Categorization and Analysis of Primary Care mHealth Apps Related to Breast Health and Breast Cancer: Systematic Search in App Stores and Content Analysis.

BACKGROUND: Breast cancer is the most common cause of cancer mortality among women globally. The use of mobile health tools such as apps and games is increasing rapidly, even in low- and middle-income countries, to promote early diagnosis and to manage care and support of survivors and patients. OBJECTIVE: The primary objective of this review was to categorize selected mobile health apps related to breast health and prevention of breast cancer, based on features such as breast self-examination (BSE) training and reminders, and to analyze their current dissemination. An ancillary objective was to highlight the limitations of existing tools and suggest ways to improve them. METHODS: We defined strict inclusion and exclusion criteria, which required apps to have titles or descriptions that suggest that they were designed for the general public, and not for patients with breast cancer or health workers. Apps that focused on awareness and primary care via self-check were included, while those that focused on topics such as alternative treatments and medical news were excluded. Apps that were not specifically related to breast cancer were also excluded. Apps (in any language) that appeared in the search with keywords were included. The database consisted of apps from AppAgg and Google Play Store. Only 85 apps met the inclusion criteria. Selected apps were categorized on the basis of their alleged interactive features. Descriptive statistics were obtained, and available language options, the number of downloads, and the cost of the apps were the main parameters reviewed. RESULTS: The selected apps were categorized on the basis of the following features: education, BSE training, reminders, and recording. Of the 85 selected apps, 72 (84.7%) focused on disseminating breast cancer information. BSE training was provided by only 47% (n=40) of the apps, and very few had reminder (n=26, 30.5%) and recording (n=11, 12.9%) features. The median number of downloads was the highest for apps with recording features (>1000 downloads) than those with education, BSE training, reminder, and recording features (>5000 downloads). Most of these apps (n=74, 83.5%) were monolingual, and around 80.3% (n=49) of these apps were in English. Almost all the apps on Google Play Store were free of charge. CONCLUSIONS: Although there exist several apps on Google Play Store to promote awareness about breast health and cancer, the usefulness of most of them appears debatable. To provide a complete breast health package to the users, such apps must have all of the following features: reminders or notifications and symptom recording and tracking. There is still an urgent need to scientifically evaluate existing apps in the target populations in order to make them more functional and user-friendly.

Metabolomic signatures in elite cyclists: differential characterization of a seeming normal endocrine status regarding three serum hormones.

INTRODUCTION: Serum phenotyping of elite cyclists regarding cortisol, IGF1 and testosterone is a way to detect endocrine disruptions possibly explained by exercise overload, non-balanced diet or by doping. This latter disruption-driven approach is supported by fundamental physiology although without any evidence of any metabolic markers. OBJECTIVES: Serum samples were distributed through Low, High or Normal endocrine classes according to hormone concentration. A 1H NMR metabolomic study of 655 serum obtained in the context of the longitudinal medical follow-up of 253 subjects was performed to discriminate the three classes for every endocrine phenotype. METHODS: An original processing algorithm was built which combined a partial-least squares-based orthogonal correction of metabolomic signals and a shrinkage discriminant analysis (SDA) to get satisfying classifications. An extended validation procedure was used to plan in larger size cohorts a minimal size to get a global prediction rate (GPR), i.e. the product of the three class prediction rates, higher than 99.9%. RESULTS: Considering the 200 most SDA-informative variables, a sigmoidal fitting of the GPR gave estimates of a minimal sample size to 929, 2346 and 1408 for cortisol, IGF1 and testosterone, respectively. Analysis of outliers from cortisol and testosterone Normal classes outside the 97.5%-confidence limit of score prediction revealed possibly (i) an inadequate protein intake for outliers or (ii) an intake of dietary ergogenics, glycine or glutamine, which might explain the significant presence of heterogeneous metabolic profiles in a supposedly normal cyclists subgroup. CONCLUSION: In a next validation metabolomics study of a so-sized cohort, anthropological, clinical and dietary metadata should be recorded in priority at the blood collection time to confirm these functional hypotheses.

The Computerized Adaptable Test Battery (BMT-i) for Rapid Assessment of Children's Academic Skills and Cognitive Functions: A Validation Study.

