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  1. Article ; Online: Development and validation of a prognostic model predicting symptomatic hemorrhagic transformation in acute ischemic stroke at scale in the OHDSI network.

    Qiong Wang / Jenna M Reps / Kristin Feeney Kostka / Patrick B Ryan / Yuhui Zou / Erica A Voss / Peter R Rijnbeek / RuiJun Chen / Gowtham A Rao / Henry Morgan Stewart / Andrew E Williams / Ross D Williams / Mui Van Zandt / Thomas Falconer / Margarita Fernandez-Chas / Rohit Vashisht / Stephen R Pfohl / Nigam H Shah / Suranga N Kasthurirathne /
    Seng Chan You / Qing Jiang / Christian Reich / Yi Zhou

    PLoS ONE, Vol 15, Iss 1, p e

    2020  Volume 0226718

    Abstract: Background and purpose Hemorrhagic transformation (HT) after cerebral infarction is a complex and multifactorial phenomenon in the acute stage of ischemic stroke, and often results in a poor prognosis. Thus, identifying risk factors and making an early ... ...

    Abstract Background and purpose Hemorrhagic transformation (HT) after cerebral infarction is a complex and multifactorial phenomenon in the acute stage of ischemic stroke, and often results in a poor prognosis. Thus, identifying risk factors and making an early prediction of HT in acute cerebral infarction contributes not only to the selections of therapeutic regimen but also, more importantly, to the improvement of prognosis of acute cerebral infarction. The purpose of this study was to develop and validate a model to predict a patient's risk of HT within 30 days of initial ischemic stroke. Methods We utilized a retrospective multicenter observational cohort study design to develop a Lasso Logistic Regression prediction model with a large, US Electronic Health Record dataset which structured to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). To examine clinical transportability, the model was externally validated across 10 additional real-world healthcare datasets include EHR records for patients from America, Europe and Asia. Results In the database the model was developed, the target population cohort contained 621,178 patients with ischemic stroke, of which 5,624 patients had HT within 30 days following initial ischemic stroke. 612 risk predictors, including the distance a patient travels in an ambulance to get to care for a HT, were identified. An area under the receiver operating characteristic curve (AUC) of 0.75 was achieved in the internal validation of the risk model. External validation was performed across 10 databases totaling 5,515,508 patients with ischemic stroke, of which 86,401 patients had HT within 30 days following initial ischemic stroke. The mean external AUC was 0.71 and ranged between 0.60-0.78. Conclusions A HT prognostic predict model was developed with Lasso Logistic Regression based on routinely collected EMR data. This model can identify patients who have a higher risk of HT than the population average with an AUC of 0.78. It shows the OMOP CDM is an ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Book ; Online: Risk of depression, suicidal ideation, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis

    Jennifer C.E Lane / James Weaver / Kristin Kostka / Talita Duarte-Salles / Maria Tereza F Abrahao / Heba Alghoul / Osaid Alser / Thamir M Alshammari / Carlos Areia / Juan M. Banda / Patricia Biedermann / Edward Burn / Paula Casajust / Kristina Fišter / Jill Hardin / Laura Hester / George Hripcsak / Benjamin Skov Kaas-Hansen / Sajan Khosla /
    Spyros Kolovos / Kristine E. Lynch / Rupa Makadia / Paras P. Mehta / Daniel R Morales / Henry Morgan-Stewart / Mees Mosseveld / Danielle Newby / Fredrik Nyberg / Anna Ostropolets / Rae Woong Park / Albert Prats-Uribe / Gowtham A. Rao / Christian Reich / Peter Rijnbeek / Anthony G. Sena / Azza Shoaibi / Matthew Spotnitz / Vignesh Subbian / Marc A Suchard / David Vizcaya / Haini Wen / Marcel de Wilde / Junqing Xie / Seng Chan You / Lin Zhang / Simon Lovestone / Patrick B Ryan / Daniel Prieto-Alhambra

    a multi-national network cohort study

    2020  

    Abstract: Objectives Concern has been raised in the rheumatological community regarding recent regulatory warnings that hydroxychloroquine used in the COVID-19 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident ... ...

