Browsing by Author "University of Washington"
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Publication Metadata only A 2-Biomarker Model Augments Clinical Prediction of Mortality in Melioidosis(2021-03-01) Shelton W. Wright; Taniya Kaewarpai; Lara Lovelace-Macon; Deirdre Ducken; Viriya Hantrakun; Kristina E. Rudd; Prapit Teparrukkul; Rungnapa Phunpang; Peeraya Ekchariyawat; Adul Dulsuk; Boonhthanom Moonmueangsan; Chumpol Morakot; Ekkachai Thiansukhon; Direk Limmathurotsakul; Narisara Chantratita; T. Eoin West; Faculty of Tropical Medicine, Mahidol University; Udon Thani Center Hospital; University of Washington School of Medicine; University of Washington; Mahidol University; University of Pittsburgh School of Medicine; Sunpasitthiprasong Hospital; Mukdahan HospitalBackground: Melioidosis, infection caused by Burkholderia pseudomallei, is a common cause of sepsis with high associated mortality in Southeast Asia. Identification of patients at high likelihood of clinical deterioration is important for guiding decisions about resource allocation and management. We sought to develop a biomarker-based model for 28-day mortality prediction in melioidosis. Methods: In a derivation set (N=113) of prospectively enrolled, hospitalized Thai patients with melioidosis, we measured concentrations of interferon-γ, interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumor necrosis factor-E', granulocyte-colony stimulating factor, and interleukin-17A. We used least absolute shrinkage and selection operator (LASSO) regression to identify a subset of predictive biomarkers and performed logistic regression and receiver operating characteristic curve analysis to evaluate biomarker-based prediction of 28-day mortality compared with clinical variables. We repeated select analyses in an internal validation set (N=78) and in a prospectively enrolled external validation set (N=161) of hospitalized adults with melioidosis. Results: All 8 cytokines were positively associated with 28-day mortality. Of these, interleukin-6 and interleukin-8 were selected by LASSO regression. A model consisting of interleukin-6, interleukin-8, and clinical variables significantly improved 28-day mortality prediction over a model of only clinical variables [AUC (95% confidence interval [CI]): 0.86 (.79-.92) vs 0.78 (.69-.87); P=.01]. In both the internal validation set (0.91 [0.84-0.97]) and the external validation set (0.81 [0.74-0.88]), the combined model including biomarkers significantly improved 28-day mortality prediction over a model limited to clinical variables. Conclusions: A 2-biomarker model augments clinical prediction of 28-day mortality in melioidosis.Publication Metadata only Comparative clinical characteristics and outcomes of patients with community acquired bacteremia caused by escherichia coli, burkholderia pseudomallei and staphylococcus aureus: A prospective observational study (ubon-sepsis)(2021-09-01) Ranjani Somayaji; Viriya Hantrakun; Prapit Teparrukkul; Gumphol Wongsuvan; Kristina E. Rudd; Nicholas P.J. Day; T. Eoin West; Direk Limmathurotsakul; Faculty of Tropical Medicine, Mahidol University; University of Washington; Nuffield Department of Medicine; University of Calgary; University of Pittsburgh School of Medicine; Sunpasitthiprasong HospitalBackground Community acquired bacteremia (CAB) is a common cause of sepsis in low and middle-income countries (LMICs). However, knowledge about factors associated with outcomes of CAB in LMICs is limited. Methodology/Principal findings A prospective observational study (Ubon-sepsis) of adults admitted to a referral hospital with community-acquired infection in Northeastern Thailand was conducted between March 1, 2013 and February 1, 2017. In the present analysis, patients with a blood culture collected within 24 hours of admission that was positive for one of the three most common pathogens were studied. Clinical features, management, and outcomes of patients with each cause of CAB were compared. Of 3,806 patients presenting with community-acquired sepsis, 155, 131 and 37 patients had a blood culture positive for Escherichia coli, Burkholderia pseudo-mallei and Staphylococcus aureus, respectively. Of these 323 CAB patients, 284 (89%) were transferred from other hospitals. 28-day mortality was highest in patients with B. pseu-domallei bactaeremia (66%), followed by those with S. aureus bacteraemia (43%) and E. coli (19%) bacteraemia. In the multivariable Cox proportional hazards model adjusted for age, sex, transfer from another hospital, empirical antibiotics prior to or during the transfer, and presence of organ dysfunction on admission, B. pseudomallei (aHR 3.78; 95%CI 2.31– 6.21) and S. aureus (aHR 2.72; 95%CI 1.40–5.28) bacteraemias were associated with higher mortality compared to E. coli bacteraemia. Receiving empirical antibiotics recom-mended for CAB caused by the etiologic organism prior to or during transfer was associated with survival (aHR 0.58; 95%CI 0.38–0.88). Conclusions/Significance Mortality of patients with CAB caused by B. pseudomallei was higher than those caused by S. aureus and E. coli, even after adjusting for presence of organ dysfunction on admission and effectiveness of empirical antibiotics received. Improving algorithms or rapid diagnostic tests to guide early empirical antibiotic may be key to improving CAB outcomes in LMICs.Publication Metadata only Corrigendum to ‘SJS/TEN 2019: From science to translation’ (Journal of Dermatological Science (2020) 98(1) (2–12), (S0923181120300645), (10.1016/j.jdermsci.2020.02.003))(2021-11-01) Wan Chun Chang; Riichiro Abe; Paul Anderson; Wanpen Anderson; Michael R. Ardern-Jones; Thomas M. Beachkofsky; Teresa Bellón; Agnieszka K. Biala; Charles Bouchard; Gianpiero L. Cavalleri; Nicole Chapman; James Chodosh; Hyon K. Choi; Ricardo R. Cibotti; Sherrie J. Divito; Karen Dewar; Ulrike Dehaeck; Mahyar Etminan; Diane Forbes; Esther Fuchs; Jennifer L. Goldman; James H. Holmes; Elyse A. Hope; Shuen Iu Hung; Chia Ling Hsieh; Alfonso