Faculty Bibliography

Abstract: Introduction: Fatigue is one of the most prevalent and under-assessed non-motor symptoms in Parkinson's disease (PD). Current therapies have limited effectiveness. Presently, tDCS has shown potential to improve certain symptoms of PD. We designed a tDCS protocol to allow study participation from the patient's home, while maintaining clinical trial standards. We utilized a live video-conferencing platform and specially designed equipment that 'unlocks' one session at a time. Study objective: To assess feasibility and explore the therapeutic potential of remotely supervised tDCS (RS-tDCS) paired with cognitive training (CT) for PD patients suffering from fatigue.
Method(s): Double-blind, randomized, sham controlled study of RS-tDCS paired with CT. Participants completed 10 daily tDCS sessions (20-minute, 2.0-mA, bi-frontal, F3-F4 montage, left anodal), with the option of 10 additional open label sessions. Evaluation of preliminary clinical effects with the fatigue severity scale (FSS) along with tolerability, safety and compliance were completed.
Result(s): Eighteen participants were screened, 17 enrolled (Table 1), one screen failure. Incidence of the systematically recorded side effects were 22.4% tingling, 11.5% burning sensation, 8.2% itching, 3.3% headache, 0.9% nausea, 0.3% dizziness and 0.3% sleepiness. No serious adverse events reported. Compliance and tolerability were 100%. Preliminary fatigue clinical effects of 10 sessions showed a significant decrease of mean FSS only in the real RS-tDCS group of 8.0 (SD 9.82) points (p < 0.05). Further analysis of 20 RS-tDCS sessions (10 DoubleBlind-real+10 Open-label) showed a further significant decrease in mean FSS of 11.47 (SD 10.7) points (p < 0.05).
Conclusion(s): At-home RS-tDCS therapy paired with CT is safe and well tolerated by PD patients, with the advantages of ease of recruitment and optimal subject compliance. At-home RS-tDCS therapy paired with CT shows potential to remediate fatigue symptoms in PD, but the small sample size limits efficacy conclusions. Our paradigm may be influential in designing future studies. [Figure presented] Introduction: Parkinson's Disease (PD) is a progressively disabling disease that affects patients and their caregivers' quality of life. PD is a chronic neurodegenerative disease affecting a large number of dopaminergic neurons in the nigrostriatal pathway, responsible for common motor dysfunction such as slowness, tremor and rigidity. The disease also leads to various non-motor symptoms, in particular, fatigue and cognitive disability. The available pharmacotherapy often allows for a relatively good control of symptoms, but complications could arise from the side effects of medications, or the progressive nature of the disease [1]. Certain alternative therapies have emerged such as non-invasive brain stimulation (NIBS) that may potentially improve declining function. Transcranial direct current stimulation (tDCS) is a low-cost, safe and practical treatment compared to other NIBS. tDCS is a portable device that utilizes a weak electrical current to modulate neuronal membrane potentials and cortical excitability [2-3]. Fatigue is a highly prevalent symptom that is largely unrecognized in PD with no current evidence-based treatment [4]. Since tDCS has shown beneficial effects in motor, mood and cognitive symptoms in PD, it may have potential to ameliorate fatigue in PD.
Method(s): The study design is a double blind randomized, sham controlled trial using at-home tDCS paired with CT. Remote supervision of tDCS sessions was performed through a video-conferencing platform. The tele-rehabilitation design has been recently validated and allows participation of patients from the comfort of their homes [5]. Feasibility and preliminary effects of RS-tDCS in PD were tested using a dorsolateral prefrontal cortex (DLPFC) montage (F3-F4 from the EEG 10x20 system). All participants received a baseline physical, neurological, fatigue and cognitive assessments. Participants were asked to complete 10 daily sessions. Once finalized, they were offered 10 additional open label (OpL) sessions. Using a detailed study "stop" criteria [6, 7] flow chart, participants were cleared at each step for their participation to proceed. The primary objectives of the study were to determine the feasibility of RS tDCS paired with CT and explore the potential to ameliorate fatigue in PD. Clinical effects on fatigue were measured with the fatigue severity scale (FSS), a scale largely validated and recommended for this population [4]. FSS was obtained at baseline and after 10 tDCS sessions of 20 minutes with 2 milliamperes (mA) intensity, while participants engaged in computerized based CT. During the visits, acceptability of therapy, tolerability, side effects and other adverse events (AEs) were collected. An optional OpL period allows for a more comprehensive exploratory evaluation of RS-tDCS effects beyond 10 sessions.
Result(s): Eighteen patients were screened and seventeen were enrolled (one screen failure). Only one participant decided to opt out of the OpL portion of the study. Patient demographic characteristics did not differ between groups (Table 1). Pain tolerability of 2.0 mA stimulation with <=6 on visual analog scale for pain (VAS-Pain) was 100%. Incidence of the systematically recorded side effects were 22.4% tingling, 11.5% burning sensation, 8.2% itching, 3.3% headache, 0.9%, nausea, 0.3% dizziness and 0.3% sleepiness. Other adverse events (AEs) are listed in figure 1. No serious AEs were reported. All required visits were completed with no attrition or interruptions (100% compliance). Preliminary fatigue clinical effects of 10 sessions showed a significant decrease of mean FSS only in the real RS-tDCS group of 8.0 (SD 9.82) points (p < 0.05). Further analysis of 20 RS-tDCS sessions (10 DoubleBlind-real+10 Open-label) showed a further significant decrease in mean FSS of 11.47 (SD 10.7) points (p < 0.05) (Figure 2). [Figure presented] Discussion and
Conclusion(s): This novel design of remotely supervised tDCS has allowed conducting tDCS sessions safely and away from the lab setting, in the comfort of participant's homes. This paradigm of NIBS is particularly suited for medical conditions limiting mobility like PD, participants with busy schedules or living far distances from clinics. The initial results of this study showed that this protocol is feasible, acceptable and safe in PD with no major adverse events. [Figure presented] Our study has shown that RS-tDCS holds therapeutic potential for fatigue in people with PD, and showed 20 sessions seemed more favorable than 10 sessions. Trials with a greater sample size and extended treatment duration might be more suitable to establish the real efficacy for this therapy as a treatment of fatigue. Study Supported by Grant No. PDF-TRG-1722 from the Parkinson's Foundation. References [1] Kalia, L. V., & Lang, A. E. Parkinson's disease. Lancet, 386(9996), 896-912. (2015) [2] Priori, A., Berardelli, A., Rona, S., Accornero, N., & Manfredi, M. Polarization of the human motor cortex through the scalp. Neuroreport, 9(10), 2257-2260. (1998) [3] Nitsche, M. A., & Paulus, W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol, 527 Pt 3, 633-639. (2000) [4] Friedman, J. H., Beck, J. C., Chou, K. L., et al. Fatigue in Parkinson's disease: report from a mutidisciplinary symposium. NPJ Parkinsons Dis, 2. (2016) [5] Biagioni, M. C., Sharma, K., Migdadi, H. A., & Cucca, A. Non-Invasive Neuromodulation Therapies for Parkinson's Disease. IntechOpen, DOI: 10.5772/intechopen.75052. (2018) [6] Kasschau, M., Sherman, K., Haider, L., et al. A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS). J Vis Exp(106), e53542. (2015) [7] Charvet, L. E., Kasschau, M., Datta, A., et al. Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols. Frontiers in Systems Neuroscience, 9(26). (2015)
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The majority of youth in the juvenile justice system have experienced multiple traumatic events in their lives, including community violence, physical abuse, neglect, and traumatic loss. These high prevalence rates, coupled with the known negative consequences of trauma in childhood and adolescence, have led to a greater emphasis on implementing trauma-informed services and practices within juvenile justice settings. However, although many stakeholders and government entities have expressed support for creating more trauma-informed juvenile justice systems, there is still limited empirical knowledge about which interventions are most effective at improving outcomes, particularly at the organizational or facility level. In an effort to fill this gap, the current study evaluated the impact of a trauma-informed milieu intervention, including skills training for youth and training for staff, on rates of violence at two secure juvenile detention facilities (N = 14,856) located in a large Northeastern city. The analyses revealed that the intervention was significantly related to a reduction of violent incidents in Facility A, with no impact on incidents in Facility B. Follow-up analyses revealed that a larger proportion of eligible youth in Facility A completed the skills group program as compared with eligible youth in Facility B (16% vs. 9%). This finding has important implications for the implementation of trauma-informed interventions for youth in juvenile detention settings, as it suggests that to impact outcomes at the facility level, a minimum threshold of youth may need to be exposed to the intervention. In addition, reductions in violence at Facility A were only realized after both staff training and youth skills components were implemented, suggesting that both components are necessary to create change at the facility level. Future research is needed to further explore the impact of organizational and implementation-level factors on trauma-informed care outcomes in juvenile justice settings.

