Publications by authors named "B Borg"

172 Publications

Mode of Arrival to the Emergency Department and Outcomes in Nontraumatic Critically Ill Adults.

Crit Care Explor 2021 Mar 25;3(3):e0350. Epub 2021 Feb 25.

Department of Medicine, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona, Tucson, AZ.

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http://dx.doi.org/10.1097/CCE.0000000000000350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909384PMC
March 2021

Patterns and processes of pathogen exposure in gray wolves across North America.

Sci Rep 2021 Feb 12;11(1):3722. Epub 2021 Feb 12.

Center for Infectious Disease Dynamics, Department of Biology, Huck Institutes of the Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA.

The presence of many pathogens varies in a predictable manner with latitude, with infections decreasing from the equator towards the poles. We investigated the geographic trends of pathogens infecting a widely distributed carnivore: the gray wolf (Canis lupus). Specifically, we investigated which variables best explain and predict geographic trends in seroprevalence across North American wolf populations and the implications of the underlying mechanisms. We compiled a large serological dataset of nearly 2000 wolves from 17 study areas, spanning 80° longitude and 50° latitude. Generalized linear mixed models were constructed to predict the probability of seropositivity of four important pathogens: canine adenovirus, herpesvirus, parvovirus, and distemper virus-and two parasites: Neospora caninum and Toxoplasma gondii. Canine adenovirus and herpesvirus were the most widely distributed pathogens, whereas N. caninum was relatively uncommon. Canine parvovirus and distemper had high annual variation, with western populations experiencing more frequent outbreaks than eastern populations. Seroprevalence of all infections increased as wolves aged, and denser wolf populations had a greater risk of exposure. Probability of exposure was positively correlated with human density, suggesting that dogs and synanthropic animals may be important pathogen reservoirs. Pathogen exposure did not appear to follow a latitudinal gradient, with the exception of N. caninum. Instead, clustered study areas were more similar: wolves from the Great Lakes region had lower odds of exposure to the viruses, but higher odds of exposure to N. caninum and T. gondii; the opposite was true for wolves from the central Rocky Mountains. Overall, mechanistic predictors were more informative of seroprevalence trends than latitude and longitude. Individual host characteristics as well as inherent features of ecosystems determined pathogen exposure risk on a large scale. This work emphasizes the importance of biogeographic wildlife surveillance, and we expound upon avenues of future research of cross-species transmission, spillover, and spatial variation in pathogen infection.
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http://dx.doi.org/10.1038/s41598-021-81192-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881161PMC
February 2021

Lumacaftor/ivacaftor-associated health stabilisation in adults with severe cystic fibrosis.

ERJ Open Res 2021 Jan 1;7(1). Epub 2021 Feb 1.

Cystic Fibrosis Service, Dept of Respiratory Medicine, Alfred Hospital, Melbourne, Australia.

Introduction: Lumacaftor/ivacaftor (LUM/IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with forced expiratory volume in 1 s (FEV) % pred >40%. We assessed the clinical utility of LUM/IVA in all eligible adult CF patients with FEV % pred <40% treated for at least 1 year under a single-centre managed access programme.

Methods: Following clinical optimisation, eligible patients (n=40) with FEV % pred <40% were commenced on LUM/IVA and monitored for tolerance and clinical outcomes, including health service utilisation, pulmonary function, weight and body composition. 24 patients reached 1 year of treatment by the time of evaluation. Six patients discontinued due to adverse events (five for increased airways reactivity) and three underwent lung transplantation.

Results: In comparison with the year prior to LUM/IVA commencement, significant reductions (median per year) were observed in the treatment year in the number of pulmonary exacerbations requiring hospitalisation (from 3 to 1.5; p=0.0002), hospitalisation days (from 27 to 17; p=0.0002) and intravenous antibiotic (IVAB) usage days (from 45 to 27; p=0.0007). Mean±sd change in FEV % pred was -2.10±1.18% per year in the year prior, with the decline reversed in the year following (+1.45±1.13% per year; p=0.035), although there was significant heterogeneity in individual responses. Mean±sd weight gain at 1 year was 2.5±4.1 kg (p=0.0007), comprising mainly fat mass (mean 2.2 kg). The proportion of patients severely underweight (body mass index <18.5 kg·m) decreased from 33% at baseline to 13% at 1 year (p=0.003).

Conclusion: This real-world evaluation study demonstrated benefits over several clinical domains (infective exacerbations requiring hospitalisation, IVABs, pulmonary function decline and nutritional parameters) in CF patients with severe lung disease.
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http://dx.doi.org/10.1183/23120541.00203-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861032PMC
January 2021

Updated prevalence, predictors and treatment outcomes for bronchiolitis obliterans syndrome after allogeneic stem cell transplantation.

Respir Med 2020 Dec 28;177:106286. Epub 2020 Dec 28.

Alfred Health, Melbourne, Australia.

Introduction: Bronchiolitis obliterans syndrome (BOS) after allogeneic haemopoietic stem cell transplant (HSCT) is an under-recognised and difficult to treat disease. This occurs in the context of limited clinical research and inconsistent diagnostic criteria.

Method: Retrospective data was collected on 275 patients who underwent allogeneic HSCT at an Australian tertiary hospital between 2007 and 2017. The prevalence of BOS, defined by 2014 National Institute of Health criteria, as well as predictors for BOS and mortality were determined. Treatment outcomes, using serial spirometry, were compared between patients who received early versus late immunosuppression for BOS.

Results: The prevalence of BOS was 9.1%. Myeloablative conditioning (OR: 2.7, 95%CI: 1.13-6.50, p = 0.03) and extra-pulmonary chronic graft-versus-host disease (OR 2.62, 95% CI: 1.04-6.60, p = 0.04) were associated with BOS. There was reduced median survival in the BOS group compared with the non-BOS group, but this was not statistically significant (4.1years (IQR: 2.8, 6.8) versus 4.6years (IQR: 2.4, 7.8), respectively, p = 0.33). The vast majority (87.5%) of BOS patients failed to attain improvement in FEV1 at 12 months, regardless of treatment strategy. Patients who underwent a late immunosuppression strategy had worse mean FEV1 decline compared to those who received early immunosuppression (-36.3% versus -1.6%, respectively, p = 0.03).

Conclusion: BOS is a common and progressive disease following HSCT and is largely refractory to current treatment strategies. Compared to late immunosuppression, early augmentation of immunosuppression may slow lung function deterioration in the short term. However, further research is urgently needed to identify effective prevention and treatment strategies for BOS.
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http://dx.doi.org/10.1016/j.rmed.2020.106286DOI Listing
December 2020

Assessing spirometry competence through certification in community-based healthcare settings in Australia and New Zealand: A position paper of the Australian and New Zealand Society of Respiratory Science.

Respirology 2021 Feb 14;26(2):147-152. Epub 2020 Dec 14.

Respiratory Laboratory, Hawke's Bay District Health Board, New Zealand, Hawke's Bay, New Zealand.

