Public health impact of Infanrix hexa™ (DTPa-HBV-IPV/Hib) reimbursement: A study programme in France. Part 2: Evolution of the acceptability of infants' vaccination against hepatitis B in general and pediatric practices - the PRALINE study.

BACKGROUND: The reimbursement of the hexavalent vaccine (Infanrix hexa™), comprising the DTPa-IPV-Hib components and the hepatitis B recombinant in a single vaccine, was approved in France in March of 2008. The impact of its reimbursement on physicians' decisions to vaccinate infants against hepatitis B was assessed in a study conducted with general practitioners and pediatricians. METHODS: The PRALINE study (NCT01777074) was a national, cross-sectional, repeated study with two measurement periods (T1 and T2) that measured the changes in physicians' acceptance of hepatitis B vaccination of infants before and for the 3 years after the approval of the hexavalent vaccine reimbursement. Two patient registers were created for each measurement period to enroll the first 15 12- to 15-month-old infants and the first 15 24- to 27-month-old children seen by the practitioners. The proportion of eligible children receiving a hepatitis B vaccine for each physician's practice was calculated. Practitioners also answered a vaccination practice questionnaire via telephone interviews. RESULTS: Across the two study periods, 418 general practitioners and 463 pediatricians were recruited and responded to the telephone interview on their vaccination practices. The overall number of children included in the study in both study periods reached almost 20,000. In the general practitioners group, there was a significant increase in the proportion of physicians "practicing hepatitis B vaccination" (i.e., at least 50% of eligible children receiving the initial hepatitis B vaccination) in children 24-27 months old (79% T2 versus 47% T1, P-value [P]<0.001). Similarly, the proportion of pediatricians initiating hepatitis B vaccination increased from 51% (T1) to 94% (T2) (P<0.0001). General practitioners offered hepatitis B vaccination to infants more systematically in the second study period (87% T2 versus 73% T1, P<0.001) and also suggested the use of the hexavalent vaccine to more patients after reimbursement (92% T2 versus 78% T1, P<0.0001). The proportion of pediatricians offering vaccination to every infant was high at T1 (94%) and remained steady (97%) with a high use of the hexavalent vaccine (94% T1 and 96% T2). CONCLUSION: The PRALINE study shows a significant and immediate change in the hepatitis B vaccination practices of general practitioners and pediatricians following hexavalent vaccine reimbursement with a significant increase in hepatitis B vaccine coverage in infants.

Public health impact of Infanrix hexa (DTPa-HBV-IPV/Hib) reimbursement: A study programme in France. Part 1: Evolution of hepatitis B vaccine coverage rates in infants aged less than 27 months, in the general population - the PopCorn study.

BACKGROUND: Reimbursement of the hexavalent vaccine (Infanrix hexa) comprising the DTPa-IPV-Hib components and the hepatitis B valence in a single vaccine was decided in March 2008 in France. The impact of its reimbursement on the hepatitis B vaccine coverage rate was assessed in a study conducted in the general population prior to and after implementation of the reimbursement policy. METHODS: The PopCorn study (NCT01782794) was a national, cross-sectional and repeated study, with four assessment periods over 3 years, from 2009 to 2012, to assess the hepatitis B vaccine coverage in 12- to 15- and 24- to 27-month-old children, vaccinated between 2007 and 2011 and selected by the quota sampling method. Face-to-face interviews were conducted at their homes and vaccination status was collected using their child's health record. Parents were also interviewed on their perceptions and acceptance of hepatitis B vaccination. Three indicators were calculated to assess hepatitis B vaccination coverage: proportions of infants with at least one dose before 6 months of age, with at least two doses before 6 months of age and with a complete schedule at 24 months of age. RESULTS: A total of 4903 children were enrolled in the study. An overall significant increase (P-value [P<0.05]) of the three indicators of interest over the four periods of time was observed for both age groups. The proportion of children receiving hepatitis B vaccination before 6 months increased from 21% at baseline (before vaccine reimbursement) to almost 75% at the last assessment period in 2012. More than 60% of 24- to 27-month-old children received a complete schedule in 2012 compared to 33% at baseline. No significant increases in the proportions of parents "favourable" and "moderately in favour" of hepatitis B vaccination were observed across the four evaluation periods (respectively, 17-22% and 48-50%, P=0.09). CONCLUSION: The rapid increase of hepatitis B vaccination coverage suggests a significant change in hepatitis B vaccination practice related to the hexavalent vaccine's reimbursement. This change was observed in a context of stability regarding parents' perceptions and acceptance of hepatitis B vaccination and of coverage rates for other infant vaccinations.