Iovieno; Julienne Jagdeo; Mee Kum Kim; David M. Koelle; Mario E. Lacouture; Sophie Le Pallec; Rannakoe J. Lehloenya; Robyn Lim; Angie Lowe; Jean McCawley; Julie McCawley; Robert G. Micheletti; Maja Mockenhaupt; Katie Niemeyer; Michael A. Norcross; Douglas Oboh; Cristina Olteanu; Helena B. Pasieka; Jonathan Peter; Munir Pirmohamed; Michael Rieder; Hajirah N. Saeed; Neil H. Shear; Christine Shieh; Sabine Straus; Chonlaphat Sukasem; Cynthia Sung; Jason A. Trubiano; Sheng Ying Tsou; Mayumi Ueta; Simona Volpi; Chen Wan; Hongsheng Wang; Zhao Qing Wang; Jessica Weintraub; Cindy Whale; Lisa M. Wheatley; Sonia Whyte-Croasdaile; Kristina B. Williams; Galen Wright; Sonia N. Yeung; Li Zhou; Wen Hung Chung; Elizabeth J. Phillips; Bruce C. Carleton; Ramathibodi Hospital; Niigata University, Graduate School of Medical and Dental Science; Chinese Academy of Medical Sciences & Peking Union Medical College; European Medicines Agency; Instituto de Investigación Sanitaria del Hospital Universitario La Paz; Xiamen Chang Gung Hospital; Genome Canada; BC Children's Hospital Research Institute; Chang Gung University College of Medicine; National Yang-Ming University Taiwan; Chang Gung Memorial Hospital; Schulich School of Medicine & Dentistry; Wake Forest University School of Medicine; Health Sciences Authority, Government of Singapore; Vanderbilt University Medical Center; Kyoto Prefectural University of Medicine; Massachusetts General Hospital; Canadian Institutes of Health Research; University of Washington School of Medicine; Washington Hospital Center; University of Melbourne; Universität Freiburg; University of Southampton, Faculty of Medicine; University of British Columbia, Faculty of Medicine; Penn Medicine; University of Liverpool; Murdoch University; University of Alberta, Faculty of Medicine and Dentistry; Children's Mercy Hospitals and Clinics; Vanderbilt Eye Institute; Health Canada; Loyola University Medical Center; University of Toronto; University of Washington; Wilford Hall Ambulatory Surgical Center; The University of British Columbia; Food and Drug Administration; Memorial Sloan-Kettering Cancer Center; National Institutes of Health (NIH); National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); Austin Health; Harvard Medical School; Seoul National University College of Medicine; University of Cape Town; Royal College of Surgeons in Ireland; SJS/TEN International Awareness (STIA); Association des malades des syndromes de Lyell et de Stevens-Johnson (Amalyste); SJ Syndrome of Texas; SJS Awareness Oregon; SJS Canada; Stevens-Johnson Syndrome Foundation; Eden Social Welfare Foundation; Genome British ColumbiaThe authors regret not all contributing authors correctly acknowledged funding. Jonathan Peter's IMARI-Africa project (AFRISCAR) is part of the EDCTP2 programme supported by the European Union (grant number TMA2017SF-1981). The authors would like to apologise for any inconvenience caused.Publication Metadata only Effectiveness of a sepsis programme in a resource-limited setting: A retrospective analysis of data of a prospective observational study (Ubon-sepsis)(2021-02-18) Suchart Booraphun; Viriya Hantrakun; Suwatthiya Siriboon; Chaiyaporn Boonsri; Pulyamon Poomthong; Bung Orn Singkaew; Oratai Wasombat; Parinya Chamnan; Ratapum Champunot; Kristina Rudd; Nicholas P.J. Day; Arjen M. Dondorp; Prapit Teparrukkul; Timothy Eoin West; DIrek Limmathurotsakul; Faculty of Tropical Medicine, Mahidol University; University of Washington; Nuffield Department of Medicine; University of Pittsburgh School of Medicine; Sunpasitthiprasong Hospital; Buddhachinaraj Phitsanulok HospitalObjective To evaluate the effectiveness of a Sepsis Fast Track (SFT) programme initiated at a regional referral hospital in Thailand in January 2015. Design A retrospective analysis using the data of a prospective observational study (Ubon-sepsis) from March 2013 to January 2017. Setting General medical wards and medical intensive care units (ICUs) of a study hospital. Participants Patients with community-acquired sepsis observed under the Ubon-sepsis cohort. Sepsis was defined as modified Sequential Organ Failure Assessment (SOFA) Score ≥2. Main exposure The SFT programme was a protocol to identify and initiate sepsis care on hospital admission, implemented at the study hospital in 2015. Patients in the SFT programme were admitted directly to the ICUs when available. The non-exposed group comprised of patients who received standard of care. Main outcome The primary outcome was 28-day mortality. The secondary outcomes were measured sepsis management interventions. Results Of 3806 sepsis patients, 903 (24%) were detected and enrolled in the SFT programme of the study hospital (SFT group) and 2903 received standard of care (non-exposed group). Patients in the SFT group had more organ dysfunction, were more likely to receive measured sepsis management and to be admitted directly to the ICU (19% vs 4%). Patients in the SFT group were more likely to survive (adjusted HR 0.72, 95% CI 0.58 to 0.88, p=0.001) adjusted for admission year, gender, age, comorbidities, modified SOFA Score and direct admission to the ICUs. Conclusions The SFT programme is associated with improved sepsis care and lower risk of death in sepsis patients in rural Thailand, where some critical care resources are limited. The survival benefit is observed even when all patients enrolled in the programme could not be admitted directly into the ICUs. Trial registration number NCT02217592.Publication Metadata only Engaging communities in non-communicable disease research and interventions in low- And middle-income countries: A realist review protocol(2021-07-21) Sonja Klingberg; Bipin Adhikari; Catherine E. Draper; Edna N. Bosire; Priscilla Tiigah; Deborah Nyirenda; Ferdinand C. Mukumbang; Faculty of Tropical Medicine, Mahidol University; Public Health England; University of the Witwatersrand Faculty of Health Sciences; University of Malawi; University of Washington; Nuffield Department of