[Evaluation of management of patients under clean intermittent catheterization by general practitioners]. / Évaluation de la prise en charge des patients sous sondage intermittent propre par les médecins généralistes.

INTRODUCTION: Clean Intermittent Catheterization (CIC) is the method of choice for bladder emptying in patients having bladder emptying disorders, acquired or pharmacologically induced, whether it is neurologically related or not. The aim of this study is to assess the theoretical and practical knowledge of general practitioners (GP) on CIC. MATERIALS: Observational prospective study (anonymous online questionnaire) was conducted with 224 GP between March and April 2020. Each physician had to complete a questionnaire about the definition of CIC, its indications and usage, the indications of urine culture, antibiotic therapy, and the complications of this method of drainage. RESULTS: Only 18.3% of GP that took part in the study gave an exact definition of CIC. As to the importance of it, 67.9% responded that it protects the upper urinary tract and 37.1% that it prevents urinary tract infections (UTI). Fifty-two per cent of physicians were unaware of the regular frequency at which it should carry out a day. Fifty eight percent prescribed sterile gloves and 57.1% an antiseptic. UTI was considered as the main complication of CIC by 87.1% of physicians and 35.7% requested a systematic urine culture for patients under CIC. For patients with an asymptomatic bacteriuria, 65.6% of GP prescribed antibiotic therapy. CONCLUSION: GP need to improve their knowledge of SIP, its framework, indications, modalities, and the way to deal with colonization or urinary tract infection. This will improve the management of impacted patients.

Is there an optimal sampling time and number of samples for assessing exposure to fast elimination endocrine disruptors with urinary biomarkers?

In studies investigating the effects of endocrine disruptors (ED) such as phthalates, bisphenols and some pesticides on human health, exposure is usually characterized with urinary metabolites. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment. This study was conducted to assess variability of urinary metabolites of ED, and to investigate how sampling time and number of samples analyzed impacts exposure assessment. Urine samples were collected over 6 months from 16 volunteers according to a random sampling design, and analyzed for 16 phthalate metabolites, 9 pesticide metabolites and 4 bisphenols. The amount of biomarkers excreted in urine at different times of the day were compared. In parallel, 2 algorithms were developed to investigate the effect of the number of urine samples analyzed per subject on exposure assessment reliability. In the 805 urine samples collected from the participants, all the biomarkers tested were detected, and 18 were present in >90% of the samples. Biomarkers variability was highlighted by the low intraclass correlation coefficients (ICC) ranging from 0.09 to 0.51. Comparing the amount of biomarkers excreted in urine at different time did not allow to identify a preferred moment for urine collection between first day urine, morning, afternoon and evening. Algorithms demonstrated that between 10 (for monobenzyl (MBzP) phthalate) and 31 (for bisphenol S) samples were necessary to correctly classify 87.5% of the subjects into quartiles according to their level of exposure. The results illustrate the high variability of urinary biomarkers of ED over time and the impossibility to reliably classify subjects based on a single urine sample (or a limited number). Results showed that classifying individuals based on urinary biomarkers requires several samples per subject, and this number is highly different for different biomarkers.

Can atmospheric pollutants influence menstrual cycle function?

A few experimental studies suggest that atmospheric pollutants could affect the endocrine system, and in particular stress hormones and the hypothalamic-hypophyseal-ovarian axis, which could in turn influence menstrual cycle function. We aimed to study the possible short-term effects of atmospheric pollutants on the length of the follicular and luteal phases and on the duration of the menstrual cycle in humans. To do so, from a nation-wide study on couples' fecundity, we recruited 184 women not using contraception who collected urine samples at least every other day during one menstrual cycle, from which a progesterone metabolite was assayed, allowing estimation of the duration of the follicular and luteal phases of the cycle. Atmospheric pollution (nitrogen dioxide and particulate matter with an aerodynamical diameter below 10 µm, PM10) levels were estimated from a dispersion model with a 1-km resolution combined with permanent monitoring stations measurements, allowing to estimate exposures in the 30-day, 1-10 and 11-30-day periods before the start of the menstrual cycle. Regression models allowed to quantify the change in cycle duration associated with atmospheric pollutants and adjusted for potential confounders. Follicular phase duration increased on average by 0.7 day (95% confidence interval, CI, 0.2; 1.3) for each increase by 10 µg/m3 in NO2 concentration averaged over the 30 days before the cycle and by 1.6 day (95% CI, 0.3; 2.9) for each increase by 10 µg/m3 in PM10. There was no strong evidence of associations of exposures in this time window with luteal phase or with total menstrual cycle durations (p > 0.2). Exposures in the 1-10 day period before the cycle start were also associated with increased follicular phase duration. This study is one of the first prospective studies to suggest short-term alterations in follicular phase duration following atmospheric pollutants exposure.

