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.

Various water-based heater-cooler devices (HCDs) have been implicated in nontuberculous mycobacteria outbreaks. Ongoing rigorous surveillance for healthcare-associated M. abscessus (HA-Mab) put in place following a prior institutional outbreak of M. abscessus alerted investigators to a cluster of 3 extrapulmonary M. abscessus infections among patients who had undergone cardiothoracic surgery.

Investigators convened a multidisciplinary team and launched a comprehensive investigation to identify potential sources of M. abscessus in the healthcare setting. Adherence to tap water avoidance protocols during patient care and HCD cleaning, disinfection, and maintenance practices were reviewed. Relevant environmental samples were obtained. Patient and environmental M. abscessus isolates were compared using multilocus-sequence typing and pulsed-field gel electrophoresis. Smoke testing was performed to evaluate the potential for aerosol generation and dispersion during HCD use. The entire HCD fleet was replaced to mitigate continued transmission.

Clinical presentations of case patients and epidemiologic data supported intraoperative acquisition. M. abscessus was isolated from HCDs used on patients and molecular comparison with patient isolates demonstrated clonality. Smoke testing simulated aerosolization of M. abscessus from HCDs during device operation. Because the HCD fleet was replaced, no additional extrapulmonary HA-Mab infections due to the unique clone identified in this cluster have been detected.

Despite adhering to HCD cleaning and disinfection strategies beyond manufacturer instructions for use, HCDs became colonized with and ultimately transmitted M. abscessus to 3 patients. Design modifications to better contain aerosols or filter exhaust during device operation are needed to prevent NTM transmission events from water-based HCDs.

We compared the number of blood-culture events before and after the introduction of a blood-culture algorithm and provider feedback. Secondary objectives were the comparison of blood-culture positivity and negative safety signals before and after the intervention.

Prospective cohort design.

Two surgical intensive care units (ICUs): general and trauma surgery and cardiothoracic surgery

Patients aged ≥18 years and admitted to the ICU at the time of the blood-culture event.

We used an interrupted time series to compare rates of blood-culture events (ie, blood-culture events per 1,000 patient days) before and after the algorithm implementation with weekly provider feedback.

The blood-culture event rate decreased from 100 to 55 blood-culture events per 1,000 patient days in the general surgery and trauma ICU (72% reduction; incidence rate ratio [IRR], 0.38; 95% confidence interval [CI], 0.32–0.46; P < .01) and from 102 to 77 blood-culture events per 1,000 patient days in the cardiothoracic surgery ICU (55% reduction; IRR, 0.45; 95% CI, 0.39–0.52; P < .01). We did not observe any differences in average monthly antibiotic days of therapy, mortality, or readmissions between the pre- and postintervention periods.

We implemented a blood-culture algorithm with data feedback in 2 surgical ICUs, and we observed significant decreases in the rates of blood-culture events without an increase in negative safety signals, including ICU length of stay, mortality, antibiotic use, or readmissions.

Urine cultures collected from catheterized patients have a high likelihood of false-positive results due to colonization. We examined the impact of a clinical decision support (CDS) tool that includes catheter information on test utilization and patient-level outcomes.

This before-and-after intervention study was conducted at 3 hospitals in North Carolina. In March 2021, a CDS tool was incorporated into urine-culture order entry in the electronic health record, providing education about indications for culture and suggesting catheter removal or exchange prior to specimen collection for catheters present >7 days. We used an interrupted time-series analysis with Poisson regression to evaluate the impact of CDS implementation on utilization of urinalyses and urine cultures, antibiotic use, and other outcomes during the pre- and postintervention periods.

The CDS tool was prompted in 38,361 instances of urine cultures ordered in all patients, including 2,133 catheterized patients during the postintervention study period. There was significant decrease in urine culture orders (1.4% decrease per month; P < .001) and antibiotic use for UTI indications (2.3% decrease per month; P = .006), but there was no significant decline in CAUTI rates in the postintervention period. Clinicians opted for urinary catheter removal in 183 (8.5%) instances. Evaluation of the safety reporting system revealed no apparent increase in safety events related to catheter removal or reinsertion.

CDS tools can aid in optimizing urine culture collection practices and can serve as a reminder for removal or exchange of long-term indwelling urinary catheters at the time of urine-culture collection.

