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Vitamin D deficiency has long been associated with reduced immune function that can lead to viral infection. Several studies have shown that Vitamin D deficiency is associated with increases the risk of infection with COVID-19. However, it is unknown if treatment with Vitamin D can reduce the associated risk of COVID-19 infection, which is the focus of this study. In the population of US veterans, we show that Vitamin D 2 and D 3 fills were associated with reductions in COVID-19 infection of 28% and 20%, respectively [(D 3 Hazard Ratio (HR) = 0.80, [95% CI 0.77, 0.83]), D 2 HR = 0.72, [95% CI 0.65, 0.79]]. Mortality within 30-days of COVID-19 infection was similarly 33% lower with Vitamin D 3 and 25% lower with D 2 (D 3 HR = 0.67, [95% CI 0.59, 0.75]; D 2 HR = 0.75, [95% CI 0.55, 1.04]). We also find that after controlling for vitamin D blood levels, veterans receiving higher dosages of Vitamin D obtained greater benefits from supplementation than veterans receiving lower dosages. Veterans with Vitamin D blood levels between 0 and 19 ng/ml exhibited the largest decrease in COVID-19 infection following supplementation. Black veterans received greater associated COVID-19 risk reductions with supplementation than White veterans. As a safe, widely available, and affordable treatment, Vitamin D may help to reduce the severity of the COVID-19 pandemic.

Background There is growing interest in using personalized mental health care to treat disorders like depression and anxiety to improve treatment engagement and efficacy. This randomized controlled trial will compare a traditional symptom severity decision-making algorithm to a novel multivariate decision-making algorithm for triage to and adaptation of mental health care. The stratified levels of care include a self-guided online wellness program, coach-guided online cognitive behavioral therapy, and clinician-delivered psychotherapy with or without pharmacotherapy. The novel multivariate algorithm will be comprised of baseline (for triage and adaptation) and time-varying variables (for adaptation) in four areas: social determinants of mental health, early adversity and life stressors, predisposing, enabling, and need influences on health service use, and comprehensive mental health status. The overarching goal is to evaluate whether the multivariate algorithm improves adherence to treatment, symptoms, and functioning above and beyond the symptom-based algorithm. Methods/design This trial will recruit a total of 1000 participants over the course of 5 years in the greater Los Angeles Metropolitan Area. Participants will be recruited from a highly diverse sample of community college students. For the symptom severity approach, initial triaging to level of care will be based on symptom severity, whereas for the multivariate approach, the triaging will be based on a comprehensive set of baseline measures. After the initial triaging, level of care will be adapted throughout the duration of the treatment, utilizing either symptom severity or multivariate statistical approaches. Participants will complete computerized assessments and self-report questionnaires at baseline and up to 40 weeks. The multivariate decision-making algorithm will be updated annually to improve predictive outcomes. Discussion Results will provide a comparison on the traditional symptom severity decision-making and the novel multivariate decision-making with respect to treatment adherence, symptom improvement, and functional recovery. Moreover, the developed multivariate decision-making algorithms may be used as a template in other community college settings. Ultimately, findings will inform the practice of level of care triage and adaptation in psychological treatments, as well as the use of personalized mental health care broadly. Trial registration ClinicalTrials.gov NCT05591937, submitted August 2022, published October 2022.

Abstract Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called “B-SNIP1” with 711 psychosis and 274 healthy persons, and the “replication sample” with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r’s from .96–.99) and temporally stable (r’s from .76–.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%–89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.

To validate the Computerized Adaptive Test Suicide Scale (CAT-SS), Veterans completed measures at baseline (n = 305), and 6- (n = 249), and 12-months (n = 185), including the CAT-SS (median items 11, duration of administration 107 seconds) and the Columbia-Suicide Severity Rating Scale (C-SSRS). Logistic regression was used to relate CAT-SS scores (baseline) to C-SSRS assessed outcomes (active ideation with plan and intent; attempt; interrupted, aborted or self-interrupted attempt, or preparatory acts or behaviors; all outcomes combined). A mixed-effects logistic regression model was used to evaluate the relationship between the lagged CAT-SS scores and outcomes (6- and 12-months). The baseline CAT-SS demonstrated predictive accuracy for all outcomes at 6-months, and similar results were found for baseline and all outcomes at and through 12-months. Longitudinal analysis revealed for every 10-point change in the CAT-SS there was a 50–77% increase in the likelihood of suicide-related outcomes. The CAT-SS demonstrated added value when compared to current suicide risk prediction practices.

