“GPS driving: a digital biomarker for preclinical Alzheimer disease” (2021) Alzheimer’s Research and Therapy
GPS driving: a digital biomarker for preclinical Alzheimer disease
(2021) Alzheimer’s Research and Therapy, 13 (1), art. no. 115, .
Bayat, S.a b , Babulal, G.M.c d e , Schindler, S.E.c d , Fagan, A.M.c d f , Morris, J.C.c d f g h i , Mihailidis, A.a b j , Roe, C.M.c d
a Institute of Biomedical Engineering, University of Toronto, 550 University Avenue, Toronto, ON M5G 1X5, Canada
b KITE Research Institute, Toronto Rehabilitation Institute, Toronto, ON, Canada
c Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, United States
d Department of Neurology, Washington University School of Medicine, St. Louis, MO, United States
e Department of Psychology, University of Johannesburg, Johannesburg, South Africa
f Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO, United States
g Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO, United States
h Department of Physical Therapy, Washington University School of Medicine, St. Louis, MO, United States
i Department of Occupational Science & Occupational Therapy, Washington University School of Medicine, St. Louis, MO, United States
j Department of Occupational Science and Occupational Therapy, University of Toronto, Toronto, ON, Canada
Abstract
Background: Alzheimer disease (AD) is the most common cause of dementia. Preclinical AD is the period during which early AD brain changes are present but cognitive symptoms have not yet manifest. The presence of AD brain changes can be ascertained by molecular biomarkers obtained via imaging and lumbar puncture. However, the use of these methods is limited by cost, acceptability, and availability. The preclinical stage of AD may have a subtle functional signature, which can impact complex behaviours such as driving. The objective of the present study was to evaluate the ability of in-vehicle GPS data loggers to distinguish cognitively normal older drivers with preclinical AD from those without preclinical AD using machine learning methods. Methods: We followed naturalistic driving in cognitively normal older drivers for 1 year with a commercial in-vehicle GPS data logger. The cohort included n = 64 individuals with and n = 75 without preclinical AD, as determined by cerebrospinal fluid biomarkers. Four Random Forest (RF) models were trained to detect preclinical AD. RF Gini index was used to identify the strongest predictors of preclinical AD. Results: The F1 score of the RF models for identifying preclinical AD was 0.85 using APOE ε4 status and age only, 0.82 using GPS-based driving indicators only, 0.88 using age and driving indicators, and 0.91 using age, APOE ε4 status, and driving. The area under the receiver operating curve for the final model was 0.96. Conclusion: The findings suggest that GPS driving may serve as an effective and accurate digital biomarker for identifying preclinical AD among older adults. © 2021, The Author(s).
Author Keywords
Global positioning system; Machine learning; Naturalistic driving; Preclinical Alzheimer disease
Funding details
National Institutes of HealthNIHP01AG003991, P01AG026276, P30AG066444, U19AG024904, U19AG032438
National Institute on AgingNIAAG056466, R01AG067428, R01AG068183
Biogen
BrightFocus FoundationBFFA2021142S
Document Type: Article
Publication Stage: Final
Source: Scopus
“Opioid dosing among patients with 3 or more years of continuous prescription opioid use before and after the CDC opioid prescribing guideline” (2021) International Journal of Drug Policy
Opioid dosing among patients with 3 or more years of continuous prescription opioid use before and after the CDC opioid prescribing guideline
(2021) International Journal of Drug Policy, 97, art. no. 103308, .
Salas, J.a b , Li, X.c , Xian, H.c , Sullivan, M.D.d , Ballantyne, J.C.e , Lustman, P.J.f g , Grucza, R.a b , Scherrer, J.F.a b
a Department of Family and Community Medicine, Saint Louis University School of Medicine, 1008 S. Spring, St. Louis, MO 63110, United States
b Advanced HEAlth Data (AHEAD) Research Institute, Saint Louis University School of Medicine, 1008 S. Spring, St. Louis, MO 63110, United States
c College of Public Health and Social Justice, Saint Louis University, 3545 Lafayette Ave, St. Louis, MO 63104, United States
d Department of Psychiatry and Behavioral Science, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195, United States
e Department of Anesthesiology and Pain Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, United States
f Department of Psychiatry, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, United States
g The Bell Street Clinic Opioid Addiction Treatment Programs, VA St. Louis Healthcare System, 915 North Grand Blvd, St. Louis, MO 63106, United States
Abstract
Background: Opioid doses declined after the Centers for Disease Control (CDC) opioid prescribing guideline was published. However, it is unknown if dose declines occurred in patients with ≥ 3 years of continuous opioid use. Methods: Optum® de-identified integrated Electronic Health Record and claims data were used to create an adult sample (n = 400) with continuous opioid use for 18 months before and after the guideline publication. Based on the morphine milligram equivalent (MME) distribution at Month 1, patients were categorized into 1–50, 51–100, 101–200, and >200 mg baseline MME. Interrupted time series analysis using segmented mixed linear regression models stratified on baseline MME estimated average monthly changes in MME in the 18-months pre- and post-guideline, before and after adjusting for time-varying pain conditions, psychiatric disorders and benzodiazepine prescription. Results: Patients were 59.6 (SD±11.8) years of age, 55.8% female and 84.0% white race. For 1–50 MME, monthly dose slope was significantly (p<0.0001) flatter post-guideline (pre b = 0.34 MME/month vs. post b = 0.12 MME/month). For 51–100 MME, the pre- and post-guideline dose slopes did not significantly differ (pre b = 0.60 MME/month vs. post b = 0.27 MME/month). For 101–200 MME, post-guideline dose slope was significantly (p<0.0001) steeper and decreasing post-guideline (pre b = 0.11 MME/month vs. post b= -1.33 MME/month). Among >200 MME, dose decreased in the pre- and post-guideline periods, and post-guideline decline was significantly (p<0.0001) steeper (b= -1. 86 MME/month vs. b= -4.13 MME/month). Conclusions: Among patients on multiyear opioid therapy, the CDC guideline was associated with a modest change in dosing, except for patients on very high doses. The guideline was not associated with decreasing MME among lower-dose, long-term users. © 2021 Elsevier B.V.
Author Keywords
dependence; epidemiology; guidelines; opioids; retrospective cohort
Funding details
Saint Louis UniversitySLU
Document Type: Article
Publication Stage: Final
Source: Scopus
“Neighborhood active aging infrastructure and cognitive function: A mixed-methods study of older Americans” (2021) Preventive Medicine
Neighborhood active aging infrastructure and cognitive function: A mixed-methods study of older Americans
(2021) Preventive Medicine, 150, art. no. 106669, .
Finlay, J.a b , Esposito, M.a c , Li, M.a d , Colabianchi, N.e , Zhou, H.a f , Judd, S.g , Clarke, P.a b
a Social Environment and Health, Survey Research Center, Institute for Social Research, University of Michigan, 426 Thompson Street, Ann Arbor, MI 48104, United States
b Center for Social Epidemiology and Population Health, Department of Epidemiology, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States
c Department of Sociology, Washington University of St. Louis, St. Louis, MO 63130, United States
d Survey Methodology Program, Institute for Social Research, University of Michigan, 426 Thompson Street, Ann Arbor, MI 48104, United States
e School of Kinesiology, University of Michigan, 1402 Washington Heights, Ann Arbor, MI 48109, United States
f Biostatistics Program, School of Public Health, University of Michigan, 1415 Washington Heights, Ann Arbor, MI 48109, United States
g School of Public Health, University of Alabama at Birmingham, 1665 University Blvd, Birmingham, AL 35233, United States
Abstract
Physical exercise benefits cognitive functioning and can protect against neurodegeneration. Neighborhood environments may be pivotal to physically active aging, and thus help shape older adults’ cognitive function. This mixed-methods study investigated where older adults exercised outside the home, and whether availability of these neighborhood sites was associated with cognitive function. We thematically analyzed qualitative data from semi-structured interviews in 2015 with 125 older adults (mean age = 71) in the Minneapolis (MN) metropolitan area. Results identified nearby public parks, fitness/sports amenities, and walkable destinations as motivators for recreational exercise and active transit among participants. These findings informed quantitative analysis of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a national sample of older Black and white Americans (n = 21,151; mean age at assessment = 67; data collected 2006–2017). We used generalized additive multilevel models to examine whether neighborhood features that qualitative participants identified as encouraging physical activity were associated with elevated levels of cognitive function. Results indicated that residing in neighborhoods with greater availability of local parks, access to recreational amenities, and business density was associated with higher levels of cognitive function. We found no evidence to suggest a significant association between availability of these neighborhood resources and rate of cognitive decline. This study identifies specific neighborhood active aging infrastructure that may support cognitive function among older adults aging in place. © 2021 Elsevier Inc.
Author Keywords
Aging in place; Cognitive aging; Leisure; Mixed-methods; Neighborhood environment; Physical activity
Funding details
F32 AG064815-01, UL1 TR002240-02
National Institutes of HealthNIH1RF1AG057540-01
U.S. Department of Health and Human ServicesHHS
National Institute on AgingNIA
National Institute of Neurological Disorders and StrokeNINDS
Document Type: Article
Publication Stage: Final
Source: Scopus
“Resting-state functional connectivity associated with gait characteristics in people with Parkinson’s disease” (2021) Behavioural Brain Research
Resting-state functional connectivity associated with gait characteristics in people with Parkinson’s disease
(2021) Behavioural Brain Research, 411, art. no. 113398, .
