Clostridioides difficile is the primary cause of healthcare-associated infectious diarrhea in hospitalized patients. The most common laboratory testing methods for C. difficile infection (CDI) are toxin detection via enzyme immunoassay (EIA) and polymerase chain reaction (PCR), which detect a toxogenic strain. This study examines the impact of Rhode Island’s largest hospital system changing from PCR-only to two-step CDI testing.

A retrospective cohort study of 2,173 adult inpatients was conducted. Patients were grouped into two cohorts: those tested for toxigenic C. difficile via PCR-only (June 2019–May 2021, n = 1,194) and those tested with the two-step algorithm (June 2021–May 2023, n = 979). Cluster analysis identified patient risk groups for hypothesis generation, and complications such as death, colectomy, intensive care unit ICU transfer, and 30-day readmission were compared across these groups.

In the moderate-risk group, there was a significant reduction in ICU transfers and readmission rates with the two-step testing by 5% and 7%, respectively. There were no other significant differences in complications between testing groups. Anti-CDI antibiotics were discontinued in 15% (n = 106) of EIA-negative patients in the two-step testing group. Moderate-risk patients were less likely to have treatment discontinued than severe-risk patients (OR = 2.00, p = 0.016).

The two-step testing algorithm did not negatively affect patient outcomes and led to a modest decrease in anti-CDI treatment, supporting the safety of two-step CDI testing in hospitalized patients.

To determine the local applicability of 2021 American Academy for the Study of Liver Diseases spontaneous bacterial peritonitis (SBP) treatment guidelines by evaluating the microbiology and clinical outcomes of SBP cases in an academic health system.

Retrospective cohort study.

Five-hospital academic health system.

Hospitalized adult patients with SBP.

This study involved 2 components. First, patients meeting inclusion criteria with peritoneal fluid cultures positive for a pathogen were included in the culture-positive group. Antibiotic susceptibilities were analyzed for these patients. Second, remaining culture-negative patients were randomly selected and sequentially evaluated until the culture-negative and culture-positive groups were approximately the same size. Clinical data for all patients were evaluated based on empiric antibiotics received.

Forty-nine patients with culture-positive SBP and 48 patients with culture-negative SBP were included. Eight (16%) positive cultures contained TGC-nonsusceptible organisms. Patients receiving empiric third-generation cephalosporin (TGC) monotherapy had similar clinical outcomes as patients receiving empiric broad-spectrum therapy, including similar 30-day mortality (36% vs 38%; P = 1.00), 90-day mortality (55% vs 55%; P = 1.00), and median duration of hospitalization (6.5 d vs 8 d; P = .25). ICU admission, recent hospitalization, and nosocomial infection were not associated with TGC-nonsusceptible pathogen isolation in a univariate logistic regression analysis.

Within our health system, 16% of isolates in culture-positive SBP patients were nonsusceptible to TGCs. No statistically significant difference was detected in clinical outcomes in patients receiving TGC or broader-spectrum antimicrobial therapy.

Community health centers (CHCs) and those most burdened by disease are important partners in setting research agendas to address the needs of people who are medically underserved.

Identify and prioritize health equity-focused research priorities using a collaborative approach to community engagement of key informants.

We used five stepwise phases from January 2021 to February 2023 to formulate and prioritize a set of health equity-focused research topics among CHC staff (leaders, clinicians), their key advisors (patients and community members), and researchers from academic medical centers in California. Phases included: (1) community advisory board formation, (2) key informant identification, (3) individual/small group interview guide development and administration, (4) initial health equity-focused topic categorization, and (5) in-person meeting with community advisors for final topic prioritization using nominal group technique.

Twenty individual or small group interviews were completed with 44 diverse participants, along with engagement from our community advisory board, which resulted in an initial list of 11 health equity-focused research topics. Ninety advisors including diverse community members, CHC staff/leaders, and researchers prioritized six overarching research topics. Final prioritized health-equity focused research topics include addressing mental health challenges, improving public’s trust in healthcare and science, healthcare delivery models to increase access and utilization, build and sustain an anti-racist healthcare system, strategies and interventions to address health misinformation, and continuing and sustaining polices based on lessons learned from COVID-19.

