Medicine and Health Sciences Commons^™

Epigenome-Wide Association Study Of Mitochondrial Genome Copy Number, Penglong Wang, Christina A Castellani, Jie Yao, Tianxiao Huan, Lawrence F Bielak, Wei Zhao, Jeffrey Haessler, Roby Joehanes, Xianbang Sun, Xiuqing Guo, Ryan J Longchamps, Joann E Manson, Megan L Grove, Jan Bressler, Kent D Taylor, Tuuli Lappalainen, Silva Kasela, David J Van Den Berg, Lifang Hou, Alexander Reiner, Yongmei Liu, Eric Boerwinkle, Jennifer A Smith, Patricia A Peyser, Myriam Fornage, Stephen S Rich, Jerome I Rotter, Charles Kooperberg, Dan E Arking, Daniel Levy, Chunyu Liu

Journal Articles

We conducted cohort- and race-specific epigenome-wide association analyses of mitochondrial deoxyribonucleic acid (mtDNA) copy number (mtDNA CN) measured in whole blood from participants of African and European origins in five cohorts (n = 6182, mean age = 57-67 years, 65% women). In the meta-analysis of all the participants, we discovered 21 mtDNA CN-associated DNA methylation sites (CpG) (P < 1 × 10-7), with a 0.7-3.0 standard deviation increase (3 CpGs) or decrease (18 CpGs) in mtDNA CN corresponding to a 1% increase in DNA methylation. Several significant CpGs have been reported to be associated with at least two risk factors (e.g. chronological age or smoking) for cardiovascular disease (CVD). Five genes [PR/SET domain 16, nuclear receptor subfamily 1 group H member 3 (NR1H3), DNA repair protein, DNA polymerase kappa and decaprenyl-diphosphate synthase subunit 2], which harbor nine significant CpGs, are known to be involved in mitochondrial biosynthesis and functions. For example, NR1H3 encodes a transcription factor that is differentially expressed during an adipose tissue transition. The methylation level of cg09548275 in NR1H3 was negatively associated with mtDNA CN (effect size = -1.71, P = 4 × 10-8) and was positively associated with the NR1H3 expression level (effect size = 0.43, P = 0.0003), which indicates that the methylation level in NR1H3 may underlie the relationship between mtDNA CN, the NR1H3 transcription factor and energy expenditure. In summary, the study results suggest that mtDNA CN variation in whole blood is associated with DNA methylation levels in genes that are involved in a wide range of mitochondrial activities. These findings will help reveal molecular mechanisms between mtDNA CN and CVD.

Phase 3 Safety And Efficacy Of Azd1222 (Chadox1 Ncov-19) Covid-19 Vaccine, Ann R Falsey, Magdalena E Sobieszczyk, Ian Hirsch, Stephanie Sproule, Merlin L Robb, Lawrence Corey, Kathleen M Neuzil, William Hahn, Julie Hunt, Mark J Mulligan, Charlene Mcevoy, Edwin Dejesus, Michael Hassman, Susan J Little, Barbara A Pahud, Anna Durbin, Paul Pickrell, Eric S Daar, Larry Bush, Joel Solis, Quito Osuna Carr, Temitope Oyedele, Susan Buchbinder, Jessica Cowden, Sergio L Vargas, Alfredo Guerreros Benavides, Robert Call, Michael C Keefer, Beth D Kirkpatrick, John Pullman, Tina Tong, Margaret Brewinski Isaacs, David Benkeser, Holly E Janes, Martha C Nason, Justin A Green, Elizabeth J Kelly, Jill Maaske, Nancy Mueller, Kathryn Shoemaker, Therese Takas, Richard P Marshall, Menelas N Pangalos, Tonya Villafana, Antonio Gonzalez-Lopez

Journal Articles

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known.

METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru.

