Most antidepressants do not independently treat impaired cognition associated with major depressive disorder (MDD). Elevated brain cortisol levels are associated with both MDD and cognitive impairment. Emestedastat is a brain-penetrant, intracellular cortisol synthesis inhibitor.

The XanaCIDD trial aimed to determine whether emestedastat 10 mg could improve both cognitive impairment and depression in a population with persistent MDD and cognitive impairment.

Participants had a diagnosis of MDD, with persistent depression (Hamilton Rating Scale for Depression-17 ≥17) and cognitive impairment (coding test ≤0.5 s.d. of normal). Randomised treatment (1:1) was continued for 6 weeks (week 6), with 4 weeks’ blinded follow-up (week 10). The primary end-point was cognition (composite of attention/working memory) at week 6. Depression end-points included Montgomery–Åsberg Depression Rating Scale (MADRS) and Patient Global Impression of Severity (PGI-S). Analyses used a mixed model for repeated measures (cognitive impairment and MADRS one-sided tests, others two-sided) and Cohen’s d effect size. No adjustments were made for multiple comparisons.

A total of 165 participants were enrolled and treated: 134 (81%) were on background antidepressants, 62% were female, mean prior number of MDD episodes was 10 and mean coding z-score was −1.47. There was no benefit on the primary cognitive end-point at week 6 (p = 0.17 favouring placebo), with the cognitive composite improving markedly in both groups without correlation to depressive symptoms or baseline characteristics (R2 ≤ 0.02). The trend towards benefit on the prespecified secondary depression end-point, MADRS, began at week 6 and was maximal at week 10 (2.7 points, Cohen’s d 0.43, p = 0.05). A trend towards potential emestedastat benefit in PGI-S scores was also maximal at week 10 (p = 0.12). Mild–moderate transaminase elevations were seen in 10% of emestedastat participants (≤2 times normal in 7 of 8 cases, 1 discontinuation) versus 1% of the placebo group.

There was no benefit of emestedastat on the primary end-point of cognitive impairment and a large placebo effect, without correlation of cognitive impairment to depression changes or baseline characteristics. Trends towards potential antidepressant activity suggest that emestedastat may be a novel antidepressant worthy of further investigation.

Autistic people are at an elevated risk of premature mortality; however, few studies have identified factors that explain this association. Co-occurring psychiatric conditions are a strong candidate, given that autistic people are at a high risk of such conditions and these conditions are broadly associated with premature mortality.

We aimed to investigate the degree to which co-occurring psychiatric conditions are associated with premature mortality in autistic people. We explored these associations across sex and co-occurring other neurodevelopmental conditions.

We conducted a cohort study based on registry linkage. We identified 2 958 317 individuals born in Sweden from 1974 to 2004, including 70 546 (2.38%) individuals with an autism diagnosis. We identified diagnoses of 13 psychiatric conditions. The cohort was followed up from age 16 to age 46 at the oldest. We compared the risk of mortality (from all-causes, suicide, other external causes and natural causes) across autistic people with psychiatric conditions and (a) non-autistic people without psychiatric diagnoses; (b) autistic people without psychiatric diagnoses; and (c) non-autistic people with psychiatric diagnoses. We conducted separate analyses by sex and co-occurring neurodevelopmental conditions.

The mortality rate in autistic people with psychiatric conditions was 3.2 deaths per 1000 person-years, which was higher than that observed in non-autistic (0.27 deaths per 1000 person-years) and autistic people without psychiatric conditions (0.96 deaths per 1000 person-years). The relative risk of premature mortality was higher in autistic people with psychiatric conditions compared with both non-autistic (hazard ratio 13.85, 12.86–14.91) and autistic people (hazard ratio 3.44, 2.94–4.02) without psychiatric conditions and also exceeded the risk of premature mortality in individuals with psychiatric conditions alone (hazard ratio 1.47, 1.37–1.58). Similar patterns emerged across sex, intellectual disability and attention-deficit hyperactivity disorder.

Co-occurring psychiatric conditions are a risk factor for premature mortality in autistic people. Timely detection and treatment of such conditions in autistic people may facilitate healthier, lengthier lives for autistic people.

