"Destigmatizing Naloxone: Associations of Perceived Availability on Opioid Use Patterns" (2021) Annals of Emergency Medicine
Destigmatizing Naloxone: Associations of Perceived Availability on Opioid Use Patterns
(2021) Annals of Emergency Medicine, 77 (1), pp. 134-135.
Ellis, M.S., Kasper, Z.A., Cicero, T.J.
Washington University in St. Louis, Department of Psychiatry, School of Medicine, St. Louis, MO, United States
Document Type: Letter
Publication Stage: Final
Source: Scopus
"Prevalence, Surgical Management, and Audiologic Impact of Sigmoid Sinus Dehiscence Causing Pulsatile Tinnitus" (2021) Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society (and) European Academy of Otology and Neurotology
Prevalence, Surgical Management, and Audiologic Impact of Sigmoid Sinus Dehiscence Causing Pulsatile Tinnitus
(2021) Otology & Neurotology: Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 42 (1), pp. 82-91.
Ettyreddy, A.R., Shew, M.A., Durakovic, N., Chole, R.A., Herzog, J., Buchman, C.A., Wick, C.C.
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States
Abstract
OBJECTIVE: To evaluate the prevalence, surgical management, and audiologic impact of pulsatile tinnitus caused by sigmoid sinus dehiscence. STUDY DESIGN AND SETTING: Retrospective chart review at a tertiary care hospital. PATIENTS: Adults with unilateral pulsatile tinnitus attributable to sigmoid sinus dehiscence who underwent resurfacing between January 2010 and January 2020. INTERVENTIONS: Transmastoid sigmoid resurfacing. MAIN OUTCOME MEASURES: Resolution of pulsatile tinnitus; audiologic outcomes; complications; tinnitus etiologies. RESULTS: Nineteen patients (89.4% women) had surgery for suspected sigmoid sinus dehiscence. The mean dehiscence size was 6.1 mm (range, 1-10.7 mm). Eight patients had concurrent sigmoid sinus diverticulum and one patient also had jugular bulb dehiscence. Only two patients (10.5%) had the defect identified by radiology. Low-frequency pure-tone average, measured at frequencies of 250 and 500 Hz, showed a significant median improvement of 8.8 dB following resurfacing (18.8 dB versus 10.0 dB, p = 0.02). The majority of patients had complete resolution of pulsatile tinnitus (16/19, 84.2%). Of those without complete resolution, two patients had partial response and one patient had no improvement. There were no significant complications. Of 41 consecutively tracked patients with a pulsatile tinnitus chief complaint, sigmoid pathology represented 32% of cases. CONCLUSIONS: Sigmoid sinus dehiscence represents a common vascular cause of pulsatile tinnitus that, if properly assessed, may be amenable to surgical intervention. Sigmoid sinus resurfacing is safe, does not require decompression, and may improve low-frequency hearing. Radiographic findings of dehiscence are often overlooked without a high index of clinical suspicion. Its relationship with transverse sinus pathology and idiopathic intracranial hypertension remain unclear.
Document Type: Article
Publication Stage: Final
Source: Scopus
"CLIP and Massively Parallel Functional Analysis of CELF6 Reveal a Role in Destabilizing Synaptic Gene mRNAs through Interaction with 3′ UTR Elements" (2020) Cell Reports
CLIP and Massively Parallel Functional Analysis of CELF6 Reveal a Role in Destabilizing Synaptic Gene mRNAs through Interaction with 3′ UTR Elements
(2020) Cell Reports, 33 (12), art. no. 108531, .
Rieger, M.A.a b , King, D.M.a , Crosby, H.a b , Liu, Y.a b , Cohen, B.A.a , Dougherty, J.D.a b
a Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, United States
b Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, United States
Abstract
CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3′ UTRs in synaptic protein-coding genes. Using a massively parallel reporter assay framework, we test the consequence of CELF6 expression on target sequences, with and without mutating putative binding motifs. Where CELF6 exerts an effect on sequences, it is largely to decrease RNA abundance, which is reversed by mutating UGU-rich motifs. This is also the case for CELF3–5, with a protein-dependent effect on magnitude. Finally, we demonstrate that targets are derepressed in CELF6-mutant mice, and at least two key CNS proteins, FOS and FGF13, show altered protein expression levels and localization. Our works find, in addition to previously identified roles in splicing, that CELF6 is associated with repression of its CNS targets via the 3′ UTR in vivo. © 2020 The Author(s)
Rieger et al. assay the function of the RNA-binding protein CELF6 by defining its targets in the brain. They show that CELF6 largely binds 3′ UTRs of synaptic mRNAs. Using a massively parallel reporter assay, they further show that CELF6 and other CELFs are associated with lower mRNA abundance and that targets are derepressed in Celf6-knockout mice in vivo. © 2020 The Author(s)
Author Keywords
3’UTR regulation; CELF; CELF6; CLIP; massively parallel reporter assay; RNA binding protein; synaptic mRNA
Funding details
National Institutes of HealthNIH5R00NS067239, 5R21MH099798, R01MH116999, 5R01HG008687
Simons FoundationSF
Document Type: Article
Publication Stage: Final
Source: Scopus
"Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer's disease pathogenesis" (2020) Science Translational Medicine
Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer’s disease pathogenesis
(2020) Science Translational Medicine, 12 (574), art. no. eaax3519, .
