Effectiveness of and overdiagnosis from mammography screening in the Netherlands: population based study.

Objective To analyse stage specific incidence of breast cancer in the Netherlands where women have been invited to biennial mammography screening since 1989 (ages 50-69) and 1997 (ages 70-75), and to assess changes in breast cancer mortality and quantified overdiagnosis.Design Population based study.Setting Mammography screening programme, the Netherlands.Participants Dutch women of all ages, 1989 to 2012.Main outcome measures Stage specific age adjusted incidence of breast cancer from 1989 to 2012. The extra numbers of in situ and stage 1 breast tumours associated with screening were estimated by comparing rates in women aged 50-74 with those in age groups not invited to screening. Overdiagnosis was estimated after subtraction of the lead time cancers. Breast cancer mortality reductions and overdiagnosis during 2010-12 were computed without (scenario 1) and with (scenario 2) a cohort effect on mortality secular trends.Results The incidence of stage 2-4 breast cancers in women aged 50 or more was 168 per 100 000 in 1989 and 166 per 100 000 in 2012. Screening would be associated with a 5% mortality reduction in scenario 1 and with no influence on mortality in scenario 2. In both scenarios, improved treatments would be associated with 28% reductions in mortality. Overdiagnosis has steadily increased over time with the extension of screening to women aged 70-75 and with the introduction of digital mammography. After deduction of clinical lead time cancers, 33% of cancers found in women invited to screening in 2010-12 and 59% of screen detected cancers would be overdiagnosed.Conclusions The Dutch mammography screening programme seems to have little impact on the burden of advanced breast cancers, which suggests a marginal effect on breast cancer mortality. About half of screen detected breast cancers would represent overdiagnosis.

Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials.

Randomised trials reported up to Dec 31, 2012, did not confirm that vitamin D supplementation could protect from non-skeletal health conditions affecting adults, as was expected on the basis of data from observational studies. To examine whether the more recently published meta-analyses and trials would change past conclusions, we systematically reviewed meta-analyses of vitamin D supplementation and non-skeletal disorders published between Jan 1, 2013, and May 31, 2017, that included study participants of all ages, including pregnant women. We also searched for randomised trials not included in meta-analyses. We identified 87 meta-analyses, of which 52 were excluded because they contained less recent literature or were of suboptimal quality. We retrieved 202 articles on trials that were not included in meta-analyses. Recent meta-analyses reinforce the finding that 10-20 µg per day of vitamin D can reduce all-cause mortality and cancer mortality in middle-aged and older people. Although vitamin D doses were greater than those assessed in the past, we found no new evidence that supplementation could have an effect on most non-skeletal conditions, including cardiovascular disease, adiposity, glucose metabolism, mood disorders, muscular function, tuberculosis, and colorectal adenomas, or on maternal and perinatal conditions. New data on cancer outcomes were scarce. The compilation of results from 83 trials showed that vitamin D supplementation had no significant effect on biomarkers of systemic inflammation. The main new finding highlighted by this systematic review is that vitamin D supplementation might help to prevent common upper respiratory tract infections and asthma exacerbations. There remains little evidence to suggest that vitamin D supplementation has an effect on most conditions, including chronic inflammation, despite use of increased doses of vitamin D, strengthening the hypothesis that low vitamin D status is a consequence of ill health, rather than its cause. We further hypothesise that vitamin D supplementation could exert immunomodulatory effects that strengthen resistance to acute infections, which would reduce the risk of death in debilitated individuals. We identified many meta-analyses of suboptimal quality, which is of concern. Future systematic reviews on vitamin D should be based on data sharing so that data for participants with the same outcomes measured in the same way can be pooled to generate stronger evidence.

Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies.

