Trajectories of Controller Therapy Use Before and After Asthma-Related Hospitalization in Children and Adults: Population-Based Retrospective Cohort Study.

BACKGROUND: Inappropriate use of inhaled corticosteroids (ICSs) for asthma impairs control and may cause exacerbation, including asthma-related hospitalization (ARH). In prospective studies, ICS use peaked around ARH, but information on routine care use is limited. Since ARH is a major outcome, controller therapy use in routine care before and after ARH should be documented. OBJECTIVE: This study aimed to distinguish ICS use typologies (trajectories) before and after ARH, and assess their relationships with sociodemographic, disease, and health care characteristics. METHODS: A retrospective cohort study was performed using a 1% random sample of the French claims database. All patients hospitalized for asthma between January 01, 2013, and December 31, 2015, were classified as either children (aged 1-10 years) or teens/adults (aged ≥11 years). Health care resource use was assessed between 24 and 12 months before ARH. ICS use was computed with the Continuous Measures of Medication Acquisition-7 (CMA7) for the 4 quarters before and after ARH. Initially, the overall impact of hospitalization on the CMA7 value was studied using a segmented regression analysis in both children and teens/adults. Then, group-based trajectory modeling differentiated the groups with similar ICS use. We tested different models having 2 to 5 distinct trajectory groups before selecting the most appropriate trajectory form. We finally selected the model with the lowest Bayesian Information Criterion, the highest proportion of patients in each group, and the maximum estimated probability of assignment to a specific group. RESULTS: Overall, 863 patients were included in the final study cohort, of which 447 (51.8%) were children and 416 (48.2%) were teens/adults. In children, the average CMA7 value was 12.6% at the start of the observation period, and there was no significant quarter-to-quarter change in the value (P=.14) before hospitalization. Immediately after hospitalization, the average CMA7 value rose by 34.9% (P=.001), before a significant decrease (P=.01) of 7.0% per quarter. In teens/adults, the average CMA7 value was 31.0% at the start, and there was no significant quarter-to-quarter change in the value (P=.08) before hospitalization. Immediately after hospitalization, the average CMA7 value rose by 26.9% (P=.002), before a significant decrease (P=.01) of 7.0% per quarter. We identified 3 and 5 trajectories before ARH in children and adults, respectively, and 5 after ARH for both groups. Trajectories were related to sociodemographic characteristics (particularly, markers of social deprivation) and to potentially inappropriate health care, such as medical management and choice of therapy. CONCLUSIONS: Although ARH had an overall positive impact on ICS use trajectories, the effect was often transient, and patient behaviors were heterogeneous. Along with overall trends, distinct trajectories were identified, which were related to specific patients and health care characteristics. Our data reinforce the evidence that inappropriate use of ICS paves the way for ARH.

Estimated number of cancers attributable to occupational exposures in France in 2017: an update using a new method for improved estimates.

BACKGROUND: Over the last 50 years, occupational exposure to carcinogenic agents has been widely regulated in France. OBJECTIVE: Report population-attributable fraction (PAF) and number of attributable cancer cases linked to occupational exposure in France based on an updated method to estimate lifetime occupational exposure prevalence. METHODS: Population-level prevalence of lifetime exposure to ten carcinogenic agents (asbestos, benzene, chromium VI, diesel engine exhaust, formaldehyde, nickel compounds, polycyclic aromatic hydrocarbons, silica dust, trichloroethylene, wood dust) and two occupational circumstances (painters and rubber industry workers) were estimated using the French Census linked with MATGÉNÉ job-exposure matrices and French occupational surveys. PAF and number of attributable cancer cases were calculated using the estimated prevalence, relative risks from systematic review and national estimates of cancer incidence in 2017. RESULTS: The lifetime occupational exposure prevalences were much higher in men than in women ranging from 0.2% (workers in the rubber industry) to 10.2% in men (silica), and from 0.10% (benzene, PAH and workers in the rubber industry) to 5.7% in women (formaldehyde). In total, 4,818 cancer cases (men: 4,223; women: 595) were attributable to the ten studied carcinogens and two occupational circumstances, representing 5.2% of cases among the studied cancer sites (M: 7.0%; W: 1.9%). In both sexes, mesothelioma (M: 689 cases; W: 160) and lung cancer (M: 3,032; W: 308) were the largest cancer sites impacted by the studied occupational agents and circumstances. SIGNIFICANCE: A moderate proportion of the cancer cases in France is linked to carcinogens in occupational settings. Our method provides more precise estimates of attributable cancer taking into account evolution of exposure to occupational agents by sex, age and time. This methodology can be easily replicated using cross-sectional occupational data to aid priority making and implementation of prevention strategies in the workplace.