Lananna, B.V.a , McKee, C.A.a , King, M.W.a , Del-Aguila, J.L.b , Dimitry, J.M.a , Farias, F.H.G.b , Nadarajah, C.J.a , Xiong, D.D.a , Guo, C.c , Cammack, A.J.a , Elias, J.A.d , Zhang, J.c , Cruchaga, C.b e , Musiek, E.S.a e
a Department of Neurology, Washington University, School of Medicine, St. Louis, MO 63110, United States
b Department of Psychiatry, Washington University, School of Medicine, St. Louis, MO 63110, United States
c Department of Pharmacological and Physiological Science, Saint Louis University, School of Medicine, St. Louis, MO 63104, United States
d Division of Medicine and Biological Sciences, Brown University, Providence, RI 02903, United States
e Knight Alzheimer’s Disease Research Center, Hope Center for Neurological Disease, Washington University, School of Medicine, St. Louis, MO 63108, United States
Abstract
Regulation of glial activation and neuroinflammation are critical factors in the pathogenesis of Alzheimer’s disease (AD). YKL-40, a primarily astrocytic protein encoded by the gene Chi3l1, is a widely studied cerebrospinal fluid biomarker that increases with aging and early in AD. However, the function of Chi3l1/YKL-40 in AD is unknown. In a cohort of patients with AD, we observed that a variant in the human CHI3L1 gene, which results in decreased CSF YKL-40 expression, was associated with slower AD progression. At baseline, Chi3l1 deletion in mice had no effect on astrocyte activation while modestly promoting microglial activation. In a mouse APP/PS1 model of AD, Chi3l1 deletion decreased amyloid plaque burden and increased periplaque expression of the microglial lysosomal marker CD68, suggesting that Chi3l1 may suppress glial phagocytic activation and promote amyloid accumulation. Accordingly, Chi3l1 knockdown increased phagocytosis of zymosan particles and of β-amyloid peptide in both astrocytes and microglia in vitro. We further observed that expression of Chi3l1 is regulated by the circadian clock, as deletion of the core clock proteins BMAL1 or CLOCK/NPAS2 strongly suppresses basal Chi3l1 expression, whereas deletion of the negative clock regulators PER1/PER2 increased Chi3l1 expression. Basal Chi3l1 mRNA was nonrhythmic because of a long mRNA half-life in astrocytes. However, inflammatory induction of Chi3l1 was gated by the clock. Our findings reveal Chi3l1/YKL-40 as a modulator of glial phagocytic activation and AD pathogenesis in both mice and humans and suggest that the astrocyte circadian clock regulates inflammatory Chi3l1 induction. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works
Funding details
Foundation for Barnes-Jewish Hospital
National Institutes of HealthNIHR01AG05777, U01AG058922, P01AG003991, RF1AG053303, U01AG052411, R01AG054517, R01AG044546, R01AG058501
National Institute on AgingNIAP50-AG05681, P01-AG03991, P01-AG026276
CDI-CORE-2015-505
Document Type: Article
Publication Stage: Final
Source: Scopus
"Biomarkers May Predict Unfavorable Neurological Outcome after Mild Traumatic Brain Injury" (2020) Journal of Neurotrauma
Biomarkers May Predict Unfavorable Neurological Outcome after Mild Traumatic Brain Injury
(2020) Journal of Neurotrauma, 37 (24), pp. 2624-2631.
