Faculty Bibliography

Introduction: Several studies have demonstrated that insomnia symptoms negatively impact adherence to Continuous Positive Airway Pressure (CPAP). Yet, little is known about psychosocial factors that may buffer the associated negative effects. The present study explored the role of resilience, the ability to function in the face of or following adversity, on reducing the negative effects of insomnia on CPAP adherence.
Method(s): The study sample included volunteers from a large sleep center enrolling individuals newly diagnosed with Obstructive Sleep Apnea (OSA). For this analysis, we examined volunteers with complete data (n=45) on insomnia severity (based on the Insomnia Severity Index (ISI)), resilience (based on the Connor Davidson Resiliency Scale (CD-RISC)), and objective median hours of CPAP use over the first 30 days of treatment.
Result(s): The mean age was 55.4 years (SD=15.7); 62.2% male, and 33% black. The mean ISI score was 13.0 (SD=6.3), mean CD-RISC was 30.7 (SD=5.7) and mean CPA use over the first 30 days was 5.9 (SD=1.9). In the linear regression, ISI was positively correlated with increased hours of CPAP use (r=-0.305, p=.047). Resilience was not significantly correlated with CPAP use (r=0.216, p=.163), likely attributable to the sample size. ISI correlated with CPAP use among those with low resilience (r=-0.461, p=.027), but not among those with high resilience (r=-0.039, p=.870). There was a significant interaction (B(SE)=0.22 (0.08); p=.005) between ISI and resilience on median hours of CPAP use, indicating that resilience may moderate the association between ISI and hours of CPAP use.
Conclusion(s): Results of our study indicated that resilience is an important factor and may reduce the negative effects of insomnia on CPAP adherence. Notably, the high resilience score in this sample could signal an important target for tailoring CPAP adherence interventions to address unique characteristics of each subgroup

Cerebral venous sinus thrombosis (CVST) requires anticoagulation to promote vessel recanalization. Current anticoagulation paradigms utilize plasma tests from peripheral venous/arterial samples for therapeutic monitoring. We describe a medically-refractory case of CVST in a 35-year-old woman later found to have JAK2 mutation and essential thrombocytosis. Despite therapeutic anticoagulation levels, worsening cerebral edema and progression to coma prompted endovascular treatment. Failed endovascular thrombectomy attempts led to placement of 2 separate indwelling microcatheters for continuous infusion of tissue plasminogen activator (tPA). Forty-hours of continuous-tPA in addition to systemic intravenous-heparin led to complete radiographic and clinical resolution of CVST. Whole blood coagulation testing using Rotational Thromboelastometry (ROTEM) from simultaneous samples taken intracranially (via cerebral microcatheters) and peripherally (via antecubital vein) all revealed prolonged intrinsic pathway activation clotting times consistent with heparin anticoagulation use. However, both intracranial ROTEM samples identified faster clotting times compared to the peripheral sample suggesting lower anticoagulation levels intracranially. Our findings were speculative and hypothesis generating as to whether this explained medical treatment failure. If there are coagulopathy differences at local sites of injury not adequately captured by peripheral blood draws, further investigation is required to identify better approaches to avoid under-treatment of similar cases.

Background: Adult MS research has identified an increased prevalence of various autoimmune conditions among family members of diagnosed patients. There has not been comparable studies of pediatric MS populations, while this cohort may represent a unique population from a risk factors perspective.
Objective(s): This study was undertaken to quantify the incidence of autoimmune conditions among first and second degree relatives of pediatric MS patients as compared to controls. The study sought to quantify both the rate, type and patterns of diagnoses seen throughout family members of pediatric MS patients.
Method(s): A multi center case-control study of risk factors for pediatric MS has been ongoing for since 2011. Pediatric patients with a diagnosis of MS and pediatric controls were recruited to provide data and biologic specimens for a number of research projects. Included in this effort was the acquisition of family history questionnaires. The medical data from these questionnaires were analyzed for the presence of certain medical diagnoses among first and second degree relatives. Logistic regression models were used to test for differences between cases and controls in reporting a family history of autoimmune diseases, when adjusting for sex, race, age, ethnicity, and mother's education level. Odds ratios and 95% confidence intervals were calculated based on the logistic regression models.
Result(s): Several conditions were found to have statistically significant differences in prevalence among first and second degree family members of MS patients as compared to controls. Diabetes, thyroid disorders and rheumatoid arthritis has the most notable differences between patients and controls while eczema and psoriasis were not different. The odds ratio of any family history of autoimmune disease was 2.27 among cases compared to controls. The odds ratio of an autoimmune disease among family members was significantly higher among paternal relatives as compared to maternal relatives (eg OR of 6.37 compared to 2.64).
Conclusion(s): This study has identified an increased prevalence of certain autoimmune disorders among first and second degree family members of pediatric MS patients. This aligns with prior findings among adult populations that found higher rates of autoimmune disorders among family members of adult onset MS patients. Novel to this study was the difference in relative risk of autoimmune conditions occurring in paternal versus maternal family members

