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2. Developing an Intuitive and Feasible Setup for In-room Control During MRI-guided Interventions

Author

Reich C. Martin, Unger Michael, Melzer Leon, Jochimsen Thies, Sattler Bernhard, Sabri Osama, and Melzer Andreas

Subjects
magnetic resonance imaging (mri), mri remote control, mri-guided interventions, interventional mri, Medicine
Abstract

Magnetic resonance image (MRI)-guidance for minimally invasive interventions instead of CT-guidance is a promising technique to reduce radiation exposure for both patients and clinicians. Technical challenges have to be managed in order to meet safety regulations while enabling inroom system control and communication. Using nonproprietary software and hardware, several gradations for a setup for interventional MRI were elaborated. Eventually, a quickly and easily installable setup was established for technical support during MRI-guided interventions in the PET/MRI suite at the Department of Nuclear Medicine at University Hospital Leipzig. It is adaptable for most MRI suites.

Published
2020
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5. How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis

Author

N’Dow, J., Smith, E.J., Shepherd, R., Ribal, M., Mottet, N., Moris, L., Lardas, M., Willemse, P-P., Gandaglia, G., Campi, R., Nicoletti, Rossella, Gacci, M., Briganti, A., Ratti, M.M., Alleva, E., Leardini, L., Sisca, E.S., Bangma, R., Roobol, M., Remmers, S., Tilki, D., Visakorpi, T., Talala, K., Tammela, T., van Hemelrijck, M., Bayer, K., Lejeune, S., Byrne, S., Fialho, L., De Meulder, P. Palaiologou B., Auffray, C., Hijazy, A., Power, S., Kermani, N. Zounemat, van Bochove, K., Kalafati, M., Moinat, M., Voss, E., Horgan, D., Fullwood, L., Holtorf, M., Lancet, D., Bernstein, G., Omar, I., MacLennan, S., Maclennan, S., Tripathee, S., Wirth, M., Froehner, M., Brenner, B., Borkowetz, A., Thomas, C., Horn, F., Reiche, K., Kreux, M., Josefsson, A., Tandefekt, D. Gasi, Hugosson, J., Huisman, H., Schalken, J., Hofmacher, T., Lindgren, P., Andersson, E., Fridhammar, A., Zong, J., Butler-Ransohoff, J-E., Herrera, R., Maass, M., Torremante, P., Voss, M.D., Devecseri, Z., Abbott, T., Dau, C., Papineni, K., Snijder, R., Lambrecht, M., Wolfinger, R., Rogiers, S., Servan, A., Antoni, L., Pacoe, K., Robinson, P., Jaton, B., Bakkard, D., Turunen, H., Kilkku, O., Pohjanjousi, P., Voima, O., Nevalaita, L., Reich, C., Araujo, S., Longden-Chapman, E., Burke, D., Agapow, P., Derkits, S., Licour, M., McCrea, C., Payne, S., Yong, A., Thompson, L., Mare, S. Le, Bussmann, M, Kotik, D., Siltari, Aino, Lönnerbro, Ragnar, Pang, Karl, Shiranov, Kirill, Asiimwe, Alex, Evans-Axelsson, Susan, Franks, Billy, Kiran, Amit, Murtola, Teemu J., Schalken, Jack, Steinbeisser, Carl, Bjartell, Anders, and Auvinen, Anssi

Published
2023
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7. Arsenic-Doped CdSeTe Solar Cells Achieve World Record 22.3% Efficiency

Author

Mallick, R., primary, Li, X., additional, Reich, C., additional, Shan, X., additional, Zhang, W., additional, Nagle, T., additional, Bok, L., additional, Bicakci, E., additional, Rosenblatt, N., additional, Modi, D., additional, Farshchi, R., additional, Lee, C., additional, Hack, J., additional, Grover, S., additional, Wolf, N., additional, Metzger, W.K., additional, Lu, D., additional, and Xiong, G., additional

Published
2023
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9. How Well do Polygenic Risk Scores Identify Men at High Risk for Prostate Cancer? Systematic Review and Meta-Analysis

Author

Siltari, Aino, primary, Lönnerbro, Ragnar, additional, Pang, Karl, additional, Shiranov, Kirill, additional, Asiimwe, Alex, additional, Evans-Axelsson, Susan, additional, Franks, Billy, additional, Kiran, Amit, additional, Murtola, Teemu J., additional, Schalken, Jack, additional, Steinbeisser, Carl, additional, Bjartell, Anders, additional, Auvinen, Anssi, additional, N’Dow, J., additional, Smith, E.J., additional, Shepherd, R., additional, Ribal, M., additional, Mottet, N., additional, Moris, L., additional, Lardas, M., additional, Willemse, P-P., additional, Gandaglia, G., additional, Campi, R., additional, Nicoletti, Rossella, additional, Gacci, M., additional, Briganti, A., additional, Ratti, M.M., additional, Alleva, E., additional, Leardini, L., additional, Sisca, E.S., additional, Bangma, R., additional, Roobol, M., additional, Remmers, S., additional, Tilki, D., additional, Visakorpi, T., additional, Talala, K., additional, Tammela, T., additional, van Hemelrijck, M., additional, Bayer, K., additional, Lejeune, S., additional, Byrne, S., additional, Fialho, L., additional, De Meulder, P. Palaiologou B., additional, Auffray, C., additional, Hijazy, A., additional, Power, S., additional, Kermani, N. Zounemat, additional, van Bochove, K., additional, Kalafati, M., additional, Moinat, M., additional, Voss, E., additional, Horgan, D., additional, Fullwood, L., additional, Holtorf, M., additional, Lancet, D., additional, Bernstein, G., additional, Omar, I., additional, MacLennan, S., additional, Maclennan, S., additional, Tripathee, S., additional, Wirth, M., additional, Froehner, M., additional, Brenner, B., additional, Borkowetz, A., additional, Thomas, C., additional, Horn, F., additional, Reiche, K., additional, Kreux, M., additional, Josefsson, A., additional, Tandefekt, D. Gasi, additional, Hugosson, J., additional, Huisman, H., additional, Schalken, J., additional, Hofmacher, T., additional, Lindgren, P., additional, Andersson, E., additional, Fridhammar, A., additional, Zong, J., additional, Butler-Ransohoff, J-E., additional, Herrera, R., additional, Maass, M., additional, Torremante, P., additional, Voss, M.D., additional, Devecseri, Z., additional, Abbott, T., additional, Dau, C., additional, Papineni, K., additional, Snijder, R., additional, Lambrecht, M., additional, Wolfinger, R., additional, Rogiers, S., additional, Servan, A., additional, Antoni, L., additional, Pacoe, K., additional, Robinson, P., additional, Jaton, B., additional, Bakkard, D., additional, Turunen, H., additional, Kilkku, O., additional, Pohjanjousi, P., additional, Voima, O., additional, Nevalaita, L., additional, Reich, C., additional, Araujo, S., additional, Longden-Chapman, E., additional, Burke, D., additional, Agapow, P., additional, Derkits, S., additional, Licour, M., additional, McCrea, C., additional, Payne, S., additional, Yong, A., additional, Thompson, L., additional, Mare, S. Le, additional, Bussmann, M, additional, and Kotik, D., additional

Published
2023
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10. Comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with different covid-19 vaccines

Author

Li, X, Burn, E, Duarte-Salles, T, Yin, C, Reich, C, Delmestri, A, Verhamme, K, Rijnbeek, P, Suchard, MA, Li, K, Mosseveld, M, John, LH, Mayer, M-A, Ramirez-Anguita, J-M, Cohet, C, Strauss, V, Prieto-Alhambra, D, Medical Informatics, and Epidemiology

Subjects
Adult, Venous Thrombosis, COVID-19 Vaccines, Adolescent, Ad26COVS1, COVID-19, Thrombosis, General Medicine, Thrombocytopenia, Cohort Studies, SDG 3 - Good Health and Well-being, Thromboembolism, Humans, BNT162 Vaccine
Abstract

