Medicine and Health Sciences Commons^™

Timing Of Surgery Following Sars-Cov-2 Infection: An International Prospective Cohort Study, Covidsurg Collaborative, Globalsurg Collaborative

Faculty, Staff and Student Publications

Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 …

Outcomes And Risk Factors Associated With Sars-Cov-2 Infection In A North American Registry Of Patients With Multiple Sclerosis, Amber Salter, Robert J Fox, Scott D Newsome, June Halper, David K B Li, Pamela Kanellis, Kathleen Costello, Bruce Bebo, Kottil Rammohan, Gary R Cutter, Anne H Cross

2020-Current year OA Pubs

Importance: Emergence of SARS-CoV-2 causing COVID-19 prompted the need to gather information on clinical outcomes and risk factors associated with morbidity and mortality in patients with multiple sclerosis (MS) and concomitant SARS-CoV-2 infections.

Objective: To examine outcomes and risk factors associated with COVID-19 clinical severity in a large, diverse cohort of North American patients with MS.

Design, Setting, and Participants: This analysis used deidentified, cross-sectional data on patients with MS and SARS-CoV-2 infection reported by health care professionals in North American academic and community practices between April 1, 2020, and December 12, 2020, in the COVID-19 Infections in MS Registry. …

Brain-Responsive Neurostimulation For The Treatment Of Adults With Epilepsy In Tuberous Sclerosis Complex: A Case Series, Danielle S Mcdermott, Emily A Mirro, Kirsten Fetrow, David E Burdette, Stephanie Chen, Jennifer Hopp, Todd Masel, Emily A Johnson, Felicia M K Elefant, Scheherazade Le, Sanjay E Patra, Mesha-Gay Brown, Zulfi Haneef

2020-Current year OA Pubs

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery.

METHODS: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc).

RESULTS: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median …

Randomized Trial Of The Efficacy And Safety Of Berotralstat (Bcx7353) As An Oral Prophylactic Therapy For Hereditary Angioedema: Results Of Apex-2 Through 48 Weeks (Part 2), H James Wedner, Et Al.

2020-Current year OA Pubs

BACKGROUND: Berotralstat (BCX7353) is a recently approved, oral, once-daily kallikrein inhibitor for hereditary angioedema (HAE) prophylaxis. In the APeX-2 trial, berotralstat reduced HAE attack rates over 24 weeks, with a favorable safety and tolerability profile.

OBJECTIVE: Evaluate berotralstat safety, tolerability, and effectiveness over 48 weeks.

METHODS: APeX-2 is a phase 3, parallel-group, multicenter trial (NCT03485911) in patients with HAE due to C1 esterase inhibitor deficiency. Part 1 was double-blind and placebo-controlled, with patients randomized to 24 weeks of berotralstat 150 mg, 110 mg, or placebo. In part 2, patients continued berotralstat the same dose or, if initially randomized to placebo, …

Association Of Clinical Factors And Recent Anticancer Therapy With Covid-19 Severity Among Patients With Cancer: A Report From The Covid-19 And Cancer Consortium, P Grivas, K E Stockerl-Goldstein, A Y Zhou, Et Al.

2020-Current year OA Pubs

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.

PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). …

Patient Perceptions And Use Of Non-Statin Lipid Lowering Therapy Among Patients With Or At Risk For Atherosclerotic Cardiovascular Disease: Insights From The Palm Registry, Angela Lowenstern, Shuang Li, Ann Marie Navar, Salim S Virani, Veronique L Roger, Jennifer G Robinson, Anne C Goldberg, Wendy Kampman, Eric D Peterson, Tracy Y Wang

Faculty, Staff and Students Publications

BACKGROUND: Non-statin lipid lowering therapies (LLTs) provide additional treatment options for patients. Use patterns and patient perceptions of non-statin LLT remain incompletely described.