Lewis, L.M.a , Papa, L.b , Bazarian, J.J.c , Weber, A.d , Howard, R.e , Welch, R.D.f
a Department of Emergency Medicine, Washington University in St. Louis, St. Louis, MO, United States
b Department of Emergency Medicine, Orlando Regional Medical Center, Orlando, FL, United States
c Emergency Medicine Research, University of Rochester, Rochester, NY, United States
d Banyan Biomarkers Inc., San Diego, CA, United States
e Veridical Solutions, Del Mar, CA, United States
f Department of Emergency Medicine, Wayne State University School of Medicine, Detroit Receiving Hospital, Detroit, MI, United States
Abstract
The objective of this study was to determine if initial or repeat measurements of serum concentrations of glial fibrillary acidic protein (GFAP) or ubiquitin C-Terminal hydrolase L1 (UCH-L1) are predictive of an acute unfavorable neurological outcome in patients who present to the emergency department (ED) with brain injury and an initial Glasgow Coma Scale Score (GCS) of 14-15. This multi-center observational trial included brain-injured adults presenting to the ED, receiving a head computed tomography (CT) and venipuncture for biomarker concentration measurements within 6 h of injury. Subjects had repeat serum sampling and GCS scores every 4 h for the first 24 h, if available for assessment. We analyzed blood samples using an enzyme-linked immunosorbent assay approved by the Food and Drug Administration (FDA). Wilcoxin two-sample test was used to compare initial and repeat serum concentrations for both biomarkers between CT-positive patients who did not have an acute unfavorable neurological outcome and those patients who did. A total of 145 enrolled subjects had adequate data for analysis; 69 were CT-positive, 74 were CT-negative, and 2 were CT-inconclusive. Five subjects developed an acute unfavorable neurological outcome, defined as need for intracranial pressure monitoring, craniotomy, persistent neurological deficits, or death resulting from brain injury. Initial median serum concentrations of GFAP and UCH-L1 (obtained <6 h from injury) were significantly greater in CT-positive patients who had an acute unfavorable neurological outcome than in CT-positive patients who did not (GFAP: 5237 pg/mL [IQR 4511, 8180] versus 283.5 pg/mL [IQR 107, 1123]; p = 0.026; UCH-L1: 3329 pg/mL [QR 1423, 5010] versus 679.5 pg/mL [IQR 363, 1100] p = 0.014). Repeat serum testing (6-< 12 h from injury) showed that UCH-L1 serum concentration, but not GFAP, was also significantly greater in the acute unfavorable neurological outcome group than in those without an unfavorable outcome: 1088 pg/mL versus 374 pg/mL; p = 0.041. © Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.
Author Keywords
biomarkers; mild traumatic brain injury; neurological deterioration
Document Type: Article
Publication Stage: Final
Source: Scopus
"Protocol for the Prognosticating Delirium Recovery Outcomes Using Wakefulness and Sleep Electroencephalography (P-DROWS-E) study: A prospective observational study of delirium in elderly cardiac surgical patients" (2020) BMJ Open
Protocol for the Prognosticating Delirium Recovery Outcomes Using Wakefulness and Sleep Electroencephalography (P-DROWS-E) study: A prospective observational study of delirium in elderly cardiac surgical patients
(2020) BMJ Open, 10 (12), art. no. e044295, .
Kendall Smith, S.a , Nguyen, T.a , Labonte, A.K.a , Kafashan, M.a , Hyche, O.a , Guay, C.S.a , Wilson, E.a , Chan, C.W.a , Luong, A.a , Brian Hickman, L.a , Fritz, B.A.a , Emmert, D.a , Graetz, T.J.a , Melby, S.J.b , Lucey, B.P.c , Ju, Y.-E.S.c , Wildes, T.S.a , Avidan, M.S.a , Palanca, B.J.A.a d e
a Department of Anesthesiology, Washington University in Saint Louis School of Medicine, Saint Louis, MO, United States
b Department of Surgery, Washington University in Saint Louis School of Medicine, Saint Louis, MO, United States
c Department of Neurology, Washington University in Saint Louis School of Medicine, Saint Louis, MO, United States
d Department of Biomedical Engineering, Washington University in St Louis, Saint Louis, MO, United States
e Division of Biology and Biomedical Sciences, Washington University in St Louis, Saint Louis, MO, United States
Abstract