Objective To quantify the comparative risk of thrombosis with thrombocytopenia syndrome or thromboembolic events associated with use of adenovirus based covid-19 vaccines versus mRNA based covid-19 vaccines. Design International network cohort study. Setting Routinely collected health data from contributing datasets in France, Germany, the Netherlands, Spain, the UK, and the US. Participants Adults (age ≥18 years) registered at any contributing database and who received at least one dose of a covid-19 vaccine (ChAdOx1-S (Oxford-AstraZeneca), BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), or Ad26.COV2.S (Janssen/Johnson & Johnson)), from December 2020 to mid-2021. Main outcome measures Thrombosis with thrombocytopenia syndrome or venous or arterial thromboembolic events within the 28 days after covid-19 vaccination. Incidence rate ratios were estimated after propensity scores matching and were calibrated using negative control outcomes. Estimates specific to the database were pooled by use of random effects meta-analyses. Results Overall, 1 332 719 of 3 829 822 first dose ChAdOx1-S recipients were matched to 2 124 339 of 2 149 679 BNT162b2 recipients from Germany and the UK. Additionally, 762 517 of 772 678 people receiving Ad26.COV2.S were matched to 2 851 976 of 7 606 693 receiving BNT162b2 in Germany, Spain, and the US. All 628 164 Ad26.COV2.S recipients from the US were matched to 2 230 157 of 3 923 371 mRNA-1273 recipients. A total of 862 thrombocytopenia events were observed in the matched first dose ChAdOx1-S recipients from Germany and the UK, and 520 events after a first dose of BNT162b2. Comparing ChAdOx1-S with a first dose of BNT162b2 revealed an increased risk of thrombocytopenia (pooled calibrated incidence rate ratio 1.33 (95% confidence interval 1.18 to 1.50) and calibrated incidence rate difference of 1.18 (0.57 to 1.8) per 1000 person years). Additionally, a pooled calibrated incidence rate ratio of 2.26 (0.93 to 5.52) for venous thrombosis with thrombocytopenia syndrome was seen with Ad26.COV2.S compared with BNT162b2. Conclusions In this multinational study, a pooled 30% increased risk of thrombocytopenia after a first dose of the ChAdOx1-S vaccine was observed, as was a trend towards an increased risk of venous thrombosis with thrombocytopenia syndrome after Ad26.COV2.S compared with BNT162b2. Although rare, the observed risks after adenovirus based vaccines should be considered when planning further immunisation campaigns and future vaccine development.

Published
2022

18. A Follow-Up Study of the Deaf.

Author

Toronto Univ. (Ontario)., Reich, P. A., and Reich, C. M.

Abstract

Followed up through interviews and questionnaires were 278 former students, average age 28 years, of two residential schools and one day school for the deaf in Ontario. Data was collected on the degree of hearing loss, use of a hearing aid, educational and occupational history, social integration, methods of communication, and attitudes toward school. A reading and writing test were also administered. Some of the data indicated that most former students has English speaking, normally hearing parents; that 88% of the predominantly prelingually deafened graduates were profoundly deaf; that slightly more than half of the former students had ever used a hearing aid; that school attendance averaged 13.3 years; that employment of deaf men were similar to employment of hearing men, although the rate of advancement and salary raise were lower; that half of the former students (all all over 35 years of age) were married; that 61% of married former students had children; that 18% of the graduates had hearing friends; that speech, writing, and reading skills were low; that 80% of former students used signing, fingerspelling, and total communication; and that day students were more oral than residential students. Approximately half the former students suggested that manual communication be introduced to the school curriculum whereas 21% of the graduates requested higher academic standards. (MC)

Published
1974

19. OHDSI Germany – Join the Journey: A Workshop

Author

Reinecke, I, Zoch, M, Reich, C, Kallfelz, M, Grewe, N, and Sedlmayr, M

Subjects
ddc: 610, OHDS, Medicine and health, studien, interoperabilität, standardisierung, OMOP
Abstract

The Observational Health Data Science and Informatics (OHDSI) is an international collaboration that enables researchers to conduct observational studies around the globe based on standardized data and methods that was founded in 2014 [ref:1]. OHDSI provides a common data model (OMOP CDM) [for full text, please go to the a.m. URL]

Published
2021
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21. Language: A Study of Fundamental Skills. No. 108.

Author

Toronto Board of Education (Ontario). Research Dept., Wright, E. N., and Reich, C. M.

Abstract

During the school year 1971-72, a study of language skills was conducted in the city of Toronto, Ontario. Scores on the Gates-MacGinitie Reading Test were analyzed for many students in grades four, six, eight, and nine. Students scored at grade level with reference to the United States norms of this test. The vocabulary and reading subsections of the Canadian Tests of Basic Skills were also administered to groups of students in grades four, six, and eight in order to compare the two tests. The relative performance of students on this test was similar to performance on the Gates-MacGinitie; however, the scores were several months lower. A questionnaire was administered to a sample of sixth graders concerning their reading activities and their parents' reading activities. In general, the sixth graders reported that they and their parents engaged in many reading activities. The favorite themes of the children were mystery, adventure, and horror. Analysis of compositions collected from a sample of eighth graders showed that most of the students can write a coherent narrative of acceptable prose. Parents' occupation was found to be related to all three measures of language ability, with higher occupational status being associated with higher scores. (MKM)

Published
1972

22. Introducing PIONEER: a project to harness big data in prostate cancer research

Author

Omar M. I., Roobol M. J., Ribal M. J., Abbott T., Agapow P. -M., Araujo S., Asiimwe A., Auffray C., Balaur I., Beyer K., Bernini C., Bjartell A., Briganti A., Butler-Ransohoff J. -E., Campi R., Cavelaars M., De Meulder B., Devecseri Z., Voss M. D., Dimitropoulos K., Evans-Axelsson S., Franks B., Fullwood L., Horgan D., Smith E. J., Kiran A., Kivinummi K., Lambrecht M., Lancet D., Lindgren P., MacLennan S., Nogueira M. M., Moen F., Moinat M., Papineni K., Reich C., Reiche K., Rogiers S., Sartini C., van Bochove K., van Diggelen F., Van Hemelrijck M., Van Poppel H., Zong J., N'Dow J., Andersson E., Arala H., Auvinen A., Bangma C., Burke D., Cardone A., Casariego J., Cuperus G., Dabestani S., Esperto F., Fossati N., Fridhammar A., Gandaglia G., Tandefelt D. G., Horn F., Huber J., Hugosson J., Huisman H., Josefsson A., Kilkku O., Kreuz M., Lardas M., Lawson J., Lefresne F., Lejeune S., Longden-Chapman E., McVie G., Moris L., Mottet N., Murtola T., Nicholls C., Pang K. H., Pascoe K., Picozzi M., Plass K., Pohjanjousi P., Reaney M., Remmers S., Robinson P., Schalken J., Schravendeel M., Seisen T., Servan A., Shiranov K., Snijder R., Steinbeisser C., Taibi N., Talala K., Tilki D., Van den Broeck T., Vassilev Z., Voima O., Vradi E., Waldeck R., Weistra W., Willemse P. -P., Wirth M., Wolfinger R., Kermani N. Z., Omar, M. I., Roobol, M. J., Ribal, M. J., Abbott, T., Agapow, P. -M., Araujo, S., Asiimwe, A., Auffray, C., Balaur, I., Beyer, K., Bernini, C., Bjartell, A., Briganti, A., Butler-Ransohoff, J. -E., Campi, R., Cavelaars, M., De Meulder, B., Devecseri, Z., Voss, M. D., Dimitropoulos, K., Evans-Axelsson, S., Franks, B., Fullwood, L., Horgan, D., Smith, E. J., Kiran, A., Kivinummi, K., Lambrecht, M., Lancet, D., Lindgren, P., Maclennan, S., Nogueira, M. M., Moen, F., Moinat, M., Papineni, K., Reich, C., Reiche, K., Rogiers, S., Sartini, C., van Bochove, K., van Diggelen, F., Van Hemelrijck, M., Van Poppel, H., Zong, J., N'Dow, J., Andersson, E., Arala, H., Auvinen, A., Bangma, C., Burke, D., Cardone, A., Casariego, J., Cuperus, G., Dabestani, S., Esperto, F., Fossati, N., Fridhammar, A., Gandaglia, G., Tandefelt, D. G., Horn, F., Huber, J., Hugosson, J., Huisman, H., Josefsson, A., Kilkku, O., Kreuz, M., Lardas, M., Lawson, J., Lefresne, F., Lejeune, S., Longden-Chapman, E., Mcvie, G., Moris, L., Mottet, N., Murtola, T., Nicholls, C., Pang, K. H., Pascoe, K., Picozzi, M., Plass, K., Pohjanjousi, P., Reaney, M., Remmers, S., Robinson, P., Schalken, J., Schravendeel, M., Seisen, T., Servan, A., Shiranov, K., Snijder, R., Steinbeisser, C., Taibi, N., Talala, K., Tilki, D., Van den Broeck, T., Vassilev, Z., Voima, O., Vradi, E., Waldeck, R., Weistra, W., Willemse, P. -P., Wirth, M., Wolfinger, R., Kermani, N. Z., Publica, and Urology

Subjects
0301 basic medicine, Prioritization, Knowledge management, Urology, media_common.quotation_subject, education, Big data, Disease, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Multidisciplinary approach, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Medicine, Quality (business), media_common, business.industry, Patient-centered outcomes, medicine.disease, 3. Good health, Patient management, 030104 developmental biology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, business
Abstract

Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate cancer management by unlocking the potential of big data. The project has identified critical evidence gaps in prostate cancer care, via a detailed prioritization exercise including all key stakeholders. By standardizing and integrating existing high-quality and multidisciplinary data sources from patients with prostate cancer across different stages of the disease, the resulting big data will be assembled into a single innovative data platform for research. Based on a unique set of methodologies, PIONEER aims to advance the field of prostate cancer care with a particular focus on improving prostate-cancer-related outcomes, health system efficiency by streamlining patient management, and the quality of health and social care delivered to all men with prostate cancer and their families worldwide.Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. In this Perspectives article, the authors introduce the PIONEER project and describe its aims and plans for ultimately improving prostate cancer care through the use of big data.