To describe the epidemiology of complex colon surgical procedures (COLO), stratified by present at time of surgery (PATOS) surgical-site infections (SSIs) and non-PATOS SSIs and their impact on the epidemiology of colon-surgery SSIs.

Retrospective cohort study.

SSI data were prospectively collected from patients undergoing colon surgical procedures (COLOs) as defined by the National Healthcare Safety Network (NHSN) at 34 community hospitals in the southeastern United States from January 2015 to June 2019. Logistic regression models identified specific characteristics of complex COLO SSIs, complex non-PATOS COLO SSIs, and complex PATOS COLO SSIs.

Over the 4.5-year study period, we identified 720 complex COLO SSIs following 28,188 COLO surgeries (prevalence rate, 2.55 per 100 procedures). Overall, 544 complex COLO SSIs (76%) were complex non-PATOS COLO SSIs (prevalence rate [PR], 1.93 per 100 procedures) and 176 (24%) complex PATOS COLO SSIs (PR, 0.62 per 100 procedures). Age >75 years and operation duration in the >75th percentile were independently associated with non-PATOS SSIs but not PATOS SSIs. Conversely, emergency surgery and hospital volume for COLO procedures were independently associated with PATOS SSIs but not non-PATOS SSIs. The proportion of polymicrobial SSIs was significantly higher for non-PATOS SSIs compared with PATOS SSIs.

Complex PATOS COLO SSIs have distinct features from complex non-PATOS COLO SSIs. Removal of PATOS COLO SSIs from public reporting allows more accurate comparisons among hospitals that perform different case mixes of colon surgeries.

Sparse recent data are available on the epidemiology of surgical site infections (SSIs) in community hospitals. Our objective was to provide updated epidemiology data on complex SSIs in community hospitals and to characterize trends of SSI prevalence rates over time.

Retrospective cohort study.

SSI data were collected from patients undergoing 26 commonly performed surgical procedures at 32 community hospitals in the southeastern United States from 2013 to 2018. SSI prevalence rates were calculated for each year and were stratified by procedure and causative pathogen.

Over the 6-year study period, 3,561 complex (deep incisional or organ-space) SSIs occurred following 669,467 total surgeries (prevalence rate, 0.53 infections per 100 procedures). The overall complex SSI prevalence rate did not change significantly during the study period: 0.58 of 100 procedures in 2013 versus 0.53 of 100 procedures in 2018 (prevalence rate ratio [PRR], 0.84; 95% CI, 0.66–1.08; P = .16). Methicillin-sensitive Staphylococcus aureus (MSSA) complex SSIs (n = 480, 13.5%) were more common than complex SSIs caused by methicillin-resistant S. aureus (MRSA; n = 363, 10.2%).

The complex SSI rate did not decrease in our cohort of community hospitals from 2013 to 2018, which is a change from prior comparisons. The reason for this stagnation is unclear. Additional research is needed to determine the proportion of or remaining SSIs that are preventable and what measures would be effective to further reduce SSI rates.

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.

Severe mental illness (SMI) is associated with increased stroke risk, but little is known about how SMI relates to stroke prognosis and receipt of acute care.

To determine the association between SMI and stroke outcomes and receipt of process-of-care quality indicators (such as timely admission to stroke unit).

We conducted a cohort study using routinely collected linked data-sets, including adults with a first hospital admission for stroke in Scotland during 1991–2014, with process-of-care quality indicator data available from 2010. We identified pre-existing schizophrenia, bipolar disorder and major depression from hospital records. We used logistic regression to evaluate 30-day, 1-year and 5-year mortality and receipt of process-of-care quality indicators by pre-existing SMI, adjusting for sociodemographic and clinical factors. We used Cox regression to evaluate further stroke and vascular events (stroke and myocardial infarction).

Among 228 699 patients who had had a stroke, 1186 (0.5%), 859 (0.4%), 7308 (3.2%) had schizophrenia, bipolar disorder and major depression, respectively. Overall, median follow-up was 2.6 years. Compared with adults without a record of mental illness, 30-day mortality was higher for schizophrenia (adjusted odds ratio (aOR) = 1.33, 95% CI 1.16–1.52), bipolar disorder (aOR = 1.37, 95% CI 1.18–1.60) and major depression (aOR = 1.11, 95% CI 1.05–1.18). Each disorder was also associated with marked increased risk of 1-year and 5-year mortality and further stroke and vascular events. There were no clear differences in receipt of process-of-care quality indicators.

