Symptoms and cognition are both utilized as indicators of recovery following pediatric concussion, yet their interrelationship is not well understood. This study aimed to investigate: 1) the association of post-concussion symptom burden and cognitive outcomes (processing speed and executive functioning [EF]) at 4 and 12 weeks after pediatric concussion, and 2) the moderating effect of sex on this association.

This prospective, multicenter cohort study included participants aged 5.00–17.99 years with acute concussion presenting to four Emergency Departments of the Pediatric Emergency Research Canada network. Five processing speed and EF tasks and the Post-Concussion Symptom Inventory (PCSI; symptom burden, defined as the difference between post-injury and retrospective [pre-injury] scores) were administered at 4 and 12 weeks post-concussion. Generalized least squares models were conducted with task performances as dependent variables and PCSI and PCSI*sex interaction as the main predictors, with important pre-injury demographic and injury characteristics as covariates.

311 children (65.0% males; median age = 11.92 [IQR = 9.14–14.21 years]) were included in the analysis. After adjusting for covariates, higher symptom burden was associated with lower Backward Digit Span (χ2 = 9.85, p = .043) and Verbal Fluency scores (χ2 = 10.48, p = .033) across time points; these associations were not moderated by sex, ps ≥ .20. Symptom burden was not associated with performance on the Coding, Continuous Performance Test, and Color-Word Interference scores, ps ≥ .17.

Higher symptom burden is associated with lower working memory and cognitive flexibility following pediatric concussion, yet these associations were not moderated by sex. Findings may inform concussion management by emphasizing the importance of multifaceted assessments of EF.

Despite a well-established link between childhood traumatic brain injury (TBI) and elevated secondary attention-deficit/hyperactivity disorder (s-ADHD) symptomology, the neurostructural correlates of these symptoms are largely unknown. Based on the influential ‘triple-network model’ of ADHD, this prospective longitudinal investigation aimed to (i) assess the effect of childhood TBI on brain morphometry of higher-order cognitive networks proposed to play a key role in ADHD pathophysiology, including the default-mode network (DMN), salience network (SN) and central executive network (CEN); and (ii) assess the independent prognostic value of DMN, SN and CEN morphometry in predicting s-ADHD symptom severity after childhood TBI.

The study sample comprised 155 participants, including 112 children with medically confirmed mild-severe TBI ascertained from consecutive hospital admissions, and 43 typically developing (TD) children matched for age, sex and socio-economic status. High-resolution structural brain magnetic resonance imaging (MRI) sequences were acquired sub-acutely in a subset of 103 children with TBI and 34 TD children. Parents completed well-validated measures of ADHD symptom severity at 12-months post injury.

Relative to TD children and those with milder levels of TBI severity (mild, complicated mild, moderate), children with severe TBI showed altered brain morphometry within large-scale, higher-order cognitive networks, including significantly diminished grey matter volumes within the DMN, SN and CEN. When compared with the TD group, the TBI group showed significantly higher ADHD symptomatology and higher rates of clinically elevated symptoms. In multivariable models adjusted for other well-established risk factors, altered DMN morphometry independently predicted higher s-ADHD symptomatology at 12-months post-injury, whilst SN and CEN morphometry were not significant independent predictors.

Our prospective study findings suggest that neurostructural alterations within higher-order cognitive circuitry may represent a prospective risk factor for s-ADHD symptomatology at 12-months post-injury in children with TBI. High-resolution structural brain MRI has potential to provide early prognostic biomarkers that may help early identification of high-risk children with TBI who are likely to benefit from early surveillance and preventive measures to optimise long-term neuropsychiatric outcomes.

Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse.

This study aims to evaluate whether the Engager intervention improves mental health outcomes following release.

The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3–5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT).

In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI –1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact.

Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

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.

Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.

We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.

Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.

Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.