Published
2020

23. Author Correction: Introducing PIONEER: a project to harness big data in prostate cancer research (Nature Reviews Urology, (2020), 17, 6, (351-362), 10.1038/s41585-020-0324-x)

Author

Omar M. I., Roobol M. J., Ribal M. J., Abbott T., Agapow P. -M., Araujo S., Asiimwe A., Auffray C., Balaur I., Beyer K., Bernini C., Bjartell A., Briganti A., Butler-Ransohoff J. -E., Campi R., Cavelaars M., De Meulder B., Devecseri Z., Voss M. D., Dimitropoulos K., Evans-Axelsson S., Franks B., Fullwood L., Horgan D., Smith E. J., Kiran A., Kivinummi K., Lambrecht M., Lancet D., Lindgren P., MacLennan S., Nogueira M. M., Moen F., Moinat M., Papineni K., Reich C., Reiche K., Rogiers S., Sartini C., van Bochove K., van Diggelen F., Van Hemelrijck M., Van Poppel H., Zong J., N'Dow J., Andersson E., Arala H., Auvinen A., Bangma C., Burke D., Cardone A., Casariego J., Cuperus G., Dabestani S., Esperto F., Fossati N., Fridhammar A., Gandaglia G., Tandefelt D. G., Horn F., Huber J., Hugosson J., Huisman H., Josefsson A., Kilkku O., Kreuz M., Lardas M., Lawson J., Lefresne F., Lejeune S., Longden-Chapman E., McVie G., Moris L., Mottet N., Murtola T., Nicholls C., Pang K. H., Pascoe K., Picozzi M., Plass K., Pohjanjousi P., Reaney M., Remmers S., Robinson P., Schalken J., Schravendeel M., Seisen T., Servan A., Shiranov K., Snijder R., Steinbeisser C., Taibi N., Talala K., Tilki D., Van den Broeck T., Vassilev Z., Voima O., Vradi E., Waldeck R., Weistra W., Willemse P. -P., Wirth M., Wolfinger R., Kermani N. Z., Omar, M. I., Roobol, M. J., Ribal, M. J., Abbott, T., Agapow, P. -M., Araujo, S., Asiimwe, A., Auffray, C., Balaur, I., Beyer, K., Bernini, C., Bjartell, A., Briganti, A., Butler-Ransohoff, J. -E., Campi, R., Cavelaars, M., De Meulder, B., Devecseri, Z., Voss, M. D., Dimitropoulos, K., Evans-Axelsson, S., Franks, B., Fullwood, L., Horgan, D., Smith, E. J., Kiran, A., Kivinummi, K., Lambrecht, M., Lancet, D., Lindgren, P., Maclennan, S., Nogueira, M. M., Moen, F., Moinat, M., Papineni, K., Reich, C., Reiche, K., Rogiers, S., Sartini, C., van Bochove, K., van Diggelen, F., Van Hemelrijck, M., Van Poppel, H., Zong, J., N'Dow, J., Andersson, E., Arala, H., Auvinen, A., Bangma, C., Burke, D., Cardone, A., Casariego, J., Cuperus, G., Dabestani, S., Esperto, F., Fossati, N., Fridhammar, A., Gandaglia, G., Tandefelt, D. G., Horn, F., Huber, J., Hugosson, J., Huisman, H., Josefsson, A., Kilkku, O., Kreuz, M., Lardas, M., Lawson, J., Lefresne, F., Lejeune, S., Longden-Chapman, E., Mcvie, G., Moris, L., Mottet, N., Murtola, T., Nicholls, C., Pang, K. H., Pascoe, K., Picozzi, M., Plass, K., Pohjanjousi, P., Reaney, M., Remmers, S., Robinson, P., Schalken, J., Schravendeel, M., Seisen, T., Servan, A., Shiranov, K., Snijder, R., Steinbeisser, C., Taibi, N., Talala, K., Tilki, D., Van den Broeck, T., Vassilev, Z., Voima, O., Vradi, E., Waldeck, R., Weistra, W., Willemse, P. -P., Wirth, M., Wolfinger, R., and Kermani, N. Z.

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

26. The human cell atlas of the hypertrophic heart reveals impaired inter-cellular cross-talks

Author

Nicin, L, primary, Bruening, R S, additional, Kattih, B, additional, Glaser, S F, additional, Abplanalp, W T, additional, Schroeter, S M, additional, Arsalan, M, additional, Holubec, T, additional, Emrich, F, additional, Meder, B, additional, Reich, C, additional, Walther, T, additional, Zeiher, A M, additional, John, D, additional, and Dimmeler, S, additional

Published
2021
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30. Author Correction: Introducing PIONEER: A project to harness big data in prostate cancer research (Nature Reviews Urology, (2020), 17, 6, (351-362), 10.1038/s41585-020-0324-x)

Author

Omar, M.I., Roobol, M.J., Ribal, M.J., Abbott, T., Agapow, P.-M., Araujo, S., Asiimwe, A., Auffray, C., Balaur, I., Beyer, K., Bernini, C., Bjartell, A., Briganti, A., Butler-Ransohoff, J.-E., Campi, R., Cavelaars, M., Meulder, B. de, Devecseri, Z., Voss, M.D., Dimitropoulos, K., Evans-Axelsson, S., Franks, B., Fullwood, L., Horgan, D., Smith, E.J., Kiran, A., Kivinummi, K., Lambrecht, M., Lancet, D., Lindgren, P., MacLennan, S., Nogueira, M.M., Moen, F., Moinat, M., Papineni, K., Reich, C., Reiche, K., Rogiers, S., Sartini, C., Bochove, K. van, Diggelen, F. van, Hemelrijck, M. van, Poppel, H. van, Zong, J., N'Dow, J., Horn, F., Kreuz, M., and Publica

Abstract

The originally published article contained errors in Figure 1 and did not reflect the current organization of the PIONEER consortium. The figure has been corrected in the HTML and PDF versions of the manuscript to reflect the correct organization of PIONEER.

Published
2020

31. Prediction of major depressive disorder following beta-blocker therapy in patients with cardiovascular diseases

Author

Jin, S. (Suho), Kostka, K. (Kristin), Posada, J.D. (Jose D.), Kim, Y. (Yeesuk), Seo, S.I. (Seung In), Lee, D.Y. (Dong Yun), Shah, N.H. (Nigam H.), Roh, S. (Sungwon), Lim, Y.-H. (Young-Hyo), Chae, S.G. (Sun Geu), Jin, U. (Uram), Son, S.J. (Sang Joon), Reich, C. (Christian), Rijnbeek, P.R. (Peter), Park, R.W. (Rae Woong), You, S.C. (Seng Chan), Jin, S. (Suho), Kostka, K. (Kristin), Posada, J.D. (Jose D.), Kim, Y. (Yeesuk), Seo, S.I. (Seung In), Lee, D.Y. (Dong Yun), Shah, N.H. (Nigam H.), Roh, S. (Sungwon), Lim, Y.-H. (Young-Hyo), Chae, S.G. (Sun Geu), Jin, U. (Uram), Son, S.J. (Sang Joon), Reich, C. (Christian), Rijnbeek, P.R. (Peter), Park, R.W. (Rae Woong), and You, S.C. (Seng Chan)

Abstract

Incident depression has been reported to be associated with poor prognosis in patients with cardiovascular disease (CVD), which might be associated with beta-blocker therapy. Because early detection and intervention can alleviate the severity of depression, we aimed to develop a machine learning (ML) model predicting the onset of major depressive disorder (MDD). A model based on L1 regularized logistic regression was trained against the South Korean nationwide administrative claims database to identify risk factors for the incident MDD after beta-blocker therapy in patients with CVD. We identified 50,397 patients initiating beta-blockers for CVD, with 774 patients developing MDD within 365 days after initiating beta-blocker therapy. An area under the receiver operating characteristic curve (AUC) of 0.74 was achieved. A history of non-selective beta-blockers and factors related to anxiety disorder, sleeping problems, and other chronic diseases were the most strong predictors. AUCs of 0.62–0.71 were achieved in the external validation conducted on six independent electronic health records and claims databases in the USA and South Korea. In conclusion, an ML model that identifies patients at high-risk for incident MDD was developed. Application of ML to identify susceptible patients for adverse events of treatment may serve as an important approach for personalized medicine.