Introduction Delirium is a potentially preventable disorder characterised by acute disturbances in attention and cognition with fluctuating severity. Postoperative delirium is associated with prolonged intensive care unit and hospital stay, cognitive decline and mortality. The development of biomarkers for tracking delirium could potentially aid in the early detection, mitigation and assessment of response to interventions. Because sleep disruption has been posited as a contributor to the development of this syndrome, expression of abnormal electroencephalography (EEG) patterns during sleep and wakefulness may be informative. Here we hypothesise that abnormal EEG patterns of sleep and wakefulness may serve as predictive and diagnostic markers for postoperative delirium. Such abnormal EEG patterns would mechanistically link disrupted thalamocortical connectivity to this important clinical syndrome. Methods and analysis P-DROWS-E (Prognosticating Delirium Recovery Outcomes Using Wakefulness and Sleep Electroencephalography) is a 220-patient prospective observational study. Patient eligibility criteria include those who are English-speaking, age 60 years or older and undergoing elective cardiac surgery requiring cardiopulmonary bypass. EEG acquisition will occur 1-2 nights preoperatively, intraoperatively, and up to 7 days postoperatively. Concurrent with EEG recordings, two times per day postoperative Confusion Assessment Method (CAM) evaluations will quantify the presence and severity of delirium. EEG slow wave activity, sleep spindle density and peak frequency of the posterior dominant rhythm will be quantified. Linear mixed-effects models will be used to evaluate the relationships between delirium severity/duration and EEG measures as a function of time. Ethics and dissemination P-DROWS-E is approved by the ethics board at Washington University in St. Louis. Recruitment began in October 2018. Dissemination plans include presentations at scientific conferences, scientific publications and mass media. Trial registration number NCT03291626. ©
Author Keywords
adult intensive & critical care; cardiothoracic surgery; delirium & cognitive disorders; neurophysiology; old age psychiatry; sleep medicine
Document Type: Article
Publication Stage: Final
Source: Scopus
"Whole Health Options and Pain Education (wHOPE): A Pragmatic Trial Comparing Whole Health Team vs Primary Care Group Education to Promote Nonpharmacological Strategies to Improve Pain, Functioning, and Quality of Life in Veterans-Rationale, Methods, and Implementation" (2020) Pain Medicine (Malden, Mass.)
Whole Health Options and Pain Education (wHOPE): A Pragmatic Trial Comparing Whole Health Team vs Primary Care Group Education to Promote Nonpharmacological Strategies to Improve Pain, Functioning, and Quality of Life in Veterans-Rationale, Methods, and Implementation
(2020) Pain Medicine (Malden, Mass.), 21 (2), pp. S91-S99.
Seal, K.H.a b , Becker, W.C.c d , Murphy, J.L.e f , Purcell, N.a b , Denneson, L.M.g h , Morasco, B.J.g h , Martin, A.M.e , Reddy, K.i j , Iseghem, T.V.i , Krebs, E.E.k l , Painter, J.M.m n , Hagedorn, H.k l , Pyne, J.M.m n , Hixon, J.a b , Maguen, S.a b , Neylan, T.C.a b , Borsari, B.a b , DeRonne, B.k , Gibson, C.a b , Matthias, M.S.o p , Frank, J.W.q r , Krishnaswamy, A.a , Li, Y.a , Bertenthal, D.a , Chan, A.a , Nunez, A.a , McCamish, N.a
a San Francisco Veterans Affairs Health Care System
b University of California, San Francisco, Mexico
c VA Connecticut Healthcare System
d Yale School of Medicine
e James A. Haley Veterans’ Hospital
f University of South Florida Morsani College of Medicine
g VA Portland Health Care System
h Oregon Health & Science University
i VA St. Louis Health Care System
j Washington University School of Medicine
k Minneapolis VA Health Care System
l University of Minnesota School of Medicine
m University of Arkansas for Medical Sciences
n Central Arkansas VA Healthcare System
o Indianapolis VA Medical Center
p Indiana University School of Medicine
q VA Eastern Colorado Health Care System
r University of Colorado School of Medicine
Abstract
BACKGROUND: The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care. DESIGN: wHOPE is a pragmatic randomized controlled trial comparing a Whole Health Team (WHT) approach to Primary Care Group Education (PC-GE); both will be compared to Usual VA Primary Care (UPC). The WHT consists of a medical provider, a complementary and integrative health (CIH) provider, and a Whole Health coach, who collaborate with VA patients to create a Personalized Health Plan emphasizing CIH approaches to chronic pain management. The active comparator, PC-GE, is adapted group cognitive behavioral therapy for chronic pain. The first aim is to test whether the WHT approach is superior to PC-GE and whether both are superior to UPC in decreasing pain interference in functioning in 750 veterans with moderate to severe chronic pain (primary outcome). Secondary outcomes include changes in pain severity, quality of life, mental health symptoms, and use of nonpharmacological and pharmacological therapies for pain. Outcomes will be collected from the VA electronic health record and patient-reported data over 12 months of follow-up. Aim 2 consists of an implementation-focused process evaluation and budget impact analysis. SUMMARY: This trial is part of the Pain Management Collaboratory, which seeks to create national-level infrastructure to support evidence-based nonpharmacological pain management approaches for veterans and military service personnel. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. This work is written by a US Government employee and is in the public domain in the US.