RESULTS: …

A Case Of Unintentional Isopropanol Poisoning Via Transdermal Absorption Delayed By Weekly Hemodialysis, Andrew R. Chavez, Michael T. Sweeney, Peter Akpunonu

Emergency Medicine Faculty Publications

BACKGROUND Isopropanol toxicity is the most common reported toxic alcohol ingestion in the United States and is well known to emergency physicians. Most toxicities result from unintentional ingestion of rubbing alcohol; however, an under-recognized mechanism of unintentional toxicity is transdermal absorption. Additionally, hemodialysis effectively removes isopropanol and its metabolites from circulation, so that in patients receiving regular hemodialysis, the manifestation of toxicity can be delayed.

CASE REPORT A 67-year-old woman with end-stage renal disease secondary to insulin-dependent type II diabetes on once-weekly hemodialysis presented to the Emergency Department via the Emergency Medical Service with acute encephalopathy, severe hypoglycemia, and hypothermia. …

Meta-Analyses Identify Dna Methylation Associated With Kidney Function And Damage, Pascal Schlosser, Adrienne Tin, Pamela R Matias-Garcia, Chris H L Thio, Roby Joehanes, Hongbo Liu, Antoine Weihs, Zhi Yu, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Monique M B Breteler, Cristian Carmeli, Layal Chaker, John C Chambers, Shelley A Cole, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R Cox, Niek De Klein, Graciela E Delgado, Arce Domingo-Relloso, Kai-Uwe Eckardt, Arif B Ekici, Karlhans Endlich, Kathryn L Evans, James S Floyd, Myriam Fornage, Lude Franke, Eliza Fraszczyk, Xu Gao, Xīn Gào, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L Grove, Sarah E Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A Hurme, Shih-Jen Hwang, Marjo-Riitta Jarvelin, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, Jaspal S Kooner, Holly Kramer, Florian Kronenberg, Brigitte Kühnel, Terho Lehtimäki, Lars Lind, Dan Liu, Yongmei Liu, Donald M Lloyd-Jones, Kurt Lohman, Stefan Lorkowski, Ake T Lu, Riccardo E Marioni, Winfried März, Daniel L Mccartney, Karlijn A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Ana Navas-Acien, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M Psaty, Olli T Raitakari, Scott M Ratliff, Alex P Reiner, Sylvia E Rosas, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A Smith, Nona Sotoodehnia, Hannah R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Maria Tellez-Plaza, Joyce B J Van Meurs, Jana V Van Vliet-Ostaptchouk, Andrea Venema, Niek Verweij, Rosie M Walker, Matthias Wielscher, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Daniel Levy, Melanie Waldenberger, Katalin Susztak, Anna Köttgen, Alexander Teumer

Journal Articles

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. to extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. …

Utility Of Blood Cellular Indices In The Risk Stratification Of Patients Presenting With Acute Pulmonary Embolism., Brett Slajus, Yevgeniy Brailovsky, Iman Darwish, Jawed Fareed, Amir Darki

Division of Cardiology Faculty Papers

Pulmonary embolism (PE) clinical manifestations vary widely, and that scope is not fully captured by current all-cause mortality risk models. PE is associated with inflammatory, coagulation, and hemostatic imbalances so blood cellular indices may be prognostically useful. Complete blood count (CBC) data may improve current risk models like the simplified pulmonary embolism severity index (sPESI) for all-cause mortality, offering greater accuracy and analytic ability. Acute PE patients (n = 228) with confirmatory diagnostic imaging were followed for all-cause mortality. Blood cellular indices were assessed for association to all-cause mortality and were supplemented into sPESI using multivariate logistic regression. Multiple blood …

Sex Modifies Apoe Ε4 Dose Effect On Brain Tau Deposition In Cognitively Impaired Individuals, Shaozhen Yan, Chaojie Zheng, Manish D Paranjpe, Yanxiao Li, Weihua Li, Xiuying Wang, Tammie L S Benzinger, Jie Lu, Yun Zhou

