Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD.

As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men.

Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects.

Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Social connection is associated with better health, including reduced risk of dementia. Personality traits are also linked to cognitive outcomes; neuroticism is associated with increased risk of dementia. Personality traits and social connection are also associated with each other. Taken together, evidence suggests the potential impacts of neuroticism and social connection on cognitive outcomes may be linked. However, very few studies have simultaneously examined the relationships between personality, social connection and health.

We tested the association between neuroticism and cognitive measures while exploring the potential mediating roles of aspects of social connection (loneliness and social isolation).

We conducted a cross-sectional study with a secondary analysis of the Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort, a sample of Canadians aged 45 to 85 years at baseline. We used only self-reported data collected at the first follow-up, between 2015 and 2018 (n= 27,765). We used structural equation modelling to assess the association between neuroticism (exposure) and six cognitive measures (Rey Auditory Verbal Learning Test immediate recall and delayed recall, Animal Fluency Test, Mental Alternation Test, Controlled Oral Word Association Test and Stroop Test interference ratio), with direct and indirect effects (through social isolation and loneliness). We included age, education and hearing in the models and stratified all analyses by sex, females (n= 14,133) and males (n=13,632).

We found positive, statistically significant associations between neuroticism and social isolation (p<0.05) and loneliness (p<0.05), for both males and females. We also found inverse, statistically significant associations between neuroticism and all cognitive measures (p<0.05), except the Stroop Test interference ratio. In these models, there was consistent evidence of indirect effects (through social isolation and loneliness) and, in some cases, evidence of direct effects. We found sex differences in the model results.

Our findings suggest that the association between neuroticism and cognitive outcomes may be mediated by aspects of social connection and differ by sex. Understanding if and how modifiable risk factors mediate the association between personality and cognitive outcomes would help develop and target intervention strategies that improve social connection and brain health.

Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.

In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.

Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.

Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.

Psychological trauma exposure and posttraumatic stress disorder (PTSD) have been associated with advanced epigenetic age. However, whether epigenetic aging measured at the time of trauma predicts the subsequent development of PTSD outcomes is unknown. Moreover, the neural substrates underlying posttraumatic outcomes associated with epigenetic aging are unclear.

We examined a multi-ancestry cohort of women and men (n = 289) who presented to the emergency department (ED) after trauma. Blood DNA was collected at ED presentation, and EPIC DNA methylation arrays were used to assess four widely used metrics of epigenetic aging (HorvathAge, HannumAge, PhenoAge, and GrimAge). PTSD symptoms were evaluated longitudinally at the time of ED presentation and over the ensuing 6 months. Structural and functional neuroimaging was performed 2 weeks after trauma.

After covariate adjustment and correction for multiple comparisons, advanced ED GrimAge predicted increased risk for 6-month probable PTSD diagnosis. Secondary analyses suggested that the prediction of PTSD by GrimAge was driven by worse trajectories for intrusive memories and nightmares. Advanced ED GrimAge was also associated with reduced volume of the whole amygdala and specific amygdala subregions, including the cortico-amygdaloid transition and the cortical and accessory basal nuclei.

Our findings shed new light on the relation between biological aging and trauma-related phenotypes, suggesting that GrimAge measured at the time of trauma predicts PTSD trajectories and is associated with relevant brain alterations. Furthering these findings has the potential to enhance early prevention and treatment of posttraumatic psychiatric sequelae.

Despite a high prevalence of problematic substance use among people living with HIV in South Africa, there remains limited access to substance use services within the HIV care system. To address this gap, our team previously developed and adapted a six-session, peer-delivered problem-solving and behavioral activation-based intervention (Khanya) to improve HIV medication adherence and reduce substance use in Cape Town. This study evaluated patient and provider perspectives on the intervention to inform implementation and future adaptation.

Following intervention completion, we conducted semi-structured individual interviews with patients (n = 23) and providers (n = 9) to understand perspectives on the feasibility, acceptability, and appropriateness of Khanya and its implementation by a peer. Patients also quantitatively ranked the usefulness of individual intervention components (problem solving for medication adherence ‘Life-Steps’, behavioral activation, mindfulness training, and relapse prevention) at post-treatment and six months follow-up, which we triangulated with qualitative feedback to examine convergence and divergence across methods.

Patients and providers reported high overall acceptability, feasibility, and appropriateness of Khanya, although there were several feasibility challenges. Mindfulness and Life-Steps were identified as particularly acceptable, feasible, and appropriate components by patients across methods, whereas relapse prevention strategies were less salient. Behavioral activation results were less consistent across methods.

Findings underscore the importance of examining patients’ perspectives on specific intervention components within intervention packages. While mindfulness training and peer delivery models were positively perceived by consumers, they are rarely used within task-shared behavioral interventions in low- and middle-income countries.

This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience.

We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression.

Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma.

These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure.

The Clinical and Translational Science Award (CTSA) Program is a Consortium of nearly 60 academic medical research centers across the USA and a natural network for evaluating the spread and uptake of translational research innovation across the Consortium.

Dissemination of the Accrual to Clinical Trials (ACT) Network, a federated clinical informatics data network for population-based cohort discovery, began January 2018 across the Consortium. Diffusion of innovation theory guided dissemination design and evaluation. Mixed-methods assessed the spread and uptake across the Consortium through July 1, 2019 (n = 48 CTSAs). Methods included prospective time activity tracking (Kaplan–Meier curves), and survey and qualitative interviews.

