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  1. Article ; Online: Curated single cell multimodal landmark datasets for R/Bioconductor.

    Kelly B Eckenrode / Dario Righelli / Marcel Ramos / Ricard Argelaguet / Christophe Vanderaa / Ludwig Geistlinger / Aedin C Culhane / Laurent Gatto / Vincent Carey / Martin Morgan / Davide Risso / Levi Waldron

    PLoS Computational Biology, Vol 19, Iss 8, p e

    2023  Volume 1011324

    Abstract: Background The majority of high-throughput single-cell molecular profiling methods quantify RNA expression; however, recent multimodal profiling methods add simultaneous measurement of genomic, proteomic, epigenetic, and/or spatial information on the ... ...

    Abstract Background The majority of high-throughput single-cell molecular profiling methods quantify RNA expression; however, recent multimodal profiling methods add simultaneous measurement of genomic, proteomic, epigenetic, and/or spatial information on the same cells. The development of new statistical and computational methods in Bioconductor for such data will be facilitated by easy availability of landmark datasets using standard data classes. Results We collected, processed, and packaged publicly available landmark datasets from important single-cell multimodal protocols, including CITE-Seq, ECCITE-Seq, SCoPE2, scNMT, 10X Multiome, seqFISH, and G&T. We integrate data modalities via the MultiAssayExperiment Bioconductor class, document and re-distribute datasets as the SingleCellMultiModal package in Bioconductor's Cloud-based ExperimentHub. The result is single-command actualization of landmark datasets from seven single-cell multimodal data generation technologies, without need for further data processing or wrangling in order to analyze and develop methods within Bioconductor's ecosystem of hundreds of packages for single-cell and multimodal data. Conclusions We provide two examples of integrative analyses that are greatly simplified by SingleCellMultiModal. The package will facilitate development of bioinformatic and statistical methods in Bioconductor to meet the challenges of integrating molecular layers and analyzing phenotypic outputs including cell differentiation, activity, and disease.
    Keywords Biology (General) ; QH301-705.5
    Subject code 004
    Language English
    Publishing date 2023-08-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis.

    Matthew Schwede / Dimitrios Spentzos / Stefan Bentink / Oliver Hofmann / Benjamin Haibe-Kains / David Harrington / John Quackenbush / Aedín C Culhane

    PLoS ONE, Vol 8, Iss 3, p e

    2013  Volume 57799

    Abstract: Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy ... ...

    Abstract Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable in the clinical management or treatment of ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Community-wide hackathons to identify central themes in single-cell multi-omics

    Kim-Anh Lê Cao / Al J. Abadi / Emily F. Davis-Marcisak / Lauren Hsu / Arshi Arora / Alexis Coullomb / Atul Deshpande / Yuzhou Feng / Pratheepa Jeganathan / Melanie Loth / Chen Meng / Wancen Mu / Vera Pancaldi / Kris Sankaran / Amrit Singh / Joshua S. Sodicoff / Genevieve L. Stein-O’Brien / Ayshwarya Subramanian / Joshua D. Welch /
    Yue You / Ricard Argelaguet / Vincent J. Carey / Ruben Dries / Casey S. Greene / Susan Holmes / Michael I. Love / Matthew E. Ritchie / Guo-Cheng Yuan / Aedin C. Culhane / Elana Fertig

    Genome Biology, Vol 22, Iss 1, Pp 1-

    2021  Volume 21

    Keywords Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Author Correction

    Kim-Anh Lê Cao / Al J. Abadi / Emily F. Davis-Marcisak / Lauren Hsu / Arshi Arora / Alexis Coullomb / Atul Deshpande / Yuzhou Feng / Pratheepa Jeganathan / Melanie Loth / Chen Meng / Wancen Mu / Vera Pancaldi / Kris Sankaran / Dario Righelli / Amrit Singh / Joshua S. Sodicoff / Genevieve L. Stein-O’Brien / Ayshwarya Subramanian /
    Joshua D. Welch / Yue You / Ricard Argelaguet / Vincent J. Carey / Ruben Dries / Casey S. Greene / Susan Holmes / Michael I. Love / Matthew E. Ritchie / Guo-Cheng Yuan / Aedin C. Culhane / Elana Fertig

    Genome Biology, Vol 22, Iss 1, Pp 1-

    Community-wide hackathons to identify central themes in single-cell multi-omics

    2021  Volume 2

    Keywords Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: RelA-Induced Interferon Response Negatively Regulates Proliferation.