BACKGROUND: Lower risk of breast cancer has been reported among physically active women, but the risk in women using hormone replacement therapy (HRT) appears to be higher. We quantified the association between physical activity and breast cancer, and we examined the influence that HRT use and other risk factors had on this association. METHODS: After a systematic literature search, prospective studies were meta-analysed using random-effect models applied on highest versus lowest level of physical activity. Dose-response analyses were conducted with studies reporting physical activity either in hours per week or in hours of metabolic equivalent per week (MET-h/week). RESULTS: The literature search identified 38 independent prospective studies published between 1987 and 2014 that included 116,304 breast cancer cases. Compared to the lowest level of physical activity, the highest level was associated with a summary relative risk (SRR) of 0.88 (95% confidence interval [CI] 0.85, 0.90) for all breast cancer, 0.89 (95% CI 0.83, 0.95) for ER+/PR+ breast cancer and 0.80 (95% CI 0.69, 0.92) for ER-/PR- breast cancer. Risk reductions were not influenced by the type of physical activity (occupational or non-occupational), adiposity, and menopausal status. Risk reductions increased with increasing amounts of physical activity without threshold effect. In six studies, the SRR was 0.78 (95% CI 0.70, 0.87) in women who never used HRT and 0.97 (95% CI 0.88, 1.07) in women who ever used HRT, without heterogeneity in results. Findings indicate that a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT. CONCLUSION: Increasing physical activity is associated with meaningful reductions in the risk of breast cancer, but in women who ever used HRT, the preventative effect of physical activity seems to be cancelled out.

Anatomical UV Exposure in French Outdoor Workers.

BACKGROUND: Solar ultraviolet has been recognized as the main causative factor for skin cancer and is currently classified as a carcinogenic agent by International Agency for Research on Cancer. METHOD: Results from a previous phone survey conducted in 2012 in France were used to assess exposure conditions to sun among outdoor workers. Satellite data were used in combination with an exposure model to assess anatomical exposure. RESULT: The yearly median exposure of the outdoor worker population is 77  kJ/m2 to 116  kJ/m2. Road workers, building workers, and gardeners are the more exposed. About 70% of the yearly dose estimate is due to the cumulative summer and spring exposures. CONCLUSIONS: This study highlights the role of individual factors in anatomical exposure and ranks the most exposed body parts and outdoor occupations. Prevention messages should put emphasis on spring exposure, which is an important contributor to the yearly dose.

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.

Occupational UV exposure in French outdoor workers.

OBJECTIVES: Occupational ultraviolet (UV) exposure was evaluated in a population-based sample in France. METHODS: A random survey was conducted in 2012 in individuals aged 25 to 69 years. The median daily standard erythemal UV dose (SED) was estimated from exposure time and place and matched to satellite UV records. RESULTS: A total of 889 individuals were exposed to solar UV with highest doses observed among gardeners (1.19 SED), construction workers (1.13 SED), agricultural workers (0.95 SED), and culture/art/social science workers (0.92 SED). Information and communication technology, industry, and transport workers were highly exposed (>0.70 SED). Significant factors associated with high occupational UV exposure were sex (P < 0.0001), phototype (P = 0.0003), and taking lunch outdoors (P < 0.0001). CONCLUSIONS: This study identified not only expected occupations with high UV exposure but also unexpected occupations with high exposures. This could serve as a basis for future prevention.

Identification of newborns with Fetal Growth Restriction (FGR) in weight and/or length based on constitutional growth potential.

This study was carried out to build statistical models for defining FGR (Fetal Growth Restriction) in weight and/or length after taking growth potential of an infant into account. From a cohort of pregnant women having given birth to 47,733 infants in 141 French maternity units, two statistical models gave individualized limits of birth weight and birth length (based on the 5th centile) below which, after adjustment for its individual growth potential, a newborn must be considered as FGR in weight and/or in length. A sample of 906 infants had measures taken of cord blood growth factors (IGF1, IGFBP3). The FGR(W) definition (weight<5th centile for growth potential) permitted the identification of infants who presented rates of maternal hypertension (13.6%) and of Apgar score at 5 min<6 (2.9%) higher than in the classical group SGA(W) (weight<5th centile for sex and gestational age) (9.6% and 2.2% respectively). By combining FGR(W) and SGA(W), a subgroup of infants, not currently recognized as SGA, presented very high rates of maternal hypertension (19.9%) and of low Apgar score (3.9%). Conversely a subgroup of infants, currently recognized as SGA(W), had rates as low as in the normal infants group, and had to be considered as "constitutionally small" (that is to say 24% of the SGA(W)). Combining FGR(W) and FGR(L) (length<5th centile of growth potential), 7.6% of infants appeared growth-restricted, and 1.8% appeared constitutionally small in weight and/or in length. The FGR(W)-FGR(L) infants showed the lowest mean values of IGF1 (126.2+/-3.2) and IGFBP3 (0.86+/-0.03). These new definitions of FGR(W) and FGR(L) could help to better identify infants at birth requiring neonatal care, and monitoring of growth catch-up and neurodevelopmental outcome.