Spirometry has been established as an essential test for diagnosing and monitoring respiratory disease, particularly asthma and COPD, as well as in occupational health surveillance. In Australia and New Zealand, there is currently no pathway for spirometry operators in community-based healthcare settings to demonstrate spirometry competence. The Australia and New Zealand Society of Respiratory Science (ANZSRS) has identified a need for developing a pathway for operators working in community-based practices in Australia and New Zealand to demonstrate spirometry competence and certification. Spirometry certification provides evidence to patients, clients, employers and organizations that an individual has participated in an assessment process that qualifies them to perform spirometry to current international spirometry standards set out by the American Thoracic Society and the European Respiratory Society (ATS/ERS). This document describes a competence assessment pathway that incorporates a portfolio and practical assessment. The completion of this pathway and the award of certification confer an individual is competent to perform spirometry for 3 years, after which re-certification is required. The adoption of this competency assessment and certification process by specialist organizations, and the commitment of operators performing spirometry to undergo this process, will enhance spirometry quality and practice in community-based healthcare settings.
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http://dx.doi.org/10.1111/resp.13987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898916PMC
February 2021

Combination Therapies Including Cilofexor and Firsocostat for Bridging Fibrosis and Cirrhosis Attributable to NASH.

Hepatology 2021 Feb;73(2):625-643

Texas Liver Institute, UT Health San Antonio, San Antonio, TX.

Background And Aims: Advanced fibrosis attributable to NASH is a leading cause of end-stage liver disease.

Approach And Results: In this phase 2b trial, 392 patients with bridging fibrosis or compensated cirrhosis (F3-F4) were randomized to receive placebo, selonsertib 18 mg, cilofexor 30 mg, or firsocostat 20 mg, alone or in two-drug combinations, once-daily for 48 weeks. The primary endpoint was a ≥1-stage improvement in fibrosis without worsening of NASH between baseline and 48 weeks based on central pathologist review. Exploratory endpoints included changes in NAFLD Activity Score (NAS), liver histology assessed using a machine learning (ML) approach, liver biochemistry, and noninvasive markers. The majority had cirrhosis (56%) and NAS ≥5 (83%). The primary endpoint was achieved in 11% of placebo-treated patients versus cilofexor/firsocostat (21%; P = 0.17), cilofexor/selonsertib (19%; P = 0.26), firsocostat/selonsertib (15%; P = 0.62), firsocostat (12%; P = 0.94), and cilofexor (12%; P = 0.96). Changes in hepatic collagen by morphometry were not significant, but cilofexor/firsocostat led to a significant decrease in ML NASH CRN fibrosis score (P = 0.040) and a shift in biopsy area from F3-F4 to ≤F2 fibrosis patterns. Compared to placebo, significantly higher proportions of cilofexor/firsocostat patients had a ≥2-point NAS reduction; reductions in steatosis, lobular inflammation, and ballooning; and significant improvements in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, bile acids, cytokeratin-18, insulin, estimated glomerular filtration rate, ELF score, and liver stiffness by transient elastography (all P ≤ 0.05). Pruritus occurred in 20%-29% of cilofexor versus 15% of placebo-treated patients.

Conclusions: In patients with bridging fibrosis and cirrhosis, 48 weeks of cilofexor/firsocostat was well tolerated, led to improvements in NASH activity, and may have an antifibrotic effect. This combination offers potential for fibrosis regression with longer-term therapy in patients with advanced fibrosis attributable to NASH.
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http://dx.doi.org/10.1002/hep.31622DOI Listing
February 2021

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Authors:
Wesley H Self Matthew W Semler Lindsay M Leither Jonathan D Casey Derek C Angus Roy G Brower Steven Y Chang Sean P Collins John C Eppensteiner Michael R Filbin D Clark Files Kevin W Gibbs Adit A Ginde Michelle N Gong Frank E Harrell Douglas L Hayden Catherine L Hough Nicholas J Johnson Akram Khan Christopher J Lindsell Michael A Matthay Marc Moss Pauline K Park Todd W Rice Bryce R H Robinson David A Schoenfeld Nathan I Shapiro Jay S Steingrub Christine A Ulysse Alexandra Weissman Donald M Yealy B Taylor Thompson Samuel M Brown Jay Steingrub Howard Smithline Bogdan Tiru Mark Tidswell Lori Kozikowski Sherell Thornton-Thompson Leslie De Souza Peter Hou Rebecca Baron Anthony Massaro Imoigele Aisiku Lauren Fredenburgh Raghu Seethala Lily Johnsky Richard Riker David Seder Teresa May Michael Baumann Ashley Eldridge Christine Lord Nathan Shapiro Daniel Talmor Thomas O’Mara Charlotte Kirk Kelly Harrison Lisa Kurt Margaret Schermerhorn Valerie Banner-Goodspeed Katherine Boyle Nicole Dubosh Michael Filbin Kathryn Hibbert Blair Parry Kendall Lavin-Parsons Natalie Pulido Brendan Lilley Carl Lodenstein Justin Margolin Kelsey Brait Alan Jones James Galbraith Rebekah Peacock Utsav Nandi Taylor Wachs Michael Matthay Kathleen Liu Kirsten Kangelaris Ralph Wang Carolyn Calfee Kimberly Yee Gregory Hendey Steven Chang George Lim Nida Qadir Andrea Tam Rebecca Beutler Joseph Levitt Jenny Wilson Angela Rogers Rosemary Vojnik Jonasel Roque Timothy Albertson James Chenoweth Jason Adams Skyler Pearson Maya Juarez Eyad Almasri Mohamed Fayed Alyssa Hughes Shelly Hillard Ryan Huebinger Henry Wang Elizabeth Vidales Bela Patel Adit Ginde Marc Moss Amiran Baduashvili Jeffrey McKeehan Lani Finck Carrie Higgins Michelle Howell Ivor Douglas Jason Haukoos Terra Hiller Carolynn Lyle Alicia Cupelo Emily Caruso Claudia Camacho Stephanie Gravitz James Finigan Christine Griesmer Pauline Park Robert Hyzy Kristine Nelson Kelli McDonough Norman Olbrich Mark Williams Raj Kapoor Jean Nash Meghan Willig Henry Ford Jayna Gardner-Gray Mayur Ramesh Montefiore Moses Michelle Ng Gong Michael Aboodi Ayesha Asghar Omowunmi Amosu Madeline Torres Savneet Kaur Jen-Ting Chen Aluko Hope Brenda Lopez Kathleen Rosales Jee Young You Jarrod Mosier Cameron Hypes Bhupinder Natt Bryan Borg Elizabeth Salvagio Campbell R Duncan Hite Kristin Hudock Autumn Cresie Faysal Alhasan Jose Gomez-Arroyo Abhijit Duggal Omar Mehkri Andrei Hastings Debasis Sahoo Francois Abi Fadel Susan Gole Valerie Shaner Allison Wimer Yvonne Meli Alexander King Thomas Terndrup Matthew Exline Sonal Pannu Emily Robart Sarah Karow Catherine Hough Bryce Robinson Nicholas Johnson Daniel Henning Monica Campo Stephanie Gundel Sakshi Seghal Sarah Katsandres Sarah Dean Akram Khan Olivia Krol Milad Jouzestani Peter Huynh Alexandra Weissman Donald Yealy Denise Scholl Peter Adams Bryan McVerry David Huang Derek Angus Jordan Schooler Steven Moore Clark Files Chadwick Miller Kevin Gibbs Mary LaRose Lori Flores Lauren Koehler Caryn Morse John Sanders Caitlyn Langford Kristen Nanney Masiku MdalaGausi Phyllis Yeboah Peter Morris Jamie Sturgill Sherif Seif Evan Cassity Sanjay Dhar Marjolein de Wit Jessica Mason Andrew Goodwin Greg Hall Abbey Grady Amy Chamberlain Samuel Brown Joseph Bledsoe Lindsay Leither Ithan Peltan Nathan Starr Melissa Fergus Valerie Aston Quinn Montgomery Rilee Smith Mardee Merrill Katie Brown Brent Armbruster Estelle Harris Elizabeth Middleton Robert Paine Stacy Johnson Macy Barrios John Eppensteiner Alexander Limkakeng Lauren McGowan Tedra Porter Andrew Bouffler J. Clancy Leahy Bennet deBoisblanc Matthew Lammi Kyle Happel Paula Lauto Wesley Self Jonathan Casey Matthew Semler Sean Collins Frank Harrell Christopher Lindsell Todd Rice William Stubblefield Christopher Gray Jakea Johnson Megan Roth Margaret Hays Donna Torr Arwa Zakaria David Schoenfeld Taylor Thompson Douglas Hayden Nancy Ringwood Cathryn Oldmixon Christine Ulysse Richard Morse Ariela Muzikansky Laura Fitzgerald Samuel Whitaker Adrian Lagakos Roy Brower Lora Reineck Neil Aggarwal Karen Bienstock Michelle Freemer Myron Maclawiw Gail Weinmann Laurie Morrison Mark Gillespie Richard Kryscio Daniel Brodie Wojciech Zareba Anne Rompalo Michael Boeckh Polly Parsons Jason Christie Jesse Hall Nicholas Horton Laurie Zoloth Neal Dickert Deborah Diercks