    Abstract Objectives Concern has been raised in the rheumatological community regarding recent regulatory warnings that hydroxychloroquine used in the COVID-19 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation, or psychosis associated with hydroxychloroquine as used for rheumatoid arthritis (RA). Methods New user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and US). RA patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine (active comparator) and followed up in the short (30-day) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation, and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HR), with estimates pooled where I2<40%. Results 918,144 and 290,383 users of hydroxychloroquine and sulfasalazine, respectively, were included. No consistent risk of psychiatric events was observed with short-term hydroxychloroquine (compared to sulfasalazine) use, with meta-analytic HRs of 0.96 [0.79-1.16] for depression, 0.94 [0.49-1.77] for suicide/suicidal ideation, and 1.03 [0.66-1.60] for psychosis. No consistent long-term risk was seen, with meta-analytic HRs 0.94 [0.71-1.26] for depression, 0.77 [0.56-1.07] for suicide/suicidal ideation, and 0.99 [0.72-1.35] for psychosis. Conclusions Hydroxychloroquine as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation, or psychosis compared to sulfasalazine. No effects were seen in the short or long term. Use at higher dose or for different indications needs further investigation.
    Keywords COVID-19 ; Hydroxychloroquine ; Safety ; Rheumatoid Arthritis ; Psychosis ; Depression ; Sulfasalazine ; Risk ; covid19
    Subject code 310
    Publishing date 2020-08-07
    Publishing country eu
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Safety of hydroxychloroquine, alone and in combination with azithromycin, in light of rapid wide-spread use for COVID-19: a multinational, network cohort and self-controlled case series study

    Jennifer C.E Lane / James Weaver / Kristin Kostka / Talita Duarte-Salles / Maria Tereza F. Abrahao / Heba Alghoul / Osaid Alser / Thamir M Alshammari / Patricia Biedermann / Edward Burn / Paula Casajust / Mitch Conover / Aedin C. Culhane / Alexander Davydov / Scott L. DuVall / Dmitry Dymshyts / Sergio Fernández Bertolín / Kristina Fišter / Jill Hardin /
    Laura Hester / George Hripcsak / Seamus Kent / Sajan Khosla / Spyros Kolovos / Christophe G. Lambert / Johan ver der Lei / Ajit A. Londhe / Kristine E. Lynch / Rupa Makadia / Andrea V. Margulis / Michael E. Matheny / Paras Mehta / Daniel R. Morales / Henry Morgan-Stewart / Mees Mosseveld / Danielle Newby / Fredrik Nyberg / Anna Ostropolets / Rae Woong Park / Albert Prats-Uribe / Gowtham A. Rao / Christian Reich / Jenna Reps / Peter Rijnbeek / Selva Muthu Kumaran Sathappan / Martijn Schuemie / Sarah Seager / Anthony Sena / Azza Shoaibi / Matthew Spotnitz / Marc A. Suchard / Joel Swerdel / Carmen Olga Torre / David Vizcaya / Haini Wen / Marcel de Wilde / Seng Chan You / Lin Zhang / Oleg Zhuk / Patrick Ryan / Daniel Prieto-Alhambra

    Abstract: Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with ... ...

    Abstract Background: Hydroxychloroquine has recently received Emergency Use Authorization by the FDA and is currently prescribed in combination with azithromycin for COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin. Methods: New user cohort studies were conducted including 16 severe adverse events (SAEs). Rheumatoid arthritis patients aged 18+ and initiating hydroxychloroquine were compared to those initiating sulfasalazine and followed up over 30 days. Self-controlled case series (SCCS) were conducted to further establish safety in wider populations. Separately, SAEs associated with hydroxychloroquine-azithromycin (compared to hydroxychloroquine-amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, Netherlands, Spain, UK, and USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (CalHRs) according to drug use. Estimates were pooled where I2<40%. Results: Overall, 956,374 and 310,350 users of hydroxychloroquine and sulfasalazine, and 323,122 and 351,956 users of hydroxychloroquine-azithromycin and hydroxychloroquine-amoxicillin were included. No excess risk of SAEs was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. SCCS confirmed these findings. However, when azithromycin was added to hydroxychloroquine, we observed an increased risk of 30-day cardiovascular mortality (CalHR2.19 [1.22-3.94]), chest pain/angina (CalHR 1.15 [95% CI 1.05-1.26]), and heart failure (CalHR 1.22 [95% CI 1.02-1.45]) Conclusions: Short-term hydroxychloroquine treatment is safe, but addition of azithromycin may induce heart failure and cardiovascular mortality, potentially due to synergistic effects on QT length. We call for caution if such combination is to be used in the management of Covid-19.
    Keywords covid19
    Publisher medrxiv
    Document type Article ; Online
    DOI 10.1101/2020.04.08.20054551
    Database COVID19