Horin, A.P.a , Myers, P.S.b , Pickett, K.A.c d , Earhart, G.M.a b e , Campbell, M.C.b f
a Program in Physical Therapy, Washington University School of Medicine, St Louis, MO, United States
b Department of Neurology, Washington University School of Medicine, St Louis, MO, United States
c Occupational Therapy Program, Department of Kinesiology, University of Wisconsin-Madison, Madison, United States
d Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, United States
e Department of Neuroscience, Washington University School of Medicine, St Louis, MO, United States
f Department of Radiology, Washington University School of Medicine, St Louis, MO, United States
Abstract
Introduction: Parkinson’s disease (PD) is a movement disorder caused by dysfunction in the basal ganglia (BG). Clinically relevant gait deficits, such as decreased velocity and increased variability, may be caused by underlying neural dysfunction. Reductions in resting-state functional connectivity (rs-FC) between networks have been identified in PD compared to controls; however, the association between gait characteristics and rs-FC of brain networks in people with PD has not yet been explored. The present study aimed to investigate these associations. Methods: Gait characteristics and rs-FC MRI data were collected for participants with PD (N = 50). Brain networks were identified from a set of seeds representing cortical, subcortical, and cerebellar regions. Gait outcomes were correlated with the strength of rs-FC within and between networks of interest. A stepwise regression analysis was also conducted to determine whether the rs-FC strength of brain networks, along with clinical motor scores, were predictive of gait characteristics. Results: Gait velocity was associated with rs-FC within the visual network and between motor and cognitive networks, most notably BG-thalamus internetwork rs-FC. The stepwise regression analysis showed strength of BG-thalamus internetwork rs-FC and clinical motor scores were predictive of gait velocity. Conclusion: The results of the present study demonstrate gait characteristics are associated with functional organization of the brain at the network level, providing insight into the neural mechanisms of clinically relevant gait characteristics. This knowledge could be used to optimize the design of gait rehabilitation interventions for people with neurological conditions. © 2021 Elsevier B.V.
Author Keywords
Functional connectivity; Gait; Networks; Parkinson’s disease
Funding details
National Institutes of HealthNIHKL2TR002374, R01NS077959, T32HD007434, UL1TR002373
American Parkinson Disease AssociationAPDA
St. Louis American Parkinson Disease Association
Document Type: Article
Publication Stage: Final
Source: Scopus
“Activated microglia mitigate Aβ-associated tau seeding and spreading” (2021) The Journal of Experimental Medicine
Activated microglia mitigate Aβ-associated tau seeding and spreading
(2021) The Journal of Experimental Medicine, 218 (8), .
Gratuze, M.a b c , Chen, Y.a b c d , Parhizkar, S.a b c , Jain, N.a b c , Strickland, M.R.a b c , Serrano, J.R.a b c , Colonna, M.b c d , Ulrich, J.D.a b c , Holtzman, D.M.a b c
a Department of Neurology, Washington University School of Medicine, St. Louis, MO
b Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO
c Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, MO
d Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
Abstract
In Alzheimer’s disease (AD) models, AD risk variants in the microglial-expressed TREM2 gene decrease Aβ plaque-associated microgliosis and increase neuritic dystrophy as well as plaque-associated seeding and spreading of tau aggregates. Whether this Aβ-enhanced tau seeding/spreading is due to loss of microglial function or a toxic gain of function in TREM2-deficient microglia is unclear. Depletion of microglia in mice with established brain amyloid has no effect on amyloid but results in less spine and neuronal loss. Microglial repopulation in aged mice improved cognitive and neuronal deficits. In the context of AD pathology, we asked whether microglial removal and repopulation decreased Aβ-driven tau seeding and spreading. We show that both TREM2KO and microglial ablation dramatically enhance tau seeding and spreading around plaques. Interestingly, although repopulated microglia clustered around plaques, they had a reduction in disease-associated microglia (DAM) gene expression and elevated tau seeding/spreading. Together, these data suggest that TREM2-dependent activation of the DAM phenotype is essential in delaying Aβ-induced pathological tau propagation. © 2021 Gratuze et al.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Childhood adversity, suicidality, and non-suicidal self-injury among children and adolescents admitted to emergency departments” (2021) Annals of Epidemiology
Childhood adversity, suicidality, and non-suicidal self-injury among children and adolescents admitted to emergency departments
(2021) Annals of Epidemiology, 60, pp. 21-27.
Carbone, J.T.a , Jackson, D.B.b , Holzer, K.J.c , Vaughn, M.G.d e
a Wayne State University, Wayne State University, School of Social Work, Integrative Biosciences (IBio) Center, Detroit, MI, United States
b Johns Hopkins University, Bloomberg School of Public Health, Department of Population, Family, and Reproductive Health, Baltimore, MD, United States
c Washington University in St. Louis, School of Medicine, Division of Clinical and Translational Research, St. Louis, MO, United States
d Saint Louis University, College for Public Health and Social Justice, School of Social Work, St. Louis, MO, United States
e Yonsei University, Department of Social WelfareSeoul, South Korea
Abstract
Purpose: This population-based study explored the associations between childhood adversity and admission to emergency departments (EDs) with non-suicidal self-injury (NSSI) and with a suicide attempt. Methods: A nationally representative cross-sectional sample of 5–17-year-olds admitted to EDs (N = 143,113,677) from 2006 to 2015 was utilized to assess the associations between childhood adversities, NSSIs, and suicide attempts. Results: ED admissions with NSSI and admissions with a suicide attempt were associated with greater odds of exposure to individual childhood adversities (aORs: 1.34 to 5.86; aORs: 2.37 to 15.69, respectively). ED admissions with a suicide attempt were associated with greater odds of exposure to childhood adversities that might be perceived as less extreme or harmful (separation or divorce aOR: 15.69) than other adversities (death of a family member aOR: 13.38; history of physical abuse aOR: 9.56) as well as greater odds of exposure to three or more childhood adversities (aOR: 20.98). Conclusion: Early detection of childhood adversities is important for identifying potential risk factors for self-harm. ED admission data can provide population-level surveillance to aid in these efforts and lead to more targeted and effective interventions aimed at reducing the negative effects of toxic stress that can result from exposure to childhood adversities. © 2021 Elsevier Inc.
Author Keywords
Abbreviations; ACEs; Adjusted odds ratios; Adverse childhood experiences; aORs; Eds; Emergency departments; Emergency medicine; ICD-10-CM; ICD-9-CM; International Classification of Diseases-Ninth Revision-Clinical Modification; International Classification of Diseases-Tenth Revision-Clinical Modification; Nationwide Emergency Department Sample; NEDS; Non-suicidal self-injury; NSSI; Pediatrics; Public health; Suicide
Document Type: Article
Publication Stage: Final
Source: Scopus
“The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial” (2021) Anesthesia and Analgesia
The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial
(2021) Anesthesia and Analgesia, 133 (1), pp. 233-242.
Vlisides, P.E.a b , Li, D.a b , McKinney, A.a , Brooks, J.a , Leis, A.M.a , Mentz, G.a , Tsodikov, A.c , Zierau, M.a , Ragheb, J.a , Clauw, D.J.d , Avidan, M.S.e , Vanini, G.a f , Mashour, G.A.a b f
a From the Department of Anesthesiology
b Center for Consciousness Science, University of Michigan Medical School, Ann Arbor, MI, United States
c Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, United States
d Department of Anesthesiology, Chronic Pain and Fatigue Research Center, University of Michigan Medical School, Ann Arbor, MI, United States
e Department of Anesthesiology, Washington University School of Medicine, St Louis, MO, United States
f Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United States
Abstract
BACKGROUND: Surgical patients are vulnerable to opioid dependency and related risks. Clinical-translational data suggest that caffeine may enhance postoperative analgesia. This trial tested the hypothesis that intraoperative caffeine would reduce postoperative opioid consumption. The secondary objective was to assess whether caffeine improves neuropsychological recovery postoperatively. METHODS: This was a single-center, randomized, placebo-controlled trial. Participants, clinicians, research teams, and data analysts were all blinded to the intervention. Adult (≥18 years old) surgical patients (n = 65) presenting for laparoscopic colorectal and gastrointestinal surgery were randomized to an intravenous caffeine citrate infusion (200 mg) or dextrose 5% in water (40 mL) during surgical closure. The primary outcome was cumulative opioid consumption through postoperative day 3. Secondary outcomes included subjective pain reporting, observer-reported pain, delirium, Trail Making Test performance, depression and anxiety screens, and affect scores. Adverse events were reported, and hemodynamic profiles were also compared between the groups. RESULTS: Sixty patients were included in the final analysis, with 30 randomized to each group. The median (interquartile range) cumulative opioid consumption (oral morphine equivalents, milligrams) was 77 mg (33-182 mg) for caffeine and 51 mg (15-117 mg) for placebo (estimated difference, 55 mg; 95% confidence interval [CI], -9 to 118; P = .092). After post hoc adjustment for baseline imbalances, caffeine was associated with increased opioid consumption (87 mg; 95% CI, 26-148; P = .005). There were otherwise no differences in prespecified pain or neuropsychological outcomes between the groups. No major adverse events were reported in relation to caffeine, and no major hemodynamic perturbations were observed with caffeine administration. CONCLUSIONS: Caffeine appears unlikely to reduce early postoperative opioid consumption. Caffeine otherwise appears well tolerated during anesthetic emergence. Copyright © 2021 International Anesthesia Research Society.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Executive Function Moderates Functional Outcomes of Engagement Strategies During Rehabilitation in Older Adults” (2021) American Journal of Physical Medicine & Rehabilitation
Executive Function Moderates Functional Outcomes of Engagement Strategies During Rehabilitation in Older Adults
(2021) American Journal of Physical Medicine & Rehabilitation, 100 (7), pp. 635-642.
Ercal, B., Rodebaugh, T.L., Bland, M.D., Barco, P., Lenard, E., Lang, C.E., Miller, J.P., Yingling, M., Lenze, E.J.
From the Healthy Mind Lab, Department of Psychiatry, Washington University School of Medicine in St. Louis (BE, EL, MY, EJL); Department of Psychological and Brain Sciences, Washington University in St. Louis (TLR); and Program in Physical Therapy (MDB, CEL), Program in Occupational Therapy (PB), and Division of Biostatistics (JPM), Washington University School of Medicine in St. Louis, Missouri
Abstract
OBJECTIVE: This study examined cognitive, affective, and medical impairments and their impact on rehabilitation approaches for improving functional outcome after hospitalization in older adults. DESIGN: A secondary analysis of a randomized clinical trial in 229 adults 65 yrs or older admitted to two skilled nursing facilities undergoing rehabilitation services was conducted. Patients were randomized to receive physical and occupational therapy by therapists trained in systematic approaches to engage patients, called Enhanced Medical Rehabilitation, or standard of care. The outcome of interest was functional improvement, defined as Barthel Index at discharge (controlling for Barthel Index upon admission). This study analyzed the relationship of measures of cognition, depression, and medical comorbidities as predictors of functional outcome and as moderators interacting with treatment group. RESULTS: Clock drawing score moderated treatment effect size; the functional improvement of Enhanced Medical Rehabilitation over standard of care therapy reduced with increasing executive impairment. In contrast, general cognitive abilities, depression, medical comorbidities, and readiness for rehabilitation were neither predictors nor moderators of functional improvement. CONCLUSIONS: For older adults undergoing rehabilitation, greater functional improvement with the motivational techniques of Enhanced Medical Rehabilitation was contingent on patients having intact executive function. Given that executive function impairments are common in rehabilitation populations, new strategies are needed to improve treatment outcomes in physical/occupational therapy. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to (1) Discuss the role of baseline affective, cognitive, and medical impairments in impacting functional outcomes of older adults undergoing rehabilitation; (2) Describe the behavioral change and motivational approaches that are core features of the novel intervention known as Enhanced Medical Rehabilitation (E-MR); and (3) Determine the role of baseline executive function in moderating the effect of rehabilitation intervention on functional outcomes in older adults.Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Neurocritical Care of the Pregnant Patient” (2021) Current Treatment Options in Neurology
Neurocritical Care of the Pregnant Patient
(2021) Current Treatment Options in Neurology, 23 (7), art. no. 22, .