2020-Current year OA Pubs

Recent studies in cognitively unimpaired elderly individuals suggest that the APOE ε4 allele exerts a dosage-dependent effect on brain tau deposition. The aim of this study was to investigate sex differences in APOE ε4 gene dosage effects on brain tau deposition in cognitively impaired individuals using quantitative 18F-flortaucipir PET. Preprocessed 18F-flortaucipir tau PET images, T1-weighted structural MRI, demographic information, global cortical amyloid-β burden measured by 18F-florbetapir PET, CSF total tau and phosphorylated tau measurements were obtained from the Alzheimer's Disease Neuroimaging Initiative database. Two hundred and sixty-eight cognitively impaired individuals with 146 APOE ε4 non-carriers and 122 carriers (85 heterozygotes …

Spinal Anesthesia Or General Anesthesia For Hip Surgery In Older Adults, Mark D. Neuman, Rui Feng, Jeffrey L. Carson, Lakisha J. Gaskins, Derek Dillane, Daniel I. Sessler, Frederick Sieber, Jay Magaziner, Edward R. Marcantonio, Samir Mehta, Diane Menio, Sabry Ayad, Trevor Stone, Steven Papp, Eric S. Schwenk, Nabil Elkassabany, Mitchell Marshall, J. Douglas Jaffe, Charles Luke, Balram Sharma, Syed Azim, Robert A. Hymes, Ki-Jinn Chin, Richard Sheppard, Barry Perlman, Joshua Sappenfield, Ellen Hauck, Mark A. Hoeft, Mark Giska, Yatish Ranganath, Tiffany Tedore, Stephen Choi, Jinlei Li, M. Kwesi Kwofie, Antoun Nader, Robert D. Sanders, Brian F. S. Allen, Kamen Vlassakov, Stephen Kates, Lee A. Fleisher, James Dattilo, Ann Tierney, Alisa J. Stephens-Shields, Susan S. Ellenberg

Department of Anesthesiology Faculty Papers

Background: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied.

Methods: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 …

Efficacy And Safety Of Fremanezumab In Clinical Trial Participants Aged ≥60 Years With Episodic Or Chronic Migraine: Pooled Results From 3 Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies, Stephanie J. Nahas, Steffen Naegel, Joshua M Cohen, Xiaoping Ning, Lindsay Janka, Verena Ramirez Campos, Lynda J Krasenbaum, Dagny Holle-Lee, David Kudrow, Christian Lampl

Department of Neurology Faculty Papers

Background: Although migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM).

Methods: This analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and …

Physical Activity And Fat-Free Mass During Growth And In Later Life, Klaas R Westerterp, Susan B Racette, Et Al.

2020-Current year OA Pubs

BACKGROUND: Physical activity may be a way to increase and maintain fat-free mass (FFM) in later life, similar to the prevention of fractures by increasing peak bone mass.

OBJECTIVES: A study is presented of the association between FFM and physical activity in relation to age.

METHODS: In a cross-sectional study, FFM was analyzed in relation to physical activity in a large participant group as compiled in the International Atomic Energy Agency Doubly Labeled Water database. The database included 2000 participants, age 3-96 y, with measurements of total energy expenditure (TEE) and resting energy expenditure (REE) to allow calculation of physical …

Influential Periods In Longitudinal Clinical Cardiovascular Health Scores, Amy E Krefman, Vito M R Muggeo, Et Al.

2020-Current year OA Pubs

The prevalence of ideal cardiovascular health (CVH) among adults in the United States is low and decreases with age. Our objective was to identify specific age windows when the loss of CVH accelerates, to ascertain preventive opportunities for intervention. Data were pooled from 5 longitudinal cohorts (Project Heartbeat!, Cardiovascular Risk in Young Finns Study, The Bogalusa Heart Study, Coronary Artery Risk Development in Young Adults, Special Turku Coronary Risk Factor Intervention Project) from the United States and Finland from 1973 to 2012. Individuals with clinical CVH factors (i.e., body mass index, blood pressure, cholesterol, blood glucose) measured from ages 8 …

Emergency Department Administration Of Covid-19 Antibody Therapies: Early Experience., Christopher Payette, Joseph T. Brooks, Robert Shesser

Emergency Medicine Faculty Publications

No abstract provided.

