Faculty Bibliography

OBJECTIVE:Retrieval practice, often using electronic flashcards, is increasingly utilized among medical students for self-study. In this study, the authors evaluated usage and satisfaction with electronic flashcards based on a medical school psychiatry curriculum. METHODS:First-year medical students at one institution consented to participate and received access to a set of pre-made flashcards. Surveys were distributed that collected demographic information along with measures of prior performance, test anxiety, and prior experience with electronic flashcards. The total number of flashcard reviews and time spent on the platform for each student were collected using statistics internally generated by the platform. Each student's final exam score was also collected. RESULTS:A total of 114 of 129 first year medical students (88%) consented to participate, and 101 students were included in the final analysis. Fifty-eight (56%) were flashcard users with a median of 660 flashcards studied over 2.95 h. A total of 87% of flashcard users found the flashcards to be helpful, and 83% of flashcard users would recommend the flashcards to someone else. Flashcard usage was not associated with final exam scores. CONCLUSIONS:This novel electronic study resource was well-received by first-year medical students for psychiatric instruction in medical school, though usage was not associated with higher exam scores.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Attention-deficit/hyperactivity disorder (ADHD) and obesity are 2 frequent conditions that co-occur, which has implications for the management of both conditions. We hypothesized that ADHD symptoms predict BMI and vice versa from late childhood (10-12 years) up to early adulthood (20-22 years). METHODS:= 2773, 52.5% male, mean age = 11 years at baseline, 5 waves up to mean age 22) from the Tracking Adolescents' Individual Lives Survey cohort. We examined bidirectional relationship between ADHD symptoms (hyperactivity/impulsivity and inattention) and BMI using the random intercept cross-lagged panel model. Time-varying covariates were pubertal status, stimulant use, depressive symptoms, and family functioning, and socioeconomic status was a time-invariant covariate. RESULTS:< .05). No longitudinal direct effects were found between ADHD symptoms and BMI during this period. CONCLUSIONS:Over the course of adolescence, the link between ADHD and BMI is stable and is predominantly with hyperactive and impulsive symptoms rather than inattention. There was no direct effect of ADHD symptoms on BMI increase nor of BMI on enhanced ADHD symptoms during this developmental period. The findings point to a shared genetic or familial background and/or potential causal effects established already earlier in childhood, thus suggesting that intervention and prevention programs targeting overweight and obesity in children with ADHD should be implemented in early childhood.

INTRODUCTION/BACKGROUND:Evidence from low-resource settings indicates that economic insecurity is a major barrier to HIV treatment adherence. Economic empowerment (EE) interventions have the potential to improve adherence outcomes among adolescents living with HIV (ALWHIV) by mitigating the effects of poverty. This study aims to assess the efficacy and cost-effectiveness of a savings-led family-based EE intervention, Suubi + Adherence, aimed at improving antiretroviral therapy (ART) adherence outcomes ALWHIV in Uganda. METHODS:Adolescents (mean age 12 years at enrolment; 56% female) receiving ART for HIV at 39 health centres were randomized to Suubi + Adherence intervention (n = 358) or bolstered standard of care (BSOC; n = 344). A difference-in-differences analysis was employed to assess the change in the proportion of virally suppressed adolescents (HIV RNA viral load <40 copies/mL) over 24 months. The cost-effectiveness analysis examined how much the intervention cost to virally suppress one additional adolescent relative to BSOC from the healthcare provider perspective. RESULTS:At 24 months, the intervention was associated with an 8.85-percentage point [95% confidence interval (CI) 0.80 to 16.90 percentage points] increase in the proportion of virally suppressed adolescents between the study arms (p = 0.032). Per-participant costs were US$177 and US$263 for the BSOC and intervention groups respectively. The incremental cost of virally suppressing one additional adolescent was estimated at US$970 [95% CI, US$508 to 10,725] over two years. CONCLUSIONS:Our results support the integration of family-based EE interventions into adherence-support strategies as part of routine HIV care in low-resource settings to address the underlying economic drivers of poor ART adherence among ALWHIV. Moreover, per-participant costs to achieve viral suppression do not seem prohibitive compared to other community-based adherence interventions targeted at ALWHIV in low-resource settings. Further research on combination interventions at the nexus of economic security and HIV treatment and care is needed to inform the development of feasible and scalable HIV policies and programmes.