JAMA 2020 12;324(21):2165-2176

Division of Pulmonary and Critical Care Medicine, Intermountain Medical Center, Murray, Utah.

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.

Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19.

Design, Setting, And Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.

Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237).

Main Outcomes And Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality.

Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]).

Conclusions And Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.

Trial Registration: ClinicalTrials.gov: NCT04332991.
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http://dx.doi.org/10.1001/jama.2020.22240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653542PMC
December 2020

Ecological insights from three decades of animal movement tracking across a changing Arctic.

Authors:
Sarah C Davidson Gil Bohrer Eliezer Gurarie Scott LaPoint Peter J Mahoney Natalie T Boelman Jan U H Eitel Laura R Prugh Lee A Vierling Jyoti Jennewein Emma Grier Ophélie Couriot Allicia P Kelly Arjan J H Meddens Ruth Y Oliver Roland Kays Martin Wikelski Tomas Aarvak Joshua T Ackerman José A Alves Erin Bayne Bryan Bedrosian Jerrold L Belant Andrew M Berdahl Alicia M Berlin Dominique Berteaux Joël Bêty Dmitrijs Boiko Travis L Booms Bridget L Borg Stan Boutin W Sean Boyd Kane Brides Stephen Brown Victor N Bulyuk Kurt K Burnham David Cabot Michael Casazza Katherine Christie Erica H Craig Shanti E Davis Tracy Davison Dominic Demma Christopher R DeSorbo Andrew Dixon Robert Domenech Götz Eichhorn Kyle Elliott Joseph R Evenson Klaus-Michael Exo Steven H Ferguson Wolfgang Fiedler Aaron Fisk Jérôme Fort Alastair Franke Mark R Fuller Stefan Garthe Gilles Gauthier Grant Gilchrist Petr Glazov Carrie E Gray David Grémillet Larry Griffin Michael T Hallworth Autumn-Lynn Harrison Holly L Hennin J Mark Hipfner James Hodson James A Johnson Kyle Joly Kimberly Jones Todd E Katzner Jeff W Kidd Elly C Knight Michael N Kochert Andrea Kölzsch Helmut Kruckenberg Benjamin J Lagassé Sandra Lai Jean-François Lamarre Richard B Lanctot Nicholas C Larter A David M Latham Christopher J Latty James P Lawler Don-Jean Léandri-Breton Hansoo Lee Stephen B Lewis Oliver P Love Jesper Madsen Mark Maftei Mark L Mallory Buck Mangipane Mikhail Y Markovets Peter P Marra Rebecca McGuire Carol L McIntyre Emily A McKinnon Tricia A Miller Sander Moonen Tong Mu Gerhard J D M Müskens Janet Ng Kerry L Nicholson Ingar Jostein Øien Cory Overton Patricia A Owen Allison Patterson Aevar Petersen Ivan Pokrovsky Luke L Powell Rui Prieto Petra Quillfeldt Jennie Rausch Kelsey Russell Sarah T Saalfeld Hans Schekkerman Joel A Schmutz Philipp Schwemmer Dale R Seip Adam Shreading Mónica A Silva Brian W Smith Fletcher Smith Jeff P Smith Katherine R S Snell Aleksandr Sokolov Vasiliy Sokolov Diana V Solovyeva Mathew S Sorum Grigori Tertitski J F Therrien Kasper Thorup T Lee Tibbitts Ingrid Tulp Brian D Uher-Koch Rob S A van Bemmelen Steven Van Wilgenburg Andrew L Von Duyke Jesse L Watson Bryan D Watts Judy A Williams Matthew T Wilson James R Wright Michael A Yates David J Yurkowski Ramūnas Žydelis Mark Hebblewhite

Science 2020 11;370(6517):712-715

Wildlife Biology Program, Department of Ecosystem and Conservation Sciences, W.A. Franke College of Forestry and Conservation, University of Montana, Missoula, MT, USA.

The Arctic is entering a new ecological state, with alarming consequences for humanity. Animal-borne sensors offer a window into these changes. Although substantial animal tracking data from the Arctic and subarctic exist, most are difficult to discover and access. Here, we present the new Arctic Animal Movement Archive (AAMA), a growing collection of more than 200 standardized terrestrial and marine animal tracking studies from 1991 to the present. The AAMA supports public data discovery, preserves fundamental baseline data for the future, and facilitates efficient, collaborative data analysis. With AAMA-based case studies, we document climatic influences on the migration phenology of eagles, geographic differences in the adaptive response of caribou reproductive phenology to climate change, and species-specific changes in terrestrial mammal movement rates in response to increasing temperature.
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http://dx.doi.org/10.1126/science.abb7080DOI Listing
November 2020

A Phase 2 Double Blinded, Randomized Controlled Trial of Saroglitazar in Patients With Nonalcoholic Steatohepatitis.

Clin Gastroenterol Hepatol 2020 Nov 2. Epub 2020 Nov 2.

Division of Gastroenterology and Hepatology, Virginia Commonwealth University, Richmond, Virginia.

Nonalcoholic steatohepatitis (NASH), the clinically aggressive variant of nonalcoholic fatty liver disease, is characterized by hepatocellular injury and inflammation. Patients with NASH are at higher risk of progression to cirrhosis and it is therefore targeted for drug development efforts. Lifestyle modifications and weight loss are the only recommended modalities and no drug is yet approved for the treatment of patients with NASH. Saroglitazar is a dual PPAR α/γ agonist, which has shown promise for treatment of nonalcoholic fatty liver disease. Because of its combined PPAR-α/γ agonism, it has a clinically favorable impact of glucose and lipid metabolism. Saroglitazar has shown to improve liver-related histology in patients with NASH and was recently approved for treatment of NASH in India. The current study builds on the published literature in this proof of concept study to determine if there is a signal for histologic improvement of NASH with saroglitazar in a Western population.
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http://dx.doi.org/10.1016/j.cgh.2020.10.051DOI Listing
November 2020

Chest Pain Severity Rating Is a Poor Predictive Tool in the Diagnosis of ST-Segment Elevation Myocardial Infarction.

