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.

In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.

A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.

We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.

The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.

Social determinants of health (SDOH) are an important contributor to health status and health outcomes. In this analysis, we compare SDOH measured both at the individual and population levels in patients with high comorbidity who receive primary care at Federally Qualified Health Centers in New York and Chicago and enrolled in the Tipping Points trial.

We analyzed individual- and population-level measures of SDOH in 1,488 patients with high comorbidity (Charlson Comorbidity Index ≥ 4) enrolled in Tipping Points. At the individual level, we used a standardized patient-reported questionnaire. At the population level, we employed patient addresses to calculate the Social Deprivation Index (SDI) and Area Deprivation Index. Multivariable regressions were conducted in addition to qualitative feedback from stakeholders.

Individual-level SDOH are distinct from population-level measures. Significant component predictors of population SDI are being unhoused, unable to pay for utilities, and difficulty accessing medical transportation. Qualitative findings mirrored these results. High comorbidity patients report significant SDOH challenges at the individual level. Fitting a binomial generalized linear model, the comorbidity score is significantly predicted by the composite individual SDOH index (p < 0.0001) controlling for age and race/ethnicity.

Individual- and population-level SDOH measures provide different risk assessments. The use of community-level SDI data is informative in the aggregate but should not be used to identify patients with individual unmet social needs. Health systems should implement a standardized individualized assessment of unmet SDOH needs and build strong, enduring partnerships with community-based organizations that can provide those services.

Develop and implement a system in the Veterans Health Administration (VA) to alert local medical center personnel in real time when an acute- or long-term care patient/resident is admitted to their facility with a history of colonization or infection with a multidrug-resistant organism (MDRO) previously identified at any VA facility across the nation.

An algorithm was developed to extract clinical microbiology and local facility census data from the VA Corporate Data Warehouse initially targeting carbapenem-resistant Enterobacterales (CRE) and methicillin-resistant Staphylococcus aureus (MRSA). The algorithm was validated with chart review of CRE cases from 2010-2018, trialed and refined in 24 VA healthcare systems over two years, expanded to other MDROs and implemented nationwide on 4/2022 as “VA Bug Alert” (VABA). Use through 8/2023 was assessed.

VABA performed well for CRE with recall of 96.3%, precision of 99.8%, and F1 score of 98.0%. At the 24 trial sites, feedback was recorded for 1,011 admissions with a history of CRE (130), MRSA (814), or both (67). Among Infection Preventionists and MDRO Prevention Coordinators, 338 (33%) reported being previously unaware of the information, and of these, 271 (80%) reported they would not have otherwise known this information. By fourteen months after nationwide implementation, 113/130 (87%) VA healthcare systems had at least one VABA subscriber.

A national system for alerting facilities in real-time of patients admitted with an MDRO history was successfully developed and implemented in VA. Next steps include understanding facilitators and barriers to use and coordination with non-VA facilities nationwide.

We summarize some of the past year's most important findings within climate change-related research. New research has improved our understanding about the remaining options to achieve the Paris Agreement goals, through overcoming political barriers to carbon pricing, taking into account non-CO2 factors, a well-designed implementation of demand-side and nature-based solutions, resilience building of ecosystems and the recognition that climate change mitigation costs can be justified by benefits to the health of humans and nature alone. We consider new insights about what to expect if we fail to include a new dimension of fire extremes and the prospect of cascading climate tipping elements.

A synthesis is made of 10 topics within climate research, where there have been significant advances since January 2020. The insights are based on input from an international open call with broad disciplinary scope. Findings include: (1) the options to still keep global warming below 1.5 °C; (2) the impact of non-CO2 factors in global warming; (3) a new dimension of fire extremes forced by climate change; (4) the increasing pressure on interconnected climate tipping elements; (5) the dimensions of climate justice; (6) political challenges impeding the effectiveness of carbon pricing; (7) demand-side solutions as vehicles of climate mitigation; (8) the potentials and caveats of nature-based solutions; (9) how building resilience of marine ecosystems is possible; and (10) that the costs of climate change mitigation policies can be more than justified by the benefits to the health of humans and nature.

How do we limit global warming to 1.5 °C and why is it crucial? See highlights of latest climate science.

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.

Urothelial carcinoma (UCC) develops in both humans and dogs and tracks to regions of high industrial activity. We hypothesize that dogs with UCC may act as sentinels for human urothelial carcinogen exposures. The aim of this pilot study was to determine whether healthy people and dogs in the same households share urinary exposures to potentially mutagenic chemical carcinogens.

We measured urinary concentrations of acrolein (as its metabolite 3-HPMA), arsenic species, 4-aminobiphenyl, and 4-chlorophenol (a metabolite of the phenoxyherbicide 2,4-D) in healthy dogs and their owners. We assessed possible chemical sources through questionnaires and screened for urothelial DNA damage using the micronucleus assay.

Biomarkers of urinary exposure to acrolein, arsenic, and 4-chlorophenol were found in the urine of 42 pet dogs and 42 owners, with 4-aminobiphenyl detected sporadically. Creatinine-adjusted urinary chemical concentrations were significantly higher, by 2.8- to 6.2-fold, in dogs compared to humans. Correlations were found for 3-HPMA (r = 0.32, P = 0.04) and monomethylarsonic acid (r = 0.37, P = 0.02) between people and their dogs. Voided urothelial cell yields were inadequate to quantify DNA damage, and questionnaires did not reveal significant associations with urinary chemical concentrations.

Healthy humans and pet dogs have shared urinary exposures to known mutagenic chemicals, with significantly higher levels in dogs. Higher urinary exposures to acrolein and arsenic in dogs correlate to higher exposures in their owners. Follow-up studies will assess the mutagenic potential of these levels in vitro and measure these biomarkers in owners of dogs with UCC.

To sustainably improve cleaning of high-touch surfaces (HTSs) in acute-care hospitals using a multimodal approach to education, reduction of barriers to cleaning, and culture change for environmental services workers.

Prospective, quasi-experimental, before-and-after intervention study.

The study was conducted in 2 academic acute-care hospitals, 2 community hospitals, and an academic pediatric and women’s hospital.

Frontline environmental services workers.

A 5-module educational program, using principles of adult learning theory, was developed and presented to environmental services workers. Audience response system (ARS), videos, demonstrations, role playing, and graphics were used to illustrate concepts of and the rationale for infection prevention strategies. Topics included hand hygiene, isolation precautions, personal protective equipment (PPE), cleaning protocols, and strategies to overcome barriers. Program evaluation included ARS questions, written evaluations, and objective assessments of occupied patient room cleaning. Changes in hospital-onset C. difficile infection (CDI) and methicillin-resistant S. aureus (MRSA) bacteremia were evaluated.

On average, 357 environmental service workers participated in each module. Most (93%) rated the presentations as ‘excellent’ or ‘very good’ and agreed that they were useful (95%), reported that they were more comfortable donning/doffing PPE (91%) and performing hand hygiene (96%) and better understood the importance of disinfecting HTSs (96%) after the program. The frequency of cleaning individual HTSs in occupied rooms increased from 26% to 62% (P < .001) following the intervention. Improvement was sustained 1-year post intervention (P < .001). A significant decrease in CDI was associated with the program.

A novel program that addressed environmental services workers’ knowledge gaps, challenges, and barriers was well received and appeared to result in learning, behavior change, and sustained improvements in cleaning.

Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.

Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.

CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.

Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.

Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined.

To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive.

Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy.

Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four.

A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery.

None.