Mental health treatment in schools has the potential to improve youth treatment access. However, school-specific barriers can make implementing evidence-based interventions difficult. Task-shifting (i.e., training lay staff to implement interventions) and computer-assisted interventions may mitigate these barriers. This paper reports on a qualitative examination of facilitators and barriers of a school-based implementation of a computer-assisted intervention for anxious youth (Camp Cope-A-Lot; CCAL). Participants (N = 45) included school staff in first through fourth grades. Providers attended a training in CCAL and received weekly, hour-long group consultation calls for three months. In the second year, the sustainability of CCAL use was assessed. Qualitative interviews were conducted after the first year (initial implementation) and second year (sustainability). Interviews were analyzed using the Consolidated Framework for Implementation Research domains to classify themes. Although participants reported that CCAL included useful skills, they expressed concerns about recommended session length (45 minutes) and frequency (weekly). Time burden of consultation calls was also a barrier. School staff facilitated implementation by enabling flexible scheduling for youth to be able to participate in the CCAL program. However, the sustainability of the program was limited due to competing school/time demands. Results suggest that even with computer assisted programs, there is a need to tailor interventions and implementation efforts to account for the time restrictions experienced by school-based service providers. Optimal fit between the intervention and specific school is important to maintain the potential benefits of computer-assisted treatments delivered by lay service providers in schools.

Background: ECHELON-2 (NCT01777152), a phase 3, randomised, double-blind, double-dummy, placebo-controlled, active-comparator, multicentre study, established the superiority of frontline brentuximab vedotin + cyclophosphamide, doxorubicin, and prednisone (A+CHP) vs cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of patients (pts) with systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCLs) (Horwitz, Lancet 2019). Both risk of progression-free survival (PFS) per blinded independent central review (primary endpoint) and overall survival (OS) events favoured A+CHP over CHOP at the primary analysis. A+CHP was the first treatment regimen to increase OS compared with CHOP in this population.
Aim(s): We report the 5-year data from ECHELON-2, including PFS per investigator (INV) data and the following key secondary endpoints: OS, PFS in sALCL, complete remission (CR) rate, and objective response rate (ORR) in re-treated pts.
Method(s): Adults with untreated CD30-positive PTCL (targeting 75% +/- 5% with sALCL) were randomized 1:1 to receive 6-8 cycles of A+CHP or CHOP. Pts were stratified by histological subtype and international prognostic index (IPI) score. Brentuximab vedotin-based subsequent therapies were allowed.
Result(s): Of 452 pts enrolled, the majority had sALCL (n=316 [70%]; 218 [48%] anaplastic lymphoma kinase [ALK]-negative, and 98 pts [22%] ALK-positive) and had advanced disease (27% Stage III, 53% Stage IV; 78% IPI >=2). At data cutoff, median follow-up was 47.6 months for PFS and 66.8 months for OS. A+CHP was favoured over CHOP with a hazard ratio (HR) for PFS per INV of 0.70 (95% confidence interval [CI]: 0.53, 0.91; p=0.0077) and OS HR of 0.72 (95% CI: 0.53, 0.99; p=0.0424). Median PFS was 62.3 months (95% CI: 42.0, not evaluable) for A+CHP, and 23.8 months (95% CI: 13.6, 60.8) for CHOP. Estimated 5-year PFS was 51.4% (95% CI: 42.8, 59.4) and 43.0% (95% CI: 35.8, 50.0) with A+CHP and CHOP, respectively. Median OS was not reached in either arm. Estimated 5-year OS was 70.1% (95% CI: 63.3, 75.9) for A+CHP vs 61.0% (95% CI: 54.0, 67.3) for CHOP. PFS in prespecified subgroups and overall PFS were generally consistent (Figure). The HR for PFS (0.55 [95% CI: 0.39, 0.79]) also favoured A+CHP over CHOP in pts with sALCL, with an estimated 5-year PFS of 60.6% (95% CI: 49.5, 69.9) for the A+CHP arm vs 48.4% (95% CI: 39.6, 56.7) for the CHOP arm. Subsequent systemic therapy with brentuximab vedotin was administered to a total of 29 pts (13%) in the A+CHP arm (sALCL [n=19]; PTCL not otherwise specified [n=5], angioimmunoblastic T-cell lymphoma [n=5]) and 54 pts (24%) in the CHOP arm. Median time to retreatment for pts in the A+CHP arm was 15.0 months (range, 3-64); 17 pts (ORR: 59%) had CR (n=11) or partial remission (n=6) after retreatment with brentuximab vedotin monotherapy (n=25) or a brentuximab vedotin-containing regimen (n=4). Of the treatment-emergent peripheral neuropathy (PN) in the A+CHP (n=117) and CHOP arms (n=124), 72% in the A+CHP arm and 78% in the CHOP arm had resolved or improved. In pts with ongoing events at last follow-up (A+CHP [n=47] vs CHOP [n=42]) PN was grade 1, 2 and 3 in 70% vs 71%, 28% vs 26% and 2% vs 2%, respectively. Summary/Conclusion: After 5 years' follow-up, frontline A+CHP continued to provide clinically meaningful improvements in PFS and OS vs CHOP, including sustained remission in 59% of re-treated pts with sALCL, as well as a manageable safety profile, including continued resolution or improvement of PN