Published
2020
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32. Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study

Author

Lane, J.C.E., Weaver, J. (JoEllen), Kostka, K., Duarte-Salles, T., Abrahao, M.T.F., Alghoul, H., Alser, O., Alshammari, T.M., Biedermann, P., Banda, J.M., Burn, E., Casajust, P., Conover, M.M., Culhane, A.C., Davydov, A., DuVall, S.L., Dymshyts, D., Fernandez-Bertolin, S., Fister, K., Hardin, J., Hester, L., Hripcsak, G. (G.), Kaas-Hansen, B.S., Kent, S., Khosla, S., Kolovos, S., Lambert, C.G., Lei, J. (Johan) van der, Lynch, K.E., Makadia, R., Margulis, A.V., Matheny, M.E., Mehta, P., Morales, D.R., Morgan-Stewart, H., Mosseveld, M. (Mees), Newby, D., Nyberg, F. (Fredrik), Ostropolets, A., Park, RW, Prats-Uribe, A., Rao, G.A., Reich, C., Reps, J., Rijnbeek, P.R. (Peter), Sathappan, S.M.K., Schuemie, M.J. (Martijn), Seager, S., Sena, A.G., Shoaibi, A., Spotnitz, M., Suchard, M.A. (Marc), Torre, C.O., Vizcaya, D., Wen, H.N., Wilde, M. (Marcel) de, Xie, J.Q., You, S.C., Zhang, L., Zhuk, O., Ryan, P., Prieto-Alhambra, D., Lane, J.C.E., Weaver, J. (JoEllen), Kostka, K., Duarte-Salles, T., Abrahao, M.T.F., Alghoul, H., Alser, O., Alshammari, T.M., Biedermann, P., Banda, J.M., Burn, E., Casajust, P., Conover, M.M., Culhane, A.C., Davydov, A., DuVall, S.L., Dymshyts, D., Fernandez-Bertolin, S., Fister, K., Hardin, J., Hester, L., Hripcsak, G. (G.), Kaas-Hansen, B.S., Kent, S., Khosla, S., Kolovos, S., Lambert, C.G., Lei, J. (Johan) van der, Lynch, K.E., Makadia, R., Margulis, A.V., Matheny, M.E., Mehta, P., Morales, D.R., Morgan-Stewart, H., Mosseveld, M. (Mees), Newby, D., Nyberg, F. (Fredrik), Ostropolets, A., Park, RW, Prats-Uribe, A., Rao, G.A., Reich, C., Reps, J., Rijnbeek, P.R. (Peter), Sathappan, S.M.K., Schuemie, M.J. (Martijn), Seager, S., Sena, A.G., Shoaibi, A., Spotnitz, M., Suchard, M.A. (Marc), Torre, C.O., Vizcaya, D., Wen, H.N., Wilde, M. (Marcel) de, Xie, J.Q., You, S.C., Zhang, L., Zhuk, O., Ryan, P., and Prieto-Alhambra, D.

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. Self-controlled c

Published
2020
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33. Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study

Author

Burn, E., You, S.C., Sena, A.G., Kostka, K., Abedtash, H., Abrahao, M.T.F., Alberga, A., Alghoul, H., Alser, O., Alshammari, T.M., Aragon, M, Areia, C., Banda, J.M., Cho, J. (Jeiwon), Culhane, A.C., Davydov, A., DeFalco, F.J., Duarte-Salles, T., DuVall, S., Falconer, T., Fernandez-Bertolin, S., Gao, W.H., Golozar, A., Hardin, J., Hripcsak, G. (G.), Huser, V, Jeon, H., Jing, Y.H., Jung, C.Y., Kaas-Hansen, B.S., Kaduk, D., Kent, S., Kim, Y., Kolovos, S., Lane, J.C.E., Lee, H. (Hang), Lynch, K.E., Makadia, R., Matheny, M.E., Mehta, P.P., Morales, D.R., Natarajan, K., Nyberg, F. (Fredrik), Ostropolets, A., Park, RW, Park, J. (Judy), Posada, J.D., Prats-Uribe, A., Rao, G., Reich, C., Rho, Y., Rijnbeek, P.R. (Peter), Schilling, LM, Schuemie, M.J. (Martijn), Shah, NH, Shoaibi, A., Song, S., Spotnitz, M., Suchard, M.A. (Marc), Swerdel, J.N., Vizcaya, D., Volpe, S., Wen, H.N., Williams, A.E., Yimer, B.B., Zhang, L., Zhuk, O., Prieto-Alhambra, D., Ryan, P., Burn, E., You, S.C., Sena, A.G., Kostka, K., Abedtash, H., Abrahao, M.T.F., Alberga, A., Alghoul, H., Alser, O., Alshammari, T.M., Aragon, M, Areia, C., Banda, J.M., Cho, J. (Jeiwon), Culhane, A.C., Davydov, A., DeFalco, F.J., Duarte-Salles, T., DuVall, S., Falconer, T., Fernandez-Bertolin, S., Gao, W.H., Golozar, A., Hardin, J., Hripcsak, G. (G.), Huser, V, Jeon, H., Jing, Y.H., Jung, C.Y., Kaas-Hansen, B.S., Kaduk, D., Kent, S., Kim, Y., Kolovos, S., Lane, J.C.E., Lee, H. (Hang), Lynch, K.E., Makadia, R., Matheny, M.E., Mehta, P.P., Morales, D.R., Natarajan, K., Nyberg, F. (Fredrik), Ostropolets, A., Park, RW, Park, J. (Judy), Posada, J.D., Prats-Uribe, A., Rao, G., Reich, C., Rho, Y., Rijnbeek, P.R. (Peter), Schilling, LM, Schuemie, M.J. (Martijn), Shah, NH, Shoaibi, A., Song, S., Spotnitz, M., Suchard, M.A. (Marc), Swerdel, J.N., Vizcaya, D., Volpe, S., Wen, H.N., Williams, A.E., Yimer, B.B., Zhang, L., Zhuk, O., Prieto-Alhambra, D., and Ryan, P.

Published
2020
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34. Comparative safety and effectiveness of alendronate versus raloxifene in women with osteoporosis

Author

Kim, Y. (Yeesuk), Tian, Y. (Yuxi), Yang, J. (Jianxiao), Huser, V. (Vojtech), Jin, P. (Peng), Lambert, C.G. (Christophe G.), Park, H. (Hojun), You, S.C. (Seng Chan), Park, R.W. (Rae Woong), Rijnbeek, P.R. (Peter), Van Zandt, M. (Mui), Reich, C. (Christian), Vashisht, R. (Rohit), Wu, Y. (Yonghui), Duke, J.D. (Jon D.), Hripcsak, G. (G.), Madigan, D. (David), Shah, N.H. (Nigam H.), Ryan, P.B. (Patrick), Schuemie, M.J. (Martijn), Suchard, M.A. (Marc), Kim, Y. (Yeesuk), Tian, Y. (Yuxi), Yang, J. (Jianxiao), Huser, V. (Vojtech), Jin, P. (Peng), Lambert, C.G. (Christophe G.), Park, H. (Hojun), You, S.C. (Seng Chan), Park, R.W. (Rae Woong), Rijnbeek, P.R. (Peter), Van Zandt, M. (Mui), Reich, C. (Christian), Vashisht, R. (Rohit), Wu, Y. (Yonghui), Duke, J.D. (Jon D.), Hripcsak, G. (G.), Madigan, D. (David), Shah, N.H. (Nigam H.), Ryan, P.B. (Patrick), Schuemie, M.J. (Martijn), and Suchard, M.A. (Marc)