Apixaban versus other anticoagulants in patients with nonvalvular fibrillation: a comparison of all-cause and event-related costs in real-life setting in France.

OBJECTIVES: Compare costs associated with all-cause healthcare resource use (HCRU), stroke/systemic thromboembolism (STE) and major bleedings (MB) between patients with non-valvular atrial fibrillation (NVAF) initiating apixaban or other oral anticoagulants (OACs). METHODS: We performed a retrospective cohort study using the French healthcare claims database, including NVAF patients between 2014/01/01 and 2016/12/31, followed until 2016/12/31. We used 4 sub-cohorts of OAC-naive patients, respectively initiating apixaban, dabigatran, rivaroxaban or VKAs. We matched patients initiating apixaban with patients initiating each other OACs using 1:n propensity score matching. All-cause HCRU and event-related costs by OAC treatment were estimated and compared between matched patients using generalised-linear models with gamma-distribution and two-part models. RESULTS: There were 175,766 patients in the apixaban-VKA, 181,809 in the apixaban-rivaroxaban, and 42,490 in the apixaban-dabigatran matched cohorts. Patients initiating apixaban had significantly lower HCRU costs than patients initiating VKA (€1,105 vs. €1,578, p < 0.0001), dabigatran (€993 vs. €1,140, p < 0.0001) and rivaroxaban (€1,013 vs. €1,088 p < 0.0001). They have had significantly lower costs related to stroke/STE and MB than patients initiating VKA (respectively, €183 vs. €449 and €147 vs. €413; p < 0.0001), rivaroxaban (respectively, €145 vs. €197 and €129 vs. €193; p < 0.0001), and lower costs related to stroke/STE than patients initiating dabigatran (€135 vs. €192, p < 0.02). Costs related to MB were not significantly different in patients initiating apixaban and those initiating dabigatran (€119 vs. €149, p = 0.07). CONCLUSIONS: HCRU and most event-related costs were lower in patients initiating apixaban compared to other OACs. Apixaban may be cost-saving compared to VKAs, and significantly cheaper than other DOACs, although cost differences are limited.

An innovative method to estimate lifetime prevalence of carcinogenic occupational circumstances: the example of painters and workers of the rubber manufacturing industry in France.

BACKGROUND: Existing methods to estimate lifetime exposure to occupational carcinogenic agents could be improved. OBJECTIVE: We propose a new method to estimate the lifetime prevalence of exposure to occupational carcinogens using the example of painters and workers of the rubber industry in France. METHODS: From census, we calculated the proportion of painters and rubber industry workers using predefined occupational codes related to each occupation by sex and 10-year age group in 1982, 1990, 1999, 2007, and 2013. Using a beta-regression model, we obtained the yearly prevalence of exposure by 10-year age group over the period 1967-2007. We estimated the age- and sex-specific lifetime prevalence of exposure of the population in 2017 over 1967-2007, summing up the estimated prevalence of exposure for years 1967, 1977, 1987, 1997, and 2007 combined with a sex- and age-specific turnover factor. Corresponding population-attributable fractions were estimated for lung and bladder cancers in 2017. RESULTS: In 2017, we estimated that 5.6 and 0.2% of men in France had ever worked as a painter or in the rubber industry, respectively, during their working time. The lifetime prevalence of ever having worked as a painter or in the rubber industry was much lower in women: 1.8% and 0.1%, respectively. We estimated that 950 lung cancer and 40 bladder cancer cases were attributable to these occupations in 2017. SIGNIFICANCE: Based on accurate data and taking into account evolution of specific jobs over time, the proposed method provides good estimates of lifetime prevalence of exposure to occupational carcinogens. It could be applied in any other country with similar data.

[Obesity and Cancer]. / Obésité et cancer.

In the past decades, obesity and overweight prevalence has been rising worldwide, in both men and women. In France, the prevalence of overweight in adults was 49% in 2015 (54% among men and 44% among women), including 17% of obese adults. According to the last evaluation performed by IARC in 2017, overweight and obesity are established risk factors for 13 cancer sites with risk estimates per 5kg/m2 varying largely depending on the cancer site. In 2015 in France, 5.4% of cancer cases could be attributed to excess weight, corresponding to 18,600 cases, including 3400 colon cancers, 2600 kidney cancers, 4500 breast cancers and 2500 endometrial cancers. Obesity is also related to worse prognosis for some cancers, in particular breast and colon cancers. Obesity in children and adolescents, also rising in many countries, has also been associated to an increase in adult cancer risk. A major cause of obesity is a disequilibrium in energy balance favoured by a diet rich in processed food, red meat, trans and saturated fatty acids, sweetened foods and beverages and poor in fruits and vegetables, legumes and whole grains. Main national and international recommendations to reduce the prevalence of obesity are to have a balanced diet and regular physical activity.