Crit Pathw Cardiol 2020 Aug 28. Epub 2020 Aug 28.

Essentia Health Heart and Vascular Center, Duluth, MN.

Current ST-segment elevation myocardial infarction (STEMI) guidelines require persistent electrocardiogram (ECG) ST-segment elevation, cardiac enzyme changes, and symptoms of myocardial ischemia. Chest pain is the determinant symptom, often measured using an 11-point scale (0-10). Greater severity of chest pain is presumed to be associated with a stronger likelihood of a true positive STEMI diagnosis. This retrospective observational cohort study considered consecutive STEMI patients from 5/02/2009-12/31/2018. Analysis of standard STEMI metrics included positive ECG-to-device and first medical contact (FMC)-to-device times, presence of comorbidities, false positive diagnosis, 30-day and 1-year mortality, and 30-day readmission. Chest pain severity was assessed upon admission to the primary percutaneous coronary intervention (PPCI) hospital. We analyzed 1409 STEMI activations (69% male, 66.3 years old ± 13.7 years). Of these, 251 (17.8%) had no obstructive lesion, consistent with false positive STEMI. 466 (33.1%) reported chest pain rating of 0 on admission, 378 (26.8%) reported mild pain (1-3), 300 (21.3%) moderate (4-6), and 265 (18.8%) severe (7-10). Patients presenting without chest pain had a significantly higher rate of false positive STEMI diagnosis. Increasing chest pain severity was associated with decreased time from FMC to device, and decreased in-hospital, 30-day and 1-year mortality. Severity of chest pain on admission did not correlate to the likelihood of a true positive STEMI diagnosis, although it was associated with improved patient prognosis, in the form of improved outcomes, and shorter times to reperfusion.
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http://dx.doi.org/10.1097/HPC.0000000000000241DOI Listing
August 2020

Cohort Profile: The Hazelwood Health Study Adult Cohort.

Int J Epidemiol 2021 Jan;49(6):1777-1778

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

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http://dx.doi.org/10.1093/ije/dyaa083DOI Listing
January 2021

Sink bathing burns: A unique opportunity for an injury prevention initiative.

Burns 2020 12 31;46(8):1875-1879. Epub 2020 May 31.

Children's Hospital of Michigan, Detroit, MI, United States. Electronic address:

Sink-bathing is common practice among parents. However, this puts infants and young children at unrecognized risk for burn injuries. As the only verified pediatric burn center in a large urban area, we treat burn patients from a large variation in socioeconomic status. This provides us a unique opportunity to examine sink-burn injury patterns, circumstances surrounding these burns, identify areas with high incidence and put in place an injury prevention outreach initiative. This retrospective study included patients treated for sink-bathing burns at our burn center in an 8.5-year period. Analysis of 71 patients revealed infants under one year of age are most commonly afflicted. Additionally, that families of low-socioeconomic means are disproportionately affected. Understanding the different circumstances surrounding sink-bathing burns allows us to be more specific in our community education efforts and efficiently guide our resources.
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http://dx.doi.org/10.1016/j.burns.2020.05.016DOI Listing
December 2020

Pediatric dog bite outcomes: infections and scars.

Trauma Surg Acute Care Open 2020 10;5(1):e000445. Epub 2020 Jun 10.

Department of Pediatric Surgery, Children's Hospital of Michigan, Detroit, Michigan, USA.

Background: There is little consensus on the management of dog bite victims. Few studies have examined long-term patient outcomes. This study was designed to evaluate two outcomes: infection and unfavorable scar formation.

Methods: A retrospective study of dog bite cases from January 2013 to May 2016 was conducted at our level I pediatric trauma center. Forty-five patients were identified who received definitive repair and had long-term follow-up for reasons other than rabies vaccination. Variables recorded were wound characteristics including presence of tissue loss, location in the hospital of the wound repair procedure, personnel performing the repair, postrepair infection, and a binary assessment of unfavorable scar formation.

Results: Unfavorable scarring was not significantly related to either repair location or personnel. Rate of infection was not significantly related to repair location. However, infection rate was significantly related to personnel performing the repair (p=0.002), with 8 of 11 (73%) infections after repair by emergency physicians compared with surgeons.

Discussion: The presence of infection was significantly related to bedside repair by emergency physicians. The data are suggestive of differences in wound preparation and repair technique between emergency department and surgical personnel. Standardizing technique could reduce infectious complications and long-term morbidity associated with repairing dog bites and other contaminated wounds. A robust and practical classification system for dog bite wounds would be helpful in stratifying these wounds for research comparison and healthcare triage.

Level Of Evidence: The level of evidence for this retrospective study is level III.
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http://dx.doi.org/10.1136/tsaco-2020-000445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292034PMC
June 2020

Recommended Intake of Key Food Groups and Cardiovascular Risk Factors in Australian Older, Rural-Dwelling Adults.

Nutrients 2020 Mar 23;12(3). Epub 2020 Mar 23.

School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Rd, Melbourne, VIC 3004, Australia.

This study examined the relationship between diet quality scores and cardiometabolic risk factors in regionally-dwelling older Australian adults with increased cardiovascular risk. This study was a cross-sectional analysis of demographic, anthropometric, and cardiometabolic risk factor data from 458 participants of the Cardiovascular Stream of the Hazelwood Health Study. Participants completed a 120 item semi-quantitative food frequency questionnaire. Multivariable linear regression adjusting for age, sex, smoking, physical activity, education, diabetes, and body mass index was used to examine the relationship between diet and cardiometabolic risk factors. Mean (SD) age of participants was 71 (8) years, and 55% were male. More than half of men and women did not meet recommended intakes of fibre, while 60% of men and 42% of women exceeded recommended dietary sodium intakes. Higher diet quality in terms of intake of vegetables, grains, and non-processed meat, as well as intake of non-fried fish, was associated with more favourable cardiometabolic risk profiles, while sugar-sweetened soft drink intake was strongly associated with adverse cardiometabolic risk factor levels. In older, regionally-dwelling adults, dietary public health strategies that address whole grain products, vegetable and fish consumption, and sugar-sweetened soft-drink intake may be of benefit in reducing cardiometabolic risk.
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http://dx.doi.org/10.3390/nu12030860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146596PMC
March 2020

Author Correction: Longest terrestrial migrations and movements around the world.

Sci Rep 2020 Jan 15;10(1):753. Epub 2020 Jan 15.

Wildlife Biology Program, W. A. Franke College of Forestry and Conservation, University of Montana, Missoula, Montana, 59812, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-57446-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6960154PMC
January 2020

Effectiveness of a locally produced ready-to-use supplementary food in preventing growth faltering for children under 2 years in Cambodia: a cluster randomised controlled trial.

Matern Child Nutr 2020 01;16(1):e12896

UMR-204 Nutripass, Institut de Recherche pour le Développement, IRD/UM/SupAgro, Montpellier, France.