Background: Learning disabilities in children are a major public health concern worldwide, having a prevalence of 8%. They are associated with lost social, educational, and ultimately, professional opportunities for individuals. These disabilities are also very costly to governments and raise the issue of the appropriate means of screening. Unfortunately, validated tools for preliminary appraisal of learning and cognitive function in struggling children are presently restricted to specific age ranges and cognitive domains. This study sought to validate a first-line battery for assessment of academic skills and cognitive functions. Materials and Methods: The computerized Adaptable Test Battery, or BMT-i, includes a panel of tests for the first-line assessment of children's academic skills and cognitive functions. The tests reflect expected abilities for the age group in question, exploring academic skills (written language and mathematical cognition) and cognitive domains (verbal, non-verbal, and attentional/executive functions). The authors relied on the results of these tests for a sample of 1,074 Francophone children representative of the mainland French school-age population (522 boys and 552 girls, ages 4-13, from 39 classes at 7 public and 5 private schools). Thirteen speech-language pathologists and neuropsychologists individually administered the tests. Results: The psychometric characteristics of the empirical data obtained showed acceptable to good test homogeneity, internal consistency (Cronbach's alpha: > 0.70), test-retest reliability (intraclass correlation coefficients: ~0.80), and consistency with reference test batteries (r: 0.44-0.96). Conclusion: The BMT-i was validated in a large sample of children in mainstream French schools, paving the way for its use in first-line screening of learning disabilities among children with complaints, whether their learning difficulties have been flagged by their parents or by their teachers.

Regularized bidimensional estimation of the hazard rate.

In epidemiological or demographic studies, with variable age at onset, a typical quantity of interest is the incidence of a disease (for example the cancer incidence). In these studies, the individuals are usually highly heterogeneous in terms of dates of birth (the cohort) and with respect to the calendar time (the period) and appropriate estimation methods are needed. In this article a new estimation method is presented which extends classical age-period-cohort analysis by allowing interactions between age, period and cohort effects. We introduce a bidimensional regularized estimate of the hazard rate where a penalty is introduced on the likelihood of the model. This penalty can be designed either to smooth the hazard rate or to enforce consecutive values of the hazard to be equal, leading to a parsimonious representation of the hazard rate. In the latter case, we make use of an iterative penalized likelihood scheme to approximate the L0 norm, which makes the computation tractable. The method is evaluated on simulated data and applied on breast cancer survival data from the SEER program.

Global blood gene expression profiles following a breast cancer diagnosis-Clinical follow-up in the NOWAC post-genome cohort.

OBJECTIVE: This explorative study aimed to assess if there are any time-dependent blood gene expression changes during the first one to eight years after breast cancer diagnosis, which can be linked to the clinical outcome of the disease. MATERIAL AND METHODS: A random distribution of follow-up time from breast cancer diagnosis till blood sampling was obtained by a nested, matched case-control design in the Norwegian Women and Cancer Post-genome Cohort. From 2002-5, women were invited to donate blood samples, regardless of any cancer diagnosis. At end of the study period in 2015, any cancer diagnoses in the 50 000 participants were obtained via linkage to the Norwegian Cancer Registry. For each breast cancer patient (n = 415), an age- and storage time-matched control was drawn. The design gave a uniform, random length of follow-up time, independent of cancer stage. Differences in blood gene expression between breast cancer cases and controls were identified using the Bioconductor R-package limma, using a moving window in time, to handle the varying time elapsed from diagnosis to blood sample. RESULTS: The number of differentially expressed genes between cases and controls were close to 2,000 in the first year after diagnosis, but fell sharply the second year. During the next years, a transient second increase was observed, but only in women with metastatic disease who later died, both compared to invasive cases that survived (p<0,001) and to metastatic cases that survived (p = 0.024). Among the differentially expressed genes there was an overrepresentation of heme metabolism and T cell-related processes. CONCLUSION: This explorative analysis identified changing trajectories in the years after diagnosis, depending on clinical stage. Hypothetically, this could represent the escape of the metastatic cancer from the immune system.

Impact of on-site clinical genetics consultations on diagnostic rate in children and young adults with autism spectrum disorder.