INTRODUCTION/BACKGROUND:Achieving optimal adherence to antiretroviral therapy (ART) among adolescents living with HIV (ALWHIV) is challenging, especially in low-resource settings. To help accurately determine who is at risk of poor adherence, we developed and internally validated models comprising multi-level factors that can help to predict the individualized risk of poor adherence among ALWHIV in a resource-limited setting such as Uganda. METHODS:We used data from a sample of 637 ALWHIV in Uganda who participated in a longitudinal study, "Suubi+Adherence" (2012 to 2018). The model was developed using the Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression to select the best subset of multi-level predictors (individual, household, community or economic-related factors) of poor adherence in one year's time using 10-fold cross-validation. Seventeen potential predictors included in the model were assessed at 36 months of follow-up, whereas adherence was assessed at 48 months of follow-up. Model performance was evaluated using discrimination and calibration measures. RESULTS:For the model predicting poor adherence, five of the 17 predictors (adherence history, adherence self-efficacy, family cohesion, child poverty and group assignment) were retained. Its ability to discriminate between individuals with and without poor adherence was acceptable; area under the curve (AUC) = 69.9; 95% CI: 62.7, 72.8. There was no evidence of possible areas of miscalibration (test statistic = 1.20; p = 0.273). The overall performance of the model was good. CONCLUSIONS:Our findings support prediction modelling as a useful tool that can be leveraged to improve outcomes across the HIV care continuum. Utilizing information from multiple sources, the risk prediction score tool applied here can be refined further with the ultimate goal of being used in a screening tool by practitioners working with ALWHIV. Specifically, the tool could help identify and provide early interventions to adolescents at the highest risk of poor adherence and/or viral non-suppression. However, further fine-tuning and external validation may be required before wide-scale implementation.

