Methods to systematically review and meta-analyse observational studies: a systematic scoping review of recommendations.

BACKGROUND: Systematic reviews and meta-analyses of observational studies are frequently performed, but no widely accepted guidance is available at present. We performed a systematic scoping review of published methodological recommendations on how to systematically review and meta-analyse observational studies. METHODS: We searched online databases and websites and contacted experts in the field to locate potentially eligible articles. We included articles that provided any type of recommendation on how to conduct systematic reviews and meta-analyses of observational studies. We extracted and summarised recommendations on pre-defined key items: protocol development, research question, search strategy, study eligibility, data extraction, dealing with different study designs, risk of bias assessment, publication bias, heterogeneity, statistical analysis. We summarised recommendations by key item, identifying areas of agreement and disagreement as well as areas where recommendations were missing or scarce. RESULTS: The searches identified 2461 articles of which 93 were eligible. Many recommendations for reviews and meta-analyses of observational studies were transferred from guidance developed for reviews and meta-analyses of RCTs. Although there was substantial agreement in some methodological areas there was also considerable disagreement on how evidence synthesis of observational studies should be conducted. Conflicting recommendations were seen on topics such as the inclusion of different study designs in systematic reviews and meta-analyses, the use of quality scales to assess the risk of bias, and the choice of model (e.g. fixed vs. random effects) for meta-analysis. CONCLUSION: There is a need for sound methodological guidance on how to conduct systematic reviews and meta-analyses of observational studies, which critically considers areas in which there are conflicting recommendations.

Two-dose schedules for human papillomavirus vaccine: Systematic review and meta-analysis.

Simpler schedules for human papillomavirus (HPV) vaccine delivery could improve vaccine coverage and the effectiveness of cervical cancer prevention. The objective of this study was to systematically review evidence about the effects of two-dose compared with three-dose schedules for human papillomavirus (HPV) vaccine and to describe the uptake of two-dose HPV vaccination schedules globally. We searched PubMed, the Cochrane Central Registry of Controlled Trials, trials registers, and manufacturers' databases from their earliest date to February 2016. We selected randomised controlled trials and controlled clinical trials that directly compared HPV vaccine schedules with two or three doses. We extracted data on immunological and clinical outcomes and used meta-analysis where appropriate. We also described the use of two-dose HPV vaccine schedules globally. We screened 1464 items and included seven eligible noninferiority trials in 11 countries. In randomised comparisons amongst adolescent girls (three trials), geometric mean concentrations (GMC) of antibodies against HPV16 and HPV18 were non-inferior or inconclusive, up to 24months after a two-dose compared with a three-dose schedule. One trial with a clinical outcome found no persistent HPV infections occurred after either two or three doses. In non-randomised comparisons, GMC were non-inferior or superior in adolescent girls receiving the two-dose schedule compared with women receiving the three-dose schedule for at least 21months after vaccination. By February 2017, 23 low and middle income and 25 high income countries had adopted a two-dose HPV vaccination schedule. A two-dose HPV vaccine schedule provides satisfactory immunological outcomes in adolescent girls, but uptake globally is limited, particularly in countries with the highest burden of cervical cancer.

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.

Are public health professionals prepared for public health genomics? A cross-sectional survey in Italy.

BACKGROUND: Public health genomics is an emerging multidisciplinary approach, which aims to integrate genome-based knowledge in a responsible and effective way into public health. Despite several surveys performed to evaluate knowledge, attitudes and professional behaviors of physicians towards predictive genetic testing, similar surveys have not been carried out for public health practitioners. This study is the first to assess knowledge, attitudes and training needs of public health professionals in the field of predictive genetic testing for chronic diseases. METHODS: A self-administered questionnaire was used to carry out a cross-sectional survey of a random sample of Italian public health professionals. RESULTS: A response rate of 67.4% (797 questionnaires) was achieved. Italian public health professionals have the necessary attitudinal background to contribute to the proper use of predictive genetic testing for chronic diseases, but they need additional training to increase their methodological knowledge. Knowledge significantly increases with exposure to predictive genetic testing during postgraduate training (odds ratio (OR) = 1.74, 95% confidence interval (CI) = 1.05-2.88), time dedicated to continuing medical education (OR = 1.53, 95% CI = 1.14-2.04) and level of English language knowledge (OR = 1.36, 95% CI = 1.07-1.72). Adequate knowledge is the strongest predictor of positive attitudes from a public health perspective (OR = 3.98, 95% CI = 2.44-6.50). Physicians show a lower level of knowledge and more public health attitudes than other public health professionals do. About 80% of public health professionals considered their knowledge inadequate and 86.0% believed that it should be improved through specific postgraduate training courses. CONCLUSIONS: Specific and targeted training initiatives are needed to develop a skilled public health workforce competent in identifying genomic technology that is ready for use in population health and in modeling public health genomic programs and primary care services that need to be developed, implemented and evaluated.

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.

Knowledge, attitudes and behavior of physicians regarding predictive genetic tests for breast and colorectal cancer.

BACKGROUND: Genetic testing for cancer susceptibility is an emerging technology in medicine. This study assessed the knowledge, attitudes and professional behavior of Italian physicians regarding the use of predictive genetic tests for breast and colorectal cancer, including the BRCA1/2 and APC tests. METHODS: A cross-sectional survey of a random sample of Italian physicians was performed in 2010 through a self-administered questionnaire. RESULTS: A response rate of 69.6% (1079 questionnaires) was achieved. A significant lack of knowledge was detected, particularly for APC testing. Less than half of the physicians agreed on the importance of efficacy and cost-effectiveness evidence in the selection of predictive genetic tests to be offered to the patients. Multiple logistic regression analyses showed that education had a positive influence on knowledge, attitudes and, to a lesser extent, professional use. The factor most strongly related to the physicians' use of genetic testing was patients requests for breast (odds ratio=12.65; 95% confidence interval 7.77-20.59) or colorectal cancer tests (odds ratio=7.02; 95% confidence interval 3.61-13.64). A high level of interest for specific training was reported by almost all physicians surveyed. CONCLUSIONS: Targeted educational programs are needed to improve the expertise of physicians, and, ultimately, to enhance the appropriate use of genetic tests in clinical practice.

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-reviewed literature.

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.

[Online communication regarding health promotion and protection: the public health perspective]. / La comunicazione on-line in tema di tutela e promozione della salute: la prospettiva di sanità pubblica.

Currently web health portals are moving away from providing institutional and administrative types of information towards a more interactive type of communication focused on providing citizens and health care professionals various services associated with health promotion and on facilitating access to healthcare services. The aim of this study was to provide guidance in the planning and conduction of online health promotion and protection communication activities that will contribute to the process of community empowerment repeatedly called upon by the WHO. For this purpose, the authors conducted an analysis of the epidemiology of the determinants of health and disease in Italy as well as two systematic revisions of the literature regarding web-based health information needs of citizens and the efficacy of health promotion and preventative interventions administered via the internet. Although current scientific evidence suggests that some interventions (e.g. expert systems or tailored interventions) are more effective with respect to others (e.g. online support groups or other types of interventions), common sense suggests that public health computer platforms such as the " citizens' channel" of the Ministry of Health web portal should implement hybrid models, i.e. models that contain various types of interventions, and should provide access to both general information and to interactive and personalized programs.