Background: Neurogenetics investigations and diagnostic yield in patients with autism spectrum disorder (ASD) have significantly improved over the last few years. Yet, many patients still fail to be systematically investigated. Methods: To improve access to services, an ambulatory team has been established since 1998, delivering on-site clinical genetics consultations and gradually upgrading services to 502 children and young adults with ASD in their standard environment across 26 day-care hospitals and specialized institutions within the Greater Paris region. The evaluation included a clinical genetics consultation, screening for fragile X syndrome, metabolic workup, chromosomal microarray analysis, and, in a proportion of patients, next-generation sequencing of genes reported in ASD and other neurodevelopmental disorders. Results: Fragile X syndrome and pathogenic copy number variants (CNVs) accounted for the disease in 10% of cases, including 4/312 (1.3%) with fragile X syndrome and 34/388 (8.8%) with pathogenic CNVs (19 de novo and 4 inherited). Importantly, adding high-throughput resequencing of reported intellectual disability/ASD genes to the screening procedure had a major impact on diagnostic yield in the 141 patients examined most recently. Pathogenic or likely pathogenic sequence variants in 27 disease genes were identified in 33/141 patients (23.4%; 23 were de novo and 10 inherited, including five X-linked and five recessive compound heterozygous variants). Diagnosed cases presented atypical and/or syndromic ASD with moderate to severe intellectual disability. The diagnostic yield of fragile X syndrome and array CGH testing combined with next-generation sequencing was significantly higher than fragile X syndrome and array CGH alone (p value 0.009). No inborn errors of metabolism were detected with the metabolic screening. Conclusion: Based on the diagnostic rate observed in this cohort, we suggest that a stepwise procedure be considered, first screening pathogenic CNVs and a limited number of disease genes in a much larger number of patients, especially those with syndromic ASD and intellectual disability.

A big-data approach to producing descriptive anthropometric references: a feasibility and validation study of paediatric growth charts.

BACKGROUND: Both national and WHO growth charts have been found to be poorly calibrated with the physical growth of children in many countries. We aimed to generate new national growth charts for French children in the context of huge datasets of physical growth measurements routinely collected by office-based health practitioners. METHODS: We recruited 32 randomly sampled primary care paediatricians and ten volunteer general practitioners from across the French metropolitan territory who used the same electronic medical records software, from which we extracted all physical growth data for the paediatric patients, with anonymisation. We included measurements from all children born from Jan 1, 1990, and aged 1 month to 18 years by Feb 8, 2018, with birthweight greater than 2500 g, to which an automated process of data cleaning developed to detect and delete measurement or transcription errors was applied. Growth charts for weight and height were derived by using generalised additive models for location, scale, and shape with the Box-Cox power exponential distribution. We compared the new charts to WHO growth charts and existing French national growth charts, and validated our charts using growth data from recent national cross-sectional surveys. FINDINGS: After data cleaning, we included 1 458 468 height and 1 690 340 weight measurements from 238 102 children. When compared with the existing French national and WHO growth charts, all height SD and weight percentile curves for the new growth charts were distinctly above those for the existing French national growth charts, as early as age 1 month, with an average difference of -0·75 SD for height and -0·50 SD for weight for both sexes. Comparison with national cross-sectional surveys showed satisfactory calibration, with generally good fit for children aged 5-6 years and 10-11 years in height and weight and small differences at age 14-15 years. INTERPRETATION: We successfully produced calibrated paediatric growth charts by using a novel big-data approach applied to data routinely collected in clinical practice that could be used in many fields other than anthropometry. FUNDING: The French Ministry of Health; Laboratoires Guigoz-General Pediatrics section of the French Society of Pediatrics-Pediatric Epidemiological Research Group; and the French Association for Ambulatory Pediatrics.

Rethinking the carcinogenesis of breast cancer: The theory of breast cancer as a child deficiency disease or a pseudo semi-allograft.