Author Keywords
Chronic Pain; Cognitive Behavior Therapy; Complementary and Integrative Health; Pragmatic Trial; Primary Care; Veterans
Document Type: Article
Publication Stage: Final
Source: Scopus
"Antipsychotic Effects on Cortical Morphology in Schizophrenia and Bipolar Disorders" (2020) Frontiers in Neuroscience
Antipsychotic Effects on Cortical Morphology in Schizophrenia and Bipolar Disorders
(2020) Frontiers in Neuroscience, 14, art. no. 579139, .
Feng, R.a b , Womer, F.Y.c , Edmiston, E.K.d , Chen, Y.b e , Wang, Y.f , Chang, M.a b , Yin, Z.b e , Wei, Y.b e , Duan, J.b e , Ren, S.a b , Li, C.a b , Liu, Z.g , Jiang, X.a b , Wei, S.a b , Li, S.a , Zhang, X.h , Zuo, X.-N.i , Tang, Y.b e , Wang, F.a b e
a Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China
b Brain Function Research Section, The First Affiliated Hospital of China Medical University, Shenyang, China
c Department of Psychiatry, Washington University School of Medicine, , St. Louis, MO, United States
d Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, United States
e Department of Psychiatry, The First Affiliated Hospital of China Medical University, Shenyang, China
f CAS Key Laboratory of Behavioral Science and Research Center for Lifespan Development of Mind and Brain (CLIMB), Institute of Psychology, Beijing, China
g School of Public Health, China Medical University, Shenyang, China
h School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China
i Key Laboratory of Brain and Education Sciences, School of Education Sciences, Nanning Normal University, Nanning, China
Abstract
Background: Previous studies of atypical antipsychotic effects on cortical structures in schizophrenia (SZ) and bipolar disorder (BD) have findings that vary between the short and long term. In particular, there has not been a study exploring the effects of atypical antipsychotics on age-related cortical structural changes in SZ and BD. This study aimed to determine whether mid- to long-term atypical antipsychotic treatment (mean duration = 20 months) is associated with cortical structural changes and whether age-related cortical structural changes are affected by atypical antipsychotics. Methods: Structural magnetic resonance imaging images were obtained from 445 participants consisting of 88 medicated patients (67 with SZ, 21 with BD), 84 unmedicated patients (50 with SZ, 34 with BD), and 273 healthy controls (HC). Surface-based analyses were employed to detect differences in thickness and area among the three groups. We examined the age-related effects of atypical antipsychotics after excluding the potential effects of illness duration. Results: Significant differences in cortical thickness were observed in the frontal, temporal, parietal, and insular areas and the isthmus of the cingulate gyrus. The medicated group showed greater cortical thinning in these regions than the unmediated group and HC; furthermore, there were age-related differences in the effects of atypical antipsychotics, and these effects did not relate to illness duration. Moreover, cortical thinning was significantly correlated with lower symptom scores and Wisconsin Card Sorting Test (WCST) deficits in patients. After false discovery rate correction, cortical thinning in the right middle temporal gyrus in patients was significantly positively correlated with lower HAMD scores. The unmedicated group showed only greater frontotemporal thickness than the HC group. Conclusion: Mid- to long-term atypical antipsychotic use may adversely affect cortical thickness over the course of treatment and ageing and may also result in worsening cognitive function. © Copyright © 2020 Feng, Womer, Edmiston, Chen, Wang, Chang, Yin, Wei, Duan, Ren, Li, Liu, Jiang, Wei, Li, Zhang, Zuo, Tang and Wang.
Author Keywords
atypical antipsychotics; bipolar disorder; cortical thickness; magnetic resonance imaging (MRI); schizophrenia
Funding details
National Natural Science Foundation of ChinaNSFC
Document Type: Article
Publication Stage: Final
Source: Scopus
"Social jetlag and prostate cancer incidence in alberta’s tomorrow project: A prospective cohort study" (2020) Cancers
Social jetlag and prostate cancer incidence in alberta’s tomorrow project: A prospective cohort study
(2020) Cancers, 12 (12), art. no. 3873, pp. 1-12.