Malaiyandi, D.a b c , James, E.a c , Peglar, L.d , Karim, N.a , Henkel, N.a , Guilliams, K.d e
a Department of Neurology, Division of Neurocritical Care, University of Toledo College of Medicine, Toledo, OH, United States
b University of Toledo/ProMedica Neurosciences Center, 2130 W Central Ave, Ste. 201, Toledo, OH, United States
c ProMedica Toledo Hospital, Toledo, OH, United States
d Department of Neurology, Washington University, St. Louis, MO, United States
e Department of Pediatrics, Washington University, St. Louis, MO, United States
Abstract
Purpose of review: To summarize recent changes in management and emerging therapies for pregnant neurocritical care patients. Recent findings: Diagnostic and treatment options for managing neurologic emergencies in pregnant patients have expanded with both greater understanding of the effects of imaging modalities and medications on pregnancy and application of standard treatments for non-pregnant patients to pregnant populations. Specifically, this includes cerebrovascular diseases (pregnancy-associated ischemic stroke, pregnancy-associated intracerebral hemorrhage, cerebral venous sinus thrombosis), post-maternal cardiac arrest care, seizures and status epilepticus, myasthenia gravis, and fetal somatic support in maternal death by neurologic criteria. Summary: With the exception of direct abdominal computed tomography (CT), most imaging studies are reasonably safe in pregnancy. When emergent imaging is needed to prevent maternal morbidity or mortality, any CT sequence with or without contrast is appropriate to pursue. Though new safety data on antiplatelets, antihypertensives, thrombolytics, and antiepileptic drugs have increased options for disease management in pregnancy, unfractionated and low-molecular weight heparin remain the safest options for anticoagulation. Early studies on hypothermia, ketamine, and immunomodulating therapies in pregnancy are promising. In myasthenia gravis, new data on adjunct devices may allow more patients to undergo safe vaginal delivery, avoiding cesarean section and the associated risk of crisis. When difficult decisions regarding preterm delivery arise, recent outcome studies can help inform discussion. Lastly, when the feared complication of maternal death by neurologic criteria occurs, fetal somatic support may help to save at least one life. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Author Keywords
Acute cerebrovascular disorders in pregnancy; Myasthenic crisis in pregnancy, neurocritical care management during pregnancy; Neurological emergencies in pregnancy; Post-maternal cardiac arrest care; Status epilepticus in pregnancy
Document Type: Review
Publication Stage: Final
Source: Scopus
“Relationships Between Viral Load, Neuroimaging, and NP in Persons Living With HIV (2021) Journal of Acquired Immune Deficiency Syndromes” (1999)
Relationships Between Viral Load, Neuroimaging, and NP in Persons Living With HIV
(2021) Journal of Acquired Immune Deficiency Syndromes (1999), 87 (3), pp. 985-992.
Cooley, S.A.a , Navid, J.a , Wisch, J.K.a , Boerwinkle, A.a , Doyle, J.a , Paul, R.H.b , Ances, B.M.a c d
a Department of Neurology, Washington University in Saint Louis, MO, Saint Louis, Seychelles
b Department of Psychology, University of Missouri, MO, Saint Louis, Seychelles
c Department of Radiology, Washington University in Saint Louis, Saint Louis, MO; and
d Hope Center for Neurological Disorders, Washington University in Saint Louis, MO, Saint Louis, Seychelles
Abstract
BACKGROUND: This study examined whether recommended viral load (VL) classifications by the Department of Health and Human Services map onto changes in brain integrity observed in people living with HIV (PLWH). METHODS: Three hundred forty-nine PLWH on combination antiretroviral therapy meeting criteria for virologic suppression (VS) (VL ≤ 20 copies/mL; n = 206), “low-level viremia” (20-200 copies/mL; n = 63), or virologic failure (VF) (>200 copies/mL; n = 80) and 195 demographically similar HIV-negative controls were compared for cognition and brain volumes from 10 regions of interest that are sensitive to HIV. Changes in cognition and brain volumes were examined in a subset of PLWH (n = 132) who completed a follow-up evaluation (mean interval = 28 months) and had no change in treatment regimen. RESULTS: Significant differences in cognition and brain volumes were observed between the HIV-negative control and VS groups compared with those in the VF groups, with few differences observed between the 3 PLWH subgroups. Longitudinally, PLWH who continued to have VF exhibited a greater decline in cognition and brain volumes compared with PLWH who remained with VS. Observed longitudinal changes in cognition correlated with brain volume changes. CONCLUSION: PLWH with continued VF (consecutive VL measurements of >200 copies/mL) represent a cause for clinical concern and may benefit from change in treatment in addition to consideration of other potential etiologies of VF to reduce loss of brain integrity. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Depression and anxiety in a manganese-exposed community” (2021) NeuroToxicology
Depression and anxiety in a manganese-exposed community
(2021) NeuroToxicology, 85, pp. 222-233.
Racette, B.A.a b , Nelson, G.b , Dlamini, W.W.a , Hershey, T.c , Prathibha, P.d , Turner, J.R.d , Checkoway, H.e , Sheppard, L.f , Searles Nielsen, S.a
a Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8111, St. Louis, MO 63110, United States
b School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Parktown, 2193, South Africa
c Departments of Psychiatry and Radiology, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8225, St. Louis, MO 63110, United States
d Department of Energy, Environmental, and Chemical Engineering, Washington University, Campus Box 1180, One Brookings Drive, St. Louis, MO 63130, United States
e Herbert Wertheim School of Public Health, University of California, San Diego, 9500 Gilman Drive, #0725, La Jolla, CA 92093, United States
f Departments of Biostatistics and Environmental and Occupational Health Sciences, University of Washington, Box 357232, Seattle, WA 98195, United States
Abstract
Objective: To characterize the association between residential environmental manganese (Mn) exposure and depression and anxiety, given prior associations among occupationally-exposed workers. Methods: We administered the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) to 697 study participants in their preferred languages. These participants represented a population-based sample of residents aged ≥40 from two predominantly Black African communities in Gauteng province, South Africa: 605 in Meyerton, adjacent to a large Mn smelter, and 92 in Ethembalethu, a comparable non-exposed community. We investigated the associations between community (Meyerton vs. Ethembalethu) and severity of depression and anxiety, using linear regression, adjusting for age and sex. To document community-level differences in Mn exposure, we measured airborne PM2.5-Mn. Results: Meyerton residents had BDI scores 5.63 points (95 % CI 3.07, 8.20) higher than Ethembalethu residents, with all questions contributing to this significant difference. STAI-state scores were marginally higher in Meyerton than Ethembalethu residents [2.12 (95 % CI -0.17, 4.41)], whereas STAI-trait scores were more similar between the communities [1.26 (95 % CI -0.82, 3.35)]. Mean PM2.5-Mn concentration was 203 ng/m3 at a long-term fixed site in Meyerton and 10 ng/m3 in Ethembalethu. Conclusion: Residence near Mn emission sources may be associated with greater depression symptomatology, and possibly current, but not lifetime, anxiety. © 2021 Elsevier B.V.
Author Keywords
Beck depression inventory; Manganese; PM2.5-Mn; South Africa; State-trait anxiety inventory
Funding details
National Institutes of HealthNIHDK064832, HD070855, NS098577, NS109487, P42ES023716, R01ES029846, R01HD098255
U.S. Department of DefenseDODPD190057
National Institute on AgingNIAP01AG055367, R01ES026187
National Institute of Environmental Health SciencesNIEHSK01ES028295, R01ES025991-02S1, R01ES026246, R01ES026891, R01ES027696, R01ES029509, R01ES029524, R01ES030937-S1, R25ES025503
National Institute for Occupational Safety and HealthNIOSHR01OH011661
U.S. Department of TransportationDOTDTFH6117C00036
Health Effects InstituteHEI
Federal Highway AdministrationFHWA
UNICEFGLA/2880/2019/002-PCA
Harvard University
University of MichiganU-M
Cure Alzheimer’s FundCAF
Hope Center for Neurological Disorders
National Institute of Occupational Safety and Health, JapanJNIOSH
Document Type: Article
Publication Stage: Final
Source: Scopus
“Re-evaluating Biopsy for Recurrent Glioblastoma: A Position Statement by the Christopher Davidson Forum Investigators” (2021) Neurosurgery
Re-evaluating Biopsy for Recurrent Glioblastoma: A Position Statement by the Christopher Davidson Forum Investigators
(2021) Neurosurgery, 89 (1), pp. 129-132.
