Despite advances in antiretroviral treatment (ART), human immunodeficiency virus (HIV) can detrimentally affect everyday functioning. Neurocognitive impairment (NCI) and current depression are common in people with HIV (PWH) and can contribute to poor functional outcomes, but potential synergies between the two conditions are less understood. Thus, the present study aimed to compare the independent and combined effects of NCI and depression on everyday functioning in PWH. We predicted worse functional outcomes with comorbid NCI and depression than either condition alone.

PWH enrolled at the UCSD HIV Neurobehavioral Research Program were assessed for neuropsychological performance, depression severity (≤minimal, mild, moderate, or severe; Beck Depression Inventory-II), and self-reported everyday functioning.

Participants were 1,973 PWH (79% male; 66% racial/ethnic minority; Age: M = 48.6; Education: M = 13.0, 66% AIDS; 82% on ART; 42% with NCI; 35% BDI>13). ANCOVA models found effects of NCI and depression symptom severity on all functional outcomes (ps < .0001). With NCI and depression severity included in the same model, both remained significant (ps < .0001), although the effects of each were attenuated, and yielded better model fit parameters (i.e., lower AIC values) than models with only NCI or only depression.

Consistent with prior literature, NCI and depression had independent effects on everyday functioning in PWH. There was also evidence for combined effects of NCI and depression, such that their comorbidity had a greater impact on functioning than either alone. Our results have implications for informing future interventions to target common, comorbid NCI and depressed mood in PWH and thus reduce HIV-related health disparities.

Interprofessional teams in the pediatric cardiac ICU consolidate their management plans in pre-family meeting huddles, a process that affects the course of family meetings but often lacks optimal communication and teamwork.

Cardiac ICU clinicians participated in an interprofessional intervention to improve how they prepared for and conducted family meetings. We conducted a pretest–posttest study with clinicians participating in huddles before family meetings. We assessed feasibility of clinician enrollment, assessed clinician perception of acceptability of the intervention via questionnaire and semi-structured interviews, and impact on team performance using a validated tool. Wilcoxon rank sum test assessed intervention impact on team performance at meeting level comparing pre- and post-intervention data.

Totally, 24 clinicians enrolled in the intervention (92% retention) with 100% completion of training. All participants recommend cardiac ICU Teams and Loved ones Communicating to others and 96% believe it improved their participation in family meetings. We exceeded an acceptable level of protocol fidelity (>75%). Team performance was significantly (p < 0.001) higher in post-intervention huddles (n = 30) than in pre-intervention (n = 28) in all domains. Median comparisons: Team structure [2 vs. 5], Leadership [3 vs. 5], Situation Monitoring [3 vs. 5], Mutual Support [ 3 vs. 5], and Communication [3 vs. 5].

Implementing an interprofessional team intervention to improve team performance in pre-family meeting huddles is feasible, acceptable, and improves team function. Future research should further assess impact on clinicians, patients, and families.

Differences in social behaviours are common in young people with neurodevelopmental conditions (NDCs). Recent research challenges the long-standing hypothesis that difficulties in social cognition explain social behaviour differences.

We examined how difficulties regulating one's behaviour, emotions and thoughts to adapt to environmental demands (i.e. dysregulation), alongside social cognition, explain social behaviours across neurodiverse young people.

We analysed cross-sectional behavioural and cognitive data of 646 6- to 18-year-old typically developing young people and those with NDCs from the Province of Ontario Neurodevelopmental Network. Social behaviours and dysregulation were measured by the caregiver-reported Adaptive Behavior Assessment System Social domain and Child Behavior Checklist Dysregulation Profile, respectively. Social cognition was assessed by the Neuropsychological Assessment Affect-Recognition and Theory-of-Mind, Reading the Mind in the Eyes Test, and Sandbox continuous false-belief task scores. We split the sample into training (n = 324) and test (n = 322) sets. We investigated how social cognition and dysregulation explained social behaviours through principal component regression and hierarchical regression in the training set. We tested social cognition-by-dysregulation interactions, and whether dysregulation mediated the social cognition–social behaviours association. We assessed model fits in the test set.

Two social cognition components adequately explained social behaviours (13.88%). Lower dysregulation further explained better social behaviours (β = −0.163, 95% CI −0.191 to −0.134). Social cognition-by-dysregulation interaction was non-significant (β = −0.001, 95% CI −0.023 to 0.021). Dysregulation partially mediated the social cognition–social behaviours association (total effect: 0.544, 95% CI 0.370–0.695). Findings were replicated in the test set.

