Predictive and diagnostic measures for kernicterus spectrum disorder: a prospective cohort study.

BACKGROUND: Kernicterus spectrum disorder (KSD) resulting from neonatal hyperbilirubinemia remains a common cause of cerebral palsy worldwide. This 12-month prospective cohort study followed neonates with hyperbilirubinemia to determine which clinical measures best predict KSD. METHODS: The study enrolled neonates ≥35 weeks gestation with total serum bilirubin (TSB) ≥ 20 mg/dl admitted to Aminu Kano Hospital, Nigeria. Clinical measures included brain MRI, TSB, modified bilirubin-induced neurologic dysfunction (BIND-M), Barry-Albright Dystonia scale (BAD), auditory brainstem response (ABR), and the modified KSD toolkit. MRI signal alteration of the globus pallidus was scored using the Hyperbilirubinemia Imaging Rating Tool (HIRT). RESULTS: Of 25 neonates enrolled, 13/25 completed 12-month follow-up and six developed KSD. Neonatal BIND-M ≥ 3 was 100% sensitive and 83% specific for KSD. Neonatal ABR was 83% specific and sensitive for KSD. Neonatal HIRT score of 2 was 67% sensitive and 75% specific for KSD; this increased to 100% specificity and sensitivity at 12 months. BAD ≥ 2 was 100% specific for KSD at 3-12 months, with 50-100% sensitivity. CONCLUSIONS: Neonatal MRIs do not reliably predict KSD. BIND-M is an excellent screening tool for KSD, while the BAD or HIRT score at 3 or 12 months can confirm KSD, allowing for early diagnosis and intervention. IMPACT: The first prospective study of children with acute bilirubin encephalopathy evaluating brain MRI findings over the first year of life. Neonatal MRI is not a reliable predictor of kernicterus spectrum disorders (KSD). Brain MRI at 3 or 12 months can confirm KSD. The modified BIND scale obtained at admission for neonatal hyperbilirubinemia is a valuable screening tool to assess risk for developing KSD. The Barry Albright Dystonia scale and brain MRI can be used to establish a diagnosis of KSD in at-risk infants as early as 3 months.

Safety, timing, and outcomes of early post-operative cardiac catheterisation following congenital heart surgery.

OBJECTIVE: The safety of early post-operative cardiac catheterisation has been described following congenital heart surgery. Optimal timing of early post-operative cardiac catheterisation remains uncertain. The aim of this study was to describe the safety of early post-operative cardiac catheterisation and its impact on cardiac ICU and hospital length of stay, duration of mechanical ventilation, and extracorporeal support. METHODS: This single-centre retrospective cohort study compared clinical and outcome variables between "early" early post-operative cardiac catheterisation (less than 72 hours after surgery) and "late" early post-operative cardiac catheterisation (greater than 72 hours after surgery) groups using Chi-squared, Student's t, and log-rank test (or appropriate nonparametric test). RESULTS: In total, 132 patients were included, 22 (16.7%) "early" early post-operative cardiac catheterisation, and 110 (83.3%) "late" early post-operative cardiac catheterisation. Interventions were performed in 63 patients (51.5%), 7 (11.1%) early and 56 (88.9%) late. Complications of catheterisation occurred in seven (5.3%) patients, two early and five late. There were no major complications. Patients in the late group trended towards a longer stay in the cardiac ICU (19 days [7, 62] versus 11.5 days [7.2, 31.5], p = 0.6) and in the hospital (26 days [9.2, 68] versus 19 days [13.2, 41.8], p = 0.8) compared to the earlier group. CONCLUSION: "Early" early post-operative cardiac catheterisation was associated with an overall low rate of complications. Earlier catheterisations trended towards shorter cardiac ICU and hospital length of stays. Earlier catheterisations may lead to earlier recovery for patients not following an expected post-operative course.

Preterm sepsis is associated with acute lung injury as measured by pulmonary severity score.

