Ecological correlation between diabetes hospitalizations and fine particulate matter in Italian provinces

Background: Exposure to particulate matter has been associated with increased risk of cardiovascular and respiratory diseases. We evaluated the ecological correlation between standardized hospital discharges with diabetes in Italian provinces and fine particulate matter (PM2.5) adjusting for common risk factors, socioeconomic factors and differences in hospitalization appropriateness. Methods: We used cross sectional data aggregated at the province level and available from official institutional databases for years 2008–2010. Covariates included prevalence of adult overweight, obese, smokers, physically inactive, education and income (as average gross domestic product per person, GDP). We reduced the number of covariates to a smaller number of factors for the subsequent statistical model by extracting meaningful components using principal component analysis (PCA). Log-linear multiple regression analysis was used to model diabetes hospital discharges with PCA components and PM2.5 levels and hospitalization appropriateness for men and women. Results: The first PCA components for both men and women were characterized by larger loadings of risk factors (obesity, overweight, physical inactivity, cigarette smoking) and lower socioeconomic factors (educational level and mean GDP). Diabetes hospitalization increases with the first PCA component and decreases with the index of hospitalization appropriateness. In fully adjusted models, diabetes hospitalizations increase with increasing annual PM2.5 concentrations, with a rise of 3.5 % (1.3 %–5.6 %) for men and of 4.0 % (1.5 %-6.4 %) for women per unit of PM2.5 increase. Conclusions: We found a significant ecological relationship between sex and age standardised hospital discharge with diabetes as principle diagnosis and mean annual PM2.5 concentrations in Italian provinces, once that covariates have been accounted for. The relationship was robust to different means of estimating PM2.5 exposure. A large portion of the variance of diabetes hospitalizations was linked to differences of hospital care appropriateness between Italian regions and this variable should routinely be included in ecological analyses of hospitalizations

Publication Delay of Randomized Trials on 2009 Influenza A (H1N1) Vaccination

Background: Randomized evidence for vaccine immunogenicity and safety is urgently needed in the setting of pandemics with new emerging infectious agents. We carried out an observational survey to evaluate how many randomized controlled trials testing 2009 H1N1 vaccines were published among those registered, and what was the time lag from their start to publication and from their completion to publication. Methods: PubMed, EMBASE and 9 clinical trial registries were searched for eligible randomized controlled trials. The units of the analysis were single randomized trials on any individual receiving influenza vaccines in any setting. Results: 73 eligible trials were identified that had been registered in 2009–2010. By June 30, 2011 only 21 (29%) of these trials had been published, representing 38 % of the randomized sample size (19905 of 52765). Trials starting later were published less rapidly (hazard ratio 0.42 per month; 95 % Confidence Interval: 0.27 to 0.64; p,0.001). Similarly, trials completed later were published less rapidly (hazard ratio 0.43 per month; 95 % CI: 0.27 to 0.67; p,0.001). Randomized controlled trials were completed promptly (median, 5 months from start to completion), but only a minority were subsequently published. Conclusions: Most registered randomized trials on vaccines for the H1N1 pandemic are not published in the peer-reviewe

Meta-Analysis of the Immunogenicity and Tolerability of Pandemic Influenza A 2009 (H1N1) Vaccines

Background: Although the 2009 (H1N1) influenza pandemic officially ended in August 2010, the virus will probably circulate in future years. Several types of H1N1 vaccines have been tested including various dosages and adjuvants, and meta-analysis is needed to identify the best formulation. Methods: We searched MEDLINE, EMBASE, and nine clinical trial registries to April 2011, in any language for randomized clinical trials (RCTs) on healthy children, adolescents, adults and the elderly. Primary outcome was the seroconversion rate according to hemagglutinination-inhibition (HI); secondary outcomes were adverse events. For the primary outcome, we used head-to-head meta-analysis and multiple-treatments meta-analysis. Results: Eighteen RCTs could be included in all primary analyses, for a total of 76 arms (16,725 subjects). After 2 doses, all 2009 H1N1 split/subunit inactivated vaccines were highly immunogenic and overcome CPMP seroconversion criteria. After 1 dose only, all split/subunit vaccines induced a satisfactory immunogenicity (> = 70%) in adults and adolescents, while only some formulations showed acceptable results for children and elderly (non-adjuvanted at high-doses and oil-in-water adjuvanted vaccines). Vaccines with oil-in-water adjuvants were more immunogenic than both nonadjuvanted and aluminum-adjuvanted vaccines at equal doses and their immunogenicity at doses < = 6 μg (even with as little as 1.875 μg of hemagglutinin antigen) was not significantly lower than that achieved after higher doses. Finally, the rate of serious vaccine-related adverse events was low for all 2009 H1N1 vaccines (3 cases, resolved in 10 days, out of 22826 vaccinated subjects). However, mild to moderate adverse reactions were more (and very) frequent for oil-in-water adjuvanted vaccines. Conclusions: Several one-dose formulations might be valid for future vaccines, but 2 doses may be needed for children, especially if a low-dose non-adjuvanted vaccine is used. Given that 15 RCTs were sponsored by vaccine manufacturers, future trials sponsored by non-industry agencies and comparing vaccines using different types of adjuvants are needed