MedicineIntroduction Engaging communities and intended beneficiaries at various stages of health research is a recommended practice. The contribution of community engagement to non-communicable disease research in low- and middle-income countries has not yet been extensively studied or synthesised. This protocol describes the steps towards generating an understanding of community engagement in the context of non-communicable disease research, prevention and health promotion using a realist review approach. A realist lens enables a rich explanatory approach to causation while capturing complexity, and an openness to multiple outcomes, including unintended consequences. The review will thus develop an understanding of community engagement without assuming that such practices result in more ethical research or effective interventions. Methods and analysis We propose a realist approach aiming to examine how, why, under what circumstances and for whom community engagement works or does not work. The iterative review steps include clarifying the review scope; searching for evidence; appraising studies and extracting data; synthesising evidence and drawing conclusions; and disseminating, implementing and evaluating the findings. Principles of meta-narrative review (pragmatism, pluralism, historicity, contestation, reflexivity and peer review) are employed to ensure practicable and contextualised review outputs. The proposed review will draw on theoretical and empirical literature beyond specific diseases or settings, but with a focus on informing non-communicable disease research and interventions in low- and middle-income countries. The synthesis of existing literature will be complemented by qualitative realist interviews and stakeholder consultation. Through drawing on multiple types of evidence and input from both experts and intended beneficiaries, the review will provide critical and pragmatic insights for research and community engagement in low- and middle-income countries. Ethics and dissemination Ethical approval has been obtained from the University of the Witwatersrand. Dissemination will include traditional academic channels, institutional communications, social media and discussions with a wide range of stakeholders.Publication Metadata only Falciparum but not vivax malaria increases the risk of hypertensive disorders of pregnancy in women followed prospectively from the first trimester(2021-12-01) Whitney E. Harrington; Kerryn A. Moore; Aung Myat Min; Mary Ellen Gilder; Nay Win Tun; Moo Kho Paw; Jacher Wiladphaingern; Stephane Proux; Kesinee Chotivanich; Marcus J. Rijken; Nicholas J. White; François Nosten; Rose McGready; Faculty of Tropical Medicine, Mahidol University; University Medical Center Utrecht; London School of Hygiene & Tropical Medicine; Children's Hospital and Regional Medical Center; University of Washington; Murdoch Children's Research Institute; Nuffield Department of Medicine; Julius Global HealthBackground: Malaria and hypertensive disorders of pregnancy (HDoP) affect millions of pregnancies worldwide, particularly those of young, first-time mothers. Small case-control studies suggest a positive association between falciparum malaria and risk of pre-eclampsia but large prospective analyses are lacking. Methods: We characterized the relationship between malaria in pregnancy and the development of HDoP in a large, prospectively followed cohort. Pregnant women living along the Thailand-Myanmar border, an area of low seasonal malaria transmission, were followed at antenatal clinics between 1986 and 2016. The relationships between falciparum and vivax malaria during pregnancy and the odds of gestational hypertension, pre-eclampsia, or eclampsia were examined using logistic regression amongst all women and then stratified by gravidity. Results: There were 23,262 singleton pregnancies in women who presented during the first trimester and were followed fortnightly. Falciparum malaria was associated with gestational hypertension amongst multigravidae (adjusted odds ratio (AOR) 2.59, 95%CI 1.59–4.23), whereas amongst primigravidae, it was associated with the combined outcome of pre-eclampsia/eclampsia (AOR 2.61, 95%CI 1.01–6.79). In contrast, there was no association between vivax malaria and HDoP. Conclusions: Falciparum but not vivax malaria during pregnancy is associated with hypertensive disorders of pregnancy.Publication Metadata only Glassy carbon microelectrode arrays enable voltage-peak separated simultaneous detection of dopamine and serotonin using fast scan cyclic voltammetry(2021-06-21) Elisa Castagnola; Sanitta Thongpang; Mieko Hirabayashi; Giorgio Nava; Surabhi Nimbalkar; Tri Nguyen; Sandra Lara; Alexis Oyawale; James Bunnell; Chet Moritz; Sam Kassegne; University of California, Riverside; San Diego State University; University of Washington; Mahidol University; Bill & Melinda Gates Center for Computer Science & EngineeringProgress in real-time, simultaneous in vivo detection of multiple neurotransmitters will help accelerate advances in neuroscience research. The need for development of probes capable of stable electrochemical detection of rapid neurotransmitter fluctuations with high sensitivity and selectivity and sub-second temporal resolution has, therefore, become compelling. Additionally, a higher spatial resolution multi-channel capability is required to capture the complex neurotransmission dynamics across different brain regions. These research needs have inspired the introduction of glassy carbon (GC) microelectrode arrays on flexible polymer substrates through carbon MEMS (C-MEMS) microfabrication process followed by a novel pattern transfer technique. These implantable GC microelectrodes provide unique advantages in electrochemical detection of electroactive neurotransmitters through the presence of active carboxyl, carbonyl, and hydroxyl functional groups. In addition, they offer fast electron transfer kinetics, capacitive electrochemical behavior, and wide electrochemical window. Here, we