Within 18 months, nearly 80% of CTSAs had joined the data network and two-thirds of CTSAs achieving technical readiness had initiated launch to local clinical investigators. Over 10,000 ACT Network queries are projected for 2019; and by 2020, nearly all CTSAs will have joined the network. Median time-from-technical-readiness-to-local-launch was 154 days (interquartile range: 87–225 days]. Quality improvement processes reduced time-to-launch by 35.2% (64 days, p = 0.0036). Lessons learned include: (1) conceptualize dissemination as two-stage adoption demonstrating value for both CTSA hub service providers and clinical investigators; (2) include institutional trial into dissemination strategies so CTSA hubs can refine internal workflows and gather local user feedback endorsement; (3) embrace designing-for-dissemination during technology development; and (4) sustain adaptive dissemination and customer relationship management to keep CTSA hubs and users engaged.

Scale-up and spread of the ACT Network provides lessons learned for others disseminating innovation across the CTSA Consortium. The Network is primed for embedded implementation research.

In clinical and translational research, data science is often and fortuitously integrated with data collection. This contrasts to the typical position of data scientists in other settings, where they are isolated from data collectors. Because of this, effective use of data science techniques to resolve translational questions requires innovation in the organization and management of these data.

We propose an operational framework that respects this important difference in how research teams are organized. To maximize the accuracy and speed of the clinical and translational data science enterprise under this framework, we define a set of eight best practices for data management.

In our own work at the University of Rochester, we have strived to utilize these practices in a customized version of the open source LabKey platform for integrated data management and collaboration. We have applied this platform to cohorts that longitudinally track multidomain data from over 3000 subjects.

We argue that this has made analytical datasets more readily available and lowered the bar to interdisciplinary collaboration, enabling a team-based data science that is unique to the clinical and translational setting.

Early career investigators have few opportunities for targeted training in supportive oncology research. To address this need, we developed, implemented, and evaluated an intensive, six-day workshop on methods in supportive oncology research for trainees and junior faculty across multiple disciplines.

A multidisciplinary team of supportive oncology researchers developed a workshop patterned after the clinical trials workshop offered jointly by the American Society of Clinical Oncology and American Association of Cancer Research. The curriculum included lectures and a mentored experience of writing a research protocol. Each year since 2015, the workshop has accepted and trained 36 early career investigators. Over the course of the workshop, participants present sections of their research protocols daily in small groups led by senior researchers, and have dedicated time to write and revise these sections. Primary outcomes for the workshop included the frequency of completed protocols by the end of the workshop, a pre- and posttest assessing participant knowledge, and follow-up surveys of the participants and their primary mentors.

Over three years, the workshop received 195 applications; 109 early career researchers were competitively selected to participate. All participants (109/109, 100%) completed writing a protocol by the end of their workshop. Participants and their primary mentors reported significant improvements in their research knowledge and skills. Each year, participants rated the workshop highly in terms of satisfaction, value, and likelihood of recommending it to a colleague. One year after the first workshop, most respondents (29/30, 96.7%) had either submitted their protocol or written at least one other protocol.

We developed a workshop on research methods in supportive oncology. More early career investigators applied for the workshop than capacity, and the workshop was fully attended each year. Both the workshop participants and their primary mentors reported improvement in research skills and knowledge.

Ketamine has recently become an agent of interest as an acute treatment for severe depression and as the anaesthetic for electroconvulsive therapy (ECT). Subanaesthetic doses result in an acute reduction in depression severity while evidence is equivocal for this antidepressant effect with anaesthetic or adjuvant doses. Recent systematic reviews call for high-quality evidence from further randomised controlled trials (RCTs).

To establish if ketamine as the anaesthetic for ECT results in fewer ECT treatments, improvements in depression severity ratings and less memory impairment than the standard anaesthetic.

Double-blind, parallel-design, RCT of intravenous ketamine (up to 2 mg/kg) with an active comparator, intravenous propofol (up to 2.5 mg/kg), as the anaesthetic for ECT in patients receiving ECT for major depression on an informal basis. (Trial registration: European Clinical Trials Database (EudraCT): 2011-000396-14 and clinicalTrials.gov: NCT01306760.)

No significant differences were found on any outcome measure during, at the end of or 1 month following the ECT course.

Ketamine as an anaesthetic does not enhance the efficacy of ECT.

A cognitive–behavioural therapy (CBT) programme designed for post-traumatic stress disorder (PTSD) in people with severe mental illness, including breathing retraining, education and cognitive restructuring, was shown to be more effective than usual services.

To evaluate the incremental benefit of adding cognitive restructuring to the breathing retraining and education components of the CBT programme (trial registration: clinicaltrials.gov identifier: NCT00494650).

In all, 201 people with severe mental illness and PTSD were randomised to 12- to 16-session CBT or a 3-session brief treatment programme (breathing retraining and education). The primary outcome was PTSD symptom severity. Secondary outcomes were PTSD diagnosis, other symptoms, functioning and quality of life.

There was greater improvement in PTSD symptoms and functioning in the CBT group than in the brief treatment group, with both groups improving on other outcomes and effects maintained 1-year post-treatment.

Cognitive restructuring has a significant impact beyond breathing retraining and education in the CBT programme, reducing PTSD symptoms and improving functioning in people with severe mental illness.