Medicine and Health Sciences Commons^™

Sickle Cell Disease Treatment With Arginine Therapy (Start): Study Protocol For A Phase 3 Randomized Controlled Trial., Chris A Rees, David C. Brousseau, Daniel M Cohen, Anthony Villella, Carlton Dampier, Kathleen Brown, Andrew Campbell, Corrie E Chumpitazi, Gladstone Airewele, Todd Chang, Christopher Denton, Angela Ellison, Alexis Thompson, Fahd Ahmad, Nitya Bakshi, Keli D Coleman, Sara Leibovich, Deborah Leake, Dunia Hatabah, Hagar Wilkinson, Michelle Robinson, T Charles Casper, Elliott Vichinsky, Claudia R Morris

Department of Pediatrics Faculty Papers

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults.

METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 …

Risk Of New Bloodstream Infections And Mortality Among People Who Inject Drugs With Infective Endocarditis., Charlie Tan, Esfandiar Shojaei, Joshua C. Wiener, Meera Shah, Sharon Koivu, Michael Silverman

Epidemiology and Biostatistics Publications

IMPORTANCE: People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU).

OBJECTIVES: To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or …

Age At Migration And The Risk Of Psychotic Disorders: A Systematic Review And Meta-Analysis., Kelly K. Anderson, Jordan Edwards

Epidemiology and Biostatistics Publications

OBJECTIVE: To conduct a systematic review and meta-analysis of the existing evidence on the association between age at migration and the risk of psychotic disorders.

METHODS: Observational studies were eligible for inclusion if they presented data on the association between age at migration and the risk of psychotic disorders among first-generation migrant groups. We used two random effects meta-analyses to pool effect estimates for each stratum of age at migration relative to (i) a native-born reference category and (ii) the youngest age stratum (0 to 2 years).

RESULTS: Ten studies met inclusion criteria, and five were included in the meta-analysis. …

Healthcare Utilization Costs Of Emerging Adults With Mood And Anxiety Disorders In An Early Intervention Treatment Program Compared To A Matched Cohort, Ava A. John-Baptiste, Lihua Li, Wanrudee Isaranuwatchai, Elizabeth Osuch, Kelly K. Anderson

Epidemiology and Biostatistics Publications

AIM: The First Episode Mood and Anxiety Disorder Program (FEMAP) provides treatment to emerging adults with mood and anxiety disorders in an accessible, youth-friendly environment. We sought to investigate FEMAP's impact on the costs of care.

METHODS: We conducted a retrospective observational study of one-year health service costs using linked administrative datasets to compare emerging adults treated at FEMAP (FEMAP users) to propensity-score matched controls (non-users). Costs from the perspective of the Ontario Ministry of Health and Long-Term Care, included drug benefit claims, inpatient, physician and ambulatory care services. We used bootstrapping to perform unadjusted comparisons between FEMAP users and …

Involuntary Hospitalization Among Young People With Early Psychosis: A Population-Based Study Using Health Administrative Data., Rebecca Rodrigues, Arlene G Macdougall, Guangyong Zou, Michael Lebenbaum, Paul Kurdyak, Lihua Li, Salimah Z Shariff, Kelly K Anderson

Epidemiology and Biostatistics Publications

OBJECTIVE: Early psychosis is an important window for establishing long-term trajectories. Involuntary hospitalization during this period may impact subsequent service engagement in people with newly diagnosed psychotic disorder. However, population-based studies of involuntary hospitalization in early psychosis are lacking. We sought to estimate the proportion of people aged 16 to 35 years with early psychosis in Ontario who are hospitalized involuntarily at first admission, and to identify the associated risk factors and outcomes.