combine the use of these GC microelectrodes with the fast scan cyclic voltammetry (FSCV) technique to optimize the co-detection of dopamine (DA) and serotonin (5-HT) in vitro and in vivo. We demonstrate that using optimized FSCV triangular waveform at scan rates ≤700 V s-1 and holding and switching at potentials of 0.4 and 1 V respectively, it is possible to discriminate voltage reduction and oxidation peaks of DA and 5-HT, with 5-HT contributing distinct multiple oxidation peaks. Taken together, our results present a compelling case for a carbon-based MEA platform rich with active functional groups that allows for repeatable and stable detection of electroactive multiple neurotransmitters at concentrations as low as 1.1 nM. This journal isPublication Metadata only Global antibiotic consumption and usage in humans, 2000–18: a spatial modelling study(2021-12-01) Annie J. Browne; Michael G. Chipeta; Georgina Haines-Woodhouse; Emmanuelle P.A. Kumaran; Bahar H.Kashef Hamadani; Sabra Zaraa; Nathaniel J. Henry; Aniruddha Deshpande; Robert C. Reiner; Nicholas P.J. Day; Alan D. Lopez; Susanna Dunachie; Catrin E. Moore; Andy Stergachis; Simon I. Hay; Christiane Dolecek; Faculty of Tropical Medicine, Mahidol University; Institute for Health Metrics and Evaluation; University of Washington School of Medicine; University of Washington; Nuffield Department of MedicineBackground: Antimicrobial resistance (AMR) is a serious threat to global public health. WHO emphasises the need for countries to monitor antibiotic consumption to combat AMR. Many low-income and middle-income countries (LMICs) lack surveillance capacity; we aimed to use multiple data sources and statistical models to estimate global antibiotic consumption. Methods: In this spatial modelling study, we used individual-level data from household surveys to inform a Bayesian geostatistical model of antibiotic usage in children (aged <5 years) with lower respiratory tract infections in LMICs. Antibiotic consumption data were obtained from multiple sources, including IQVIA, WHO, and the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). The estimates of the antibiotic usage model were used alongside sociodemographic and health covariates to inform a model of total antibiotic consumption in LMICs. This was combined with a single model of antibiotic consumption in high-income countries to produce estimates of antibiotic consumption covering 204 countries and 19 years. Findings: We analysed 209 surveys done between 2000 and 2018, covering 284 045 children with lower respiratory tract infections. We identified large national and subnational variations of antibiotic usage in LMICs, with the lowest levels estimated in sub-Saharan Africa and the highest in eastern Europe and central Asia. We estimated a global antibiotic consumption rate of 14·3 (95% uncertainty interval 13·2–15·6) defined daily doses (DDD) per 1000 population per day in 2018 (40·2 [37·2–43·7] billion DDD), an increase of 46% from 9·8 (9·2–10·5) DDD per 1000 per day in 2000. We identified large spatial disparities, with antibiotic consumption rates varying from 5·0 (4·8–5·3) DDD per 1000 per day in the Philippines to 45·9 DDD per 1000 per day in Greece in 2018. Additionally, we present trends in consumption of different classes of antibiotics for selected Global Burden of Disease study regions using the IQVIA, WHO, and ESAC-net input data. We identified large increases in the consumption of fluoroquinolones and third-generation cephalosporins in North Africa and Middle East, and south Asia. Interpretation: To our knowledge, this is the first study that incorporates antibiotic usage and consumption data and uses geostatistical modelling techniques to estimate antibiotic consumption for 204 countries from 2000 to 2018. Our analysis identifies both high rates of antibiotic consumption and a lack of access to antibiotics, providing a benchmark for future interventions. Funding: Fleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill & Melinda Gates Foundation.Publication Metadata only HRS/EHRA/APHRS/LAHRS/ACC/AHA Worldwide Practice Update for Telehealth and Arrhythmia Monitoring During and After a Pandemic(2020-07-01) Niraj Varma; Nassir F. Marrouche; Luis Aguinaga; Christine M. Albert; Elena Arbelo; Jong Il Choi; Mina K. Chung; Giulio Conte; Lilas Dagher; Laurence M. Epstein; Hamid Ghanbari; Janet K. Han; Hein Heidbuchel; He Huang; Dhanunjaya R. Lakkireddy; Tachapong Ngarmukos; Andrea M. Russo; Eduardo B. Saad; Luis C. Saenz Morales; Kristin E. Sandau; Arun Raghav M. Sridhar; Eric C. Stecker; Paul D. Varosy; Korea University Medical Center; Renmin Hospital of Wuhan University; Hospital Pro-Cardiaco; University of California, Los Angeles; Cleveland Clinic Foundation; North Shore University Hospital; Oregon Health & Science University; Faculty of Medicine, Ramathibodi Hospital, Mahidol University; Tulane University School of Medicine; Cooper Medical School of Rowan University; Bethel University; Antwerp University and University Hospital; University of Washington; Cedars-Sinai Medical Center; Kansas City Heart Rhythm Institute and Research Foundation; University of Michigan's; CardioInfantil Foundation; Universitat de Barcelona; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV); Cardiocentro; Centro Privado de CardiologíaPublication Metadata only HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic Developed in partnership with and endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), the European Heart Rhythm Association (EHRA), the Heart Rhythm Society (HRS), and the Latin American Heart Rhythm Society (LAHRS).