The risk of cancer attributable to diagnostic medical radiation: Estimation for France in 2015.

Although medical ionizing radiation (IR) has clear clinical benefits, it is an established carcinogen. Our study estimates the number of new cancer cases in France in 2015 attributable to IR exposure from medical procedures. Exposures from external (X-rays, CT scans, interventional radiology) and internal (nuclear medicine) sources were considered. We used 2007 national frequencies of diagnostic examinations by sex and age to estimate the lifetime organ dose exposure adjusted for changes in the use of such procedures over time. The Biological Effects of Ionizing Radiation VII risk models were used to estimate the corresponding excess cancer risk, assuming an average latency period of 10 years. Additionally, we used cancer incidence data from the French Cancer Registries Network. Of the 346,000 estimated new cancer cases in adults in France in 2015, 2300 cases (940 among men and 1360 among women) were attributable to diagnostic IR, representing 0.7% of all new cancer cases (0.5% for men and 0.9% for women). The leading cancers attributable to medical IR were female breast (n = 560 cases), lung (n = 500 cases) and colon (n = 290 cases) cancers. Compared to other risk factors, the contribution of medical IR to the cancer burden is small, and the benefits largely outweigh its harms. However, some of these IR-associated cancer cases may be preventable through dose optimization of and enhanced justification for diagnostic examinations.

Cancers in France in 2015 attributable to occupational exposures.

BACKGROUND: Recent and comprehensive estimates for the number of new cancer cases in France attributable to occupational exposures are lacking. OBJECTIVES: To estimate the number of new cancer cases attributable to occupational exposures, using a newly developed methodology and the most recent data, for a comprehensive set of occupational carcinogens in France in 2015. METHODS: Surveys among employees, the national labor force data, a cohort of agricultural workers, national monitoring of workers exposed to ionizing radiation and job-exposure matrix in France were used. The number and proportion of new cancer cases attributable to established occupational carcinogens (Group 1) was estimated using estimation of lifetime exposure and risk estimates from cohort studies. Cancer data were obtained from the French Cancer Registries Network. RESULTS: In France in 2015, an estimated 7905 new cancer cases, 7336 among men and 569 among women, were attributable to occupational exposures, representing 2.3% of all new cancer cases (3.9% and 0.4% among men and women respectively). Among men and women, lung cancer was impacted the most, followed by mesothelioma and bladder cancer in men, and by mesothelioma and ovary in women. These cancers contributed to 89% of the total cancers attributable to occupational carcinogens in men, and to 80% in women. The main contributing occupational agent was asbestos among men (45%) and women (60%). CONCLUSIONS: Currently, occupational exposures contribute to a substantial burden of cancer in France. Enhanced monitoring and implementation of protective labor policies could potentially prevent a large proportion of these cancers.

Cancers related to lifestyle and environmental factors in France in 2015.

BACKGROUND: Cancer is a major cause of premature illness and death in France. To quantify how cancer prevention could reduce the burden, we present estimates of the contribution of lifestyle and environmental risk factors to cancer incidence in France in 2015, comparing these with other high-income countries. METHOD: Prevalences of, and relative risks for tobacco smoking, alcohol consumption, inadequate diet, overweight and obesity, physical inactivity, exogenous hormones, suboptimal breastfeeding, infectious agents, ionising radiation, air pollution, ultraviolet exposure, occupational exposures, arsenic in drinking water and indoor benzene were obtained to estimate the population attributable fraction (PAF) and the number of attributable cancers by the cancer site and sex. RESULTS: In 2015, 41% (or 142,000 of 346,000) of all new cancers diagnosed in France could be attributed to the aforementioned risk factors. The numbers and PAF were slightly higher in men than in women (84,000 versus 58,000 cases and 44% versus 37%, respectively). Smoking (PAF: 20%), alcohol consumption (PAF: 8%), dietary factors (PAF: 5%) and excess weight (PAF: 5%) were the most important factors. Infections and occupational exposures each contributed to an additional 4% of the cancer cases in 2015. CONCLUSION: Today, two-fifths of cancers in France are attributable to preventable risk factors. The variations in the key amenable factors responsible in France relative to other economically similar countries highlight the need for tailored approaches to cancer education and prevention. Reducing smoking and alcohol consumption and the adoption of healthier diet and body weight remain important targets to reduce the increasing number of new cancer patients in France in the decades to follow.

