Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin.

Retrospective cohort study.

Community health system.

Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10–14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen.

Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI.

The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07–0.56, p < 0.002).

Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.

Despite an elevated risk of psychopathology stemming from COVID-19-related stress, many essential workers stigmatise and avoid psychiatric care. This randomised controlled trial was designed to compare five versions of a social-contact-based brief video intervention for essential workers, differing by protagonist gender and race/ethnicity.

We examined intervention efficacy on treatment-related stigma (‘stigma’) and openness to seeking treatment (‘openness’), especially among workers who had not received prior mental healthcare. We assessed effectiveness and whether viewer/protagonist demographic concordance heightened effectiveness.

Essential workers (N = 2734) randomly viewed a control video or brief video of an actor portraying an essential worker describing hardships, COVID-related anxiety and depression, and psychotherapy benefits. Five video versions (Black/Latinx/White and male/female) followed an identical 3 min script. Half the intervention group participants rewatched their video 14 days later. Stigma and openness were assessed at baseline, post-intervention, and at 14- and 30-day follow-ups. Trial registration: NCT04964570.

All video intervention groups reported immediately decreased stigma (P < 0.0001; Cohen's d = 0.10) and increased openness (P < 0.0001; d = 0.23). The initial increase in openness was largely maintained in the repeated-video group at day 14 (P < 0.0001; d = 0.18), particularly among viewers without history of psychiatric treatment (P < 0.0001; d = 0.32). Increases were not sustained at follow-up. Female participants viewing a female protagonist and Black participants viewing a Black protagonist demonstrated greater openness than other demographic pairings.

Brief video-based interventions improved immediate stigma and openness. Greater effects among female and Black individuals viewing demographically matched protagonists emphasise the value of tailored interventions, especially for socially oppressed groups. This easily disseminated intervention may proactively increase care-seeking, encouraging treatment among workers in need. Future studies should examine intervention mechanisms and whether linking referrals to psychiatric services generates treatment-seeking.

This study compared the per capita annual global incidence rate of disasters caused by natural hazards with the annual world real gross domestic product, GDP (per global capita), as reported during 1961 through 2020.

Sixty (60) values for the world real GDP per global capita (in constant 2015 $USD) were compared to corresponding annual values for global incidence rates for five natural disaster subgroups and then for a total of twelve individual disaster types that comprise the subgroups; each expressed as an annual global incidence rate (in terms of annual incidence per 100,000 persons). Calculations of multiple linear regression, ANOVA, and Pearson’s correlation coefficient were performed for comparing population-adjusted values for GDP to corresponding values.

Four out of five hydrological and meteorological disasters were found to have a positive correlation with GDP. Results of the analysis revealed a relatively high degree of correlation between world GDP and the annual incidence of flood and storm disasters (P = 6.21 × 10−10 and P = 4.23 × 10−4, respectively). The annual incidence of heat waves and cold weather disasters also appeared to correlate with GDP (P = .002 and P = .019, respectively). In comparison, wet landslides indicated no such correlation (P = .862). No significant associations were found among the seven other individual biological, climatological, and geophysical disasters and GDP.

The global incidence of four extreme weather (hydrometeorological) disasters appear to be positively associated with world real GDP during 1961-2020. These findings contradict previous postulates that the risk of disaster incidence is inversely associated with the capacity of the population.

Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.

To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.

Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.

Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.

AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.

Many healthcare workers do not seek help, despite their enormous stress and greater risk for anxiety, depression and post-traumatic stress disorder (PTSD).

This study screened for psychopathology and evaluated the efficacy of a brief, social contact-based video intervention in increasing treatment-seeking intentions among healthcare workers (trial registration: NCT04497415). We anticipated finding high rates of psychopathology and greater treatment-seeking intentions post-intervention.

Healthcare workers (n = 350) were randomised to (a) a brief video-based intervention at day 1, coupled with a booster video at day 14; (b) the video at day 1 only; or (c) a non-intervention control. In the 3 min video, a female nurse described difficulty coping with stress, her anxieties and depression, barriers to care and how therapy helped her. Assessments were conducted pre- and post-intervention and at 14- and 30-day follow-ups.

Of the 350 healthcare workers, 281 (80%) reported probable anxiety, depression and/or PTSD. Participants were principally nurses (n = 237; 68%), physicians (n = 52; 15%) and emergency medical technicians (n = 30; 9%). The brief video-based intervention yielded greater increases in treatment-seeking intentions than the control condition, particularly among participants in the repeat-video group. Exploratory analysis revealed that in both video groups, we found greater effect among nurses than non-nurses.

A brief video-based intervention increased treatment-seeking intention, possibly through identification and emotional engagement with the video protagonist. A booster video magnified that effect. This easily disseminated intervention could increase the likelihood of seeking care and offer employers a proactive approach to encourage employees to search for help if needed.

During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.

Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.

The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.

Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.

Clinical Trial Registration: NCT01778335

To develop a pediatric research agenda focused on pediatric healthcare-associated infections and antimicrobial stewardship topics that will yield the highest impact on child health.

The study included 26 geographically diverse adult and pediatric infectious diseases clinicians with expertise in healthcare-associated infection prevention and/or antimicrobial stewardship (topic identification and ranking of priorities), as well as members of the Division of Healthcare Quality and Promotion at the Centers for Disease Control and Prevention (topic identification).

Using a modified Delphi approach, expert recommendations were generated through an iterative process for identifying pediatric research priorities in healthcare associated infection prevention and antimicrobial stewardship. The multistep, 7-month process included a literature review, interactive teleconferences, web-based surveys, and 2 in-person meetings.

A final list of 12 high-priority research topics were generated in the 2 domains. High-priority healthcare-associated infection topics included judicious testing for Clostridioides difficile infection, chlorhexidine (CHG) bathing, measuring and preventing hospital-onset bloodstream infection rates, surgical site infection prevention, surveillance and prevention of multidrug resistant gram-negative rod infections. Antimicrobial stewardship topics included β-lactam allergy de-labeling, judicious use of perioperative antibiotics, intravenous to oral conversion of antimicrobial therapy, developing a patient-level “harm index” for antibiotic exposure, and benchmarking and or peer comparison of antibiotic use for common inpatient conditions.

We identified 6 healthcare-associated infection topics and 6 antimicrobial stewardship topics as potentially high-impact targets for pediatric research.