Hu, L.a b , Harper, A.b , Heer, E.b , McNeil, J.b , Cao, C.c , Park, Y.d , Martell, K.e , Gotto, G.f , Shen‐tu, G.g , Peters, C.b d h , Brenner, D.e , Yang, L.b e h
a Department of Sport and Exercise Science, Zhejiang University, Hangzhou, Zhejiang 310028, China
b Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, AB T2S 3C3, Canada
c Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States
d Washington University School of Medicine, St. Louis, MO 63110, United States
e Department of Oncology, University of Calgary, Calgary, AB T2N 4N2, Canada
f Department of Surgery, University of Calgary, Calgary, AB T2N 4N2, Canada
g Cancer Care Alberta, Alberta Health Services, Calgary, AB T2T 5C7, Canada
h Department of Community Health Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada
Abstract
We investigated the association of social jetlag (misalignment between the internal clock and socially required timing of activities) and prostate cancer incidence in a prospective cohort in Alberta, Canada. Data were collected from 7455 cancer‐free men aged 35–69 years enrolled in Alberta’s Tomorrow Project (ATP) from 2001–2007. In the 2008 survey, participants reported usual bed‐ and wake‐times on weekdays and weekend days. Social jetlag was defined as the absolute difference in waking time between weekday and weekend days, and was categorized into three groups: 0‐<1 h (from 0 to anything smaller than 1), 1‐<2 h (from 1 to anything smaller than 2), and 2+ h. ATP facilitated data linkage with the Alberta Cancer Registry in June 2018 to determine incident prostate cancer cases (n = 250). Hazard ratios (HR) were estimated using Cox proportional hazards regressions, adjusting for a range of covariates. Median follow‐up was 9.57 years, yielding 68,499 person‐years. Baseline presence of social jetlag of 1‐<2 h (HR = 1.52, 95% CI: 1.10 to 2.01), and 2+ hours (HR = 1.69, 95% CI: 1.15 to 2.46) were associated with increased prostate cancer risk vs. those reporting no social jetlag (P for trend = 0.004). These associations remained after adjusting for sleep duration (P for trend = 0.006). With respect to chronotype, the association between social jetlag and prostate cancer risk remained significant in men with early chronotypes (P for trend = 0.003) but attenuated to null in men with intermediate (P for trend = 0.150) or late chronotype (P for trend = 0.381). Our findings suggest that greater than one hour of habitual social jetlag is associated with an increased risk of prostate cancer. Longitudinal studies with repeated measures of social jetlag and large samples with sufficient advanced prostate cancer cases are needed to confirm these findings. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Circadian disruption; Prostate cancer incidence; Social jetlag
Funding details
Zhejiang UniversityZJU
China Scholarship CouncilCSC201806325023
Document Type: Article
Publication Stage: Final
Source: Scopus
"Seeing Parkinson Disease in the Retina" (2020) JAMA Ophthalmology
Seeing Parkinson Disease in the Retina
(2020) JAMA Ophthalmology, .
Lin, J.B.a , Apte, R.S.b c
a Department of Ophthalmology, Harvard Medical School, Boston, MA, United States
b Department of Ophthalmology and Visual Sciences, Washington University in St Louis, St Louis, MO, United States
c Department of Developmental Biology and Medicine, Washington University in St Louis, St Louis, MO, United States
Document Type: Note
Publication Stage: Article in Press
Source: Scopus
"Effect of Motor Skill Training in Functional Activities vs Strength and Flexibility Exercise on Function in People with Chronic Low Back Pain: A Randomized Clinical Trial" (2020) JAMA Neurology
Effect of Motor Skill Training in Functional Activities vs Strength and Flexibility Exercise on Function in People with Chronic Low Back Pain: A Randomized Clinical Trial
(2020) JAMA Neurology, .