Pre-existing SMI was associated with higher risks of mortality and further vascular events. Urgent action is needed to better understand and address the reasons for these disparities.

A novel paediatric disease, multi-system inflammatory syndrome in children, has emerged during the 2019 coronavirus disease pandemic.

To describe the short-term evolution of cardiac complications and associated risk factors in patients with multi-system inflammatory syndrome in children.

Retrospective single-centre study of confirmed multi-system inflammatory syndrome in children treated from 29 March, 2020 to 1 September, 2020. Cardiac complications during the acute phase were defined as decreased systolic function, coronary artery abnormalities, pericardial effusion, or mitral and/or tricuspid valve regurgitation. Patients with or without cardiac complications were compared with chi-square, Fisher’s exact, and Wilcoxon rank sum.

Thirty-nine children with median (interquartile range) age 7.8 (3.6–12.7) years were included. Nineteen (49%) patients developed cardiac complications including systolic dysfunction (33%), valvular regurgitation (31%), coronary artery abnormalities (18%), and pericardial effusion (5%). At the time of the most recent follow-up, at a median (interquartile range) of 49 (26–61) days, cardiac complications resolved in 16/19 (84%) patients. Two patients had persistent mild systolic dysfunction and one patient had persistent coronary artery abnormality. Children with cardiac complications were more likely to have higher N-terminal B-type natriuretic peptide (p = 0.01), higher white blood cell count (p = 0.01), higher neutrophil count (p = 0.02), severe lymphopenia (p = 0.05), use of milrinone (p = 0.03), and intensive care requirement (p = 0.04).

Patients with multi-system inflammatory syndrome in children had a high rate of cardiac complications in the acute phase, with associated inflammatory markers. Although cardiac complications resolved in 84% of patients, further long-term studies are needed to assess if the cardiac abnormalities (transient or persistent) are associated with major cardiac events.

There is a growing literature in support of the effectiveness of task-shared mental health interventions in resource-limited settings globally. However, despite evidence that effect sizes are greater in research studies than actual care, the literature is sparse on the impact of such interventions as delivered in routine care. In this paper, we examine the clinical outcomes of routine depression care in a task-shared mental health system established in rural Haiti by the international health care organization Partners In Health, in collaboration with the Haitian Ministry of Health, following the 2010 earthquake.

For patients seeking depression care betw|een January 2016 and December 2019, we conducted mixed-effects longitudinal regression to quantify the effect of depression visit dose on symptoms, incorporating interaction effects to examine the relationship between baseline severity and dose.

306 patients attended 2052 visits. Each visit was associated with an average reduction of 1.11 in depression score (range 0–39), controlling for sex, age, and days in treatment (95% CI −1.478 to −0.91; p < 0.001). Patients with more severe symptoms experienced greater improvement as a function of visits (p = 0.04). Psychotherapy was provided less frequently and medication more often than expected for patients with moderate symptoms.

Our findings support the potential positive impact of scaling up routine mental health services in low- and middle-income countries, despite greater than expected variability in service provision, as well as the importance of understanding potential barriers and facilitators to care as they occur in resource-limited settings.

The US National Institutes of Health (NIH) established the Clinical and Translational Science Award (CTSA) program in response to the challenges of translating biomedical and behavioral interventions from discovery to real-world use. To address the challenge of translating evidence-based interventions (EBIs) into practice, the field of implementation science has emerged as a distinct discipline. With the distinction between EBI effectiveness research and implementation research comes differences in study design and methodology, shifting focus from clinical outcomes to the systems that support adoption and delivery of EBIs with fidelity.

Implementation research designs share many of the foundational elements and assumptions of efficacy/effectiveness research. Designs and methods that are currently applied in implementation research include experimental, quasi-experimental, observational, hybrid effectiveness–implementation, simulation modeling, and configurational comparative methods.

Examples of specific research designs and methods illustrate their use in implementation science. We propose that the CTSA program takes advantage of the momentum of the field's capacity building in three ways: 1) integrate state-of-the-science implementation methods and designs into its existing body of research; 2) position itself at the forefront of advancing the science of implementation science by collaborating with other NIH institutes that share the goal of advancing implementation science; and 3) provide adequate training in implementation science.

As implementation methodologies mature, both implementation science and the CTSA program would greatly benefit from cross-fertilizing expertise and shared infrastructures that aim to advance healthcare in the USA and around the world.