Although workplace mental health screening is often implemented to aid early identification of mental health symptoms and facilitate access to treatment, supporting evidence is limited.

We aimed to evaluate the effect of independently conducted, confidential, online mental health screening, paired with automated tailored feedback recommending referral services, on help-seeking and psychological distress.

We conducted a cluster-randomised controlled trial with firefighters from an Australian fire and rescue service. Randomisation occurred by station (N = 264). Firefighters at stations allocated to the intervention group received tailored information detailing suitable mental health services based on their Kessler-6 psychological distress score (K6). The control group received generic feedback on services irrespective of K6 score. The primary outcome was help-seeking at 3-months post-intervention for those with at least moderate levels of psychological distress at baseline (K6 ≥14). The study was registered with Australian New Zealand Clinical Trials Registry (no. ANZCTR 12621001457831).

Of the 459 firefighters screened, 141 (30.72%) scored ≥14 on K6. Among this subgroup at 3 months, no differences were observed in rates of overall help-seeking between the intervention and control groups (P = 0.31). In contrast, levels of psychological distress remained high in the intervention group but declined in the control group (t[111] = 2.29, 95% CI: 0.24, 3.23, P = 0.024). The difference in psychological distress associated with workplace mental health screening equated to an effect size of −0.42 (95% CI: −0.04, −0.79).

Our findings suggest that independent, confidential online mental health screening, paired with tailored online feedback and information on available treatment, does not significantly increase help-seeking and may sustain psychological distress over time compared with receiving generic information. As such, it should not be implemented to promote help-seeking and reduce levels of psychological distress. These findings are relevant for workplaces, mental health researchers and practitioners alike, highlighting the potential risk and potential harm of mental health screening conducted in this way on individuals.

While evidence-based clinical practice guidelines promote high-quality care, their absence may create unwarranted variation in disease management, leading to suboptimal outcomes. This study aimed to identify existing clinical practice guidelines for tardive dyskinesia (TD) in France, Germany, Italy, Spain, and the United Kingdom (EU4+UK), assessing the evidence for recommended TD treatments.

MEDLINE, PubMed, and other sources (e.g., government/public agencies, associations, patient/research organizations) were searched to identify clinical practice guidelines for TD published between January 2000 and February 2025 in EU4+UK. Mentions of TD treatments in identified documents were classified as “recommendations” or “descriptions.” Recommendations were ranked according to the Scottish Intercollegiate Guidelines Network grading system or received a “no-rank” label. Subanalyses on tetrabenazine and tiapride, were performed.

Of the 31 documents identified, only two were TD-specific, with the remainder primarily developed for schizophrenia, major depressive disorder, and bipolar disorder. Data extraction led to 112 mentions of TD treatments (40 recommendations, 72 descriptions). Most recommendations focused on antipsychotic regimen modification (75%) and had no rank (88%). Only five recommendations (no rank) proposed a pharmaceutical (add-on) treatment: three for tetrabenazine and one each for amantadine and buspirone. Neither of the TD-specific guidelines contained TD treatment recommendations.

No specific clinical practice guidelines for TD in EU4 + UK were found, although TD management was mentioned in guidelines for other disorders. Most recommendations were not supported by high-quality evidence. To improve quality of care for patients with TD in Europe, updated treatment recommendations are needed based on high-quality studies.

Load balancing of constrained healthcare resources has become a critical aspect of assuring access to care during periods of pandemic related surge. These impacts include patient surges, staffing shortages, and limited access to specialty resources. This research focuses on the creation and work of a novel statewide coordination center, the Washington Medical Coordination Center (WMCC), whose primary goal is the load balancing of patients across the healthcare continuum of Washington State.

This article discusses the origins, development, and operations of the WMCC including key partners, cooperative agreements, and structure necessary to create a patient load balancing system on a statewide level.

As of April 21, 2022, the WMCC received 3821 requests from Washington State hospitals. Nearly 90% were received during the pandemic surge. Nearly 75% originated from rural hospitals that are most often limited in their ability to transfer patients when referral centers are also overwhelmed.