Nduom, E.K.a , Gephart, M.H.b , Chheda, M.G.c , Suva, M.L.d , Amankulor, N.e , Battiste, J.D.f , Campian, J.L.g , Dacey, R.G.h , Das, S.i , Fecci, P.E.j , Hadjipanayis, C.G.k , Hoang, K.B.a , Jalali, A.l , Orringer, D.m , Patel, A.J.l , Placantonakis, D.m , Rodriguez, A.n , Yang, I.o , Yu, J.S.p , Zipfel, G.J.h , Dunn, G.P.h , Leuthardt, E.C.h , Kim, A.H.h
a Department of Neurological Surgery, Emory University School of Medicine, Atlanta, GA, United States
b Department of Neurological Surgery, Stanford University School of Medicine, Palo Alto, CA, United States
c Departments of Medicine and Neurology, Washington University School of Medicine, St Louis, MO, United States
d Department of Pathology, Harvard Medical School, Boston, MA, United States
e Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
f Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States
g Department of Medicine, Washington University School of Medicine, St Louis, MO, United States
h Department of Neurological Surgery, Washington University School of Medicine, St Louis, MO, United States
i Division of Neurosurgery, University of Toronto, Toronto, Canada
j Department of Neurosurgery, Duke University Medical Center, Durham, NC, United States
k Department of Neurosurgery, Icahn School of Medicine at Mount SinaiNY, United States
l Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
m Department of Neurosurgery, NYU Grossman School of MedicineNY, United States
n Department of Neurosurgery, University of Arkansas for Medical Sciences, Little RockAR, United States
o Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States
p Department of Radiation Oncology and Cancer Biology, Cleveland Clinic, Cleveland, OH, United States
Abstract
Patients with glioblastoma (GBM) need bold new approaches to their treatment, yet progress has been hindered by a relative inability to dynamically track treatment response, mechanisms of resistance, evolution of targetable mutations, and changes in mutational burden. We are writing on behalf of a multidisciplinary group of academic neuro-oncology professionals who met at the collaborative Christopher Davidson Forum at Washington University in St Louis in the fall of 2019. We propose a dramatic but necessary change to the routine management of patients with GBM to advance the field: to routinely biopsy recurrent GBM at the time of presumed recurrence. Data derived from these samples will identify true recurrence vs treatment effect, avoid treatments with little chance of success, enable clinical trial access, and aid in the scientific advancement of our understanding of GBM. © Congress of Neurological Surgeons 2021.
Author Keywords
Clinical trials; Glioblastoma; Personalized medicine; Pseudoprogression; Recurrent glioblastoma; Stereotactic biopsy
Document Type: Article
Publication Stage: Final
Source: Scopus
“Meningioma: A Pathology Perspective” (2021) Neurosurgery
Meningioma: A Pathology Perspective
(2021) Neurosurgery, 89 (1), pp. 11-21.
Toland, A.a , Huntoon, K.b , Dahiya, S.M.c
a Department of Pathology, Stanford University, Stanford, CA, United States
b Department of Neurological Surgery, Ohio State University Wexner Medical Center, Columbus, OH, United States
c Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States
Abstract
Meningiomas are dural-based neoplasms that account for ∼37% of all intracranial tumors in the adult population. They can occur anywhere within the central nervous system and have a predilection for females. The World Health Organization classifies meningiomas into 3 grades based on increased risk of recurrence and associated mortality in grade III tumors. Although most tumors are categorized as low-grade, up to ∼15%-20% demonstrate more aggressive behavior. With the long-recognized association with neurofibromatosis type 2 gene mutation, putative driver mutations can be attributed to ∼80% of tumors. Several germline mutations have also been identified in some cases of familial meningiomatosis such as SMARCE1, SUFU, PTEN, and BAP1. Finally, in addition to genetic data, epigenetic alterations, specifically deoxyribonucleic acid methylation, are being increasingly recognized for their prognostic value, potentially adding objectivity to a currently subjective grading scheme. © Congress of Neurological Surgeons 2021.
Author Keywords
Cytogenetics; Histologic variants; Immunohistochemistry; Meningioma; Molecular; WHO grade
Document Type: Article
Publication Stage: Final
Source: Scopus
“Prognostic factors for chronic post-surgical pain after lung or pleural surgery: A protocol for a systematic review and meta-analysis” (2021) BMJ Open
Prognostic factors for chronic post-surgical pain after lung or pleural surgery: A protocol for a systematic review and meta-analysis
(2021) BMJ Open, 11 (6), art. no. e051554, .
Clephas, P.R.D.a , Hoeks, S.E.a , Trivella, M.b , Guay, C.S.c , Singh, P.M.c , Klimek, M.a , Heesen, M.d
a Anesthesiology, Erasmus MC, Rotterdam, Zuid-Holland, Netherlands
b Cardiovascular Medicine, Clinical Sciences Division, Oxford University, Oxford, Oxfordshire, United Kingdom
c Anesthesiology, Washington University School of Medicine in St Louis, St Louis, MO, United States
d Anesthesiology, Kantonsspital Baden AG, Baden, Switzerland
Abstract
Introduction Chronic post-surgical pain (CPSP) after lung or pleural surgery is a common complication and associated with a decrease in quality of life, long-term use of pain medication and substantial economic costs. An abundant number of primary prognostic factor studies are published each year, but findings are often inconsistent, methods heterogeneous and the methodological quality questionable. Systematic reviews and meta-analyses are therefore needed to summarise the evidence. Methods and analysis The reporting of this protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist. We will include retrospective and prospective studies with a follow-up of at least 3 months reporting patient-related factors and surgery-related factors for any adult population. Randomised controlled trials will be included if they report on prognostic factors for CPSP after lung or pleural surgery. We will exclude case series, case reports, literature reviews, studies that do not report results for lung or pleural surgery separately and studies that modified the treatment or prognostic factor based on pain during the observation period. MEDLINE, Scopus, Web of Science, Embase, Cochrane, CINAHL, Google Scholar and relevant literature reviews will be searched. Independent pairs of two reviewers will assess studies in two stages based on the PICOTS criteria. We will use the Quality in Prognostic Studies tool for the quality assessment and the CHARMS-PF checklist for the data extraction of the included studies. The analyses will all be conducted separately for each identified prognostic factor. We will analyse adjusted and unadjusted estimated measures separately. When possible, evidence will be summarised with a meta-analysis and otherwise narratively. We will quantify heterogeneity by calculating the Q and I 2 statistics. The heterogeneity will be further explored with meta-regression and subgroup analyses based on clinical knowledge. The quality of the evidence obtained will be evaluated according to the Grades of Recommendation Assessment, Development and Evaluation guideline 28. Ethics and dissemination Ethical approval will not be necessary, as all data are already in the public domain. Results will be published in a peer-reviewed scientific journal. PROSPERO registration number CRD42021227888. © 2021 BMJ Publishing Group. All rights reserved.
Author Keywords
adult anaesthesia; pain management; thoracic surgery
Document Type: Review
Publication Stage: Final
Source: Scopus
“Development and Preliminary Evaluation of the Tinnitus Severity Short Form” (2021) American Journal of Audiology
Development and Preliminary Evaluation of the Tinnitus Severity Short Form
(2021) American Journal of Audiology, 30 (2), pp. 404-415.
Frumkin, M.R.a , Kallogjeri, D.b , Piccirillo, J.F.b , Beukes, E.W.c d , Manchaiah, V.c e , Andersson, G.f g , Rodebaugh, T.L.a
a Department of Psychological & Brain Sciences, Washington University in St. Louis, MO, Norway
b Department of Otolaryngology – Head & Neck Surgery, Washington University in St. Louis, MO, Norway
c Department of Speech and Hearing Sciences, Lamar University, TX, Beaumont, France
d Psychology and Sport Sciences, Anglia Ruskin University, Cambridge, United Kingdom
e Department of Speech and Hearing, School of Allied Health Sciences, Manipal UniversityKarnataka, India
f Department of Behavioral Sciences and Learning, Linköping University, Sweden
g Department of Clinical Neuroscience, Division of Psychiatry, Karolinska InstituteStockholm, Sweden
Abstract
Purpose Tinnitus, or the perception of sounds that occur without an external sound source, is a prevalent condition worldwide. For a subset of adults, tinnitus causes significant distress and impairment. Several patient-reported outcome measures have been developed to assess severity of tinnitus distress. However, at present, the field lacks a brief measure that is sensitive to treatment change. The purpose of the current study was to develop and preliminarily validate a brief questionnaire for tinnitus severity from two existing measures of tinnitus-related distress, the Tinnitus Handicap Inventory (THI) and Tinnitus Functional Index (TFI). Method Using data from nine study samples in the United States and United Kingdom, we conducted exploratory and confirmatory factor analyses to identify a short measure with good psychometric properties. We also assessed sensitivity to treatment-related change by examining associations with change in the TFI and THI. Finally, we conducted a confirmatory factor analysis of the final short questionnaire in a new sample of adults seeking treatment for tinnitus-related distress. Results We identified 10 items from the THI and TFI that exhibited limited loadings on secondary factors. The resulting Tinnitus Severity Short Form achieved good to excellent fit, including in a unique sample of individuals seeking online treatment for tinnitus, and appeared sensitive to treatment-related change. Conclusions The Tinnitus Severity Short Form developed in the current study may be a useful tool for the assessment of subjective severity and distress associated with tinnitus, especially when patient burden is a concern. Further research is necessary to fully validate the questionnaire for the assessment of treatment-related change.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Outcome after acute ischemic stroke is linked to sex-specific lesion patterns” (2021) Nature Communications
Outcome after acute ischemic stroke is linked to sex-specific lesion patterns
(2021) Nature Communications, 12 (1), p. 3289.