Introduction Despite stimulants being highly efficacious in short-term randomised controlled trials (RCTs), not all patients respond or can successfully tolerate them. A number of novel non-stimulant options are currently in the pipeline for the treatment of ADHD. Areas covered The authors conducted a systematic review of RCTs registered in ClinicalTrials.gov in the past five years (January 2014 and February 2019), supplemented by searches in PubMed, Web of Science, and drug manufacturers websites to find recent RCTs on novel non-stimulant ADHD medications. Expert opinion The authors found 28 pertinent RCTs of compounds acting on a variety of biological targets, including Dasotraline, Viloxazine (SPN-812), Centanafadine SR (CTN SR), OPC-64005, Fasoracetam (NFC-1, AEVI-001), Metadoxine (MDX), Vortioxetine, Tipepidine Hibenzate, Oxytocin, Sativex (delta-9-tetrahydrocannabinol (THC) plus cannabidiol), Mazindol, and Molindone hydrochloride (SPN-810). Given the high effect size found in RCTs of stimulants in terms of efficacy on ADHD core symptoms, it is unlikely that these novel agents will show better efficacy than stimulants, at the group level. However, they may offer comparable or better tolerability. Additionally, agents acting on etiopathophysiological targets disrupted in specific subgroups of patients with ADHD will move forward the pharmacotherapy of ADHD from a "one size fits all" to a "precision medicine" approach.