The WMCC served as an effective tool to carry out patient load balancing activities during the COVID-19 pandemic surge in Washington State. It (the WMCC) has been shown to be an equity enhancing, cost effective means of managing healthcare surge events across a broad geographic region.

Non-penetrating head and neck trauma is associated with extracranial traumatic vertebral artery injury (eTVAI) in approximately 1–2% of cases. Most patients are initially asymptomatic but have an increased risk for delayed stroke and mortality. Limited evidence is available to guide the management of asymptomatic eTVAI. As such, we sought to investigate national practice patterns regarding screening, treatment, and follow-up domains.

A cross-sectional, electronic survey was distributed to members of the Canadian Neurosurgical Society and Canadian Spine Society. We presented two cases of asymptomatic eTVAI, stratified by injury mechanism, fracture type, and angiographic findings. Screening questions were answered prior to presentation of angiographic findings. Survey responses were analyzed using descriptive statistics.

One hundred-eight of 232 (46%) participants, representing 20 academic institutions, completed the survey. Case 1: 78% of respondents would screen for eTVAI with computed topography angiography (CTA) (97%), immediately (88%). The majority of respondents (97%) would treat with aspirin (89%) for 3–6 months (46%). Respondents would follow up clinically (89%) or radiographically (75%), every 1–3 months. Case 2: 73% of respondents would screen with CTA (96%), immediately (88%). Most respondents (94%) would treat with aspirin (50%) for 3–6 months (35%). Thirty-six percent of respondents would utilize endovascular therapy. Respondents would follow up clinically (97%) or radiographically (89%), every 1–3 months.

This survey of Canadian practice patterns highlights consistency in the approach to screening, treatment, and follow-up of asymptomatic eTVAI. These findings are relevant to neurosurgeons, spinal surgeons, stroke neurologists, and neuro-interventionalists.

There is some evidence that autism spectrum disorder (ASD) frequently co-occurs with immune-mediated conditions including asthma. We aimed to explore the familial co-aggregation of ASD and asthma using different genetically informed designs.

We first examined familial co-aggregation of asthma and ASD in individuals born in Sweden from 1992 to 2007 (n = 1 569 944), including their full- and half-siblings (n = 1 704 388 and 356 544 pairs) and full cousins (n = 3 921 890 pairs), identified using Swedish register data. We then applied quantitative genetic modeling to siblings (n = 620 994 pairs) and twins who participated in the Child and Adolescent Twin Study in Sweden (n = 15 963 pairs) to estimate the contribution of genetic and environmental factors to the co-aggregation. Finally, we estimated genetic correlations between traits using linkage disequilibrium score regression (LDSC).

We observed a within-individual association [adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.28–1.37] and familial co-aggregation between asthma and ASD, and the magnitude of the associations decreased as the degree of relatedness decreased (full-siblings: OR 1.44, 95% CI 1.38–1.50, maternal half-siblings: OR 1.28, 95% CI 1.18–1.39, paternal half-siblings: OR 1.05, 95% CI 0.96–1.15, full cousins: OR 1.06, 95% CI 1.03–1.09), suggesting shared familial liability. Quantitative genetic models estimated statistically significant genetic correlations between ASD traits and asthma. Using the LDSC approach, we did not find statistically significant genetic correlations between asthma and ASD (coefficients between −0.09 and 0.12).

Using different genetically informed designs, we found some evidence of familial co-aggregation between asthma and ASD, suggesting the weak association between these disorders was influenced by shared genetics.

Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.

This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.

We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.

For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.

We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

There is evidence that autism spectrum disorders (ASDs) co-occur with bipolar disorder (BD) relatively frequently. Individuals with BD often report symptoms of mania and hypomania during adolescence, prior to the age of onset for BD. It is unknown whether these symptoms are associated with ASDs. We examined whether diagnoses of ASDs and autistic traits were associated with hypomania in a large, population-based Swedish twin sample.

Parental structured interviews assessed autistic traits, and were used to assign screening diagnoses of ASDs, when twins were aged 9 or 12 (N = 13 533 pairs). Parents then completed questionnaires assessing hypomania when the twins were aged 15 and 18 (N = 3852 pairs at age 15, and 3013 pairs at age 18). After investigating the phenotypic associations between these measures, we used the classical twin design to test whether genetic and environmental influences on autistic traits influence variation in adolescent hypomania.