HYPOTHESIS: The guideline-recommended statin intensity remains underutilized in patients treated with and without non-statin LLT.

METHODS: The PALM Registry collected LLT information on patients with or at risk of ASCVD treated at 125 US clinics in 2015. We compared patient perceptions, lipid levels and statin use among patients treated with and without non-statin LLT.

RESULTS: Among 7720 patients, 1930 (25.0%) were treated with a non-statin LLT (1249 fish oil, 417 fibrates, 329 ezetimibe, 196 niacin). Concurrent statin …

Speckle-Tracking Echocardiography For Detecting Subclinical Left Ventricular Dysfunction In Patients With Familial Hypercholesterolemia, Rongjuan Li, Jinjie Xie, Bo Jiang, Zhonghua Sun, Lvya Wang, Zhaoting Leng, Yueli Wang, Ya Yang

The Texas Heart Institute Journal

Myocardial ischemia and left ventricular dysfunction have been documented in young adults with familial hypercholesterolemia. We investigated whether speckle-tracking echocardiography can be used to detect subclinically impaired global and regional myocardial function in patients with this lipid disorder. This single-center study included 47 patients with familial hypercholesterolemia and 37 healthy control subjects who underwent transthoracic Doppler echocardiography and speckle-tracking echocardiography from January 2003 through December 2016. Conventional echocardiographic and strain parameters in the 2 groups were analyzed and compared. Left ventricular dimensions were significantly larger at end-diastole (P=0.02) and end-systole (P=0.013), left ventricular walls were significantly thicker (P

Psychological Impact Of Genetic And Clinical Screening For Pulmonary Fibrosis On Asymptomatic First-Degree Relatives Of Affected Individuals, Nikkola Carmichael, Jose M Martinez Manzano, Luisa D Quesada-Arias, Sergio De Frías Poli, Maura Alvarez Baumgartner, Maria A Planchart Ferretto, Lisa Digianni, Shannon Gampala-Sagar, Dominick A Leone, Swati Gulati, Souheil Y El-Chemaly, Hilary J Goldberg, Rachel Putman, Hiroto Hatabu, Ivan O Rosas, Gary M Hunninghake, Benjamin A Raby

Faculty, Staff and Students Publications

Screening for pulmonary fibrosis may help to identify early stages of the disease. We assessed the psychological impact of screening undiagnosed first-degree relatives of patients with pulmonary fibrosis by administering two validated measures after participants received their results: the Decisional Regret Scale and the Feelings About genomiC Testing Results Questionnaire. More than 90% of relatives reported either no or mild decisional regret. Increased measures of decisional regret and negative feelings were present in those found to have a low diffusion capacity of carbon monoxide or interstitial lung abnormalities. Results of telomere length and genetic testing did not significantly impact regret.

Two Mechanisms Of Chromosome Fragility At Replication-Termination Sites In Bacteria, Qian Mei, Devon M Fitzgerald, Jingjing Liu, Jun Xia, John P Pribis, Yin Zhai, Ralf B Nehring, Jacob Paiano, Heyuan Li, Andre Nussenzweig, P J Hastings, Susan M Rosenberg

Faculty, Staff and Students Publications

Chromosomal fragile sites are implicated in promoting genome instability, which drives cancers and neurological diseases. Yet, the causes and mechanisms of chromosome fragility remain speculative. Here, we identify three spontaneous fragile sites in the Escherichia coli genome and define their DNA damage and repair intermediates at high resolution. We find that all three sites, all in the region of replication termination, display recurrent four-way DNA or Holliday junctions (HJs) and recurrent DNA breaks. Homology-directed double-strand break repair generates the recurrent HJs at all of these sites; however, distinct mechanisms of DNA breakage are implicated: replication fork collapse at natural replication …