(2021-02-01) Niraj Varma; Nassir F. Marrouche; Luis Aguinaga; Christine M. Albert; Elena Arbelo; Jong Il Choi; Mina K. Chung; Giulio Conte; Lilas Dagher; Laurence M. Epstein; Hamid Ghanbari; Janet K. Han; Hein Heidbuchel; He Huang; Dhanunjaya R. Lakkireddy; Tachapong Ngarmukos; Andrea M. Russo; Eduardo B. Saad; Luis C. Saenz Morales; Kristin E. Sandau; Arun Raghav M. Sridhar; Eric C. Stecker; Paul D. Varosy; Centro de Investigación en Red en Enfermedades Cardiovasculares; Korea University Medicine; Hospital Pro-Cardiaco; Wuhan University; University of Michigan, Ann Arbor; Cleveland Clinic Foundation; North Shore University Hospital; Oregon Health & Science University; Cedars-Sinai Medical Center; Faculty of Medicine Ramathibodi Hospital, Mahidol University; University of Washington; Tulane University School of Medicine; Cooper Medical School of Rowan University; Universiteit Antwerpen; VA Eastern Colorado Health Care System; Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS; Bethel University; David Geffen School of Medicine at UCLA; Universitat de Barcelona; Kansas City Heart Rhythm Institute and Research Foundation; CardioInfantil Foundation; Cardiocentro; Centro Privado de CardiologíaPublication Metadata only In-hospital mortality of hepatorenal syndrome in the United States: Nationwide inpatient sample(2021-12-07) Wisit Kaewput; Charat Thongprayoon; Carissa Y. Dumancas; Swetha R. Kanduri; Karthik Kovvuru; Chalermrat Kaewput; Pattharawin Pattharanitima; Tananchai Petnak; Ploypin Lertjitbanjong; Boonphiphop Boonpheng; Karn Wijarnpreecha; Jose L. Zabala Genovez; Saraschandra Vallabhajosyula; Caroline C. Jadlowiec; Fawad Qureshi; Wisit Cheungpasitporn; Ramathibodi Hospital; Siriraj Hospital; Wake Forest University School of Medicine; Mayo Clinic Scottsdale-Phoenix, Arizona; University of Michigan, Ann Arbor; Ochsner Health System; University of Washington; Faculty of Medicine, Thammasat University; Phramongkutklao College of Medicine; Mayo Clinic; University of Tennessee Health Science CenterBACKGROUND Hepatorenal syndrome (HRS) is a life-threatening condition among patients with advanced liver disease. Data trends specific to hospital mortality and hospital admission resource utilization for HRS remain limited. AIM To assess the temporal trend in mortality and identify the predictors for mortality among hospital admissions for HRS in the United States. METHODS We used the National Inpatient Sample database to identify an unweighted sample of 4938 hospital admissions for HRS from 2005 to 2014 (weighted sample of 23973 admissions). The primary outcomes were temporal trends in mortality as well as predictors for hospital mortality. We estimated odds ratios from multilevel mixed effect logistic regression to identify patient characteristics and treatments associated with hospital mortality. RESULTS Overall hospital mortality was 32%. Hospital mortality decreased from 44% in 2005 to 24% in 2014 (P < 0.001), while there was an increase in the rate of liver transplantation (P = 0.02), renal replacement therapy (P < 0.001), length of hospital stay (P < 0.001), and hospitalization cost (P < 0.001). On multivariable analysis, older age, alcohol use, coagulopathy, neurological disorder, and need for mechanical ventilation predicted higher hospital mortality, whereas liver transplantation, transjugular intrahepatic portosystemic shunt, and abdominal paracentesis were associated with lower hospital mortality. CONCLUSION Although there was an increase in resource utilizations, hospital mortality among patients admitted for HRS significantly improved. Several predictors for hospital mortality were identified.Publication Metadata only Melioidosis Patient Survival Correlates With Strong IFN-γ Secreting T Cell Responses Against Hcp1 and TssM(2021-07-30) Sineenart Sengyee; Atchara Yarasai; Rachan Janon; Chumpol Morakot; Orawan Ottiwet; Lindsey K. Schmidt; T. Eoin West; Mary N. Burtnick; Narisara Chantratita; Paul J. Brett; Faculty of Tropical Medicine, Mahidol University; University of Washington; University of Nevada School of Medicine; Harborview Medical Center; Mukdahan HospitalMelioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a serious infectious disease with diverse clinical manifestations. The morbidity and mortality of melioidosis is high in Southeast Asia and no licensed vaccines currently exist. This study was aimed at evaluating human cellular and humoral immune responses in Thai adults against four melioidosis vaccine candidate antigens. Blood samples from 91 melioidosis patients and 100 healthy donors from northeast Thailand were examined for immune responses against B. pseudomallei Hcp1, AhpC, TssM and LolC using a variety of cellular and humoral immune assays including IFN-γ ELISpot assays, flow cytometry and ELISA. PHA and a CPI peptide pool were also used as control stimuli in the ELISpot assays. Hcp1 and TssM stimulated strong IFN-γ secreting T cell responses in acute melioidosis patients which correlated with survival. High IFN-γ secreting CD4+ T cell responses were observed during acute melioidosis. Interestingly, while T cell responses of melioidosis patients against the CPI peptide pool were low at the time of enrollment, the levels increased to the same as in healthy donors by day 28. Although high IgG levels against Hcp1 and AhpC were detected in acute melioidosis patients, no significant differences between survivors and non-survivors were observed. Collectively, these studies help to further our understanding of immunity against disease following natural exposure of humans to B. pseudomallei as well as provide important insights for the selection of candidate antigens for use in the development of safe and effective melioidosis subunit vaccines.Publication Metadata only Metabolic profiles, energy expenditures, and body compositions of the weight regain versus sustained weight loss patients who underwent Roux-en-Y gastric bypass(2021-12-01) Prapimporn Chattranukulchai Shantavasinkul; Phillip Omotosho; Michael J. Muehlbauer; Michael Natoli; Leonor Corsino; Jenny Tong; Dana Portenier; Alfonso Torquati; Duke University Medical Center; Rush University Medical Center; Faculty of Medicine Ramathibodi Hospital, Mahidol University; University of Washington; Duke University School of MedicineBackground: Weight regain (WR) has been an emerging problem after Roux-en Y gastric bypass (RYGB) and little