A human huntingtin SNP alters post-translational modification and pathogenic proteolysis of the protein causing Huntington disease.

Post-translational modifications (PTMs) are key modulators of protein function. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin (HTT) gene. A spectrum of PTMs have been shown to modify the normal functions of HTT, including proteolysis, phosphorylation and lipidation, but the full contribution of these PTMs to the molecular pathogenesis of HD remains unclear. In this study, we examine all commonly occurring missense mutations in HTT to identify potential human modifiers of HTT PTMs relevant to HD biology. We reveal a SNP that modifies post-translational myristoylation of HTT, resulting in downstream alterations to toxic HTT proteolysis in human cells. This is the first SNP shown to functionally modify a PTM in HD and the first validated genetic modifier of post-translational myristoylation. This SNP is a high-priority candidate modifier of HD phenotypes and may illuminate HD biology in human studies.

Epigenetics as a mechanism linking developmental exposures to long-term toxicity.

A variety of experimental and epidemiological studies lend support to the Developmental Origin of Health and Disease (DOHaD) concept. Yet, the actual mechanisms accounting for mid- and long-term effects of early-life exposures remain unclear. Epigenetic alterations such as changes in DNA methylation, histone modifications and the expression of certain RNAs have been suggested as possible mediators of long-term health effects of environmental stressors. This report captures discussions and conclusions debated during the last Prenatal Programming and Toxicity meeting held in Japan. Its first aim is to propose a number of criteria that are critical to support the primary contribution of epigenetics in DOHaD and intergenerational transmission of environmental stressors effects. The main criteria are the full characterization of the stressors, the actual window of exposure, the target tissue and function, the specificity of the epigenetic changes and the biological plausibility of the linkage between those changes and health outcomes. The second aim is to discuss long-term effects of a number of stressors such as smoking, air pollution and endocrine disruptors in order to identify the arguments supporting the involvement of an epigenetic mechanism. Based on the developed criteria, missing evidence and suggestions for future research will be identified. The third aim is to critically analyze the evidence supporting the involvement of epigenetic mechanisms in intergenerational and transgenerational effects of environmental exposure and to particularly discuss the role of placenta and sperm. While the article is not a systematic review and is not meant to be exhaustive, it critically assesses the contribution of epigenetics in the long-term effects of environmental exposures as well as provides insight for future research.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Cumulative incidence rate of medical consultation for fecundity problems--analysis of a prevalent cohort using competing risks.