This cluster randomised controlled trial tested the effectiveness of a locally produced, fish-based, ready-to-use supplementary food (RUSF) to prevent growth faltering (decline in z-scores). Cambodian infants (n= 485), aged 6 to 11 months, were randomised by site to receive the RUSF, Corn-Soy Blend++ (CSB++), micronutrient powders (MNP), or no supplement (control). The intervention was for 6 months. In unadjusted analysis, the control group had statistically significantly decreased weight-for-age z-scores (WAZ; -0.02, 95%CI = -0.03 - -0.01, P= 0.001) and height-for-age z-scores (HAZ; -0.07, 95%CI = -0.09 - -0.05, P < 0.001), and increased mid-upper arm-circumference (MUAC; 0.02cm, 95%CI = 0.01 - 0.04, P = 0.010), but no statistically significant change in weight-for-height z-scores (WHZ). The RUSF group did not differ significantly from the control for WAZ, HAZ or WHZ (in other words, WAZ and HAZ decreased and WHZ did not change), but had increased MUAC in comparison to the control (0.04cm, 95%CI = 0.01 - 0.06, P = 0.008). There were no statistically significant differences between the RUSF group and the CSB++ or MNP groups with respect to WAZ, HAZ, WHZ or MUAC. Interestingly, in adjusted analysis, low consumers of RUSF had increased WAZ, WHZ and MUAC (0.03, 95%CI = 0.01-0.06, P = 0.006; 0.04, 95%CI = 0.01-0.08, P = 0.026; and 0.05cm, 95%CI = 0.02-0.09, P = 0.004, respectively) compared with the control. The novel RUSF, particularly in small quantities, protected against ponderal growth faltering, but the improvements were of limited clinical significance.
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http://dx.doi.org/10.1111/mcn.12896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7038903PMC
January 2020

Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

Authors:
Duminda N Wijeysundera W Scott Beattie Graham S Hillis Tom E F Abbott Mark A Shulman Gareth L Ackland C David Mazer Paul S Myles Rupert M Pearse Brian H Cuthbertson P S Myles M A Shulman S Wallace C Farrington B Thompson M Ellis B Borg R K Kerridge J Douglas J Brannan J Pretto M G Godsall N Beauchamp S Allen A Kennedy E Wright J Malherbe H Ismail B Riedel A Melville H Sivakumar A Murmane K Kenchington Y Kirabiyik U Gurunathan C Stonell K Brunello K Steele O Tronstad P Masel A Dent E Smith A Bodger M Abolfathi P Sivalingam A Hall T W Painter S Macklin A Elliott A M Carrera N C S Terblanche S Pitt J Samuels C Wilde K Leslie A MacCormick D Bramley A M Southcott J Grant H Taylor S Bates M Towns A Tippett F Marshall C D Mazer J Kunasingam A Yagnik C Crescini S Yagnik C J L McCartney S Choi P Somascanthan K Flores D N Wijeysundera W S Beattie K Karkouti H A Clarke A Jerath S A McCluskey M Wasowicz J T Granton L Day J Pazmino-Canizares P Oh R Belliard L Lee K Dobson V Chan R Brull N Ami M Stanbrook K Hagen D Campbell T Short J Van Der Westhuizen K Higgie H Lindsay R Jang C Wong D Mcallister M Ali J Kumar E Waymouth C Kim J Dimech M Lorimer J Tai R Miller R Sara A Collingwood S Olliff S Gabriel H Houston P Dalley S Hurford A Hunt L Andrews L Navarra A Jason-Smith H Thompson N McMillan G Back B L Croal M Lum D Martin S James H Filipe M Pinto S Kynaston R M Pearse T E F Abbott M Phull C Beilstein P Bodger K Everingham Y Hu E Niebrzegowska C Corriea T Creary M Januszewska T Ahmad J Whalley R Haslop J McNeil A Brown N MacDonald M Pakats K Greaves S Jhanji R Raobaikady E Black M Rooms H Lawrence M Koutra K Pirie M Gertsman S Jack M Celinski D Levett M Edwards K Salmon C Bolger L Loughney L Seaward H Collins B Tyrell N Tantony K Golder G L Ackland R C M Stephens L Gallego-Paredes A Reyes A Gutierrez Del Arroyo A Raj R Lifford

Br J Anaesth 2020 03 19;124(3):261-270. Epub 2019 Dec 19.

Whipps Cross Hospital, United Kingdom.

Background: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications.

Methods: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes.

Results: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05).

Conclusions: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.
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http://dx.doi.org/10.1016/j.bja.2019.11.025DOI Listing
March 2020

Circumstances surrounding gun violence with youths in an urban setting.

J Pediatr Surg 2020 Jul 1;55(7):1234-1237. Epub 2019 Nov 1.

Department of Pediatric Surgery, Children's Hospital of Michigan, Detroit, Michigan.

Background: Our pediatric trauma center has noted an increase in the occurrence of gunshot wounds in children. We aimed to understand the circumstances surrounding these injuries in order to provide targeted injury prevention methodologies.

Methods: A retrospective review was performed on patients who presented with a gunshot wound to our Level I Pediatric Trauma Center and two neighboring Adult Trauma Centers between 2013 and 2017.

Results: Three hundred twenty-six patients (6 months to 18 years) were treated for gunshot wounds. Patients were African American (86%), Caucasian (9%), and other races (5%). Eight zip-codes were identified as high-risk, accounting for 52% of patients. Most injuries (86%) were from powder firearms. Known circumstances (n = 275) included drive-by shootings (47%), unlocked guns (19%), crime related (13%), altercation between adolescents (7%), cross-fire from adult altercation (6%), home invasion (6%), and suicide attempts (2%). There was a progressive increase of 50% over the last 4 years. The increase in incidence was predominantly from an increase in drive-by shootings; however, the incidence of injuries from unlocked guns has remained relatively constant per year. Mortality was 6%.

Conclusion: Identifying high-risk zones for drive-by shootings and other crimes is critical for developing system-focused interventions. Zip-code data stratified by age and circumstances, will allow for targeted community outreach on gun safety education, in an effort to reduce the incidence of injuries from unlocked guns.

Level Of Evidence: Prognostic and Epidemiologic study, Level III.
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http://dx.doi.org/10.1016/j.jpedsurg.2019.09.015DOI Listing
July 2020

Longest terrestrial migrations and movements around the world.

Sci Rep 2019 10 25;9(1):15333. Epub 2019 Oct 25.

Wildlife Biology Program, W. A. Franke College of Forestry and Conservation, University of Montana, Missoula, Montana, 59812, USA.

Long-distance terrestrial migrations are imperiled globally. We determined both round-trip migration distances (straight-line measurements between migratory end points) and total annual movement (sum of the distances between successive relocations over a year) for a suite of large mammals that had potential for long-distance movements to test which species displayed the longest of both. We found that caribou likely do exhibit the longest terrestrial migrations on the planet, but, over the course of a year, gray wolves move the most. Our results were consistent with the trophic-level based hypothesis that predators would move more than their prey. Herbivores in low productivity environments moved more than herbivores in more productive habitats. We also found that larger members of the same guild moved less than smaller members, supporting the 'gastro-centric' hypothesis. A better understanding of migration and movements of large mammals should aid in their conservation by helping delineate conservation area boundaries and determine priority corridors for protection to preserve connectivity. The magnitude of the migrations and movements we documented should also provide guidance on the scale of conservation efforts required and assist conservation planning across agency and even national boundaries.
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http://dx.doi.org/10.1038/s41598-019-51884-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814704PMC
October 2019

Development and testing of locally-produced ready-to-use therapeutic and supplementary foods (RUTFs and RUSFs) in Cambodia: lessons learned.