Abstract

Alendronate and raloxifene are among the most popular anti-osteoporosis medications. However, there is a lack of head-to-head comparative effectiveness studies comparing the two treatments. We conducted a retrospective large-scale multicenter study encompassing over 300 million patients across nine databases encoded in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The primary outcome was the incidence of osteoporotic hip fracture, while secondary outcomes were vertebral fracture, atypical femoral fracture (AFF), osteonecrosis of the jaw (ONJ), and esophageal cancer. We used propensity score trimming and stratification based on an expansive propensity score model with all pre-treatment patient characteritistcs. We accounted for unmeasured confounding using negative control outcomes to estimate and adjust for residual systematic bias in each data source. We identified 283,586 alendronate patients and 40,463 raloxifene patients. There were 7.48 hip fracture, 8.18 vertebral fracture, 1.14 AFF, 0.21 esophageal cancer and 0.09 ONJ events per 1,000 person-years in the alendronate cohort and 6.62, 7.36, 0.69, 0.22 and 0.06 events per 1,000 person-years, respectively, in the raloxifene cohort. Alendronate and raloxifene have a similar hip fracture risk (hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.94–1.13), but alendronate users are more likely to have vertebral fractures (HR 1.07, 95% CI 1.01–1.14). Alendronate has higher risk for AFF (HR 1.51, 95% CI 1.23–1.84) but similar risk for esophageal cancer (HR 0.95, 95% CI 0.53–1.70), and ONJ (HR 1.62, 95% CI 0.78–3.34). We demonstrated substantial control of measured confounding by propensity score adjustment, and minimal residual systematic bias through negative control experiments, lending credibility to our effect estimates. Raloxifene is as effective as alendronate and may remain an option in the prevention of osteoporotic fracture.

Published
2020
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35. Development and validation of a prognostic model predicting symptomatic hemorrhagic transformation in acute ischemic stroke at scale in the OHDSI network

Author

Wang, Q. (Qiong), Reps, J.M. (Jenna M.), Kostka, K.F. (Kristin Feeney), Ryan, P.B. (Patrick B.), Zou, Y. (Yuhui), Voss, E.A. (Erica), Rijnbeek, P.R. (Peter), Chen, R. (RuiJun), Rao, G.A. (Gowtham A.), Morgan Stewart, H. (Henry), Williams, A.E. (Andrew E.), Williams, R.D. (Ross D.), Van Zandt, M. (Mui), Falconer, T. (Thomas), Fernandez-Chas, M. (Margarita), Vashisht, R. (Rohit), Pfohl, S.R. (Stephen R.), Shah, N.H. (Nigam H.), Kasthurirathne, S.N. (Suranga N.), You, S.C. (Seng Chan), Jiang, Q. (Qing), Reich, C. (Christian), Zhou, Y. (Yi), Wang, Q. (Qiong), Reps, J.M. (Jenna M.), Kostka, K.F. (Kristin Feeney), Ryan, P.B. (Patrick B.), Zou, Y. (Yuhui), Voss, E.A. (Erica), Rijnbeek, P.R. (Peter), Chen, R. (RuiJun), Rao, G.A. (Gowtham A.), Morgan Stewart, H. (Henry), Williams, A.E. (Andrew E.), Williams, R.D. (Ross D.), Van Zandt, M. (Mui), Falconer, T. (Thomas), Fernandez-Chas, M. (Margarita), Vashisht, R. (Rohit), Pfohl, S.R. (Stephen R.), Shah, N.H. (Nigam H.), Kasthurirathne, S.N. (Suranga N.), You, S.C. (Seng Chan), Jiang, Q. (Qing), Reich, C. (Christian), and Zhou, Y. (Yi)

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

Published
2020
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36. Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study

Author

Lane, JCE, Weaver, J, Kostka, K, Duarte-Salles, T, Abrahao, MTF, Alghoul, H, Alser, O, Alshammari, TM, Biedermann, P, Banda, JM, Burn, E, Casajust, P, Conover, MM, Culhane, AC, Davydov, A, DuVall, SL, Dymshyts, D, Fernandez-Bertolin, S, Fister, K, Hardin, J, Hester, L, Hripcsak, G, Kaas-Hansen, BS, Kent, S, Khosla, S, Kolovos, S, Lambert, CG, van der Lei, J, Lynch, KE, Makadia, R, Margulis, A, Matheny, ME, Mehta, P, Morales, DR, Morgan-Stewart, H, Mosseveld, M, Newby, D, Nyberg, F, Ostropolets, A, Park, RW, Prats-Uribe, A, Rao, GA, Reich, C, Reps, J, Rijnbeek, P, Sathappan, SMK, Schuemie, M, Seager, S, Sena, AG, Shoaibi, A, Spotnitz, M, Suchard, MA, Torre, CO, Vizcaya, D, Wen, H, de Wilde, M, Xie, J, You, SC, Zhang, L, Zhuk, O, Ryan, P, Prieto-Alhambra, D, Lane, JCE, Weaver, J, Kostka, K, Duarte-Salles, T, Abrahao, MTF, Alghoul, H, Alser, O, Alshammari, TM, Biedermann, P, Banda, JM, Burn, E, Casajust, P, Conover, MM, Culhane, AC, Davydov, A, DuVall, SL, Dymshyts, D, Fernandez-Bertolin, S, Fister, K, Hardin, J, Hester, L, Hripcsak, G, Kaas-Hansen, BS, Kent, S, Khosla, S, Kolovos, S, Lambert, CG, van der Lei, J, Lynch, KE, Makadia, R, Margulis, A, Matheny, ME, Mehta, P, Morales, DR, Morgan-Stewart, H, Mosseveld, M, Newby, D, Nyberg, F, Ostropolets, A, Park, RW, Prats-Uribe, A, Rao, GA, Reich, C, Reps, J, Rijnbeek, P, Sathappan, SMK, Schuemie, M, Seager, S, Sena, AG, Shoaibi, A, Spotnitz, M, Suchard, MA, Torre, CO, Vizcaya, D, Wen, H, de Wilde, M, Xie, J, You, SC, Zhang, L, Zhuk, O, Ryan, P, and Prieto-Alhambra, D

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 I 2 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. Self-controlled 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·

Published
2020

37. Deep phenotyping of 34,128 patients hospitalised with COVID-19 and a comparison with 81,596 influenza patients in America, Europe and Asia: an international network study.

Author

Burn, E, You, SC, Sena, A, Kostka, K, Abedtash, H, Abrahao, MTF, Alberga, A, Alghoul, H, Alser, O, Alshammari, TM, Aragon, M, Areia, C, Banda, JM, Cho, J, Culhane, AC, Davydov, A, DeFalco, FJ, Duarte-Salles, T, DuVall, SL, Falconer, T, Fernandez-Bertolin, S, Gao, W, Golozar, A, Hardin, J, Hripcsak, G, Huser, V, Jeon, H, Jing, Y, Jung, CY, Kaas-Hansen, BS, Kaduk, D, Kent, S, Kim, Y, Kolovos, S, Lane, J, Lee, H, Lynch, KE, Makadia, R, Matheny, ME, Mehta, P, Morales, DR, Natarajan, K, Nyberg, F, Ostropolets, A, Park, RW, Park, J, Posada, JD, Prats-Uribe, A, Rao, GA, Reich, C, Rho, Y, Rijnbeek, P, Schilling, LM, Schuemie, M, Shah, NH, Shoaibi, A, Song, S, Spotnitz, M, Suchard, MA, Swerdel, J, Vizcaya, D, Volpe, S, Wen, H, Williams, AE, Yimer, BB, Zhang, L, Zhuk, O, Prieto-Alhambra, D, Ryan, P, Burn, E, You, SC, Sena, A, Kostka, K, Abedtash, H, Abrahao, MTF, Alberga, A, Alghoul, H, Alser, O, Alshammari, TM, Aragon, M, Areia, C, Banda, JM, Cho, J, Culhane, AC, Davydov, A, DeFalco, FJ, Duarte-Salles, T, DuVall, SL, Falconer, T, Fernandez-Bertolin, S, Gao, W, Golozar, A, Hardin, J, Hripcsak, G, Huser, V, Jeon, H, Jing, Y, Jung, CY, Kaas-Hansen, BS, Kaduk, D, Kent, S, Kim, Y, Kolovos, S, Lane, J, Lee, H, Lynch, KE, Makadia, R, Matheny, ME, Mehta, P, Morales, DR, Natarajan, K, Nyberg, F, Ostropolets, A, Park, RW, Park, J, Posada, JD, Prats-Uribe, A, Rao, GA, Reich, C, Rho, Y, Rijnbeek, P, Schilling, LM, Schuemie, M, Shah, NH, Shoaibi, A, Song, S, Spotnitz, M, Suchard, MA, Swerdel, J, Vizcaya, D, Volpe, S, Wen, H, Williams, AE, Yimer, BB, Zhang, L, Zhuk, O, Prieto-Alhambra, D, and Ryan, P

