In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Major depressive disorder (MDD) is the leading cause of disability globally, with moderate heritability and well-established socio-environmental risk factors. Genetic studies have been mostly restricted to European settings, with polygenic scores (PGS) demonstrating low portability across diverse global populations.

This study examines genetic architecture, polygenic prediction, and socio-environmental correlates of MDD in a family-based sample of 10 032 individuals from Nepal with array genotyping data. We used genome-based restricted maximum likelihood to estimate heritability, applied S-LDXR to estimate the cross-ancestry genetic correlation between Nepalese and European samples, and modeled PGS trained on a GWAS meta-analysis of European and East Asian ancestry samples.

We estimated the narrow-sense heritability of lifetime MDD in Nepal to be 0.26 (95% CI 0.18–0.34, p = 8.5 × 10−6). Our analysis was underpowered to estimate the cross-ancestry genetic correlation (rg = 0.26, 95% CI −0.29 to 0.81). MDD risk was associated with higher age (beta = 0.071, 95% CI 0.06–0.08), female sex (beta = 0.160, 95% CI 0.15–0.17), and childhood exposure to potentially traumatic events (beta = 0.050, 95% CI 0.03–0.07), while neither the depression PGS (beta = 0.004, 95% CI −0.004 to 0.01) or its interaction with childhood trauma (beta = 0.007, 95% CI −0.01 to 0.03) were strongly associated with MDD.

Estimates of lifetime MDD heritability in this Nepalese sample were similar to previous European ancestry samples, but PGS trained on European data did not predict MDD in this sample. This may be due to differences in ancestry-linked causal variants, differences in depression phenotyping between the training and target data, or setting-specific environmental factors that modulate genetic effects. Additional research among under-represented global populations will ensure equitable translation of genomic findings.

Introduction: Second-generation antipsychotics are widely used in psychiatry but are associated with weight gain. Obesity is more prevalent in mental illness and may contribute to the mortality gap. Non-pharmacological management of antipsychotic-induced weight gain (AIWG) has limited success whilst pharmacological treatment typically involves antidiabetic medications that psychiatrists have less experience with. Recent developments in the field have shown promise with using centrally-acting opioid receptor antagonists (CORAs) at treating AIWG.

Objective: Review and synthesise the available RCT evidence on the efficacy of CORAs at treating AIWG.

Methodology: Four databases (Medline, Embase, PsycINFO, Cochrane) were searched, from database inception to present, for RCTs using CORAs (naloxone, naltrexone, samidorphan) to reduce AIWG. Our primary outcome sought was weight change in kilograms, with secondary outcomes of change in percentage of body weight, waist circumference and 7% or 10% weight change thresholds. We used random-effects meta-analysis due to study heterogeneity.

A total of 450 articles were found (319 post-deduplication), of which seven met criteria (samidorphan = 4, naltrexone = 3, naloxone = 0) including n = 1,416 patients. On meta-analysis, change in body weight (kg) for CORAs as a class was statistically significant (RE = 1.37 kg; 95% CI: 0.51, 2.24). However, change in BMI was not statistically significant (RE = 0.61kg/m2; 95% CI: −0.56, 1.78). Remaining analysis was only available for samidorphan, which showed statistically significant improvement in change in body weight (%) (RE = 1.81%; 95% CI: 1.07, 2.55), absolute risk of weight gain ≥7% (RE = 12.41%; 95% CI: 6.55, 18.27), absolute risk of weight gain ≥10% (RE = 10.83%; 95% CI: 5.46, 16.21), and change in waist circumference (RE = 1.50 cm; 95% CI: 0.32, 2.67).

Evidence is strongest for samidorphan, though CORAs as a class remains poorly researched and the benefits are modest. Additionally, samidorphan is currently only available in the combination medication olanzapine-samidorphan and the literature reflects this. Further research is needed to examine its efficacy in AIWG from other antipsychotics.

We sought to validate available tools for predicting recurrent C. difficile infection (CDI) including recurrence risk scores (by Larrainzar-Coghen, Reveles, D’Agostino, Cobo, and Eyre et al) alongside consensus guidelines risk criteria, the leading severity score (ATLAS), and PCR cycle threshold (as marker of fecal organism burden) using electronic medical records.

Retrospective cohort study validating previously described tools.

Tertiary care academic hospital.

Hospitalized adult patients with CDI at University of Virginia Medical Center.