Introduction: Dans PARADIGMS, premiere etude phase III en double aveugle dans la SEP pediatrique, le fingolimod a diminue significativement le taux annualise de poussees (TAP) de 82 % versus l'interferon (IFN) beta-1a. Objectifs: Effectuer des analyses dans des sous-groupes (anticorps neutralisants anti-IFN, naifs de traitement); evaluer l'effet chez les patients plus jeunes et prepuberes, la progression du handicap, la qualite de vie. Patients et Methodes: Les analyses de sous-groupes des criteres principal (TAP) et secondaire principal (nouvelles lesions T2, NT2) et post-hoc sur la progression confirmee du handicap ont ete realisees. La qualite de vie (QdV) liee a la sante a ete evaluee par les patients ou les parents a l'aide du questionnaire PedsQL (Quality of Life) avant et a la fin de l'etude (jusqu'a 2 ans): changements du score total et des scores sante physique et sante psychosociale. Resultats: Dans toutes les analyses de sous-groupes, le fingolimod a diminue significativement le TAP (81,5-85,8 %) et NT2 (47,6-53,4 %) versus l'IFNbeta-1a. Le risque de progression du handicap confirmee a 3 mois etait reduit de 77,2 % ([HR] = 0,23, p = 0,007). L'analyse post-hoc a confirme son effet positif sur les scores totaux et de sante physique de QdV rapportes par les patients et les parents, et de sante psychosociale rapporte par les patients versus l'IFN beta-1a (tous p < 0,05). Discussion(s): Le fingolimod dans la SEP pediatrique a ete associe a un controle de l'activite de la maladie dans toutes les analyses complementaires, chez les patients traites precedemment ou non, et ce de maniere plus marquee chez les patients plus jeunes. Des benefices sur la progression du handicap ont ete observes sur une duree de traitement allant jusqu'a 2 ans. Conclusion(s): Le fingolimod versus IFN beta-1a a ete associe a une amelioration significative du controle de l'activite de la maladie et de la qualite de vie liee a la sante.

PURPOSE OF REVIEW/OBJECTIVE:To review the history, pharmacology, and clinical science of cannabidiol (CBD) in the treatment of epilepsy. RECENT FINDINGS/RESULTS:Phase III randomized controlled trials and prospective open label trials have provided efficacy and safety data for the use of CBD in pediatric onset severe epilepsies. The product that was studied in the vast majority of these published trials, Epidiolex (>99% of CBD and <0.10% Δ9-tetrahydrocannabinol (THC); GW pharmaceuticals, Cambridge, UK), has now been FDA approved based on this published data. SUMMARY/CONCLUSIONS:Identification of CBD, Δ9-THC, and the endocannabinoid system in the mid-20th century has led to advancement of cannabis-based therapies for epilepsy. Based on clinical trial data, Epidiolex is the first CBD medication approved by a national regulatory agency (US Food and Drug Administration for Dravet and Lennox Gastaut syndrome; European Medicines Agency for Lennox Gastaut syndrome). Approval of CBD as a treatment for these rare and severe pediatric-onset epilepsy syndromes is an important milestone, but the complete spectrum of use of cannabis-derived products, and the use of CBD for other epilepsy syndromes remains to be determined.

BACKGROUND:Fatigue is one of the most commonly experienced symptoms in multiple sclerosis (MS). The neural correlates of fatigue in MS, in general and specifically in early onset, remain poorly understood. This study employed resting-state fMRI (rsfMRI) to investigate the functional connectivity of fatigue in MS patients with early age onset. METHODS:Twenty-seven relapsing-remitting MS patients (20 ± 7yo at the age of diagnosis and 26.0 ± 5.5yo at the time of study) were recruited and 22 patients were studied. Structural and rsfMRI sequences were performed on a 3-Tesla Seimens MRI scanner. Seed-based analysis was performed using CONN Functional Connectivity Toolbox for Statistic Parametric Mapping. The Fatigue Severity Scale (FSS) and the Modified Fatigue Impact scale (MFIS) as well as EDSS, Beck Depression Inventory, and symptomatology were measured. Non-fatigued (N = 12) and fatigued patients (N = 10) were separated based on FSS scores, with a score of 5 or greater being classified as fatigued. Group differences in rsfMRI between non-fatigued and fatigued patients were analyzed. Correlations between these functional connectivity differences and behavioral fatigue scores were also analyzed. RESULTS: = 0.402, p = 0.006). Correlations remained significant after accounting for depression scores. CONCLUSIONS:rsfMRI identified Alterations in two distinct connections (the connectivity between insula and posterior cingulate gyrus and between the right thalamus and right precentral gyrus) that differed between fatigued and non-fatigued patients, as well as correlated with cognitive fatigue severity. These findings suggest that disruption of sensorimotor, high-order motor, and non-motor executive function likely contributes to the neural mechanism of fatigue in MS. Knowledge of the neural mechanisms of underlying MS fatigue could inform more effective treatment strategies.

