Acute stroke treatments are highly time-sensitive, with geographical disparities affecting access to care. This study examined the impact of driving distance to the nearest comprehensive stroke center (CSC) and rurality on the use of thrombectomy or thrombolysis in Ontario, Canada.

This retrospective cohort study used administrative data to identify adults hospitalized with acute ischemic stroke between 2017 and 2022. Driving time from patients’ residences to the nearest CSC was calculated using the Ontario Road Network File and postal codes. Rurality was categorized using postal codes. Multivariable logistic regression, adjusted for baseline differences, estimated the association between driving distance and treatment with thrombectomy (primary outcome) or thrombolysis (secondary outcome). Driving time was modeled as a continuous variable using restricted cubic splines.

Data from 57,678 patients (median age 74 years, IQR 64–83) were analyzed. Increased driving time was negatively associated with thrombectomy in a nonlinear fashion. Patients living 120 minutes from a CSC were 20% less likely to receive thrombectomy (adjusted odds ratio [aOR] 0.80, 95% CI 0.62–1.04), and those 240 minutes away were 60% less likely (aOR 0.41, 95% CI 0.28–0.60). Driving time did not affect thrombolysis rates, even at 240 minutes (aOR 1.0, 95% CI 0.70–1.42). Thrombectomy use was similar in medium urban areas (aOR 0.80, 95% CI 0.56–1.16) and small towns (aOR 0.78, 95% CI 0.57–1.06) compared to large urban areas.

Thrombolysis access is equitable across Ontario, but thrombectomy access decreases with increased driving distance to CSCs. A multifaceted approach, combining healthcare policy innovation and infrastructure development, is necessary for equitable thrombectomy delivery.

Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a ‘next-step’. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted.

The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored.

Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to ‘next-step’ treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI.

SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

Trait dissociation has not been examined from a structural human brain mapping perspective in healthy adults or children. Non-pathological dissociation shares some features with daydreaming and mind-wandering, but also involves subtle disruptions in affect and autobiographical memory.

To identify neurostructural biomarkers of trait dissociation in healthy children.

Typically developing 9- to 15-year-olds (n = 180) without psychological or behavioural disorders were enrolled in the Developmental Chronnecto-Genomics (DevCoG) study of healthy brain development and completed psychological assessments of trauma exposure and dissociation, along with a structural T1-weighted magnetic resonance imaging. We conducted univariate ANCOVA generalised linear models for each region of the default mode network examining the effects of trait dissociation, including scanner site, age, gender and trauma as covariates and correcting for multiple comparison.

We found that the precuneus was significantly larger in children with higher levels of trait dissociation but this was not related to trauma exposure. The inferior parietal volume was smaller in children with higher levels of trauma but was not related to dissociation. No other regions of interest, including frontal and limbic structures, were significantly related to trait dissociation even before multiple comparison correction.

Trait dissociation reflects subtle cognitive disruptions worthy of study in healthy people and warrants study as a potential risk factor for psychopathology. This neurostructural study of trait dissociation in healthy children identified the precuneus as an essential brain region to consider in future dissociation research.

A combination of olanzapine and samidorphan (OLZ/SAM) that provides the efficacy of olanzapine while mitigating weight gain was recently approved by the FDA for the treatment of schizophrenia and bipolar I disorder. To improve communication of the OLZ/SAM benefit-risk profile, a structured framework was utilized.

The Benefit-Risk Action Team framework was used to evaluate OLZ/SAM, with analyses completed for each pivotal study. ENLIGHTEN-1 evaluated antipsychotic efficacy and safety. ENLIGHTEN-2 evaluated the weight profile of OLZ/SAM vs olanzapine. Benefit-risk outcomes were selected based on study outcome parameters, known risks of olanzapine and samidorphan, and public health importance. A subset of opioid antagonist risks was not assessed due to clinical trial exclusions; however, they were factored into the overall evaluation. Risk differences and confidence intervals were analyzed.

In ENLIGHTEN-1, OLZ/SAM had a lower risk of psychiatric discontinuation and nonresponse to treatment compared with placebo; higher risks of hyperprolactinemia, weight gain (≥7%), sedation, and worsening of fasting triglycerides and glucose, and no difference for fasting total and LDL cholesterol, neutropenia, orthostatic hypotension, and movement disorders. In ENLIGHTEN-2, OLZ/SAM had reduced risks of weight gain and waist circumference increase compared to olanzapine along with similar risks of relapse and psychiatric discontinuation and no difference in metabolic worsening, neutropenia, hyperprolactinemia, orthostatic hypotension, sedation, and movement disorders.

Based on this assessment, OLZ/SAM has comparable efficacy and a safety profile consistent with olanzapine, with reduced weight gain. A structured approach to assessing the benefit-risk profile of a product facilitates transparent evaluation and communication.

Alkermes, Inc.

Patients with single ventricle heart disease are living into adulthood due to medical and surgical advancements but have significant physical comorbidities and an increased risk for psychological comorbidities compared to healthy subjects or those with other CHD diagnoses. This study aimed to systematically review psychological functioning in paediatric single ventricle heart disease.

Literature was searched using PubMed, Embase, PsycInfo, CINAHL Complete and Scopus. Peer-reviewed articles that included patients ages 0–25 years with single ventricle heart disease, and quantitative measures of psychological outcomes were included. Meta-analysis using a fixed-effect model was conducted for internalising and externalising t-scores, utilised by the Achenbach Child Behavior Checklist.

Twenty-nine records met the criteria for inclusion. 13/24 studies demonstrated increased risk for internalising disorders, such as anxiety/depression; 16/22 studies demonstrated risk for externalising disorders, such as attention or behavioural problems. Meta-analysis of four studies revealed that paediatric single ventricle heart disease patients had no significant difference in internalising and externalising t-scores compared to normative values.

The current review demonstrates the need for further studies to better understand psychological functioning in patients with single ventricle heart disease, with a majority of studies showing increased risk for psychological problems despite no difference seen in a small meta-analysis. This summary of the literature underscores the need for regular psychological screening, earlier intervention and integrated mental health therapies in paediatric single ventricle heart disease.