[Incidence of rotavirus gastroenteritis among children under 5 years consulting a paediatrician or a general practitioner in France]. / Incidence des gastroentérites à rotavirus chez les enfants de moins de cinq ans consultant un pédiatre ou un médecin généraliste en France.

BACKGROUND: Rotavirus (RV) is the main infectious agent of severe acute gastroenteritis (AGE) in infants and children under 5 years. Given the recent availability of new vaccines, it is important to accurately assess the incidence of rotavirus gastroenteritis (GERV) and their medical and epidemiological consequences. METHODS: This work is the French part of study program called SPRIK, a multicenter, prospective, observational study conducted from October 2005 to May 2007 to estimate the annual incidence of GERV within children under 5 years visiting a general practitioner or pediatrician. It presents data collected by 41 general practitioners and 36 paediatricians located throughout the French metropolitan territory. A stool sample was taken for every child. Rotavirus presence was sought by the physician using a rapid immunochromatographic test. French results are presented in this article. RESULTS: A total of 1648 GEA episodes corresponding to 1463 eligible patients were included in the study mainly from December to May (peak in February-March). The incidence rate of GERV leading to consultations in general practice was 1357 cases per 100,000 patient-years (PY) (1.36%), with a 95% confidence interval of [1345-1368]. The peak incidence occurs before 2 years. GERV accounted for 21% of all GEA cases seen by paediatricians and general practitioners. Patients with GERV were younger (14.1 ± 10.8 versus 18.4 ± 13.9 months for other GEA, P<0.0001) and had more severe clinical symptoms: presence of fever (32.6% versus 20.0%, P<0.0001), behavioural symptoms (45.6% versus 20.8%, P<0.0001) and dehydration (48.7% versus 21.2%, P<0.0001). GERV episodes were considered severe in 79.7% of cases, using the Vesikari scale. More than 86% patients received oral rehydration during the episode and 13 patients (5.8%) were hospitalized. Nearly 80% GERV episodes were considered severe using the Vesikari scale. Main genotypes were G1P[8] rotavirus (44%) and G9P[8] rotavirus (35%) types. CONCLUSION: The incidence rate reported in this study is close to results of previous studies done in Europe. The frequency and severity relative to GERV support vaccination in very young children to reduce the burden associated with this pathology.

[Impact of Rotavirus gastroenteritis requiring hospitalization or presenting to emergency room among children less than 5 years in France]. / Impact des gastroentérites à Rotavirus chez les enfants de moins de cinq ans hospitalisés ou consultant en services d'urgences en France.

BACKGROUND: In France, Rotavirus infections are responsible for approximately 300,000 cases of acute gastroenteritis (AGE) in children less than 5 years every year, 138,000 outpatient consultations and 18,000 hospitalizations. Surveillance for Rotavirus Infections in Hospitalized Kids (SHRIK) is a European prospective observational study conducted to assess the burden related to Rotavirus gastroenteritis (RVGE) in these children. METHODS: Patients less than 5 years visiting emergency rooms for AGE (U-AGE), who were hospitalized (H-AGE) or who developed RVGE 48 hours after hospitalization (N-AGE) were included in the study over a year. A stool sample was collected for every child and analyzed by ELISA. RESULTS: Results are presented for patients enrolled in France. A total of 755 eligible patients with AGE were included (357 for U-AGE, 372 for H-AGE and 26 for N-AGE). Among them, the proportion of RVGE was 49.1% (n=114) for U-AGE and 64.4% (n=186) for H-AGE. Most cases of RVGE (89%) involved children less than 2 years. GERV were frequently more severe than GEA non related to Rotavirus (NRVGE), according to the Vesikari scale, (68.4% against 41.9%, P<0.0001). Oral rehydration was performed for nearly 50% of RVGE patients before coming to hospital, versus 36.2% for NRVGE (P<0.002). All RV-positive strains were genotyped: the most frequent strains were G1P[8] (U-AGE, 42%; H-AGE, 46%) and G9P[8] (U-AGE, 38%; H-AGE, 31%). CONCLUSION: SHRIK study followed up all GEA visiting emergency room or requiring hospitalization for one year and showed that the burden of Rotavirus disease is high with a ratio over 70% of all hospital GEA during the winter peak.

IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC).

Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02-1.86), P = 0.01, and 1.44 (95% CI 1.04-1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60-1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50-1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57-1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19-1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.

Body mass index, waist circumference and waist-hip ratio and serum levels of IGF-I and IGFBP-3 in European women.