STUDY QUESTION: What is the incidence of medical consultation for fecundity problems in the French population, taking into account pregnancy occurrence and resumption of contraceptive use?. SUMMARY ANSWER: Considering the occurrence of a pregnancy and resumption of use of contraception as competing risks, the cumulative incidence rate of medical consultation for fecundity problems was 9.0% [95% confidence interval (CI): 6.5%; 11.9%] after 12 months of unprotected intercourse and 12.2% [95% CI: 9.6%; 15.3%] after 24 months. WHAT IS KNOWN ALREADY: Estimates of the prevalence of medical consultation due to involuntary infertility among couples who have sought a pregnancy for more than 12 months range from 25 to 50%. Most of the studies however are limited by retrospective data collection, without considering the duration of time since the beginning of the period of unprotected intercourse (PUI) and without considering medical consultation for fecundity problems as a competing risk. STUDY DESIGN, SIZE, DURATION: This study is based on the Observatory of Fecundity in France survey, a population-based probability survey designed to estimate the frequency of involuntary infertility on a nationwide basis and to explore the associations with environmental factors. Women answered two telephone questionnaires, the first at the time of enrolment in 2007, the second at follow-up 1 year later. The current analysis was performed among a subsample of 6577 women recruited before or during a PUI and followed-up for 1 year. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study sample comprised 940 women aged 18-44 years who had a PUI between the time of enrolment and the 1-year follow-up, and who had not consulted a physician for fecundity problems for the current PUI prior to enrolment. Women reported all the medical consultations they had because of difficulties becoming pregnant during the current PUI. The date of each consultation was carefully assessed. In France, women can consult a gynaecologist directly without referral by their general practitioner. The occurrence of a pregnancy and resumption of contraceptive use were considered as informative censoring events, using a competing risk model. MAIN RESULTS AND THE ROLE OF CHANCE: Using the competing risk survival model, the cumulative incidence rate of first consultation was 9.0% [95% CI: 6.5%; 11.9%] 12 months after the start of the PUI and 12.2% [95% CI: 9.6%; 15.3%] after 24 months. The Kaplan-Meier method, which does not take competing risks into account, yielded substantially higher estimates: 26.0% [95% CI: 18.8%; 32.5%] at 12 months and 56.8% [95% CI: 44.2%; 66.6%] at 24 months. Among the 219 women who had attempted to become pregnant for at least 12 months, cumulative incidences of first medical consultations were 28.2% [18.7-38.9%] 24 months after the start of the PUI, and 31.2% [21.3- 42.4%] after 36 months. The rates were higher among nulliparous but non-nulligravid women, followed by nulligravid women, as compared with parous women. Age was not strongly related to the occurrence of medical consultation. LIMITATIONS, REASONS FOR CAUTION: The main limitation of this study is the number of women lost to follow-up (29.7%). In addition, results regarding the absence of an age effect should be taken with caution as few women in our study were aged over 35 years. Although such an attrition rate is commonly observed in prospective studies in the general population, it could have induced a selection bias that may have led to an underestimation of the rates of medical consultation. Sensitivity analyses, using the inverse probability weighting method suggest that our results are unlikely to be biased. WIDER IMPLICATIONS OF THE FINDINGS: This study reveals frequencies of medical consultation for fertility problems, which, after considering competing events such as pregnancy in a relevant statistical model, are lower than generally reported in the literature. The results also indicate the existence of a difference between the potential need and the actual use of medical care for fecundity problems. This suggests a need for studies to look for factors other than medical recommendations that may play a role in the patterns of medical seeking behaviours for fecundity problems, such as women's reproductive history, socio-economic characteristics or accessibility to infertility services. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by grants from ANR (French Agency for Research, SEST call on Environmental and Occupational Health), ANSES (French Agency for Food, environmental and Occupational Health Safety, EST call on Environmental and Occupational Health), InVS (French Institute for Public Health Surveillance). The team of Environmental Epidemiology applied to Fecundity and Reproduction has been funded by an AVENIR grant from Inserm (2007). Authors declare no conflict of interest.

[Impact of chemical and physical environmental factors on the course and outcome of pregnancy]. / Impact des facteurs environnementaux physiques et chimiques sur le déroulement et les issues de grossesse.

We review the epidemiological literature on the possible impact of chemical and physical factors on pregnancy outcome. Effects of in-utero exposures on child health are not considered here. The highest levels of evidence concern the effects of passive smoking (on fetal growth), of lead (pregnancy-induced hypertension, fetal growth), of some Polychlorinated Biphenyls (PCB; on fetal growth) and, to a lesser extent, of atmospheric pollutants (on fetal growth and preterm delivery). For the other compounds, in particular non-persistent chemicals, the literature, which is generally based on poor exposure assessment, is less informative. In conclusion, the last decades have witnessed the development of mother-child cohorts in which exposure biomarkers have been assayed, allowing a large number of publications. For some persistent compounds, for which efficient exposure assessment approaches have been used, the literature indicates a likely impact on pregnancy outcomes. With the exception of air pollutants, the literature on non-persistent compounds is little conclusive; the assay of exposure biomarkers in repeated biological samples collected at relevant time points could help further increase knowledge regarding any health impact.

