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Quality of life outcomes in APOLLO, the phase 3 trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis

Obici, Laura; Berk, John L; González-Duarte, Alejandra; Coelho, Teresa; Gillmore, Julian; Schmidt, Hartmut H-J; Schilling, Matthias; Yamashita, Taro; Labeyrie, Céline; Brannagan, Thomas H; Ajroud-Driss, Senda; Gorevic, Peter; Kristen, Arnt V; Franklin, Jaclyn; Chen, Jihong; Sweetser, Marianne T; Wang, Jing Jing; Adams, David
PMID: 32131641
ISSN: 1744-2818
CID: 4930532

Spinal neurovascular complications with anterior thoracolumbar spine surgery: a systematic review and review of thoracolumbar vascular anatomy

Shlobin, Nathan A; Raz, Eytan; Shapiro, Maksim; Clark, Jeffrey R; Hoffman, Steven C; Shaibani, Ali; Hurley, Michael C; Ansari, Sameer A; Jahromi, Babak S; Dahdaleh, Nader S; Potts, Matthew B
OBJECTIVE:Spinal cord infarction due to interruption of the spinal vascular supply during anterior thoracolumbar surgery is a rare but devastating complication. Here, the authors sought to summarize the data on this complication in terms of its incidence, risk factors, and operative considerations. They also sought to summarize the relevant spinal vascular anatomy. METHODS:They performed a systematic literature review of the PubMed, Scopus, and Embase databases to identify reports of spinal cord vascular injury related to anterior thoracolumbar spine procedures as well as operative adjuncts and considerations related to management of the segmental artery ligation during such anterior procedures. Titles and abstracts were screened, and studies meeting inclusion criteria were reviewed in full. RESULTS:Of 1200 articles identified on the initial screening, 16 met the inclusion criteria and consisted of 2 prospective cohort studies, 10 retrospective cohort studies, and 4 case reports. Four studies reported on the incidence of spinal cord ischemia with anterior thoracolumbar surgery, which ranged from 0% to 0.75%. Eight studies presented patient-level data for 13 cases of spinal cord ischemia after anterior thoracolumbar spine surgery. Proposed risk factors for vasculogenic spinal injury with anterior thoracolumbar surgery included hyperkyphosis, prior spinal deformity surgery, combined anterior-posterior procedures, left-sided approaches, operating on the concavity side of a scoliotic curve, and intra- or postoperative hypotension. In addition, eight studies analyzed operative considerations to reduce spinal cord ischemic complications in anterior thoracolumbar surgery, including intraoperative neuromonitoring and preoperative spinal angiography. CONCLUSIONS:While spinal cord infarction related to anterior thoracolumbar surgery is rare, it warrants proper consideration in the pre-, intra-, and postoperative periods. The spine surgeon must be aware of the relevant risk factors as well as the pre- and intraoperative adjuncts that can minimize these risks. Most importantly, an understanding of the relevant spinal vascular anatomy is critical to minimizing the risks associated with anterior thoracolumbar spine surgery.
PMID: 32871559
ISSN: 1092-0684
CID: 4583162

Timing of the Diagnosis of Autism in African American Children

Constantino, John N; Abbacchi, Anna M; Saulnier, Celine; Klaiman, Cheryl; Mandell, David S; Zhang, Yi; Hawks, Zoe; Bates, Julianna; Klin, Ami; Shattuck, Paul; Molholm, Sophie; Fitzgerald, Robert; Roux, Anne; Lowe, Jennifer K; Geschwind, Daniel H
OBJECTIVES/OBJECTIVE:African American (AA) children affected by autism spectrum disorder (ASD) experience delays in diagnosis and obstacles to service access, as well as a disproportionate burden of intellectual disability (ID) as documented in surveillance data recently published by the US Centers for Disease Control and Prevention. Our objective in this study was to analyze data from the largest-available repository of diagnostic and phenotypic information on AA children with ASD, and to explore the wide variation in outcome within the cohort as a function of sociodemographic risk and specific obstacles to service access for the purpose of informing a national approach to resolution of these disparities. METHODS:Parents of 584 AA children with autism consecutively enrolled in the Autism Genetic Resource Exchange across 4 US data collection sites completed event history calendar interviews of the diagnostic odysseys for their children with ASD. These data were examined in relation to developmental outcomes of the children with autism and their unaffected siblings. RESULTS:The average age of ASD diagnosis was 64.9 months (±49.6), on average 42.3 months (±45.1) after parents' first concerns about their children's development. The relationship between timing of diagnosis and ASD severity was complex, and ID comorbidity was not predicted in a straightforward manner by familial factors associated with cognitive variation in the general population. CONCLUSIONS:These findings document significant opportunity to expedite diagnosis, the need to further understand causes of ID comorbidity, and the necessity to identify effective approaches to the resolution of disparities in severity-of-outcome for AA children with autism.
PMID: 32839243
ISSN: 1098-4275
CID: 4575382

Validation of the Neurogenic Orthostatic Hypotension Ratio with Active Standing [Letter]

