Understanding the effects of ketamine on depressive symptoms could help identify which patients might benefit and clarify its mechanism of action in both the early (≤1 day post-infusion) and late (e.g. 2–30 days post-infusion) post-infusion periods. Symptom network analyses could provide complementary information regarding relationships between symptoms.

To identify the effects of ketamine on symptom-level changes in depression across both the early and late post-infusion periods and on depressive symptom network changes.

In this secondary analysis of 152 adults with treatment-resistant depression (with 38.8% reporting suicidal ideation at baseline), we compared symptom changes in the early and late post-infusion periods between individuals randomised to a single 40 min infusion of intravenous ketamine 0.5 mg/kg (n = 103) or saline (n = 49) and identified changes in symptom networks between pre- and post-ketamine treatment using network analyses.

In the early post-infusion period, the greatest improvement (comparing ketamine with saline) was in depressive symptoms related to sadness. In network analyses, symptom network connectivity increased following ketamine infusion. Symptoms of sadness and lassitude showed persistent improvement in the first week post-infusion, whereas improvements in suicidal thoughts first emerged 3–4 weeks post-infusion.

Ketamine improved all symptoms but showed the greatest effect on symptoms of sadness, both immediately and in the initial week after treatment. Ketamine also rapidly altered the topology of symptom networks, strengthening interrelationships between residual symptoms. The efficacy of ketamine (compared with saline) regarding suicidal symptoms emerged later. Our findings suggest potentially divergent efficacy, time courses and mechanisms for different symptoms of depression.

The grief of relatives of patients who died of COVID-19 in an intensive care unit (ICU) has exacted an enormous toll worldwide.

To determine the prevalence of probable prolonged grief disorder (PGD) at 12 months post-loss and beyond. We also sought to examine circumstances of the death during the COVID-19 pandemic that might pose a heightened risk of PGD, and the associations between probable PGD diagnosis, quality of life and social disconnection.

We conducted an observational, cross-sectional multicentre study of the next of kin of those who died of COVID-19 between March 2020 and December 2021. Participants were recruited from ICUs in South-East London. The Prolonged Grief Disorder Scale (PG-13-R), Quality-of-Life Scale (QOLS) and Oxford Grief-Social Disconnection Scale (OG-SD) were used.

A total of 73 relatives were recruited and assessed, all of them over a year after their loss. Twenty-five (34.2%; 95% CI 23.1–45.4%) relatives of patients who died in the ICU met the criteria for PGD. Those who met the criteria had significantly worse quality of life (QOLS score mean difference 26; 95% CI 17–34; P < 0.001) and endorsed greater social disconnection (OG-SD score means difference 41; 95% CI 27–54; P < 0.001).

The findings suggest that rates of PGD are elevated among relatives of patients who died of COVID-19 in the ICU. This, coupled with worse quality of life and greater social disconnection experienced by those meeting the criteria, suggests the need to attend to the social deprivations and social dysfunctions of this population group.

Childhood trauma and adversity are common across societies and have strong associations with physical and psychiatric morbidity throughout the life-course. One possible mechanism through which childhood trauma may predispose individuals to poor psychiatric outcomes is via associations with brain structure. This study aimed to elucidate the associations between childhood trauma and brain structure across two large, independent community cohorts.

The two samples comprised (i) a subsample of Generation Scotland (n=1,024); and (ii) individuals from UK Biobank (n=27,202). This comprised n=28,226 for mega-analysis. MRI scans were processed using Free Surfer, providing cortical, subcortical, and global brain metrics. Regression models were used to determine associations between childhood trauma measures and brain metrics and psychiatric phenotypes.

Childhood trauma associated with lifetime depression across cohorts (OR 1.06 GS, 1.23 UKB), and related to early onset and recurrent course within both samples. There was evidence for associations between childhood trauma and structural brain metrics. This included reduced global brain volume, and reduced cortical surface area with highest effects in the frontal (β=−0.0385, SE=0.0048, p(FDR)=5.43x10−15) and parietal lobes (β=−0.0387, SE=0.005, p(FDR)=1.56x10−14). At a regional level the ventral diencephalon (VDc) displayed significant associations with childhood trauma measures across both cohorts and at mega-analysis (β=−0.0232, SE=0.0039, p(FDR)=2.91x10−8). There were also associations with reduced hippocampus, thalamus, and nucleus accumbens volumes.