Phase I Study Of Single Agent Niz985, A Recombinant Heterodimeric Il-15 Agonist, In Adult Patients With Metastatic Or Unresectable Solid Tumors, Kevin Conlon, Andrea Wang-Gillam, Et Al

2020-Current year OA Pubs

BACKGROUND: NIZ985 is a recombinant heterodimer of physiologically active interleukin (IL-)15 and IL-15 receptor alpha. In preclinical models, NIZ985 promotes cytotoxic lymphocyte proliferation, killing function, and organ/tumor infiltration, with resultant anticancer effects. In this first-in-human study, we assessed the safety, pharmacokinetics, and immune effects of NIZ985 in patients with metastatic or unresectable solid tumors.

METHODS: Single agent NIZ985 dose escalation data are reported from a phase I dose escalation/expansion study of NIZ985 as monotherapy. Adult patients (N=14) received 0.25, 0.5, 1, 2 or 4 µg/kg subcutaneous NIZ985 three times weekly (TIW) for the first 2 weeks of each 28-day cycle, …

Risk Factors For Progression Or Death After First-Line Platinum-Based Chemotherapy In Real-World Patients In The Usa With Ovarian Cancer From 2011 To 2018, Shannon N Westin, Melinda Louie-Gao, Divya Gupta, Premal H Thaker

2020-Current year OA Pubs

No abstract provided.

Modulation In Cortical Excitability Disrupts Information Transfer In Perceptual-Level Stimulus Processing, Ladan Moheimanian, Sivylla E Paraskevopoulou, Markus Adamek, Gerwin Schalk, Peter Brunner

2020-Current year OA Pubs

Despite significant interest in the neural underpinnings of behavioral variability, little light has been shed on the cortical mechanism underlying the failure to respond to perceptual-level stimuli. We hypothesized that cortical activity resulting from perceptual-level stimuli is sensitive to the moment-to-moment fluctuations in cortical excitability, and thus may not suffice to produce a behavioral response. We tested this hypothesis using electrocorticographic recordings to follow the propagation of cortical activity in six human subjects that responded to perceptual-level auditory stimuli. Here we show that for presentations that did not result in a behavioral response, the likelihood of cortical activity decreased from …

Clinical Outcomes Of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia In A County Hospital System, Effrosyni Apostolidou, Curtis Lachowiez, Harinder S Juneja, Wei Qiao, Onyebuchi Ononogbu, Courtney Nicole Miller-Chism, Mark Udden, Hilary Ma, Martha Pritchett Mims

Journal Articles

BACKGROUND: Major advances in the treatment of acute lymphoblastic leukemia (ALL) over the past decade have resulted in 5-year overall survival (OS) rates of 80% in mature B cell ALL, 50% in precursor B cell ALL, 50% to 60% in T cell ALL, and 60% to 70% in Philadelphia chromosome-positive (Ph+) ALL, as reported in studies from large, specialized centers. However, many patients treated in the community have limited access to novel therapies and stem cell transplantation (HSCT).

PATIENTS AND METHODS: The purpose of this retrospective cohort analysis was to evaluate the clinical outcomes of patients ≥ 16 years with …

Phase 1b Study Of Avb-500 In Combination With Paclitaxel Or Pegylated Liposomal Doxorubicin Platinum-Resistant Recurrent Ovarian Cancer, Katherine C Fuh, Michael A Bookman, Joyce F Liu, Robert L Coleman, Thomas J Herzog, Premal H Thaker, Bradley J Monk, Randy Anderson, Gail Mcintyre, Reshma Rangwala, Kathleen N Moore

2020-Current year OA Pubs

OBJECTIVE: GAS6 and AXL are expressed in high-grade serous ovarian cancer but not in normal ovarian tissue. AVB-500, a novel high affinity Fc-sAXL fusion protein, binds GAS6 preventing AXL signaling. This Phase 1b study (NCT03639246) evaluated safety, efficacy, and exploratory predictive markers of AVB-500 combined with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (PROC), and used a model informed drug development (MIDD) approach for identification of the recommended phase 2 dose (RP2D).