is known about the mechanisms of WR after RYGB. Objective: To evaluate the mechanisms of WR after RYGB through the postprandial gut hormones response, particularly glucagon-like peptide-1 (GLP-1), which regulates appetite control, energy expenditure, body composition, physical activities, dietary intake, and psychological factors. Setting: Duke University Medical Center, Durham, North Carolina. Methods: A cross sectional study of 34 patients who underwent RYGB at least 2 years and achieved ≥50% of excess weight loss at 1year was conducted. The subjects were categorized into WR group or sustained weight loss group, based upon whether their WR was ≥15% of postoperative lowest weight. Results: The WR group had less augmented postprandial GLP-1 response but exaggerated hyperinsulinemia. Postprandial peptide YY, ghrelin, and glucose were not different between group. Patients who regained weight required less weight-adjusted energy expenditure and had more percentage body fat and less percentage lean mass. The caloric intake and diet composition were comparable between groups; however, the WR group had higher depression scores, binge eating scales, and hunger rating and spent significantly less time on vigorous exercise. Conclusions: The mechanisms of WR in patients who were initially successful after RYGB are complex and involved not only the role of postprandial gut hormone response but are also related to energy expenditure adaptation and body composition changes. Moreover, food preference and physical activity may play roles in weight control after bariatric surgery. Further prospective controlled trial is needed to explore the mechanisms of WR.Publication Metadata only Optimization of Plasmodium vivax sporozoite production from Anopheles stephensi in South West India(2021-12-01) Ajeet Kumar Mohanty; Charles de Souza; Deepika Harjai; Prathamesh Ghavanalkar; Mezia Fernandes; Anvily Almeida; Jayashri Walke; Suresh Kumar Manoharan; Ligia Pereira; Rashmi Dash; Anjali Mascarenhas; Edwin Gomes; Thanyapit Thita; Laura Chery; Anupkumar R. Anvikar; Ashwani Kumar; Neena Valecha; Pradipsinh K. Rathod; Rapatbhorn Patrapuvich; Faculty of Tropical Medicine, Mahidol University; Vector Control Research Centre India; National Institute of Malaria Research India; Goa Medical College & Hospital; University of Washington; National Institute of Malaria ResearchBackground: Efforts to study the biology of Plasmodium vivax liver stages, particularly the latent hypnozoites, have been hampered by the limited availability of P. vivax sporozoites. Anopheles stephensi is a major urban malaria vector in Goa and elsewhere in South Asia. Using P. vivax patient blood samples, a series of standard membrane-feeding experiments were performed with An. stephensi under the US NIH International Center of Excellence for Malaria Research (ICEMR) for Malaria Evolution in South Asia (MESA). The goal was to understand the dynamics of parasite development in mosquitoes as well as the production of P. vivax sporozoites. To obtain a robust supply of P. vivax sporozoites, mosquito-rearing and mosquito membrane-feeding techniques were optimized, which are described here. Methods: Membrane-feeding experiments were conducted using both wild and laboratory-colonized An. stephensi mosquitoes and patient-derived P. vivax collected at the Goa Medical College and Hospital. Parasite development to midgut oocysts and salivary gland sporozoites was assessed on days 7 and 14 post-feeding, respectively. The optimal conditions for mosquito rearing and feeding were evaluated to produce high-quality mosquitoes and to yield a high sporozoite rate, respectively. Results: Laboratory-colonized mosquitoes could be starved for a shorter time before successful blood feeding compared with wild-caught mosquitoes. Optimizing the mosquito-rearing methods significantly increased mosquito survival. For mosquito feeding, replacing patient plasma with naïve serum increased sporozoite production > two-fold. With these changes, the sporozoite infection rate was high (> 85%) and resulted in an average of ~ 22,000 sporozoites per mosquito. Some mosquitoes reached up to 73,000 sporozoites. Sporozoite production could not be predicted from gametocyte density but could be predicted by measuring oocyst infection and oocyst load. Conclusions: Optimized conditions for the production of high-quality P. vivax sporozoite-infected An. stephensi were established at a field site in South West India. This report describes techniques for producing a ready resource of P. vivax sporozoites. The improved protocols can help in future research on the biology of P. vivax liver stages, including hypnozoites, in India, as well as the development of anti-relapse interventions for vivax malaria.Publication Metadata only Partial protection against P. vivax infection diminishes hypnozoite burden and blood-stage relapses(2021-05-12) Carola Schäfer; Nicholas Dambrauskas; Laura M. Reynolds; Olesya Trakhimets; Andrew Raappana; Erika L. Flannery; Wanlapa Roobsoong; Jetsumon Sattabongkot; Sebastian A. Mikolajczak; Stefan H.I. Kappe; D. Noah Sather; Faculty of Tropical Medicine, Mahidol University; University of Washington; Seattle Biomedical Research InstituteLatent forms of Plasmodium vivax, called hypnozoites, cause malaria relapses from the liver into the bloodstream and are a major obstacle to malaria eradication. To experimentally assess the impact of a partially protective pre-erythrocytic vaccine on reducing Plasmodium vivax relapses, we developed a liver-humanized mouse model that allows monitoring of relapses directly in the blood. We passively infused these mice with a suboptimal dose of an antibody that targets the circumsporozoite protein prior to challenge with P. vivax sporozoites. Although this regimen did not completely prevent primary infection, antibody-treated mice experienced 62% fewer relapses. The data constitute unprecedented direct experimental evidence that suboptimal efficacy of infection-blocking antibodies, while