INTRODUCTION Up to 20% of older adults in the United States have mild cognitive impairment (MCI), and about one‐third of people with MCI are predicted to transition to Alzheimer's disease (AD) within 5 years. Standard cognitive assessments are long and require a trained technician to administer. We developed the first computerized adaptive test (CAT) based on multidimensional item response theory (MIRT) to more precisely, rapidly, and repeatedly assesses cognitive abilities across the adult lifespan. We present results for a prototype CAT (pCAT‐COG) for assessment of global cognitive function. METHODS We sampled items across five cognitive domains central to neuropsychological testing (episodic memory [EM], semantic memory/language [SM], working memory [WM], executive function/flexible thinking, and processing speed [PS]). The item bank consists of 54 items, with 9 items of varying difficulty drawn from six different cognitive tasks. Each of the 54 items has 3 response trials, yielding an ordinal score (0–3 trials correct). We also include three long‐term memory items not designed for adaptive administration, for a total bank of 57 items. Calibration data were collected in‐person and online, calibrated using a bifactor MIRT model, and pCAT‐COG scores validated against a technician‐administered neuropsychological battery. RESULTS The bifactor MIRT model improved fit over a unidimensional IRT model (p < 0.0001). The global pCAT‐COG scores were inversely correlated with age (r = –0.44, p < 0.0001). Simulated adaptive administration of 11 items maintained a correlation of r = 0.94 with the total item bank scores. Significant differences between mild and no cognitive impairment (NCI) were found (effect size of 1.08 SD units). The pCAT‐COG correlated with clinician‐based global measure (r = 0.64). DISCUSSION MIRT‐based CAT is feasible and valid for the assessment of global cognitive impairment, laying the foundation for the development of a full CAT‐COG that will draw from a much larger item bank with both global and domain specific measures of cognitive impairment. Highlights As Americans age, numbers at risk for developing cognitive impairment are increasing. Aging‐related declines in cognition begins decades prior to the onset of obvious cognitive impairment. Traditional assessment is burdensome and requires trained clinicians. We developed an adaptive testing framework using multidimensional item response theory. It is comparable to lengthier in‐person assessments that require trained psychometrists.

Many factors affect the risks for neurodevelopmental maladies such as autism spectrum disorders (ASD) and intellectual disability (ID). To compare environmental, phenotypic, socioeconomic and state-policy factors in a unified geospatial framework, we analyzed the spatial incidence patterns of ASD and ID using an insurance claims dataset covering nearly one third of the US population. Following epidemiologic evidence, we used the rate of congenital malformations of the reproductive system as a surrogate for environmental exposure of parents to unmeasured developmental risk factors, including toxins. Adjusted for gender, ethnic, socioeconomic, and geopolitical factors, the ASD incidence rates were strongly linked to population-normalized rates of congenital malformations of the reproductive system in males (an increase in ASD incidence by 283% for every percent increase in incidence of malformations, 95% CI: [91%, 576%], p<6×10(-5)). Such congenital malformations were barely significant for ID (94% increase, 95% CI: [1%, 250%], p = 0.0384). Other congenital malformations in males (excluding those affecting the reproductive system) appeared to significantly affect both phenotypes: 31.8% ASD rate increase (CI: [12%, 52%], p<6×10(-5)), and 43% ID rate increase (CI: [23%, 67%], p<6×10(-5)). Furthermore, the state-mandated rigor of diagnosis of ASD by a pediatrician or clinician for consideration in the special education system was predictive of a considerable decrease in ASD and ID incidence rates (98.6%, CI: [28%, 99.99%], p = 0.02475 and 99% CI: [68%, 99.99%], p = 0.00637 respectively). Thus, the observed spatial variability of both ID and ASD rates is associated with environmental and state-level regulatory factors; the magnitude of influence of compound environmental predictors was approximately three times greater than that of state-level incentives. The estimated county-level random effects exhibited marked spatial clustering, strongly indicating existence of as yet unidentified localized factors driving apparent disease incidence. Finally, we found that the rates of ASD and ID at the county level were weakly but significantly correlated (Pearson product-moment correlation 0.0589, p = 0.00101), while for females the correlation was much stronger (0.197, p<2.26×10(-16)).

We previously showed that folic acid prescriptions for any indication were associated with lower rates of suicidal behaviour. Given that future randomised clinical trials are likely to focus on psychiatric disorders carrying elevated risk for suicide, we now report on the moderating effects of prior suicidal behaviour, psychiatric diagnoses and psychotropic medications on potential antisuicidal effects of folic acid. Data were obtained from the MarketScan Commercial Claims and Encounters databases that cover 164 million insured persons from 2005–2017, from which a cohort of 866 586 patients was derived. Analysis revealed no significant moderation effects on the antisuicidal effect of folic acid. These findings indicate that the potential benefit of folic acid for preventing suicidal behaviour is comparable in psychiatric populations at higher risk of suicide and that it may be additive to any benefit from psychotropic medications.