METHODS: Eligible patients received AVB-500 at 10, 15, or 20 mg/kg IV q2wk combined with PAC (n = 23) or PLD (n …

Understanding The Groups Of Care Transition Strategies Used By U.S. Hospitals: An Application Of Factor Analytic And Latent Class Methods, Glen Mays, Jing Li, Jessica Miller Clouser, Gaixin Du, Arnold Stromberg, Brian Jack, Huong Q Nguyen, Mark V Williams

2020-Current year OA Pubs

BACKGROUND: After activation of the Hospital Readmission Reduction Program (HRRP) in 2012, hospitals nationwide experimented broadly with the implementation of Transitional Care (TC) strategies to reduce hospital readmissions. Although numerous evidence-based TC models exist, they are often adapted to local contexts, rendering large-scale evaluation difficult. Little systematic evidence exists about prevailing implementation patterns of TC strategies among hospitals, nor which strategies in which combinations are most effective at improving patient outcomes. We aimed to identify and define combinations of TC strategies, or groups of transitional care activities, implemented among a large and diverse cohort of U.S. hospitals, with the ultimate …

Effects Of The Tailored Activity Program (Tap) On Dementia-Related Symptoms, Health Events And Caregiver Wellbeing: A Randomized Controlled Trial, Laura N Gitlin, Katherine Marx, Catherine V. Piersol, Nancy A Hodgson, Jin Huang, David L Roth, Constantine Lyketsos

Department of Occupational Therapy Faculty Papers

BACKGROUND: People living with dementia (PLWD) and caregivers are adversely impacted by lack of meaningful activity leading to worse symptoms and impaired quality-of-life. There is a critical need to develop effective and well-tolerated treatments that mitigate clinical symptoms, engage PLWD and support caregiver wellbeing. We tested whether, compared to attention control, the Tailored Activity Program (TAP) reduced clinical symptoms and health-related events, and improved caregiver wellbeing, and if TAP activities were well-tolerated.

METHODS: We conducted a single-blind randomized controlled trial among 250 dyads recruited from Baltimore-Washington DC (2012-2016) with a dementia diagnosis and clinically significant agitation/aggression. Dyads were randomized to …

Trem2 Modulates Differential Deposition Of Modified And Non-Modified Aβ Species In Extracellular Plaques And Intraneuronal Deposits, Pranav Joshi, Florian Riffel, Sathish Kumar, Nàdia Villacampa, Sandra Theil, Samira Parhizkar, Christian Haass, Marco Colonna, Michael T Heneka, Thomas Arzberger, Jochen Herms, Jochen Walter

2020-Current year OA Pubs

Progressive accumulation of Amyloid-β (Aβ) deposits in the brain is a characteristic neuropathological hallmark of Alzheimer's disease (AD). During disease progression, extracellular Aβ plaques undergo specific changes in their composition by the sequential deposition of different modified Aβ species. Microglia are implicated in the restriction of amyloid deposits and play a major role in internalization and degradation of Aβ. Recent studies showed that rare variants of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) are associated with an increased risk for AD. Post-translational modifications of Aβ could modulate the interaction with TREM2, and the uptake by microglia. Here, we …

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …

Ovarian Cancer Epidemiology, Healthcare Access And Disparities (Orchid): Methodology For A Population-Based Study Of Black, Hispanic And White Patients With Ovarian Cancer, Tomi Akinyemiju, April Deveaux, Lauren Wilson, Anjali Gupta, Ashwini Joshi, Malcolm Bevel, Chioma Omeogu, Onyinye Ohamadike, Bin Huang, Maria Pisu, Margaret Liang, Molly Mcfatrich, Erin Daniell, Laura Jane Fish, Kevin Ward, Maria Schymura, Andrew Berchuck, Arnold L. Potosky