Non-publication and delayed publication of randomized trials on vaccines: survey

Objective To evaluate the extent of non-publication or delayed publication of registered randomized trials on vaccines, and to investigate potential determinants of delay to publication. Design Survey. Data sources Trials registry websites, Scopus, PubMed, Google. Study selection Randomized controlled trials evaluating the safety or the efficacy or immunogenicity of human papillomavirus (HPV), pandemic A/H1N1 2009 influenza, and meningococcal, pneumococcal, and rotavirus vaccines that were registered in ClinicalTrials.gov, Current Controlled Trials, WHO International Clinical Trials Registry Platform, Clinical Study Register, or Indian, Australian-New Zealand, and Chinese trial registries in 2006-12. Electronic databases were searched up to February 2014 to identify published manuscripts containing trial results. These were reviewed and classified as positive, mixed, or negative. We also reviewed the results available in ClinicalTrials.gov. Main outcome measures Publication status of trial results and time from completion to publication in peer reviewed journals. Data synthesis Cox proportional hazards regression was used to evaluate potential predictors of publication delay. Results We analysed 384 trials (85% sponsored by industry). Of 355 trials (404 758 participants) that were completed, 176 (n=151 379) had been published in peer reviewed journals. Another 42 trials (total sample 62 765) remained unpublished but reported results in ClinicalTrials.gov. The proportion of trials published 12, 24, 36, and 48 months after completion was 12%, 29%, 53%, and 73%, respectively. Including results posted in ClinicalTrials.gov, 48 months after study completion results were available for 82% of the trials and 90% of the participants. Delay to publication between non-industry and industry sponsored trials did not differ, but non-industry sponsored trials were 4.42-fold (P=0.008) more likely to report negative or mixed findings. Negative results were reported by only 2% of the published trials. Conclusions Most vaccine trials are published eventually or the results posted in ClinicalTrials.gov, but delays to publication of several years are common. Actions should focus on the timely dissemination of data from vaccine trials to the public

Non-publication and delayed publication of randomized trials on vaccines: survey

Objective To evaluate the extent of non-publication or delayed publication of registered randomized trials on vaccines, and to investigate potential determinants of delay to publication. Design Survey. Data sources: Trials registry websites, Scopus, PubMed, Google. Study selection Randomized controlled trials evaluating the safety or the efficacy or immunogenicity of human papillomavirus (HPV), pandemic A/H1N1 2009 influenza, and meningococcal, pneumococcal, and rotavirus vaccines that were registered in Clinical Trials.gov, Current Controlled Trials, WHO International Clinical Trials Registry Platform, Clinical Study Register, or Indian, Australian-New Zealand, and Chinese trial registries in 2006-12. Electronic databases were searched up to February 2014 to identify published manuscripts containing trial results. These were reviewed and classified as positive, mixed, or negative. We also reviewed the results available in ClinicalTrials.gov. Main outcome measures Publication status of trial results and time from completion to publication in peer reviewed journals. Data synthesis Cox proportional hazards regression was used to evaluate potential predictors of publication delay. Results We analysed 384 trials (85% sponsored by industry). Of 355 trials (404 758 participants) that were completed, 176 (n=151 379) had been published in peer reviewed journals. Another 42 trials (total sample 62 765) remained unpublished but reported results in ClinicalTrials.gov. The proportion of trials published 12, 24, 36, and 48 months after completion was 12%, 29%, 53%, and 73%, respectively. Including results posted in ClinicalTrials.gov, 48 months after study completion results were available for 82% of the trials and 90% of the participants. Delay to publication between non-industry and industry sponsored trials did not differ, but non-industry sponsored trials were 4.42-fold (P=0.008) more likely to report negative or mixed findings. Negative results were reported by only 2% of the published trials. Conclusions Most vaccine trials are published eventually or the results posted in ClinicalTrials.gov, but delays to publication of several years are common. Actions should focus on the timely dissemination of data from vaccine trials to the public