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BackgroundAlcohol use disorder (AUD) imposes a high mortality and economic burden. Effective treatment is available, though underutilized.ObjectiveDescribe trends in AUD pharmacotherapy, variation in prescribing, and associated patient factors.DesignRetrospective cohort using electronic health records from 2010 to 2019.ParticipantsPrimary care patients from 39 clinics in Ohio and Florida with diagnostic codes for alcohol dependence or abuse plus social history indicating alcohol use. PCPs in family or internal medicine with at least 20 AUD patients.Main MeasuresPharmacotherapy for AUD (naltrexone, acamprosate, and disulfiram), abstinence from alcohol, patient demographics, and comorbidities. Generalized linear mixed models were used to identify patient factors associated with prescriptions and the association of pharmacotherapy with abstinence.Key ResultsWe identified 13,250 patients; average age was 54 years, 66.9% were male, 75.0% were White, and median household income was $51,776 per year. Over 10 years, the prescription rate rose from 4.4 to 5.6%. Patients who were Black (aOR 0.74; 95% CI 0.58, 0.94) and insured by Medicare versus commercial insurance (aOR 0.61; 95% CI 0.48, 0.78) were less likely to be treated. Higher median household income ($10,000 increment, aOR 1.06; 95% CI 1.03, 1.10) and Medicaid versus commercial insurance (aOR 1.52; 95% CI 1.24, 1.87) were associated with treatment. Receiving pharmacotherapy was associated with subsequent documented abstinence from alcohol (aOR 1.60; 95% CI 1.33, 1.92). We identified 236 PCPs. The average prescription rate was 3.6% (range 0 to 24%). The top decile prescribed to 14.6% of their patients. The bottom 4 deciles had no prescriptions. Family physicians had higher rates of pharmacotherapy than internists (OR 1.50; 95% CI 1.21, 1.85).ConclusionsMedications for AUD are infrequently prescribed, but there is considerable variation among PCPs. Increasing the use of pharmacotherapy by non-prescribers may increase abstinence from alcohol.

Lithium remains the gold standard for the treatment of bipolar disorder (BD); however, its use has declined over the years mainly due to the side effects and the subjective experience of cognitive numbness reported by patients. In the present study, we aim to methodically test the effects of lithium on neurocognitive functioning in the largest single cohort (n = 262) of BD patients reported to date by harnessing the power of a multi-site, ongoing clinical trial of lithium monotherapy. At the cross-sectional level, multivariate analysis of covariance (MANCOVA) was conducted to examine potential group differences across neurocognitive tests [California Verbal Learning Test (CVLT trials 1–5,CVLT delayed recall), Wechsler Digit Symbol, Trail-making Test parts A and B (TMT-A; TMT-B), and a global cognition index]. At the longitudinal level, on a subset of patients (n = 88) who achieved mood stabilization with lithium monotherapy, we explored the effect of lithium treatment across time on neurocognitive functioning. There were no differences at baseline between BD patients that were taking lithium compared with those that were not. At follow-up a significant neurocognitive improvement in the global cognitive index score [F = 31.69; p < 0.001], CVLT trials 1–5 [F = 29.81; p < 0.001], CVLT delayed recall [F = 15.27; p < 0.001], and TMT-B [F = 6.64, p = 0.012] was detected. The cross-sectional and longitudinal (on a subset of 88 patients) investigations suggest that lithium may be beneficial to neurocognitive functioning in patients with BD and that at the very least it does not seem to significantly impair cognition when used therapeutically.

Background Hospitalized older adults spend as much as 95% of their time in bed, which can result in adverse events and delay recovery while increasing costs. Observational studies have shown that general mobility interventions (e.g., ambulation) can mitigate adverse events and improve patients’ functional status. Mobility technicians (MTs) may address the need for patients to engage in mobility interventions without overburdening nurses. There is no data, however, on the effect of MT-assisted ambulation on adverse events or functional status, or on the cost tradeoffs if a MT were employed. The AMBULATE study aims to determine whether MT-assisted ambulation improves mobility status and decreases adverse events for older medical inpatients. It will also include analyses to identify the patients that benefit most from MT-assisted mobility and assess the cost-effectiveness of employing a MT. Methods The AMBULATE study is a multicenter, single-blind, parallel control design, individual-level randomized trial. It will include patients admitted to a medical service in five hospitals in two regions of the USA. Patients over age 65 with mild functional deficits will be randomized using a block randomization scheme. Those in the intervention group will ambulate with the MT up to three times daily, guided by the Johns Hopkins Mobility Goal Calculator. The intervention will conclude at hospital discharge, or after 10 days if the hospitalization is prolonged. The primary outcome is the Short Physical Performance Battery score at discharge. Secondary outcomes are discharge disposition, length of stay, hospital-acquired complications (falls, venous thromboembolism, pressure ulcers, and hospital-acquired pneumonia), and post-hospital functional status. Discussion While functional decline in the hospital is multifactorial, ambulation is a modifiable factor for many patients. The AMBULATE study will be the largest randomized controlled trial to test the clinical effects of dedicating a single care team member to facilitating mobility for older hospitalized patients. It will also provide a useful estimation of cost implications to help hospital administrators assess the feasibility and utility of employing MTs. Trial registration Registered in the United States National Library of Medicine clinicaltrials.gov (# NCT05725928). February 13, 2023.