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 characte

Published
2020

38. 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

Author

C.E.Lane, J, Weaver, J, Kostka, K, Duarte-Salles, T, Abrahao, MT, Alghoul, H, Alser, O, Alshammari, T, Biedermann, P, Burn, E, Casajust, P, Conover, M, Culhane, A, Davydov, A, DuVall, S, Dymshyts, D, Fernandez-Bertolin, S, Fišter, K, Hardin, J, Hester, L, Hripcsak, G, Kent, S, Khosla, S, Kolovos, S, Lambert, C, van der Lei, J, Londhe, A, Lynch, K, Makadia, R, Margulis, A, Matheny, M, Mehta, P, Morales, D, Morgan-Stewart, H, Mosseveld, M, Newby, D, Nyberg, F, Ostropolets, A, Park, RW, Prats-Uribe, A, Rao, G, Reich, C, Reps, J, Rijnbeek, P, Kumaran Sathappan, SM, Schuemie, M, Seager, S, Sena, A, Shoaibi, A, Spotnitz, M, Suchard, M, Swerdel, J, Torre, C, Vizcaya, D, Wen, H, de Wilde, M, You, SC, Zhang, L, Zhuk, O, Ryan, P, Prieto-Alhambra, D, C.E.Lane, J, Weaver, J, Kostka, K, Duarte-Salles, T, Abrahao, MT, Alghoul, H, Alser, O, Alshammari, T, Biedermann, P, Burn, E, Casajust, P, Conover, M, Culhane, A, Davydov, A, DuVall, S, Dymshyts, D, Fernandez-Bertolin, S, Fišter, K, Hardin, J, Hester, L, Hripcsak, G, Kent, S, Khosla, S, Kolovos, S, Lambert, C, van der Lei, J, Londhe, A, Lynch, K, Makadia, R, Margulis, A, Matheny, M, Mehta, P, Morales, D, Morgan-Stewart, H, Mosseveld, M, Newby, D, Nyberg, F, Ostropolets, A, Park, RW, Prats-Uribe, A, Rao, G, Reich, C, Reps, J, Rijnbeek, P, Kumaran Sathappan, SM, Schuemie, M, Seager, S, Sena, A, Shoaibi, A, Spotnitz, M, Suchard, M, Swerdel, J, Torre, C, Vizcaya, D, Wen, H, de Wilde, M, You, SC, Zhang, L, Zhuk, O, Ryan, P, and Prieto-Alhambra, D

Abstract

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

Published
2020

39. Can we trust the prediction model? Demonstrating the importance of external validation by investigating the COVID-19 Vulnerability (C-19) Index across an international network of observational healthcare datasets

Author

Reps, J, Kim, C, Williams, R, Markus, A, Yang, C, Salles, TD, Falconer, T, Jonnagaddala, J, Williams, A, Fernández-Bertolín, S, DuVall, S, Kostka, K, Rao, G, Shoaibi, A, Ostropolets, A, Spotnitz, M, Zhang, L, Casajust, P, Steyerberg, E, Nyberg, F, Kaas-Hansen, BS, Choi, YH, Morales, D, Liaw, S-T, Fernandes Abrahão, MT, Areia, C, Matheny, M, Aragón, M, Park, RW, Hripcsak, G, Reich, C, Suchard, M, You, SC, Ryan, P, Prieto-Alhambra, D, Rijnbeek, P, Reps, J, Kim, C, Williams, R, Markus, A, Yang, C, Salles, TD, Falconer, T, Jonnagaddala, J, Williams, A, Fernández-Bertolín, S, DuVall, S, Kostka, K, Rao, G, Shoaibi, A, Ostropolets, A, Spotnitz, M, Zhang, L, Casajust, P, Steyerberg, E, Nyberg, F, Kaas-Hansen, BS, Choi, YH, Morales, D, Liaw, S-T, Fernandes Abrahão, MT, Areia, C, Matheny, M, Aragón, M, Park, RW, Hripcsak, G, Reich, C, Suchard, M, You, SC, Ryan, P, Prieto-Alhambra, D, and Rijnbeek, P

Abstract

Background

SARS-CoV-2 is straining healthcare systems globally. The burden on hospitals during the pandemic could be reduced by implementing prediction models that can discriminate between patients requiring hospitalization and those who do not. The COVID-19 vulnerability (C-19) index, a model that predicts which patients will be admitted to hospital for treatment of pneumonia or pneumonia proxies, has been developed and proposed as a valuable tool for decision making during the pandemic. However, the model is at high risk of bias according to the Prediction model Risk Of Bias ASsessment Tool and has not been externally validated.

Methods

We followed the OHDSI framework for external validation to assess the reliability of the C-19 model. We evaluated the model on two different target populations: i) 41,381 patients that have SARS-CoV-2 at an outpatient or emergency room visit and ii) 9,429,285 patients that have influenza or related symptoms during an outpatient or emergency room visit, to predict their risk of hospitalization with pneumonia during the following 0 to 30 days. In total we validated the model across a network of 14 databases spanning the US, Europe, Australia and Asia.

Findings

The internal validation performance of the C-19 index was a c-statistic of 0.73 and calibration was not reported by the authors. When we externally validated it by transporting it to SARS-CoV-2 data the model obtained c-statistics of 0.36, 0.53 (0.473-0.584) and 0.56 (0.488-0.636) on Spanish, US and South Korean datasets respectively. The calibration was poor with the model under-estimating risk. When validated on 12 datasets containing influenza patients across the OHDSI network the c-statistics ranged between 0.40-0.68.

Interpretation

The results show that the discriminative performance of the C-19 model is low for influenza cohorts, and even worse amongst COVID-19 patients in the US, Spain and South Korea. These results suggest that C-19 s

Published
2020

40. Risk of depression, suicidal ideation, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multi-national network cohort study

Author

Lane, JCE, Weaver, J, Kostka, K, Duarte-Salles, T, Abrahao, MT, Alghoul, H, Alser, O, Alshammari, T, Areia, C, Biedermann, P, Banda, J, Burn, E, Casajust, P, Fišer, K, Hardin, J, Hester, L, Hripcsak, G, Kaas-Hansen, BS, Khosla, S, Kolovos, S, Lynch, K, Makadia, R, Mehta, P, Morales, D, Morgan-Stewart, H, Mosseveld, M, Newby, D, Nyberg, F, Ostropolets, A, Park, RW, Prats-Uribe, A, Rao, G, Reich, C, Rijnbeek, P, Sena, A, Shoaibi, A, Spotnitz, M, Subbian, V, Suchard, M, Vizcaya, D, Wen, H, de Wilde, M, Xie, J, You, SC, Zhang, L, Lovestone, S, Ryan, P, Prieto-Alhambra, D, Lane, JCE, Weaver, J, Kostka, K, Duarte-Salles, T, Abrahao, MT, Alghoul, H, Alser, O, Alshammari, T, Areia, C, Biedermann, P, Banda, J, Burn, E, Casajust, P, Fišer, K, Hardin, J, Hester, L, Hripcsak, G, Kaas-Hansen, BS, Khosla, S, Kolovos, S, Lynch, K, Makadia, R, Mehta, P, Morales, D, Morgan-Stewart, H, Mosseveld, M, Newby, D, Nyberg, F, Ostropolets, A, Park, RW, Prats-Uribe, A, Rao, G, Reich, C, Rijnbeek, P, Sena, A, Shoaibi, A, Spotnitz, M, Subbian, V, Suchard, M, Vizcaya, D, Wen, H, de Wilde, M, Xie, J, You, SC, Zhang, L, Lovestone, S, Ryan, P, and Prieto-Alhambra, D

Abstract

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 I 2 <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.