Estimation of the frequency of involuntary infertility on a nation-wide basis.

BACKGROUND: Assessing couple fecundity on a nation-wide basis without excluding couples who eventually remain infertile is challenging. Our aim was to describe couple fecundity (in terms of frequency of involuntary infertility) among the general population living in France. METHODS: We used a current-duration design. A random sample of 64 262 households was selected in 2007-2008, allowing us to identify 15 810 women aged 18-44 years. Eligible women (n= 1089) were those having regular sexual intercourse with a male partner, not using any method of contraception and not having delivered in the previous 3 months. These women reported information on the current duration of unprotected intercourse (CDUI, the time elapsed between the start of the period of unprotected intercourse and the time of inclusion in the study). The CDUI distribution was used to estimate the frequency of involuntary infertility, using a newly developed statistical technique that does not require couples to be followed up until the end of the period of unprotected intercourse. RESULTS: CDUI was defined for 867 women. An estimated 46% of couples had no detected pregnancy conceived during the first 6 months of unprotected intercourse [95% confidence interval (CI), 36-56%]. The proportions of couples with no detected pregnancy within 12 and 24 months were 24% (19-30%) and 11% (8-14%), respectively. CONCLUSIONS: These results constitute one of the few descriptions of the fecundity of a nation-wide representative sample of couples from the general population, not limited to couples who eventually conceived or to those resorting to medical help.

Influence of fetal and parental factors on intrauterine growth measurements: results of the EDEN mother-child cohort.

OBJECTIVE: In small-for-gestational-age neonates, parental and fetal characteristics can be used to distinguish between constitutionally small size and growth restriction, which is associated with a higher risk of morbidity and mortality. The aim of this study was to quantify relationships of parental and fetal characteristics with fetal ultrasound measurements. METHODS: The EDEN mother-child cohort included 2002 pregnant women with singleton pregnancies attending one of two university hospitals. Data from two routine ultrasound examinations for fetal biometry were recorded, at 20-25 and 30-35 weeks of gestation. Biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and estimated fetal weight (EFW) were studied as a function of prepregnancy maternal body mass index (BMI), maternal height, paternal height, fetal sex and gestational age. RESULTS: Data were obtained at the first scan from 1833 women and at the second scan from 1752 women. Parental anthropometric characteristics were significantly associated with ultrasound measurements at both scans. Maternal BMI was more strongly associated with AC and EFW, whereas both maternal and paternal height were more strongly associated with FL. An association was also found between fetal sex and all ultrasound measurements other than FL. CONCLUSION: Maternal and paternal anthropometric characteristics are significantly associated with ultrasound measurements in mid to late pregnancy. These relationships provide support for the use of these characteristics in ultrasound fetal size reference charts.

Malformative uropathies and kidney transplantation.