Most ward risk scores were created using subjective opinion in individual hospitals and only use vital signs. To develop and validate a risk score using commonly collected electronic health record data. All patients hospitalized on the wards in five hospitals were included in this observational cohort study. Discrete-time survival analysis was used to predict the combined outcome of cardiac arrest (CA), intensive care unit (ICU) transfer, or death on the wards. Laboratory results, vital signs, and demographics were used as predictor variables. The model was developed in the first 60% of the data at each hospital and then validated in the remaining 40%. The final model was compared with the Modified Early Warning Score (MEWS) using the area under the receiver operating characteristic curve and the net reclassification index (NRI). A total of 269,999 patient admissions were included, with 424 CAs, 13,188 ICU transfers, and 2,840 deaths occurring during the study period. The derived model was more accurate than the MEWS in the validation dataset for all outcomes (area under the receiver operating characteristic curve, 0.83 vs. 0.71 for CA; 0.75 vs. 0.68 for ICU transfer; 0.93 vs. 0.88 for death; and 0.77 vs. 0.70 for the combined outcome; P value < 0.01 for all comparisons). This accuracy improvement was seen across all hospitals. The NRI for the electronic Cardiac Arrest Risk Triage compared with the MEWS was 0.28 (0.18-0.38), with a positive NRI of 0.19 (0.09-0.29) and a negative NRI of 0.09 (0.09-0.09). We developed an accurate ward risk stratification tool using commonly collected electronic health record variables in a large multicenter dataset. Further study is needed to determine whether implementation in real-time would improve patient outcomes.

AbstractObjectivesTo assess: (1) the prevalence of mental health and substance use in patients presenting to the emergency department (ED) through use of a computer adaptive test (CAT‐MH), (2) the correlation among CAT‐MH scores and self‐ and clinician‐reported assessments, and (3) the association between CAT‐MH scores and ED utilization in the year prior and 30 days after enrollment. MethodsThis was a single‐center observational study of adult patients presenting to the ED for somatic complaints (97%) from May 2019 to March 2020. The main outcomes were computer‐adaptive‐assessed domains of suicidality, depression, anxiety, post‐traumatic stress disorder (PTSD), and substance use. We conducted Pearson correlations and logistic regression for objectives 2 and 3, respectively. ResultsFrom a sample of 794 patients, the proportion of those at moderate/severe risk was: 24.1% (suicidality), 8.3% (depression), 16.5% (anxiety), 12.3% (PTSD), and 20.4% (substance use). CAT‐MH domains were highly correlated with self‐report assessments ( r = 0.49–0.79). Individuals who had 2 or more ED visits in the prior year had 62% increased odds of being in the intermediate‐high suicide risk category (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.07–2.44) compared to those with zero prior ED visits. Individuals who scored in the intermediate‐high‐suicide risk group had 63% greater odds of an ED visit within 30 days after enrollment compared to those who scored as low risk (OR, 1.63; 95% CI, 1.09, 2.44). ConclusionThe CAT‐MH documented that a considerable proportion of ED patients presenting for somatic problems had mental health conditions, even if mild. Mental health problems were also associated with ED utilization.

Background/Objectives. Vagal block therapy (vBloc) is effective for moderate to severe obesity at one year. Subjects/Methods. The ReCharge trial is a double-blind, randomized controlled clinical trial of 239 participants with body mass index (BMI) of 40 to 45 kg/m or 35 to 40 kg/m with one or more obesity-related conditions. Interventions were implantation of either vBloc or Sham devices and weight management counseling. Mixed models assessed percent excess weight loss (%EWL) and total weight loss (%TWL) in intent-to-treat analyses. At 18 months, 142 (88%) vBloc and 64 (83%) Sham patients remained enrolled in the study. Results. 18-month weight loss was 23% EWL (8.8% TWL) for vBloc and 10% EWL (3.8% TWL) for Sham (P<0.0001). vBloc patients largely maintained 12-month weight loss of 26% EWL (9.7% TWL). Sham regained over 40% of the 17% EWL (6.4% TWL) by 18 months. Most weight regain preceded unblinding. Common adverse events of vBloc through 18 months were heartburn/dyspepsia and abdominal pain; 98% of events were reported as mild or moderate and 79% had resolved. Conclusions. Weight loss with vBloc was sustained through 18 months, while Sham regained weight between 12 and 18 months. vBloc is effective with a low rate of serious complications.