The Synergy Of Bet Inhibitors With Aurora A Kinase Inhibitors In Mycn-Amplified Neuroblastoma Is Heightened With Functional Tp53, Joanna S Yi, Oscar Sias-Garcia, Nicole Nasholm, Xiaoyu Hu, Amanda Balboni Iniguez, Matthew D Hall, Mindy Davis, Rajarshi Guha, Myrthala Moreno-Smith, Eveline Barbieri, Kevin Duong, Jessica Koach, Jun Qi, James E Bradner, Kimberly Stegmaier, William A Weiss, W Clay Gustafson

Faculty, Staff and Students Publications

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN-amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN-amplified NBL cell lines. Compared …

A Novel Biomarker Panel For The Early Detection And Risk Assessment Of Hepatocellular Carcinoma In Patients With Cirrhosis, Ilvira M Khan, Donjeta Gjuka, Jingjing Jiao, Xiaoling Song, Ying Wang, Jing Wang, Peng Wei, Hashem B El-Serag, Jorge A Marrero, Laura Beretta

Faculty, Staff and Students Publications

Novel biomarkers for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis are urgently needed. We previously identified osteopontin (OPN) as a promising biomarker for the early detection of HCC. This study is to further validate the performance of OPN and identify fatty acids (FA) that could improve OPN's performance in HCC risk assessment in patients with cirrhosis. To that end, we selected 103 patients with cirrhosis under surveillance. Among them, 40 patients developed HCC during follow-up. We investigated in these 103 patients, the association between HCC incidence and prediagnostic serum levels of AFP, OPN, and 46 FAs. OPN performance was …

Advantage Of 16s Rrna Amplicon Sequencing In Helicobacter Pylori Diagnosis, Boldbaatar Gantuya, Hashem B El Serag, Batsaikhan Saruuljavkhlan, Dashdorj Azzaya, Takashi Matsumoto, Tomohisa Uchida, Khasag Oyuntsetseg, Nyamdorj Oyunbileg, Duger Davaadorj, Yoshio Yamaoka

Faculty, Staff and Students Publications

BACKGROUND: 16S rRNA amplicon sequencing is an accurate method of detecting microbial infection without culture. It is unclear if sequencing has additional benefits over routine diagnostic methods for Helicobacter pylori testing.

METHODS: We enrolled Mongolian volunteers with dyspepsia. Using routine diagnostic methods, positive H. pylori was defined as positive results on histology/immunohistochemistry, culture, rapid urease test, or serology; negative H. pylori was defined by negative results from all these tests. We performed 16S rRNA sequencing on gastric biopsy specimens and calculated cutoffs for operational taxonomic units (OTUs) and relative abundance (RA) to define positive results using ROC curves.

RESULTS: We …

Effects Of Pathogen Reduction Technology And Storage Duration On The Ability Of Cryoprecipitate To Rescue Induced Coagulopathies In Vitro, Kimberly A Thomas, Susan M Shea, Philip C Spinella

2020-Current year OA Pubs

BACKGROUND: Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (<6 h). Pathogen reduction (PR) of cryoprecipitate would provide a shelf-stable immediately available adjunct containing factors important for rescuing hemostatic dysfunction.

STUDY DESIGN AND METHODS: Hemostatic adjunct study products were psoralen-treated PR-cryoprecipitated fibrinogen complex (PR-Cryo FC), cryoprecipitate (Cryo), and fibrinogen concentrates (FibCon). PR-Cryo FC and Cryo were stored for 10 days at 20-24°C. Adjuncts were …

Clinical Epigenomics: Genome-Wide Dna Methylation Analysis For The Diagnosis Of Mendelian Disorders, Bekim Sadikovic, Jorge L Granadillo, Et Al.

2020-Current year OA Pubs

PURPOSE: We describe the clinical implementation of genome-wide DNA methylation analysis in rare disorders across the EpiSign diagnostic laboratory network and the assessment of results and clinical impact in the first subjects tested.