METHODS: Using linked population-based health administrative data, we identified incident cases of non-affective psychosis over a five-year period (2009-2013) and followed cases for two years to ascertain …

Serum Nutrient Levels And Aging Effects On Periodontitis, Jeffrey L Ebersole, Joshua Lambert, Heather Bush, Pinar Emecen Huja, Arpita Basu

Biostatistics Faculty Publications

Periodontal disease damages tissues as a result of dysregulated host responses against the chronic bacterial biofilm insult and approximately 50% of US adults > 30 years old exhibit periodontitis. The association of five blood nutrients and periodontitis were evaluated due to our previous findings regarding a potential protective effect for these nutrients in periodontal disease derived from the US population sampled as part of the National Health and Nutrition Examination Survey (1999–2004). Data from over 15,000 subjects was analyzed for blood levels of cis-β-carotene, β-cryptoxanthin, folate, vitamin D, and vitamin E, linked with analysis of the presence and severity of periodontitis. …

Safety, Tolerability, And Pharmacokinetics Of Long-Acting Injectable Cabotegravir In Low-Risk Hiv-Uninfected Individuals: Hptn 077, A Phase 2a Randomized Controlled Trial., Raphael J Landovitz, Sue Li, Beatriz Grinsztejn, Halima Dawood, Albert Y Liu, Manya Magnus, Mina C Hosseinipour, Ravindre Panchia, Leslie Cottle, Gordon Chau, Paul Richardson, Mark A Marzinke, Craig W Hendrix, Susan H Eshleman, Yinfeng Zhang, Elizabeth Tolley, Jeremy Sugarman, Ryan Kofron, Adeola Adeyeye, David Burns, Alex R Rinehart, David Margolis, William R Spreen, Myron S Cohen, Marybeth Mccauley, Joseph J Eron

Epidemiology Faculty Publications

BACKGROUND: Cabotegravir (CAB) is a novel strand-transfer integrase inhibitor being developed for HIV treatment and prevention. CAB is formulated both as an immediate-release oral tablet for daily administration and as a long-acting injectable suspension (long-acting CAB [CAB LA]) for intramuscular (IM) administration, which delivers prolonged plasma exposure to the drug after IM injection. HIV Prevention Trials Network study 077 (HPTN 077) evaluated the safety, tolerability, and pharmacokinetics of CAB LA in HIV-uninfected males and females at 8 sites in Brazil, Malawi, South Africa, and the United States.

METHODS AND FINDINGS: HPTN 077 was a double-blind, placebo-controlled phase 2a trial. Healthy …

Increased Birth Weight Is Associated With Altered Gene Expression In Neonatal Foreskin, Leryn J. Reynolds, Rebecca I. Pollack, Richard J. Charnigo, Cetewayo S. Rashid, Arnold J. Stromberg, Shu Shen, John O'Brien, Kevin J. Pearson

Pharmacology and Nutritional Sciences Faculty Publications

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n = 7) v. the remainder of the cohort (n = 40). Multivariate linear regression models were fit to relate expression levels on differentially …

Treatment Pathway Of Bone Sarcoma In Children, Adolescents, And Young Adults, Damon R. Reed, Masanori Hayashi, Lars M. Wagner, Odion Binitie, Diana A. Steppan, Andrew S. Brohl, Eric T. Shinohara, Julia A. Bridge, David M. Loeb, Scott C. Borinstein, Michael S. Isakoff

Pediatrics Faculty Publications

When pediatric, adolescent, and young adult patients present with a bone sarcoma, treatment decisions, especially after relapse, are complex and require a multidisciplinary approach. This review presents scenarios commonly encountered in the therapy of bone sarcomas with the goal of objectively presenting a consensus, multidisciplinary management approach. Little variation was found in the authors' group with respect to local control or systemic therapy. Clinical trials were universally prioritized in all settings. Decisions regarding relapse therapies in the absence of a clinical trial had very minor variations initially, but a consensus was reached after a literature review and discussion. This review …

Demographics, Patterns Of Care, And Survival In Pediatric Medulloblastoma, Emily V. Dressler, Therese A. Dolecek, Meng Liu, John L. Villano

Internal Medicine Faculty Publications

We evaluated the American College of Surgeon’s National Cancer Data Base (NCDB) to describe current hospital-based epidemiologic frequency, survival, and patterns of care of pediatric medulloblastoma. We analyzed NCDB 1998–2011 data on medulloblastoma for children ages 0–19 years using logistic and poisson regression, Kaplan–Meier survival estimates, and Cox proportional hazards models. 3647 cases of medulloblastoma in those aged 0–19 years were identified. Chemotherapy was received by 79 and 74% received radiation, with 65% receiving both therapies. Those who received radiation were more likely to be older than four, while those who received chemotherapy were more likely to be age four …

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …

Albuminuria Changes And Cardiovascular And Renal Outcomes In Type 1 Diabetes: The Dcct/Edic Study., Ian H De Boer, Xiaoyu Gao, Patricia A Cleary, Ionut Bebu, John M Lachin, Mark E Molitch, Trevor Orchard, Andrew D Paterson, Bruce A Perkins, Michael W Steffes, Bernard Zinman

Epidemiology Faculty Publications

Background and objectives In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes.

Design, setting, participants, & measurements We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER …

A Randomized, Double-Blind, Placebo-Controlled Study To Assess The Effect Of Recombinant Human Erythropoietin On Functional Outcomes In Anemic, Critically Ill, Trauma Subjects: The Long Term Trauma Outcomes Study, Fred Luchette, Michael Pasquale, Timothy Fabian, Wayne Langholff, Marsha Wolfson

Michael D Pasquale MD, FACS, FCCM

BACKGROUND: Achieving a higher hemoglobin (Hb) level might allow the anemic, critically ill, trauma patient to have an improved outcome during rehabilitation therapy. METHODS: Patients with major blunt trauma orthopedic injuries were administered epoetin alfa or placebo weekly both in hospital and for up to 12 weeks after discharge or until the Hb level was >12.0 g/dL, whichever occurred first. The 36-question Short Form Health Assessment questionnaire (SF-36) was used to evaluate physical function (PF) outcomes at baseline, at hospital discharge, and at several time points posthospital discharge. RESULTS: One hundred ninety-two patients were enrolled (epoetin alfa [n = 97], …

Determinants Of Negative Pathways To Care And Their Impact On Service Disengagement In First-Episode Psychosis., Kelly K. Anderson, Rebecca Fuhrer, Norbert Schmitz, Ashok K Malla

Epidemiology and Biostatistics Publications

PURPOSE: Although there have been numerous studies on pathways to care in first-episode psychosis (FEP), few have examined the determinants of the pathway to care and its impact on subsequent engagement with mental health services.

METHODS: Using a sample of 324 FEP patients from a catchment area-based early intervention (EI) program in Montréal, we estimated the association of several socio-demographic, clinical, and service-level factors with negative pathways to care and treatment delay. We also assessed the impact of the pathway to care on time to disengagement from EI services.

RESULTS: Few socio-demographic or clinical factors were predictive of negative pathways …

Pilot Study Of The Characteristics Of Acute Stroke Events In Patients Discharged From The Carolina University Hospital, Puerto Rico In 2007, Juan Carlos Zevallos, Juan Gonzalez, Fernando Santiago, Rafael Rodriguez, Ada Rivera, Ana Michelle Garcia, Felixa Flecha, Marielys Colon, Jorge L. Yarzebski

Jorge L. Yarzebski

BACKGROUND: Stroke is the third leading cause of death in Puerto Rico. We examined the pre-hospital phase, management and case-fatality-rates (CFR) of patients discharged with acute stroke from the Carolina University of Puerto Rico Hospital during 2007.

METHODS: Trained personnel collected information on demographics, delay-time, mode-of-transportation, management, and mortality from all medical records. STATAa was utilized to conduct univariate comparison of demographics, mode-of-transportation, therapeutics and diagnostic characteristics. Logistic regression analysis assessed cohort effect and controlled for confounders.

RESULTS: The average age was 69.1 years, and 53% were males. The average delay between onset of symptoms suggestive of stroke and arrival …