Risk scores were calculated within ±48 hours of index CDI diagnosis using a large retrospective cohort of 1,519 inpatient infections spanning 7 years and compared using area under the receiver operating characteristic curve (AUROC) and the DeLong test. Recurrent CDI events (defined as a repeat positive test or symptom relapse within 60 days requiring retreatment) were confirmed by clinician chart review.

Reveles et al tool achieved the highest AUROC of 0.523 (and 0.537 among a subcohort of 1,230 patients with their first occurrence of CDI), which was not substantially better than other tools including the current IDSA/SHEA C. difficile guidelines or PCR cycle threshold (AUROC: 0.564), regardless of prior infection history.

All tools performed poorly for predicting recurrent C. difficile infection (AUROC range: 0.488–0.564), especially among patients with a prior history of infection (AUROC range: 0.436–0.591). Future studies may benefit from considering novel biomarkers and/or higher-dimensional models that could augment or replace existing tools that underperform.

In the United States, all 50 states and the District of Columbia have Good Samaritan Laws (GSLs). Designed to encourage bystanders to aid at the scene of an emergency, GSLs generally limit the risk of civil tort liability if the care is rendered in good faith. Nation-wide, a leading cause of preventable death is uncontrolled external hemorrhage. Public bleeding control initiatives aim to train the public to recognize life-threatening external bleeding, perform life-sustaining interventions (including direct pressure, tourniquet application, and wound packing), and to promote access to bleeding control equipment to ensure a rapid response from bystanders.

This study sought to identify the GSLs in each state and the District of Columbia to identify what type of responder is covered by the law (eg, all laypersons, only trained individuals, or only licensed health care providers) and if bleeding control is explicitly included or excluded in their Good Samaritan coverage.

Good Samaritan Laws providing civil liability qualified immunity were identified in all 50 states and the District of Columbia. One state, Oklahoma, specifically includes bleeding control in its GSLs. Six states – Connecticut, Illinois, Kansas, Kentucky, Michigan, and Missouri – have laws that define those covered under Good Samaritan immunity, generally limiting protection to individuals trained in a standard first aid or resuscitation course or health care clinicians. No state explicitly excludes bleeding control from their GSLs, and one state expressly includes it.

Nation-wide across the United States, most states have broad bystander coverage within GSLs for emergency medical conditions of all types, including bleeding emergencies, and no state explicitly excludes bleeding control interventions. Some states restrict coverage to those health care personnel or bystanders who have completed a specific training program. Opportunity exists for additional research into those states whose GSLs may not be inclusive of bleeding control interventions.

People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally.

We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation.

Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups

The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Deployment of law enforcement operational canines (OpK9s) risks injuries to the animals. This study’s aim was to assess the current status of states’ OpK9 (veterinary Emergency Medical Services [VEMS]) laws and care protocols within the United States.

Cross-sectional standardized review of state laws/regulations and OpK9 VEMS treatment protocols was undertaken. For each state and for the District of Columbia (DC), the presence of OpK9 legislation and/or care protocols was ascertained. Information was obtained through governmental records and from stakeholders (eg, state EMS medical directors and state veterinary boards).

The main endpoints were proportions of states with OpK9 laws and/or treatment protocols. Proportions are reported with 95% confidence intervals (CIs). Fisher’s exact test (P <.05) assessed whether presence of an OpK9 law in a given jurisdiction was associated with presence of an OpK9 care protocol, and whether there was geographic variation (based on United States Census Bureau regions) in presence of OpK9 laws or protocols.

Of 51 jurisdictions, 20 (39.2%) had OpK9 legislation and 23 (45.1%) had state-wide protocols for EMS treatment of OpK9s. There was no association (P = .991) between presence of legislation and presence of protocols. There was no association (P = .144) between presence of legislation and region: Northeast 66.7% (95% CI, 29.9-92.5%), Midwest 50.0% (95% CI, 21.1-78.9%), South 29.4% (95% CI, 10.3-56.0%), and West 23.1% (95% CI, 5.0-53.8%). There was significant (P = .001) regional variation in presence of state-wide OpK9 treatment protocols: Northeast 100.0% (95% CI, 66.4-100.0%), Midwest 16.7% (95% CI, 2.1-48.4%), South 47.1% (95% CI, 23.0-72.2%), and West 30.8% (95% CI, 9.1-61.4%).

There is substantial disparity with regard to presence of OpK9 legal and/or clinical guidance. National collaborative guidelines development is advisable to optimize and standardize care of OpK9s. Additional attention should be paid to educational and training programs to best utilize the limited available training budgets.