BACKGROUND: Sepsis related acute lung injury (ALI) is established in adults but has not been investigated in premature infants. Herein, we used pulmonary severity score (PSS) trajectories and C-reactive protein (CRP) to examine the relation between sepsis and ALI in premature infants. METHODS: This retrospective study identified 211 sepsis and 123 rule out (RO) events in 443 infants born <31 weeks and <1500 grams. The PSS was calculated prior to, at the time of, and up to 1 week after each event. Initial and peak CRP values were collected for each event. RESULTS: PSS significantly increased at 0 h from baseline (-72h) and remained increased at all subsequent time points (all p < 0.002) in sepsis events. Mean PSS in sepsis episodes were also higher compared to RO events at +24 h, +48 h, +72 h, and +168 h (all p < 0.004). A positive correlation was noted between peak CRP values in sepsis events and PSS at 0 h, +24 h, +48 h, and +72 h. CONCLUSIONS: The temporal PSS trends and correlation with CRP levels observed in sepsis but not in RO events supports the hypothesis that neonatal sepsis is associated with ALI and contributes to the accumulating evidence that neonatal ARDS occurs. IMPACT: To evaluate pulmonary severity scores and c-reactive protein values over time to establish an association between preterm neonatal sepsis and acute lung injury (ALI). Though sepsis is well established as the most common indirect cause of ALI leading to acute respiratory distress syndrome (ARDS) in adults and pediatrics, this phenomenon remains undefined in neonates. This study validates the proposal by the Neonatal ARDS Project that ARDS also occurs in neonates by demonstrating acute and sustained changes in markers of pulmonary injury temporally related to a diagnosis of neonatal sepsis in preterm infants.

Criterion validity of wrist accelerometry for assessing energy intake via the intake-balance technique.

BACKGROUND: Intake-balance assessments measure energy intake (EI) by summing energy expenditure (EE) with concurrent change in energy storage (ΔES). Prior work has not examined the validity of such calculations when EE is estimated via open-source techniques for research-grade accelerometry devices. The purpose of this study was to test the criterion validity of accelerometry-based intake-balance methods for a wrist-worn ActiGraph device. METHODS: Healthy adults (n = 24) completed two 14-day measurement periods while wearing an ActiGraph accelerometer on the non-dominant wrist. During each period, criterion values of EI were determined based on ΔES measured by dual X-ray absorptiometry and EE measured by doubly labeled water. A total of 11 prediction methods were tested, 8 derived from the accelerometer and 3 from non-accelerometry methods (e.g., diet recall; included for comparison). Group-level validity was assessed through mean bias, while individual-level validity was assessed through mean absolute error, mean absolute percentage error, and Bland-Altman analysis. RESULTS: Mean bias for the three best accelerometry-based methods ranged from -167 to 124 kcal/day, versus -104 to 134 kcal/day for the non-accelerometry-based methods. The same three accelerometry-based methods had mean absolute error of 323-362 kcal/day and mean absolute percentage error of 18.1-19.3%, versus 353-464 kcal/day and 19.5-24.4% for the non-accelerometry-based methods. All 11 methods demonstrated systematic bias in the Bland-Altman analysis. CONCLUSIONS: Accelerometry-based intake-balance methods have promise for advancing EI assessment, but ongoing refinement is necessary. We provide an R package to facilitate implementation and refinement of accelerometry-based methods in future research (see paulhibbing.com/IntakeBalance).

Oxygenation index in the first three weeks of life is a predictor of bronchopulmonary dysplasia grade in very preterm infants.

BACKGROUND: The new bronchopulmonary dysplasia (BPD) grading system was developed based on its correlation with long-term respiratory and neurodevelopmental outcomes and may provide better personalized prognostication. Identifying early-life predictors for accurate BPD grade prediction may allow interventions to be tailored to individual needs. This study aimed to assess whether oxygenation index (OI) dynamics in the first three weeks of life are a predictor of BPD grade. METHODS: A single-center retrospective study was performed. Generalized additive mixed modeling was used to model OI trajectories for each BPD grade subgroup. A multinomial regression model was then developed to quantify the association between OI dynamics and BPD grade. RESULTS: Two hundred fifty-four infants were identified for inclusion in the trajectory modeling. A total of 6,243 OI data points were available for modeling. OI trajectory estimates showed distinct patterns in the three groups, most prominent during the third week of life. The average daily OI change was -0.33 ± 0.52 (n = 85) in the No-BPD group, -0.04 ± 0.75 (n = 82) in the Low-Grade BPD group, and 0.22 ± 0.65 (n = 75) in the High-Grade BPD group (p < 0.001). A multinomial regression analysis showed the initial OI value and the average daily OI change both independently correlated with BPD grade outcomes after adjusting for birth gestation, birth weight z-score, sex, and the duration of invasive ventilation. CONCLUSION: Early-life OI dynamics may be a useful independent marker for BPD grade prediction. Prospective studies may be warranted to further validate the findings.