Results offer future direction for community-engaged research agendas to advance health equity among medically underserved and vulnerable patient populations.

Non-suicidal self-injury (NSSI) often emerges during adolescence and young adulthood. A prior open-label pilot study suggested that N-acetylcysteine (NAC) may reduce NSSI frequency in young individuals.

This study investigated potential NSSI-related biological markers for NAC in young adults with a history of NSSI using a placebo-controlled, randomised clinical trial of two NAC dosage regimens.

Forty-three individuals (assigned female at birth) aged 16–24 years and with a history of NSSI were randomly assigned to either low-dose NAC (3600 mg/day), high-dose NAC (5400 mg/day) or placebo treatment for 4 weeks. Participants underwent blood draws, magnetic resonance imaging with spectroscopy and clinical assessments before and after treatment. Primary outcomes included brain glutathione (GSH), blood reduced to oxidised GSH ratio and brain glutamate. Secondary outcomes included antioxidant protein levels, brain gamma-aminobutyric acid concentrations, functional connectivity (between amygdala and insula) and clinical outcomes. Pharmacokinetics, tolerability and correlations among measures were also explored.

For 39 participants who completed study assessments at follow-up, weekly NSSI and depression symptoms improved similarly across both treatment and placebo groups, with no significant group differences in primary or secondary outcomes at follow-up. Some significant correlations emerged.

The study did not support the proposed biological signatures of NAC in young adults with NSSI, although exploratory findings suggested potential biological correlates of clinical improvement. Further research is necessary to explore neurobiologically based treatments for young adults with NSSI.

The rate at which psychosis drugs can be reduced in dose remains unclear. Anecdotal reports exist of people experiencing worsening of mental state before their next dose of long-acting injectable antipsychotic. No research has previously explored this phenomenon, but understanding this may advise on the rate of receptor occupancy change that provokes the emergence of psychotic symptoms.

Exploring the relationship between psychotic symptoms and variations in plasma concentration (and calculated receptor occupancy) of long-acting injectable antipsychotics.

This longitudinal study monitored mental state variation within dosing cycles of people taking depot flupentixol and zuclopenthixol. The Positive and Negative Syndrome Scale (PANSS) monitored global mental state changes, and was stratified into domains according to a five-factor model. Plasma assays at maximal and minimal concentrations allowed prediction of striatal D2 occupancy from published data. We examined correlations between receptor occupancy and the emergence of psychotic symptoms.

Preliminary results from ten participants with psychotic disorders suggest that global mental state deterioration may correlate with increased rate of D2 occupancy reduction. Increased rate of D2 occupancy reduction led to deterioration in ‘positive’ (r = 0.637 [CI: 0.013, 0.904], P = 0.047) and ‘resistance’ (r = 0.726 [CI: 0.177, 0.930], P = 0.018) PANSS clinical domains at minimal concentrations. PANSS score differences were not related to absolute reduction in D2 occupancy.

Our novel observational study design has been demonstrated to be feasible and practicable. Faster reductions in D2 occupancy may increase the risk of increased positive psychotic symptoms and irritability. Slower reductions may minimise this effect. Further recruitment is required before this can be confirmed.

Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.

We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.

We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).

Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.

Neuropsychiatry training in the UK currently lacks a formal scheme or qualification, and its demand and availability have not been systematically explored. We conducted the largest UK-wide survey of psychiatry trainees to examine their experiences in neuropsychiatry training.

In total, 185 trainees from all UK training regions completed the survey. Although 43.6% expressed interest in a neuropsychiatry career, only 10% felt they would gain sufficient experience by the end of training. Insufficient access to clinical rotations was the most common barrier, with significantly better access in London compared with other regions. Most respondents were in favour of additional neurology training (83%) and a formal accreditation in neuropsychiatry (90%).