The theory of breast cancer as a child deficiency disease is an inversion of the current paradigm, which considers full-term pregnancies to be a protective factor and uses nulliparous women as the reference group. Instead, the theory of breast cancer as a child deficiency disease says that women with the highest parity (about 20, which is the limit of human fertility) are those with the lowest risk and should be used as the reference group in risk estimations. This theory is explained biologically by converting parity from the simple value of number of children into an understanding of the long-lasting biological and immunological effects of pregnancy. These effects can be reflected, as measured by functional genomics, in gene expression of the immune cells in the blood. Each pregnancy represents a unique fetus or semi-allograft, which provokes the creation and deposit of memory cell clones in the mother. Gene expression levels have been found to change linearly with number of full-term pregnancies in healthy women, but not in breast cancer patients. High hormone levels are necessary for a successful pregnancy, as they modulate the immune response from adaptive to innate in order to protect the fetus (considered as a semi-allograft) from rejection. At the end of the pregnancy, hormone levels drop, and the immune system recognizes the semi-allograft, but not in time for rejection to occur before birth. High hormones levels are also classified as carcinogens illustrating that carcinogenesis in the breast could be viewed as a war or balance between later exposures to hormonal carcinogens and the protection of the immune system. We propose that breast tumors are pseudo semi-allografts made up of transformed breast tissue cells. Assuming that the sensitivity to the exposure to increased levels of endogenous or exogenous hormones in women with breast cancer mimic those that occur in pregnancy, these breast tumor cells are protected against the body's immune reaction, just as the fetus is during pregnancy. However, with more pregnancies, the potential to eradicate the pseudo semi-allograft might increase due to enhanced immune surveillance. The theory of breast cancer as a child deficiency disease proposes that the protective effect of pregnancy on breast cancer incidence via the immune system is independent of other risk factors.

Each pregnancy linearly changes immune gene expression in the blood of healthy women compared with breast cancer patients.

BACKGROUND: There is a large body of evidence demonstrating long-lasting protective effect of each full-term pregnancy (FTP) on the development of breast cancer (BC) later in life, a phenomenon that could be related to both hormonal and immunological changes during pregnancies. In this work, we studied the pregnancy-associated differences in peripheral blood gene expression profiles between healthy women and women diagnosed with BC in a prospective design. METHODS: Using an integrated system epidemiology approach, we modeled BC incidence as a function of parity in the Norwegian Women and Cancer (NOWAC) cohort (165,000 women) and then tested the resulting mathematical model using gene expression profiles in blood in a nested case-control study (460 invasive case-control pairs) of women from the NOWAC postgenome cohort. Lastly, we undertook a gene set enrichment analysis for immunological gene sets. RESULTS: A linear trend fitted the dataset precisely showing an 8% decrease in risk of BC for each FTP, independent of stratification on other risk factors and lasting for decades after a woman's last FTP. Women with six children demonstrated 48% reduction in the incidence of BC compared to nulliparous. When we looked at gene expression, we found that 756 genes showed linear trends in cancer-free controls (false discovery rate [FDR] 5%), but this was not the case for any of the genes in BC cases. Gene set enrichment analysis of immunologic gene sets (C7 collection in Molecular Signatures Database) revealed 215 significantly enriched human gene sets (FDR 5%). CONCLUSION: We found marked differences in gene expression and enrichment profiles of immunologic gene sets between BC cases and healthy controls, suggesting an important protective effect of the immune system on BC risk.

Levonorgestrel-releasing intrauterine system use is associated with a decreased risk of ovarian and endometrial cancer, without increased risk of breast cancer. Results from the NOWAC Study.

OBJECTIVE: Women with ovarian cancer have poor survival rates, which have proven difficult to improve; therefore primary prevention is important. The levonorgestrel-releasing intrauterine system (LNG-IUS) prevents endometrial cancer, and recent studies suggested that it may also prevent ovarian cancer, but with a concurrent increased risk of breast cancer. We compared adjusted risks of ovarian, endometrial, and breast cancer in ever users and never users of LNG-IUS. METHODS: Our study cohort consisted of 104,318 women from the Norwegian Women and Cancer Study, 9144 of whom were ever users and 95,174 of whom were never users of LNG-IUS. Exposure information was taken from self-administered questionnaires, and cancer cases were identified through linkage to the Cancer Registry of Norway. Relative risks (RRs) with 95% confidence intervals (CIs) were estimated with Poisson regression using robust error estimates. RESULTS: Median age at inclusion was 52years and mean follow-up time was 12.5 (standard deviation 3.7) years, for a total of 1,305,435 person-years. Among ever users of LNG-IUS there were 18 cases of epithelial ovarian cancer, 15 cases of endometrial cancer, and 297 cases of breast cancer. When ever users were compared to never users of LNG-IUS, the multivariable RR of ovarian, endometrial, and breast cancer was 0.53 (95% CI: 0.32, 0.88), 0.22 (0.13, 0.40), and 1.03 (0.91, 1.17), respectively. CONCLUSION: In this population-based prospective cohort study, ever users of LNG-IUS had a strongly reduced risk of ovarian and endometrial cancer compared to never users, with no increased risk of breast cancer.