Data on the impact of the ketogenic diet (KD) on children's growth remain controversial. Here, we retrospectively investigated the occurrence of linear growth retardation in 34 children (47% males; age range: 2-17 years) diagnosed with drug-resistant epilepsy (DRE; n = 14) or glucose transporter type 1 deficiency syndrome (GLUT1-DS; n = 20) who had been treated with the KD for 12 months. The general characteristics of children with and without growth retardation were also compared. All participants received a full-calorie, traditional KD supplemented with vitamins, minerals, and citrate. Most children (80%; 11/14 in the DRE subgroup and 16/20 in the GLUT1-DS subgroup) treated with the KD did not show growth retardation at 12 months. Although participants with and without delay of growth did not differ in terms of baseline clinical characteristics, dietary prescriptions, or supplementation patterns, marked ketosis at 12 months tended to occur more frequently in the latter group. Altogether, our results indicate that growth retardation may occur in a minority of children treated with the KD. However, further research is required to identify children at risk and to clarify how increased ketones levels may affect endocrine pathways regulating growth during KD administration.

Adult hippocampal neurogenesis has been reported to be decreased, increased, or not changed in Alzheimer's disease (AD) patients and related transgenic mouse models. These disparate findings may relate to differences in disease stage, or the presence of seizures, which are associated with AD and can stimulate neurogenesis. In this study, we investigate a transgenic mouse model of AD that exhibits seizures similarly to AD patients and find that neurogenesis is increased in early stages of disease, as spontaneous seizures became evident, but is decreased below control levels as seizures recur. Treatment with the antiseizure drug levetiracetam restores neurogenesis and improves performance in a neurogenesis-associated spatial discrimination task. Our results suggest that seizures stimulate, and later accelerate the depletion of, the hippocampal neural stem cell pool. These results have implications for AD as well as any disorder accompanied by recurrent seizures, such as epilepsy.

Introduction Hispanics are the largest ethnic minority group in the United States. The prevalence of depression and co-morbid depression in the Hispanic population is well-recognized. The positive association between physical activity and psychological health improves mood, emotional well-being, and prognostic outcome. Objectives There are two aspects of our research paper. First, it critically reviews the available literature showing the correlation between physical exercise and depression. Second, it analyzes the association between exercise and depression in uncontrolled diabetic Hispanics using data collected from the local community intervention program. Method A chi-square analysis was conducted to examine whether levels of physical activity reported at the baseline were associated with the frequency of depressed mood and anhedonia self-reported for the previous two weeks. This study utilized the use of the PHQ-2 scale for the assessment of depressive symptoms. The PHQ-2 scale is a useful tool to screen for depression in the integrated care setting. Participants from a local community intervention program were stratified on the basis of their gender and preferred language. Data were collected and represented in tables according to demographic characteristics. Results Our study established a statistically significant association between the levels of physical activity and the frequency of depression symptoms among Spanish speaking participants from the local community intervention program. These results provide convincing evidence that biological, developmental, social, and psychological factors facilitate the association between physical activity and depression.

This review describes developments in epilepsy research during the last 3 to 4 decades that focused on the dentate gyrus (DG) and its role in temporal lobe epilepsy (TLE). The emphasis is on basic research in laboratory animals and is chronological, starting with hypotheses that attracted a lot of attention in the 1980s. Then experiments are described that addressed the questions, as well as new methods that often made the experiments possible. In addition, where new questions arose and the implications for clinical epilepsy are discussed.

