Maria Bota

Diabetes and breast cancer risk: a meta-analysis

Background:The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research.Methods:A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk.Results:Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16–1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12–1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13–1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74–1.35) and SRR 0.86 (95% CI, 0.66–1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08–1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18–1.51)).Conclusion:The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes.

Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database

Objective To examine changes in colorectal cancer mortality in 34 European countries between 1970 and 2011. Design Retrospective trend analysis. Data source World Health Organization mortality database. Population Deaths from colorectal cancer between 1970 and 2011. Profound changes in screening and treatment efficiency took place after 1988; therefore, particular attention was paid to the evolution of colorectal cancer mortality in the subsequent period. Main outcomes measures Time trends in rates of colorectal cancer mortality, using joinpoint regression analysis. Rates were age adjusted using the standard European population. Results From 1989 to 2011, colorectal cancer mortality increased by a median of 6.0% for men and decreased by a median of 14.7% for women in the 34 European countries. Reductions in colorectal cancer mortality of more than 25% in men and 30% in women occurred in Austria, Switzerland, Germany, the United Kingdom, Belgium, the Czech Republic, Luxembourg, and Ireland. By contrast, mortality rates fell by less than 17% in the Netherlands and Sweden for both sexes. Over the same period, smaller or no declines occurred in most central European countries. Substantial mortality increases occurred in Croatia, the former Yugoslav republic of Macedonia, and Romania for both sexes and in most eastern European countries for men. In countries with decreasing mortality, reductions were more important for women of all ages and men younger than 65 years. In the 27 European Union member states, colorectal cancer mortality fell by 13.0% in men and 27.0% in women, compared with corresponding reductions of 39.8% and 38.8% in the United States. Conclusion Over the past 40 years, there has been considerable disparity in the level of colorectal cancer mortality between European countries, as well as between men and women and age categories. Countries with the largest reductions in colorectal cancer mortality are characterised by better accessibility to screening services, especially endoscopic screening, and specialised care.

DataSHIELD: taking the analysis to the data, not the data to the analysis

Background: Research in modern biomedicine and social science requires sample sizes so large that they can often only be achieved through a pooled co-analysis of data from several studies. But the pooling of information from individuals in a central database that may be queried by researchers raises important ethico-legal questions and can be controversial. In the UK this has been highlighted by recent debate and controversy relating to the UK’s proposed ‘care.data’ initiative, and these issues reflect important societal and professional concerns about privacy, confidentiality and intellectual property. DataSHIELD provides a novel technological solution that can circumvent some of the most basic challenges in facilitating the access of researchers and other healthcare professionals to individual-level data. Methods: Commands are sent from a central analysis computer (AC) to several data computers (DCs) storing the data to be co-analysed. The data sets are analysed simultaneously but in parallel. The separate parallelized analyses are linked by non-disclosive summary statistics and commands transmitted back and forth between the DCs and the AC. This paper describes the technical implementation of DataSHIELD using a modified R statistical environment linked to an Opal database deployed behind the computer firewall of each DC. Analysis is controlled through a standard R environment at the AC. Results: Based on this Opal/R implementation, DataSHIELD is currently used by the Healthy Obese Project and the Environmental Core Project (BioSHaRE-EU) for the federated analysis of 10 data sets across eight European countries, and this illustrates the opportunities and challenges presented by the DataSHIELD approach. Conclusions: DataSHIELD facilitates important research in settings where: (i) a co-analysis of individual-level data from several studies is scientifically necessary but governance restrictions prohibit the release or sharing of some of the required data, and/or render data access unacceptably slow; (ii) a research group (e.g. in a developing nation) is particularly vulnerable to loss of intellectual property—the researchers want to fully share the information held in their data with national and international collaborators, but do not wish to hand over the physical data themselves; and (iii) a data set is to be included in an individual-level co-analysis but the physical size of the data precludes direct transfer to a new site for analysis.

Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: a meta-analysis

To review and quantify the association between endogenous and exogenous testosterone and prostate‐specific antigen (PSA) and prostate cancer.