BMC Public Health 2019 Aug 30;19(1):1200. Epub 2019 Aug 30.

UMR Nutripass, Institut de Recherche pour le Développement, IRD/UM/SupAgro, Montpellier, France.

Background: Rates of childhood undernutrition are persistently high in Cambodia. Existing ready-to-use supplementary and therapeutic foods (RUSFs and RUTFs) have had limited acceptance and effectiveness. Therefore, our project developed and trialled a locally-produced, multiple micronutrient fortified lipid-based nutrient supplement (LNS) with therapeutic and supplementary versions. This ready-to-use food (RUF) is innovative in that, unlike many RUFs, it contains fish instead of milk. Development began in 2013 and the RUF was finalised in 2015. From 2015 until the present, both the RUTF and the RUSF versions were trialled for acceptability and effectiveness.

Methods: This paper draws on project implementation records and semi-structured interviews to describe the partnership between the Cambodian Ministries of Health and Agriculture, Forestry and Fisheries, UNICEF, the French National Research Institute for Sustainable Development (IRD), universities, and Vissot factory. It discusses the project implementation and lessons learned from the development and trialling process, and insights into positioning nutrition on the health agenda in low and middle-income countries.

Results: The lessons learned relate to the importance of project planning, management, and documentation in order to seize opportunities in the research, policy, advocacy, and programming environment while ensuring adequate day-to-day project administration and resourcing.

Conclusions: We conclude that projects such as ours, that collaborate to develop and test novel, locally-produced RUTFs and RUSFs, offer an exciting opportunity to respond to both local programmatic and broader research needs.
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http://dx.doi.org/10.1186/s12889-019-7445-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717373PMC
August 2019

Deletion of the RNA regulator HuR in tumor-associated microglia and macrophages stimulates anti-tumor immunity and attenuates glioma growth.

Glia 2019 12 10;67(12):2424-2439. Epub 2019 Aug 10.

Department of Neurology, University of Alabama, Birmingham, Alabama.

Glioblastoma is a malignant brain tumor that portends a poor prognosis. Its resilience, in part, is related to a remarkable capacity for manipulating the microenvironment to promote its growth and survival. Microglia/macrophages are prime targets, being drawn into the tumor and stimulated to produce factors that support tumor growth and evasion from the immune system. Here we show that the RNA regulator, HuR, plays a key role in the tumor-promoting response of microglia/macrophages. Knockout (KO) of HuR led to reduced tumor growth and proliferation associated with prolonged survival in a murine model of glioblastoma. Analysis of tumor composition by flow cytometry showed that tumor-associated macrophages (TAMs) were decreased, more polarized toward an M1-like phenotype, and had reduced PD-L1 expression. There was an overall increase in infiltrating CD4 cells, including Th1 and cytotoxic effector cells, and a concomitant reduction in tumor-associated polymorphonuclear myeloid-derived suppressor cells. Molecular and cellular analyses of HuR KO TAMs and cultured microglia showed changes in migration, chemoattraction, and chemokine/cytokine profiles that provide potential mechanisms for the altered tumor microenvironment and reduced tumor growth in HuR KO mice. In summary, HuR is a key modulator of pro-glioma responses by microglia/macrophages through the molecular regulation of chemokines, cytokines, and other factors. Our findings underscore the relevance of HuR as a therapeutic target in glioblastoma.
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http://dx.doi.org/10.1002/glia.23696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008520PMC
December 2019

Ovarian fluid in the three-spined stickleback Gasterosteus aculeatus: effects of egg overripening and sex steroid treatment.

J Fish Biol 2019 Mar;94(3):446-457

Department of Zoology, Stockholm University, Stockholm, Sweden.

The ovarian fluid properties of the three-spined stickleback Gasterosteus aculeatus were studied in overripe and non-overripe ovulated female sticklebacks and in females that were implanted with Silastic capsules containing testosterone (T), oestradiol (E2), 17,20β-dihydroxypregn-4-en-3-one (17,20β-P) or progesterone (P4) into the abdominal cavity. Overripe females had less ovarian fluid than non-overripe females, but with higher dry mass, higher protein concentration and lower viscosity. T and 17,20β-P increased the amount of ovarian fluid and the fluid protein concentration was increased by 17,20β-P. 1-D sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that ovarian fluid contains several proteins, with high individual variability but with no consistent differences between groups. Some of the ovarian fluid proteins appeared to correspond to proteins from the eggs. The results suggest that secretion of ovarian fluid may be influenced by steroid hormones and that changes in its properties are related to the overripening of ovulated eggs. In at least some respects it appears that the changes in the ovarian fluid is a result, rather than the cause of overripening.
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http://dx.doi.org/10.1111/jfb.13915DOI Listing
March 2019

Acceptability of locally-produced Ready-to-Use Supplementary Food (RUSF) for children under two years in Cambodia: A cluster randomised trial.

Matern Child Nutr 2019 07 20;15(3):e12780. Epub 2019 Feb 20.

UMR-204 Nutripass, Institut de Recherche pour le Développement, IRD/UM/SupAgro, Montpellier, France.

In Cambodia, existing food products for treating or preventing undernutrition have met with limited success. Therefore, in 2014, alternative ready-to-use foods were developed. This trial aimed to assess the acceptability of the novel ready-to-use supplementary food (RUSF) as a snack or mixed with borbor (white rice porridge), compared with corn-soy blend plus plus (CSB++) and borbor fortified with micronutrient powder (MNP). The nonblinded, randomised 4 × 4 crossover trial recruited 95 children aged 9-23 months from communities in peri-urban Phnom Penh. Small quantities (100 g for porridges, 42 g for snack) of each food were offered for three consecutive days at testing sites (homes of health volunteers). Main outcomes were children's consumption, caregivers' assessment of children's preferences, and caregivers' ranking of the foods. Median percentage consumed of the test food servings ranged from 21 to 50% (p = 0.003). The odds of children consuming over 50% were greatest for borbor fortified with MNP versus RUSF snack (unadjusted OR = 6.79, CI = 2.80-16.47, p < 0.001). However, the median energy children received when consuming the RUSF with borbor (57 kcals) or as a snack (48 kcals) was greater than with CSB++ (15 kcals) or borbor fortified with MNP (18 kcals; p < 0.001). Therefore, although children ate less RUSF, it provided approximately three times more kilocalories. Caregivers reported that their children had the highest preference for borbor fortified with MNP. Caregivers themselves ranked the novel RUSF snack highest. Thus, the innovative RUSF was considered sufficiently acceptable to proceed to an effectiveness trial.
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http://dx.doi.org/10.1111/mcn.12780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7198957PMC
July 2019

Why Is Hyperparathyroidism Underdiagnosed and Undertreated in Older Adults?

Clin Med Insights Endocrinol Diabetes 2018 12;11:1179551418815916. Epub 2018 Dec 12.

Department of Surgery, The University of Alabama at Birmingham, Birmingham, AL, USA.

Introduction: Hyperparathyroidism significantly decreases quality of life, yet elderly patients are underdiagnosed and undertreated even though parathyroidectomy offers definitive cure with minimal morbidity. The purpose of this study is to determine why older patients with hyperparathyroidism are not appropriately diagnosed and referred for parathyroidectomy.

