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Overdiagnosis is a harmful consequence of screening which is particularly challenging to estimate. An unbiased setting to measure overdiagnosis in breast cancer screening requires comparative data from a screened and an unscreened cohort for at least 30 years. Such randomised data will not become available, leaving us with observational data over shorter time periods and outcomes of modelling. This collaborative effort of the International Cancer Screening Network quantified the variation in estimated breast cancer overdiagnosis in organised programmes with evaluation of both observed and simulated data, and presented examples of how modelling can provide additional insights. Reliable observational data, analysed with study design accounting for methodological pitfalls, and modelling studies with different approaches, indicate that overdiagnosis accounts for less than 10% of invasive breast cancer cases in a screening target population of women aged 50 to 69. Estimates above this level are likely to derive from inaccuracies in study design. The widely discrepant estimates of overdiagnosis reported from observational data could substantially be reduced by use of a cohort study design with at least 10 years of follow‐up after screening stops. In contexts where concomitant opportunistic screening or gradual implementation of screening occurs, and data on valid comparison groups are not readily available, modelling of screening intervention becomes an advantageous option to obtain reliable estimates of breast cancer overdiagnosis. What's new The detection of breast cancer before symptoms arise greatly increases the chance of prolonging survival or even curing malignancy. However, the assumption that asymptomatic disease progresses to symptomatic disease is a major factor in breast cancer overdiagnosis. While estimates of overdiagnosis vary substantially, the present analysis of observational data and data from modelling studies shows that overdiagnosis accounts for less than 10 percent of invasive breast cancer cases among women ages 50 to 69. The findings reaffirm the idea that observational studies require careful design to avoid methodological pitfalls and highlight the value of insight gained from well‐calibrated modelling studies. [ABSTRACT FROM AUTHOR]

Background: Although breast cancer screening reduces breast cancer mortality at the population level, subgroups of women may benefit differently. We investigated the impact of health status on the effect of breast cancer screening. Methods: The study included 181 299 women invited in two population‐based screening programs in Denmark and 1 526 446 control subjects, followed from April 1981 to December 2014. Poisson regressions were used to compare the observed breast cancer mortality rate in women invited to screening with the expected rate in the absence of screening among women with and without chronic diseases. Chronic diseases were defined as any diagnosis in the Charlson Comorbidity Index during 4 years before the first invitation to screening. Results: Almost 10% of women had chronic diseases before first invitation to screening. Whereas we observed a reduction in breast cancer mortality following invitation to screening of 28% (95% CI, 20% to 35%) among women without chronic diseases, only a 7% (95% CI, −39% to 37%) reduction was seen for women with chronic diseases (P‐value for interaction =.22). For participants, the reduction, corrected for selection bias, was 35% (95% CI 16% to 49%) for women without, and 4% (95% CI −146% to 62%) for women with chronic diseases (P‐value for interaction =.43). Conclusion: Our data indicate a marginal effect of mammography screening on breast cancer mortality in women with chronic diseases. If our results are confirmed in other populations, the presence of chronic diseases will be an important factor to take into consideration in personalized screening. [ABSTRACT FROM AUTHOR]

