Garzon, Juan F.

Importance The potential utility of real-time digital therapeutics that identify impending behavioral outbursts to proactively apply evidence-based interventions for managing children with disruptive behavior disorder has not been tested. Objectives To evaluate feasibility and adherence of a digitally augmented, real-time, proactive behavioral intervention (smartwatch) for children with disruptive behaviors. Design, Setting, and Participants This randomized clinical trial was conducted between March 1, 2022, and December 31, 2023, at Mayo Clinic in Rochester, Minnesota. The study enrolled children aged 3 to 7 years with externalizing behavior problems rated above the clinically significant range (I score ≥120; T score ≥60) on the Eyberg Child Behavior Inventory (ECBI). Interventions Twelve weekly sessions of parent-child interaction therapy (PCIT) (treatment as usual [TAU] arm) vs artificial intelligence (AI)–enhanced PCIT augmented with real-time behavioral outburst alerts (PCIT-AI arm). Main Outcomes and Measures The primary outcome was achieving the a priori feasibility benchmark set at greater than 70% for both completion of PCIT sessions and daily smartwatch wear. Parental reaction time to behavior prompts was measured in seconds. Secondary outcomes were percentage changes in ECBI and Pediatric Sleep Questionnaire scores. Behavioral outburst duration was examined based on parental logs of start and end times of observed tantrums using a smartphone application. Result This study enrolled 50 children (median [IQR] age, 5.0 [4.0-6.0] years; 34 [68%] male and 16 [32%] female; 28 randomized to the PCIT-AI arm and 22 to the PCIT-TAU arm). Of these children, 37 (74%; 21 in the PCIT-AI arm and 16 in the PCIT-TAU arm) completed PCIT, with children wearing the watch a median (IQR) 75.7% (67.8%-82.9%) of the time, thus achieving the feasibility benchmark (primary outcome). Median (IQR) response time to behavior prompts in the PCIT-AI arm was 3.65 (2.07-7.08) seconds. Assessing between-group differences, there was no statistically significantly greater numerical improvement in ECBI-intensity percentage change (13.86%; 95% CI, −1.41% to 29.14%), ECBI-problem percentage change subscale scores (38.59%; 95% CI, −1.22% to 78.40%), or absolute change in Pediatric Sleep Questionnaire scores (−0.16; 95% CI, −1.85 to 1.53) with the PCIT-AI arm than with the PCIT-TAU arm. Children in the PCIT-AI arm had significantly shorter mean (SD) tantrum durations (10.4 [20.8] minutes vs 22.1 [30.0] minutes; P < .001) and lower odds of tantrums lasting for 15 minutes or more (odds ratio, 3.66; 95% CI, 2.72-4.95). Conclusions and Relevance In this randomized clinical trial, both recruitment and technology feasibility benchmarks were achieved. The findings inform the design of fully powered efficacy study of wearable, digitally augmented PCIT for children with disruptive behaviors. Trial Registration ClinicalTrials.gov Identifier: NCT05077722

Introduction: Transcranial magnetic stimulation (TMS) is a promising intervention for adolescents with treatment-resistant depression (TRD). However, the durability of TMS-related improvement in adolescents is unclear. This 6-month study followed adolescents with TRD who had responded to TMS and provided TMS retreatment for adolescents with a partial relapse. Methods: The study enrolled adolescents (12–21 years) with TRD who had at least a partial response to sham or active TMS in a randomized controlled trial. Partial response was defined as ≥25% reduction of Hamilton Depression Rating Scale-24 (HAMD24). Participants with a partial relapse (≥1 point increase in Clinical Global Impression–Severity) received retreatment with daily 10 Hz TMS sessions until depressive symptom severity returned to the baseline score or after 30 TMS treatments. Results: There were 84 eligible participants, 66 were enrolled, and 41 completed the 6-month study. Twenty-eight participants (42%) were retreated with TMS. TMS retreatment courses had a mean of 22 sessions. At the 6-month follow-up, the complete sample exhibited reduced depressive symptoms (mean HAMD24 of 5.24) compared with baseline at entry into follow-up (mean HAMD24 of 8.21). Baseline depressive symptom severity was positively correlated with the risk of partial relapse, while the number of previous TMS interventions showed no correlation with the risk of partial relapse. TMS was well tolerated. Conclusions: This is the largest, long-term follow-up study with TMS retreatment for adolescents with TRD. These findings demonstrate the feasibility and clinical effects of a TMS retreatment protocol for adolescents with TRD, following a standard course of acute TMS.