Associations between childhood trauma and reduced global and regional brain volumes were found, across two independent UK cohorts, and at mega-analysis. This provides robust evidence for a lasting effect of childhood adversity on brain structure.

To determine whether a clinician-directed acute respiratory tract infection (ARI) intervention was associated with improved antibiotic prescribing and patient outcomes across a large US healthcare system.

Multicenter retrospective quasi-experimental analysis of outpatient visits with a diagnosis of uncomplicated ARI over a 7-year period.

Outpatients with ARI diagnoses: sinusitis, pharyngitis, bronchitis, and unspecified upper respiratory tract infection (URI-NOS). Outpatients with concurrent infection or select comorbid conditions were excluded.

Audit and feedback with peer comparison of antibiotic prescribing rates and academic detailing of clinicians with frequent ARI visits. Antimicrobial stewards and academic detailing personnel delivered the intervention; facility and clinician participation were voluntary.

We calculated the probability to receive antibiotics for an ARI before and after implementation. Secondary outcomes included probability for a return clinic visits or infection-related hospitalization, before and after implementation. Intervention effects were assessed with logistic generalized estimating equation models. Facility participation was tracked, and results were stratified by quartile of facility intervention intensity.

We reviewed 1,003,509 and 323,023 uncomplicated ARI visits before and after the implementation of the intervention, respectively. The probability to receive antibiotics for ARI decreased after implementation (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.78–0.86). Facilities with the highest quartile of intervention intensity demonstrated larger reductions in antibiotic prescribing (OR, 0.69; 95% CI, 0.59–0.80) compared to nonparticipating facilities (OR, 0.89; 95% CI, 0.73–1.09). Return visits (OR, 1.00; 95% CI, 0.94–1.07) and infection-related hospitalizations (OR, 1.21; 95% CI, 0.92–1.59) were not different before and after implementation within facilities that performed intensive implementation.

Implementation of a nationwide ARI management intervention (ie, audit and feedback with academic detailing) was associated with improved ARI management in an intervention intensity–dependent manner. No impact on ARI-related clinical outcomes was observed.

To better understand coronavirus disease 2019 (COVID-19) transmission among healthcare workers (HCWs), we investigated occupational and nonoccupational risk factors associated with cumulative COVID-19 incidence among a Massachusetts HCW cohort.

The retrospective cohort study included adult HCWs in a single healthcare system from March 9 to June 3, 2020.

The SARS-CoV-2 nasopharyngeal RT-PCR results and demographics of the study participants were deidentified and extracted from an established occupational health, COVID-19 database at the healthcare system. HCWs from each particular job grouping had been categorized into frontline or nonfrontline workers. Incidence rate ratios (IRRs) and odds ratios (ORs) were used to compare subgroups after excluding HCWs involved in early infection clusters before universal masking began. A sensitivity analysis was performed comparing jobs with the greatest potential occupational risks with others.

Of 5,177 HCWs, 152 (2.94%) were diagnosed with COVID-19. Affected HCWs resided in areas with higher community attack rates (median, 1,755.2 vs 1,412.4 cases per 100,000; P < .001; multivariate-adjusted IRR, 1.89; 95% CI, 1.03–3.44 comparing fifth to first quintile of community rates). After multivariate adjustment, African-American and Hispanic HCWs had higher incidence of COVID-19 than non-Hispanic white HCWs (IRR, 2.78; 95% CI, 1.78–4.33; and IRR, 2.41, 95% CI, 1.42–4.07, respectively). After adjusting for race and residential rates, frontline HCWs had a higher IRR (1.73, 95% CI, 1.16–2.54) than nonfrontline HCWs overall, but not within specific job categories nor when comparing the highest risk jobs to others.

After universal masking was instituted, the strongest risk factors associated with HCW COVID-19 infection were residential community infection rate and race.

While the burden of dementia is increasing in low- and middle-income countries, there is a low rate of diagnosis and paucity of research in these regions. A major challenge to study dementia is the limited availability of standardised diagnostic tools for use in populations with linguistic and educational diversity. The objectives of the study were to develop a standardised and comprehensive neurocognitive test battery to diagnose dementia and mild cognitive impairment (MCI) due to varied etiologies, across different languages and educational levels in India, to facilitate research efforts in diverse settings.