TRIAL REGISTRATION

Registered with EU PAS; Reference number EUPAS34497 ( h

Published
2020

41. Deep phenotyping of 34,128 adult patients hospitalised with COVID-19 in an international network study

Author

Burn, E, You, SC, Sena, AG, Kostka, K, Abedtash, H, Abrahao, MTF, Alberga, A, Alghoul, H, Alser, O, Alshammari, TM, Aragon, M, Areia, C, Banda, JM, Cho, J, Culhane, AC, Davydov, A, DeFalco, FJ, Duarte-Salles, T, DuVall, S, Falconer, T, Fernandez-Bertolin, S, Gao, W, Golozar, A, Hardin, J, Hripcsak, G, Huser, V, Jeon, H, Jing, Y, Jung, CY, Kaas-Hansen, BS, Kaduk, D, Kent, S, Kim, Y, Kolovos, S, Lane, JCE, Lee, H, Lynch, KE, Makadia, R, Matheny, ME, Mehta, PP, Morales, DR, Natarajan, K, Nyberg, F, Ostropolets, A, Park, RW, Park, J, Posada, JD, Prats-Uribe, A, Rao, G, Reich, C, Rho, Y, Rijnbeek, P, Schilling, LM, Schuemie, M, Shah, NH, Shoaibi, A, Song, S, Spotnitz, M, Suchard, MA, Swerdel, JN, Vizcaya, D, Volpe, S, Wen, H, Williams, AE, Yimer, BB, Zhang, L, Zhuk, O, Prieto-Alhambra, D, Ryan, P, Burn, E, You, SC, Sena, AG, Kostka, K, Abedtash, H, Abrahao, MTF, Alberga, A, Alghoul, H, Alser, O, Alshammari, TM, Aragon, M, Areia, C, Banda, JM, Cho, J, Culhane, AC, Davydov, A, DeFalco, FJ, Duarte-Salles, T, DuVall, S, Falconer, T, Fernandez-Bertolin, S, Gao, W, Golozar, A, Hardin, J, Hripcsak, G, Huser, V, Jeon, H, Jing, Y, Jung, CY, Kaas-Hansen, BS, Kaduk, D, Kent, S, Kim, Y, Kolovos, S, Lane, JCE, Lee, H, Lynch, KE, Makadia, R, Matheny, ME, Mehta, PP, Morales, DR, Natarajan, K, Nyberg, F, Ostropolets, A, Park, RW, Park, J, Posada, JD, Prats-Uribe, A, Rao, G, Reich, C, Rho, Y, Rijnbeek, P, Schilling, LM, Schuemie, M, Shah, NH, Shoaibi, A, Song, S, Spotnitz, M, Suchard, MA, Swerdel, JN, Vizcaya, D, Volpe, S, Wen, H, Williams, AE, Yimer, BB, Zhang, L, Zhuk, O, Prieto-Alhambra, D, and Ryan, P

Abstract

Comorbid conditions appear to be common among individuals hospitalised with coronavirus disease 2019 (COVID-19) but estimates of prevalence vary and little is known about the prior medication use of patients. Here, we describe the characteristics of adults hospitalised with COVID-19 and compare them with influenza patients. We include 34,128 (US: 8362, South Korea: 7341, Spain: 18,425) COVID-19 patients, summarising between 4811 and 11,643 unique aggregate characteristics. COVID-19 patients have been majority male in the US and Spain, but predominantly female in South Korea. Age profiles vary across data sources. Compared to 84,585 individuals hospitalised with influenza in 2014-19, COVID-19 patients have more typically been male, younger, and with fewer comorbidities and lower medication use. While protecting groups vulnerable to influenza is likely a useful starting point in the response to COVID-19, strategies will likely need to be broadened to reflect the particular characteristics of individuals being hospitalised with COVID-19.

Published
2020

42. Characteristics and outcomes of 627 044 COVID-19 patients with and without obesity in the United States, Spain, and the United Kingdom

Author

Recalde, M, Roel, E, Pistillo, A, Sena, A, Prats-Uribe, A, Ahmed, W-U-R, Alghoul, H, Alshammari, T, Alser, O, Areia, C, Burn, E, Casajust, P, Dawoud, D, DuVall, S, Falconer, T, Fernández-Bertolín, S, Golozar, A, Gong, M, Lai, LYH, Lane, JCE, Lynch, K, Matheny, M, Mehta, P, Morales, D, Natarjan, K, Nyberg, F, Posada, J, Reich, C, Schilling, L, Shah, K, Shah, N, Subbian, V, Zhang, L, Zhu, H, Ryan, P, Prieto-Alhambra, D, Kostka, K, Duarte-Salles, T, Recalde, M, Roel, E, Pistillo, A, Sena, A, Prats-Uribe, A, Ahmed, W-U-R, Alghoul, H, Alshammari, T, Alser, O, Areia, C, Burn, E, Casajust, P, Dawoud, D, DuVall, S, Falconer, T, Fernández-Bertolín, S, Golozar, A, Gong, M, Lai, LYH, Lane, JCE, Lynch, K, Matheny, M, Mehta, P, Morales, D, Natarjan, K, Nyberg, F, Posada, J, Reich, C, Schilling, L, Shah, K, Shah, N, Subbian, V, Zhang, L, Zhu, H, Ryan, P, Prieto-Alhambra, D, Kostka, K, and Duarte-Salles, T

Abstract

Background

COVID-19 may differentially impact people with obesity. We aimed to describe and compare the demographics, comorbidities, and outcomes of obese patients with COVID-19 to those of non-obese patients with COVID-19, or obese patients with seasonal influenza.

Methods

We conducted a cohort study based on outpatient/inpatient care, and claims data from January to June 2020 from the US, Spain, and the UK. We used six databases standardized to the OMOP common data model. We defined two cohorts of patients diagnosed and/or hospitalized with COVID-19. We created corresponding cohorts for patients with influenza in 2017-2018. We followed patients from index date to 30 days or death. We report the frequency of socio-demographics, prior comorbidities, and 30-days outcomes (hospitalization, events, and death) by obesity status.

Findings

We included 627 044 COVID-19 (US: 502 650, Spain: 122 058, UK: 2336) and 4 549 568 influenza (US: 4 431 801, Spain: 115 224, UK: 2543) patients. The prevalence of obesity was higher among hospitalized COVID-19 (range: 38% to 54%) than diagnosed COVID-19 (30% to 47%), or diagnosed (15% to 47%) or hospitalized (27% to 48%) influenza patients. Obese hospitalized COVID-19 patients were more often female and younger than non-obese COVID-19 patients or obese influenza patients. Obese COVID-19 patients were more likely to have prior comorbidities, present with cardiovascular and respiratory events during hospitalization, require intensive services, or die compared to non-obese COVID-19 patients. Obese COVID-19 patients were more likely to require intensive services or die compared to obese influenza patients, despite presenting with fewer comorbidities.

Interpretation

We show that obesity is more common amongst COVID-19 than influenza patients, and that obese patients present with more severe forms of COVID-19 with higher hospitalization, intensive services, and fatality than non-obese patients. These data a

Published
2020

43. Seek COVER: Development and validation of a personalized risk calculator for COVID-19 outcomes in an international network

Author

Williams, R, Markus, A, Yang, C, Salles, TD, DuVall, S, Falconer, T, Jonnagaddala, J, Kim, C, Rho, Y, Williams, A, Alberga, A, An, MH, Aragón, M, Areia, C, Burn, E, Choi, YH, Drakos, I, Fernandes Abrahão, MT, Fernández-Bertolín, S, Hripcsak, G, Kaas-Hansen, BS, Kandukuri, P, Kors, J, Kostka, K, Liaw, S-T, Lynch, K, Machnicki, G, Matheny, M, Morales, D, Nyberg, F, Park, RW, Prats-Uribe, A, Pratt, N, Rao, G, Reich, C, Rivera, M, Seinen, T, Shoaibi, A, Spotnitz, M, Steyerberg, E, Suchard, M, You, SC, Zhang, L, Zhou, L, Ryan, P, Prieto-Alhambra, D, Reps, J, Rijnbeek, P, Williams, R, Markus, A, Yang, C, Salles, TD, DuVall, S, Falconer, T, Jonnagaddala, J, Kim, C, Rho, Y, Williams, A, Alberga, A, An, MH, Aragón, M, Areia, C, Burn, E, Choi, YH, Drakos, I, Fernandes Abrahão, MT, Fernández-Bertolín, S, Hripcsak, G, Kaas-Hansen, BS, Kandukuri, P, Kors, J, Kostka, K, Liaw, S-T, Lynch, K, Machnicki, G, Matheny, M, Morales, D, Nyberg, F, Park, RW, Prats-Uribe, A, Pratt, N, Rao, G, Reich, C, Rivera, M, Seinen, T, Shoaibi, A, Spotnitz, M, Steyerberg, E, Suchard, M, You, SC, Zhang, L, Zhou, L, Ryan, P, Prieto-Alhambra, D, Reps, J, and Rijnbeek, P

Abstract

Objective

To develop and externally validate COVID-19 Estimated Risk (COVER) scores that quantify a patient’s risk of hospital admission (COVER-H), requiring intensive services (COVER-I), or fatality (COVER-F) in the 30-days following COVID-19 diagnosis.