INTRODUCTION: Malformative uropathies are a frequent cause of end-stage renal disease (ESRD) requiring renal replacement therapy (RRT). Medical management of urinary tract infections and advances in surgical reconstruction procedures resulted in good outcomes of kidney transplantation among these patients. The aim of this article was to describe the epidemiological profiles and outcomes of patients who underwent transplantation for ESRD related to malformative uropathies. PATIENTS AND METHODS: Among 493 kidney recipients at our center from 1986 to 2009, 47 had malformative uropathies as the cause of ESRD. We retrospectively studied the incidence of acute rejection episodes, acute tubular necrosis, as well as patient and graft survivals, comparing these results to those observed in patients without malformative uropathies using chi-square tests for qualitative parameters and nonpaired Student t tests for continuous variables. Log-rank tests were used for comparisons of survival curves. RESULTS: The 47 patients, representing 9.53% of our kidney transplant recipients, included 27 men and 20 women (sex ratio=1.35) with an overall mean age of 27.6±9.1 years (range, 10-49). The common etiology was vesico-ureteral reflux (78.7%). Hemodialysis was the main RRT modality (68%) with a median duration of 41 months. Also, 82.9% of patients received transplants from living donors. Acute tubular necrosis occurred in 4 of these (8.5%) versus 22.06% of the other patients (P=.03). Acute rejection episodes were observed in 13 of these patients (27.6%) versus 23.1% of the other patients (P=not significant [NS]). After a cumulative follow-up period of 3744 months (median, 41.8 months), 5 patients had died (1.6 death/y/100 patients) and 5 had lost their allografts and returned to dialysis (1.6 case/y/100 patients). Graft survival rates at 1, 5, and 10 years were 97.8%, 93.2%, and 79.9%, which were comparable with 95.9%, 87.6%, and 78.9% among the other patients, respectively (P=NS). Patient survival rates at 1, 5, and 10 years were 100%, 88.5%, and 82.6% versus 96%, 87.6%, and 79.6%, respectively (P=NS). CONCLUSION: Kidney transplantation in patients with malformative uropathies is increasingly frequent. The incidence of acute rejection episodes as well as patient and graft survivals were comparable with those of subjects without malformative uropathies.

Identifying adult asthma phenotypes using a clustering approach.

There is a need to improve asthma characterisation by integrating multiple aspects of the disease. The aim of the present study was to identify distinct asthma phenotypes by applying latent class analysis (LCA), a model-based clustering method, to two large epidemiological studies. Adults with asthma who participated in the follow-up of the Epidemiological Study on the Genetics and Environment of Asthma (EGEA2) (n = 641) and the European Community Respiratory Health Survey (ECRHSII) (n = 1,895) were included. 19 variables covering personal characteristics, asthma symptoms, exacerbations and treatment, age of asthma onset, allergic characteristics, lung function and airway hyperresponsiveness were considered in the LCA. Four asthma phenotypes were distinguished by the LCA in each sample. Two phenotypes were similar in EGEA2 and ECRHSII: active treated allergic childhood-onset asthma and active treated adult-onset asthma. The other two phenotypes were composed of subjects with inactive or mild untreated asthma, who differed by atopy status and age of asthma onset (childhood or adulthood). The phenotypes clearly discriminated populations in terms of quality of life, and blood eosinophil and neutrophil counts. The LCAs revealed four distinct asthma phenotypes in each sample. Considering these more homogeneous phenotypes in future studies may lead to a better identification of risk factors for asthma.

Short- and long-term outcomes of living donors in Tunisia: a retrospective study.

Despite initiatives to increase cadaveric donation, there is still a shortfall in donor organs. Kidneys from living donors now makes a significant contribution to increasing the number of organs available for transplantation in Tunisia. We performed a retrospective study of 405 kidney transplantations, including 321 (79.3%) from living donors performed from June 1986 to December 2007. We obtained information on only 162 (50.4%), namely, 64 men (39.5%) and 98 women (60.5%), whose mean age at the time of donation was 42.3 ± 12.2 years. Twelve (8.22%) perioperative complications occurred: wound infections (n = 4), pneumothorax (n = 4), phlebitis (n = 1), hematomas (n = 2), and urinary infection (n = 1). The mean follow-up period was 117.4 ± 74.4 months. Hypertension occurred in 42 donors (25.9%) with mean values of 134 ± 20 for systolic and 79 ± 10 for diastolic blood pressure. Twelve donors (7.4%) developed proteinuria (mean proteinuria, 0.08 ± 1.25 g/d). Renal insufficiency was found in 28 donors (19.44%), 2 of whom developed chronic renal failure requiring dialysis at intervals of 36 and 84 months. In both cases, we diagnosed a familial form of focal segmental glomerulosclerosis. Two donors (1.2%) died within 10 years after kidney donation due to senility. The relatively favorable outcomes suggest that living-donor kidney transplantation is an acceptable approach, in view of the superior results it yields in recipients. However, efforts to increase the number of cadaveric donors in Tunisia should be made. It is also important to develop a registry of long-term kidney function after kidney donation.