Self-regulation, beyond social cognition, substantially explains social behaviours across neurodiverse young people.

Studies show stimulant medications are effective for different ADHD presentations (predominantly inattentive [IA], predominantly hyperactive-impulsive [HI] or combined [C]); however, few studies have evaluated nonstimulant efficacy in different ADHD presentations. Viloxazine ER [VLX ER] is a nonstimulant, FDA-approved medication for pediatric (≥6 yrs) and adult ADHD. This post-hoc analysis of 4 double-blind (DB), Phase 3, clinical trials (2 in adolescents [NCT03247517 and NCT03247556], 2 in children [NCT03247530 and NCT03247543]), evaluates VLX ER efficacy by ADHD presentation as derived from ADHD Rating Scale, 5th Edition (ADHD-RS-5) assessments at Baseline.

Children and adolescents with ADHD and an ADHD-RS-5 Total score ≥ 28 were eligible for enrollment. ADHD presentation was defined as a rating of ≥2 on at least 6 of 9 ADHD-RS-5 inattention items, or hyperactive-impulsive items or both. For each ADHD presentation, the change from Baseline (CFB) in ADHD-RS-5 Total score (primary outcome in each study) was assessed using mixed models for repeated measures (MMRM). Responder rate (secondary outcome), ≥50% reduction from baseline in ADHD-RS-5 Total score, was analyzed using generalized estimating equations (GEE).

Of 1354 subjects [placebo N = 452, VLX ER N = 902], ADHD presentation was assigned as 288 (21.3%) [IA], 1010 (74.5%) [C], 40 (3.0%) [HI], 16 (1.2%) [none of these]. Due to the small sample size of [HI], only the [IA] and [C] results are presented. At Week 6 (pooled data endpoint), ADHD-RS-5 Total scores were significantly improved for VLX ER relative to placebo for both the [IA] and [C] ADHD presentations. LS mean (SE) treatment differences, p-values were: [IA] -3.1 (1.35), p = 0.0219, and [C] 5.8 (0.97), p < 0.0001. Responder rates were also significantly higher for VLX ER: 43.0% [IA] and 42.7% [C] relative to placebo 29.5% [IA] and 25.5 % [C] (p=.0311 and p<.0001).

Viloxazine ER significantly reduced ADHD symptoms in individuals meeting criteria for ADHD [IA] or [C] presentations at Baseline. Limitations include post-hoc methodology, smaller sample sizes of [IA] and [HI] groups, and the ADHD-RS-5 ≥ 28 eligibility requirement, that may favor enrollment of individuals with ADHD [C] over ADHD [IA] or [HI] presentations. Consistency of response during long-term use should be evaluated.

Supernus Pharmaceuticals, Inc.

Zuranolone is an investigational positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and a neuroactive steroid in clinical development as a once-daily, oral, 14-day treatment course for adults with major depressive disorder or postpartum depression (PPD). The randomized, double-blind, placebo-controlled SKYLARK Study (NCT04442503) demonstrated that zuranolone 50 mg significantly improved depressive symptoms (as assessed by 17-item Hamilton Rating Scale for Depression total score) at Day 15 (primary endpoint; p<0.001) and was generally well tolerated in adults with PPD.

In the SKYLARK Study, patients were randomized 1:1 to receive zuranolone 50 mg or placebo for 14 days. Safety and tolerability were assessed by the incidence and severity of treatment-emergent adverse events (TEAEs), rates of dose reduction and treatment discontinuation, as well as weight gain and sexual dysfunction.

The SKYLARK Study assessed safety data from 98 patients treated with zuranolone 50 mg and 98 patients treated with placebo. TEAEs were reported in 66.3% of zuranolone-treated patients and 53.1% of placebo-treated patients. In patients that experienced TEAEs, most reported mild (zuranolone, 50.8%; placebo, 75%) or moderate (zuranolone, 44.6%; placebo, 23.1%) events. The most common (≥5%) TEAEs were somnolence (26.5%), dizziness (13.3%), sedation (11.2%), headache (9.2%), diarrhea (6.1%), nausea (5.1%), urinary tract infection (5.1%), and COVID-19 (5.1%) with zuranolone, and headache (13.3%), dizziness (10.2%), nausea (6.1%), and somnolence (5.1%) with placebo. Dose reduction due to TEAEs was 16.3% in patients receiving zuranolone vs 1.0% in patients receiving placebo; the most common TEAEs (>1 patient) leading to zuranolone dose reduction were somnolence (7.1%), dizziness (6.1%), and sedation (3.1%). Treatment discontinuation due to TEAEs was 4.1% in patients receiving zuranolone vs 2.0% in patients receiving placebo; TEAEs leading to zuranolone discontinuation in >1 patient included somnolence (2.0%). Serious TEAEs were reported in 2.0% of zuranolone-treated and 0% of placebo-treated patients; these included upper abdominal pain (1.0%, [1/98]), peripheral edema (1.0%, [1/98]), perinatal depression (1.0%, [1/98]), and hypertension (1.0%, [1/98]). Per investigators, serious TEAEs were not related to zuranolone. No signals for weight gain or sexual dysfunction were identified.