Methods: We reviewed charts for a random sample of 25 patients aged 75 and older who had hyperparathyroidism and were referred for surgical evaluation, and 25 who were not referred. Two reviewers independently evaluated medical records to identify reasons for delayed diagnosis of hyperparathyroidism and reasons for nonreferral for parathyroidectomy.

Results: The median age of our cohort was 84 (80-96) years, 90% were women, 60% were white, and median follow-up was 5.5 (1-17) years. In 58% of all patients, an elevated serum calcium was not acknowledged. Even when calcium and parathyroid hormone levels were both elevated, the diagnosis was missed in 28% of patients, and 16% with clear symptoms of hyperparathyroidism remained undiagnosed. For 42% of patients, a nonsurgeon informed them that surgery offered no benefit. Surgery was also rejected as a treatment for 36% of patients despite the development of new symptoms or rising calcium.

Conclusions: Substantial gaps exist in processes for diagnosis and referral of patients with hyperparathyroidism that lead to underdiagnosis and undertreatment. To improve rates of diagnosis and treatment, strategies are needed to educate nonsurgeons and patients about the benefits of surgery and to modify care processes to more efficiently diagnose and refer patients.
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http://dx.doi.org/10.1177/1179551418815916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291858PMC
December 2018

Alcohol misuse and outpatient follow-up after hospital discharge: a retrospective cohort study.

Addict Sci Clin Pract 2018 12 4;13(1):24. Epub 2018 Dec 4.

Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Anschutz Medical Campus, Box C272, RC2, 9th Floor, 12700 East 19th Avenue, Aurora, CO, 80045, USA.

Purpose: Patients with alcohol misuse are less likely to receive preventive health services but more likely to utilize emergency health services. However, the association between alcohol misuse and outpatient follow-up after hospitalization is unknown and may depend on whether a patient experiences a critical illness. We sought to determine whether alcohol misuse was associated with lower rates of outpatient follow-up after hospital discharge and whether the magnitude of this association differed in patients who experienced a critical illness.

Materials And Methods: This was a retrospective cohort study using administrative data from an urban safety net hospital. Patients were included if they were admitted between 2011 and 2015, were between the ages of 18 and 89, resided within the safety net county, were discharged home, and were at moderate to high risk for hospital readmission within the subsequent 30 days. Alcohol misuse was identified using a combination of ICD-9 codes and response to a single screening question. The primary outcome was a combined measure of follow-up with a primary care physician or specialist provider in the 30 days following hospital discharge. Multivariable logistic regression was used to adjust for factors known to be associated with healthcare utilization.

Results: Overall, 17,575 patients were included in the analysis; 4984 (28%) had alcohol misuse. In the 30 days following hospital discharge, 46% of patients saw any outpatient provider. In an unadjusted analysis, the association between alcohol misuse and attending any outpatient follow-up was dependent on whether patients had a critical illness (p value < 0.0001) with the highest rates of follow-up in survivors of critical illness without alcohol misuse (53%, 95% CI 51%, 55%) followed by patients without alcohol misuse or critical illness (49%; 95% CI 48%, 50%), patients with alcohol misuse without critical illness (38%; 95% CI 36%, 39%), and patients with alcohol misuse and a critical illness (37%; 95% CI 35%, 40%). Adjusting for factors associated with healthcare utilization, these findings were modestly attenuated but unchanged.

Conclusions: Patients with alcohol misuse who are at moderate to high risk for hospital readmission may benefit from targeted interventions to increase rates of outpatient follow-up after hospital discharge.
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http://dx.doi.org/10.1186/s13722-018-0125-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278064PMC
December 2018

Development and Acceptability of Locally Made Fish-Based, Ready-to-Use Products for the Prevention and Treatment of Malnutrition in Cambodia.

Food Nutr Bull 2018 09 9;39(3):420-434. Epub 2018 Aug 9.

5 IUMR-204, Institut de Recherche pour le Dévelopment, IRD/Université de Montpellier/SupAgro, Montpellier, France.

Background: Cambodia has a high prevalence of moderate acute malnutrition and severe acute malnutrition (SAM). The SAM treatment requires ready-to-use therapeutic foods (RUTFs), whereas ready-to-use supplementary foods (RUSFs) are used for prevention of acute malnutrition. Three locally produced fish-based products were developed: an RUTF paste (NumTrey-Paste) for treatment and 2 wafer versions, one for prevention (NumTrey-RUSF) and one for treatment (NumTrey-RUTF).

Objective: To assess the acceptability of NumTrey-Paste and NumTrey-RUSF in comparison to a standard biscuit product (BP-100) used for the treatment of SAM.

Methods: Acceptability of NumTrey-RUSF and NumTrey-Paste was tested in a nonblinded crossover taste trial among children (n = 52), aged ≥ 6 months to 18 years, and their caregivers. Eight organoleptic qualities were assessed on a 5-point hedonic scale, as well as a ranking test. A score of 1 to 3 was categorized as acceptable. The acceptability of NumTrey-RUTF was assessed using the caregivers' perception during an SAM treatment intervention.

Results: Taste trial: The proportion of children categorizing products as overall acceptable was lowest for NumTrey-Paste compared to for BP-100 and NumTrey-RUSF (21% vs 43% [BP-100] and 36% [NumTrey-RUSF]). No difference was found in the proportion of children who ranked BP-100 or NumTrey-RUSF as "liked most" ( P > .05). Acceptability of NumTrey-RUSF ranked highest in appearance and taste (caregiver), whereas acceptability of NumTrey-Paste was ranked lowest in appearance and smell among the products. Intervention trial: The acceptability of NumTrey-RUTF increased from 72% to 86%.

Conclusions: The overall acceptability was ranked lowest for a pure paste product. However, filling the paste into a wafer made the product more acceptable.
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http://dx.doi.org/10.1177/0379572118788266DOI Listing
September 2018

Emricasan (IDN-6556) Lowers Portal Pressure in Patients With Compensated Cirrhosis and Severe Portal Hypertension.

Hepatology 2019 02 26;69(2):717-728. Epub 2018 Nov 26.

Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain.

Caspases play a central role in apoptosis, inflammation, and fibrosis. They produce hemodynamically active, proinflammatory microparticles that cause intrahepatic inflammation, vasoconstriction, and extrahepatic splanchnic vasodilation. Emricasan is a pan-caspase inhibitor that lowers portal hypertension (PH) and improves survival in murine models of cirrhosis. This exploratory study assessed whether emricasan lowers PH in patients with compensated cirrhosis. This multicenter, open-label study enrolled 23 subjects with compensated cirrhosis and PH (hepatic vein pressure gradient [HVPG] >5 mm Hg). Emricasan 25 mg twice daily was given for 28 days. HVPG measurements were standardized and performed before and after emricasan. A single expert read all HVPG tracings. Median age was 59 (range 49-80); 70% were male. Cirrhosis etiologies were nonalcoholic steatohepatitis and hepatitis C virus. Subjects were Child class A (87%) with a median Model for End-Stage Liver Disease score of 8 (range 6-15). Twelve had severe PH (HVPG ≥12 mm Hg). Overall, there was no significant change in HVPG after emricasan (mean [standard deviation, SD] -1.1 [4.57] mm Hg). HVPG decreased significantly (mean [SD] -3.7[4.05] mm Hg; P = 0.003) in those with severe PH: 4/12 had a ≥20% decrease, 8/12 had a ≥10% decrease, and 2/12 HVPG decreased below 12 mm Hg. There were no significant changes in blood pressure or heart rate. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) decreased significantly in the entire group and in those with severe PH. Serum cleaved cytokeratin 18 and caspase-3/7 decreased significantly. Emricasan was well tolerated. One subject discontinued for nonserious adverse events. Conclusion: Emricasan administered for 28 days decreased HVPG in patients with compensated cirrhosis and severe PH; an effect upon portal venous inflow is likely, and concomitant decreases in AST/ALT suggest an intrahepatic anti-inflammatory effect.
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http://dx.doi.org/10.1002/hep.30199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587783PMC
February 2019

Substantial variation exists in spirometry interpretation practices for airflow obstruction in accredited lung function laboratories across Australia and New Zealand.