Fanciulli, Alessandra; Kerer, Katharina; Leys, Fabian; Seppi, Klaus; Kaufmann, Horacio; Norcliffe-Kaufmann, Lucy; Wenning, Gregor K
PMID: 32596818
ISSN: 1531-8249
CID: 4545782

The SOFIA Study: Negative Multi-center Study of Low Dose Fluoxetine on Repetitive Behaviors in Children and Adolescents with Autistic Disorder

Herscu, Paul; Handen, Benjamin L; Arnold, L Eugene; Snape, Michael F; Bregman, Joel D; Ginsberg, Lawrence; Hendren, Robert; Kolevzon, Alexander; Melmed, Raun; Mintz, Mark; Minshew, Nancy; Sikich, Linmarie; Attalla, Ashraf; King, Brian; Owley, Thomas; Childress, Ann; Chugani, Harry; Frazier, Jean; Cartwright, Charles; Murphy, Tanya
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive-compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5-17 years). Following 14 treatment weeks (mean dose 11.8 mg/day), no significant differences were noted on the Children's Yale-Brown Obsessive Compulsive Scale; the proportion of responders was similar (fluoxetine: 36%; placebo: 41%). There were similar rates of AEs (e.g., insomnia, diarrhea, vomiting); high rates of activation were reported in both groups (fluoxetine: 42%; placebo: 45%). Overly cautious dosing/duration may have prevented attainment of a therapeutic level. Results are consistent with other SSRI RCTs treating RRBs in ASD.Trial Registration: clinicaltrials.gov Identifier: NCT00515320.
PMID: 31267292
ISSN: 1573-3432
CID: 3968082

Attitudes and Beliefs Towards Advance Care Planning among Underserved Chinese-American Immigrants

Dhingra, Lara; Cheung, William; Breuer, Brenda; Huang, Philip; Lam, Kin; Chen, Jack; Zhou, Xiaotian; Chang, Victor; Chui, Timothy; Hicks, Stephanie; Portenoy, Russell
CONTEXT/BACKGROUND:Many in the rapidly-growing Chinese-American population are non-English-speaking and medically-underserved, and few engage in advance care planning (ACP). Evaluating culturally-determined factors that may inhibit ACP can inform programs designed to increase ACP engagement. OBJECTIVES/OBJECTIVE:To describe attitudes and beliefs concerning ACP in older, non-English speaking Chinese-Americans in a medically-underserved urban region. METHODS:Patients were consecutively recruited from a primary care practice in New York City to participate in a cross-sectional survey. Attitudes and beliefs were measured using an ACP Survey tool and the validated Traditional Chinese Death Beliefs measure. Exploratory analyses evaluated associations between these two measures, and between each measure and sociodemographics, primary dialect, acculturation (using The Suinn-Lew Asian Self Identity Acculturation Scale), and health status (using the Short Form-8 Health Survey). RESULTS:Patients (n=179) were 68.2 years on average; 55.9% were women, and 81.0% were non-English speaking (42.8% Cantonese, 15.2% Mandarin, 19.3% Toisanese, 19.3% Fuzhounese). Most had low acculturation (mean=1.7/5.0), and highly-rated physical and mental health (means=70.1/100 and 81.5/100). Few patients (15.1%) had an advance directive and 56.8% were unfamiliar with any type; 74.4% were willing to complete one in the future. Thirty-two percent "agreed" that "talking about death in the presence of a dying person would accelerate death". The analyses revealed no significant associations. CONCLUSION/CONCLUSIONS:These Chinese-American older adults had low acculturation and very limited knowledge of, or engagement in, ACP. Factors that may predict culturally-determined attitudes and beliefs about ACP were not identified. Further research can inform efforts to improve ACP engagement in this population.
PMID: 32335203
ISSN: 1873-6513
CID: 4411692

Emerging technologies to study glial cells

Hirbec, Hélène; Déglon, Nicole; Foo, Lynette C; Goshen, Inbal; Grutzendler, Jaime; Hangen, Emilie; Kreisel, Tirzah; Linck, Nathalie; Muffat, Julien; Regio, Sara; Rion, Sybille; Escartin, Carole
Development, physiological functions, and pathologies of the brain depend on tight interactions between neurons and different types of glial cells, such as astrocytes, microglia, oligodendrocytes, and oligodendrocyte precursor cells. Assessing the relative contribution of different glial cell types is required for the full understanding of brain function and dysfunction. Over the recent years, several technological breakthroughs were achieved, allowing "glio-scientists" to address new challenging biological questions. These technical developments make it possible to study the roles of specific cell types with medium or high-content workflows and perform fine analysis of their mutual interactions in a preserved environment. This review illustrates the potency of several cutting-edge experimental approaches (advanced cell cultures, induced pluripotent stem cell (iPSC)-derived human glial cells, viral vectors, in situ glia imaging, opto- and chemogenetic approaches, and high-content molecular analysis) to unravel the role of glial cells in specific brain functions or diseases. It also illustrates the translation of some techniques to the clinics, to monitor glial cells in patients, through specific brain imaging methods. The advantages, pitfalls, and future developments are discussed for each technique, and selected examples are provided to illustrate how specific "gliobiological" questions can now be tackled.
PMID: 31958188
ISSN: 1098-1136
CID: 4272702