[Submaximal exercise capacity and quality of life in exclusive water-pipe smokers]. / Aptitude aérobie sous-maximale et qualité de vie des fumeurs exclusifs de narguilé

BACKGROUND: It is well known that oxidative stress is increased significantly by regular water-pipe smoking (WPS). This could lead to muscle dysfunction and thus to impairments of exercise and quality of life (QOL). Considering the impressive number of WP smokers, we intend to investigate the potential effect of WPS on submaximal exercise capacity and QOL. AIMS: (1). To evaluate the submaximal exercise capacity by the 6-minutes walking test (6-MWT). (2). To compare the deficiency, incapacity and QOL data of exclusive WPS with those of two control groups (never smokers and exclusive cigarette smokers). (3). To determine the factors influencing the 6-minutes walk distance (6-MWD) of WPS subjects. METHODS: A multicentre study including 180 exclusive WPS [> or =5 WP-year] men aged > or =40 years. Cigar or cigarette smoking, contraindications to the 6-MWT or cortico-steroid therapy will be exclusion criteria. QOL evaluation, spirometry, electrocardiogram and two 6-MWT will be performed. Signs of exercise impairment will be: 6-MWD< or =lower limit of normal, end of walk dyspnoea > or =5/10, haemoglobin saturation fall > or =5 points. Data from WPS subjects will be compared with those from 90 never smoking subjects and 90 exclusives cigarettes smokers. EXPECTED RESULTS: (1). WPS will affect significantly the submaximal exercise capacity. (2). Resting spirometric, 6-MWT and QOL data of exclusive WPS subjects will be significantly reduced compared to never smoking subjects. (3). The 6-MWD's of exclusive WPS subjects will be significantly influenced by cumulative WP consumption, by resting spirometric data, by obesity and by physical activity score.

Prenatal mercury contamination: relationship with maternal seafood consumption during pregnancy and fetal growth in the 'EDEN mother-child' cohort.

Maternal seafood intake is of great health interest since it constitutes an important source of n-3 fatty acids, but provides also an important pathway for fetal exposure to Hg. The objective of the present study was to determine associations between Hg contamination and both maternal seafood consumption and fetal growth in French pregnant women. Pregnant women included in the 'EDEN mother-child' cohort study answered FFQ on their usual diet in the year before and during the last 3 months of pregnancy, from which frequencies of seafood intake were evaluated. Total hair-Hg level was determined for the first 691 included women. Associations between Hg level, seafood intake and several neonatal measurements were studied using linear regressions adjusted for confounding variables. The median Hg level for mothers was 0.52 µg/g. Maternal seafood intake was associated with Hg level (r 0.33; P < 0.0001). There was no association between Hg level and fetal growth in the whole sample of women, except for an early negative relationship with biparietal diameter. A positive association was found between seafood intake and fetal growth in overweight women only which remained unchanged after adjustment for Hg level (birth weight: +101 g for a difference of 1 sd in seafood consumption; P = 0.008). Although seafood intake was associated with Hg contamination in French pregnant women, the contamination level was low. There was no consistent association between Hg level and fetal growth. Taking into account Hg level did not modify associations between seafood intake and fetal growth.

[Evaluation of the deficiency and the submaximal exercise capacity in obstructive sleep apnoea patients]. / Exploration de la déficience et de l'incapacité des patients atteints d'un syndrome d'apnées hypopnées obstructives du sommeil.