Biostatistics Faculty Publications

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to …

Co-Contraction Of Ankle Muscle Activity During Quiet Standing In Individuals With Incomplete Spinal Cord Injury Is Associated With Postural Instability, Kai Lon Fok, Jae W Lee, Janelle Unger, Katherine Chan, Kristin E Musselman, Kei Masani

Physical Therapy Publications

Previous findings indicate that co-contractions of plantarflexors and dorsiflexors during quiet standing increase the ankle mechanical joint stiffness, resulting in increased postural sway. Balance impairments in individuals with incomplete spinal cord injury (iSCI) may be due to co-contractions like in other individuals with reduced balance ability. Here we investigated the effect of co-contraction between plantar- and dorsiflexors on postural balance in individuals with iSCI (iSCI-group) and able-bodied individuals (AB-group). Thirteen able-bodied individuals and 13 individuals with iSCI were asked to perform quiet standing with their eyes open (EO) and eyes closed (EC). Kinetics and electromyograms from the tibialis anterior (TA), …

Functional Reach Test, Single-Leg Stance Test, And Tinetti Performance-Oriented Mobility Assessment For The Prediction Of Falls In Older Adults: A Systematic Review, Humberto Omaña, Kari Bezaire, Kyla Brady, Jayme Davies, Nancy Louwagie, Sean Power, Sydney Santin, Susan W. Hunter

Physical Therapy Publications

OBJECTIVE: The authors sought to systematically review the existing literature on the falls-related diagnostic test properties of the Functional Reach Test (FRT), single-leg stance test (SLST), and Tinetti Performance-Oriented Mobility Assessment (POMA) in older adults across settings and patient populations.

METHODS: The PubMed, EMBASE, and CINAHL databases were searched (inception-July 2020). Inclusion criteria were participants aged 60 years or more, prospectively recorded falls, and the reporting of falls-related predictive validity. Manuscripts not published in English were excluded. Methodological quality of reporting was assessed using the Tooth Scale.

RESULTS: Of 1071 studies reviewed, 21 met the inclusion criteria (12 POMA, 8 …

Real-World Assessment Of Asthma Specialist Visits Among U.S. Patients With Severe Asthma., Jessica F Most, Christopher S Ambrose, Yen Chung, James L Kreindler, Aimee Near, Stephen Brunton, Yao Cao, Huan Huang, Xiaohui Zhao

Division of Pulmonary and Critical Care Medicine Faculty Papers

BACKGROUND: U.S. guidelines recommend that patients with severe asthma be referred to specialists (allergists/immunologists or pulmonologists) for systematic assessment or comanagement; however, contemporary, real-world data on the frequency and impact of specialist care among U.S. severe asthma patients are lacking.

OBJECTIVES: To quantify the frequency of asthma specialist visits among U.S. patients with severe asthma, identify patient demographic and clinical characteristics associated with specialist visits and describe health outcomes following specialist care.

METHODS: Severe asthma patients aged 6 years or older were identified between January 1, 2015, and December 31, 2017, in the IQVIA PharMetrics® Plus database of commercially insured …

Multicenter, Double-Blind, Placebo-Controlled Trial Of Seviprotimut-L Polyvalent Melanoma Vaccine In Patients With Post-Resection Melanoma At High Risk Of Recurrence, Craig L Slingluff, Leonel Hernandez-Aya, Et Al

2020-Current year OA Pubs

BACKGROUND: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here.

METHODS: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For …

White Matter Plasticity In Healthy Older Adults: The Effects Of Aerobic Exercise, Andrea Mendez Colmenares, Michelle W Voss, Jason Fanning, Elizabeth A Salerno, Neha P Gothe, Michael L Thomas, Edward Mcauley, Arthur F Kramer, Agnieszka Z Burzynska

2020-Current year OA Pubs

White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60-79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions …

Ct Findings And Patterns Of E-Cigarette Or Vaping Product Use-Associated Lung Injury: A Multicenter Cohort Of 160 Cases, Seth J Kligerman, Constantine A Raptis, Kaitlin M Marquis, Et Al.