METHODS: We outline the logistics and data flow between an integrated network of clinical diagnostics laboratories in Europe, the United States, and Canada. We describe the clinical validation of EpiSign using 211 specimens and assess the test performance and diagnostic yield in the first 207 subjects tested involving two patient subgroups: the targeted cohort (subjects with previous ambiguous/inconclusive genetic findings including genetic variants of unknown clinical significance) …

Integration Of Immunotherapy Into Adjuvant Therapy For Resected Non-Small-Cell Lung Cancer: Alchemist Chemo-Io (Accio), Jacob M Sands, Ramaswamy Govindan, Jhanelle Gray, Et Al

2020-Current year OA Pubs

Non-small-cell lung cancer (NSCLC) causes significant mortality each year. After successful resection of disease stage IB (>4 cm) to IIIA (per AJCC 7), adjuvant platinum-based chemotherapy improves median overall survival and is the standard of care, but many patients still experience recurrence of disease. An adjuvant regimen with greater efficacy could substantially improve outcomes. Pembrolizumab, a programmed cell death-1 inhibitor, has become an important option in the treatment of metastatic NSCLC. ALCHEMIST is a clinical trial platform of the National Cancer Institute that includes biomarker analysis for resected NSCLC and supports therapeutic trials including A081801 (ACCIO), a three-arm study …

Multiparametric Early Detection And Prediction Of Cardiotoxicity Using Myocardial Strain, T1 And T2 Mapping, And Biochemical Markers: A Longitudinal Cardiac Resonance Imaging Study During 2 Years Of Follow-Up, Sorin Giusca, Grigorios Korosoglou, Moritz Montenbruck, Blaž Geršak, Arne Kristian Schwarz, Sebastian Esch, Sebastian Kelle, Pia Wülfing, Susan Dent, Daniel Lenihan, Henning Steen

2020-Current year OA Pubs

BACKGROUND: Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed.

METHODS: Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and …

Safety And Efficacy Of Umbilical Cord-Derived Wharton's Jelly Compared To Hyaluronic Acid And Saline For Knee Osteoarthritis: Study Protocol For A Randomized, Controlled, Single-Blind, Multi-Center Trial, Ashim Gupta, Nicola Maffulli, Hugo C Rodriguez, Eric W Carson, Randa A Bascharon, Kristin Delfino, Howard J Levy, Saadiq F El-Amin

2020-Current year OA Pubs

BACKGROUND: Osteoarthritis (OA) is the most common joint disorder in the United States of America (USA) with a fast-rising prevalence. Current treatment modalities are limited, and total knee replacement surgeries have shown disadvantages, especially for grade II/III OA. The interest in the use of biologics, including umbilical cord (UC)-derived Wharton's jelly (WJ), has grown in recent years. The results from a preliminary study demonstrated the presence of essential components of regenerative medicine, namely growth factors, cytokines, hyaluronic acid (HA), and extracellular vesicles, including exosomes, in WJ. The proposed study aims to evaluate the safety and efficacy of intra-articular injection of …

Integrating Genomics And Metabolomics For Scalable Non-Ribosomal Peptide Discovery., Bahar Behsaz, Edna Bode, Alexey Gurevich, Yan-Ni Shi, Florian Grundmann, Deepa Acharya, Andrés Mauricio Caraballo-Rodríguez, Amina Bouslimani, Morgan Panitchpakdi, Annabell Linck, Changhui Guan, Julia Oh, Pieter C Dorrestein, Helge B Bode, Pavel A Pevzner, Hosein Mohimani

Faculty Research 2021

Non-Ribosomal Peptides (NRPs) represent a biomedically important class of natural products that include a multitude of antibiotics and other clinically used drugs. NRPs are not directly encoded in the genome but are instead produced by metabolic pathways encoded by biosynthetic gene clusters (BGCs). Since the existing genome mining tools predict many putative NRPs synthesized by a given BGC, it remains unclear which of these putative NRPs are correct and how to identify post-assembly modifications of amino acids in these NRPs in a blind mode, without knowing which modifications exist in the sample. To address this challenge, here we report NRPminer, …