Autistic traits and ASD diagnoses in childhood were associated with elevated scores on the measures of adolescent hypomania. Twin analyses indicated that 6–9% of the variance in hypomania was explained by genetic influences that were shared with autistic traits in childhood. When repeating these analyses for specific autistic trait domains, we found a stronger association between social interaction difficulties and hypomania than for other autistic trait domains.

These results indicate a genetic link between autistic traits and hypomania in adolescence. This adds to the growing evidence base of genetic factors associated with ASDs showing links with psychiatric outcomes across childhood and into adulthood.

Many psychiatric disorders show gender differences in prevalence. Recent studies suggest that female patients diagnosed with anxiety and depression carry more genetic risks related to attention-deficit hyperactivity disorder (ADHD) compared with affected males.

In this register-based study, we aimed to test whether female patients who received clinical diagnoses of anxiety, depressive, bipolar and eating disorders are at higher familial risk for ADHD and other neurodevelopmental disorders, compared with diagnosed male patients.

We analysed data from a record-linkage of several Swedish national registers, including 151 025 sibling pairs from 103 941 unique index individuals diagnosed with anxiety, depressive, bipolar or eating disorders, as well as data from 646 948 cousin pairs. We compared the likelihood of having a relative diagnosed with ADHD/neurodevelopmental disorders in index males and females.

Female patients with anxiety disorders were more likely than affected males to have a brother with ADHD (odd ratio (OR) = 1.13, 95% CI 1.05–1.22). Results for broader neurodevelopmental disorders were similar and were driven by ADHD diagnoses. Follow-up analyses revealed similar point estimates for several categories of anxiety disorders, with the strongest effect observed for agoraphobia (OR = 1.64, 95% CI 1.12–2.39). No significant associations were found in individuals with depressive, bipolar or eating disorders, or in cousins.

These results provide modest support for the possibility that familial/genetic risks for ADHD may show gender-specific phenotypic expression. Alternatively, there could be gender-specific biases in diagnoses of anxiety and ADHD. These factors could play a small role in the observed gender differences in prevalence of ADHD and anxiety.

The updated common rule, for human subjects research, requires that consents “begin with a ‘concise and focused’ presentation of the key information that will most likely help someone make a decision about whether to participate in a study” (Menikoff, Kaneshiro, Pritchard. The New England Journal of Medicine. 2017; 376(7): 613–615.). We utilized a community-engaged technology development approach to inform feature options within the REDCap software platform centered around collection and storage of electronic consent (eConsent) to address issues of transparency, clinical trial efficiency, and regulatory compliance for informed consent (Harris, et al. Journal of Biomedical Informatics 2009; 42(2): 377–381.). eConsent may also improve recruitment and retention in clinical research studies by addressing: (1) barriers for accessing rural populations by facilitating remote consent and (2) cultural and literacy barriers by including optional explanatory material (e.g., defining terms by hovering over them with the cursor) or the choice of displaying different videos/images based on participant’s race, ethnicity, or educational level (Phillippi, et al. Journal of Obstetric, Gynecologic, & Neonatal Nursing. 2018; 47(4): 529–534.).

We developed and pilot tested our eConsent framework to provide a personalized consent experience whereby users are guided through a consent document that utilizes avatars, contextual glossary information supplements, and videos, to facilitate communication of information.

The eConsent framework includes a portfolio of eight features, reviewed by community stakeholders, and tested at two academic medical centers.

Early adoption and utilization of this eConsent framework have demonstrated acceptability. Next steps will emphasize testing efficacy of features to improve participant engagement with the consent process.

Accumulating evidence suggests that many psychiatric disorders etiologically represent the extreme end of dimensionally distributed features rather than distinct entities. The extent to which this applies to eating disorders (EDs) is unknown.

We investigated if there is similar etiology in (a) the continuous distribution of the Eating Disorder Inventory-2 (EDI-2), (b) the extremes of EDI-2 score, and (c) registered ED diagnoses, in 1481 female twin pairs at age 18 years (born 1992–1999). EDI-2 scores were self-reported at age 18. ED diagnoses were identified through the Swedish National Patient Register, parent-reported treatment and/or self-reported purging behavior of a frequency and duration consistent with DSM-IV criteria. We differentiated between anorexia nervosa (AN) and other EDs.