not completely preventing primary infection, has a pronounced benefit in reducing the number of relapses. These findings suggest that a partially efficacious pre-erythrocytic Plasmodium vivax vaccine can have a disproportionately high impact in positive public health outcomes.Publication Metadata only Performance of a fully‐automated system on a WHO malaria microscopy evaluation slide set(2021-12-01) Matthew P. Horning; Charles B. Delahunt; Christine M. Bachman; Jennifer Luchavez; Christian Luna; Liming Hu; Mayoore S. Jaiswal; Clay M. Thompson; Sourabh Kulhare; Samantha Janko; Benjamin K. Wilson; Travis Ostbye; Martha Mehanian; Roman Gebrehiwot; Grace Yun; David Bell; Stephane Proux; Jane Y. Carter; Wellington Oyibo; Dionicia Gamboa; Mehul Dhorda; Ranitha Vongpromek; Peter L. Chiodini; Bernhards Ogutu; Earl G. Long; Kyaw Tun; Thomas R. Burkot; Ken Lilley; Courosh Mehanian; Mahidol Oxford Tropical Medicine Research Unit; Gokila; Universidad Peruana Cayetano Heredia; Kenya Medical Research Institute; Amref Health Africa; London School of Hygiene & Tropical Medicine; Centers for Disease Control and Prevention; James Cook University; University of Washington; Mahidol University; University of Lagos; Arizona State University; Australian Defence Force Malaria and Infectious Disease Institute; Independent Consultant; Asia Regional Centre; Defence Services Medical Academy; Creative Creek, LLC; Intellectual Ventures Global Good Fund; Intellectual VenturesBackground: Manual microscopy remains a widely-used tool for malaria diagnosis and clinical studies, but it has inconsistent quality in the field due to variability in training and field practices. Automated diagnostic systems based on machine learning hold promise to improve quality and reproducibility of field microscopy. The World Health Organization (WHO) has designed a 55-slide set (WHO 55) for their External Competence Assessment of Malaria Microscopists (ECAMM) programme, which can also serve as a valuable benchmark for automated systems. The performance of a fully-automated malaria diagnostic system, EasyScan GO, on a WHO 55 slide set was evaluated. Methods: The WHO 55 slide set is designed to evaluate microscopist competence in three areas of malaria diagnosis using Giemsa-stained blood films, focused on crucial field needs: malaria parasite detection, malaria parasite species identification (ID), and malaria parasite quantitation. The EasyScan GO is a fully-automated system that combines scanning of Giemsa-stained blood films with assessment algorithms to deliver malaria diagnoses. This system was tested on a WHO 55 slide set. Results: The EasyScan GO achieved 94.3 % detection accuracy, 82.9 % species ID accuracy, and 50 % quantitation accuracy, corresponding to WHO microscopy competence Levels 1, 2, and 1, respectively. This is, to our knowledge, the best performance of a fully-automated system on a WHO 55 set. Conclusions: EasyScan GO’s expert ratings in detection and quantitation on the WHO 55 slide set point towards its potential value in drug efficacy use-cases, as well as in some case management situations with less stringent species ID needs. Improved runtime may enable use in general case management settings.Publication Metadata only piNET: a versatile web platform for downstream analysis and visualization of proteomics data(2020-07-02) Behrouz Shamsaei; Szymon Chojnacki; Marcin Pilarczyk; Mehdi Najafabadi; Wen Niu; Chuming Chen; Karen Ross; Andrea Matlock; Jeremy Muhlich; Somchai Chutipongtanate; Jie Zheng; John Turner; Dušica Vidović; Jake Jaffe; Michael MacCoss; Cathy Wu; Ajay Pillai; Avi Ma'ayan; Stephan Schürer; Michal Kouril; Mario Medvedovic; Jarek Meller; Cincinnati Children's Hospital Medical Center; University of Cincinnati; University of Delaware; Georgetown University Medical Center; University of Cincinnati College of Medicine; Cedars-Sinai Medical Center; Icahn School of Medicine at Mount Sinai; Mahidol University; Sylvester Comprehensive Cancer Center; National Institutes of Health (NIH); University of Pennsylvania Perelman School of Medicine; Harvard Medical School; Broad Institute; University of Washington© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. Rapid progress in proteomics and large-scale profiling of biological systems at the protein level necessitates the continued development of efficient computational tools for the analysis and interpretation of proteomics data. Here, we present the piNET server that facilitates integrated annotation, analysis and visualization of quantitative proteomics data, with emphasis on PTM networks and integration with the LINCS library of chemical and genetic perturbation signatures in order to provide further mechanistic and functional insights. The primary input for the server consists of a set of peptides or proteins, optionally with PTM sites, and their corresponding abundance values. Several interconnected workflows can be used to generate: (i) interactive graphs and tables providing comprehensive annotation and mapping between peptides and proteins with PTM sites; (ii) high resolution and interactive visualization for enzyme-substrate networks, including kinases and their phospho-peptide targets; (iii) mapping and visualization of LINCS signature connectivity for chemical inhibitors or genetic knockdown of enzymes upstream of their target PTM sites. piNET has been built using a modular Spring-Boot JAVA platform as a fast, versatile and easy to use tool. The Apache Lucene indexing is used for fast mapping of peptides into UniProt entries for the human, mouse and other commonly used model organism proteomes. PTM-centric network analyses combine PhosphoSitePlus, iPTMnet and SIGNOR databases of validated enzyme-substrate relationships, for kinase networks augmented by DeepPhos predictions and sequence-based mapping of PhosphoSitePlus consensus motifs. Concordant LINCS signatures are mapped using iLINCS. For each workflow, a RESTful API counterpart can be used to generate the results programmatically