Exome Sequencing Revealed Pde11a As A Novel Candidate Gene For Early-Onset Alzheimer's Disease, Wei Qin, Aihong Zhou, Xiumei Zuo, Longfei Jia, Fangyu Li, Qi Wang, Ying Li, Yiping Wei, Hongmei Jin, Carlos Cruchaga, Bruno A Benitez, Jianping Jia

2020-Current year OA Pubs

To identify novel risk genes and better understand the molecular pathway underlying Alzheimer's disease (AD), whole-exome sequencing was performed in 215 early-onset AD (EOAD) patients and 255 unrelated healthy controls of Han Chinese ethnicity. Subsequent validation, computational annotation and in vitro functional studies were performed to evaluate the role of candidate variants in EOAD. We identified two rare missense variants in the phosphodiesterase 11A (PDE11A) gene in individuals with EOAD. Both variants are located in evolutionarily highly conserved amino acids, are predicted to alter the protein conformation and are classified as pathogenic. Furthermore, we found significantly decreased protein levels of …

Common Concerns, Barriers To Care, And The Lived Experience Of Individuals With Hepatitis B: A Qualitative Study., Catherine Freeland, Sean Farrell, Priyanka Kumar, Maureen Kamischke, Michaela Jackson, Sierra Bodor, Timothy M Block, Rosemary Frasso Phd, Msc, Cph, Chari Cohen

College of Population Health Faculty Papers

BACKGROUND: An estimated between 257 and 292 million people live with chronic HBV globally. While much is known about the causes, and epidemiology of HBV, little is understood about the quality of life and impact of HBV on those living with the infection.

METHODS: A random sample of HBV-related email queries sent to the Hepatitis B Foundation, a U.S.-based non-profit organization, over a 12-month period in 2018-2019 were retrieved, tabulated, and analyzed qualitatively to highlight information needs and explore the experiences of people living with HBV and their families and loved ones. Codebook development was informed by the literature and …

Digital Technology Needs In Maternal Mental Health: A Qualitative Inquiry, Alexandra Zingg, Laura Carter, Deevakar Rogith, Amy Franklin, Sudhakar Selvaraj, Jerrie Refuerzo, Sahiti Myneni

Faculty, Staff and Student Publications

Digital technologies offer many opportunities to improve mental healthcare management for women seeking pre- and-postnatal care. They provide a discrete, practical medium that is well-suited for the sensitive nature of mental health. Women who are more prone to experiencing peripartum depression (PPD), such as those of low-socioeconomic background or in high-risk pregnancies, can benefit the most from such technologies. However, current digital interventions directed towards this population provide suboptimal support, and their responsiveness to end user needs is quite limited. Our objective is to understand the digital terrain of information needs for low-socioeconomic status women with high-risk pregnancies, specifically within …

How Will The Future Of Work Shape Osh Research And Practice? A Workshop Summary, Sarah A Felknor, Jessica M K Streit, Michelle Mcdaniel, Paul A Schulte, L Casey Chosewood, George L Delclos

Faculty, Staff and Student Publications

Growth of the information economy and globalization of labor markets will be marked by exponential growth in emerging technologies that will cause considerable disruption of the social and economic sectors that drive the global job market. These disruptions will alter the way we work, where we work, and will be further affected by the changing demographic characteristics and level of training of the available workforce. These changes will likely result in scenarios where existing workplace hazards are exacerbated and new hazards with unknown health effects are created. The pace of these changes heralds an urgent need for a proactive approach …

Cell Lineage Tracing Links Erα Loss In Erbb2-Positive Breast Cancers To The Arising Of A Highly Aggressive Breast Cancer Subtype, Yunfeng Ding, Yonghong Liu, Dong-Kee Lee, Zhangwei Tong, Xiaobin Yu, Yi Li, Yong Xu, Rainer B Lanz, Bert W O'Malley, Jianming Xu