Moderators of peak respiratory exchange ratio during exercise testing in children and adolescents with Fontan physiology.

OBJECTIVES: Many patients with Fontan physiology are unable to achieve the minimum criteria for peak effort during cardiopulmonary exercise testing. The purpose of this study is to determine the influence of physical activity and other clinical predictors related to achieving peak exercise criteria, signified by respiratory exchange ratio ≥ 1.1 in youth with Fontan physiology. METHODS: Secondary analysis of a cross-sectional study of 8-18-year-olds with single ventricle post-Fontan palliation who underwent cardiopulmonary exercise testing (James cycle protocol) and completed a past-year physical activity survey. Bivariate associations were assessed by Wilcoxon rank-sum test and simple regression. Conditional inference forest algorithm was used to classify participants achieving respiratory exchange ratio > 1.1 and to predict peak respiratory exchange ratio. RESULTS: Of the n = 43 participants, 65% were male, mean age was 14.0 ± 2.4 years, and 67.4% (n = 29) achieved respiratory exchange ratio ≥ 1.1. Despite some cardiopulmonary exercise stress test variables achieving statistical significance in bivariate associations with participants achieving respiratory exchange ratio > 1.1, the classification accuracy had area under the precision recall curve of 0.55. All variables together explained 21.4% of the variance in respiratory exchange ratio, with peak oxygen pulse being the most informative. CONCLUSION: Demographic, physical activity, and cardiopulmonary exercise test measures could not classify meeting peak exercise criteria (respiratory exchange ratio ≥ 1.1) at a satisfactory accuracy. Correlations between respiratory exchange ratio and oxygen pulse suggest the augmentation of stroke volume with exercise may affect the Fontan patient's ability to sustain high-intensity exercise.

Transcranial direct current stimulation to modulate fMRI drug cue reactivity in methamphetamine users: A randomized clinical trial.

Transcranial direct current stimulation (tDCS) has been studied as a therapeutic option to alter maladaptive brain functions associated with chronic substance use. We present a randomized, triple-blind, sham-controlled, clinical trial to determine the neural substrates of tDCS effects on drug craving. Sixty participants with methamphetamine use disorder were assigned to two groups: active tDCS (5 x 7 cm2 , 2 mA, 20 min, anode/cathode over the F4/Fp1) and sham stimulation. Neuroimaging data of a methamphetamine cue reactivity task were collected immediately before and after stimulation. There was a significant reduction in self-reported craving after stimulation without any significant effect of time-by-group interaction. Our whole-brain analysis demonstrated that there was a global decrease in brain reactivity to cues following sham but not active tDCS. There were significant time-by-group interactions in five main clusters in middle and inferior frontal gyri, anterior insula, inferior parietal lobule, and precuneus with higher activations after active stimulation. There was a significant effect of stimulation type in the relationship between electrical current at the individual level and changes in task-modulated activation. Brain regions with the highest electric current in the prefrontal cortex showed a significant time-by-group interaction in task-modulated connectivity in the frontoparietal network. In this trial, there was no significant effect of the one session of active-F4/Fp1 tDCS on drug craving self-report compared to sham stimulation. However, activation and connectivity differences induced by active compared to sham stimulation suggested some potential mechanisms of tDCS to modulate neural response to drug cues.

Commercial Devices Provide Estimates of Energy Balance with Varying Degrees of Validity in Free-Living Adults.