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  4. Article ; Online: An international characterisation of patients hospitalised with COVID-19 and a comparison with those previously hospitalised with influenza

    Edward Burn / Seng Chan You / Anthony Sena / Kristin Kostka / Hamed Abedtash / Maria Tereza F. Abrahao / Amanda Alberga / Heba Alghoul / Osaid Alser / Thamir M Alshammari / Carlos Areia / Juan M Banda / Jaehyeong Cho / Aedin C Culhane / Alexander Davydov / Frank J DeFalco / Talita Duarte-Salles / Scott L DuVall / Thomas Falconer /
    Weihua Gao / Asieh Golozar / Jill Hardin / George Hripcsak / Vojtech Huser / Hokyun Jeon / Yonghua Jing / Chi Young Jung / Benjamin Skov Kaas-Hansen / Denys Kaduk / Seamus Kent / Yeesuk Kim / Spyros Kolovos / Jennifer Lane / Hyejin Lee / Kristine E. Lynch / Rupa Makadia / Michael E. Matheny / Paras Mehta / Daniel R. Morales / Karthik Natarajan / Fredrik Nyberg / Anna Ostropolets / Rae Woong Park / Jimyung Park / Jose D. Posada / Albert Prats-Uribe / Gowtham A. Rao / Christian Reich / Yeunsook Rho / Peter Rijnbeek / Selva Muthu Kumaran Sathappan / Lisa M. Schilling / Martijn Schuemie / Nigam H. Shah / Azza Shoaibi / Seokyoung Song / Matthew Spotnitz / Marc A. Suchard / Joel Swerdel / David Vizcaya / Salvatore Volpe / Haini Wen / Andrew E Williams / Belay B Yimer / Lin Zhang / Oleg Zhuk / Daniel Prieto-Alhambra / Patrick Ryan

    Abstract: Background To better understand the profile of individuals with severe coronavirus disease 2019 (COVID-19), we characterised individuals hospitalised with COVID-19 and compared them to individuals previously hospitalised with influenza. Methods We report ...

    Abstract Background To better understand the profile of individuals with severe coronavirus disease 2019 (COVID-19), we characterised individuals hospitalised with COVID-19 and compared them to individuals previously hospitalised with influenza. Methods We report the characteristics (demographics, prior conditions and medication use) of patients hospitalised with COVID-19 between December 2019 and April 2020 in the US (Columbia University Irving Medical Center [CUIMC], STAnford Medicine Research data Repository [STARR-OMOP], and the Department of Veterans Affairs [VA OMOP]) and Health Insurance Review & Assessment [HIRA] of South Korea. Patients hospitalised with COVID-19 were compared with patients previously hospitalised with influenza in 2014-19. Results 6,806 (US: 1,634, South Korea: 5,172) individuals hospitalised with COVID-19 were included. Patients in the US were majority male (VA OMOP: 94%, STARR-OMOP: 57%, CUIMC: 52%), but were majority female in HIRA (56%). Age profiles varied across data sources. Prevalence of asthma ranged from 7% to 14%, diabetes from 18% to 43%, and hypertensive disorder from 22% to 70% across data sources, while between 9% and 39% were taking drugs acting on the renin-angiotensin system in the 30 days prior to their hospitalisation. Compared to 52,422 individuals hospitalised with influenza, patients admitted with COVID-19 were more likely male, younger, and, in the US, had fewer comorbidities and lower medication use. Conclusions Rates of comorbidities and medication use are high among individuals hospitalised with COVID-19. However, COVID-19 patients are more likely to be male and appear to be younger and, in the US, generally healthier than those typically admitted with influenza.
    Keywords covid19
    Publisher medrxiv
    Document type Article ; Online
    DOI 10.1101/2020.04.22.20074336
    Database COVID19