Intern Med J 2019 Jan;49(1):41-47

Department of Respiratory Medicine, The Alfred Hospital, Melbourne, Victoria, Australia.

Background: Spirometry forms the foundation investigation for the diagnosis and monitoring of common pulmonary conditions. However, potential variation in spirometry interpretation for airflow obstruction may impact subsequent clinical management.

Aim: To audit spirometry interpretation practices for airflow obstruction in Thoracic Society of Australia and New Zealand accredited laboratories.

Methods: Thirty-nine accredited complex lung function laboratories were invited to participate in an online survey. The survey enquired about demographics, definition of lower limit of normal range for spirometry parameters, spirometric parameters used for identifying airflow obstruction, spirometric definition of airflow obstruction, definition of significant bronchodilator response and chosen spirometry reference equations.

Results: Thirty-six laboratories provided complete responses (response rate, 92%). To define the lower limit of normal, 26 of 36 used the 5th percentile, 7 of 36 used a fixed cut-off and 3 used other. Twenty-nine laboratories utilised forced expiratory volume in 1 s/forced vital capacity (FEV /FVC) as the sole parameter to identify airflow obstruction, 3 of 36 used FEV /FVC and FEF , and 4 used other. To define airflow obstruction, 25 of 36 laboratories used FEV /FVC < 5th percentile, 9 of 36 used a fixed cut-off (FEV /FVC < 0.7, 6/36; FEV /FVC < 0.8, 2/36; FEV /FVC < 0.75, 1/36) and 2 of 36 used other. Twenty-six laboratories defined a significant bronchodilator response as an increase of at least 200 mL and 12% in FEV and/or FVC, 9 of 36 used ≥200 mL and ≥ 12% increase in FEV only, and 1 used other criteria. Reference equations utilised for interpretation of spirometry data included: Quanjer 2012 Global Lung Initiative (16/36), the third National Health and Nutritional Examination Survey (8/36), European Community of Coal and Steel (8/36) and other (4/36).

Conclusions: Significant heterogeneity in spirometry interpretation for airflow obstruction exists across Australian and New Zealand accredited lung function laboratories. Lack of standardisation may translate into clinically appreciable differences for the diagnosis and management of common respiratory conditions. Ongoing discussion regarding formal standardisation is required.
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http://dx.doi.org/10.1111/imj.14047DOI Listing
January 2019

Randomised controlled trial to test the effectiveness of a locally-produced ready-to-use supplementary food (RUSF) in preventing growth faltering and improving micronutrient status for children under two years in Cambodia: a study protocol.

Nutr J 2018 03 16;17(1):39. Epub 2018 Mar 16.

UMR Nutripass, Institut de Recherche pour le Développement, IRD/UM/SupAgro, Montpellier, France.

Background: Existing ready-to-use supplementary and therapeutic foods (RUSFs and RUTFs) have had limited acceptance and effectiveness in Cambodia. This has hampered the treatment and prevention of child malnutrition. An innovative, locally produced, multiple micronutrient fortified lipid-based nutrient supplement (LNS) has been developed for use as an RUSF. Unlike most RUSFs, which contain milk, this product contains fish as the animal protein. Few RUSFs have been formulated using non-milk animal-source foods and they have not been widely tested. An acceptability trial that was conducted on this novel RUSF in June 2015 demonstrated that children will eat the RUSF and that caregivers will feed it to their children. The current trial aims to evaluate the effectiveness of the RUSF in preventing growth faltering and improving micronutrient status in Cambodian children.

Methods And Analysis: This trial is a six-month, prospective, cluster randomised, non-blinded controlled trial among infants in peri-urban Phnom Penh. The trial aims to establish the superiority of the novel RUSF, compared to three alternatives (Corn-Soy Blend Plus Plus (CSB++) and Sprinkles micronutrient powders as active comparators, and the unimproved diet as a control). The allocation ratio is 1:1. Healthy children (N = 540) aged six to eleven months will be recruited. Data will be collected at baseline, and monthly thereafter for a period of six months. Participants will be provided with a monthly supply of the food to which their village has been allocated.

Discussion: There is an urgent need to develop locally produced and culturally acceptable RUSFs, and to compare these with existing options in terms of their potential for preventing malnutrition, in Cambodia and elsewhere. This trial will contribute much-needed data on the effectiveness of supplementary foods with an animal-source food other than milk, by comparing a novel RUSF based on fish to one that uses milk (CSB++). Moreover, it will deepen the understanding of the impact of multiple micronutrients provided with or without macronutrients, by comparing the novel RUSF and CSB++, which combine macronutrients with multiple micronutrients, to Sprinkles, which contains no macronutrients. In addition, it will augment the body of evidence from Asia.

Trial Registration: ClinicalTrials.gov, Identifier: LNS-CAMB-INFANTS-EFF; NCT02257762 .
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http://dx.doi.org/10.1186/s12937-018-0346-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5857085PMC
March 2018

Characteristics of patients who progress from bridging to long-term oxygen therapy.

Intern Med J 2018 Nov;48(11):1376-1381

Respiratory Medicine Department, The Alfred Hospital, Melbourne, Victoria, Australia.

Background: Patients with persistent hypoxia following an acute hospital admission may be discharged with 'bridging' domiciliary oxygen as per criteria defined by the Thoracic Society of Australia and New Zealand. The need for continuous long-term oxygen therapy (LTOT) is then reassessed at a clinic review 1-2 months later.

Aim: To describe the characteristics of patients discharged from an acute hospital admission with continuous short-term oxygen therapy (STOT), and subsequently to investigate for differences between subjects who proceeded to qualify for continuous LTOT versus those who were able to cease STOT at review.

Methods: This is a retrospective cohort study involving all subjects discharged from Alfred Health between 2011 and 2015 inclusive with bridging domiciliary oxygen. Multiple biochemical, physiological and demographic characteristics were collated and analysed.

Results: Of all patients prescribed continuous STOT at time of discharge, 47.3% qualified for LTOT at outpatient review. This cohort had a significantly lower PaO measurement at time of discharge, compared with those who no longer qualified.

Conclusion: PaO at time of discharge provides a signal with the potential to identify who will require continuous LTOT following an acute hospital admission. Additionally, this study highlights the need to re-evaluate patients' oxygen requirements during a period of clinical stability.
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http://dx.doi.org/10.1111/imj.13737DOI Listing
November 2018