Methods

We analyzed a federated network of electronic medical records and administrative claims data from 14 data sources and 6 countries. We developed and validated 3 scores using 6,869,127 patients with a general practice, emergency room, or outpatient visit with diagnosed influenza or flu-like symptoms any time prior to 2020. The scores were validated on patients with confirmed or suspected COVID-19 diagnosis across five databases from South Korea, Spain and the United States. Outcomes included i) hospitalization with pneumonia, ii) hospitalization with pneumonia requiring intensive services or death iii) death in the 30 days after index date.

Results

Overall, 44,507 COVID-19 patients were included for model validation. We identified 7 predictors (history of cancer, chronic obstructive pulmonary disease, diabetes, heart disease, hypertension, hyperlipidemia, kidney disease) which combined with age and sex discriminated which patients would experience any of our three outcomes. The models achieved high performance in influenza. When transported to COVID-19 cohorts, the AUC ranges were, COVER-H: 0.69-0.81, COVER-I: 0.73-0.91, and COVER-F: 0.72-0.90. Calibration was overall acceptable.

Conclusions

A 9-predictor model performs well for COVID-19 patients for predicting hospitalization, intensive services and fatality. The models could aid in providing reassurance for low risk patients and shield high risk patients from COVID-19 during de-confinement to reduce the virus’ impact on morbidity and mortality.

Published
2020

44. Heterogeneity and temporal variation in the management of COVID-19: a multinational drug utilization study including 71,921 hospitalized patients from China, South Korea, Spain, and the United States of America

Author

Prats-Uribe, A, Sena, A, Hui Lai, LY, Ahmed, W-U-R, Alghoul, H, Alser, O, Alshammari, T, Areia, C, Carter, W, Casajust, P, Dawoud, D, Golozar, A, Jonnagaddala, J, Mehta, P, Gong, M, Morales, D, Nyberg, F, Posada, J, Recalde, M, Roel, E, Shah, K, H. Shah, N, Schilling, L, Subbian, V, Vizcaya, D, Williams, A, Zhang, L, Zhang, Y, Zhu, H, Liu, L, Rijnbeek, P, Hripcsak, G, Lane, JCE, Burn, E, Reich, C, Suchard, M, Duarte-Salles, T, Kostka, K, Ryan, P, Prieto-Alhambra, D, Prats-Uribe, A, Sena, A, Hui Lai, LY, Ahmed, W-U-R, Alghoul, H, Alser, O, Alshammari, T, Areia, C, Carter, W, Casajust, P, Dawoud, D, Golozar, A, Jonnagaddala, J, Mehta, P, Gong, M, Morales, D, Nyberg, F, Posada, J, Recalde, M, Roel, E, Shah, K, H. Shah, N, Schilling, L, Subbian, V, Vizcaya, D, Williams, A, Zhang, L, Zhang, Y, Zhu, H, Liu, L, Rijnbeek, P, Hripcsak, G, Lane, JCE, Burn, E, Reich, C, Suchard, M, Duarte-Salles, T, Kostka, K, Ryan, P, and Prieto-Alhambra, D

Abstract

Objectives

A plethora of medicines have been repurposed or used as adjunctive therapies for COVID-19. We characterized the utilization of medicines as prescribed in routine practice amongst patients hospitalized for COVID-19 in South Korea, China, Spain, and the USA.

Design

International network cohort

Setting

Hospital electronic health records from Columbia University Irving Medical Centre (NYC, USA), Stanford (CA, USA), Tufts (MA, USA), Premier (USA), Optum EHR (USA), department of veterans affairs (USA), NFHCRD (Honghu, China) and HM Hospitals (Spain); and nationwide claims from HIRA (South Korea)

Participants

patients hospitalized for COVID-19 from January to June 2020

Main outcome measures

Prescription/dispensation of any medicine on or 30 days after hospital admission date

Analyses

Number and percentage of users overall and over time

Results

71,921 people were included: 304 from China, 2,089 from Spain, 7,599 from South Korea, and 61,929 from the USA. A total of 3,455 medicines were identified. Common repurposed medicines included hydroxychloroquine (<2% in NFHCRD to 85.4% in HM), azithromycin (4.9% in NFHCRD to 56.5% in HM), lopinavir/ritonavir (<3% in all US but 34.9% in HIRA and 56.5% in HM), and umifenovir (0% in all except 78.3% in NFHCRD). Adjunctive medicines were used with great variability, with the ten most used treatments being (in descending order): bemiparin, enoxaparin, heparin, ceftriaxone, aspirin, vitamin D, famotidine, vitamin C, dexamethasone, and metformin. Hydroxychloroquine and azithromycin increased rapidly in use in March-April but declined steeply in May-June.

Conclusions

Multiple medicines were used in the first months of COVID-19 pandemic, with substantial geographic and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed medicines. Antithrombotics, antibiotics, H2 receptor

Published
2020

45. Comparative safety and effectiveness of alendronate versus raloxifene in women with osteoporosis

Author

Kim, Y, Tian, YX, Yang, JX, Huser, V, Jin, P, Lambert, CG, Park, H, You, SC, Park, RW, Rijnbeek, Peter, Van Zandt, M, Reich, C, Vashisht, R, Wu, YH, Duke, J, Hripcsak, G, Madigan, D, Shah, NH, Ryan, PB, Schuemie, MJ, Suchard, MA, Kim, Y, Tian, YX, Yang, JX, Huser, V, Jin, P, Lambert, CG, Park, H, You, SC, Park, RW, Rijnbeek, Peter, Van Zandt, M, Reich, C, Vashisht, R, Wu, YH, Duke, J, Hripcsak, G, Madigan, D, Shah, NH, Ryan, PB, Schuemie, MJ, and Suchard, MA

Published
2020

46. Development and validation of a prognostic model predicting symptomatic hemorrhagic transformation in acute ischemic stroke at scale in the OHDSI network

Author

Wang, Q, Reps, JM, Kostka, KF, Ryan, PB, Zou, Y, Voss, Erica, Rijnbeek, Peter, Chen, R, Rao, GA, Stewart, HM, Williams, AE, Williams, Ross, Van Zandt, M, Falconer, T, Fernandez-Chas, M, Vashisht, R, Pfohl, SR, Shah, NH, Kasthurirathne, SN, You, SC, Jiang, Q, Reich, C, Zhou, Y, Wang, Q, Reps, JM, Kostka, KF, Ryan, PB, Zou, Y, Voss, Erica, Rijnbeek, Peter, Chen, R, Rao, GA, Stewart, HM, Williams, AE, Williams, Ross, Van Zandt, M, Falconer, T, Fernandez-Chas, M, Vashisht, R, Pfohl, SR, Shah, NH, Kasthurirathne, SN, You, SC, Jiang, Q, Reich, C, and Zhou, Y

Published
2020

48. Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?

Author

Heesen, C., Nawrath, L., Reich, C., Bauer, N., Schulz, K.-H., and Gold, S.M.

Subjects
Multiple sclerosis -- Physiological aspects, Fatigue -- Development and progression, Fatigue -- Research, Cytokines -- Comparative analysis, Interleukins -- Comparative analysis, Hypothalamic-pituitary-adrenal axis -- Physiological aspects, Health, Psychology and mental health
Published
2006

50. Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight

Author

Loh, N. D., Hampton, C. Y., Martin, A. V., Starodub, D., Sierra, R. G., Barty, A., Aquila, A., Schulz, J., Lomb, L., Steinbrener, J., Shoeman, R. L., Kassemeyer, S., Bostedt, C., Bozek, J., Epp, S. W., Erk, B., Hartmann, R., Rolles, D., Rudenko, A., Rudek, B., Foucar, L., Kimmel, N., Weidenspointner, G., Hauser, G., Holl, P., Pedersoli, E., Liang, M., Hunter, M. M., Gumprecht, L., Coppola, N., Wunderer, C., Graafsma, H., Maia, F. R. N. C., Ekeberg, T., Hantke, M., Fleckenstein, H., Hirsemann, H., Nass, K., White, T. A., Tobias, H. J., Farquar, G. R., Benner, W. H., Hau-Riege, S. P., Reich, C., Hartmann, A., Soltau, H., Marchesini, S., Bajt, S., Barthelmess, M., Bucksbaum, P., Hodgson, K. O., Strüder, L., Ullrich, J., Frank, M., Schlichting, I., Chapman, H. N., and Bogan, M. J.

Published
2012
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