Objective: Asthma affects between 3% to 8% of pregnant women. Previous studies have suggested that women's prescriptions for asthma medications change during pregnancy. The aim was to describe the prescription of asthma medications before and during pregnancy in France. Methods: Women from the EFEMERIS, a French database assessing the drugs prescribed, dispensed and reimbursed during pregnancy, delivering between July 2004 and December 2012, were included. Women, who were dispensed asthma medications on at least two dates from 3 months prior to pregnancy through delivery, were considered. Results: 2,977 women out of 69,205 (4%) were selected. They were prescribed 2.4 ± 1.2 different anti-asthmatic drugs with 3.5 ± 2.7 different dispensing dates. Almost 62% of the women were dispensed at least one prescription for short-acting β2-agonist (SABA), 63% at least one inhaled corticosteroid (IC), 42% a fixed-combination of an IC and a long-acting β2-agonist (LABA) and 8% a LABA. An increase in SABA and IC prescriptions and a decrease in fixed-combination prescriptions were observed during pregnancy compared to pre-pregnancy period. A rapid drop in prescriptions for montelukast was observed. Among the 1,507 women who were prescribed asthma medication before pregnancy, one third had a drop in dispensed asthma medications from the beginning of pregnancy. Conclusions: The prevalence of dispensed asthma medications varies during pregnancy. There is a decrease in the prescriptions of fixed-combinations during pregnancy and an increase in the prescriptions of ICs. It appears important to study the potential impact of such changes on fetuses and newborns. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to evaluate the potential effect of in utero exposure to drugs with atropinic properties on infant psychological development using atropinic burden (AB) scales. Methods Women from the EFEMERIS cohort, a French database including prescribed and dispensed reimbursed drugs during pregnancy and pregnancy outcomes, delivering between 2004 and 2010 were included ( n = 43 740). Each drug was classified as having no (score = 0), few (score = 1) or strong (score = 3) atropinic properties. AB per woman was calculated by adding the atropinic scores of drugs prescribed during pregnancy. AB was categorized as exposure or no exposure. Secondary analyses were performed by dividing the exposure into four scores = [0], [1-8], [9-17] and [≥18]. Data for psychological development were extracted from children's medical certificates completed at 9 and 24 months. Results Thirty-four% ( n = 14 925) of women received at least one atropinic drug during pregnancy. Women with AB ≥1 were older and received more drugs during pregnancy than unexposed women. At 24 months, more infants of mothers with AB ≥1 had difficulties to 'name a picture' (ORa, 1.18, 95% CI 1.03, 1.36) and to 'understand instructions' (ORa, 1.61, 95% CI 1.13, , 2.30]) compared with infants of unexposed women. Analyses of four groups of exposure and analyses excluding women receiving psychotropics led to similar results. Conclusions The study showed significant association between in utero exposure to drugs with atropinic properties and fewer infant cognitive acquisitions at 24 months. Further exploring the potential effect of simultaneous use of drugs with atropinic effects among pregnant women will bring into consideration whether such prescriptions could be inappropriate for the child. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to develop a new pharmacoepidemiological method to take into account intensity and evolution of drug exposure, applied to pregnant women. Methods Pregnant women were classified according to their drug exposure, in three steps: Conversion of prescription data into exposure variables (using ATC-DDD), Construction of individual trajectories of exposure, Clustering of individual trajectories of exposure (using the R package Kml), We applied this method to psychotropic drugs prescribed during pregnancy. The present study involved women, included in the EFEMERIS database, who gave birth in Haute-Garonne (France) between 2004 and 2010 ( N = 54 918). Results Exposure to psychotropic drugs of 3708 pregnant women was studied (6.7%). The pregnant women could be classified into four groups with homogeneous trajectories of exposure: low constant exposure during pregnancy (Cluster A: 70.8% of women); decreasing exposure during the first trimester of pregnancy and low constant exposure thereafter (Cluster B: 19.6%); moderate constant exposure (Cluster C: 8.2%); and high albeit decreasing exposure (Cluster D: 1.4%). Conclusions The proposed new method enabled us to describe more precisely women's exposure to drugs during pregnancy, and to distinguish different profiles of exposure. This method could be used to investigate specific outcomes related to duration and intensity of drug exposure during pregnancy, and also to study adverse drug reactions throughout life. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective There are few published data about possible effects of veinotonics in pregnant women. The present study investigates potential adverse drug reactions of veinotonics in pregnancy. Method EFEMERIS is a database including prescribed and dispensed reimbursed drugs during pregnancy (data from Caisse Primaire d’Assurance Maladie) and outcomes (data from Maternal and Infant Protection Service and Antenatal diagnostic Centre). Women who delivered from 1 July 2004 to December 2007 in Haute-Garonne and were registered in the French Health Insurance Service have been included in the EFEMERIS database. We compared pregnancy outcomes and newborn health between women exposed to veinotonics during pregnancy and unexposed women. Results We found that 8998 women (24%) had received at least one prescription for venotonic agents during their pregnancy, corresponding to the period of organogenesis in 1200 cases. We compared data for these women with those for the 27,963 women for whom these drugs were not prescribed during pregnancy. The most widely used veinotonics were hesperidin, diosmin and troxerutin. Pregnancies led to 98.4% versus 93.6% of live births, 0.2% versus 0.2% of postnatal deaths and 1.6% versus 6.4% of pregnancy termination (miscarriage, ectopic pregnancy, medical termination, intrauterine death) in exposed and non-exposed groups, respectively. The risks of pregnancy termination (HR = 0.71 (0.60–0.84)) and prematurity (HR = 0.82 (0.73–0.93)) remained significantly lower in the women exposed to venotonics than in unexposed women. In the group of newborns whose mother had a prescription of veinotonics during organogenesis, 39 out of 1200 (3.4%) had a malformation versus 789 (3.0%) in the control group (ORa = 1.134 (0.873–1.472)). The risk of neonatal diseases was not increased by exposure to venotonic agents in the third trimester (4.9% versus 6.1% for the controls, ORa = 1.07 (0.95–1.20)). Conclusion We found no increased risk of adverse pregnancy outcome among women exposed to veinotonics compared with unexposed pregnant women. [ABSTRACT FROM AUTHOR]

The article presents an analysis of Surveillance, Epidemiology, and End Results (SEER) data according to which mammography screening is more effective to the women's suffering from breast cancer. Topics discussed include Welch-analysis of mammography screening effectiveness; breast cancer incidence in Denmark; and analysis of effect of breast cancer screening.