Bonkhoff, A.K.a , Schirmer, M.D.a b , Bretzner, M.a c , Hong, S.a , Regenhardt, R.W.a , Brudfors, M.d , Donahue, K.L.a , Nardin, M.J.a , Dalca, A.V.e f , Giese, A.-K.g , Etherton, M.R.a , Hancock, B.L.f , Mocking, S.J.T.f , McIntosh, E.C.f , Attia, J.h i , Benavente, O.R.j , Bevan, S.k , Cole, J.W.l , Donatti, A.m , Griessenauer, C.J.n o , Heitsch, L.p q , Holmegaard, L.r s , Jood, K.r s , Jimenez-Conde, J.t , Kittner, S.J.l , Lemmens, R.u v , Levi, C.R.i w , McDonough, C.W.x , Meschia, J.F.y , Phuah, C.-L.q , Rolfs, A.z , Ropele, S.aa , Rosand, J.a f ab , Roquer, J.t , Rundek, T.ac , Sacco, R.L.ac , Schmidt, R.aa , Sharma, P.ad ae , Slowik, A.af , Söderholm, M.ag ah , Sousa, A.m , Stanne, T.M.ai , Strbian, D.aj , Tatlisumak, T.s ak , Thijs, V.al am , Vagal, A.an , Wasselius, J.ao ap , Woo, D.aq , Zand, R.ar , McArdle, P.F.as , Worrall, B.B.at , Jern, C.ai au , Lindgren, A.G.av aw , Maguire, J.ax , Bzdok, D.ay az , Wu, O.f , Rost, N.S.a , MRI-GENIE and GISCOME Investigators and the International Stroke Genetics Consortiumba
a J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Harvard Medical School, MA, Boston, United States
b Clinic for Neuroradiology, University Hospital Bonn, Bonn, Germany
c Univ. Lille, Inserm, U1171 – LilNCog (JPARC) – Lille Neurosciences & Cognition, CHU Lille, Lille, F-59000, France
d School of Biomedical Engineering & Imaging Sciences, King’s College London, London, United Kingdom
e Computer Science and Artificial Intelligence Lab, Massachusetts Institute of Technology, MA, Boston, United States
f Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, MA, Charlestown, United States
g Department of Neurology, University Medical Center Hamburg-EppendorfHamburg, Germany
h Hunter Medical Research Institute, NSW, Newcastle, Australia
i School of Medicine and Public Health, University of Newcastle, NSW, Newcastle, Australia
j Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, Canada
k School of Life Sciences, University of Lincoln, Lincoln, United Kingdom
l Department of Neurology, University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, MD, Baltimore, United States
m School of Medical Sciences, University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, Sao Paulo, Brazil
n Department of Neurosurgery, Geisinger, Danville, United States
o Research Institute of Neurointervention, Paracelsus Medical UniversitySalzburg, Austria
p Department of Emergency Medicine, Washington University School of Medicine, St Louis, MO, USA
q Department of Neurology, Washington University School of Medicine & Barnes-Jewish Hospital, St Louis, MO, USA
r Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
s Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden
t Department of Neurology, Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d’Investigacions Mèdiques), Universitat Autonoma de Barcelona, Barcelona, Spain
u KU Leuven – University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND), Leuven, Belgium
v VIB, Vesalius Research Center, Laboratory of Neurobiology, University Hospitals Leuven, Department of Neurology, Leuven, Belgium
w Department of Neurology, John Hunter Hospital, NSW, Newcastle, Australia
x Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, FL, Gainesville, United States
y Department of Neurology, Mayo Clinic, FL, Jacksonville, United States
z Centogene AG, Rostock, Germany
aa Department of Neurology, Clinical Division of Neurogeriatrics, Medical University Graz, Graz, Austria
ab Center for Genomic Medicine, Massachusetts General Hospital, MA, Boston, United States
ac Department of Neurology and Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, FL, Miami, United States
ad Institute of Cardiovascular Research, Royal Holloway University of London (ICR2UL), Egham, United Kingdom
ae St Peter’s and Ashford Hospitals, Egham, United Kingdom
af Department of Neurology, Jagiellonian University Medical College, Krakow, Poland
ag Department of clinical sciences Malmö, Lund University, Lund, Sweden
ah Department of Neurology, Skåne University Hospital, Sweden
ai Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
aj Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
ak Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden
al Stroke Division, Florey Institute of Neuroscience and Mental Health, Heidelberg, Australia
am Department of Neurology, Austin Health, Heidelberg, Australia
an Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
ao Department of Clinical Sciences Lund, Radiology, Lund University, Lund, Sweden
ap Department of Radiology, Neuroradiology, Skåne University Hospital, Lund, Sweden
aq Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA
ar Department of Neurology, Geisinger, Danville, United States
as Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, MD, Baltimore, United States
at Departments of Neurology and Public Health Sciences, University of Virginia, VA, Charlottesville, United States
au Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, Gothenburg, Sweden
av Department of Neurology, Skåne University Hospital, Lund, Sweden
aw Department of Clinical Sciences Lund, Neurology, Lund University, Lund, Sweden
ax University of Technology Sydney, NSW, Sydney, Australia
ay Department of Biomedical Engineering, McConnell Brain Imaging Centre, Montreal Neurological Institute, Faculty of Medicine, School of Computer Science, McGill University, QC, Montreal, Canada
az QC, Montreal, Canada
Abstract
Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
Document Type: Article
Publication Stage: Final
Source: Scopus
“Role of anesthetics and their adjuvants in neurovascular protection in secondary brain injury after aneurysmal subarachnoid hemorrhage” (2021) International Journal of Molecular Sciences
Role of anesthetics and their adjuvants in neurovascular protection in secondary brain injury after aneurysmal subarachnoid hemorrhage
(2021) International Journal of Molecular Sciences, 22 (12), art. no. 6550, .
Athiraman, U.a , Zipfel, G.J.b
a Department of Anesthesiology, Washington University, Saint Louis, MO 63110, United States
b Department of Neurological Surgery, Washington University, Saint Louis, MO 63110, United States
Abstract
Aneurysmal rupture accounts for the majority of subarachnoid hemorrhage and is responsible for most cerebrovascular deaths with high mortality and morbidity. Initial hemorrhage severity and secondary brain injury due to early brain injury and delayed cerebral ischemia are the major determinants of outcomes after aneurysmal subarachnoid hemorrhage. Several therapies have been explored to prevent these secondary brain injury processes after aneurysmal subarachnoid hemorrhage with limited clinical success. Experimental and clinical studies have shown a neuropro-tective role of certain anesthetics in cerebrovascular disorders including aneurysmal subarachnoid hemorrhage. The vast majority of aneurysmal subarachnoid hemorrhage patients require general anesthesia for surgical or endovascular repair of their aneurysm. Given the potential impact certain anesthetics have on secondary brain injury after SAH, appropriate selection of anesthetics may prove impactful on overall outcome of these patients. This narrative review focuses on the available evidence of anesthetics and their adjuvants in neurovascular protection in aneurysmal subarachnoid hemorrhage and discusses current impact on clinical care and future investigative directions. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Author Keywords
Anesthetic adjuvants; Anesthetics; Aneurysmal subarachnoid hemorrhage; Delayed cerebral ischemia; Early brain injury; Neurological outcomes; Neurovascular protection
Funding details
National Institutes of HealthNIHR01 NS091603
Document Type: Review
Publication Stage: Final
Source: Scopus
“Positive Psychosocial Factors and Oxytocin in the Ovarian Tumor Microenvironment” (2021) Psychosomatic Medicine
Positive Psychosocial Factors and Oxytocin in the Ovarian Tumor Microenvironment
(2021) Psychosomatic Medicine, 83 (5), pp. 417-422.
Cuneo, M.G.a , Szeto, A.b , Schrepf, A.a , Thaker, P.H.c , Goodheart, M.d e , Cole, S.W.d e f , Sood, A.K.g , McCabe, P.M.b , Mendez, A.J.h , Lutgendorf, S.K.a
a Department of Psychological and Brain Sciences, University of Iowa, G60 Psychological and Brain Sciences Building, Iowa City, IA 52242, United States
b Department of Psychology, University of Miami, Coral Gables, FL, United States
c Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, MO, United States
d Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, United States
e Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Iowa, Iowa City, IA, United States
f Department of Medicine, Division of Hematology/Oncology and Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, United States
g Departments of Gynecologic Oncology, Cancer Biology and Center for Rna Interference and Noncoding Rna, University of Texas Md Anderson Cancer Center, Houston, TX, United States
h Diabetes Research Institute, Division of Endocrinology Diabetes and Metabolism, Department of Medicine, Miller School of Medicine, University of Miami, Coral Gables, FL, United States
Abstract
Objective Clinical ovarian cancer research shows relationships between psychosocial factors and disease-promoting aspects of the stress response (e.g., norepinephrine and cortisol). However, little is known about how psychosocial factors might relate to beneficial hormones in the ovarian tumor microenvironment. Here we examine relationships between psychosocial factors and tumor-Associated oxytocin, a hormone linked to survival and antitumor processes in ovarian cancer. Methods Patients with ovarian cancer (n = 96) completed assessments of positive psychosocial factors (social support, positive affect, and purpose in life) and distress (perceived stress and depression) at the time of surgery. Levels of oxytocin and interleukin (IL) 6 in ascites fluid were obtained during surgery and analyzed by enzyme-linked immunosorbent assay. Multiple regression analyses adjusting a priori for patient age and disease stage examined associations between psychosocial factors and ascites oxytocin. IL-6 was used as a covariate in secondary analyses to examine the potentially confounding effects of inflammation in these relationships. Results Higher levels of positive affect (β = 0.22, p =.034), purpose in life (β = 0.31, p =.021), and social nurturance (β = 0.24, p =.024) were all related to higher levels of tumor-Associated oxytocin at the time of surgery. In contrast, we found no effects for distress or social attachment. Relationships between oxytocin, purpose in life, and social nurturance were independent of IL-6, whereas positive affect was no longer significant with IL-6 in the model. Conclusions Tumor-Associated oxytocin may be a previously uninvestigated link in the relationship between psychosocial factors and health in ovarian cancer. Future studies should examine causal mechanisms of relationships observed in this study. © Lippincott Williams and Wilkins.
Author Keywords
IL-6 = interleukin-6; ovarian cancer; oxytocin; positive affect; psychological well-being; social nurturance; tumor microenvironment
Funding details
National Institutes of HealthNIHAG017265, AG043404, CA109298, CA140933, CA193249, HL-116387, P30CA086862, R35 CA209904, T32GM108540
American Cancer SocietyACS
Document Type: Article
Publication Stage: Final
Source: Scopus
“Safety of Using a Combinatorial Pharmacogenomic Test for Patients with Major Depressive Disorder in the GUIDED trial” (2021) CNS Spectrums
Safety of Using a Combinatorial Pharmacogenomic Test for Patients with Major Depressive Disorder in the GUIDED trial
(2021) CNS Spectrums, 26 (2), pp. 169-170.