OBJECTIVE:/UNASSIGNED:Despite the potential benefits of mobile mental health apps, real-world results indicate engagement issues because of low uptake and sustained use. This review examined how studies have measured and reported on user engagement indicators (UEIs) for mental health apps. METHODS:/UNASSIGNED:A systematic review of multiple databases was performed in July 2018 for studies of mental health apps for depression, bipolar disorder, schizophrenia, and anxiety that reported on UEIs, namely usability, user satisfaction, acceptability, and feasibility. The subjective and objective criteria used to assess UEIs, among other data, were extracted from each study. RESULTS:/UNASSIGNED:Of 925 results, 40 studies were eligible. Every study reported positive results for the usability, satisfaction, acceptability, or feasibility of the app. Of the 40 studies, 36 (90%) employed 371 indistinct subjective criteria that were assessed with surveys, interviews, or both, and 23 studies used custom subjective scales, rather than preexisting standardized assessment tools. A total of 25 studies (63%) used objective criteria-with 71 indistinct measures. No two studies used the same combination of subjective or objective criteria to assess UEIs of the app. CONCLUSIONS:/UNASSIGNED:The high heterogeneity and use of custom criteria to assess mental health apps in terms of usability, user satisfaction, acceptability, or feasibility present a challenge for understanding real-world low uptake of these apps. Every study reviewed claimed that UEIs for the app were rated highly, which suggests a need for the field to focus on engagement by creating reporting standards and more carefully considering claims.

OBJECTIVE:/UNASSIGNED:To explore cognitive strategies clinicians apply while performing a medication reconciliation task, handling incomplete and conflicting information. BACKGROUND:/UNASSIGNED:Medication reconciliation is a method clinicians apply to find and resolve inconsistencies in patients' medications and medical conditions lists. The cognitive strategies clinicians use during reconciliation are unclear. Controlled lab experiments can explore how clinicians make sense of uncertain, missing, or conflicting information and therefore support the development of a human performance model. We hypothesize that clinicians apply varied cognitive strategies to handle this task and that profession and experience affect these strategies. METHOD:/UNASSIGNED:130 clinicians participated in a tablet-based experiment conducted in a large American teaching hospital. They were asked to simulate medication reconciliation using a card sorting task (CaST) to organize medication and medical condition lists of a specific clinical case. Later on, they were presented with new information and were asked to add it to their arrangements. We quantitatively and qualitatively analyzed the ways clinicians arranged patient information. RESULTS:/UNASSIGNED:Four distinct cognitive strategies were identified ("Conditions first": n = 76 clinicians, "Medications first": n = 7, "Crossover": n = 17, and "Alternating": n = 10). The strategy clinicians applied was affected by their experience ( p = .02) but not by their profession. At the appearance of new information, clinicians moved medication cards more frequently (75.2 movements vs. 49.6 movements, p < .001), suggesting that they match medications to medical conditions. CONCLUSION:/UNASSIGNED:Clinicians apply various cognitive strategies while reconciling medications and medical conditions. APPLICATION:/UNASSIGNED:Clinical information systems should support multiple cognitive strategies, allowing flexibility in organizing information.

Electrophysiological activity measured at the scalp surface using electroencephalography or magnetoencephalography (EEG or MEG) contains prominent ongoing rhythmic activity across a mixture of different frequency bands. This rhythmic oscillatory activity is present during both rest and task performance. The most visible rhythm in the adult human brain is in the band between approximately 8-12 Hz, and is referred to as alpha activity. While sometimes dismissed by neurophysiologists as a nuisance biological artefact, since it often interferes with the recording of event-related potentials (ERPs), there has been an explosion of research linking it to specific functional roles in cognition and behavior over the past two decades. Here, we review some of the research into the functional significance of alpha oscillations with respect to attention and expectation. We focus our discussion on how the amplitude and phase of alpha activity might be involved in the prioritization of relevant sensory input. In addition to summarizing the literature, we also endeavor to provide a critical appraisal as well as highlight limitations and conceptual gaps in the field.