BACKGROUND: The challenges of accurate estimation of energy intake (EI) are well-documented, with self-reported values 12%-20% below expected values. New approaches rely on gold-standard assessments of the other components of energy balance, energy expenditure (EE) and energy storage (ES), to estimate EI. OBJECTIVES: The purpose of this study was to evaluate the validity, repeatability, and measurement error of consumer devices when estimating energy balance in a free-living population. METHODS: Twenty-four healthy adults (14 women, 10 men; mean ± SD age: 30.7 ± 8.2 y) completed two 14-d assessment periods, including assessments of EE and ES using gold-standard [doubly labeled water (DLW) and DXA] and commercial devices [Fitbit Alta HR activity monitor (Alta) and Fitbit Aria wireless body composition scale (Aria)], and of EI by dietician-administered recalls. Accuracy and validity were assessed using Spearman correlation, interclass correlation, mean absolute percentage error, and equivalency testing. We also applied linear measurement error modeling including error in gold-standard devices and within-subject repeated-measures design to calibrate consumer devices and quantify error. RESULTS: There was moderate to strong agreement for EE between the Fitbit Alta and DLW at each time point (rs = 0.82 and 0.66 for Times 1 and 2, respectively). There was weak agreement for ES between the Fitbit Aria and DXA (rs = 0.15 and 0.49 for Times 1 and 2, respectively). Correlations between methods to assess EI ranged from weak to strong, with agreement between the DXA/DLW-calculated EI and dietary recalls being the highest (rs = 0.63 for Time 1 and 0.73 for Time 2). Only EE from the Fitbit Alta at Time 1 was equivalent to the DLW value using equivalency testing. CONCLUSIONS: Commercial devices provide estimates of energy balance in free-living adults with varying degrees of validity compared to gold-standard techniques. EE estimates were the most robust overall, whereas ES estimates were generally poor.

Behavioral activation therapy for depression is associated with a reduction in the concentration of circulating quinolinic acid.

BACKGROUND: An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown. METHODS: Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA). RESULTS: BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). Neither the change in KynA/QA, nor baseline KynA/QA were associated with response to BA therapy. CONCLUSION: The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.

Kernicterus Spectrum Disorders Diagnostic Toolkit: validation using retrospective chart review.

BACKGROUND: Kernicterus Spectrum Disorders (KSDs) result from hyperbilirubinemia-induced brain injury. We developed a Toolkit (KSD-TK) to predict the likelihood of KSDs. This study aims to validate the KSD-TK by comparing it to clinical diagnoses made by the Kernicterus Clinic in the Division of Neurology. METHODS: Through retrospective chart review, we completed a KSD-TK for 37 patients evaluated between 2011 and 2019 using highest bilirubin, newborn risk factors, neonatal exam, follow-up exam, auditory testing, tooth enamel, and MRI brain results. KSD-TK results were compared to the clinical diagnoses given by a kernicterus expert (SS). RESULTS: Of 37 patients, 29 were clinically diagnosed with kernicterus, including 14/14 with KSD-TK scored as "definite", 14/15 "probable", and 1/2 with "possible" kernicterus. None of 6 patients with KSD-TK "not kernicterus" were clinically diagnosed with kernicterus. Combining KSD-TK "definite" and "probable", the KSD-TK has 96.6% sensitivity and 87.5% specificity. Each KSD-TK component had high sensitivity, but only three had specificity ≥0.75: auditory neuropathy spectrum disorder, abnormal movements and/or tone on follow-up exam, and abnormal globus pallidus and/or subthalamic nucleus on MRI. CONCLUSION: The KSD-TK is a promising screening tool for patients at risk for kernicterus. IMPACT: This study provides validation of a Kernicterus Spectrum Disorders (KSDs) Toolkit. The toolkit provides screening criteria for predicting KSD diagnosis. Scores of definite or probable have high sensitivity and specificity for KSDs. Abnormal auditory processing, exam, and MRI were most specific for KSDs.

Motivating Behavior Change in Parents for Suicide Prevention in the Midwest, USA.

Safe storage of lethal means is an evidence-based approach to suicide prevention that is underutilized. This naturalistic study investigated whether a presentation on parenting teenagers that includes education about safe storage of firearms and medications, paired with tools to enact change, can impact storage practices. Ten community presentations for parents were given between November 2018 and September 2019 in the Midwest region of the United States. Multiple topics pertinent to parenting adolescents were included with an emphasis on safe storage of firearms and medications to reduce suicide risk. Toolkits including medication storage boxes and cable gun locks were offered to help parents enact recommended changes. Surveys were completed prior to the presentation (T1), immediately following the presentation (T2), and 2 weeks after the presentation (T3). Five-hundred eighty-one parents comprised the initial study sample, of whom 410 (70.6%) completed the primary study endpoint. Generalized linear mixed models with and without worst-case imputation were used to evaluate changes in safe storage practices. Results suggested the odds of storing firearms in the safest manner possible increased 5.9 times (95% CI 2.6-13.5, p < 0.001) without imputation and increased 2.0 times (95% CI 1.1-3.4, p = 0.02) with the worst-case imputation. Among participants with unlocked medications at baseline, 56.5% reported they had disposed of old medications and 53.0% reported locking up bottles of medication by the primary study endpoint. This study provides preliminary evidence that safe storage education paired with tools for behavior change motivates parents to enact safe storage measures.

