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Physical interventions to interrupt or reduce the spread of respiratory viruses

AbstractObjective To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses.Data selection Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow up. Non randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias.Data synthesis 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta analysis of six case control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure that is, the higher the risk the longer the distancing period.Conclusion Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. Overall, epidemics account for most of the 7% of total deaths from respiratory tract infections in the world.3 Our 2007 Cochrane review showed that physical interventions (personal hygiene, barriers, and distancing) are highly effective.4 However, the current mainstay of pandemic interventions still seems to be vaccines and antiviral drugs, with no evidence supporting their widespread use,5 6 7 8 9 10 especially against a seemingly mild threat such as the novel H1N1 virus. For example, in the most recent guidance document on planning for pandemic influenza from the World Health Organization, handwashing and masks were mentioned only twice and gloves and gowns once each, but vaccines and antivirals were cited 24 and 18 times, respectively.11We carried out a systematic review to update our 2007 Cochrane review on the evidence of the effectiveness of public health measures such as isolation, distancing, and barriers to interrupt or reduce the spread of respiratory viruses.MethodsWe considered trials (individual level or cluster randomised, or quasi randomised), observational studies (cohort and case control designs), and any other comparative design, carried out in people of all ages and provided that some attempt had been made to control for confounding. We included any intervention to prevent the transmission of respiratory viruses from animal to human or from human to human (isolation, quarantine, social distancing, barriers, personal protection, or hygiene) compared with no intervention ("do nothing") or another intervention. We excluded vaccines and antivirals.Outcome measures were mortality, numbers of cases of viral illness, the severity of viral illness, or proxies for any of these, and other measures of disease burden (such as admissions to hospital). No language restrictions were applied. Filters for study design included trials, cohort, case control and crossover studies, before and after, and time series. We scanned the references of included studies for other potentially relevant studies.We scanned the titles and abstracts of the studies identified by our search. When a study seemed to meet our eligibility criteria or information was insufficient to exclude it, we obtained the full text articles. We used a standardised form to assess the eligibility of each study, on the basis of the full article.Quality assessmentWe analysed randomised and non randomised studies separately. Risk of bias in the randomised studies was assessed for the method of randomisation, generation of the allocation sequence, allocation concealment, blinding, and follow up. Non randomised studies were assessed for the presence of potential confounders using the appropriate Newcastle Ottawa scales12 for case control and cohort studies, and a three point checklist for controlled before and after and ecological studies.13We assigned categories for risk of bias on the basis of the number of items judged inadequate in each study: up to one inadequate item represented a low risk of bias, up to three items a medium risk, and more than three items a high risk.Aggregation of data depended on the study design, types of comparisons, sensitivity, and homogeneity of definitions of exposure, populations, Hermes birkin bags fake and outcomes used. We calculated the I2 statistic for each pooled estimate to assess the impact of statistical heterogeneity.14 15When possible we carried out a quantitative analysis and summarised replica hermes handbags effectiveness as an odds ratio, with 95% confidence intervals. When a result was significant we calculated absolute intervention effectiveness as a percentage using the formula: intervention effectiveness=1odds ratio.ResultsOf a total 2958 potentially relevant studies scanned for the 2007 review and its 2009 update, 2790 were excluded on the basis of their titles or abstracts, and the full papers of the remaining 168 trials were retrieved. Fifty eight papers of 59 studies were finally included (table 1); eight of these studies were incorporated in the 2009 update. A list of excluded studies will be available in the published Cochrane update.Table 1 Overview of results of physical interventions and types of evidence to interrupt or reduce the spread of respiratory virusesView this table:View popupView inlineThe quality of the included randomised controlled trials varied (see web extra table). Three of the four trials were poorly reported, with two papers (three studies) giving no description of the randomisation sequence, allocation, or allocation concealment.16 17 One trial reported the generation of randomisation, but blinding was impossible owing to the nature of the intervention (gargling with water with or without povidone iodine compared with standard gargling with no attempt to mask the taste of iodine).18 Information provided in a subsequent brief report contradicted the original report.19 The design of the two trials was artificial and therefore the results were not generalisable to daily practice.17The quality of the cluster randomised trials varied (see web extra table). Only the highest quality trials20 21 22 29 reported cluster coefficients and carried out analysis of data by unit of (cluster) randomisation. Other common problems were a lack of description of randomisation procedures, partial reporting of outcomes, unclear numerators or denominators, unexplained attrition,23 24 25 26 and complete failure of double blinding27 or inappropriate choice of placebo.28 Two cluster randomised trials involving the use of face masks29 30 by contacts of patients with influenza and influenza like illness had poor compliance. This illustrates the difficulty of