Children’s Nutrition Research Center Staff Publications

HER2-positive (HER2+) breast cancers (BrCs) contain approximately equal numbers of ERα+HER2+ and ERα−HER2+ cases. An enduring obstacle is the unclear cell lineage-related characteristics of these BrCs. Although ERα+HER2+ BrCs could lose ERα to become ERα−HER2+ BrCs, direct evidence is missing. To investigate ERα dependencies and their implications during BrC growth and metastasis, we generated ERαCreRFP-T mice that produce an RFP-marked ERα+ mammary gland epithelial cell (MGEC) lineage. RCAS virus-mediated expression of Erbb2, a rodent Her2 homolog, first produced comparable numbers of ERα+RFP+Erbb2+ and ERα−RFP−Erbb2+ MGECs. Early hyperplasia developed mostly from ERα+RFP+Erbb2+ cells and ERα−RFP−Erbb2+ cells in these lesions were rare. …

Novel Autosegmentation Spatial Similarity Metrics Capture The Time Required To Correct Segmentations Better Than Traditional Metrics In A Thoracic Cavity Segmentation Workflow, Kendall J Kiser, Arko Barman, Sonja Stieb, Clifton D Fuller, Luca Giancardo

2020-Current year OA Pubs

Automated segmentation templates can save clinicians time compared to de novo segmentation but may still take substantial time to review and correct. It has not been thoroughly investigated which automated segmentation-corrected segmentation similarity metrics best predict clinician correction time. Bilateral thoracic cavity volumes in 329 CT scans were segmented by a UNet-inspired deep learning segmentation tool and subsequently corrected by a fourth-year medical student. Eight spatial similarity metrics were calculated between the automated and corrected segmentations and associated with correction times using Spearman's rank correlation coefficients. Nine clinical variables were also associated with metrics and correction times using Spearman's rank …

Electronic Clinical Decision Support For Children With Minor Head Trauma And Intracranial Injuries: A Sociotechnical Analysis, Jacob K Greenberg, Ayodamola Otun, Azzah Nasraddin, Ross C Brownson, Nathan Kuppermann, David D Limbrick, Po-Yin Yen, Randi E Foraker

2020-Current year OA Pubs

BACKGROUND: Current management of children with minor head trauma (MHT) and intracranial injuries is not evidence-based and may place some children at risk of harm. Evidence-based electronic clinical decision support (CDS) for management of these children may improve patient safety and decrease resource use. To guide these efforts, we evaluated the sociotechnical environment impacting the implementation of electronic CDS, including workflow and communication, institutional culture, and hardware and software infrastructure, among other factors.

METHODS: Between March and May, 2020 semi-structured qualitative focus group interviews were conducted to identify sociotechnical influences on CDS implementation. Physicians from neurosurgery, emergency medicine, critical care, …

A Method To Delineate De Novo Missense Variants Across Pathways Prioritizes Genes Linked To Autism, Amanda Koire, Panagiotis Katsonis, Young Won Kim, Christie Buchovecky, Stephen J Wilson, Olivier Lichtarge

Faculty, Staff and Students Publications

Genotype-phenotype relationships shape health and population fitness but remain difficult to predict and interpret. Here, we apply an evolutionary action method in mutational landscapes to unravel genes and pathways connected to autism spectrum disorder (ASD). Evolutionary action predicts the impact of missense variants on protein function by measuring motions in fitness landscapes, based on phylogenetic distances and substitution odds in homologous sequences. By examining 368 pathways across 2,384 individuals with ASD (probands), we found that 23 pathways, a total of 398 genes, had de novo missense variants biased to higher evolutionary action scores than expected by random chance, including axonogenesis, …

One-Year Urinary And Sexual Outcome Trajectories Among Prostate Cancer Patients Treated By Radical Prostatectomy: A Prospective Study, Lin Yang, Jung Ae Lee, Emily Heer, Claire Pernar, Graham A Colditz, Ratna Pakpahan, Kellie R Imm, Eric H Kim, Robert L Grubb 3rd, Kathleen Y Wolin, Adam S Kibel, Siobhan Sutcliffe

2020-Current year OA Pubs

BACKGROUND: To examine one-year trajectories of urinary and sexual outcomes, and correlates of these trajectories, among prostate cancer patients treated by radical prostatectomy (RP).