No overdiagnosis in the Norwegian Breast Cancer Screening Program estimated by combining record linkage and questionnaire information in the Norwegian Women and Cancer study.

BACKGROUND: The Norwegian Breast Cancer Screening Program (NBCSP) was implemented across the country in 2005 and has been criticised for potential 'overdiagnosis', i.e. a breast cancer diagnosis that otherwise would not have been detected or treated in a woman's lifetime. We aimed to estimate overdiagnosis in the NBCSP based on the Norwegian Women and Cancer (NOWAC) study using both questionnaire information and record linkage information from NBCSP. METHOD: For 124,978 women aged 49-79 years from the NOWAC study, information on screened women could be cross-validated from the NBCSP database. Based on information from the NOWAC questionnaire, unscreened women were further divided into those who had mammograms taken only outside the NBCSP and those who had never had taken a mammogram. Breast cancers diagnosed in 2005-2013 were identified through linkage to the Cancer Registry of Norway; in situ or DCIS 417; invasive 2845; combined 3262. Cumulative incidence rates (CIRs) for ages 49-79 years of breast cancer were compared using the log-rank test. RESULTS: After exclusion of women with a family history of breast cancer, screened women had a CIR of 9.7% for combined breast cancer, non-significantly lower compared with unscreened women. Screened women had a 1.1% increased CIR or 13.0% increased relative risk of breast cancer diagnosis (significant) compared with women who had never had a mammogram, but for invasive breast cancer alone the difference was reduced to -0.2% (95% CI: -9.1; 8.8). Invasive breast cancers were significantly smaller (<2.5 cm) in screened versus unscreened women. There was a borderline significant decrease in lymph node positive cancer among screened (p = 0.06). CONCLUSION: The findings of no significant overdiagnosis combined with smaller tumours and less lymph node metastases suggest that the prevailing view of overdiagnosis in the NBCSP should be challenged.

Ovulatory status and menstrual cycle duration assessed by self-collection of urine on pH strips in a population-based sample of French women not using hormonal contraception.

BACKGROUND: Assessing menstrual cycle function in the general population using a non-invasive method is challenging, both in non-industrialized and industrialized countries. SUBJECTS AND METHODS: The Observatory of Fecundity in France (Obseff) recruited on a nationwide basis a random sample of 943 women aged 18-44 years with unprotected intercourse. A sub-study was set up to assess the characteristics of a menstrual cycle by using a non-invasive method adapted to the general population. Voluntary women were sent a collection kit by the post and requested to collect urine samples on pH strips, together with daily recording of reproductive-related information during a full menstrual cycle. A total of 48 women collected urine every day, whereas 160 women collected urine every other day. Immunoassays were used to measure pregnanediol-3-α-glucuronide, estrone-3-glucuronide and creatinine. Ovulation occurrence and follicular phase duration were estimated using ovulation detection algorithms, compared to a gold standard consisting of three external experts in reproductive medicine. RESULTS: Every other day urine collection gave consistent results in terms of ovulation detection with every day collection (intraclass coefficient of correlation, 0.84, 95% confidence interval, 0.76-0.98). The proportion of anovulatory menstrual cycles was 8%. The characteristics of the ovulatory cycles were length 28 (26-34), follicular phase 16 (12-23), luteal phase 13 (10-16) days median (10th-90th percentiles). DISCUSSION-CONCLUSION: Assessing menstrual cycle characteristics based on urine sample spot only collected every other day in population-based studies through a non-invasive, well accepted and cost-limited procedure not requiring any direct contact with the survey team appears feasible and accurate.

What is the care pathway of patients who undergo thyroid surgery in France and its potential pitfalls? A national cohort.