using bulky equipment in clinical trials in the absence of a real threat. In one trial the intervention targeted (randomised) clusters comprising households of index patients with influenza, up to three days after the onset of symptoms in the index case.29 This almost certainly underestimates the effect of the interventions, given that influenza how much is a hermes bag infectivity is highest soon after infection. Another study was underpowered to detect differences in effect between different types of masks.30 A further cluster randomised trial was rated as being at low risk of bias owing to careful evaluation of compliance in the intervention arm (hand sanitiser wipes and disinfection of surfaces).31Five of the seven case control studies had a medium risk of bias32 33 34 35 36 and two a low risk,37 38 mostly because of inconsistencies in the text and lack of adequate description of controls (see web extra table). Six of the 16 prospective cohort studies had a low risk of bias,39 40 41 42 43 44 six a medium risk,45 46 47 48 49 50 and three a high risk (see web extra table).51 52 53 One was a brief report of a small study with insufficient details to allow assessment.54 All five retrospective cohort studies had a high risk of bias (see web extra table).55 56 57 58 59 Six of the 13 controlled before and after studies had a low risk of bias,60 61 62 63 64 65 two a medium risk,66 67 and five a high risk (see web extra table).68 69 70 71 72 Many of the observational studies were poorly reported and the retrospective designs were prone to recall Hermes bag season with the main color coordination bias. The most common problem in all of these studies, however, was that circulation of the virus within the reference population was not reported, questioning the interpretation and generalisability of the conclusions.Reported results from randomised studiesHandwashing with or without antisepticsThree randomised controlled trials tested the effects of cleaning hands on inactivating the virus and preventing experimental colds due to rhinovirus. This resulted either in a reduction in the incidence of rhinovirus infection among volunteers using different combinations of acids for cleaning (P=0.025)17 or did not reach statistical significance (13% v 30% with combined denominator of only 60).17 When iodine treatment of the fingers was used, one of 10 volunteers in the intervention arm became infected compared with six of 10 in the placebo arm (P=0.06, Fisher's exact test).16Eight cluster randomised studies tested educational programmes to promote handwashing with or without antiseptic agents on the incidence of acute respiratory tract infections either in schools or in households. As a result of different definitions, comparisons, lack of reporting of cluster coefficients, and, in two cases, missing data for participants,23 24 meta analysis was not feasible. Three of the trials reported a lack of effect for the prevention of acute respiratory illness: risk ratios 0.94 (95% confidence interval 0.66 to 2.43),24 0.97 (0.72 to 1.30),22 and 1.10 (0.97 to 1.24).31 A possible explanation for the lack of effect is that because exposure to respiratory viruses is ubiquitous, repeated hand hygiene would be needed, which is not practical in busy settings such as schools. Nevertheless, the highest quality trials reported a significant decrease in respiratory illness in children aged up to 24 months (risk ratio 0.90, 0.83 to 0.97), although the decrease was not significant in older children (0.95, 0.89 to 1.01),21 and a 50% (65% to 34%) lower incidence of pneumonia in children aged less than 5 years in a low income country.20 Another study reported a decrease in respiratory tract infections of up to 38% with additional hand rubbing with benzalkonium chloride (risk ratios 0.69 for incidence of absence due to illness and 0.71 for duration of absence).26 One study reported a 43% reduction in absenteeism from school with the use of alcohol gel in addition to handwashing.25 Repeated handwashing significantly reduced the incidence of colds by as much as 20% in two trials.23 73Impregnated disposable handkerchiefsThree cluster randomised studies tested the effects of disposable handkerchiefs impregnated with virucide on the incidence and spread of acute respiratory tract infections. One study reported a reduced incidence from 14% to 5% in households over 26 weeks.27 A similar study reported a small non significant (5%) decrease across families.27 However, as the reduction in incidence was confined to primary illness, which would be unaffected by use of the tissues, it might be assumed that the tissues were ineffective. A community trial also reported a non significant reduction in secondary attack rates of acute respiratory tract infection (18.7% v 11.8%) during high circulation of influenza H3N2 and rhinoviruses in the community.28 This result is likely to be an underestimate because of the barrier effect of the untreated tissue wipes used as control.GarglingOne trial from Japan tested the effects of gargling with water compared with gargling with povidone iodine or gargling as usual.18 This trial is linked by its registration number to a subsequent short report19 and the reporting of the two is confusing. The incidence rate ratio for gargling with water was 0.64 (95% confidence interval 0.41 to 0.99) and for gargling with povidone iodine was 0.89 (0.60 to 1.33). Gargling with povidone iodine seemed to affect compliance because two participants switched to using water. Perhaps this potentially important study, totalling 387 participants in three arms, should be repeated in a larger population and with clearer reporting.Face masksTwo cluster randomised trials assessed the effects on transmission of wearing face masks. In one study carried out in Hong Kong29 face masks were worn after a rapid diagnosis for influenza. Households of the index case were randomised to wearing face masks plus education, handwashing with alcohol sanitiser soap plus education, or education on illness prevention (control group). Surgical face masks were worn by all household members when the index patient was at home. This is likely to be an underestimate of the effect because of the study design.

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