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  5. Article ; Online: Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis

    Jennifer C E Lane / James Weaver / Kristin Kostka / Talita Duarte-Salles / Maria Tereza F Abrahao / Heba Alghoul / Osaid Alser / Thamir M Alshammari / Patricia Biedermann / Juan M Banda / Edward Burn / Paula Casajust / Mitchell M Conover / Aedin C Culhane / Alexander Davydov / Scott L DuVall / Dmitry Dymshyts / Sergio Fernandez-Bertolin / Kristina Fišter /
    Jill Hardin / Laura Hester / George Hripcsak / Benjamin Skov Kaas-Hansen / Seamus Kent / Sajan Khosla / Spyros Kolovos / Christophe G Lambert / Johan van der Lei / Kristine E Lynch / Rupa Makadia / Andrea V Margulis / Michael E Matheny / Paras Mehta / Daniel R Morales / Henry Morgan-Stewart / Mees Mosseveld / Danielle Newby / Fredrik Nyberg / Anna Ostropolets / Rae Woong Park / Albert Prats-Uribe / Gowtham A Rao / Christian Reich / Jenna Reps / Peter Rijnbeek / Selva Muthu Kumaran Sathappan / Martijn Schuemie / Sarah Seager / Anthony G Sena / Azza Shoaibi / Matthew Spotnitz / Marc A Suchard / Carmen O Torre / David Vizcaya / Haini Wen / Marcel de Wilde / Junqing Xie / Seng Chan You / Lin Zhang / Oleg Zhuk / Patrick Ryan / Daniel Prieto-Alhambra / OHDSI-COVID-19 consortium

    The Lancet Rheumatology

    a multinational, retrospective study

    2020  

    Abstract: Background Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We ... ...

    Abstract Background Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis. Methods In this multinational, retrospective study, new user cohort studies in patients with rheumatoid arthritis aged 18 years or older and initiating hydroxychloroquine were compared with those initiating sulfasalazine and followed up over 30 days, with 16 severe adverse events studied. Self-controlled case series were done to further establish safety in wider populations, and included all users of hydroxychloroquine regardless of rheumatoid arthritis status or indication. Separately, severe adverse events associated with hydroxychloroquine plus azithromycin (compared with hydroxychloroquine plus amoxicillin) were studied. Data comprised 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the UK, and the USA. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate calibrated hazard ratios (HRs) according to drug use. Estimates were pooled where the I² value was less than 0·4. Findings The study included 956 374 users of hydroxychloroquine, 310 350 users of sulfasalazine, 323 122 users of hydroxychloroquine plus azithromycin, and 351 956 users of hydroxychloroquine plus amoxicillin. No excess risk of severe adverse events was identified when 30-day hydroxychloroquine and sulfasalazine use were compared. Selfcontrolled case series confirmed these findings. However, long-term use of hydroxychloroquine appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12–2·44]). Addition of azithromycin appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22–3·95]), chest pain or angina (1·15 [1·05–1·26]), and heart failure (1·22 [1·02–1·45]). Interpretation Hydroxychloroquine treatment appears to have no increased risk in the short term among patients with rheumatoid arthritis, but in the long term it appears to be associated with excess cardiovascular mortality. The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit–risk trade-off when counselling those on hydroxychloroquine treatment.
    Keywords Hydroxychloroquine ; Sulfasalazine ; Azithromycin ; Adverse events ; Rheumatoid arthritis ; Safety ; COVID-19 ; Pneumonia ; covid19
    Subject code 610
    Publishing date 2020-10-13
    Publishing country eu
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Book ; Online: Deep phenotyping of 34,128 patients hospitalised with COVID-19 and a comparison with 81,596 influenza patients in America, Europe and Asia

