Cost-effectiveness analysis of a GP- and parent-directed intervention to reduce antibiotic prescribing for children with respiratory tract infections in primary care.

OBJECTIVES: We evaluated costs and effects of the RAAK (RAtional Antibiotic use Kids) intervention (GP online training and information booklets for parents), aiming to reduce antibiotic prescribing for children with respiratory tract infection (RTI). METHODS: We conducted a trial-based cost-effectiveness analysis from a societal perspective. We included children consulting the GP with RTI for whom parents kept a 2 week (cost) diary. The antibiotic prescribing rate was the percentage of children receiving an antibiotic prescription at the index consultation and during the 2 weeks of follow-up. The cost difference between the intervention and usual care groups per percentage decrease in antibiotic prescribing was calculated. Bootstrapping was used to assess uncertainty surrounding the outcomes. RESULTS: Costs and effects of 153 children in the intervention group and 107 children in the usual care group were available for analysis. Antibiotic prescribing was 12% lower in the intervention group and costs were €10.27 higher in the intervention group compared with the usual care group. This resulted in an incremental cost-effectiveness ratio of €0.85 per percentage decrease in antibiotic prescribing. The probability that the intervention was more effective, but more expensive, was 53%, whereas the probability that the intervention was more effective and less expensive compared with usual care was 41%. CONCLUSIONS: The online training for GPs and the information booklet for parents resulted in a decrease in antibiotic prescribing in children with RTI, at very low cost, and should therefore be considered for implementation in primary care.

A systematic literature review and network meta-analysis feasibility study to assess the comparative efficacy and comparative effectiveness of pneumococcal conjugate vaccines.

Background: No head-to-head studies are currently available comparing pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with 13-valent pneumococcal conjugate vaccine (PCV-13). This study explored the feasibility of using network meta-analysis (NMA) to conduct an indirect comparison of the relative efficacy or effectiveness of the two vaccines.Methods: A systematic literature search was conducted for published randomized controlled trials (RCTs) and non-RCT studies reporting data on vaccine efficacy or effectiveness against invasive pneumococcal disease in children aged <5 years receiving 7-valent pneumococcal conjugate vaccine (PCV-7), PHiD-CV or PCV-13. Study quality was evaluated using published scales. NMA feasibility was assessed by considering whether a connected network could be constructed by examining published studies for differences in study or patient characteristics that could act as potential treatment effect modifiers or confounding variables.Results: A total of 26 publications were included; 2 RCTs (4 publications), 7 indirect cohort studies, and 14 case-control studies (15 publications). Study quality was generally good. The RCTs could not be connected in a network as there was no common comparator. The studies differed considerably in design, dose number, administration schedules, and subgroups analyzed. Reporting of exposure status and subject characteristics was inconsistent.Conclusion: NMA to compare the relative efficacy or effectiveness of PHiD-CV and PCV-13 is not feasible on the current evidence base, due to the absence of a connected network across the two RCTs and major heterogeneity between studies. NMA may be possible in future if sufficient RCTs become available to construct a connected network.

Association between age at menarche and cardiovascular disease: A systematic review on risk and potential mechanisms.

Age at menarche (AAM) has been reported to be associated with the risk of cardiovascular disease (CVD), but the shape of and the mechanisms behind this association remain unclear. We reviewed the data on the association between AAM and different subtypes of CVD, and used shared genetic loci to identify possible mechanisms underlying this association using shared genetic association. We searched the databases of PubMed, Web of Science and Embase through to April 2017. We included articles with any clinically manifest CVD endpoint and for any ethnicity. We identified single nucleotide polymorphisms (SNPs) for AAM in genome-wide association studies (GWAS) in Caucasians through PubMed and HuGE Navigator, and searched whether these SNPs or any of their proxies were associated with any CVD-related trait. Eight studies in Caucasian populations reported an inverse linear relation between AAM and CVD risk, whereas one large study reported a significant U-shaped relation between them. Data from Asian populations were contradictory and inconclusive. In total, 122 AAM SNPs were identified at a genome-wide significance level (p<5×10-8). Of those, 18 were also associated with various CVD-related traits, primarily body mass index (BMI), obesity, and height. In conclusion, early AAM and possibly also late AAM increase the risk of CVD in Caucasian populations. Weight and height may be part of the mechanism underlying the relation between AAM and CVD risk in Caucasians. Data on other ethnicities are too limited for meaningful analysis and conclusions.