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Article ; Online: Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis.

Lecronier, Marie / Beurton, Alexandra / Burrel, Sonia / Haudebourg, Luc / Deleris, Robin / Le Marec, Julien / Virolle, Sara / Nemlaghi, Safaa / Bureau, Côme / Mora, Pierre / De Sarcus, Martin / Clovet, Olivier / Duceau, Baptiste / Grisot, Paul Henri / Pari, Marie Hélène / Arzoine, Jérémy / Clarac, Ulrich / Boutolleau, David / Raux, Mathieu /

Delemazure, Julie / Faure, Morgane / Decavele, Maxens / Morawiec, Elise / Mayaux, Julien / Demoule, Alexandre / Dres, Martin

Critical care (London, England)

2020 Volume 24, Issue 1, Page(s) 418

Abstract: Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, ... ...

Abstract	Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. Results: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. Conclusion: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.
MeSH term(s)	Aged ; COVID-19 ; Coronavirus Infections/drug therapy ; Critical Illness ; Drug Combinations ; Female ; Humans ; Hydroxychloroquine/therapeutic use ; Lopinavir/therapeutic use ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral/drug therapy ; Retrospective Studies ; Ritonavir/therapeutic use ; Standard of Care ; Treatment Outcome
Chemical Substances	Drug Combinations ; Lopinavir (2494G1JF75) ; Hydroxychloroquine (4QWG6N8QKH) ; Ritonavir (O3J8G9O825)
Keywords	covid19
Language	English
Publishing date	2020-07-11
Publishing country	England
Document type	Comparative Study ; Journal Article
ZDB-ID	2041406-7
ISSN	1466-609X ; 1364-8535
ISSN (online)	1466-609X
ISSN	1364-8535
DOI	10.1186/s13054-020-03117-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis

Delemazure, Julie / Faure, Morgane / Decavele, Maxens / Morawiec, Elise / Mayaux, Julien / Demoule, Alexandre / Dres, Martin

Crit Care

Abstract: BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, ... ...

Abstract	BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. METHODS: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7. RESULTS: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7. CONCLUSION: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #638653
Database	COVID19

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Article ; Online: Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia

Delemazure, Julie / Faure, Morgane / Decavele, Maxens / Morawiec, Elise / Mayaux, Julien / Demoule, Alexandre / Dres, Martin

ISSN: 1364-8535 ; EISSN: 1466-609X ; Critical Care ; https://hal.sorbonne-universite.fr/hal-02935265 ; Critical Care, BioMed Central, 2020, 24 (1), pp.418. ⟨10.1186/s13054-020-03117-9⟩

an opportunistic retrospective analysis

2020

Abstract: International audience ... Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir ... ...

Abstract	International audience Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.Results: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7.Conclusion: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.
Keywords	Hydroxychloroquine ; Intensive care unit ; Lopinavir/ritonavir ; SARS-CoV-2 ; Standard of care ; [SDV]Life Sciences [q-bio] ; covid19
Subject code	610
Language	English
Publisher	HAL CCSD
Publishing country	fr
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia

Delemazure, Julie / Faure, Morgane / Decavele, Maxens / Morawiec, Elise / Mayaux, Julien / Demoule, Alexandre / Dres, Martin

ISSN: 1364-8535 ; EISSN: 1466-609X ; Critical Care ; https://hal.sorbonne-universite.fr/hal-02935265 ; Critical Care, BioMed Central, 2020, 24 (1), pp.418. ⟨10.1186/s13054-020-03117-9⟩

an opportunistic retrospective analysis

2020

Abstract	International audience Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.Results: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7.Conclusion: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.
Keywords	Hydroxychloroquine ; Intensive care unit ; Lopinavir/ritonavir ; SARS-CoV-2 ; Standard of care ; [SDV]Life Sciences [q-bio] ; covid19
Subject code	610
Language	English
Publisher	HAL CCSD
Publishing country	fr
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia

Delemazure, Julie / Faure, Morgane / Decavele, Maxens / Morawiec, Elise / Mayaux, Julien / Demoule, Alexandre / Dres, Martin

ISSN: 1364-8535 ; EISSN: 1466-609X ; Critical Care ; https://hal.sorbonne-universite.fr/hal-02935265 ; Critical Care, BioMed Central, 2020, 24 (1), pp.418. ⟨10.1186/s13054-020-03117-9⟩

an opportunistic retrospective analysis

2020

Abstract	International audience Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.Results: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7.Conclusion: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.
Keywords	Hydroxychloroquine ; Intensive care unit ; Lopinavir/ritonavir ; SARS-CoV-2 ; Standard of care ; [SDV]Life Sciences [q-bio] ; covid19
Subject code	610
Language	English
Publisher	HAL CCSD
Publishing country	fr
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia

Delemazure, Julie / Faure, Morgane / Decavele, Maxens / Morawiec, Elise / Mayaux, Julien / Demoule, Alexandre / Dres, Martin

ISSN: 1364-8535 ; EISSN: 1466-609X ; Critical Care ; https://hal.sorbonne-universite.fr/hal-02935265 ; Critical Care, BioMed Central, 2020, 24 (1), pp.418. ⟨10.1186/s13054-020-03117-9⟩

an opportunistic retrospective analysis

2020

Abstract	International audience Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.Results: Eighty patients were treated during a 4-week period and included in the analysis: 22 (28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir associated to standard of care, and 38 (47%) patients received hydroxychloroquine and standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, respectively (p = 0.567). There was no significant difference between groups regarding the number of ventilator-free days at day 28 and mortality at day 14 and day 28. Finally, there was no significant change between groups in viral respiratory or plasma load between admission and day 7.Conclusion: In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care only on the proportion of patients who needed treatment escalation at day 28. Further randomized controlled trials are required to demonstrate whether these drugs may be useful in this context. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients.
Keywords	Hydroxychloroquine ; Intensive care unit ; Lopinavir/ritonavir ; SARS-CoV-2 ; Standard of care ; [SDV]Life Sciences [q-bio] ; covid19
Subject code	610
Language	English
Publisher	HAL CCSD
Publishing country	fr
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

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Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia

Delemazure, Julie / Faure, Morgane / Decavele, Maxens / Morawiec, Elise / Mayaux, Julien / Demoule, Alexandre / Dres, Martin

Critical Care

an opportunistic retrospective analysis

2020 Volume 24, Issue 1

Keywords	Critical Care and Intensive Care Medicine ; covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	2041406-7
ISSN	1364-8535
ISSN	1364-8535
DOI	10.1186/s13054-020-03117-9
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prevalence and outcome of heparin-induced thrombocytopenia diagnosed under veno-arterial extracorporeal membrane oxygenation: a retrospective nationwide study.

Kimmoun, Antoine / Oulehri, Walid / Sonneville, Romain / Grisot, Paul-Henri / Zogheib, Elie / Amour, Julien / Aissaoui, Nadia / Megarbane, Bruno / Mongardon, Nicolas / Renou, Amelie / Schmidt, Matthieu / Besnier, Emmanuel / Delmas, Clément / Dessertaine, Geraldine / Guidon, Catherine / Nesseler, Nicolas / Labro, Guylaine / Rozec, Bertrand / Pierrot, Marc /

Helms, Julie / Bougon, David / Chardonnal, Laurent / Medard, Anne / Ouattara, Alexandre / Girerd, Nicolas / Lamiral, Zohra / Borie, Marc / Ajzenberg, Nadine / Levy, Bruno

Intensive care medicine

2018 Volume 44, Issue 9, Page(s) 1460–1469

Abstract: Purpose: Thrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced ... ...

Abstract	Purpose: Thrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO. Methods: This retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3 days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT. Results: A total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% [95% CI] [0.21-0.52]). Fourteen of 39 patients (35.9% [20.8-50.9]) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (p = 0.073). The platelet course was similar between Confirmed and Excluded HIT (p = 0.65). Mortality rate was 33.3% [13.2-53.5] in Confirmed and 50% [23.8-76.2] in Excluded HIT (p = 0.48). Conclusions: Prevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.
MeSH term(s)	Adult ; Aged ; Anticoagulants/adverse effects ; Critical Care/statistics & numerical data ; Diagnosis, Differential ; Extracorporeal Membrane Oxygenation/adverse effects ; Extracorporeal Membrane Oxygenation/mortality ; Female ; France/epidemiology ; Heparin/adverse effects ; Humans ; Male ; Middle Aged ; Pipecolic Acids/therapeutic use ; Platelet Aggregation Inhibitors/therapeutic use ; Platelet Count ; Prevalence ; Retrospective Studies ; Shock, Cardiogenic/mortality ; Shock, Cardiogenic/therapy ; Thrombocytopenia/chemically induced ; Thrombocytopenia/drug therapy ; Thrombocytopenia/mortality ; Treatment Outcome
Chemical Substances	Anticoagulants ; Pipecolic Acids ; Platelet Aggregation Inhibitors ; Heparin (9005-49-6) ; argatroban (IY90U61Z3S)
Language	English
Publishing date	2018-08-22
Publishing country	United States
Document type	Journal Article ; Multicenter Study
ZDB-ID	80387-x
ISSN	1432-1238 ; 0340-0964 ; 0342-4642 ; 0935-1701
ISSN (online)	1432-1238
ISSN	0340-0964 ; 0342-4642 ; 0935-1701
DOI	10.1007/s00134-018-5346-y
Database	MEDical Literature Analysis and Retrieval System OnLINE

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