Strong trainee interest in neuropsychiatry contrasts with the limited training opportunities currently available nationally. Our survey highlights the need for increased neuropsychiatry training opportunities, development of a formalised training programme and a clinical accreditation pathway for neuropsychiatry in the UK.

Negative symptoms are a key feature of several psychiatric disorders. Difficulty identifying common neurobiological mechanisms that cut across diagnostic boundaries might result from equifinality (i.e., multiple mechanistic pathways to the same clinical profile), both within and across disorders. This study used a data-driven approach to identify unique subgroups of participants with distinct reward processing profiles to determine which profiles predicted negative symptoms.

Participants were a transdiagnostic sample of youth from a multisite study of psychosis risk, including 110 individuals at clinical high-risk for psychosis (CHR; meeting psychosis-risk syndrome criteria), 88 help-seeking participants who failed to meet CHR criteria and/or who presented with other psychiatric diagnoses, and a reference group of 66 healthy controls. Participants completed clinical interviews and behavioral tasks assessing four reward processing constructs indexed by the RDoC Positive Valence Systems: hedonic reactivity, reinforcement learning, value representation, and effort–cost computation.

k-means cluster analysis of clinical participants identified three subgroups with distinct reward processing profiles, primarily characterized by: a value representation deficit (54%), a generalized reward processing deficit (17%), and a hedonic reactivity deficit (29%). Clusters did not differ in rates of clinical group membership or psychiatric diagnoses. Elevated negative symptoms were only present in the generalized deficit cluster, which also displayed greater functional impairment and higher psychosis conversion probability scores.

Contrary to the equifinality hypothesis, results suggested one global reward processing deficit pathway to negative symptoms independent of diagnostic classification. Assessment of reward processing profiles may have utility for individualized clinical prediction and treatment.

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.

Mind-wandering is defined as a spontaneous shift of attention away from the external environment to inner thoughts. With mind-wandering being a ubiquitous phenomenon, there has been increasing interest in examining the role these spontaneous, and often unintentional, thought processes may have for metrics of cognitive and psychological health. However, much of this literature is mired with inconsistencies, potentially stemming from the use of variegated experimental methods and quantification of mind-wandering through different metrics. For example, mind-wandering has been investigated through endorsement of self-report probes embedded in tasks of sustained attention, with participants asking to endorse whether they were engaging in task-unrelated thoughts or task-related, but evaluative thoughts about the task (task-related interference). Other studies have instead focused on behavioral metrics of task performance, like omission and commission errors, the variability in response time (RTCV), and speeding or slowing prior to errors to quantify mind-wandering. In this study, employing a large sample of older adults, and implementing the novel technique of partial least squares regression, we examined the combined and simultaneous effect of different mind-wandering metrics in explaining variance in fluid cognition and psychological health in older adults.

One hundred and fifty older adults with normal cognition or mild cognitive impairment were administered a Go/No-Go Task (GNG) with embedded mind-wandering probes, the Conners CPT-3, the NIH Toolbox-Cognition Battery, and the WHO Quality of Life Assessment Brief Version at baseline in a clinical trial examining the impact of two mind-body interventions on aging. Based on previous research, the following variables were considered behavioral measures of mind-wandering: quantity of omission and commission errors, RTCV, pre-error speeding, and post-error slowing. Percentage of self-reported task-related interference (i.e. evaluating current performance) and task-unrelated thoughts were included as self-report measures of mind-wandering. These mind-wandering measures, along with demographic variables (age, sex, and education), were regressed using Partial Least Squares Regression to determine the impact of mind-wandering measures on fluid cognition (NIHT-CB) and perceived psychological well-being (WHOQOL-BBREF). Validation tests were completed to assess model fit.

A single latent factor explained 26% of the variance in fluid cognition (p=0.0001). Higher levels of age, errors of omission on both tasks, and task-related interference were all associated with worse fluid cognition, whereas task-unrelated thoughts were associated with better fluid cognition.