Parikh, S.V.a , Khazanov, G.K.b , Thase, M.E.b , Rothschild, A.J.c , Dunlop, B.W.d , DeBattista, C.e , Conway, C.R.f , Forester, B.P.g , Shelton, R.C.h , Macaluso, M.i , Li, J.j , Yu, K.j , Jablonski, M.R.j , Meek, S.k , Greden, J.F.a
a University of Michigan, Comprehensive Depression Center and Department of Psychiatry, National Network of Depression Centers, MI, Ann Arbor, United States
b University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States
c University of Massachusetts Medical School and UMass Memorial Healthcare, MA, Worcester, United States
d Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, United States
e Stanford University School of Medicine, Stanford, CA, USA
f Washington University School of Medicine, St. Louis, MO, USA
g McLean Hospital, MA, Belmont, United States
h The University of Alabama at Birmingham, Birmingham, AL, USA
i University of Kansas School of Medicine-Wichita, Wichita, United States
j Myriad Neuroscience, Mason, OH, USA
k Myriad Genetics, Inc., UT, Salt Lake City, United States
Abstract
BACKGROUND: Pharmacogenomic testing has emerged to aid medication selection for patients with major depressive disorder (MDD) by identifying potential gene-drug interactions (GDI). Many pharmacogenomic tests are available with varying levels of supporting evidence, including direct-to-consumer and physician-ordered tests. We retrospectively evaluated the safety of using a physician-ordered combinatorial pharmacogenomic test (GeneSight) to guide medication selection for patients with MDD in a large, randomized, controlled trial (GUIDED). MATERIALS AND METHODS: Patients diagnosed with MDD who had an inadequate response to ≥1 psychotropic medication were randomized to treatment as usual (TAU) or combinatorial pharmacogenomic test-guided care (guided-care). All received combinatorial pharmacogenomic testing and medications were categorized by predicted GDI (no, moderate, or significant GDI). Patients and raters were blinded to study arm, and physicians were blinded to test results for patients in TAU, through week 8. Measures included adverse events (AEs, present/absent), worsening suicidal ideation (increase of ≥1 on the corresponding HAM-D17 question), or symptom worsening (HAM-D17 increase of ≥1). These measures were evaluated based on medication changes [add only, drop only, switch (add and drop), any, and none] and study arm, as well as baseline medication GDI. RESULTS: Most patients had a medication change between baseline and week 8 (938/1,166; 80.5%), including 269 (23.1%) who added only, 80 (6.9%) who dropped only, and 589 (50.5%) who switched medications. In the full cohort, changing medications resulted in an increased relative risk (RR) of experiencing AEs at both week 4 and 8 [RR 2.00 (95% CI 1.41-2.83) and RR 2.25 (95% CI 1.39-3.65), respectively]. This was true regardless of arm, with no significant difference observed between guided-care and TAU, though the RRs for guided-care were lower than for TAU. Medication change was not associated with increased suicidal ideation or symptom worsening, regardless of study arm or type of medication change. Special attention was focused on patients who entered the study taking medications identified by pharmacogenomic testing as likely having significant GDI; those who were only taking medications subject to no or moderate GDI at week 8 were significantly less likely to experience AEs than those who were still taking at least one medication subject to significant GDI (RR 0.39, 95% CI 0.15-0.99, p=0.048). No other significant differences in risk were observed at week 8. CONCLUSION: These data indicate that patient safety in the combinatorial pharmacogenomic test-guided care arm was no worse than TAU in the GUIDED trial. Moreover, combinatorial pharmacogenomic-guided medication selection may reduce some safety concerns. Collectively, these data demonstrate that combinatorial pharmacogenomic testing can be adopted safely into clinical practice without risking symptom degradation among patients. FUNDING: Myriad Neuroscience/Assurex Health.
Document Type: Article
Publication Stage: Final
Source: Scopus
“CROI 2021: Neurologic Complications of HIV-1 Infection or COVID-19” (2021) Topics in Antiviral Medicine
CROI 2021: Neurologic Complications of HIV-1 Infection or COVID-19
(2021) Topics in Antiviral Medicine, 29 (2), pp. 334-343.
Ances, B.M.a , Anderson, A.M.b , Letendre, S.L.c
a Washington University, St Louis, MO, USA
b Emory University, Atlanta, United States
c University of California San Diego, San Diego, CA, USA
Abstract
The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and important findings about the neurologic complications of HIV-1, human polyomavirus 2 (also known as JC Virus), and cryptococcus. New long-term analyses of cognition in people with HIV-1 identified that cognitive decline over time is associated with multimorbidity, particularly diabetes, chronic lung disease, and vascular disease risk conditions. These conditions are associated with aging, and the question of whether people with HIV are at risk for premature aging was addressed by several reports. New findings from large analyses of resting state networks also provided valuable information on the structural and functional networks that are affected by HIV-1 infection and cognitive impairment. Several reports addressed changes after initiating or switching antiretroviral therapy (ART). Findings that will improve understanding of the biologic mechanisms of brain injury in people with HIV were also presented and included evidence that host (eg, myeloid activation, inflammation, and endothelial activation) and viral (eg, transcriptional activity and compartmentalization) factors adversely affect brain health. Other research focused on adjunctive therapies to treat HIV-1 and its complications in the central nervous system. This summary will review these and other findings in greater detail and identify key gaps and opportunities for researchers and clinicians.
Document Type: Article
Publication Stage: Final
Source: Scopus
“The effect of cannabis policies on treatment outcomes for cannabis use among U.S. adults” (2021) Journal of Substance Abuse Treatment
The effect of cannabis policies on treatment outcomes for cannabis use among U.S. adults
(2021) Journal of Substance Abuse Treatment, art. no. 108535, .
Bourdon, J.L.a , Francis, M.W.b c , Jia, L.d , Liang, C.c f , Robinson, H.I.b , Grucza, R.A.e
a Wellbridge Center for Addiction Treatment and Research
b Brown School of Social Work, Washington University in St. Louis, 1 Brookings Drive, St. Louis, MO 63130, United States
c Department of Psychiatry, Washington University in St. Louis, 4560 Clayton Avenue, Suite 1000, St. Louis, MO 63110, United States
d Washington University School of Medicine, 660 S Euclid Avenue, St. Louis, MO 63110, United States
e Department of Psychiatry, St. Louis University, 660 S Euclid Avenue, St. Louis, MO 63110, United States
f Yale University School of Medicine, 333 Cedar St, New Haven, CT 06510, United States
Abstract
Background: Research has explored the impact of various medical cannabis policies on substance use treatment admission in recent years, but we know little about factors related to participants’ treatment engagement and outcome. To fill this gap in the existing literature, this study used national data to examine the influence of cannabis policies (decriminalized, medical, and recreational) and referral sources (criminal justice vs. voluntary) on treatment completion and length of stay. Methods: Data came from the Treatment Episode Data Set-Discharge (2006–2017) on adults 18+ whose primary drug at treatment admission was cannabis. Difference-in-difference analyses using logistic regression examined the effect of cannabis policies on outpatient treatment completion (yes/no; n = 2,192,807) and length of stay (more/fewer than 90 days; n = 1,863,585) in those with a criminal justice or voluntary referral source. Results: Cannabis policy was not associated with treatment completion in either those with a criminal justice or voluntary referral source. Compared to individuals in states where cannabis use was strictly illegal, those in states with a decriminalization policy were less likely to stay in treatment for 91+ days regardless of the referral source. Conclusions: Cannabis policy appears to have a differential effect on treatment completion versus length of stay, with policy having no impact on successful treatment completion. Specifically, we found that decriminalization policies hinder treatment engagement past 90 days. In this sense, length of stay may be a more useful measure of treatment outcome for research than treatment completion moving forward. Furthermore, our study found that neither medical nor recreational policies affected length of stay or treatment completion, regardless of referral source. © 2021 Elsevier Inc.
Author Keywords
Cannabis; Marijuana; Policy; TEDS-D; Treatment
Funding details
National Institute on Drug AbuseNIDAT32DA01035
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“White matter integrity of contralesional and transcallosal tracts may predict response to upper limb task-specific training in chronic stroke” (2021) NeuroImage: Clinical
White matter integrity of contralesional and transcallosal tracts may predict response to upper limb task-specific training in chronic stroke
(2021) NeuroImage: Clinical, 31, art. no. 102710, .
Mattos, D.J.S.a , Rutlin, J.b , Hong, X.c , Zinn, K.f , Shimony, J.S.d , Carter, A.R.e
a Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, United States
b Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110, United States
c Department of Genetics, Washington University School of Medicine, Saint Louis, MO 63110, United States
d Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
e Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, United States
f Department of Radiology, Washington University School of Medicine, Saint Louis, MO 63110, United States
Abstract
Objective: To investigate white matter (WM) plasticity induced by intensive upper limb (UL) task specific training (TST) in chronic stroke. Methods: Diffusion tensor imaging data and UL function measured by the Action Research Arm Test (ARAT) were collected in 30 individuals with chronic stroke prior to and after intensive TST. ANOVAs tested the effects of training on the entire sample and on the Responders [ΔARAT ≥ 5.8, N = 13] and Non-Responders [ΔARAT < 5.8, N = 17] groups. Baseline fractional anisotropy (FA) values were correlated with ARATpost TST controlling for baseline ARAT and age to identify voxels predictive of response to TST. Results. While ARAT scores increased following training (p < 0.0001), FA changes within major WM tracts were not significant at p < 0.05. In the Responder group, larger baseline FA of both contralesional (CL) and transcallosal tracts predicted larger ARAT scores post-TST. Subcortical lesions and more severe damage to transcallosal tracts were more pronounced in the Non-Responder than in the Responder group. Conclusions: The motor improvements post-TST in the Responder group may reflect the engagement of interhemispheric processes not available to the Non-Responder group. Future studies should clarify differences in the role of CL and transcallosal pathways as biomarkers of recovery in response to training for individuals with cortical and subcortical stroke. This knowledge may help to identify sources of heterogeneity in stroke recovery, which is necessary for the development of customized rehabilitation interventions. © 2021
Author Keywords
Diffusion tensor imaging; Neuroimaging biomarker; Stroke rehabilitation; Task specific training; Transcallosal fibers; Upper limb
Funding details
National Institutes of HealthNIHU54 HD087011
University of WashingtonUW
Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD
Document Type: Article
Publication Stage: Final
Source: Scopus
“Collateral status reperfusion and outcomes after endovascular therapy: Insight from the Endovascular Treatment in Ischemic Stroke (ETIS) Registry” (2021) Journal of NeuroInterventional Surgery
Collateral status reperfusion and outcomes after endovascular therapy: Insight from the Endovascular Treatment in Ischemic Stroke (ETIS) Registry
(2021) Journal of NeuroInterventional Surgery, art. no. neurintsurg-2021-017553, .