Bipolar disorder (BD) is a serious mood disorder associated with circadian rhythm abnormalities. Risk for BD is genetically encoded and overlaps with systems that maintain circadian rhythms. Lithium is an effective mood stabilizer treatment for BD, but only a minority of patients fully respond to monotherapy. Presently, we hypothesized that lithium-responsive BD patients (Li-R) would show characteristic differences in chronotype and cellular circadian rhythms compared to lithium non-responders (Li-NR). Selecting patients from a prospective, multi-center, clinical trial of lithium monotherapy, we examined morning vs. evening preference (chronotype) as a dimension of circadian rhythm function in 193 Li-R and Li-NR BD patients. From a subset of 59 patient donors, we measured circadian rhythms in skin fibroblasts longitudinally over 5 days using a bioluminescent reporter (Per2-luc). We then estimated circadian rhythm parameters (amplitude, period, phase) and the pharmacological effects of lithium on rhythms in cells from Li-R and Li-NR donors. Compared to Li-NRs, Li-Rs showed a difference in chronotype, with higher levels of morningness. Evening chronotype was associated with increased mood symptoms at baseline, including depression, mania, and insomnia. Cells from Li-Rs were more likely to exhibit a short circadian period, a linear relationship between period and phase, and period shortening effects of lithium. Common genetic variation in the IP3 signaling pathway may account for some of the individual differences in the effects of lithium on cellular rhythms. We conclude that circadian rhythms may influence response to lithium in maintenance treatment of BD.

Lithium (Li) is one of the most effective drugs for treating bipolar disorder (BD), however, there is presently no way to predict response to guide treatment. The aim of this study is to identify functional genes and pathways that distinguish BD Li responders (LR) from BD Li non-responders (NR). An initial Pharmacogenomics of Bipolar Disorder study (PGBD) GWAS of lithium response did not provide any significant results. As a result, we then employed network-based integrative analysis of transcriptomic and genomic data. In transcriptomic study of iPSC-derived neurons, 41 significantly differentially expressed (DE) genes were identified in LR vs NR regardless of lithium exposure. In the PGBD, post-GWAS gene prioritization using the GWA-boosting (GWAB) approach identified 1119 candidate genes. Following DE-derived network propagation, there was a highly significant overlap of genes between the top 500- and top 2000-proximal gene networks and the GWAB gene list ( P hypergeometric  = 1.28E–09 and 4.10E–18, respectively). Functional enrichment analyses of the top 500 proximal network genes identified focal adhesion and the extracellular matrix (ECM) as the most significant functions. Our findings suggest that the difference between LR and NR was a much greater effect than that of lithium. The direct impact of dysregulation of focal adhesion on axon guidance and neuronal circuits could underpin mechanisms of response to lithium, as well as underlying BD. It also highlights the power of integrative multi-omics analysis of transcriptomic and genomic profiling to gain molecular insights into lithium response in BD.

Alcohol use disorders (AUD) are commonly comorbid with anxiety and mood disorders; however, a strategy for AUD prevention remains unclear in the presence of three competing etiological models that each recommends different high-risk groups. Therefore, the investigation of the three hypotheses in a characteristically unique cohort is critical to identifying pervasive characteristics of AUD that can inform a universal prevention strategy. The current study evaluated the temporality and onset of comorbid AUD and psychiatric disorders in a representative sample of 528 Ohio Army National Guard soldiers using structured clinical interviews from 2009 to 2012. We examined temporality both statistically and graphically to identify patterns that could inform prevention. General estimating equations with dichotomous predictor variables were used to estimate odds ratios between comorbid psychiatric disorders and AUDs. An annualized rate of 13.5 % persons per year was diagnosed with any AUD between 2010 and 2012. About an equal proportion of participants with comorbid psychiatric disorders and AUD initiated the psychiatric disorder prior to the AUD and half initiated the psychiatric disorder after the AUD. Regardless of onset, however, the majority (80 %) AUD initiated during a short interval between the ages of 16 and 23. Focused primary prevention during this narrow age range (16–23 years) may have the greatest potential to reduce population mental health burden of AUD, irrespective of the sequencing of comorbid psychiatric disorder.

To report the reliability and validity of key mental health assessments in an ongoing study of the Ohio Army National Guard (OHARNG). The 2616 OHARNG soldiers received hour-long structured telephone surveys including the post-traumatic stress disorder (PTSD) checklist (PCV-C) and Patient Health Questionnaire - 9 (PHQ-9). A subset (N=500) participated in two hour clinical reappraisals, using the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM (SCID). The telephone survey assessment for PTSD and for any depressive disorder were both highly specific [92% (standard error, SE 0.01), 83% (SE 0.02)] with moderate sensitivity [54% (SE 0.09), 51% (SE 0.05)]. Other psychopathologies assessed included alcohol abuse [sensitivity 40%, (SE 0.04) and specificity 80% (SE 0.02)] and alcohol dependence [sensitivity, 60% (SE 0.05) and specificity 81% (SE 0.02)].The baseline prevalence estimates from the telephone study suggest alcohol abuse and dependence may be higher in this sample than the general population. Validity and reliability statistics suggest specific, but moderately sensitive instruments. Copyright © 2014 John Wiley & Sons, Ltd.

Based on available literature, this review article investigates traumatic stress studies in Japan from the late 19th century to the present for English speaking audiences. First, traumatic neuroses of war victims, A-bomb survivors, and victims of work-related accidents are discussed. Second, traumatic stress studies of victims of other manmade disasters, such as the sarin gas attacks in Tokyo, and burn injuries are discussed. Third, psychological outcomes of natural disaster studies are discussed in relation to social support and help-seeking tendencies of Japan disaster victims.