A two-factor latent model explained 12% of the variance in perceived psychological well-being (p=0.0004). Age and task-unrelated thoughts were positively associated with psychological well-being. In contrast, errors of omission on both tasks, response time variability on the CPT, and task-related interference were negatively associated with perceived psychological well-being.

Mind-wandering is associated with fluid cognition and perceived psychological well-being in older adults. Select behavioral measures were better than self-report measures at linking mind-wandering to fluid cognition and perceived psychological well-being. Interestingly task-unrelated thoughts, but not task-related interference, was positively associated with fluid cognition, supporting the cognitive resource-based account of mind-wandering. The result of our study provides novel insights into differential relationships between various metrics of mind-wandering and cognitive and psychological health.

Among patients with a history of ESBL infection, uncertainty remains regarding whether all of these patients require ESBL-targeted therapy when presenting with a subsequent infection. We sought to determine the risks associated with a subsequent ESBL infection to help inform empiric antibiotic decisions.

A retrospective cohort study of adult patients with positive index culture for Escherichia coli or Klebsiella pneumoniae (EC/KP) receiving medical care during 2017 was conducted. Risk assessments were performed to identify factors associated with subsequent infection caused by ESBL-producing EC/KP.

In total, 200 patients were included in the cohort, 100 with ESBL-producing EC/KP and 100 with ESBL-negative EC/KP. Of 100 patients (50%) who developed a subsequent infection, 22 infections were ESBL-producing EC/KP, 43 were other bacteria, and 35 had no or negative cultures. Subsequent infection caused by ESBL-producing EC/KP only occurred when the index culture was also ESBL-producing (22 vs 0). Among those with ESBL-producing index culture, the incidences of subsequent infection caused by ESBL-producing EC/KP versus other bacterial subsequent infection were similar (22 vs 18; P = .428). Factors associated with subsequent infection caused by ESBL-producing EC/KP include history of ESBL-producing index culture, time ≤180 days between index culture and subsequent infection, male sex, and Charlson comorbidity index score >3.

History of ESBL-producing EC/KP culture is associated with subsequent infection caused by ESBL-producing EC/KP, particularly within 180 days after the historical culture. Among patients presenting with infection and a history of ESBL-producing EC/KP, other factors should be considered in making empiric antibiotic decisions, and ESBL-targeted therapy may not always be warranted.

Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.

Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.

As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.

We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.

DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.

Patients with Fontan physiology require non-cardiac surgery. Our objectives were to characterise perioperative outcomes of patients with Fontan physiology undergoing non-cardiac surgery and to identify characteristics which predict discharge on the same day.

Children and young adults with Fontan physiology who underwent a non-cardiac surgery or an imaging study under anaesthesia between 2013 and 2019 at a single-centre academic children’s hospital were reviewed in a retrospective observational study. Continuous variables were compared using the Wilcoxon rank sum test, and categorical variables were analysed using the Chi-square test or Fisher’s exact test. Multivariable logistic regression analysis results are presented by adjusted odds ratios with 95% confidence intervals and p values.

182 patients underwent 344 non-cardiac procedures with anaesthesia. The median age was 11 years (IQR 5.2–18), 56.4% were male. General anaesthesia was administered in 289 (84%). 125 patients (36.3%) were discharged on the same day. On multivariable analysis, independent predictors that reduced the odds of same-day discharge included the chronic condition index (OR 0.91 per additional chronic condition, 95% CI 0.76–0.98, p = 0.022), undergoing a major surgical procedure (OR 0.17, 95% CI 0.05–0.64, p = 0.009), the use of intraoperative inotropes (OR 0.48, 95% CI 0.25–0.94, p = 0.031), and preoperative admission (OR = 0.24, 95% CI: 0.1–0.57, p = 0.001).

In a contemporary cohort of paediatric and young adults with Fontan physiology, 36.3% were able to be discharged on the same day of their non-cardiac procedure. Well selected patients with Fontan physiology can undergo anaesthesia without complications and be discharged same day.