CONTEXT: The rate of thyroid cancer is increasing in France, as well as concerns about overdiagnosis and treatment. OBJECTIVES: To examine the care pathway of patients who undergo thyroid surgery in France and detect potential pitfalls. DESIGN: A large observational study based on medical reimbursements, 2009-2011. SETTING: Data from the Sniiram (National Health Insurance Information System). PATIENTS: Patients with thyroid surgery in 2010, classified into 4 groups: thyroid cancer, benign nodule, goitre or multiple nodules, other (hyperthyroidism, head-neck cancer). MAIN OUTCOME MEASURES: Medical investigations during, prior and after thyroidectomy. RESULTS: A total of 35 367 patients underwent surgery (mean age 51 years, 80% women): 17% had a reported diagnosis of thyroid cancer, 20% benign nodule, 38% goitre or multiple nodules and 25% another diagnosis. The ratio of thyroidectomies with cancer over thyroidectomies with benign nodule was 0.8 and varied across regions. In the year preceding surgery, 82% of patients had an investigation by thyroid ultrasonography, 21% thyroid scintigraphy, 34% fine-needle aspiration cytology, 40% serum calcitonin assay and 54% serum calcium assay. In the following year, all patients with total thyroidectomy and 44% of patients with partial thyroidectomy and a diagnosis of benign nodule were taking thyroid hormone therapy. 100 patients had been reoperated for a compressive haematoma and 63 died during the first month, half of whom had been operated for cancer. Mean rates of recurrent laryngeal nerve injury and hypocalcaemia (requiring blood tests plus treatments within 4-12 months) were estimated at 1.5% and 3.4%, respectively, and were higher in the cancer group (2.3% and 5.7%). CONCLUSIONS: This almost nationwide study demonstrates the suboptimal management of patients prior to thyroidectomy in France. It suggests overdiagnosis and potential harms to patients, and calls for a review of the relevance of thyroidectomy, particularly with regard to microcancers.

A new statistical method for curve group analysis of longitudinal gene expression data illustrated for breast cancer in the NOWAC postgenome cohort as a proof of principle.

BACKGROUND: The understanding of changes in temporal processes related to human carcinogenesis is limited. One approach for prospective functional genomic studies is to compile trajectories of differential expression of genes, based on measurements from many case-control pairs. We propose a new statistical method that does not assume any parametric shape for the gene trajectories. METHODS: The trajectory of a gene is defined as the curve representing the changes in gene expression levels in the blood as a function of time to cancer diagnosis. In a nested case-control design it consists of differences in gene expression levels between cases and controls. Genes can be grouped into curve groups, each curve group corresponding to genes with a similar development over time. The proposed new statistical approach is based on a set of hypothesis testing that can determine whether or not there is development in gene expression levels over time, and whether this development varies among different strata. Curve group analysis may reveal significant differences in gene expression levels over time among the different strata considered. This new method was applied as a "proof of concept" to breast cancer in the Norwegian Women and Cancer (NOWAC) postgenome cohort, using blood samples collected prospectively that were specifically preserved for transcriptomic analyses (PAX tube). Cohort members diagnosed with invasive breast cancer through 2009 were identified through linkage to the Cancer Registry of Norway, and for each case a random control from the postgenome cohort was also selected, matched by birth year and time of blood sampling, to create a case-control pair. After exclusions, 441 case-control pairs were available for analyses, in which we considered strata of lymph node status at time of diagnosis and time of diagnosis with respect to breast cancer screening visits. RESULTS: The development of gene expression levels in the NOWAC postgenome cohort varied in the last years before breast cancer diagnosis, and this development differed by lymph node status and participation in the Norwegian Breast Cancer Screening Program. The differences among the investigated strata appeared larger in the year before breast cancer diagnosis compared to earlier years. CONCLUSIONS: This approach shows good properties in term of statistical power and type 1 error under minimal assumptions. When applied to a real data set it was able to discriminate between groups of genes with non-linear similar patterns before diagnosis.

Biosocial correlates of age at menarche in a British cohort.

BACKGROUND: A large number of biosocial variables have been shown to associate with age at menarche, but the results are inconsistent and differentiate not only between countries but within countries as well. AIM: This study examined age at menarche in a British national cohort in relation to 21 biosocial and anthropometric variables. SUBJECTS AND METHODS: The analyses were based on 4483 girls from the British National Child Development Study (NCDS). RESULTS: The majority of girls reached menarche between 12-14 years of age. Girls from smaller families, those living in the East and South East, South West, West Midlands and Wales regions, in tied housing and uncrowded conditions, not sharing a bedroom, not having free school meals, whose families lived in households without financial problems had started menstruating earlier than their peers from families with lower socioeconomic status. However, when all the significant variables were analysed together significant associations remained only for mother's age at menarche, height and weight at 7 years, family size and tenure. CONCLUSIONS: The results of this study support the hypotheses that intra-uterine growth and conditions in early life as well as socio-economic background are associated with the timing of menarche and that greater childhood growth and better SES are related to earlier menarche.

A processual model for functional analyses of carcinogenesis in the prospective cohort design.