2020-Current year OA Pubs

BACKGROUND: e-Cigarette or vaping-induced lung injury (EVALI) causes a spectrum of CT lung injury patterns. Relative frequencies and associations with vaping behavior are unknown.

RESEARCH QUESTION: What are the frequencies of imaging findings and CT patterns in EVALI and what is the relationship to vaping behavior?

STUDY DESIGN AND METHODS: CT scans of 160 subjects with EVALI from 15 institutions were retrospectively reviewed. CT findings and patterns were defined and agreed on via consensus. The parenchymal organizing pneumonia (OP) pattern was defined as regional or diffuse ground-glass opacity (GGO) ± consolidation without centrilobular nodules (CNs). An airway-centered OP pattern was …

Management And Outcomes Of Cardiogenic Shock In Cardiac Icus With Versus Without Shock Teams., Alexander I Papolos, Benjamin B Kenigsberg, David D Berg, Carlos L Alviar, Erin Bohula, James A Burke Md, Anthony P Carnicelli, Sunit-Preet Chaudhry, Stavros Drakos, Daniel A Gerber, Jianping Guo, James M Horowitz, Jason N Katz, Ellen C Keeley, Thomas S Metkus, Jose Nativi-Nicolau, Jeffrey R Snell, Shashank S Sinha, Wayne J Tymchak, Sean Van Diepen, David A Morrow, Christopher F Barnett

Cardiology Division

BACKGROUND: Single-center studies suggest that implementation of multidisciplinary cardiogenic shock (CS) teams is associated with improved CS survival.

OBJECTIVES: The aim was to characterize practice patterns and outcomes in the management of CS across multiple centers with versus without shock teams.

METHODS: The Critical Care Cardiology Trials Network is a multicenter network of cardiac intensive care units (CICUs) in North America. All consecutive medical admissions to each CICU (n = 24) were captured during annual 2-month collection periods (2017-2019; n = 6,872). Shock management and CICU mortality among centers with versus without shock teams were compared using inverse probability weighting. …

Outpatient Prescription Practices In Patients With Atrial Fibrillation (From The Ncdr Pinnacle Registry), Jonathan C Hsu, Matthew R Reynolds, Yang Song, Gheorghe Doros, Steven A Lubitz, Anil K Gehi, Mintu P Turakhia, Thomas M Maddox

2020-Current year OA Pubs

This study sought to evaluate inappropriate prescribing practices in an atrial fibrillation (AF) population, as outlined by the 2016 ACC/AHA Clinical Performance and Quality Measures for Adults with Atrial Fibrillation or Atrial Flutter document. The 2016 AF quality measures document specified medications to avoid in certain AF populations, including aspirin and anticoagulant combination therapy in patients without cardiovascular disease, and non-dihydropyridine calcium channel blockers in patients with reduced ejection fraction. Using data from the NCDR PINNACLE registry, a national outpatient cardiology practice registry, we assessed rates of inappropriate prescription of two types of medications among AF outpatients from 5/1/2008-5/1/2016. Overall …

Is Comprehensiveness Critical? Comparing Short And Long Format Cognitive Assessments In Preclinical Alzheimer Disease, Jason Hassenstab, Jessica Nicosia, Megan Larose, Andrew J Aschenbrenner, Brian A Gordon, Tammie L S Benzinger, Chengjie Xiong, John C Morris

2020-Current year OA Pubs

BACKGROUND: Comprehensive testing of cognitive functioning is standard practice in studies of Alzheimer disease (AD). Short-form tests like the Montreal Cognitive Assessment (MoCA) use a "sampling" of measures, administering key items in a shortened format to efficiently assess cognition while reducing time requirements, participant burden, and administrative costs. We compared the MoCA to a commonly used long-form cognitive battery in predicting AD symptom onset and sensitivity to AD neuroimaging biomarkers.

METHODS: Survival, area under the receiver operating characteristic (ROC) curve (AUC), and multiple regression analyses compared the MoCA and long-form measures in predicting time to symptom onset in cognitively normal …