OBJECTIVE: To examine the relationship between body mass index (BMI) and waist-hip ratio (WHR) with serum levels of insulin-like growth factor-I (IGF-I), and its binding protein (IGFBP)-3. DESIGN: Cross-sectional study on 2139 women participating in a case-control study on breast cancer and endogenous hormones. Data on lifestyle and reproductive factors were collected by means of questionnaires. Body height, weight, waist and hip circumferences were measured. Serum levels of IGF-I and insulin-like binding protein (IGFBP)-3 were measured by enzyme-linked immunosorbent assays. Adjusted mean levels of IGF-I and IGFBP-3 across quintiles of BMI, waist circumference, and WHR were calculated by linear regression. Results were adjusted for potential confounders associated with IGF-I and IGFBP-3. RESULTS: Adjusted mean serum IGF-I values were lower in women with BMI<22.5 kg/m(2) or BMI>29.2 kg/m(2) compared to women with BMI within this range (P(heterogeneity)<0.0001, P(trend)=0.35). Insulin-like growth factor-I was not related to WHR after adjustment for BMI. IGF-binding protein-3 was linearly positively related to waist and WHR after mutual adjustment. The molar ratio IGF-I/IGFBP-3 had a non-linear relation with BMI and a linear inverse relationship with WHR (P (trend)=0.005). CONCLUSIONS: Our data confirm the nonlinear relationship of circulating IGF-I to total adiposity in women. Serum IGFBP-3 was positively related to central adiposity. These suggest that bioavailable IGF-I levels could be lower in obese compared to non-obese women and inversely related to central adiposity.

Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study.

Insulin-like growth factor I (IGF-I) stimulates cell proliferation and can enhance the development of tumours in different organs. Epidemiological studies have shown that an elevated level of circulating IGF-I is associated with increased risk of breast cancer, as well as of other cancers. Most of circulating IGF-I is bound to an acid-labile subunit and to one of six insulin-like growth factor binding proteins (IGFBPs), among which the most important are IGFBP-3 and IGFBP-1. Polymorphisms of the IGF1 gene and of genes encoding for the major IGF-I carriers may predict circulating levels of IGF-I and have an impact on cancer risk. We tested this hypothesis with a case-control study of 807 breast cancer patients and 1588 matched control subjects, nested within the European Prospective Investigation into Cancer and Nutrition. We genotyped 23 common single nucleotide polymorphisms in IGF1, IGFBP1, IGFBP3 and IGFALS, and measured serum levels of IGF-I and IGFBP-3 in samples of cases and controls. We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings. Common genetic variation in these candidate genes does not play a major role in altering breast cancer risk in Caucasians.

Several anthropometric measurements and breast cancer risk: results of the E3N cohort study.

OBJECTIVE: To investigate the association between various anthropometric characteristics and breast cancer. DESIGN: Longitudinal prospective cohort study. Follow-up between 1995 and 2000. SUBJECTS: In total, 69 116 women (age: 45-70 years; mean follow-up: 3.6 years), 275 premenopausal and 860 postmenopausal incident invasive breast cancers. MEASUREMENTS: Self-reported height, weight, breast, thorax, waist and hip circumferences and calculated body mass index (BMI) and waist-to-hip ratio (WHR) at baseline. RESULTS: A slight increase in risk with increasing height was found. Weight, BMI, thorax and waist circumferences and WHR were negatively related to breast cancer risk among premenopausal women. The relationships became non significant after additional adjustment for BMI. An increased risk of premenopausal breast cancer with an android body shape (WHR>0.87) might possibly be confined to obese women. Among postmenopausal women, all anthropometric measurements of corpulence were positively associated with breast cancer risk but became non significant after additional adjustment for BMI. No difference in risk of postmenopausal breast cancer according to HRT use was observed. CONCLUSION: The study confirmed that adiposity was negatively associated to premenopausal breast cancer risk and positively associated to postmenopausal breast cancer risk. Further studies will be needed to specify clearly the association between WHR and breast cancer risk, particularly before menopause.

Age at menarche in relation to adult height: the EPIC study.