The aim of the study was to evaluate the association between in utero exposure to drugs that potentially exhibit immunosuppressive activity and occurrence of infections during the first year of life. We conducted a cohort study on the prescription data of pregnant women and their children registered in EFEMERIS cohort (France), during a one-year period. We classified in utero child exposure according to the number of reimbursements for immunosuppressive drugs during pregnancy. The number of infectious episodes during the first year of life was estimated through the number of anti-infective drugs dispensed. The association was estimated by a quasi-Poisson regression with adjustment for confounders. The study population consisted of 9614 children, 3141 of whom had been exposed to immunosuppressive drugs during pregnancy. The most frequently immunosuppressive drugs prescribed were corticosteroids. The mean number of infectious episodes during the first year after birth gradually increased with the number of immunosuppressive drugs dispensed during pregnancy (from 2.38 in controls to 3.88 in the most exposed group). After adjustment for potential confounders, in utero exposure to immunosuppressive drugs was significantly associated with the number of infectious episodes during the first year of life (RR 3ormoreexposuresVS0 = 1.35, 95% CI 1.24–1.46). Intrauterine exposure to potentially immunosuppressive drugs could be associated with an increased susceptibility to infections in early childhood. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to examine the potential benefit to take into account duration and intensity of drug exposure using the recently published method based on individual drug trajectories. This approach was used to define profiles of exposure to anxiolytics/hypnotics during pregnancy and to evaluate the potential effect on newborn health., Methods: The study was performed in EFEMERIS database (54 918 mother-children pairs). An estimation of adaptation to extrauterine life was assessed using several criteria especially cardio-respiratory symptoms. A proxy variable called "neonatal pathology" was created. The occurrence of this event was studied using two approaches: The Standard Method comparing exposed and unexposed newborns, The Trajectory Method comparing the different profiles of exposure., Results: Around 5% of newborns (n = 2768) were identified to be exposed to anxiolytics or hypnotics during pregnancy. Using the Standard Method, 6.2% of exposed newborns developed a "neonatal pathology" against 4.8% of unexposed newborns (odds ratios [OR] = 0.9[0.8-1.2], p = 0.7). With the Trajectory Method taking into account evolution of exposure during pregnancy and treatment intensity, four profiles of pregnant women were identified. A significant difference in the rates of "neonatal pathologies" was observed between profiles (p = 0.0002). Newborns of the two profiles exposed in utero to high constant level of anxiolytics or hypnotics were more at risk of developing "neonatal pathology" than unexposed newborns (OR 1  = 2.0 [1.0-3.9] and OR 2  = 7.6 [2.8-20.5])., Conclusions: The present study demonstrates the interest of this method based on individual drug trajectories for the evaluation of outcomes in pharmaco-epidemiological studies and more specifically during pregnancy. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

Objective  To evaluate the possible effects of exposure to neuraminidase inhibitors during embryo-fetal life with respect to adverse neonatal outcomes and congenital malformations. Design  Population based multinational observational cohort study and meta-analysis. Setting  National registers covering information on maternal healthcare, births, and prescriptions in Denmark, Norway, and Sweden and the EFEMERIS database from the Haute-Garonne district in France. Participants  All women together with their singleton infants born between 1 January 2008 and 31 December 2010. Only infants born at 154 days of gestation or later were included. Infants were defined as exposed if the women filled a prescription during pregnancy for either of the two neuraminidase inhibitors oseltamivir or zanamivir. Main outcomes  Low birth weight, low Apgar score, preterm birth, small for gestational age birth, stillbirth, neonatal mortality, neonatal morbidity, and congenital malformations. Crude and adjusted hazard ratios of preterm birth were estimated using Cox regression models. Crude and adjusted odds ratios for other outcomes were estimated by logistic regression models. Results  The study included 5824 (0.8%) exposed women and their infants and 692 232 who were not exposed. Exposure to neuraminidase inhibitors in utero was not associated with increased risks of any of the investigated neonatal outcomes, including low birth weight (adjusted odds ratio 0.77, 95% confidence interval 0.65 to 0.91), low Apgar score (adjusted odds ratio 0.87, 0.67 to 1.14), preterm birth (adjusted hazard ratio 0.97, 0.86 to 1.10), small for gestational age birth (adjusted odds ratio 0.72, 0.59 to 0.87), stillbirth (adjusted odds ratio 0.81, 0.51 to 1.30), neonatal mortality (adjusted odds ratio 1.13, 0.56 to 2.28), and neonatal morbidity (adjusted odds ratio 0.92, 0.86 to 1.00). No increased risk of congenital malformations overall associated with maternal exposure was observed during the first trimester (adjusted odds ratio 1.06, 0.77 to 1.48). Similarly, no significantly increased risks of any of the outcomes were observed in an analysis restricted to oseltamivir alone. Conclusions  This large multinational register study found no increased risks of adverse neonatal outcomes or congenital malformations associated with exposure to neuraminidase inhibitors during embryo-fetal life. The results support previously reported findings that the use of neuraminidase inhibitors is not associated with increased risks of adverse fetal or neonatal outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)