BACKGROUND:Specialty courts have emerged as a model of care for U.S. youth impacted by commercial sexual exploitation (CSE) to ensure comprehensive service provision. However, there is a lack of published research that documents the extent to which these programs achieve this goal. OBJECTIVE:We sought to understand a specialty juvenile justice court's role in identifying mental health and substance use treatment needs, providing linkages to services, and facilitating stability for youth with histories of CSE. PARTICIPANTS AND SETTING/METHODS:We conducted an exhaustive court file review of the 364 participants in a U.S. based juvenile delinquency specialty court for youth affected by CSE. The observation period spanned 2012-2017. METHODS:The research team systematically transferred data from court files into a secure, electronic database. Descriptive statistics and Chisquared tests were calculated to explore potential associations. RESULTS:Participation in the specialty court for youth impacted by CSE suggests an increase in identification of mental health and substance use needs and linkages and referrals to mental health and substance use treatment services. In addition, there was increased stabilization as indicated by decreased substantiated child welfare allegations, fewer running away episodes, and placements and criminal involvement. CONCLUSIONS:Specialty courts that incorporate a multidisciplinary, trauma-informed approach offer a promising intervention model for meeting the high treatment needs of youth impacted by CSE.

BACKGROUND:Little work investigates the effect of behavioral health system efforts to increase use of evidence-based practices or how organizational characteristics moderate the effect of these efforts. The objective of this study was to investigate clinician practice change in a system encouraging implementation of evidence-based practices over 5 years and how organizational characteristics moderate this effect. We hypothesized that evidence-based techniques would increase over time, whereas use of non-evidence-based techniques would remain static. METHOD/METHODS:Using a repeated cross-sectional design, data were collected three times from 2013 to 2017 in Philadelphia's public behavioral health system. Clinicians from 20 behavioral health outpatient clinics serving youth were surveyed three times over 5 years (n = 340; overall response rate = 60%). All organizations and clinicians were exposed to system-level support provided by the Evidence-based Practice Innovation Center from 2013 to 2017. Additionally, approximately half of the clinicians participated in city-funded evidence-based practice training initiatives. The main outcome included clinician self-reported use of cognitive-behavioral and psychodynamic techniques measured by the Therapy Procedures Checklist-Family Revised. RESULTS:Clinicians were 80% female and averaged 37.52 years of age (SD = 11.40); there were no significant differences in clinician characteristics across waves (all ps > .05). Controlling for organizational and clinician covariates, average use of CBT techniques increased by 6% from wave 1 (M = 3.18) to wave 3 (M = 3.37, p = .021, d = .29), compared to no change in psychodynamic techniques (p = .570). Each evidence-based practice training initiative in which clinicians participated predicted a 3% increase in CBT use (p = .019) but no change in psychodynamic technique use (p = .709). In organizations with more proficient cultures at baseline, clinicians exhibited greater increases in CBT use compared to organizations with less proficient cultures (8% increase vs. 2% decrease, p = .048). CONCLUSIONS:System implementation of evidence-based practices is associated with modest changes in clinician practice; these effects are moderated by organizational characteristics. Findings identify preliminary targets to improve implementation.

Objective/UNASSIGNED:Traditional measures for assessing functioning with adult patients with schizophrenia have been shown to be insufficient for assessing the issues that occur in adolescents and young adults at clinical high risk (CHR) for psychosis. The current study provides an expanded validation of the Global Functioning: Social (GF:Social) and Role (GF:Role) scales developed specifically for use with CHR individuals and explores the reliability and accuracy of the ratings, the validity of the scores in comparison to other established clinical measures, stability of functioning over a 2-year period, and psychosis predictive ability. Methods/UNASSIGNED:Seven hundred fifty-five CHR individuals and 277 healthy control (HC) participants completed the GF:Social and Role scales at baseline as part of the North American Prodrome Longitudinal Study (NAPLS2). Results/UNASSIGNED:Inter-rater reliability and accuracy were high for both scales. Correlations between the GF scores and other established clinical measures demonstrated acceptable convergent and discriminant validity. In addition, GF:Social and Role scores were unrelated to positive symptoms. CHR participants showed large impairments in social and role functioning over 2-years, relative to the HCs, even after adjusting for age, IQ, and attenuated positive symptoms. Finally, social decline prior to baseline was more pronounced in CHR converters, relative to non-converters. Conclusions/UNASSIGNED:The GF scales can be administered in a large-scale multi-site study with excellent inter-rater reliability and accuracy. CHR individuals showed social and role functioning impairments over time that were not confounded by positive symptom severity levels. The results of this study demonstrate that social decline is a particularly effective predictor of conversion outcome.