Heart Rate Recovery Following Exercise Testing in Pediatric Patients with Acyanotic Repaired Congenital Heart Disease.

Attenuated heart rate recovery (HRR) following peak exercise has been shown to be a predictor of mortality in populations of adults with Fontan palliation, coronary artery disease, heart failure, and heart transplantation. However, few have studied HRR in children and adolescents with congenital heart disease (CHD). This case-control study compared HRR patterns from exercise stress testing in children and adolescents with and without repaired acyanotic CHD (raCHD). Retrospective analysis included patients aged 10-18 years who had exercise testing between 2007 and 2017. The raCHD cohort included patients with Tetralogy of Fallot, transposition of the great arteries, coarctation, truncus arteriosus, atrioventricular septal defect, pulmonary outflow obstruction, aortic stenosis and/or insufficiency, or septal defects. Those in the control cohort were matched for age, sex, BMI, peak METs achieved, and peak heart rate (HR). HR at 1-min intervals throughout the 10-min recovery period and HRR patterns were analyzed. The study included n = 584 individuals (raCHD: n = 146), median age 14 years old, 67.1% male. The cohorts had similar resting and peak HRs. Linear mixed-effects models (LMM) suggested statistically significant cohort-by-time interaction for HR in exercise recovery, with the largest mean difference at minute-6 (2.9 bpm, p = 0.008). When comparing lesion types, LMM found no cohort or cohort-by-time interaction. While minute-6 of exercise recovery was statistically significant, the difference was 2.9 bpm and may not have clinical significance. These results suggest that HRR in pediatric raCHD patients should not vary from their healthy peers, and an attenuated HRR may not be directly attributed to underlying raCHD.

Latent variables for region of interest activation during the monetary incentive delay task.

BACKGROUND: The Monetary Incentive Delay task (MID) has been used extensively to probe anticipatory reward processes. However, individual differences evident during this task may relate to other constructs such as general arousal or valence processing (i.e., anticipation of negative versus positive outcomes). This investigation used a latent variable approach to parse activation patterns during the MID within a transdiagnostic clinical sample. METHODS: Participants were drawn from the first 500 individuals recruited for the Tulsa-1000 (T1000), a naturalistic longitudinal study of 1000 participants aged 18-55 (n = 476 with MID data). We employed a multiview latent analysis method, group factor analysis, to characterize factors within and across variable sets consisting of: (1) region of interest (ROI)-based blood oxygenation level-dependent (BOLD) contrasts during reward and loss anticipation; and (2) self-report measures of positive and negative valence and related constructs. RESULTS: Three factors comprised of ROI indicators emerged to accounted for >43% of variance and loaded on variables representing: (1) general arousal or general activation; (2) valence, with dissociable responses to anticipation of win versus loss; and (3) region-specific activation, with dissociable activation in salience versus perceptual brain networks. Two additional factors were comprised of self-report variables, which appeared to represent arousal and valence. CONCLUSIONS: Results indicate that multiview techniques to identify latent variables offer a novel approach for differentiating brain activation patterns during task engagement. Such approaches may offer insight into neural processing patterns through dimension reduction, be useful for probing individual differences, and aid in the development of optimal explanatory or predictive frameworks.

Consensus features nested cross-validation.