Anadani, M.a b , Finitsis, S.c , Clarençon, F.d e , Richard, S.f , Marnat, G.g , Bourcier, R.h , Sibon, I.i , Dargazanli, C.j , Arquizan, C.k , Blanc, R.l , Lapergue, B.m , Consoli, A.n o , Eugene, F.p , Vannier, S.q , Spelle, L.r , Denier, C.s , Boulanger, M.t , Gauberti, M.u , Liebeskind, D.S.v , De Havenon, A.w , Saleme, S.x , MacIan, F.y , Rosso, C.z , Naggara, O.u , Turc, G.u , Ozkul-Wermester, O.aa , Papagiannaki, C.aa , Viguier, A.ab , Cognard, C.ac , Le Bras, A.ad ae , Evain, S.af , Wolff, V.ag , Pop, R.ah , Timsit, S.ai , Gentric, J.-C.aj , Bourdain, F.ak , Veunac, L.al , Maier, B.am , Gory, B.an
a Department of Neurology, Washington University School of Medicine in Saint Louis, Saint Louis, MO, United States
b Neurology, Neurosurgery, Medical University of South Carolina, College of Medicine, Charleston, SC, United States
c Neuroradiolology, University General Hospital of Thessaloniki Ahepa, Thessaloniki, Greece
d Neuroradiology, Pitié-Salpêtrière Hospital, Paris, France
e Neuroradiology, Sorbonne Université, Paris, Paris, France
f Neurology Stroke Unit, University Hospital Centre Nancy, Nancy, France
g Interventional and Diagnostic Neuroradiology, Bordeaux University Hospital, Bordeaux, France
h Neuroradiology, University Hospital of Nantes, Nantes, France
i Neuroradiology, Chu de Bordeaux, Bordeaux, France
j Neuroradiology, Centre Hospitalier Regional Universitaire de Montpellier, Languedoc-Roussillon, Montpellier, France
k Neurology, Chru Gui de Chauliac, Montpellier, France
l Interventional Neuroradiology, Fondation Rothschild, Paris, Île-de-France, France
m Neurology, Stroke Unit, Foch Hospital, Suresnes, France
n Diagnostic and Interventional Neuroradiology, Hospital Foch, Suresnes, France
o Interventional Neurovascular Unit, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy
p Radiologie, Chu Rennes, Rennes, France
q Department of Neurology, Chu Rennes, Rennes, Bretagne, France
r Department of Neuroradiolology, Chu Kremlin Bicêtre, Paris, France
s Neurology, Hopital Bicetre, Le Kremlin-Bicetre, France
t Department of Neurology, Chu Caen, Caen, France
u Neurology, Stroke Unit, Hôpital Saint Anne, Paris, France
v Neurology, University of California, Los Angeles, Los Angeles, CA, United States
w Department of Neurology, University of Utah, Salt Lake City, UT, United States
x Neuroradiology, Chu Dupuytren, Limoges, France
y Department of Neurology, Chu Limoges, Limoges, France
z Department of Neurology, Chu Pitié-Salpétrière, Paris, France
aa Department of Neurology, Chu Rouen, Rouen, Normandie, France
ab Department of Neurology, Chu Toulouse, Toulouse, France
ac Diagnostic and Therapeutic Neuroradiology, Hôpital Purpan, Toulouse, France
ad Department of Radiology, Ch Bretagne Atlantique, Vannes, France
ae Department of Neurology, Chu Rennes Service de Radiologie et d’Imagerie Médicale, Rennes, France
af Department of Neurology, Centre Hospitalier Bretagne Atlantique, Vannes, Bretagne, France
ag Stroke Unit, Strasbourg University Hospitals, Strasbourg, France
ah Department of Neuroradiolology, Chu Strasbourg, Strasbourg, France
ai Department of Neurology, Chu Brest, Brest, France
aj Interventional Neuroradiology, Chu Brest, Brest, Bretagne, France
ak Department of Neurology, Ch Côte Basque, Bayonne, France
al Department of Neuroradiolology, Ch Côte Basque, Bayonne, France
am Interventional Neuroradiology, Adolphe de Rothschild Ophthalmological Foundation, Paris, France
an Diagnostic and Interventional Neuroradiology, Centre Hospitalier Universitaire de Nancy, Nancy, France
Abstract
Background: Studies have suggested that collateral status modifies the effect of successful reperfusion on functional outcome after endovascular therapy (EVT). We aimed to assess the association between collateral status and EVT outcomes and to investigate whether collateral status modified the effect of successful reperfusion on EVT outcomes. Methods: We used data from the ongoing, prospective, multicenter Endovascular Treatment in Ischemic Stroke (ETIS) Registry. Collaterals were graded according to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) guidelines. Patients were divided into two groups based on angiographic collateral status: poor (grade 0-2) versus good (grade 3-4) collaterals. Results: Among 2020 patients included in the study, 959 (47%) had good collaterals. Good collaterals were associated with favorable outcome (90-day modified Rankin Scale (mRS) 0-2) (OR 1.5, 95% CI 1.19 to 1.88). Probability of good outcome decreased with increased time from onset to reperfusion in both good and poor collateral groups. Successful reperfusion was associated with higher odds of favorable outcome in good collaterals (OR 6.01, 95% CI 3.27 to 11.04) and poor collaterals (OR 5.65, 95% CI 3.32 to 9.63) with no significant interaction. Similarly, successful reperfusion was associated with higher odds of excellent outcome (90-day mRS 0-1) and lower odds of mortality in both groups with no significant interaction. The benefit of successful reperfusion decreased with time from onset in both groups, but the curve was steeper in the poor collateral group. Conclusions: Collateral status predicted functional outcome after EVT. However, collateral status on the pretreatment angiogram did not decrease the clinical benefit of successful reperfusion. © Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
Author Keywords
blood flow; stroke; thrombectomy
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Racial and Ethnic Disparities in Heart and Cerebrovascular Disease Deaths during the COVID-19 Pandemic in the United States” (2021) Circulation
Racial and Ethnic Disparities in Heart and Cerebrovascular Disease Deaths during the COVID-19 Pandemic in the United States
(2021) Circulation, pp. 2346-2354. Cited 1 time.
Wadhera, R.K.a , Figueroa, J.F.b , Rodriguez, F.c , Liu, M.a d , Tian, W.a , Kazi, D.S.a , Song, Y.a , Yeh, R.W.a , Joynt Maddox, K.E.e
a Richard A. and Susan F. Smith Center for Outcomes Research, Beth Israel Deaconess Medical Center, Boston, MA, United States
b Department of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, MA, United States
c Division of Cardiovascular Medicine, Stanford UniversityCA, United States
d Harvard Medical School, Boston, MA, United States
e Cardiovascular Division, Washington University School of Medicine, Saint Louis, MO, United States
Abstract
Background: Cardiovascular deaths increased during the early phase of the COVID-19 pandemic in the United States. However, it is unclear whether diverse racial/ethnic populations have experienced a disproportionate rise in heart disease and cerebrovascular disease deaths. Methods: We used the National Center for Health Statistics to identify heart disease and cerebrovascular disease deaths for non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic individuals from March to August 2020 (pandemic period), as well as for the corresponding months in 2019 (historical control). We determined the age- and sex-standardized deaths per million by race/ethnicity for each year. We then fit a modified Poisson model with robust SEs to compare change in deaths by race/ethnicity for each condition in 2020 versus 2019. Results: There were a total of 339 076 heart disease and 76 767 cerebrovascular disease deaths from March through August 2020, compared with 321 218 and 72 190 deaths during the same months in 2019. Heart disease deaths increased during the pandemic in 2020, compared with the corresponding period in 2019, for non-Hispanic White (age-sex standardized deaths per million, 1234.2 versus 1208.7; risk ratio for death [RR], 1.02 [95% CI, 1.02-1.03]), non-Hispanic Black (1783.7 versus 1503.8; RR, 1.19 [95% CI, 1.17-1.20]), non-Hispanic Asian (685.7 versus 577.4; RR, 1.19 [95% CI, 1.15-1.22]), and Hispanic (968.5 versus 820.4; RR, 1.18 [95% CI, 1.16-1.20]) populations. Cerebrovascular disease deaths also increased for non-Hispanic White (268.7 versus 258.2; RR, 1.04 [95% CI, 1.03-1.05]), non-Hispanic Black (430.7 versus 379.7; RR, 1.13 [95% CI, 1.10-1.17]), non-Hispanic Asian (236.5 versus 207.4; RR, 1.15 [95% CI, 1.09-1.21]), and Hispanic (264.4 versus 235.9; RR, 1.12 [95% CI, 1.08-1.16]) populations. For both heart disease and cerebrovascular disease deaths, Black, Asian, and Hispanic populations experienced a larger relative increase in deaths than the non-Hispanic White population (interaction term, P<0.001). Conclusions: During the COVID-19 pandemic in the United States, Black, Hispanic, and Asian populations experienced a disproportionate rise in deaths caused by heart disease and cerebrovascular disease, suggesting that these groups have been most impacted by the indirect effects of the pandemic. Public health and policy strategies are needed to mitigate the short- and long-term adverse effects of the pandemic on the cardiovascular health of diverse populations. © 2021 Georg Thieme Verlag. All rights reserved.
Author Keywords
cardiovascular disease; cerebrovascular disease; COVID-19; health disparities; mortality; pandemic; race/ethnicity
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“DIAPH1 Variants in Non–East Asian Patients with Sporadic Moyamoya Disease” (2021) JAMA Neurology
DIAPH1 Variants in Non–East Asian Patients with Sporadic Moyamoya Disease
(2021) JAMA Neurology, .