Background: Major adverse cardiovascular events (MACE), including myocardial infarction, acute coronary syndrome, ischemic heart disease requiring revascularization, stroke, and heart failure, have been documented as significant contributors to mortality in cancer survivors. Coronary artery calcium (CAC) can predict MACE in non-cancer populations, while calcium in the aorta (CA) has not been evaluated as a prognostic marker. Every patient diagnosed with cancer undergoes a standard-of-care Positron Emission Tomography-Computed Tomography (PET-CT) or a chest CT before the initiation of chemotherapy. Hypothesis: To determine whether the CAC or CA of patients with Hodgkin's or non-Hodgkin's lymphoma, derived from standard-of-care PET-CT/chest CT, can predict the incidence of MACE. Methods: Patients treated with anthracycline-based chemotherapy, diagnosed and followed from January 1, 2013, through June 30, 2023, were included. Patients who did not undergo a PET-CT or CT, and/or developed MACE before treatment initiation were excluded. Univariate and multivariate adjusted Cox regression models were employed to assess whether the presence of CAC, CA, or CAC-CA was associated with the development of MACE. Calcium was retrospectively quantified using TeraRecon software (Durham NC) and categorized as: 0, 1-99, and >100. Outcome analyses was estimated using the Kaplan-Meier method. Results: 326 patients were included, mean age of 55 years (range: 52-60), predominantly male 201 (61%) and white 314 (96%), CAC was found in 89 patients and CA in 140. In the univariate regression model, a statistically significant association was found with values >100 for CA, CAC and CAC-CA with the risk of MACE. (Fig 1a/b/c). CAC equal to 0 demonstrated a significant protective effect against MACE. (Fig 1a). In the multivariable analysis, these associations persisted even after adjusting for comorbidities. (Table 1). Conclusion: CAC, CA and CAC/CA >100 in the standard-of-care CT/PET CT are predictors of MACE in lymphoma patients undergoing anthracycline treatment, a CAC equal to 0 has protective effect, these relationships remained statistically significant after adjusting for comorbidities.

AbstractIntroductionInvasive neuromodulation interventions such as deep brain stimulation (DBS) and vagal nerve stimulation (VNS) are important treatments for movement disorders and epilepsy, but literature focused on young patients treated with DBS and VNS is limited. This retrospective study aimed to examine naturalistic outcomes of VNS and DBS treatment of epilepsy and dystonia in children, adolescents, and young adults.MethodsWe retrospectively assessed patient demographic and outcome data that were obtained from electronic health records. Two researchers used the Clinical Global Impression scale to retrospectively rate the severity of neurologic and psychiatric symptoms before and after patients underwent surgery to implant DBS electrodes or a VNS device. Descriptive and inferential statistics were used to examine clinical effects.ResultsData from 73 patients were evaluated. Neurologic symptoms improved for patients treated with DBS and VNS (p < .001). Patients treated with DBS did not have a change in psychiatric symptoms, whereas psychiatric symptoms worsened for patients treated with VNS (p = .008). The frequency of postoperative complications did not differ between VNS and DBS groups.ConclusionYoung patients may have distinct vulnerabilities for increased psychiatric symptoms during treatment with invasive neuromodulation. Child and adolescent psychiatrists should consider a more proactive approach and greater engagement with DBS and VNS teams that treat younger patients.

Background: The cortical silent period (CSP) and long-interval intracortical inhibition (LICI) are putative markers of γ-aminobutyric acid receptor type B (GABAB)-mediated inhibitory neurotransmission. We aimed to assess the association between LICI and CSP in youths. Methods: We analyzed data from three previous studies of youth who underwent CSP and LICI measurements with transcranial magnetic stimulation and electromyography. We assessed CSP and LICI association using Spearman rank correlation tests and multiple linear regression analyses adjusted for demographic and clinical covariates. Results: The sample included 16 healthy participants and 45 participants with depression. The general mean (SD) age was 15.5 (1.7), 14.3 (1.7) for healthy participants, and 15.9 (1.6) years for participants with depression. Measures were nonnormally distributed (Shapiro–Wilk, p < 0.001). CSP and LICI were not correlated at 100-millisecond (ρ = −0.2421, p = 0.06), 150-millisecond (ρ = −0.1612, p = 0.21), or 200-millisecond (ρ = −0.0507, p = 0.70) interstimulus intervals using Spearman rank correlation test. No correlations were found in the multiple regression analysis (p = 0.35). Conclusions: Although previous studies suggest that cortical silent period and long-interval intracortical inhibition measure GABAB receptor-mediated activity, these biomarkers were not associated in our sample of youths. Future studies should focus on the specific physiologic and pharmacodynamic properties assessed by CSP and LICI in younger populations.

Abstract Aim To appraise the current evidence on the efficacy and safety of lamotrigine (LAM) in the treatment of pediatric mood disorders (PMD) (i.e., Major Depressive disorder [MDD], bipolar disorder [BD]). Methods Major databases were searched for randomized controlled trials (RCTs), open‐label trials, and observational studies reporting on pediatric (age < 18 years) patients treated with LAM for mood disorders. Results A total of 3061 abstracts were screened and seven articles were selected for inclusion. Seven studies (319 BD and 43 MDD patients), including one RCT ( n = 173), three prospective ( n = 105), and three retrospective ( n = 84) studies, met the study criteria with a study duration range from 8 to 60.9 weeks. The mean age of this pooled data is 14.6 ± 2.0 years. LAM daily dosage varied from 12.5 to 391.3 mg/day among the studies. In an important finding, the RCT reported favorable outcomes with LAM (HR = 0.46; p = 0.02) in 13‐ to 17‐year‐old age group as compared with 10‐ to 12‐year‐old age group (HR = 0.93; p = 0.88). In addition, time to occurrence of a bipolar event trended toward favoring LAM over placebo. All the studies identified LAM as an effective and safe drug in PMDs especially, BDs. Overall, LAM was well tolerated with no major significant side effects and no cases of Stevens–Johnson syndrome. Conclusions Most studies suggested that LAM was safe and effective in pediatric patients with mood disorders. However, the data regarding the therapeutic range for LAM are lacking. Based on the data, there is inconsistent evidence to make conclusive recommendations on therapeutic LAM dosage for mood improvement in the pediatric population. Further studies including larger sample sizes are required to address this relevant clinical question.