In the last two centuries, age at menarche has decreased in several European populations, whereas adult height has increased. It is unclear whether these trends have ceased in recent years or how age at menarche and height are related in individuals. In this study, the authors first investigated trends in age at menarche and adult height among 286,205 women from nine European countries by computing the mean age at menarche and height in 5-year birth cohorts, adjusted for differences in socioeconomic status. Second, the relation between age at menarche and height was estimated by linear regression models, adjusted for age at enrollment between 1992 and 1998 and socioeconomic status. Mean age at menarche decreased by 44 days per 5-year birth cohort (beta = -0.12, standard error = 0.002), varying from 18 days in the United Kingdom to 58 days in Spain and Germany. Women grew 0.29 cm taller per 5-year birth cohort (standard error = 0.007), varying from 0.42 cm in Italy to 0.98 cm in Denmark. Furthermore, women grew approximately 0.31 cm taller when menarche occurred 1 year later (range by country: 0.13-0.50 cm). Based on time trends, more recent birth cohorts have their menarche earlier and grow taller. However, women with earlier menarche reach a shorter adult height compared with women who have menarche at a later age.

Body silhouette, menstrual function at adolescence and breast cancer risk in the E3N cohort study.

We analysed the relation between adult breast cancer risk and adiposity in ages 8-25, and among 90 509 women included in the E3N cohort study, and investigated the potential modification effect of certain factors. Participants completed a questionnaire that included a set of eight silhouettes corresponding to body shape at different ages. During the follow-up (mean=11.4 years), 3491 breast cancer cases were identified. Negative trends in risk of breast cancer with increasing body silhouettes at age 8 and at menarche were observed, irrespective of menopausal status, with relative risks of 0.73 (0.53-0.99) and 0.82 (0.66-1.02) for women who reported a silhouette equal or greater than the fifth silhouette at age 8 and at menarche, respectively. We observed no clear effect modification by age at menarche, delay between age at menarche, regular cycling, regularity of cycles in adult life or body mass index at baseline.

Anthropometric measurements and body silhouette of women: validity and perception.

OBJECTIVE: To examine the validity of self-reported values for current anthropometric measurements and factors related to misreporting. DESIGN: E3N, a prospective cohort study of cancer risk factors, conducted in France and part of the European Prospective Investigation on Cancer. E3N comprises 100,000 women, born between 1925 and 1950, followed with self-administered questionnaires sent every 18 to 24 months starting in 1990. SUBJECTS: 152 women for the validation study of self-reported anthropometric measurements, and 91,815 women selected to evaluate factors affecting misreporting of body silhouette. STATISTICAL ANALYSIS: Paired t tests, Pearson and Spearman correlations were applied to evaluate the validity of self-reported measures, and analysis of variance and logistic regression were used to assess the factors influencing misreporting of silhouette. RESULTS: The correlation coefficients between self- and external measurements were high. All but sitting height (r = 0.56) were more than 0.80, with weight and bust (nipples) measurement correlation coefficients attaining 0.94. The correlation between body mass index (BMI), measured by the technician and the self-reported silhouette, was 0.78. Small height was always associated with misclassification. Specific factors related to a more favorable perception of body silhouette were: being overweight, small height, younger age, and a lower level of education. These women were also more frequently unmarried, more physically active, and had had a slender body shape during adolescence. Results denoting a less favorable perception of body shape were reversed. CONCLUSION/APPLICATIONS: Self-reported measurements (made with or without help) are valid measures in epidemiological studies. Body silhouettes are simple and useful indicators of body mass index. However they should be interpreted with caution in certain instances, especially for overweight subjects.

Overweight, obesity and fat distribution in 50- to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE: To describe anthropometric characteristics of participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN: A cross-sectional analysis of baseline data of a European prospective cohort study. SUBJECTS: This analysis includes study populations from 25 centres in nine European countries. The British populations comprised both a population-based and a 'health-conscious' group. The analysis was restricted to 83 178 men and 163 851 women aged 50-64 years, this group being represented in all centres. METHODS: Anthropometric examinations were undertaken by trained observers using standardised methods and included measurements of weight, height, and waist and hip circumferences. In the 'health-conscious' group (UK), anthropometric measures were predicted from self-reports. RESULTS: Except in the 'health-conscious' group (UK) and in the French centres, mean body mass index (BMI) exceeded 25.0 kg m-2. The prevalence of obesity (BMI> or =30 kg m(-2)) varied from 8% to 40% in men, and from 5% to 53% in women, with high prevalences (>25%) in the centres from Spain, Greece, Ragusa and Naples (Italy) and the lowest prevalences (<10%) in the French centres and the 'health-conscious' group (UK). The prevalence of a large waist circumference or a high waist-to-hip ratio was high in centres from Spain, Greece, Ragusa and Naples (Italy) and among women from centres in Germany and Bilthoven (The Netherlands). CONCLUSIONS: Anthropometric measures varied considerably within the EPIC population. These data provide a strong base for further investigation of anthropometric measures in relation to the risk of chronic diseases, especially cancer.