New cancer cases attributable to diet among adults aged 30-84 years in France in 2015.

This study aimed to estimate the number of new cancer cases attributable to diet among adults aged 30-84 years in France in 2015, where convincing or probable evidence of a causal association exists, and, in a secondary analysis, where at least limited but suggestive evidence of a causal association exists. Cancer cases attributable to diet were estimated assuming a 10-year latency period. Dietary intake data were obtained from the 2006 French National Nutrition and Health Survey. Counterfactual scenarios of dietary intake were based on dietary guidelines. Corresponding risk relation estimates were obtained from meta-analyses, cohort studies and one case-control study. Cancer incidence data were obtained from the French Network of Cancer Registries. Nationally, unfavourable dietary habits led to 16 930 new cancer cases, representing 5·4 % of all new cancer cases. Low intake of fruit and dietary fibre was the largest contributor to this burden, being responsible for 4787 and 4389 new cancer cases, respectively. If this is expanded to dietary component and cancer pairs with at least limited but suggestive evidence of a causal association, 36 049 new cancer cases, representing 11·6 % of all new cancer cases, were estimated to be attributable to diet. These findings suggest that unfavourable dietary habits lead to a substantial number of new cancer cases in France; however, there is a large degree of uncertainty as to the number of cancers attributable to diet, including through indirect mechanisms such as obesity, and therefore additional research is needed to determine how diet affects cancer risk.

Quantitative health impact of indoor radon in France.

Radon is the second leading cause of lung cancer after smoking. Since the previous quantitative risk assessment of indoor radon conducted in France, input data have changed such as, estimates of indoor radon concentrations, lung cancer rates and the prevalence of tobacco consumption. The aim of this work was to update the risk assessment of lung cancer mortality attributable to indoor radon in France using recent risk models and data, improving the consideration of smoking, and providing results at a fine geographical scale. The data used were population data (2012), vital statistics on death from lung cancer (2008-2012), domestic radon exposure from a recent database that combines measurement results of indoor radon concentration and the geogenic radon potential map for France (2015), and smoking prevalence (2010). The risk model used was derived from a European epidemiological study, considering that lung cancer risk increased by 16% per 100 becquerels per cubic meter (Bq/m3) indoor radon concentration. The estimated number of lung cancer deaths attributable to indoor radon exposure is about 3000 (1000; 5000), which corresponds to about 10% of all lung cancer deaths each year in France. About 33% of lung cancer deaths attributable to radon are due to exposure levels above 100 Bq/m3. Considering the combined effect of tobacco and radon, the study shows that 75% of estimated radon-attributable lung cancer deaths occur among current smokers, 20% among ex-smokers and 5% among never-smokers. It is concluded that the results of this study, which are based on precise estimates of indoor radon concentrations at finest geographical scale, can serve as a basis for defining French policy against radon risk.

Occupational exposures and cancer: a review of agents and relative risk estimates.

OBJECTIVES: The contribution of occupational exposures to the cancer burden can be estimated using population-attributable fractions, which is of great importance for policy making. This paper reviews occupational carcinogens, and presents the most relevant risk relations to cancer in high-income countries using France as an example, to provide a framework for national estimation of cancer burden attributable to occupational exposure. METHODS: Occupational exposures that should be included in cancer burden studies were evaluated using multiple criteria: classified as carcinogenic or probably carcinogenic by the International Agency for Research on Cancer (IARC) Monographs volumes 1-114, being a primary occupational exposure, historical and current presence of the exposure in France and the availability of exposure and risk relation data. Relative risk estimates were obtained from published systematic reviews and from the IARC Monographs. RESULTS: Of the 118 group 1 and 75 group 2A carcinogens, 37 exposures and 73 exposure-cancer site pairs were relevant. Lung cancer was associated with the most occupational carcinogenic exposures (namely, 18), followed by bladder cancer and non-Hodgkin's lymphoma. Ionising radiation was associated with the highest number of cancer sites (namely, 20), followed by asbestos and working in the rubber manufacturing industry. Asbestos, bis(chloromethyl)ether, nickel and wood dust had the strongest effect on cancer, with relative risks above 5. CONCLUSIONS: A large number of occupational exposures continues to impact the burden of cancer in high-income countries such as France. Information on types of exposures, affected jobs, industries and cancer sites affected is key for prioritising policy and prevention initiatives.

