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发表于 2014-7-12 16:47:59
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hazard ratios
Neuraminidase inhibitors for preventing and treating influenza in healthy adults
Main outcome measures Duration and incidence of symptoms; incidence of lower respiratory tract infections, or their proxies; and adverse events.Data extraction Two reviewers applied inclusion criteria, assessed trial quality, and extracted data.Data analysis Comparisons were structured into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose.Results 20 trials were included: four on prophylaxis, 12 on treatment, and four on postexposure prophylaxis. For prophylaxis, neuraminidase inhibitors had no effect against influenza like illness or asymptomatic influenza. The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily and 73% (0.27,hogan scarpe, 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily was 62% efficacious (0.38, 0.17 to 0.85). Oseltamivir for postexposure prophylaxis had an efficacy of 58% (95% confidence interval 15% to 79%) and 84% (49% to 95%) in two trials of households. Zanamivir performed similarly. The hazard ratios for time to alleviation of influenza like illness symptoms were in favour of treatment: 1.20 (95% confidence interval 1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Eight unpublished studies on complications were ineligible and therefore excluded. The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35). From trial evidence, oseltamivir induced nausea (odds ratio 1.79,hogan rebel online, 95% confidence interval 1.10 to 2.93). Evidence of rarer adverse events from pharmacovigilance was of poor quality or possibly under reported.Conclusion Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir's prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed.IntroductionNeuraminidase inhibitors comprise nebulised zanamivir (Relenza; Glaxo Wellcome) and oral oseltamivir (Tamiflu; Gilead Sciences and F Hoffmann La Roche),hogan outlet 2014, and others still under development for parenteral or long acting use.1 Inhibiting neuraminidase which, as with haemagglutin, is specific to influenza blocks the exit of the influenza virus from the host cell, thereby preventing replication in other than a few host cells.2The use of neuraminidase inhibitors has increased dramatically with the spread of the influenza A/H1N1 pandemic that began in April 2009, a novel and potentially serious infection. Partly because of the rise in resistance to amantadine and rimantadine and the lack of an effective vaccine, neuraminidase inhibitors became a widespread public health intervention. This criticism centred on one paper in particular,nike air max 95, a meta analysis of the effects of oseltamivir on complications of influenza.10 Only two of 10 randomised sets of data had been published, and Hayashi was concerned that information was insufficient to assess methods, reliability, and applicability of the eight remaining datasets.In updating our review we addressed these additional concerns while answering the original questions: what is the evidence on the effects of neuraminidase inhibitors in preventing or ameliorating influenza, transmission of the virus, and influenza related complications in otherwise healthy adults,nike tn 2014, and what is the frequency of adverse effects? Our original review had found positive evidence on all of these effects, and gastrointestinal harms.MethodsWe updated a search previously undertaken in any language for randomised or quasirandomised studies that compared oseltamivir or zanamivir in otherwise healthy people exposed to naturally occurring influenza, against placebo, control antivirals,hogan interactive outlet, or no intervention (or compared doses or schedules of the neuraminidase inhibitors) with the outcomes of influenza (efficacy) or influenza like illness (effectiveness).6 We excluded experimental influenza challenge studies as their generalisability and comparability with field studies is uncertain. Studies had to include 75% or more of patients aged 14 60 (excluding older people at higher risk of complications). The updated search is summarised in the web extra. It included checking the references of other systematic reviews.4 5 7 8 9Two of us separately read all titles and studies retrieved in the search and applied inclusion criteria. Disagreements were resolved by discussion with a third reviewer. Data were extracted on to standard forms,nike air max womens, checked,hogan rebel outlet, and recorded. Assessing for risk of bias (using established criteria)11 became a major focus of this review.Among complications we included a combined outcome of pneumonia, bronchitis,hogan bambino, sinusitis, and otitis media requiring antibiotics in people with laboratory confirmed influenza. We were unable to meta analyse the same outcomes reported by Kaiser et al10 because the data for those outcomes were not available to us for individual trials. We carried out a sensitivity analysis of complications by excluding the unpublished trials included in the Kaiser review criticised by Hayashi.We used random effects methods to compare dichotomous outcomes (risk ratio for efficacy and odds ratio for safety); therefore estimates meta analysed over multiple trials are average treatment effects. Where hazard ratios were not provided we converted the ratio of medians of treatment groups into (log) hazard ratios (estimating the variance of these)12 to enable meta analysis of time to event outcomes. We were obliged to exclude this meta analysis because we were unable to determine the number of healthy adults experiencing complications in each study (some studies contained mixed populations of healthy and comorbid participants), nor the number of patients experiencing one or more of "bronchitis, lower respiratory tract infection,air max 95, or pneumonia" presenting to each study.Evidence of benefitsProphylaxis against influenzaWe found no new studies of benefit fulfilling our criteria. Two trials compared a total of 697 adults treated with inhaled zanamivir 10 mg daily and 602 with placebo (followed for 22 days),nike air max 1,21 30 and two trials compared 675 adults treated with oral oseltamivir 75 mg daily and 413 with placebo (followed for 49 days).22 36 Evidence was insufficient to support or refute the effect of neuraminidase inhibitors on prophylaxis of influenza like illness: risk ratio 1.28 (95% confidence interval 0.45 to 3.66) for oseltamivir and 1.51 (0.77 to 2.95) for zanamivir.19 21 36 Higher dosages made no difference, although this conclusion is based on a single study with only nine events (fig 3).36Fig 3Effect of neuraminidase inhibitors compared with placebo on prophylaxis against influenza like illnessZanamivir reduced the chance of symptomatic laboratory confirmed influenza (0.38,nike air max trainers, 0.17 to 0.85 for 10 mg daily). Oseltamivir was similarly efficacious (0.39, 0.18 to 0.85 for 75 mg daily; fig 4). Neither protected against asymptomatic influenza.22 30 36相关的主题文章:
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