Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 4 de 4
Filter
1.
BMJ ; 373: n949, 2021 04 26.
Article in English | MEDLINE | ID: covidwho-1203960

ABSTRACT

OBJECTIVE: To determine and compare the effects of drug prophylaxis on SARS-CoV-2 infection and covid-19. DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature to 25 March 2021, and six additional Chinese databases to 20 February 2021. STUDY SELECTION: Randomised trials of people at risk of covid-19 who were assigned to receive prophylaxis or no prophylaxis (standard care or placebo). Pairs of reviewers independently screened potentially eligible articles. METHODS: Random effects bayesian network meta-analysis was performed after duplicate data abstraction. Included studies were assessed for risk of bias using a modification of the Cochrane risk of bias 2.0 tool, and certainty of evidence was assessed using the grading of recommendations assessment, development, and evaluation (GRADE) approach. RESULTS: The first iteration of this living network meta-analysis includes nine randomised trials-six of hydroxychloroquine (n=6059 participants), one of ivermectin combined with iota-carrageenan (n=234), and two of ivermectin alone (n=540), all compared with standard care or placebo. Two trials (one of ramipril and one of bromhexine hydrochloride) did not meet the sample size requirements for network meta-analysis. Hydroxychloroquine has trivial to no effect on admission to hospital (risk difference 1 fewer per 1000 participants, 95% credible interval 3 fewer to 4 more; high certainty evidence) or mortality (1 fewer per 1000, 2 fewer to 3 more; high certainty). Hydroxychloroquine probably does not reduce the risk of laboratory confirmed SARS-CoV-2 infection (2 more per 1000, 18 fewer to 28 more; moderate certainty), probably increases adverse effects leading to drug discontinuation (19 more per 1000, 1 fewer to 70 more; moderate certainty), and may have trivial to no effect on suspected, probable, or laboratory confirmed SARS-CoV-2 infection (15 fewer per 1000, 64 fewer to 41 more; low certainty). Owing to serious risk of bias and very serious imprecision, and thus very low certainty of evidence, the effects of ivermectin combined with iota-carrageenan on laboratory confirmed covid-19 (52 fewer per 1000, 58 fewer to 37 fewer), ivermectin alone on laboratory confirmed infection (50 fewer per 1000, 59 fewer to 16 fewer) and suspected, probable, or laboratory confirmed infection (159 fewer per 1000, 165 fewer to 144 fewer) remain very uncertain. CONCLUSIONS: Hydroxychloroquine prophylaxis has trivial to no effect on hospital admission and mortality, probably increases adverse effects, and probably does not reduce the risk of SARS-CoV-2 infection. Because of serious risk of bias and very serious imprecision, it is highly uncertain whether ivermectin combined with iota-carrageenan and ivermectin alone reduce the risk of SARS-CoV-2 infection. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol established a priori is included as a supplement. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.


Subject(s)
COVID-19 , Carrageenan/pharmacology , Global Health/statistics & numerical data , Hydroxychloroquine/pharmacology , Ivermectin/pharmacology , Anti-Infective Agents/pharmacology , COVID-19/prevention & control , Chemoprevention/methods , Chemoprevention/statistics & numerical data , Humans , SARS-CoV-2 , Treatment Outcome , Uncertainty
2.
J Clin Epidemiol ; 129: 1-11, 2021 01.
Article in English | MEDLINE | ID: covidwho-1012425

ABSTRACT

OBJECTIVES: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields. STUDY DESIGN AND SETTING: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan. CONCLUSION: An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest.


Subject(s)
Information Management , Practice Guidelines as Topic/standards , Consensus , Evidence-Based Medicine/standards , Evidence-Based Medicine/trends , Humans , Information Management/methods , Information Management/organization & administration , Outcome Assessment, Health Care/methods , Outcome Assessment, Health Care/organization & administration , Systematic Reviews as Topic
3.
BMJ Open ; 10(12): e041868, 2020 12 02.
Article in English | MEDLINE | ID: covidwho-955459

ABSTRACT

INTRODUCTION: Rapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic. METHODS AND ANALYSIS: We plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019. We will supplement our search with studies mapped by Cochrane Fertility and Gynaecology group, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), COVID-19 study repositories, reference lists and social media blogs. The search will be updated every week and not be restricted by language. We will include observational cohort (≥10 participants) and randomised studies reporting on prevalence of COVID-19 in pregnant and postpartum women, the rates of clinical manifestations and outcomes, risk factors in pregnant and postpartum women alone or in comparison with non-pregnant women with COVID-19 or pregnant women without COVID-19 and studies on tests and treatments for COVID-19. We will additionally include case reports and series with evidence on mother-to-child transmission of SARS-CoV-2 in utero, intrapartum or postpartum. We will appraise the quality of the included studies using appropriate tools to assess the risk of bias. At least two independent reviewers will undertake study selection, quality assessment and data extraction every 2 weeks. We will synthesise the findings using quantitative random effects meta-analysis and report OR or proportions with 95% CIs and prediction intervals. Case reports and series will be reported as qualitative narrative synthesis. Heterogeneity will be reported as I2 and τ2 statistics. ETHICS AND DISSEMINATION: Ethical approval is not required as this is a synthesis of primary data. Regular updates of the results will be published on a dedicated website (https://www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and disseminated through publications, social media and webinars. PROSPERO REGISTRATION NUMBER: CRD42020178076.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , COVID-19/diagnosis , COVID-19/physiopathology , COVID-19/therapy , COVID-19/transmission , Female , Humans , Infectious Disease Transmission, Vertical , Meta-Analysis as Topic , Postpartum Period , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/physiopathology , Pregnancy Complications, Infectious/therapy , Pregnancy Outcome , Risk Factors , Systematic Reviews as Topic
4.
BMJ ; 370: m2980, 2020 07 30.
Article in English | MEDLINE | ID: covidwho-691120

ABSTRACT

OBJECTIVE: To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN: Living systematic review and network meta-analysis. DATA SOURCES: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis. STUDY SELECTION: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS: After duplicate data abstraction, a bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development, and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS: 196 trials enrolling 76 767 patients were included; 111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration; 113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty), mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty). Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty). Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty), mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty). The impact of remdesivir on mortality and most other outcomes is uncertain. The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality. In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low. CONCLUSION: Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19. Janus kinase inhibitors appear to have promising benefits, but certainty is low. Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits. Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain. SYSTEMATIC REVIEW REGISTRATION: This review was not registered. The protocol is publicly available in the supplementary material. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.


Subject(s)
Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Respiration, Artificial/statistics & numerical data , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Betacoronavirus/pathogenicity , COVID-19 , Centers for Disease Control and Prevention, U.S./statistics & numerical data , China/epidemiology , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/mortality , Coronavirus Infections/virology , Databases, Factual/statistics & numerical data , Drug Combinations , Evidence-Based Medicine/methods , Evidence-Based Medicine/statistics & numerical data , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Lopinavir/therapeutic use , Network Meta-Analysis , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Randomized Controlled Trials as Topic , Ritonavir/therapeutic use , SARS-CoV-2 , Severity of Illness Index , Standard of Care , Treatment Outcome , United States/epidemiology
SELECTION OF CITATIONS
SEARCH DETAIL