Kundishora, A.J.a , Peters, S.T.b , Pinard, A.a , Duran, D.b , Panchagnula, S.c , Barak, T.c d e f , Miyagishima, D.F.c d e f , Dong, W.d g , Smith, H.a , Ocken, J.a , Dunbar, A.c , Nelson-Williams, C.d , Haider, S.h , Walker, R.L.i , Li, B.j , Zhao, H.j , Thumkeo, D.k , Marlier, A.c , Duy, P.Q.a , Diab, N.S.c d , Reeves, B.C.a , Robert, S.M.c , Sujijantarat, N.c , Stratman, A.N.l , Chen, Y.-H.m , Zhao, S.m , Roszko, I.n , Lu, Q.o , Zhang, B.n , Mane, S.p , Castaldi, C.p , López-Giráldez, F.p , Knight, J.R.p , Bamshad, M.J.q , Nickerson, D.A.q , Geschwind, D.H.r , Chen, S.-S.L.s , Storm, P.B.s , Diluna, M.L.c , Matouk, C.C.c , Orbach, D.B.t , Alper, S.L.u , Smith, E.R.t , Lifton, R.P.d g , Gunel, M.c d , Milewicz, D.M.a , Jin, S.C.m , Kahle, K.T.c v w
a Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, United States
b Department of Neurosurgery, University of Mississippi Medical Center, Jackson, United States
c Department of Neurosurgery, Yale School of Medicine, New Haven, CT, United States
d Department of Genetics, Yale School of Medicine, New Haven, CT, United States
e Department of Neuroscience, Yale School of Medicine, New Haven, CT, United States
f Yale Program on Neurogenetics, Yale School of Medicine, New Haven, CT, United States
g Laboratory of Human Genetics and Genomics, The Rockefeller University, New York, NY, United States
h Department of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London, United Kingdom
i Department of Neurology, Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, United States
j Department of Biostatistics, Yale School of Public Health, New Haven, CT, United States
k Department of Drug Discovery Medicine, Kyoto University, Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan
l Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO, United States
m Department of Genetics, Washington University School of Medicine, St Louis, MO, United States
n Department of Developmental Biology, Center of Regenerative Medicine, Washington University School of Medicine, St Louis, MO, United States
o Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, United States
p Yale Center for Genome Analysis, West Haven, CT, United States
q Genome Sciences, University of Washington School of Medicine, Seattle, United States
r Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, United States
s Division of Neurosurgery, Children’s Hospital of Philadelphia, Department of Neurosurgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, United States
t Department of Neurosurgery, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States
u Division of Nephrology, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School, Boston, MA, United States
v Department of Pediatrics, Yale School of Medicine, New Haven, CT, United States
w Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, United States
Abstract
Importance: Moyamoya disease (MMD), a progressive vasculopathy leading to narrowing and ultimate occlusion of the intracranial internal carotid arteries, is a cause of childhood stroke. The cause of MMD is poorly understood, but genetic factors play a role. Several familial forms of MMD have been identified, but the cause of most cases remains elusive, especially among non-East Asian individuals. Objective: To assess whether ultrarare de novo and rare, damaging transmitted variants with large effect sizes are associated with MMD risk. Design, Setting, and Participants: A genetic association study was conducted using whole-exome sequencing case-parent MMD trios in a small discovery cohort collected over 3.5 years (2016-2019); data were analyzed in 2020. Medical records from US hospitals spanning a range of 1 month to 1.5 years were reviewed for phenotyping. Exomes from a larger validation cohort were analyzed to identify additional rare, large-effect variants in the top candidate gene. Participants included patients with MMD and, when available, their parents. All participants who met criteria and were presented with the option to join the study agreed to do so; none were excluded. Twenty-four probands (22 trios and 2 singletons) composed the discovery cohort, and 84 probands (29 trios and 55 singletons) composed the validation cohort. Main Outcomes and Measures: Gene variants were identified and filtered using stringent criteria. Enrichment and case-control tests assessed gene-level variant burden. In silico modeling estimated the probability of variant association with protein structure. Integrative genomics assessed expression patterns of MMD risk genes derived from single-cell RNA sequencing data of human and mouse brain tissue. Results: Of the 24 patients in the discovery cohort, 14 (58.3%) were men and 18 (75.0%) were of European ancestry. Three of 24 discovery cohort probands contained 2 do novo (1-tailed Poisson P = 1.1 × 10-6) and 1 rare, transmitted damaging variant (12.5% of cases) in DIAPH1 (mammalian diaphanous-1), a key regulator of actin remodeling in vascular cells and platelets. Four additional ultrarare damaging heterozygous DIAPH1 variants (3 unphased) were identified in 3 other patients in an 84-proband validation cohort (73.8% female, 77.4% European). All 6 patients were non-East Asian. Compound heterozygous variants were identified in ena/vasodilator-stimulated phosphoproteinlike protein EVL, a mammalian diaphanous-1 interactor that regulates actin polymerization. DIAPH1 and EVL mutant probands had severe, bilateral MMD associated with transfusion-dependent thrombocytopenia. DIAPH1 and other MMD risk genes are enriched in mural cells of midgestational human brain. The DIAPH1 coexpression network converges in vascular cell actin cytoskeleton regulatory pathways. Conclusions and Relevance: These findings provide the largest collection to date of non-East Asian individuals with sporadic MMD harboring pathogenic variants in the same gene. The results suggest that DIAPH1 is a novel MMD risk gene and impaired vascular cell actin remodeling in MMD pathogenesis, with diagnostic and therapeutic ramifications.. © 2021 American Medical Association. All rights reserved.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Evolving Techniques in Peripheral Nerve Regeneration” (2021) Journal of Hand Surgery
Evolving Techniques in Peripheral Nerve Regeneration
(2021) Journal of Hand Surgery, .
Lanier, S.T.a , Hill, J.R.a , Dy, C.J.a b , Brogan, D.M.a
a Department of Orthopaedic Surgery, Washington University in St. Louis
b Department of Surgery, Division of Public Health Sciences, Washington University in St. Louis, St. Louis, MO, United States
Abstract
Reliable and robust peripheral nerve regeneration after a nerve injury and repair remains an elusive goal. A variety of strategies have been proposed to mitigate the effects of Wallerian degeneration (through molecular therapies), enhance axonal regeneration across the repair site (through electrical stimulation and gene therapy), and explore alternatives to suture coaptation (through the fusion of transected ends). Although most of these techniques are in their infancy, animal data and some clinical trials have demonstrated promise for improving the restoration of function after these devastating injuries. © 2021 American Society for Surgery of the Hand
Author Keywords
Electrical stimulation; nerve regeneration; peripheral nerve; SARM-1
Document Type: Review
Publication Stage: Article in Press
Source: Scopus
“Callous-Unemotional Traits as an Intervention Target and Moderator of Parent–Child Interaction Therapy—Emotion Development Treatment for Preschool Depression and Conduct Problems” (2021) Journal of the American Academy of Child and Adolescent Psychiatry
Callous-Unemotional Traits as an Intervention Target and Moderator of Parent–Child Interaction Therapy—Emotion Development Treatment for Preschool Depression and Conduct Problems
(2021) Journal of the American Academy of Child and Adolescent Psychiatry, . Cited 1 time.
Donohue, M.R., Hoyniak, C.P., Tillman, R., Barch, D.M., Luby, J.
Washington University School of Medicine, St. Louis, MO, United States
Abstract
Objective: Callous-unemotional (CU) traits—characterized by low empathy, prosociality, and guilt—predict severe and persistent conduct problems. Although some interventions for conduct problems have been less effective in children with high levels of CU traits, studies have not examined whether CU traits interfere with treatment for other childhood disorders. Moreover, few treatments have demonstrated efficacy in decreasing CU traits themselves in early childhood. This study examined whether Parent–Child Interaction Therapy—Emotion Development (PCIT-ED), a novel PCIT adaptation that promotes emotional competence with demonstrated efficacy in treating preschool-onset major depressive disorder and oppositional defiant disorder, was also effective in treating these disorders in children displaying higher levels of CU traits. The study also examined whether PCIT-ED treatment produced significant and sustained decreases in CU traits. Method: This study examined 3- to 5-year-olds (N = 114) with preschool-onset major depressive disorder who completed the PCIT-ED trial. Children were randomly assigned to either immediate PCIT-ED treatment (n = 64) or a waitlist control condition (n = 50) in which they received the active treatment after 18 weeks. Psychiatric diagnoses and severity and CU traits in children were assessed at baseline, immediately after treatment, and 18 weeks after treatment completion. Results: Compared with the waitlist, PCIT-ED effectively reduced major depressive disorder and oppositional defiant disorder in preschoolers, regardless of initial levels of CU traits. Moreover, CU traits decreased from before to after treatment, and this treatment effect was sustained 18 weeks after treatment. Conclusion: Results support that novel interventions that enhance emotional development display significant promise in treating CU traits—behaviors that left untreated predict severe conduct problems, criminality, and substance use. Clinical trial registration information: A Randomized Controlled Trial of PCIT-ED for Preschool Depression; https://clinicaltrials.gov; NCT02076425. © 2021 American Academy of Child & Adolescent Psychiatry
Author Keywords
callous-unemotional behavior; conduct problems; intervention; limited prosocial emotions; preschool
Funding details
National Institutes of HealthNIHR01MH064769-06A1, T32MH100019
Document Type: Article
Publication Stage: Article in Press
Source: Scopus
“Chronic nerve injuries and delays in surgical treatment negatively impact patient-reported quality of life” (2021) Plastic and Reconstructive Surgery – Global Open
Chronic nerve injuries and delays in surgical treatment negatively impact patient-reported quality of life
(2021) Plastic and Reconstructive Surgery – Global Open, art. no. e3570, .
Felder, J.M.a , Ducic, I.b
a Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University in St. Louis, St. Louis, MO, United States
b Washington Nerve Institute, McLean, VA, United States
Abstract
Background: Little emphasis has been paid to characterize quality of life (QoL) burdens experienced by patients seeking surgical treatment for nerve injuries and neuropathic pain. Methods: A cross-sectional survey was distributed to all patients (N = 767) from a single nerve surgeon’s practice between 2014 and 2019. Data collected included demographics, specifics of the injury and symptoms, time to referral, and effects of the injury, surgery, and timing of surgery on QoL. Results: Of the 767 patients, 209 (27.2%) completed the survey. Average age was 48.8 years; 68.9% of patients were women and 31.1% men. At presentation, 68% had experienced symptoms for more than 1 year; 86.1% reported severity as being profound; 97.6% reported QoL was at least moderately negatively impacted by nerve injury; 70% felt they should have been referred earlier for surgical evaluation; 51.2% were not told that nerve surgery was an option for their problem; 83.1% felt that earlier referral would have improved their QoL. After surgery, symptoms were significantly mitigated in 55.5% of the patients, moderately mitigated in 21.5%. Patients reported QoL was significantly (59.8%) or at least moderately (76.6%) improved by nerve surgery. Conclusions: The majority of patients reported that nerve injuries imparted a moderate to severe impact on QoL, and that surgical treatment improved QoL. Most patients felt that earlier referral for surgical intervention would have led to better outcome and positively impacted QoL. Interdisciplinary treatment algorithms, including a role for surgical intervention, may be helpful in facilitating timely diagnosis, referral, and thus improved outcomes. Copyright © 2021 The Authors.
Document Type: Article
Publication Stage: Article in Press
Source: Scopus