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The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia: a meta-analysis |
Jackson J L, Gibbons R, Meyer G, Inouye L |
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Authors' objectives To determine if treatment with oral acyclovir reduces the incidence of postherpetic neuralgia in immunocompetent adults.
Searching MEDLINE was searched from 1966 to 1996 for English language publications, using the MeSH terms 'acyclovir', 'herpes zoster' and 'randomised clinical trials'; it was also searched for citations using 'acyclovir' and 'herpes zoster', and articles thus identified were manually reviewed. In addition, a supplementary search was performed by a professional librarian, and the National Institute of Health database and Cochrane Controlled Trials Register were searched for published and unpublished data.
Study selection Study designs of evaluations included in the reviewRandomised controlled trials (RCTs) were included.
Specific interventions included in the reviewOral acyclovir at a dose of 800 mg, 5 times daily, for periods ranging from 7 to 21 days.
Participants included in the reviewImmunocompetent adults with herpes zoster were included.
Outcomes assessed in the reviewPresence of any pain during the distribution of the rash at 6 months.
How were decisions on the relevance of primary studies made?The authors do not state how the papers were selected for the review, or how many of the authors performed the selection.
Assessment of study quality The quality of included articles was assessed by factors including the method of randomisation, the effectiveness of blinding, a statement of intention to treat analysis, information on patient withdrawal, and availability of patients for follow-up. Retrieved articles were stripped of identifying features and reviewed by two investigators for study quality, according to the criteria of Chalmers et al. (see Other Publications of Related Interest no.1).
Data extraction The data extraction was performed by committee consensus in an unblinded manner. The author was contacted if data could not be directly extracted from the publication.
Methods of synthesis How were the studies combined?The unweighted data from the studies were combined and analysed using the fixed-effect model of Peto (see Other Publications of Related Interest no.2), giving a summary odds ratio (OR) with 95% confidence interval (CI) and the number-needed-to-treat (NNT).
How were differences between studies investigated?The propriety of pooling was tested, although the method used is not described. The result of heterogeneity testing was reported as 'homogeneity confirmed', although no numerical value is given. A graphical display of the overall average effect, along with the results of all single studies, is presented. No numerical values are given of individual study results. There is no investigation of possible sources of heterogeneity between studies.
Results of the review Five RCTs (792 patients) with a 6-month follow-up were included. The number of patients originally randomised was not stated.
The summary OR for incidence of any pain at 6 months was 0.54 (95% CI: 0.36, 0.81), with an absolute risk reduction of 0.16. The NNT to prevent 1 case of postherpetic neuralgia is 6.3.
Cost information The NNT to prevent one case of postherpetic neuralgia is 6.3, at a cost of US$1,224.88 (10 days treatment) per case averted.
Authors' conclusions Patients treated within 72 hours of rash onset may experience a 46% reduction in the incidence of pain during the distribution of the rash at 6 months.
CRD commentary The review used an extensive search. There are no stated criteria for the inclusion of studies; in particular, it is not stated whether the included trials were only of patients treated with acyclovir within 72 hours of appearance of the herpes zoster rash. Also, there are no criteria on what constituted a diagnosis of herpes zoster in the original studies. The introduction states that older patients are at higher risk of postherpetic neuralgia, but 'older' is not defined. Participants in the included studies had mean ages of 49, 51, 61, 66 and 71 years; it is unclear whether these patients were a homogeneous group with comparable rates of postherpetic neuralgia. It is not stated if the data were extracted in an intention to treat format or how drop-outs were counted. The included studies were noted by the authors to have flaws, e.g. lack of information on method of randomisation, lack of information on patient withdrawal, and significant patient unavailability for follow-up. It is unclear whether the information obtained directly from the original authors provided the missing details; if this information was not made available there is the potential for bias in the results. It is unclear how the figure of 16% for the absolute risk reduction was calculated.
Implications of the review for practice and research In view of the uncertainties mentioned above it is unclear whether treatment with acyclovir can reduce the incidence of postherpetic neuralgia. Further good quality RCTs may be required to answer this question.
Bibliographic details Jackson J L, Gibbons R, Meyer G, Inouye L. The effect of treating herpes zoster with oral acyclovir in preventing postherpetic neuralgia: a meta-analysis. Archives of Internal Medicine 1997; 157(8): 909-912 Other publications of related interest 1. Chalmers TC, Smith H, Blackburn B, Silverman B, Schroeder B, Reitman D, et al. A method for asssessing the quality of a randomized control trial. Control Clin Trials 1981;2:31-49. 2. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985;27:335-71.
Indexing Status Subject indexing assigned by NLM MeSH Acyclovir /therapeutic use; Antiviral Agents /therapeutic use; Herpes Zoster /complications /drug therapy; Humans; Incidence; Neuralgia /prevention & Odds Ratio; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome; control /virology AccessionNumber 11997008103 Date bibliographic record published 31/07/1998 Date abstract record published 31/07/1998 Record Status This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn. |
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