METHODS: Study participants were recruited from 2011 to 2014 at two US institutions. Self-reported urinary and sexual outcomes were measured at baseline before surgery, and 5 weeks, 6 months and 12 months after surgery, using the modified Expanded Prostate Cancer Index Composite-50 (EPIC-50). Changes in EPIC-50 scores from baseline were categorized as improved (beyond baseline), maintained, or impaired (below baseline), using previously-reported minimum clinically important differences.

RESULTS: Of the 426 eligible participants who completed the baseline …

Long Term Safety, Tolerability, And Efficacy Of Intracutaneous Zolmitriptan (M207) In The Acute Treatment Of Migraine., Stephanie J. Nahas, Nada Hindiyeh, Deborah I. Friedman, Nada Elbuluk, Donald J. Kellerman, Pamela K. Foreman, Peter Schmidt

Department of Neurology Faculty Papers

OBJECTIVE: To determine the long-term safety and tolerability profile of M207 in the acute treatment of migraine.

BACKGROUND: M207 is an investigational microneedle-based system for intracutaneous delivery of zolmitriptan for the treatment of migraine attacks. Following on the positive results of a Phase 2/3 placebo-controlled efficacy study (ZOTRIP), this study was designed to evaluate the safety of this novel product during repeated use for the treatment of migraine attacks.

METHODS: In this 6-12 month open-label, multicenter observational study, participants used an eDiary to record headache symptoms and adverse events at specified intervals up to 48 h following treatment of a …

Community Support Model On Breastfeeding And Complementary Feeding Practices In Remote Areas In Vietnam: Implementation, Cost, And Effectiveness, Tuan T. Nguyen, Nemat Hajeebhoy, Jia Li, Chung T. Do, Roger Mathisen, Edward A. Frongillo Jr.

Faculty Publications

Background

Poor access to healthcare facilities and consequently nutrition counseling services hinders the uptake of recommended infant and young child feeding (IYCF) practices. To address these barriers and improve IYCF practices, Alive & Thrive (A&T) initiated community support groups in remote villages across nine provinces in Vietnam.

Objective

This study examines the effectiveness of the support group model and related project costs for reaching underserved areas to improve IYCF practices.

Methods

To evaluate the model’s implementation and project costs, we reviewed implementation guidelines, expenditure and coverage reports, monitoring data, and budgets for the nine provinces. To evaluate the model’s effectiveness, …

Models Of Care For Patients With Hypertension And Diabetes In Humanitarian Crises: A Systematic Review, Michael S Jaung, Ruth Willis, Piyu Sharma, Sigiriya Aebischer Perone, Signe Frederiksen, Claudia Truppa, Bayard Roberts, Pablo Perel, Karl Blanchet, Éimhín Ansbro

Faculty, Staff and Students Publications

Care for non-communicable diseases, including hypertension and diabetes (HTN/DM), is recognized as a growing challenge in humanitarian crises, particularly in low- and middle-income countries (LMICs) where most crises occur. There is little evidence to support humanitarian actors and governments in designing efficient, effective, and context-adapted models of care for HTN/DM in such settings. This article aimed to systematically review the evidence on models of care targeting people with HTN/DM affected by humanitarian crises in LMICs. A search of the MEDLINE, Embase, Global Health, Global Indexus Medicus, Web of Science, and EconLit bibliographic databases and grey literature sources was performed. Studies …