BACKGROUND:Adults with bipolar disorder (BD) often experience neurocognitive impairment that negatively impacts functioning and quality of life. Previous trials have found that dopamine agonist agents improve cognition in healthy volunteers and that adults with BD who have stable mood and mild cognitive deficits may also benefit. We hypothesized that pramipexole, a dopamine agonist, would improve neurocognitive function in patients with BD. METHODS:We recruited 60 adults (aged 18-65 years) with a diagnosis of BD I or II for an 8-week, double-blind, placebo-controlled trial (NCT02397837). All had stable mood and clinically significant neurocognitive impairment at baseline. Participants were randomized to receive pramipexole (n = 31) or a placebo (n = 29), dose was initiated at 0.125 mg 2 times a day and increased to a target of 4.5 mg/d. RESULTS:At trial end, the primary outcome, MATRICS Consensus Cognitive Battery composite score, had not improved more in the pramipexole group (mean [SD] = 1.15 [5.4]) than in the placebo group (mean [SD] = 4.12 [5.2], Cohen's d = 0.56, P = 0.049), and mixed models, controlling for symptoms, showed no association between treatment group and MATRICS Consensus Cognitive Battery scores. No serious adverse events were reported. CONCLUSIONS:These results suggest that pramipexole is not an efficacious cognitive enhancement agent in BD, even in a sample enriched for characteristics that were associated with a beneficial response in prior work. There are distinct cognitive subgroups among adults with BD and may be related differences in neurobiology that affect response to pramipexole. Additional research to better understand the onset and nature of the cognitive deficits in people with BD will be an important step toward a more personalized approach to treatment.

Functional abdominal pain (FAP) is one of the most common childhood medical complaints, associated with significant distress and impairment. Little is known about how children understand their pain. Do they attribute it to personal weakness? Do they perceive pain as having global impact, affecting a variety of activities? How do they cope with pain? We explored the pain beliefs of 5- to 9-year-old children with FAP using a novel Teddy Bear Interview task in which children answered questions about a Teddy bear's pain. Responses were analyzed quantitatively and qualitatively. Results indicate that the majority of young children with FAP are optimistic about pain outcomes. Children generated many types of coping strategies for Teddy's pain and adjusted their calibration of Teddy's pain tolerance dependent on the activity being performed. Early warning signs also emerged: a subset of children were pessimistic about Teddy's pain, and several children identified coping strategies that, while developmentally appropriate, could lead to excessive help seeking if not intervened upon (e.g., physician consultation and shot). The Teddy Bear Interview allows children to externalize their pain, making it a useful tool to access cognitive pain constructs in younger children. Thus, these findings highlight the importance of early intervention for childhood FAP.

Alcohol consumption is mediated by several important neuromodulatory systems, including the endocannabinoid and neuropeptide Y (NPY) systems in the limbic brain circuitry. However, molecular mechanisms through which cannabinoid-1 (CB1) receptors regulate alcohol consumption are still unclear. Here, we investigated the role of the CB1 receptor-mediated downstream regulation of NPY via epigenetic mechanisms in the amygdala. Alcohol drinking behavior was measured in adult male C57BL/6J mice treated with a CB1 receptor neutral antagonist AM4113 using a two-bottle choice paradigm while anxiety-like behavior was assessed in the light-dark box (LDB) test. The CB1 receptor-mediated changes in the protein levels of phosphorylated cAMP-responsive element binding protein (pCREB), CREB binding protein (CBP), H3K9ac, H3K14ac and NPY, and the mRNA levels of Creb1, Cbp, and Npy were measured in amygdaloid brain structures. Npy-specific changes in the levels of acetylated histone (H3K9/14ac) and CBP in the amygdala were also measured. We found that the pharmacological blockade of CB1 receptors with AM4113 reduced alcohol consumption and, in an ethanol-naïve cohort, reduced anxiety-like behavior in the LDB. Treatment with AM4113 also increased the mRNA levels of Creb1 and Cbp in the amygdala as well as the protein levels of pCREB, CBP, H3K9ac and H3K14ac in the central and medial nucleus of amygdala, but not in the basolateral amygdala. Additionally, AM4113 treatment increased occupancy of CBP and H3K9/14ac at the Npy gene promoter, leading to an increase in both mRNA and protein levels of NPY in the amygdala. These novel findings suggest that CB1 receptor-mediated CREB signaling plays an important role in the modulation of NPY function through an epigenetic mechanism and further support the potential use of CB1 receptor neutral antagonists for the treatment of alcohol use disorder.