The impact of historical breastfeeding practices on the incidence of cancer in France in 2015.

PURPOSE: The purpose of the study was to estimate the number of new breast cancer cases in France in 2015 attributable to breastfeeding for durations below recommendations (at least 6 months per child), and cases prevented through historical breastfeeding. As a secondary analysis, the corresponding numbers for ovarian cancer were estimated. METHODS: Historical breastfeeding data were obtained from population surveys. Duration of breastfeeding data were obtained from the French Épifane cohort study. Relative risks were obtained from meta-analyses, cohort, and case-control studies. Cancer incidence data were obtained from the French Network of Cancer Registries. A 10-year latency period was assumed. RESULTS: Among parous women 25 years of age and older, 14.1% breastfed for at least 6 months per child born before 2006. As a result, 1,712 new breast cancer cases (3.2% of all new breast cancer cases) were attributable to breastfeeding for < 6 months per child, while actual breastfeeding practices prevented 765 breast cancer cases. Furthermore, 411 new ovarian cancer cases (8.6% of all new ovarian cancer cases) may be attributable to breastfeeding for < 6 months per child, with breastfeeding preventing 163 ovarian cancer cases. CONCLUSIONS: The historically low breastfeeding prevalence and duration in France led to numerous avoidable cancer cases.

New cancer cases in France in 2015 attributable to different levels of alcohol consumption.

BACKGROUND AND AIMS: Alcohol consumption increases the risk of cancer. Thus, to inform policy decisions, this study estimated the number of new cancer cases in France in 2015 attributable to alcohol consumption generally and to light (< 20 g per day (g/day) among women; < 40 g/day among men), moderate (20 to < 40 g/day among women; 40 to < 60 g/day among men) and heavy drinking (≥ 40 g/day among women; ≥ 60 g/day among men), and the number of cancer cases that would have been prevented assuming a previous 10% decrease in alcohol consumption. DESIGN: New cancer cases attributable to alcohol were estimated using a population-attributable fraction methodology, assuming a 10-year latency period between exposure and diagnosis. SETTING AND PARTICIPANTS: Population of France, 2015. MEASUREMENTS: Alcohol consumption was estimated by coordinating data from the Baromètre santé 2005, a national representative survey (n = 30 455), with data from the Global Information System on Alcohol and Health. Relative risks were obtained from meta-analyses. Cancer data were estimated based on data from the French Cancer Registries Network. Uncertainty intervals (UI) were estimated using a Monte Carlo procedure. FINDINGS: In France in 2015, an estimated 27 894 (95% UI = 24 287-30 996) or 7.9% of all new cancer cases were attributable to alcohol. The number of alcohol-attributable new cancer cases was similar for both men and women, with oesophageal squamous cell carcinomas having the largest attributable fraction (57.7%). Light, moderate, heavy and former alcohol drinking were responsible for 1.5, 1.3, 4.4 and 0.6% of all new cancer cases, respectively. Lastly, if there had been a previous 10% reduction in alcohol consumption, 2178 (95% UI = 1687-2601) new cancer cases would have been prevented. CONCLUSIONS: Alcohol consumption in France appears to cause almost 8% of new cancer cases, with light and moderate drinking contributing appreciably to this burden. A 10% drop in drinking in France would have prevented more than 2000 (estimated) new cancer cases in 2015.

New cancer cases in France in 2015 attributable to infectious agents: a systematic review and meta-analysis.

To provide an assessment of the burden of cancer in France in 2015 attributable to infectious agents. A systematic literature review in French representative cancer cases series was undertaken of the prevalence of infectious agents with the major associated cancer types. PubMed was searched for original studies published up to September 2016; random-effects meta-analyses were performed. Cancer incidence data were obtained from the French Cancer Registries Network, thereby allowing the calculation of national incidence estimates. The number of new cancer cases attributable to infectious agents was calculated using population-attributable fractions according to published methods. Of the 352,000 new cancer cases in France in 2015, 14,336 (4.1% of all new cancer cases) were attributable to infectious agents. The largest contributors were human papillomavirus (HPV) and Helicobacter pylori, responsible for 6333 and 4406 new cancer cases (1.8 and 1.3% of all new cancer cases) respectively. Infectious agents caused a non-negligible number of new cancer cases in France in 2015. Most of these cancers were preventable. The expansion of vaccination (i.e., for hepatitis B virus and HPV) and screen-and-treat programs (for HPV and hepatitis C virus, and possibly for H. pylori) could greatly reduce this cancer burden.