***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To estimate the global prevalence and incidence of herpes simplex virus type 2 ( HSV-2 ) infection in 2003 . METHODS A systematic review was undertaken of published seroprevalence surveys describing the prevalence or incidence of HSV-2 by age and gender . For each of 12 regions , pooled prevalence values by age and gender were generated in a r and om-effect model . HSV-2 incidence was then estimated from these pooled values using a constant-incidence model . Values of the HSV-2 seroprevalence from the model fits were applied to the total population to estimate the numbers of people infected . FINDINGS The total number of people aged 15 - 49 years who were living with HSV-2 infection worldwide in 2003 is estimated to be 536 million , while the total number of people who were newly infected with HSV-2 in 2003 is estimated to be 23.6 million . While the estimates are limited by poor availability of data , general trends are evident . For example , more women than men were infected , and the number infected increased with age . Although prevalence varied substantially by region , predicted prevalence was mostly higher in developing regions than developed regions . CONCLUSION The prevalence of HSV-2 is relatively easy to measure since infection is lifelong and has a specific serological test . The burden of disease is less easy to quantify . Despite the often sparse data on which these estimates are based , it is clear that HSV-2 infection is widespread . The dramatic differences in prevalence between regions are worthy of further exploration The antiherpes drug acyclovir breaks chromosomes in vitro at millimolar concentrations and at highly toxic doses in rodents but does not induce single-gene mutations . Recurrent genital herpes patients were examined to determine if such chromosomal damage occurs in peripheral lymphocytes during acute or chronic acyclovir therapy . Patients were r and omly assigned to receive acyclovir suppressively and for recurrences , placebo suppressively and acyclovir for recurrences , or placebo suppressively and for recurrences ( n greater than or equal to 20 for each group ; all treatment double-blind ) . Normal volunteers and acyclovir-treated cultures served as additional controls . Cytogenetic analyses were done at enrollment ( pretreatment ) , on day 5 of acute acyclovir or placebo treatment for the first postenrollment recurrence ( postacute ) , and at the end of a year on study ( postchronic ) . Cells in metaphase , 150 for each patient , were examined at each time point for structural and numerical chromosomal abnormalities . No cytogenetic effects of chronic or acute oral acyclovir treatment were found relative to lifestyle controls , pretreatment controls , or placebo treatment A new measure of treatment satisfaction ( GHerpTSQ ) for recurrent genital herpes simplex virus ( HSV ) was vali date d and used to evaluate two therapeutic strategies widely used for the management of HSV : episodic treatment , where individual herpes outbreaks are treated as they arise ; suppressive therapy , where treatment is taken daily to prevent HSV outbreaks . Satisfaction with treatment is important since daily dosing with suppressive therapy is necessary in the absence of symptoms . A 12-item question naire was design ed using a modified form of the Diabetes treatment satisfaction question naire ( DTSQ ) . The psychometric properties of the GHerpTSQ were evaluated within a sample of 125 Canadians with a history of HSV ( type 1 , 2 ) infection participating in a 48 week r and omised cross-over trial . Factor analysis suggested that the items can be analysed as two separate subscales corresponding to Control/effectiveness , and Convenience/lifestyle ; the single item concerning side effects was retained for separate analysis . Forced one-factor analysis showed that the two subscales can be combined to obtain a total score relating to overall treatment satisfaction . The GHerpTSQ has good internal reliability , clear structure with little overlap of subscales and evidence of good sensitivity to changes in treatment Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Background Direct empirical evidence for the existence of outcome reporting bias is accumulating and this source of bias is recognised as a potential threat to the validity of meta- analysis of r and omised clinical trials . Methods A method for calculating the maximum bias in a meta- analysis due to publication bias is adapted for the setting where within- study selective non-reporting of outcomes is suspected , and compared to the alternative approach of missing data imputation . The properties