SUMMARY: Feature selection can improve the accuracy of machine-learning models, but appropriate steps must be taken to avoid overfitting. Nested cross-validation (nCV) is a common approach that chooses the classification model and features to represent a given outer fold based on features that give the maximum inner-fold accuracy. Differential privacy is a related technique to avoid overfitting that uses a privacy-preserving noise mechanism to identify features that are stable between training and holdout sets.We develop consensus nested cross-validation (cnCV) that combines the idea of feature stability from differential privacy with nCV. Feature selection is applied in each inner fold and the consensus of top features across folds is used as a measure of feature stability or reliability instead of classification accuracy, which is used in standard nCV. We use simulated data with main effects, correlation and interactions to compare the classification accuracy and feature selection performance of the new cnCV with standard nCV, Elastic Net optimized by cross-validation, differential privacy and private evaporative cooling (pEC). We also compare these methods using real RNA-seq data from a study of major depressive disorder.The cnCV method has similar training and validation accuracy to nCV, but cnCV has much shorter run times because it does not construct classifiers in the inner folds. The cnCV method chooses a more parsimonious set of features with fewer false positives than nCV. The cnCV method has similar accuracy to pEC and cnCV selects stable features between folds without the need to specify a privacy threshold. We show that cnCV is an effective and efficient approach for combining feature selection with classification. AVAILABILITY AND IMPLEMENTATION: Code available at https://github.com/insilico/cncv. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

COVID-19, Telehealth, and Pediatric Integrated Primary Care: Disparities in Service Use.

OBJECTIVE: The coronavirus disease 2019 pandemic (COVID-19) may increase pediatric mental health needs due to its social, economic, and public health threats, especially among Black, Indigenous, and People of Color and those served within disadvantaged communities. COVID-19 protocols have resulted in increased provision of telehealth in integrated primary care (IPC) but little is known about pediatric telehealth IPC utilization during the pandemic for diverse and traditionally underserved groups. METHODS: A comparative study was conducted to explore variability between in-person (pre-COVID-19; n = 106) and telehealth (mid-COVID-19; n = 120) IPC consultation utilization among children 1-19 years old served through a large, inner-city primary care clinic. Logistic regression modeling was used to examine the association between service delivery modality (i.e., in-person vs. telehealth) and attendance, referral concerns, and several sociodemographic variables. RESULTS: Service delivery modality and attendance, referral concerns, and race/ethnicity were significantly associated. The odds of non-attendance were greater for children scheduled for telehealth, the odds of children with internalizing problems being scheduled for telehealth were greater than those with externalizing problems, and the odds of Black children being scheduled for telehealth were less compared to White children. CONCLUSION: Though telehealth has helped provide IPC continuity during COVID-19, findings from this study show troubling preliminary data regarding reduced attendance, increased internalizing concerns, and disparities in scheduling for Black patients. Specific actions to monitor and address these early but alarming indications of telehealth and Covid-19 related behavioral health disparities are discussed.

Methylphenidate augmentation of escitalopram to enhance adherence to antidepressant treatment: a pilot randomized controlled trial.

BACKGROUND: Adherence to treatment, i.e. the extent to which a patient's therapeutic engagement coincides with the prescribed treatment, is among the most important problems in mental health care. The current study investigated the influence of pairing an acute positive reinforcing dopaminergic/noradrenergic effect (methylphenidate, MPH) with a standard antidepressant on the rates of adherence to medication treatment. The primary objective of this study was to determine whether MPH + escitalopram resulted in higher rates of medication adherence relative to placebo + escitalopram. METHODS: Twenty participants with moderate to severe depression were 1-1 randomized to either (1) 5 mg MPH + 10 mg escitalopram or (2) placebo + 10 mg escitalopram with the possibility for a dose increase at 4 weeks. A Bayesian analysis was conducted to evaluate the outcomes. RESULTS: First, neither percent Pill count nor Medication Electronic Monitoring System adherence showed that MPH was superior to placebo. In fact, placebo showed slightly higher adherence rates on the primary (7.82% better than MPH) and secondary (7.07% better than MPH) outcomes. There was a less than 25% chance of MPH augmentation showing at least as good or better adherence than placebo. Second, both groups showed a significant effect of treatment on the QIDS-SR with a median effect of an 8.6-point score reduction. Third, neither subjective measures of adherence attitudes nor socio-demographic covariates had a significant influence on the primary or secondary outcome variables. CONCLUSIONS: These data do not support the use of MPH to increase adherence to antidepressant medication in individuals with moderate to severe depression. CLINICALTRIALS. GOV IDENTIFIER: NCT03388164 , registered on 01/02/2018.

Extracurricular Activities, Screen Media Activity, and Sleep May Be Modifiable Factors Related to Children's Cognitive Functioning: Evidence From the ABCD Study®.