Seizure Activity Across Scales From Neuronal Population Firing to Clonic Motor Semiology

Tobochnik, Steven; Tai, Peter; McKhann, Guy M; Schevon, Catherine A
The correlation of clinical semiology with neuronal firing in human seizures has not been well described. Similarly, the neuronal firing patterns underlying high-frequency oscillations during seizures remain controversial. Using implanted subdural electrodes and a microelectrode array in a patient with focal status epilepticus, in which 40 habitual focal motor seizures and 101 subclinical seizures were captured, the authors analyzed the association of EEG, high-frequency oscillations, and multiunit activity to facial motor semiology. The development of ictal high-frequency oscillations in subdural electrodes overlying face motor cortex was temporally associated with clonic facial movements. In representative seizures selected for multiunit analysis, synchronization of neuronal firing in the adjacent microelectrode array aligned with clinical onset and was greater in clinical seizures compared with subclinical seizures. This report demonstrates the electrophysiologic signatures of focal seizures at the level of neuronal firing, high-frequency oscillations, and EEG as they organize from microscale to macroscale, with clinical correlation.
PMID: 32501950
ISSN: 1537-1603
CID: 4469542

Tele-Neuro-Ophthalmology: Vision for 20/20 and Beyond

Ko, Melissa; Busis, Neil A
BACKGROUND:Telehealth provides health care to a patient from a provider at a distant location. Prior to the COVID-19 pandemic adoption of telehealth modalities was increasing slowly but steadily. During the public health emergency rapid widespread telehealth implementation has been encouraged to promote patient and provider safety and preserve access to health care. EVIDENCE ACQUISITION/METHODS:Evidence was acquired from English language Internet-searches of medical and business literature and following breaking news on the COVID-19 pandemic and responses from health care stakeholders including policy makers, payers, physicians and health care organizations, and patients. We also had extensive discussions with colleagues who are developing telehealth techniques relevant to neuro-ophthalmology. RESULTS:Regulatory, legal, reimbursement and cultural barriers impeded the widespread adoption of telehealth prior to the COVID-19 pandemic. With the increased use of telehealth in response to the public health emergency, we are rapidly accumulating experience and an evidence base identifying opportunities and challenges related to the widespread adoption of tele-neuro-ophthalmology. One of the major challenges is the current inability to adequately perform funduscopy remotely. CONCLUSIONS:Telehealth is an increasingly recognized means of healthcare delivery. Tele-neuro-ophthalmology adoption is necessary for the sake of our patients, the survival of our subspecialty, and the education of our trainees and students. Telehealth does not supplant but supplements and complements in-person neuro-ophthalmologic care. Innovations in digital optical fundus photography, mobile vision testing applications, artificial intelligence and principles of channel management will facilitate further adoption of tele-neuro-ophthalmology and bring the specialty to the leading edge of healthcare delivery.
PMID: 32604247
ISSN: 1536-5166
CID: 4529222

Associations of Sociodemographic Factors and Psychiatric Disorders With Type of School-Based Mental Health Services Received by Youth

Green, Jennifer Greif; McLaughlin, Katie A; Alegría, Margarita; Bettini, Elizabeth; Gruber, Michael; Hoagwood, Kimberly; Le Tai, Lana; Sampson, Nancy; Zaslavsky, Alan M; Xuan, Ziming; Kessler, Ronald C
PURPOSE/OBJECTIVE:Schools provide access to mental health services for traditionally underserved youth. However, there is variability in the types of school-based services students receive (e.g., school counseling, services in separate classrooms, or schools serving students with psychiatric disorders). Prior research has typically not distinguished among these different types of school-based services. The present study examines sociodemographic characteristics and disorders associated with the types of services received in schools. METHODS:Data were analyzed from a sample of adolescent-parent pairs in the U.S. National Comorbidity Survey Adolescent Supplement who received school mental health services (N = 1,204). DSM-IV diagnoses were based on the Composite International Diagnostic Interview administered to adolescents and questionnaires self-administered to parents. Adolescents (aged 13-18 years) and parents also responded to questions about lifetime school-based mental health service receipt. RESULTS:Among those receiving school-based mental health services, almost one-third (29.7%) received services in a separate classroom and almost one-fourth (22.3%) in a separate school. Increased likelihood of lifetime placement in a separate classroom or school was detected among older youth, males, blacks, Latinos, youth with learning disabilities, those whose parents had fewer years of education, and those who received community-based mental health services. Oppositional defiant disorder was associated with increased lifetime placement in a separate school. CONCLUSIONS:The results advance the evidence base by indicating that racial/ethnic minority youth and those whose parents have fewer years of education were more likely to receive school-based mental health services in separate settings. These results provide more context to studies of school-based mental health service receipt.
PMID: 32317207
ISSN: 1879-1972
CID: 4401442