of both methods are investigated in realistic small sample situations . Results The results suggest that the adapted Copas and Jackson approach is the preferred method for review ers to apply as an initial assessment of robustness to within- study selective non-reporting . Conclusion The Copas and Jackson approach is a useful method for systematic review ers to apply to assess robustness to outcome reporting bias Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose The potential utility of intermittent regimens of oral acyclovir for suppression of recurrent genital herpes  depends on how long the suppressive effect of the drug persists during pauses in treatment . To study this question , we admitted 38 patients in a double-blind controlled trial comparing the results of daily acyclovir treatment ( 200 mg t.i.d . ) with treatment on weekend days only ( 400 mg t.i.d . on Saturday and Sunday ) for suppression of recurrent genital herpes . Of the 35 patients completing the study , significantly more failures occurred in the weekend group ( 13/17 ) than in the daily group ( 3/18 , P less than 0.001 ) . Failures on the weekend regimen were more frequent as the week progressed ( P = 0.005 ) . The findings suggest a short-term persistence of suppression by acyclovir and hence that intermittent regimens with more closely spaced periods of treatment may be more effective than the regimen we studied . Most virus isolates studied , including all of those isolated from the patients during treatment , were sensitive to acyclovir BACKGROUND Skin and mucosal herpes simplex virus type 2 ( HSV-2 ) shedding predominantly occurs in short sub clinical episodes . We assessed whether st and ard-dose or high-dose antiviral therapy reduces the frequency of such shedding . METHODS HSV-2-seropositive , HIV-seronegative people were enrolled at the University of Washington Virology Research Clinic ( WA , USA ) . We did three separate but complementary open-label cross-over studies comparing no medication with aciclovir 400 mg twice daily ( st and ard-dose aciclovir ) , valaciclovir 500 mg daily ( st and ard-dose valaciclovir ) with aciclovir 800 mg three times daily ( high-dose aciclovir ) , and st and ard-dose valaciclovir with valaciclovir 1 g three times daily ( high-dose valaciclovir ) . The allocation sequence was generated by a r and om number generator . Study drugs were supplied in identical , numbered , sealed boxes . Study periods lasted 4 - 7 weeks , separated by 1 week wash-out . Participants collected genital swabs four times daily for quantitative HSV DNA PCR . Clinical data were masked from laboratory personnel . The primary endpoint was within-person comparison of shedding rate in each study group . Analysis was per protocol . The trials are registered at Clinical Trials.gov ( NCT00362297 , NCT00723229 , NCT01346475 ) . RESULTS Of 113 participants r and omised , 90 were eligible for analysis of the primary endpoint . Participants collected 23 605 swabs ; 1272 ( 5·4 % ) were HSV-positive . The frequency of HSV shedding was significantly higher in the no medication group ( n=384 , 18·1 % of swabs ) than in the st and ard-dose aciclovir group ( 25 , 1·2 % ; incidence rate ratio [ IRR ] 0·05 , 95 % CI 0·03 - 0·08 ) . High-dose aciclovir was associated with less shedding  than st and ard-dose valaciclovir ( 198 [ 4·2 % ] vs 209 [ 4·5 % ] ; IRR 0·79 , 95 % CI 0·63 - 1·00 ) . Shedding was less frequent in the high-dose valaciclovir group than in the st and ard-dose valaciclovir group ( 164 [ 3·3 % ] vs 292 [ 5·8 % ] ; 0·54 , 0·44 - 0·66 ) . The number of episodes per person-year did not differ significantly for st and ard-dose valaciclovir ( 22·6 ) versus high-dose aciclovir ( 20·2 ; p=0·54 ) , and st and ard-dose valaciclovir ( 14·9 ) versus high-dose valaciclovir ( 16·5 ; p=0·34 ) , but did for no medication ( 28·7 ) and st and ard-dose aciclovir ( 10·0 ; p=0·001 ) . Median episode duration was longer for no medication than for st and ard-dose aciclovir ( 13 h vs 7 h ; p=0·01 ) and for st and ard-dose valaciclovir than for high-dose valaciclovir ( 10 h vs 7 h ; p=0·03 ) , but did not differ significantly between st and ard-dose valaciclovir and high-dose aciclovir ( 8 h vs 8 h ; p= 
    Output:
    
Owing to risk of bias and inconsistency , there is low quality evidence that suppressive antiviral therapy with acyclovir , valacyclovir or famciclovir in pacients experiencing at least four recurrences of genital herpes per year decreases the number of pacients with at least one recurrence as compared with placebo .
Network meta- analysis of the few direct comparisons and the indirect comparisons did not show superiority of one drug over another