Securing the Data Economy: Translating Privacy and Enacting Security in the Development of DataSHIELD

Contemporary bioscience is seeing the emergence of a new data economy: with data as its fundamental unit of exchange. While sharing data within this new ‘economy’ provides many potential advantages, the sharing of individual data raises important social and ethical concerns. We examine ongoing development of one technology, DataSHIELD, which appears to elide privacy concerns about sharing data by enabling shared analysis while not actually sharing any individual-level data. We combine presentation of the development of DataSHIELD with presentation of an ethnographic study of a workshop to test the technology. DataSHIELD produced an application of the norm of privacy that was practical, flexible and operationalizable in researchers’ everyday activities, and one which fulfilled the requirements of ethics committees. We demonstrated that an analysis run via DataSHIELD could precisely replicate results produced by a standard analysis where all data are physically pooled and analyzed together. In developing DataSHIELD, the ethical concept of privacy was transformed into an issue of security. Development of DataSHIELD was based on social practices as well as scientific and ethical motivations. Therefore, the ‘success’ of DataSHIELD would, likewise, be dependent on more than just the mathematics and the security of the technology.

Securing the data economy: translating privacy and enacting security in the development of DataSHIELD.

Contemporary bioscience is seeing the emergence of a new data economy: with data as its fundamental unit of exchange. While sharing data within this new ‘economy’ provides many potential advantages, the sharing of individual data raises important social and ethical concerns. We examine ongoing development of one technology, DataSHIELD, which appears to elide privacy concerns about sharing data by enabling shared analysis while not actually sharing any individual-level data. We combine presentation of the development of DataSHIELD with presentation of an ethnographic study of a workshop to test the technology. DataSHIELD produced an application of the norm of privacy that was practical, flexible and operationalizable in researchers’ everyday activities, and one which fulfilled the requirements of ethics committees. We demonstrated that an analysis run via DataSHIELD could precisely replicate results produced by a standard analysis where all data are physically pooled and analyzed together. In developing DataSHIELD, the ethical concept of privacy was transformed into an issue of security. Development of DataSHIELD was based on social practices as well as scientific and ethical motivations. Therefore, the ‘success’ of DataSHIELD would, likewise, be dependent on more than just the mathematics and the security of the technology.

Incretin-Based Therapies and the Short-term Risk of Pancreatic Cancer: Results From Two Retrospective Cohort Studies

OBJECTIVE Concerns have been raised about a possible increased risk of pancreatic cancer associated with incretin-based therapies. We examined the risk of pancreatic cancer among patients with diabetes prescribed incretin drugs. RESEARCH DESIGN AND METHODS With the use of public health insurance databases of Belgium and the Lombardy Region, Italy, we created two retrospective cohorts that included adult patients who were first prescribed an incretin drug or another noninsulin antidiabetic drug (NIAD) from 1 July 2008 to 31 December 2013 in Belgium and from 1 January 2008 to 31 December 2012 in the Lombardy Region. The risk of pancreatic cancer was evaluated by multivariate-adjusted Cox models that included time-dependent variables. Adjusted hazard ratios (aHRs) from Belgium and Italy were pooled by using fixed-effects meta-analyses. RESULTS The cohorts included 525,733 patients with diabetes treated with NIADs and 33,292 with incretin drugs. Results in both cohorts were similar. Eighty-five and 1,589 subjects who developed pancreatic cancer were registered among the incretin and NIAD new users, respectively, which represented an aHR of pancreatic cancer of 2.14 (95% CI 1.71–2.67) among those prescribed an incretin compared with an NIAD. The aHR with a drug use lag exposure of 6 months was 1.69 (1.24–2.32). The aHR decreased from 3.35 (2.32–4.84) in the first 3 months after the first incretin prescription to 2.12 (1.22–3.66) in months 3–5.9, 1.95 (1.20–3.16) in months 6–11.9, and 1.69 (1.12–2.55) after 12 months. Among those prescribed an NIAD, pancreatic cancer occurred mostly within the year after the first prescription. The risk of pancreatic cancer among patients subsequently prescribed insulin was 6.89 (6.05–7.85). CONCLUSIONS The recent prescription of incretin therapy is associated with an increased risk of pancreatic cancer. The reason for such an increase is likely the consequence of an occult pancreatic cancer that provokes or aggravates diabetes. Studies are warranted for assessing the risk of pancreatic cancer associated with long-term use of incretin drugs.