Antivirals for treatment of influenza: a systematic review and meta-analysis of observational studies.

BACKGROUND: Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza. PURPOSE: To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists. STUDY SELECTION: Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness. DATA EXTRACTION: Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: 74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine. LIMITATIONS: Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias. CONCLUSION: Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University.

Randomized controlled trial comparing telephone and mail follow-up for recruitment of participants into a clinical trial of colorectal cancer screening.

BACKGROUND: Investigators often face challenges when recruiting participants into randomized controlled trials (RCTs). Some data suggest that telephone reminders may lead to greater participant enrollment. METHODS: Patients aged 50 to 70 years from family practice rosters were initially mailed invitations to participate in an RCT of colorectal cancer screening. Patients who did not respond were randomly allocated to follow-up invitations by either telephone or mail four weeks after the initial invitation. The primary outcome was attendance for eligibility screening with the study nurse. RESULTS: After mailing invitations to 1,348 patients, 104 patients were initially enrolled in the RCT of colon cancer screening. Of 952 patients who did not respond to the initial mailed invitation, we randomly allocated 480 to follow-up invitation by telephone and 472 to follow-up invitation by mail. Attendance for eligibility screening with the study nurse was more frequent when non-responders were followed-up by telephone (84/480, 17.5%) than by mail (43/472, 9.1%) (relative risk (RR) 1.92, 95% confidence interval (CI) 1.36 to 2.71, P < 0.001). Enrollment into the RCT was also greater among patients followed-up by telephone (59/480, 12.3%) compared to those followed-up by mail (35/472, 7.4%) (RR 1.66, 95% CI 1.11 to 2.47, P=0.01). CONCLUSIONS: Telephone-based follow-up results in greater enrollment compared to a mail-based method. Our findings should be of interest to investigators conducting RCTs, particularly trials of screening interventions involving asymptomatic participants for which volunteer participation may be challenging. TRIAL REGISTRATION: Clinicaltrials.gov NCT00865527.

Antivirals for influenza: a summary of a systematic review and meta-analysis of observational studies.

Despite the use of antivirals to treat patients with severe influenza, questions remain with respect to effects and safety. Although a recent systematic review has provided some indication of benefit, the analysis is limited by the quality of the available evidence from randomized controlled trials. To supplement the existing information, the authors conducted a systematic review of observational studies of antiviral treatment for influenza. This report summarises the findings of that review. Similar to the randomised trials, the confidence in the estimates of the effects for decision-making is low to very low primarily due to the risk of selection and publication bias in the observational studies. From these observational studies, the summary estimates suggest that oseltamivir may reduce mortality, hospitalisation and duration of symptoms compared with no treatment. Inhaled zanamivir may also reduce symptom duration and hospitalisations, but patients may experience more complications compared with no treatment. Earlier treatment with antivirals is generally associated with better outcomes than later treatment. Further high-quality evidence is needed to inform treatment guidelines because of the overall low to very low quality of evidence.