    Edward Burn / Seng Chan You / Anthony Sena / Kristin Kostka / Hamed Abedtash / Maria Tereza F. Abrahao / Amanda Alberga / Heba Alghoul / Osaid Alser / Thamir M Alshammari / Maria Aragon / Carlos Areia / Juan M Banda / Jaehyeong Cho / Aedin C Culhane / Alexander Davydov / Frank J DeFalco / Talita Duarte-Salles / Scott L DuVall /
    Thomas Falconer / Sergio Fernandez-Bertolin / Weihua Gao / Asieh Golozar / Jill Hardin / George Hripcsak / Vojtech Huser / Hokyun Jeon / Yonghua Jing / Chi Young Jung / Benjamin Skov Kaas-Hansen / Denys Kaduk / Seamus Kent / Yeesuk Kim / Spyros Kolovos / Jennifer Lane / Hyejin Lee / Kristine E. Lynch / Rupa Makadia / Michael E. Matheny / Paras Mehta / Daniel R. Morales / Karthik Natarajan / Fredrik Nyberg / Anna Ostropolets / Rae Woong Park / Jimyung Park / Jose D. Posada / Albert Prats-Uribe / Gowtham A. Rao / Christian Reich / Yeunsook Rho / Peter Rijnbeek / Lisa M. Schilling / Martijn Schuemie / Nigam H. Shah / Azza Shoaibi / Seokyoung Song / Matthew Spotnitz / Marc A. Suchard / Joel Swerdel / David Vizcaya / Salvatore Volpe / Haini Wen / Andrew E Williams / Belay B Yimer / Lin Zhang / Oleg Zhuk / Daniel Prieto-Alhambra / Patrick Ryan

    an international network study

    2020  

    Abstract: Background In this study we phenotyped individuals hospitalised with coronavirus disease 2019 (COVID-19) in depth, summarising entire medical histories, including medications, as captured in routinely collected data drawn from databases across three ... ...

    Abstract Background In this study we phenotyped individuals hospitalised with coronavirus disease 2019 (COVID-19) in depth, summarising entire medical histories, including medications, as captured in routinely collected data drawn from databases across three continents. We then compared individuals hospitalised with COVID-19 to those previously hospitalised with influenza. Methods We report demographics, previously recorded conditions and medication use of patients hospitalised with COVID-19 in the US (Columbia University Irving Medical Center [CUIMC], Premier Healthcare Database [PHD], UCHealth System Health Data Compass Database [UC HDC], and the Department of Veterans Affairs [VA OMOP]), in South Korea (Health Insurance Review & Assessment [HIRA]), and Spain (The Information System for Research in Primary Care [SIDIAP] and HM Hospitales [HM]). These patients were then compared with patients hospitalised with influenza in 2014-19. Results 34,128 (US: 8,362, South Korea: 7,341, Spain: 18,425) individuals hospitalised with COVID-19 were included. Between 4,811 (HM) and 11,643 (CUIMC) unique aggregate characteristics were extracted per patient, with all summarised in an accompanying interactive website (http://evidence.ohdsi.org/Covid19CharacterizationHospitalization/). Patients were majority male in the US (CUIMC: 52%, PHD: 52%, UC HDC: 54%, VA OMOP: 94%,) and Spain (SIDIAP: 54%, HM: 60%), but were predominantly female in South Korea (HIRA: 60%). Age profiles varied across data sources. Prevalence of asthma ranged from 4% to 15%, diabetes from 13% to 43%, and hypertensive disorder from 24% to 70% across data sources. Between 14% and 33% were taking drugs acting on the renin-angiotensin system in the 30 days prior to hospitalisation. Compared to 81,596 individuals hospitalised with influenza in 2014-19, patients admitted with COVID-19 were more typically male, younger, and healthier, with fewer comorbidities and lower medication use. Conclusions We provide a detailed characterisation of patients hospitalised with COVID-19. Protecting groups known to be vulnerable to influenza is a useful starting point to minimize the number of hospital admissions needed for COVID-19. However, such strategies will also likely need to be broadened so as to reflect the particular characteristics of individuals hospitalised with COVID-19.
    Keywords COVID-19 ; Influenza ; Hospitalisation ; Phenotype ; covid19
    Subject code 610
    Publishing date 2020-06-28
    Publishing country eu
    Document type Book ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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