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.

People with mental disorders have worse physical health compared with the general population, which could be attributable to receiving poorer quality healthcare.

To examine the relationship between severe and common mental disorders and risk of emergency hospital admissions for ambulatory care sensitive conditions (ACSCs), and factors associated with increased risk.

Baseline data for England (N = 445 814) were taken from UK Biobank, which recruited participants aged 37–73 years during 2006–2010, and linked to hospital admission records up to 31 December 2019. Participants were grouped into those with a history of either schizophrenia, bipolar disorder, depression or anxiety, or no mental disorder. Survival analysis was used to assess the risk of hospital admission for ACSCs among those with mental disorders compared with those without, adjusting for factors in different domains (sociodemographic, socioeconomic, health and biomarkers, health-related behaviours, social isolation and psychological).

People with schizophrenia had the highest (unadjusted) risk of hospital admission for ACSCs compared with those with no mental disorder (hazard ratio 4.40, 95% CI 4.04–4.80). People with bipolar disorder (hazard ratio 2.48, 95% CI 2.28–2.69) and depression or anxiety (hazard ratio 1.76, 95% CI 1.73–1.80) also had higher risk. Associations were more conservative when including all admissions, as opposed to first admissions only. The observed associations persisted after adjusting for a range of factors.

People with severe mental disorders have the highest risk of preventable hospital admissions. Ensuring people with mental disorders receive adequate ambulatory care is essential to reduce the large health inequalities they experience.

To establish the epidemiology of cardiac implantable electronic device (CIED) infections in Alberta, Canada, using validated administrative data.

Retrospective, population-based cohort study.

Alberta Health Services is a province-wide health system that services all of Alberta, Canada.

Adult patients who underwent first-time CIED implantation or generator replacement in Alberta, Canada, between January 1, 2011, and December 31, 2019.

CIED implant patients were identified from the Paceart database. Patients who developed an infection within 1 year of the index procedure were identified through validated administrative data (International Classification of Diseases, Tenth Revision in Canada). Demographic characteristics of patients were summarized. Logistic regression models were used to analyze device type, comorbidities, and demographics associated with infection rates and mortality.

Among 27,830 CIED implants, there were 205 infections (0.74%). Having 2 or more comorbidities was associated with higher infection risk. Generator replacement procedures (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.34–0.84; P = .008), age increase of every 10 years (OR, 0.73; 95% CI, 0.66–0.82; P ≤ .001), and index procedure after 2014 were associated with decreased risk. Comparing the infected to uninfected groups, the hospitalization rates were 2.63 compared to 0.69, and the mortality rates were 10.73% compared to 3.49%, respectively (P < .001).

There is a slightly lower overall rate of CIED infections Alberta, Canada compared to previously described epidemiology. Implants after 2014, and generator replacements showed a decreased burden of infection. Patients with younger age, and 2 or more comorbidities are at greatest risk of CIED infection. The burden of hospitalization and mortality is substantially higher in infected patients.

The COVID-19 pandemic caused considerable burden on mental health worldwide. To address this emergency in Peru, Socios en Salud (SES) implemented an innovative digital system for the diagnosis and psychological therapy in vulnerable populations. We describe the development, implementation, and participant outcomes of this intervention.

We conducted an intervention in a general population of Lima, Peru using a digital tool, ChatBot-Juntos, incorporating the abbreviated Self-Reporting Questionnaire (SRQ) to screen psychological distress. Participants positive for psychological distress received remote Psychological First Aid (PFA) and grief therapy if needed. Participants with a mental health condition or safety concern were referred to mental health services. SRQ scores were collected 3 months after PFA sessions. Differences between screening and follow-up scores were compared using Wilcoxon sign-rank test.

In total, 2027 people were screened; 1581 (77.9%) screened positive for psychological distress. Nine hundred ninety-seven (63%) people with psychological distress received PFA, and 320 (32.1%) of those were also referred for mental health care. At 3 months after follow-up, SRQ scores were collected for 579 (58%) participants. Significant reduction in SRQ scores was observed 3 months after PFA [median SRQ score changed from 9 to 5 (p < 0.001)], and after PFA plus referral to mental health services [median SRQ score changed from 11 to 6 (p < 0.001)].

Digital technology can be used to screen for psychological distress and deliver mental health support for populations affected by the COVID-19 pandemic. More research is needed to determine whether technology contributes to improved mental health outcomes.

Subsidised or cost-offset community-supported agriculture (CO-CSA) connects farms directly to low-income households and can improve fruit and vegetable intake. This analysis identifies factors associated with participation in CO-CSA.