This study used a machine learning framework in conjunction with a large battery of measures from 9,718 school-age children (ages 9-11) from the Adolescent Brain Cognitive DevelopmentSM (ABCD) Study to identify factors associated with fluid cognitive functioning (FCF), or the capacity to learn, solve problems, and adapt to novel situations. The identified algorithm explained 14.74% of the variance in FCF, replicating previously reported socioeconomic and mental health contributors to FCF, and adding novel and potentially modifiable contributors, including extracurricular involvement, screen media activity, and sleep duration. Pragmatic interventions targeting these contributors may enhance cognitive performance and protect against their negative impact on FCF in children.

A pragmatic clinical trial examining the impact of a resilience program on college student mental health.

BACKGROUND: One in three college students experience significant depression or anxiety interfering with daily functioning. Resilience programs that can be administered to all students offer an opportunity for addressing this public health problem. The current study objective was to assess the benefit of a brief, universal resilience program for first-year college students. METHOD: First-year students at a private, midwestern university participated. This trial used a pragmatic design, delivering the intervention within university-identified orientation courses and was not randomized. The four-session resilience program included goal-building, mindfulness, and resilience skills. The comparison was orientation-as-usual. Primary outcomes included PROMIS® Depression and Anxiety and Connor-Davidson Resilience Scale. Secondary and exploratory outcomes included the Perceived Stress Scale, Emotion Regulation, and Cognitive Behavioral Therapy (CBT) Skills Questionnaires, and Freiburg Mindfulness Inventory. Time by treatment interactions at post-training and semester-end were examined using linear mixed models. RESULTS: Analysis included 252 students, 126 who completed resilience programming and a matched comparison sample. Resilience programming did not relate to improvements in depression at post-training (CI: -2.53 to 1.02; p = .404, d =-0.08), but did at semester-end (95% CI: -4.27 to -0.72; p = .006, d = -0.25) and improvements in perceived stress were observed at post-training (CI: -3.31 to -0.44; p = .011, d = -0.24) and semester-end (CI: -3.30 to -0.41; p = .013, d = -0.24). Emotion regulation, mindfulness, and CBT skills increased, with CBT skills mediating clinical improvements. CONCLUSIONS: Universal implementation of a brief, resilience intervention may be effective for improving college student mental health.

Randomized trial of vitamin D3 to prevent worsening of musculoskeletal symptoms in women with breast cancer receiving adjuvant letrozole. The VITAL trial.

PURPOSE: Aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) frequently occur in women being treated for breast cancer. Prior studies suggest high prevalence of vitamin D deficiency in breast cancer patients with musculoskeletal (MS) pain. We conducted a randomized, placebo-controlled trial to determine if 30,000 IU vitamin D3 per week (VitD3) would prevent worsening of AIMSS in women starting adjuvant letrozole for breast cancer. METHODS: Women with stage I-III breast cancer starting adjuvant letrozole and 25(OH)D level ≤40 ng/ml were eligible. All subjects received standard daily supplement of 1200 mg calcium and 600 IU vitamin D3 and were randomized to 30,000 IU oral VitD3/week or placebo. Pain, disability, fatigue, quality of life, 25(OH)D levels, and hand grip strength were assessed at baseline, 12, and 24 weeks. The primary endpoint was incidence of an AIMSS event. RESULTS: Median age of the 160 subjects (80/arm) was 61. Median 25OHD (ng/ml) was 25 at baseline, 32 at 12 weeks, and 31 at 24 weeks in the placebo arm and 22, 53, and 57 in the VitD3 arm. There were no serious adverse events. At week 24, 51% of women assigned to placebo had a protocol defined AIMSS event (worsening of joint pain using a categorical pain intensity scale (CPIS), disability from joint pain using HAQ-II, or discontinuation of letrozole due to MS symptoms) vs. 37% of women assigned to VitD3 (p = 0.069). When the brief pain inventory (BPI) was used instead of CPIS, the difference was statistically significant: 56 vs. 39% (p = 0.024). CONCLUSIONS: Although 30,000 IU/week of oral vitamin D3 is safe and effective in achieving adequate vitamin D levels, it was not associated with a decrease in AIMSS events based on the primary endpoint. Post-hoc analysis using a different tool suggests potential benefit of vitamin D3 in reducing AIMSS.