Van Dillen, L.R.a b , Lanier, V.M.a b , Steger-May, K.c , Wallendorf, M.c , Norton, B.J.a d , Civello, J.M.a , Czuppon, S.L.a b , Francois, S.J.a , Roles, K.a , Lang, C.E.a d e
a Program in Physical Therapy, Washington University School of Medicine in St Louis, St Louis, MO, United States
b Department of Orthopaedic Surgery, Washington University School of Medicine in St Louis, St Louis, MO, United States
c Division of Biostatistics, Washington University School of Medicine in St Louis, St Louis, MO, United States
d Department of Neurology, Washington University School of Medicine in St Louis, St Louis, MO, United States
e Program in Occupational Therapy, Washington University School of Medicine in St Louis, St Louis, MO, United States
Abstract
Importance: Chronic low back pain (LBP) is the most prevalent chronic pain in adults, and there is no optimal nonpharmacologic management. Exercise is recommended, but no specific exercise-based treatment has been found to be most effective. Objective: To determine whether an exercise-based treatment of person-specific motor skill training (MST) in performance of functional activities is more effective in improving function than strength and flexibility exercise (SFE) immediately, 6 months, and 12 months following treatment. The effect of booster treatments 6 months following treatment also was examined. Design, Setting, and Participants: In this single-blind, randomized clinical trial of people with chronic, nonspecific LBP with 12-month follow-up, recruitment spanned December 2013 to August 2016 (final follow-up, November 2017), and testing and treatment were performed at an academic medical center. Recruitment was conducted by way of flyers, physician and physical therapy offices, advertisements, and media interviews at Washington University in St Louis, Missouri. Of 1595 adults screened for eligibility, 1301 did not meet the inclusion criteria and 140 could not be scheduled for the first visit. A total of 154 people with at least 12 months of chronic, nonspecific LBP, aged 18 to 60 years, with modified Oswestry Disability Questionnaire (MODQ) score of at least 20% were randomized to either MST or SFE. Data were analyzed between December 1, 2017, and October 6, 2020. Interventions: Participants received 6 weekly 1-hour sessions of MST in functional activity performance or SFE of the trunk and lower limbs. Half of the participants in each group received up to 3 booster treatments 6 months following treatment. Main Outcomes and Measures: The primary outcome was the modified Oswestry Disability Questionnaire (MODQ) score (0%-100%) evaluated immediately, 6 months, and 12 months following treatment. Results: A total of 149 participants (91 women; mean [SD] age, 42.5 [11.7] years) received some treatment and were included in the intention-To-Treat analysis. Following treatment, MODQ scores were lower for MST than SFE by 7.9 (95% CI, 4.7 to 11.0; P <.001). During the follow-up phase, the MST group maintained lower MODQ scores than the SFE group, 5.6 lower at 6 months (95% CI, 2.1 to 9.1) and 5.7 lower at 12 months (95% CI, 2.2 to 9.1). Booster sessions did not change MODQ scores in either treatment. Conclusions and Relevance: People with chronic LBP who received MST had greater short-Term and long-Term improvements in function than those who received SFE. Person-specific MST in functional activities limited owing to LBP should be considered in the treatment of people with chronic LBP. Trial Registration: ClinicalTrials.gov Identifier: NCT02027623. © 2020 American Medical Association. All rights reserved.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Add-On Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial" (2020) JAMA Neurology
Add-On Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial
(2020) JAMA Neurology, .
Thiele, E.A.a , Bebin, E.M.b , Bhathal, H.c , Jansen, F.E.d , Kotulska, K.e f , Lawson, J.A.g , O’Callaghan, F.J.h , Wong, M.i , Sahebkar, F.j , Checketts, D.k , Knappertz, V.j
a Pediatric Epilepsy Program, Massachusetts General Hospital, 175 Cambridge St, Ste 340, Boston, MA 02114, United States
b Department of Neurology and Pediatrics, University of Alabama School of Medicine, Birmingham, United States
c Centro Médico Teknon, Neurocenter Barcelona, Barcelona, Spain
d Department of Pediatric Neurology, Brain Center University Medical Center, Utrecht, Netherlands
e Department of Neurology and Epileptology, Children’s Memorial Health Institute, Warsaw, Poland
f EpiCare: A European Reference Network for Rare or Low Prevalence Complex Diseases, Bron, France
g Neurology Department, Sydney Children’s Hospital, Randwick, Australia
h Neurosciences Unit, UCL Institute of Child Health, London, United Kingdom
i Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
j Greenwich Biosciences Inc, Carlsbad, CA, United States
k GW Research Ltd, Cambridge, United Kingdom
Abstract
