Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Child and Adolescent Psychiatry
Total Results:
11295
Pramipexole to Improve Cognition in Bipolar Disorder: A Randomized Controlled Trial
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.
PMCID:8238822
PMID: 33956703
ISSN: 1533-712x
CID: 5005132
A Qualitative Examination of a School-Based Implementation of Computer-Assisted Cognitive-Behavioral Therapy for Child Anxiety
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.
PMCID:8223963
PMID: 34178162
ISSN: 1866-2625
CID: 4926122
Echelon-2, (NCT01777152), 5-year results of a randomised, double-blind, phase 3 study of frontline brentuximab vedotin + CHP vs chop in patients with CD30-positive peripheral t-cell lymphoma [Meeting Abstract]
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
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
EMBASE:635849075
ISSN: 2572-9241
CID: 4983562
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology
Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies.
PMID: 34002096
ISSN: 1546-1718
CID: 4876872
Olfactory Language: Context Is Everything [Letter]
PMID: 33757701
ISSN: 1879-307x
CID: 4822632
The efficacy and cost-effectiveness of a family-based economic empowerment intervention (Suubi + Adherence) on suppression of HIV viral loads among adolescents living with HIV: results from a Cluster Randomized Controlled Trial in southern Uganda
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.
PMCID:8236226
PMID: 34176245
ISSN: 1758-2652
CID: 4926062
Exploring the relations between interpersonal risk and adolescent suicidality during treatment
OBJECTIVE:Despite considerable evidence that supports perceived burdensomeness (PB) and thwarted belongingness (TB) as risk factors for suicidal ideation (SI), far less is known about the direction of effects between these constructs in treatments for suicidal adolescents. The present study examined bidirectional relations between PB, TB, and adolescents' suicidal ideation (SI) during a 16-week randomized clinical trial. METHOD/METHODS:129 depressed and suicidal adolescents completed PB, TB, and SI measures at three time points: baseline (T1), mid-treatment (T2), and treatment completion (T3). Random-intercept cross-lagged panel models (RI-CLPM) examined within-subject direction of effects between interpersonal variables (PB & TB) and suicidal ideation (SI) in the first and second halves of treatment. RESULTS:Within-subjects, autoregressive paths indicated significant carryover in PB and SI. In the first half of treatment, a significant cross-lagged path indicated that T1 PB predicted change in T2 SI, and in the last half of treatment change in T2 SI predicted change in T3 PB. There were no significant auto-regressive or cross-lagged effects for TB. CONCLUSIONS:In the first half of treatment, baseline PB predicted fewer reductions in SI suggesting that PB initially moderated adolescents' response to treatment. However, in the last half of treatment, initial reductions in SI predicted subsequent reductions in PB suggesting that adolescents' initial response to treatment decreased their perceptions of burdening others. The clinical and treatment implications of these bidirectional findings are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
PMID: 34264700
ISSN: 1939-2117
CID: 4938842
World psychiatry : official journal of the World Psychiatric Association (WPA). 2021:20(2):244-275.DOI: 10.1002/wps.20881
Efficacy and acceptability of pharmacological, psychosocial, and brain stimulation interventions in children and adolescents with mental disorders: an umbrella review
Top-tier evidence on the safety/tolerability of 80 medications in children/adolescents with mental disorders has recently been reviewed in this jour-nal. To guide clinical practice, such data must be combined with evidence on efficacy and acceptability. Besides medications, psychosocial inter-ventions and brain stimulation techniques are treatment options for children/adolescents with mental disorders. For this umbrella review, we systematically searched network meta-analyses (NMAs) and meta-analyses (MAs) of randomized controlled trials (RCTs) evaluating 48 medications, 20 psychosocial interventions, and four brain stimulation techniques in children/adolescents with 52 different mental disorders or groups of mental disorders, reporting on 20 different efficacy/acceptability outcomes. Co-primary outcomes were disease-specific symptom reduction and all-cause discontinuation ("acceptability"). We included 14 NMAs and 90 MAs, reporting on 15 mental disorders or groups of mental disorders. Overall, 21 medications outperformed placebo regarding the co-primary outcomes, and three psychosocial interventions did so (while seven outperformed waiting list/no treatment). Based on the meta-analytic evidence, the most convincing efficacy profile emerged for amphetamines, methylphenidate and, to a smaller extent, behavioral therapy in attention-deficit/hyperactivity disorder; aripiprazole, risperidone and several psychosocial interventions in autism; risperidone and behavioral interventions in disruptive behavior disorders; several antipsychotics in schizophrenia spectrum disorders; fluoxetine, the combination of fluoxetine and cognitive behavioral therapy (CBT), and interpersonal therapy in depression; aripiprazole in mania; fluoxetine and group CBT in anxiety disorders; fluoxetine/selective serotonin reuptake inhibitors, CBT, and behavioral therapy with exposure and response prevention in obsessive-compulsive disorder; CBT in post-traumatic stress disorder; imipramine and alarm behavioral intervention in enuresis; behavioral therapy in encopresis; and family therapy in anorexia nervosa. Results from this umbrella review of interventions for mental disorders in children/adolescents provide evidence-based information for clinical decision making.
PMID: 34002501
ISSN: 1723-8617
CID: 4876902
Longitudinal Associations Between Symptoms of ADHD and BMI From Late Childhood to Early Adulthood
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.
PMID: 34039717
ISSN: 1098-4275
CID: 4888062
A constrained single-index regression for estimating interactions between a treatment and covariates
We consider a single-index regression model, uniquely constrained to estimate interactions between a set of pretreatment covariates and a treatment variable on their effects on a response variable, in the context of analyzing data from randomized clinical trials. We represent interaction effect terms of the model through a set of treatment-specific flexible link functions on a linear combination of the covariates (a single index), subject to the constraint that the expected value given the covariates equals zero, while leaving the main effects of the covariates unspecified. We show that the proposed semiparametric estimator is consistent for the interaction term of the model, and that the efficiency of the estimator can be improved with an augmentation procedure. The proposed single-index regression provides a flexible and interpretable modeling approach to optimizing individualized treatment rules based on patients' data measured at baseline, as illustrated by simulation examples and an application to data from a depression clinical trial. This article is protected by copyright. All rights reserved.
PMID: 32573759
ISSN: 1541-0420
CID: 4493012