Traditionally, the prospective design has been chosen for risk factor analyses of lifestyle and cancer using mainly estimation by survival analysis methods. With new technologies, epidemiologists can expand their prospective studies to include functional genomics given either as transcriptomics, mRNA and microRNA, or epigenetics in blood or other biological materials. The novel functional analyses should not be assessed using classical survival analyses since the main goal is not risk estimation, but the analysis of functional genomics as part of the dynamic carcinogenic process over time, i.e., a "processual" approach. In the risk factor model, time to event is analysed as a function of exposure variables known at start of follow-up (fixed covariates) or changing over the follow-up period (time-dependent covariates). In the processual model, transcriptomics or epigenetics is considered as functions of time and exposures. The success of this novel approach depends on the development of new statistical methods with the capacity of describing and analysing the time-dependent curves or trajectories for tens of thousands of genes simultaneously. This approach also focuses on multilevel or integrative analyses introducing novel statistical methods in epidemiology. The processual approach as part of systems epidemiology might represent in a near future an alternative to human in vitro studies using human biological material for understanding the mechanisms and pathways involved in carcinogenesis.

Is human mating for height associated with fertility? Results from a British National Cohort Study.

OBJECTIVES: Very few studies have investigated whether spousal similarity for height is related to fertility. This study examined the relationship between mating for height and fertility after correction for spousal age, social class, education, and region. METHODS: The data used were collected as part of the British National Child Development Study and 6,535 husband-wife pairs for whom data were available on measured height, spousal age, education, social class, region, and the number of children were studied. RESULTS: Fertility varied between the regions with the highest fertility in Scotland. Fertility tended to increase from more to less educated and from higher to lower social classes in both sexes. These relationships remained significant after correction for mean age. A negative association between husband's height in relation to fertility was noted as well as the negative and the quadratic term for wife's height. Both the linear as well as the quadratic effects of parental height difference were significantly related to fertility, but after removing the effects of mean age, age difference and mean height these effects disappeared. Analysis of region, mean age, social class, education, height, and differences in age, social class, education, and height together revealed that 32.4% of variation in fertility was explained but only mean age, mean social class and mean height and difference in social class remained significant. CONCLUSIONS: The results did not provide any evidence that differential fertility was associated with spousal height difference after taking into account age, social class, education and region.

Prostate cancer outcomes in France: treatments, adverse effects and two-year mortality.

BACKGROUND: This very large population-based study investigated outcomes after a diagnosis of prostate cancer (PCa) in terms of mortality rates, treatments and adverse effects. METHODS: Among the 11 million men aged 40 years and over covered by the general national health insurance scheme, those with newly managed PCa in 2009 were followed for two years based on data from the national health insurance information system (SNIIRAM). Patients were identified using hospitalisation diagnoses and specific refunds related to PCa and PCa treatments. Adverse effects of PCa treatments were identified by using hospital diagnoses, specific procedures and drug refunds. RESULTS: The age-standardised two-year all-cause mortality rate among the 43,460 men included in the study was 8.4%, twice that of all men aged 40 years and over. Among the 36,734 two-year survivors, 38% had undergone prostatectomy, 36% had been treated by hormone therapy, 29% by radiotherapy, 3% by brachytherapy and 20% were not treated. The frequency of treatment-related adverse effects varied according to age and type of treatment. Among men between 50 and 69 years of age treated by prostatectomy alone, 61% were treated for erectile dysfunction and 24% were treated for urinary disorders. The frequency of treatment for these disorders decreased during the second year compared to the first year (erectile dysfunction: 41% vs 53%, urinary disorders: 9% vs 20%). The frequencies of these treatments among men treated by external beam radiotherapy alone were 7% and 14%, respectively. Among men between 50 and 69 years with treated PCa, 46% received treatments for erectile dysfunction and 22% for urinary disorders. For controls without PCa but treated surgically for benign prostatic hyperplasia, these frequencies were 1.5% and 6.0%, respectively. CONCLUSIONS: We report high survival rates two years after a diagnosis of PCa, but a high frequency of PCa treatment-related adverse effects. These frequencies remain underestimated, as they are based on treatments for erectile dysfunction and urinary disorders and do not reflect all functional outcomes. These results should help urologists and general practitioners to inform their patients about outcomes at the time of screening and diagnosis, and especially about potential treatment-related adverse effects.