Importance: Efficacy of cannabidiol has been demonstrated in seizures associated with Lennox-Gastaut and Dravet syndromes but appears not yet to have been established in conditions with primarily focal seizures, such as tuberous sclerosis complex (TSC). Objective: To evaluate efficacy and safety of 25-mg/kg/day and 50-mg/kg/day cannabidiol dosages vs placebo against seizures associated with TSC. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial (GWPCARE6) enrolled patients between April 6, 2016, and October 4, 2018; follow-up was completed on February 15, 2019. The trial was conducted at 46 sites in Australia, Poland, Spain, the Netherlands, United Kingdom, and United States. Eligible patients (aged 1-65 years) were those with a clinical diagnosis of TSC and medication-resistant epilepsy who had had at least 8 TSC-associated seizures during the 4-week baseline period, with at least 1 seizure occurring in at least 3 of the 4 weeks, and were currently taking at least 1 antiepileptic medication. Interventions: Patients received oral cannabidiol at 25 mg/kg/day (CBD25) or 50 mg/kg/day (CBD50) or a matched placebo for 16 weeks. Main Outcomes and Measures: The prespecified primary outcome was the change from baseline in number of TSC-associated seizures for cannabidiol vs placebo during the treatment period. Results: Of 255 patients screened for eligibility, 31 were excluded and 224 were randomized. Of the 224 included patients (median [range] age, 11.4 [1.1-56.8] years; 93 female patients [41.5%]), 75 were randomized to CBD25, 73 to CBD50, and 76 to placebo, with 201 completing treatment. The percentage reduction from baseline in the type of seizures considered the primary end point was 48.6% (95% CI, 40.4%-55.8%) for the CBD25 group, 47.5% (95% CI, 39.0%-54.8%) for the CBD50 group, and 26.5% (95% CI, 14.9%-36.5%) for the placebo group; the percentage reduction from placebo was 30.1% (95% CI, 13.9%-43.3%; P <.001) for the CBD25 group and 28.5% (95% CI, 11.9%-42.0%; nominal P =.002) for the CBD50 group. The most common adverse events were diarrhea (placebo group, 19 [25%]; CBD25 group, 23 [31%]; CBD50 group, 41 [56%]) and somnolence (placebo group, 7 [9%]; CBD25 group, 10 [13%]; CBD50 group, 19 [26%]), which occurred more frequently with cannabidiol than placebo. Eight patients in CBD25 group, 10 in CBD50 group, and 2 in the placebo group discontinued treatment because of adverse events. Twenty-eight patients taking cannabidiol (18.9%) had elevated liver transaminase levels vs none taking placebo. Conclusions and Relevance: Cannabidiol significantly reduced TSC-associated seizures compared with placebo. The 25-mg/kg/day dosage had a better safety profile than the 50-mg/kg/day dosage. © 2020 American Medical Association. All rights reserved.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
"Influences of Repair Site Tension and Conduit Splinting on Peripheral Nerve Reconstruction" (2020) Hand
Influences of Repair Site Tension and Conduit Splinting on Peripheral Nerve Reconstruction
(2020) Hand, .
Brogan, D.M.a , Dy, C.J.a , Rioux-Forker, D.b , Wever, J.a , Leversedge, F.J.c
a Washington University in St. LouisMO, United States
b University of Missouri, Columbia, MO, United States
c University of Colorado, Aurora, CO, United States
Abstract
Background: We investigated the use of a conduit splinting technique to mitigate tension at the coaptation site of a rodent nerve defect model to determine the optimal reconstruction method for segmental nerve defects. Methods: A rat sciatic nerve segmental defect model was created by excising 5mm of the sciatic nerve unilaterally. Four groups of 10 rats were each reconstructed using 1 of 4 techniques: primary repair, repair with conduit splinting, reverse isograft with conduit splinting, and reverse isograft without splinting. Functional outcomes were assessed at 6 weeks by measurement of Sciatic Functional Index (SFI), and sciatic nerves were harvested at the nonsurvival surgery. Histomorphologic measurements were reported as a value normalized to the average measurements of the control side. The primary outcomes were assessment of nerve continuity and the proportion of nerve fibers in the regenerating nerve compared with the uninjured side. Results: The number of repair site rupture rates was lower when a conduit splint was used—less than half of the primary repairs under tension remained intact at 6 weeks. No difference was seen in axon number, size, and density between primary repairs and those augmented by conduit splints, but worse functional outcomes and more debris were present compared with the intact primary repairs. Conclusions: Nerve conduit splinting reduced rupture rates, particularly for nerve repairs associated with a segmental defect. No significant difference was seen in the number of axons among techniques. Primary nerve repair under tension that did not rupture demonstrated superior SFI. © The Author(s) 2020.
Author Keywords
gap; peripheral nerve; segmental defect; tension
Funding details
Washington University in St. LouisWUSTL
National Institutes of HealthNIHKL2 TR002346
National Center for Advancing Translational SciencesNCATS
Document Type: Article
Publication Stage: Article in Press
Source: Scopus