Farm Fresh Foods for Healthy Kids (F3HK) provided a half-price, summer CO-CSA plus healthy eating classes to low-income households with children. Community characteristics (population, socio-demographics and health statistics) and CO-CSA operational practices (share sizes, pick up sites, payment options and produce selection) are described and associations with participation levels are examined.

Ten communities in New York (NY), North Carolina (NC), Vermont and Washington states in USA.

Caregiver–child dyads enrolled in spring 2016 or 2017.

Residents of micropolitan communities had more education and less poverty than in small towns. The one rural location (NC2) had the fewest college graduates (10 %) and most poverty (23 %) and poor health statistics. Most F3HK participants were white, except in NC where 45·2 % were African American. CO-CSA participation varied significantly across communities from 33 % (NC2) to 89 % (NY1) of weeks picked up. Most CO-CSA farms offered multiple share sizes (69·2 %) and participation was higher than when not offered (76·8 % v. 57·7 % of weeks); whereas 53·8 % offered a community pick up location, and participation in these communities was lower than elsewhere (64·7 % v. 78·2 % of weeks).

CO-CSA programmes should consider offering a choice of share sizes and innovate to address potential barriers such as rural location and limited education and income among residents. Future research is needed to better understand barriers to participation, particularly among participants utilising community pick up locations.

Ensuring equitable access to health care is a widely agreed-upon goal in medicine, yet access to care is a multidimensional concept that is difficult to measure. Although frameworks exist to evaluate access to care generally, the concept of “access to genomic medicine” is largely unexplored and a clear framework for studying and addressing major dimensions is lacking.

Comprised of seven clinical genomic research projects, the Clinical Sequencing Evidence-Generating Research consortium (CSER) presented opportunities to examine access to genomic medicine across diverse contexts. CSER emphasized engaging historically underrepresented and/or underserved populations. We used descriptive analysis of CSER participant survey data and qualitative case studies to explore anticipated and encountered access barriers and interventions to address them.

CSER’s enrolled population was largely lower income and racially and ethnically diverse, with many Spanish-preferring individuals. In surveys, less than a fifth (18.7%) of participants reported experiencing barriers to care. However, CSER project case studies revealed a more nuanced picture that highlighted the blurred boundary between access to genomic research and clinical care. Drawing on insights from CSER, we build on an existing framework to characterize the concept and dimensions of access to genomic medicine along with associated measures and improvement strategies.

Our findings support adopting a broad conceptualization of access to care encompassing multiple dimensions, using mixed methods to study access issues, and investing in innovative improvement strategies. This conceptualization may inform clinical translation of other cutting-edge technologies and contribute to the promotion of equitable, effective, and efficient access to genomic medicine.

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.

To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission.

This cohort study was conducted during March 22–May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California.

Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription–polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.

Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages.

Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.

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.

The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia.

As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years.

Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status.

Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.

To evaluate the validity and reproducibility of a 152-item semi-quantitative FFQ (SFFQ) for estimating flavonoid intakes.

Over a 1-year period, participants completed two SFFQ and two weighed 7-d dietary records (7DDR). Flavonoid intakes from the SFFQ were estimated separately using Harvard (SFFQHarvard) and Phenol-Explorer (SFFQPE) food composition databases. 7DDR flavonoid intakes were derived using the Phenol-Explorer database (7DDRPE). Validity was assessed using Spearman’s rank correlation coefficients deattenuated for random measurement error (r s ), and reproducibility was assessed using rank intraclass correlation coefficients.

This validation study included primarily participants from two large observational cohort studies.

Six hundred forty-one men and 724 women.

When compared with two 7DDRPE, the validity of total flavonoid intake assessed by SFFQPE was high for both men and women (r s = 0·77 and r s = 0·74, respectively). The r s for flavonoid subclasses ranged from 0·47 for flavones to 0·78 for anthocyanins in men and from 0·46 for flavonols to 0·77 for anthocyanins in women. We observed similarly moderate (0·4–0·7) to high (≥0·7) validity when using SFFQHarvard estimates, except for flavonesHarvard (r s = 0·25 for men and r s = 0·19 for women). The SFFQ demonstrated high reproducibility for total flavonoid and flavonoid subclass intake estimates when using either food composition database. The intraclass correlation coefficients ranged from 0·69 (flavonolsPE) to 0·80 (proanthocyanidinsPE) in men and from 0·67 (flavonolsPE) to 0·77 (flavan-3-ol monomersHarvard) in women.

SFFQ-derived intakes of total flavonoids and flavonoid subclasses (except for flavones) are valid and reproducible for both men and women.

Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population.

The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials.

The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner.

Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients.