Medicine and Health Sciences Commons^™

Population Pharmacokinetics Of Liposomal Amphotericin B In Immunocompromised Children., Jodi M Lestner, Andreas H Groll, Ghaith Aljayyoussi, Nita L Seibel, Aziza Shad, Corina Gonzalez, Lauren V Wood, Paul F Jarosinski, Thomas J Walsh, William W Hope

Pediatrics Faculty Publications

Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg(-1) daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = …

Tx-004hr Improves Sexual Function As Measured By The Female Sexual Function Index In Postmenopausal Women With Vulvar And Vaginal Atrophy: The Rejoice Trial., Sheryl A Kingsberg, Leonard Derogatis, James A Simon, Ginger D Constantine, Shelli Graham, Brian Bernick, Gina Gasper, Sebastian Mirkin

Obstetrics and Gynecology Faculty Publications

INTRODUCTION: TX-004HR is an investigational, applicator-free, vaginal soft gel capsule containing low-dose solubilized 17β-estradiol. The phase 3, randomized, double-blinded, placebo-controlled, multicenter REJOICE trial has shown TX-004HR to be safe and effective for the treatment of moderate to severe dyspareunia in postmenopausal women with vulvar and vaginal atrophy (VVA).

AIM: To evaluate the effect of TX-004HR on female sexual dysfunction in postmenopausal women with VVA.

METHODS: The REJOICE study compared the effects of 12-week treatment with TX-004HR (4, 10, or 25 μg) with placebo in postmenopausal women (40-75 years old) with VVA and a most bothersome symptom of moderate to severe …

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 …

Concluding Commentary: Children In All Cancer Prevention Policy Decisions., Cynthia F Bearer, Lynn Goldman

Environmental and Occupational Health Faculty Publications

This interesting series of articles on Opportunities for Cancer Prevention During Early Life brings many ideas for the primary prevention of cancer in childhood, or in adults due to early life events. The economic burden not only of cancer mortality but also of lifelong morbidity among cancer survivors, as shown by Guy et al,1 raises the importance of this critical public health issue. The topics of these articles were developed during online seminars with the pioneers in this area, some of whom authored the articles. They reflect the determinants of health diagrammed so eloquently in Healthy People 2020.2 …

Can Academic Medicine Lead The Way In The Refugee Crisis?, Amir A Afkhami

Psychiatry and Behavioral Sciences Faculty Publications

The world is currently in the midst of the largest refugee crisis since World War II, with the highest interval of mass displacement in recorded history according to the United Nations. The United States has pledged to maintain its position as one of the world's top resettlement countries in response to this crisis. These new immigrants will arrive with exceptional chronic and acute medical needs, including higher rates of behavioral health disorders. The author describes the health care challenges experienced by refugees seeking asylum in the United States and outlines the ways in which our health care system is currently …

Characterizing The Reproduction Number Of Epidemics With Early Subexponential Growth Dynamics., Gerardo Chowell, Cécile Viboud, Lone Simonsen, Seyed M Moghadas

Global Health Faculty Publications

Early estimates of the transmission potential of emerging and re-emerging infections are increasingly used to inform public health authorities on the level of risk posed by outbreaks. Existing methods to estimate the reproduction number generally assume exponential growth in case incidence in the first few disease generations, before susceptible depletion sets in. In reality, outbreaks can display subexponential (i.e. polynomial) growth in the first few disease generations, owing to clustering in contact patterns, spatial effects, inhomogeneous mixing, reactive behaviour changes or other mechanisms. Here, we introduce the generalized growth model to characterize the early growth profile of outbreaks and estimate …

Fto Genotype And Weight Loss: Systematic Review And Meta-Analysis Of 9563 Individual Participant Data From Eight Randomised Controlled Trials., Katherine M Livingstone, Carlos Celis-Morales, George D Papandonatos, Bahar Erar, Jose C Florez, Kathleen A Jablonski, Cristina Razquin, Amelia Marti, Yoriko Heianza, Tao Huang, Frank M Sacks, Mathilde Svendstrup, Xuemei Sui, Timothy S Church, Tiina Jääskeläinen, Jaana Lindström, Jaakko Tuomilehto, Matti Uusitupa, Tuomo Rankinen, Wim H M Saris, Torben Hansen, Oluf Pedersen, Arne Astrup, Thorkild I A Sørensen, Lu Qi, George A Bray, Miguel A Martinez-Gonzalez, J Alfredo Martinez, Paul W Franks, Jeanne M Mccaffery, Jose Lara, John C Mathers

Epidemiology Faculty Publications

OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.

DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.

DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.

ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual …

Method And Phantom To Study Combined Effects Of In-Plane (X,Y) And Z-Axis Resolution For 3d Ct Imaging., David Goodenough, Josh Levy, Smari Kristinsson, Jesper Fredriksson, Hildur Olafsdottir, Austin Healy

Radiology Faculty Publications

Increasingly, the advent of multislice CT scanners, volume CT scanners, and total body spiral acquisition modes has led to the use of Multi Planar Reconstruction and 3D datasets. In considering 3D resolution properties of a CT system it is important to note that both the in-plane (x,y) and z-axis (slice thickness) influence the visual-ization and detection of objects within the scanned volume. This study investigates ways to consider both the in-plane resolution and the z-axis resolution in a single phantom wherein analytic or visualized analysis can yield information on these combined effects. A new phantom called the "Wave Phantom" is …

Schools Of Public Health In Low And Middle-Income Countries: An Imperative Investment For Improving The Health Of Populations?, Fauziah Rabbani, Leah Shipton, Franklin White, Iman Nuwayhid, Leslie London, Abdul Ghaffar, Bui Thi Thu Ha, Göran Tomson, Rajiv Rimal, Anwar Islam, Amirhossein Takian, Samuel Wong, Shehla Zaidi, Kausar Khan, Rozina Karmaliani, Imran Naeem Abbasi, Farhat Abbas

Prevention and Community Health Faculty Publications

BACKGROUND: Public health has multicultural origins. By the close of the nineteenth century, Schools of Public Health (SPHs) began to emerge in western countries in response to major contemporary public health challenges. The Flexner Report (1910) emphasized the centrality of preventive medicine, sanitation, and public health measures in health professional education. The Alma Ata Declaration on Primary Health Care (PHC) in 1978 was a critical milestone, especially for low and middle-income countries (LMICs), conceptualizing a close working relationship between PHC and public health measures. The Commission on Social Determinants of Health (2005-2008) strengthened the case for SPHs in LMICs as …

Prospective Evaluation Of The Influence Of Iterative Reconstruction On The Reproducibility Of Coronary Calcium Quantification In Reduced Radiation Dose 320 Detector Row Ct., Andrew D Choi, Eric S Leifer, Jeannie Yu, Sujata M Shanbhag, Kathie Bronson, Andrew E Arai, Marcus Y Chen

Radiology Faculty Publications

BACKGROUND: Coronary artery calcium (CAC) predicts coronary heart disease events and is important for individualized cardiac risk assessment. This report assesses the interscan variability of CT for coronary calcium quantification using image acquisition with standard and reduced radiation dose protocols and whether the use of reduced radiation dose acquisition with iterative reconstruction (IR; "reduced-dose/IR ") allows for similar image quality and reproducibility when compared to standard radiation dose acquisition with filtered back projection (FBP; "standard-dose/FBP") on 320-detector row computed tomography (320-CT).

METHODS: 200 consecutive patients (60 ± 9 years, 59% male) prospectively underwent two standard- and two reduced-dose acquisitions (800 …

Spontaneous Subarachnoid Hemorrhage: A Systematic Review And Meta-Analysis Describing The Diagnostic Accuracy Of History, Physical Examination, Imaging, And Lumbar Puncture With An Exploration Of Test Thresholds., Christopher R Carpenter, Adnan M Hussain, Michael J Ward, Gregory J Zipfel, Susan Fowler, Jesse M Pines, Marco L A Sivilotti

Emergency Medicine Faculty Publications

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) is a rare, but serious etiology of headache. The diagnosis of SAH is especially challenging in alert, neurologically intact patients, as missed or delayed diagnosis can be catastrophic.

OBJECTIVES: The objective was to perform a diagnostic accuracy systematic review and meta-analysis of history, physical examination, cerebrospinal fluid (CSF) tests, computed tomography (CT), and clinical decision rules for spontaneous SAH. A secondary objective was to delineate probability of disease thresholds for imaging and lumbar puncture (LP).

METHODS: PubMed, Embase, Scopus, and research meeting abstracts were searched up to June 2015 for studies of emergency department patients …

Expanding The Phenotype Associated With Naa10-Related N-Terminal Acetylation Deficiency., Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas Ahmew, +Several Additional Authors

Pediatrics Faculty Publications

N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ …

The Impact Of Patient Navigation On The Delivery Of Diagnostic Breast Cancer Care In The National Patient Navigation Research Program: A Prospective Meta-Analysis., Tracy A Battaglia, Julie S Darnell, Naomi Ko, Fred Snyder, Electra D Paskett, Kristen J Wells, Elizabeth M Whitley, Jennifer J Griggs, Anand Karnad, Heather Young, Victoria Warren-Mears, Melissa A Simon, Elizabeth Calhoun

Epidemiology Faculty Publications

Patient navigation is emerging as a standard in breast cancer care delivery, yet multi-site data on the impact of navigation at reducing delays along the continuum of care are lacking. The purpose of this study was to determine the effect of navigation on reaching diagnostic resolution at specific time points after an abnormal breast cancer screening test among a national sample. A prospective meta-analysis estimated the adjusted odds of achieving timely diagnostic resolution at 60, 180, and 365 days. Exploratory analyses were conducted on the pooled sample to identify which groups had the most benefit from navigation. Clinics from six …

Webpoisoncontrol: Can Poison Control Be Automated?, Toby Litovitz, Blaine E Benson, Susan Smolinske

Emergency Medicine Faculty Publications

BACKGROUND: A free webPOISONCONTROL app allows the public to determine the appropriate triage of poison ingestions without calling poison control. If accepted and safe, this alternative expands access to reliable poison control services to those who prefer the Internet over the telephone. This study assesses feasibility, safety, and user-acceptance of automated online triage of asymptomatic, nonsuicidal poison ingestion cases.

METHODS: The user provides substance name, amount, age, and weight in an automated online tool or downloadable app, and is given a specific triage recommendation to stay home, go to the emergency department, or call poison control for further guidance. Safety …

Detection Of Zoonotic Enteropathogens In Children And Domestic Animals In A Semirural Community In Ecuador., Karla Vasco, Jay P Graham, Gabriel Trueba

Environmental and Occupational Health Faculty Publications

UNLABELLED: Animals are important reservoirs of zoonotic enteropathogens, and transmission to humans occurs more frequently in low- and middle-income countries (LMICs), where small-scale livestock production is common. In this study, we investigated the presence of zoonotic enteropathogens in stool samples from 64 asymptomatic children and 203 domestic animals of 62 households in a semirural community in Ecuador between June and August 2014. Multilocus sequence typing (MLST) was used to assess zoonotic transmission of Campylobacter jejuni and atypical enteropathogenic Escherichia coli (aEPEC), which were the most prevalent bacterial pathogens in children and domestic animals (30.7% and 10.5%, respectively). Four sequence types …

The Respiratory Protection Effectiveness Clinical Trial (Respect): A Cluster-Randomized Comparison Of Respirator And Medical Mask Effectiveness Against Respiratory Infections In Healthcare Personnel., Lewis J Radonovich, Mary T Bessesen, Derek A Cummings, Aaron Eagan, Charlotte Gaydos, Cynthia Gibert, Geoffrey J Gorse, Ann-Christine Nyquist, Nicholas G Reich, Maria Rodrigues-Barradas, Connie Savor-Price, Ronald E Shaffer, Michael S Simberkoff, Trish M Perl

Medicine Faculty Publications

BACKGROUND: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts.

METHODS: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to …

A Clinical Score To Predict Dose Reductions Of Antidiabetes Medications With Intentional Weight Loss: A Retrospective Cohort Study., Ghanshyam Palamaner Subash Shantha, Anita Ashok Kumar, Vimal Ravi, Rohit C Khanna, Scott Kahan, Lawrence J Cheskin

Health Policy and Management Faculty Publications

Abstract

Background

We assessed the predictive accuracy of an empirically-derived score (weight loss, insulin resistance, and glycemic control: “WIG”) to predict patients who will be successful in reducing diabetes mellitus (DM) medication use with weight loss.

Methods

Case records of 121 overweight and obese patients with DM at two outpatient weight management centers were analyzed.

Results

Mean period of follow-up was 12.5 ± 3.5 months. To derive the “WIG” scoring algorithm, one point each was assigned to “W” (loss of 5% of initial body weight within the first 3 months of attempting weight loss), “I” (triglyceride [TGL]/highdensity lipoprotein ratio >3 …

How Complicated Can It Be? The Link Between Apol1 Risk Variants And Lipoprotein Heterogeneity In Kidney And Cardiovascular Diseases., Chien-An A Hu, Patricio E Ray

Pediatrics Faculty Publications

The beginning of human apolipoprotein L1 study (gene: APOL1; protein: ApoL1) originated from the identification of circulating ApoL1 as an interacting protein of ApoA1 and a minor component of high-density lipoprotein subfraction 3 (HDL3) in 1997 [1]. In the past 18 years, ApoL1 has been investigated in the context of complex human diseases such as African sleeping sickness, schizophrenia, host innate immunity, cancer, hyperlipidemia, cardiovascular diseases, stroke and type 2 diabetes [2–10]. A major breakthrough, however, was the documentation of two haplotypes of APOL1, harboring three coding-sequence mutations as risk variants associated with non-diabetic …

Hydroxycarbamide Versus Chronic Transfusion For Maintenance Of Transcranial Doppler Flow Velocities In Children With Sickle Cell Anaemia-Tcd With Transfusions Changing To Hydroxyurea (Twitch): A Multicentre, Open-Label, Phase 3, Non-Inferiority Trial., Russell E Ware, Barry R Davis, William H Schultz, R Clark Brown, Banu Aygun, Sharada Sarnaik, Lori Luchtman-Jones, +Several Additional Authors

Pediatrics Faculty Publications

BACKGROUND: For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.

METHODS: TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (≥ 200 cm/s) but no severe vasculopathy. After screening, eligible …

Membranoproliferative Glomerulonephritis Recurrence After Kidney Transplantation: Using The New Classification., Sami Alasfar, Naima Carter-Monroe, Avi Z Rosenberg, Robert A Montgomery, Nada Alachkar

Pathology Faculty Publications

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon glomerular disorder that may lead to end stage renal disease (ESRD). With new understanding of the disease pathogenesis, the classical classification as MPGN types I, II, III has changed. Data on post-transplant MPGN, in particular with the newly refined classification, is limited. We present our center's experience of MPGN after kidney transplantation using the new classification.

METHODS: This is a retrospective study of 34 patients with ESRD due to MPGN who received 40 kidney transplants between 1994 and 2014. We reviewed the available biopsies' data using the new classification. We assessed post transplantation …

The Application Of Digital Pathology To Improve Accuracy In Glomerular Enumeration In Renal Biopsies., Avi Z Rosenberg, Matthew Palmer, Lino Merlino, Jonathan P Troost, Adil Gasim, Serena Bagnasco, Carmen Avila-Casado, Duncan Johnstone, Jeffrey B Hodgin, Catherine Conway, Brenda W Gillespie, Cynthia C Nast, Laura Barisoni, Stephen M Hewitt

Pathology Faculty Publications

BACKGROUND: In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.

DESIGN: We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are …

Arsenic In Drinking Water And Lung Cancer Mortality In The United States: An Analysis Based On Us Counties And 30 Years Of Observation (1950-1979)., Hamid Ferdosi, Elisabeth K Dissen, Nana Ama Afari-Dwamena, Ji Li, Rusan Chen, Manning Feinleib, Steven H Lamm

Epidemiology Faculty Publications

Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10-934 µg/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3-59 µg/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of ≥3 µg/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. …

The Synergistic Roles Of Cholecystokinin B And Dopamine D5 Receptors On The Regulation Of Renal Sodium Excretion., Xiaoliang Jiang, Wei Chen, Xing Liu, Zihao Wang, Yunpeng Liu, Robin A Felder, John J Gildea, Pedro A. Jose, Chuan Qin, Zhiwei Yang

Medicine Faculty Publications

Renal dopamine D1-like receptors (D1R and D5R) and the gastrin receptor (CCKBR) are involved in the maintenance of sodium homeostasis. The D1R has been found to interact synergistically with CCKBR in renal proximal tubule (RPT) cells to promote natriuresis and diuresis. D5R, which has a higher affinity for dopamine than D1R, has some constitutive activity. Hence, we sought to investigate the interaction between D5R and CCKBR in the regulation of renal sodium excretion. In present study, we found D5R and CCKBR increase each other's expression in a concentration- and time-dependent manner in the HK-2 cell, the specificity of which was …

Identification And Use Of Frailty Indicators From Text To Examine Associations With Clinical Outcomes Among Patients With Heart Failure., Yijun Shao, April F Mohanty, Ali Ahmed, Charlene R Weir, Bruce E Bray, Rashmee U Shah, Douglas Redd, Qing Zeng-Treitler

Clinical Research and Leadership Faculty Publications

Frailty is an important health outcomes indicator and valuable for guiding healthcare decisions in older adults, but is rarely collected in a quantitative, systematic fashion in routine healthcare. Using a cohort of 12,000 Veterans with heart failure, we investigated the feasibility of topic modeling to identify frailty topics in clinical notes. Topics were generated through unsupervised learning and then manually reviewed by an expert. A total of 53 frailty topics were identified from 100,000 notes. We further examined associations of frailty with age-, sex-, and Charlson Comorbidity Index-adjusted 1-year hospitalizations and mortality (composite outcome) using logistic regression. Frailty (≤ 4 …