the number of synaptic AMPARs is regulated. Here, we show that UNC-116, the C. elegans homolog of vertebrate kinesin-1 heavy chain (KIF5), modifies synaptic strength by mediating the rapid delivery, removal, and redistribution of synaptic AMPARs. Furthermore, by studying the real-time transport of C. elegans AMPAR subunits in vivo, we demonstrate that although homomeric GLR-1 AMPARs can diffuse to and accumulate at synapses in unc-116 mutants, glutamate-gated currents are diminished because heteromeric GLR-1/GLR-2 receptors do not reach synapses in the absence of UNC-116/KIF5-mediated transport. Our data support a model in which ongoing motor-driven delivery and removal of AMPARs controls not only the number but also the composition of synaptic AMPARs, and thus the strength of synaptic transmission.

Cornichons control ER export of AMPA receptors to regulate synaptic excitability.

The strength of synaptic communication at central synapses depends on the number of ionotropic glutamate receptors, particularly the class gated by the agonist AMPA (AMPARs). Cornichon proteins, evolutionarily conserved endoplasmic reticulum cargo adaptors, modify the properties of vertebrate AMPARs when coexpressed in heterologous cells. However, the contribution of cornichons to behavior and in vivo nervous system function has yet to be determined. Here, we take a genetic approach to these questions by studying CNI-1--the sole cornichon homolog in C. elegans. cni-1 mutants hyperreverse, a phenotype associated with increased glutamatergic synaptic transmission. Consistent with this behavior, we find larger glutamate-gated currents in cni-1 mutants with a corresponding increase in AMPAR number. Furthermore, we observe opposite phenotypes in transgenic worms that overexpress CNI-1 or vertebrate homologs. In reconstitution studies, we provide support for an evolutionarily conserved role for cornichons in regulating the export of vertebrate and invertebrate AMPARs.