The heritability of the EDI-2 score was 0.65 (95% CI 0.61–0.68). The group heritabilities in DeFries–Fulker extremes analyses were consistent over different percentile-based extreme groups [0.59 (95% CI 0.37–0.81) to 0.65 (95% CI 0.55–0.75)]. Similarly, the heritabilities in liability threshold models were consistent over different levels of severity. In joint categorical-continuous models, the twin-based genetic correlation was 0.52 (95% CI 0.39–0.65) between EDI-2 score and diagnoses of other EDs, and 0.26 (95% CI 0.08–0.42) between EDI-2 score and diagnoses of AN. The non-shared environmental correlations were 0.52 (95% CI 0.32–0.70) and 0.60 (95% CI 0.38–0.79), respectively.

Our findings suggest that some EDs can partly be conceptualized as the extreme manifestation of continuously distributed ED features. AN, however, might be more distinctly genetically demarcated from ED features in the general population than other EDs.

Performing an extended Focused Assessment with Sonography in Trauma (eFAST) exam is common practice in the initial assessment of trauma patients. The objective of this study was to systematically review the published literature on diagnostic accuracy of all components of the eFAST exam.

We searched Medline and Embase from inception through October 2018, for diagnostic studies examining the sensitivity and specificity of the eFAST exam. After removal of duplicates, 767 records remained for screening, of which 119 underwent full text review. Meta-DiSc™ software was used to create pooled sensitivities and specificities for included studies. Study quality was assessed using the Quality in Prognostic Studies (QUADAS-2) tool.

Seventy-five studies representing 24,350 patients satisfied our selection criteria. Studies were published between 1989 and 2017. Pooled sensitivities and specificities were calculated for the detection of pneumothorax (69% and 99% respectively), pericardial effusion (91% and 94% respectively), and intra-abdominal free fluid (74% and 98% respectively). Sub-group analysis was completed for detection of intra-abdominal free fluid in hypotensive (sensitivity 74% and specificity 95%), adult normotensive (sensitivity 76% and specificity 98%) and pediatric patients (sensitivity 71% and specificity 95%).

Our systematic review and meta-analysis suggests that e-FAST is a useful bedside tool for ruling in pneumothorax, pericardial effusion, and intra-abdominal free fluid in the trauma setting. Its usefulness as a rule-out tool is not supported by these results.

Traits of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are strongly associated in children and adolescents, largely due to genetic factors. Less is known about the phenotypic and aetiological overlap between ADHD and ASD traits in adults.

We studied 6866 individuals aged 20–28 years from the Swedish Study of Young Adult Twins. Inattention (IA) and hyperactivity/impulsivity (HI) were assessed using the WHO Adult ADHD Self-Report Scale-V1.1. Repetitive and restricted behaviours (RRB) and social interaction and communication (SIC) were assessed using the Autism-Tics, ADHD, and other Comorbidities inventory. We used structural equation modelling to decompose covariance between these ADHD and ASD trait dimensions into genetic and shared/non-shared environmental components.

At the phenotypic level, IA was similarly correlated with RRB (r = 0.33; 95% Confidence Interval (CI) 0.31–0.36) and with SIC (r = 0.32; 95% CI 0.29–0.34), whereas HI was more strongly associated with RRB (r = 0.38; 95% CI 0.35–0.40) than with SIC (r = 0.24; 95% CI 0.21–0.26). Genetic and non-shared environmental effects accounted for similar proportions of the phenotypic correlations, whereas shared environmental effects were of minimal importance. The highest genetic correlation was between HI and RRB (r = 0.56; 95% 0.46–0.65), and the lowest was between HI and SIC (r = 0.33; 95% CI 0.23–0.43).

We found evidence for dimension-specific phenotypic and aetiological overlap between ADHD and ASD traits in adults. Future studies investigating mechanisms underlying comorbidity between ADHD and ASD may benefit from exploring several symptom-dimensions, rather than considering only broad diagnostic categories.