In adults with PPD, zuranolone 50 mg was generally well tolerated. Most TEAEs were mild or moderate in severity. Dose reduction due to TEAEs mainly resulted from somnolence, dizziness, and sedation, while treatment discontinuation due to TEAEs was low. No signals for weight gain or sexual dysfunction were identified.

Sage Therapeutics, Inc., and Biogen Inc.

We developed survey items to assess the characteristics of systems thinker, process innovator, boundary spanner, team player, and skilled communicator. Data were collected from a national sample of 281 participants in the I-Corps@NCATS program. Using post-then-retrospective-pre survey items, participants self-reported their ability to perform skills associated with each of the translational scientist characteristics. Additionally, two open-ended survey questions explored how the program shifted participants’ translational orientation, generating 211 comments. These comments were coded through a team-based, iterative process.

Respondents reported the greatest increases in self-assessed abilities related to systems thinking and skilled communication. Participants indicated the highest levels of abilities related to team player and boundary crosser. From the coding of open-ended comments, we identified two additional characteristics of translational scientists: intellectual humility and cognitive flexibility.

Participation in I-Corps@NCATS accelerates translational science in two ways: 1) by teaching the process of scientific translation from research ideas to real-world solutions, and 2) by encouraging growth in the mindset and characteristics of a translational scientist.

Society of Thoracic Surgeons Congenital Heart Surgery Database is the largest congenital heart surgery database worldwide but does not provide information beyond primary episode of care. Linkage to hospital electronic health records would capture complications and comorbidities along with long-term outcomes for patients with CHD surgeries. The current study explores linkage success between Society of Thoracic Surgeons Congenital Heart Surgery Database and electronic health record data in North Carolina and Georgia.

The Society of Thoracic Surgeons Congenital Heart Surgery Database was linked to hospital electronic health records from four North Carolina congenital heart surgery using indirect identifiers like date of birth, sex, admission, and discharge dates, from 2008 to 2013. Indirect linkage was performed at the admissions level and compared to two other linkages using a “direct identifier,” medical record number: (1) linkage between Society of Thoracic Surgeons Congenital Heart Surgery Database and electronic health records from a subset of patients from one North Carolina institution and (2) linkage between Society of Thoracic Surgeons data from two Georgia facilities and Georgia’s CHD repository, which also uses direct identifiers for linkage.

Indirect identifiers successfully linked 79% (3692/4685) of Society of Thoracic Surgeons Congenital Heart Surgery Database admissions across four North Carolina hospitals. Direct linkage techniques successfully matched Society of Thoracic Surgeons Congenital Heart Surgery Database to 90.2% of electronic health records from the North Carolina subsample. Linkage between Society of Thoracic Surgeons and Georgia’s CHD repository was 99.5% (7,544/7,585).

Linkage methodology was successfully demonstrated between surgical data and hospital-based electronic health records in North Carolina and Georgia, uniting granular procedural details with clinical, developmental, and economic data. Indirect identifiers linked most patients, consistent with similar linkages in adult populations. Future directions include applying these linkage techniques with other data sources and exploring long-term outcomes in linked populations.

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.

Clinical research requires a competent workforce of clinical research professionals (CRPs) who are well-trained to perform varied and complex tasks within their roles. The Joint Task Force for Clinical Trial Competency (JTF) framework established essential domains for conducting high-quality clinical research that can guide professional development of CRPs. The Research Professionals Network (RPN) Workshops were established in 2017 to focus on developing ongoing inter-institutional, peer-led, JTF-centric continuing education for CRPs. Four institutions and their affiliates are part of the collaboration.

Workshop participant survey data and other metrics were collected over four academic years. Both quantitative and qualitative analyses were performed to assess participant experience and identify relevant themes.

Participants demonstrated overall high satisfaction with the workshops and significantly value the interpersonal, inter-institutional collaboration made possible through the workshops.

These inter-institutional RPN Workshops have evolved into a Community of Practice, which can be expanded into future opportunities.