in the json format. The server is available at http://pinet-server.org, and it is free and open to all users without login requirement.Publication Metadata only Pragmatic recommendations for infection prevention and control practices for healthcare facilities in low- And middle-income countries during the COVID-19 pandemic(2021-03-01) Natalie Cobb; Alfred Papali; Luigi Pisani; Marcus J. Schultz; Juliana C. Ferreira; University of Washington Medical Center; University of Oxford; University of Washington; Mahidol University; Universidade de São Paulo; Amsterdam UMC - University of Amsterdam; Doctors with Africa CUAMM; Division of Pulmonary and Critical Care MedicineInfection prevention and control (IPC) strategies are key in preventing nosocomial transmission of COVID-19. Several commonly used IPC practices are resource-intensive and may be challenging to implement in resource-constrained settings. An international group of healthcare professionals from or with experience in low- and middle-income countries (LMICs) searched the literature for relevant evidence. We report on a set of pragmatic recommendations for hospital-based IPC practices in resource-constrained settings of LMICs. For cases of confirmed or suspected COVID-19, we suggest that patients be placed in a single isolation room, whenever possible. When single isolation rooms are unavailable or limited, we recommend cohorting patients with COVID-19 on dedicated wards or in dedicated hospitals. We also recommend that cases of suspected COVID-19 be cohorted separately from those with confirmed disease, whenever possible, to minimize the risk of patient-to-patient transmission in settings where confirmatory testing may be limited. We suggest that healthcare workers be designated to care exclusively for patients with COVID-19, whenever possible, as another approach to minimize nosocomial spread. This approach may also be beneficial in conserving limited supplies of reusable personal protective equipment (PPE). We recommend that visitors be restricted for patients with COVID-19. In settings where family members or visitors are necessary for caregiving, we recommend that the appropriate PPE be used by visitors. We also recommend that education regarding hand hygiene and donning/doffing procedures for PPE be provided. Last, we suggest that all visitors be screened for symptoms before visitation and that visitor logs be maintained.Publication Metadata only Pragmatic recommendations for safety while caring for hospitalized patients with COVID-19 in low- And middle-income countries(2021-03-01) Rebecca Inglis; Lia Barros; William Checkley; Elif A. Cizmeci; Faith Lelei-Mailu; Rajyabardhan Pattnaik; Alfred Papali; Marcus J. Schultz; Juliana C. Ferreira; Ispat General Hospital; Africa Inland Church Kijabe Hospital; University of Toronto; University of Washington; Mahosot Hospital, Lao; Mahidol University; Universidade de São Paulo; Amsterdam UMC - University of Amsterdam; Johns Hopkins School of Medicine; Division of Pulmonary and Critical Care MedicineInfection prevention and control measures to control the spread of COVID-19 are challenging to implement in many low- and middle-income countries (LMICs). This is compounded by the fact that most recommendations are based on evidence that mainly originates in high-income countries. There are often availability, affordability, and feasibility barriers to applying such recommendations in LMICs, and therefore, there is a need for developing recommendations that are achievable in LMICs. We used a modified version of the GRADE method to select important questions, searched the literature for relevant evidence, and formulated pragmatic recommendations for safety while caring for patients with COVID-19 in LMICs. We selected five questions related to safety, covering minimal requirements for personal protective equipment (PPE), recommendations for extended use and reuse of PPE, restriction on the number of times healthcare workers enter patients’ rooms, hand hygiene, and environmental ventilation. We formulated 21 recommendations that are feasible and affordable in LMICs.Publication Metadata only Pragmatic recommendations for tracheostomy, discharge, and rehabilitation measures in hospitalized patients recovering from severe COVID-19 in low- And middle-income countries(2021-03-01) T. Eoin West; Marcus J. Schultz; Hanan Y. Ahmed; Gentle S. Shrestha; Alfred Papali; Tribhuvan University Teaching Hospital; Addis Ababa University; University of Oxford; University of Washington; Mahidol University; Amsterdam UMC - University of Amsterdam; Division of Pulmonary and Critical Care MedicineNew studies of COVID-19 are constantly updating best practices in clinical care. However, research mainly originates in resource-rich settings in high-income countries. Often, it is impractical to apply recommendations based on these investigations to resource-constrained settings in low- and middle-income countries (LMICs). We report on a set of pragmatic recommendations for tracheostomy, discharge, and rehabilitation measures in hospitalized patients recovering from severe COVID-19 in LMICs. We recommend that tracheostomy be performed in a negative pressure room or negative pressure operating room, if possible, and otherwise in a single room with a closed door. We recommend using the technique that is most familiar to the institution and that can be conducted most safely. We recommend using fit-tested enhanced personal protection equipment, with the fewest people required, and incorporating strategies to minimize aerosolization of the virus. For recovering patients, we suggest following local, regional, or national hospital discharge guidelines. If these are lacking, we suggest deisolation and hospital discharge using symptom-based criteria, rather than with testing. We likewise suggest taking into consideration the capability of primary caregivers to provide the necessary care to meet the psychological, physical, and neurocognitive needs of the patient.
