Neuraminidase inhibitors: who, when, where?

Although the neuraminidase inhibitors (NIs), oseltamivir and zanamivir were first licensed in 1999, their clinical effectiveness is still hotly debated. Two rigorous systematic reviews and meta-analyses of the data from clinical trials conducted in community settings against relatively benign influenza, both suggest that reductions in symptom duration are extremely modest, under one day. Whilst one of these reviews could find no evidence of reductions in complications, the most recent review reported clinically meaningful and statistically significant reductions in the likelihood of requiring antibiotics (44%) and hospitalizations (63%) in adult patients with confirmed influenza, treated with oseltamivir. A further meta-analysis of observational data from the 2009 influenza A(H1N1) pandemic suggested that, in hospitalised patients, NIs significantly reduced mortality in adults by 25% overall, and by 62% if started within 48 hours of symptom onset, compared with no treatment. But, the effectiveness of NIs in children is far less clear. Taken together, these data suggest that NIs should be reserved for patients with influenza who are at high-risk of complications, or when clinically assessed found to be markedly unwell, or rapidly deteriorating. In such patients, treatment should be initiated empirically, as soon as possible, preferably with follow-on virological confirmation.

History of knee injuries and knee osteoarthritis: a meta-analysis of observational studies.

OBJECTIVES: Although knee injury has been implicated as a risk factor for the development of knee osteoarthritis (OA), there is great disparity in the magnitude of quantifiable risk. Our aim was to systematically review the relationship between history of knee injuries and knee OA. METHODS: Six electronic databases were searched between August and October 2010. Relative risk estimates or odds ratio (OR) and 95% confidence intervals (95% CI) were extracted or calculated from observational studies meeting the inclusion criteria. Publication bias was determined using funnel plot and the Egger's test. Heterogeneity was examined using Cochran Q test and I(2) statistic. Random effects model was used to pool the heterogeneous results and OR was used to present the results. Subgroup analyses were performed to examine potential causes of heterogeneity. RESULTS: Twenty-four observational studies (20,997 subjects) were included in the meta-analysis of which there were seven cohort, five cross-sectional and 12 case-control studies. The overall pooled OR was 4.20 (95% CI 3.11-5.66, I(2) = 81.0%). Association between history of knee injuries and knee OA was significantly different for specified injuries such as ligament or tendon injuries; meniscus damage or meniscectomy; and fracture of femur, knee or lower part of the leg (OR = 5.95, 95% 4.57-7.75), compared to unspecified injuries (OR = 3.12, 95% 2.17-4.50). CONCLUSION: History of knee injury is a major risk factor for the development of knee OA irrespective of study design and definition of knee injury. As one of the few modifiable/preventable risk factors, knee injury should be part of the future prevention programme in reducing the risk of knee OA.

Occupational risk factors for osteoarthritis of the knee: a meta-analysis.

INTRODUCTION: Systematic reviews agree that knee osteoarthritis (OA) is related to occupational activities, but have not quantified the overall risks. METHODS: Systematic review of observational studies of knee OA and occupation. Job titles, elite sport, heavy work, kneeling, and other activities were included. Relative risk estimate and 95% confidence interval (CI) compared to sedentary work were retrieved or calculated for meta-analysis. Publication bias was examined with Egger tests and heterogeneity was determined with I(2) values and Q tests. Subgroup analysis was performed to examine causes of heterogeneity. A random effects model was performed to combine the data. RESULTS: Studies of knee OA (n=51), persistent knee pain (n=12) and knee OA progression (n=3) were retrieved. Occupational risks for knee OA were examined in a total of 526,343 subjects in 8 cohort/prospective/longitudinal studies, 25 cross-sectional studies and 18 case control studies. The overall odds ratio (OR) was 1.61 (95% CI 1.45-1.78) with significant heterogeneity (I(2)=83.6%). Study designs showed a positive association between knee OA and occupational activities; cohort (OR 1.38, 95% CI 1.10-1.74), cross-sectional (OR 1.57, 95% CI 1.37-1.81) and case control (OR 1.80, 95% CI 1.48-2.19). Overall there was evidence of publication bias (P<0.0001) which was apparent in the cross-sectional and case control studies (P<0.0001 and P=0.0247 respectively). CONCLUSIONS: Some occupational activities increase the risk of knee OA, although the influences of publication bias and heterogeneity are important limitations of this study. Prospective studies would greatly improve the evidence base.