A multidisciplinary expert group formed by Indian Council of Medical Research (ICMR) collaborated towards adapting and validating a neurocognitive test battery, that is, the ICMR Neurocognitive Tool Box (ICMR-NCTB) in five Indian languages (Hindi, Bengali, Telugu, Kannada, and Malayalam), for illiterates and literates, to standardise diagnosis of dementia and MCI in India.

Following a review of existing international and national efforts at standardising dementia diagnosis, the ICMR-NCTB was developed and adapted to the Indian setting of sociolinguistic diversity. The battery consisted of tests of cognition, behaviour, and functional activities. A uniform protocol for diagnosis of normal cognition, MCI, and dementia due to neurodegenerative diseases and stroke was followed in six centres. A systematic plan for validating the ICMR-NCTB and establishing cut-off values in a diverse multicentric cohort was developed.

A key outcome was the development of a comprehensive diagnostic tool for diagnosis of dementia and MCI due to varied etiologies, in the diverse socio-demographic setting of India.

Treatment for hoarding disorder is typically performed by mental health professionals, potentially limiting access to care in underserved areas.

We aimed to conduct a non-inferiority trial of group peer-facilitated therapy (G-PFT) and group psychologist-led cognitive–behavioural therapy (G-CBT).

We randomised 323 adults with hording disorder 15 weeks of G-PFT or 16 weeks of G-CBT and assessed at baseline, post-treatment and longitudinally (≥3 months post-treatment: mean 14.4 months, range 3–25). Predictors of treatment response were examined.

G-PFT (effect size 1.20) was as effective as G-CBT (effect size 1.21; between-group difference 1.82 points, t = −1.71, d.f. = 245, P = 0.04). More homework completion and ongoing help from family and friends resulted in lower severity scores at longitudinal follow-up (t = 2.79, d.f. = 175, P = 0.006; t = 2.89, d.f. = 175, P = 0.004).

Peer-led groups were as effective as psychologist-led groups, providing a novel treatment avenue for individuals without access to mental health professionals.

C.A.M. has received grant funding from the National Institutes of Health (NIH) and travel reimbursement and speakers’ honoraria from the Tourette Association of America (TAA), as well as honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. K.D. receives research support from the NIH and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. R.S.M. receives research support from the National Institute of Mental Health, National Institute of Aging, the Hillblom Foundation, Janssen Pharmaceuticals (research grant) and the Alzheimer's Association. R.S.M. has also received travel support from the National Institute of Mental Health for Workshop participation. J.Y.T. receives research support from the NIH, Patient-Centered Outcomes Research Institute and the California Tobacco Related Research Program, and honoraria and travel reimbursement from the NIH for serving as an NIH Study Section reviewer. All other authors report no conflicts of interest.

Major depressive disorder (MDD) and anxiety disorders (ANX) are debilitating and prevalent conditions that often co-occur in adolescence and young adulthood. The leading theoretical models of their co-morbidity include the direct causation model and the shared etiology model. The present study compared these etiological models of MDD–ANX co-morbidity in a large, prospective, non-clinical sample of adolescents tracked through age 30.

Logistic regression was used to examine cross-sectional associations between ANX and MDD at Time 1 (T1). In prospective analyses, Cox proportional hazards models were used to examine T1 predictors of subsequent disorder onset, including risk factors specific to each disorder or common to both disorders. Prospective predictive effect of a lifetime history of one disorder (e.g. MDD) on the subsequent onset of the second disorder (e.g. ANX) was then examined. This step was repeated while controlling for common risk factors.

The findings supported relatively distinct profiles of risk between MDD and ANX depending on order of development. Whereas the shared etiology model best explained co-morbid cases in which MDD preceded ANX, direct causation was supported for co-morbid cases in which ANX preceded MDD.

Consistent with previous research, significant cross-sectional and prospective associations were found between MDD and ANX. The results of the present study suggest that different etiological models may characterize the co-morbidity between MDD and ANX based upon the temporal order of onset. Implications for classification and prevention efforts are discussed.