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2018 ; 6
(6
): CD012713
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Ribavirin for treating Crimean Congo haemorrhagic fever
#MMPMID29869797
Johnson S
; Henschke N
; Maayan N
; Mills I
; Buckley BS
; Kakourou A
; Marshall R
Cochrane Database Syst Rev
2018[Jun]; 6
(6
): CD012713
PMID29869797
show ga
BACKGROUND: Crimean Congo haemorrhagic fever (CCHF) is a tick-borne disease that
occurs in parts of Asia, Europe and Africa. Since 2000 the infection has caused
epidemics in Turkey, Iran, Russia, Uganda and Pakistan. Good-quality general
supportive medical care helps reduce mortality. There is uncertainty and
controversy about treating CCHF with the antiviral drug ribavirin. OBJECTIVES: To
assess the effects of ribavirin for treating people with Crimean Congo
haemorrhagic fever. SEARCH METHODS: We searched the Cochrane Infectious Diseases
Group Specialized Register; the Central Register of Controlled Trials (CENTRAL);
MEDLINE (PubMed); Embase (OVID); Science Citation Index-Expanded, Social Sciences
Citation index, conference proceedings (Web of Science); and CINAHL (EBSCOHost).
We also searched the WHO International Clinical Trials Registry Platform (ICTRP)
and ClinicalTrials.gov for trials in progress. We conducted all searches up to 16
October 2017. We also contacted experts in the field and obtained further studies
from these sources. SELECTION CRITERIA: We evaluated studies assessing the use of
ribavirin in people with suspected or confirmed Crimean Congo haemorrhagic fever.
We included randomised control trials (RCTs); non-randomised studies (NRSs) that
included more than 10 participants designed as cohort studies with comparators;
and case-control studies. DATA COLLECTION AND ANALYSIS: Two review authors
assessed eligibility, risk of bias, and extracted data. For non-randomized
studies we used the ROBINS-I tool to assess risk of bias. The main effects
analysis included all studies where we judged the risk of bias to be low,
moderate or high. We summarized dichotomous outcomes using risk ratios (RRs) and
continuous outcomes using mean differences (MDs), and used meta-analyses where
appropriate. We carried out a subsidiary appraisal and analysis of studies with
critical risk of bias for the primary outcome, as these are often cited to
support using ribavirin. MAIN RESULTS: For the main effects analysis, five
studies met our inclusion criteria: one RCT with 136 participants and four
non-randomized studies with 612 participants. We excluded 18 non-randomized
studies with critical risk of bias, where none had attempted to control for
confounding.We do not know if ribavirin reduces mortality (1 RCT; RR 1.13, 95%
confidence interval (CI) 0.29 to 4.32; 136 participants; very low-certainty
evidence; 3 non-randomized studies; RR 0.72, 95% CI 0.41 to 1.28; 549
participants; very low-certainty evidence). We do not know if ribavirin reduces
the length of stay in hospital (1 RCT: mean difference (MD) 0.70 days, 95% CI
-0.39 to 1.79; 136 participants; and 1 non-randomized study: MD -0.80, 95% CI
-2.70 to 1.10; 50 participants; very low-certainty evidence). We do not know if
it reduces the risk of patients needing platelet transfusions (1 RCT: RR 1.23,
95% CI 0.77 to 1.96; 136 participants; very low-certainty evidence). For adverse
effects (including haemolytic anaemia and a need to discontinue treatment), we do
not know whether there is an increased risk with ribavirin in people with CCHF as
data are insufficient.We do not know if adding ribavirin to early supportive care
improves outcomes. One non-randomized study assessed mortality in people
receiving ribavirin and supportive care within four days or less from symptom
onset compared to after four days since symptom onset: mortality was lower in the
group receiving early supportive care and ribavirin, but it is not possible to
distinguish between the effects of ribavirin and early supportive medical care
alone.In the subsidiary analysis, 18 studies compared people receiving ribavirin
with those not receiving ribavirin. All had a critical risk of bias due to
confounding, reflected in the mortality point estimates favouring ribavirin.
AUTHORS' CONCLUSIONS: We do not know if ribavirin is effective for treating
Crimean Congo haemorrhagic fever. Non-randomized studies are often cited as
evidence of an effect, but the risk of bias in these studies is high.
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