    Bose S Kochupurakkal / Zhigang C Wang / Tony Hua / Aedin C Culhane / Scott J Rodig / Koraljka Rajkovic-Molek / Jean-Bernard Lazaro / Andrea L Richardson / Debajit K Biswas / J Dirk Iglehart

    PLoS ONE, Vol 10, Iss 10, p e

    2015  Volume 0140243

    Abstract: Both oncogenic and tumor-suppressor activities are attributed to the Nuclear Factor kappa B (NF-kB) pathway. Moreover, NF-kB may positively or negatively regulate proliferation. The molecular determinants of these opposing roles of NF-kB are unclear. ... ...

    Abstract Both oncogenic and tumor-suppressor activities are attributed to the Nuclear Factor kappa B (NF-kB) pathway. Moreover, NF-kB may positively or negatively regulate proliferation. The molecular determinants of these opposing roles of NF-kB are unclear. Using primary human mammary epithelial cells (HMEC) as a model, we show that increased RelA levels and consequent increase in basal transcriptional activity of RelA induces IRF1, a target gene. Induced IRF1 upregulates STAT1 and IRF7, and in consort, these factors induce the expression of interferon response genes. Activation of the interferon pathway down-regulates CDK4 and up-regulates p27 resulting in Rb hypo-phosphorylation and cell cycle arrest. Stimulation of HMEC with IFN-γ elicits similar phenotypic and molecular changes suggesting that basal activity of RelA and IFN-γ converge on IRF1 to regulate proliferation. The anti-proliferative RelA-IRF1-CDK4 signaling axis is retained in ER+/HER2- breast tumors analyzed by The Cancer Genome Atlas (TCGA). Using immuno-histochemical analysis of breast tumors, we confirm the negative correlation between RelA levels and proliferation rate in ER+/HER2- breast tumors. These findings attribute an anti-proliferative tumor-suppressor role to basal RelA activity. Inactivation of Rb, down-regulation of RelA or IRF1, or upregulation of CDK4 or IRF2 rescues the RelA-IRF1-CDK4 induced proliferation arrest in HMEC and are points of disruption in aggressive tumors. Activity of the RelA-IRF1-CDK4 axis may explain favorable response to CDK4/6 inhibition observed in patients with ER+ Rb competent tumors.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Significance analysis of prognostic signatures.

    Andrew H Beck / Nicholas W Knoblauch / Marco M Hefti / Jennifer Kaplan / Stuart J Schnitt / Aedin C Culhane / Markus S Schroeder / Thomas Risch / John Quackenbush / Benjamin Haibe-Kains

    PLoS Computational Biology, Vol 9, Iss 1, p e

    2013  Volume 1002875

    Abstract: A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic ... ...

    Abstract A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that "random" gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS) which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date) of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically annotated genomic datasets.
    Keywords Biology (General) ; QH301-705.5
    Subject code 004
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study

    Edward Burn / Seng Chan You / Anthony G. Sena / Kristin Kostka / Hamed Abedtash / Maria Tereza F. Abrahão / 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 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 C. E. Lane / Hyejin Lee / Kristine E. Lynch / Rupa Makadia / Michael E. Matheny / Paras P. Mehta / Daniel R. Morales / Karthik Natarajan / Fredrik Nyberg / Anna Ostropolets / Rae Woong Park / Jimyung Park / Jose D. Posada / Albert Prats-Uribe / Gowtham Rao / Christian Reich

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 11

    Abstract: Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with ... ...

    Abstract Detailed knowledge of the characteristics of COVID-19 patients helps with public health planning. Here, the authors use routinely-collected data from seven databases in three countries to describe the characteristics of >30,000 patients admitted with COVID-19 and compare them with those admitted for influenza in previous years.
    Keywords Science ; Q
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. 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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  9. 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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  10. 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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