BACKGROUND: In addition to excessive daytime somnolence, exercise limitation is a likely consequence of the cardiorespiratory problems that occur in patients who have obstructive sleep apnoea (OSA). However, few studies have evaluated the aerobic capacity of this patient group. AIMS: To evaluate submaximal exercise capacity over the 6-minute walking test (6-MWT). To determine the factors that influence 6-minutes walking distance (6-MWD). INCLUSION CRITERIA: 120 consecutive patients with severe OSA treated by continuous positive airway pressure who were medically stable will be included. EXCLUSION CRITERIA: 6-MWT contraindications, orthopaedic or rheumatologic diseases likely to influence walking capacity and corticosteroid therapy. INVESTIGATIONS: polysomnography, electrocardiogram, plethysmography, and two 6-MWT's. Indicators of impaired exercise capacity: stops during the walk, 6-MWD less than or equal to predicted lower limit of normal, end walking dyspnoea greater than or equal to 5/10, oxygen saturation fall greater than or equal to five points, end walking heart rate less than or equal to 60 % maximal predicted. Data from our obese patients aged 40-60 years old will be compared with data from 45 age-matched obese subjects free from OSA. EXPECTED RESULTS: OSA will significantly affect the submaximal exercise capacity and will accelerate the ageing of the cardiorespiratory-muscle chain. Submaximal exercise capacity of obese subjects having OSA, compared to subjects free from OSA, will be significantly deteriorated. 6-MWD of OSA patients will be significantly influenced by: resting plethysmographic data, apnoea hypopnoea index, arterial hypertension, obesity or smoking histories.

Reproductive life events in the population living in the vicinity of a nuclear waste reprocessing plant.

OBJECTIVE: There is concern about the health of populations living close to nuclear waste reprocessing plants. A comparative study was conducted on reproductive life events in the general population living near the nuclear waste reprocessing plant in Beaumont-Hague, France and a reference area in Brittany. DESIGN, SETTING AND PARTICIPANTS: Women were randomly selected and retrospectively questioned on reproductive life events occurring between 1985 and 2000. The monthly probability of pregnancy (assessed by time to pregnancy for pregnancy attempts leading or not to a live birth), occurrence of involuntary infertility, miscarriage and birth weight were compared between both areas using regression models with random effect. RESULTS: Compared with the reference area (326 couples) and after adjustment for sociodemographic and behavioural factors, couples from Beaumont-Hague (857 couples) had an estimated hazard ratio of pregnancy of 1.19 (95% CI 0.89 to 1.58). The prevalence ratio of 12-month involuntary infertility was 0.99 (95% CI 0.64 to 1.55) and the odds ratio of miscarriage was 0.86 (95% CI 0.85 to 1.33) for Beaumont-Hague, compared with the reference area. Mean birth weight was similar in both areas (95% CI of difference -85 g to 53 g). CONCLUSION: No increased risk of adverse reproductive life events was highlighted in the population living in the vicinity of the French nuclear waste reprocessing plant, compared with the reference area. Reproductive health is unlikely to be strongly altered in the general population of Beaumont-Hague.

The impact of a decline in fecundity and of pregnancy postponement on final number of children and demand for assisted reproduction technology.

BACKGROUND: Over the past decades, the proportion of couples who resort to infertility treatment has tremendously increased, and fertility (the final number of children) sharply declined. We explored the roles of two potential causes of these trends: a temporal decline in the couples' fecundability and a postponement of age at initiation of pregnancy attempts. METHODS: We conducted a Monte-Carlo simulation for the reproductive history of 100,000 women based on the fertility and socio-demographic characteristics of the 1968 birth cohort in France. Declines in fecundability of various amplitudes have been implemented, as well as increases in the distribution of age at initiation of pregnancy attempts. RESULTS: A decline in fecundability by 15% implied a decrease in fertility by 4%, and an increase in the proportion of couples eligible for infertility treatments by 73%. An increase in the mean age at initiation of first pregnancy attempt by 2.5 years from 25 years entailed a decrease by 5% in fertility and an increase by 32% in the proportion of couples eligible for infertility treatments. CONCLUSION: A relatively important decrease in fecundability and an increase by 2.5 years in age at first pregnancy attempt are likely to have only a limited impact on fertility. However, they may have a large impact on the proportion of involuntarily infertile couples, likely to resort to assisted reproduction techniques.

[Breakthroughs in the study of the influence of environmental factors on male reproductive health]. / Nouvelles avancées dans l'etude de l'influence de l'environnement sur la santé reproductive masculine.

BACKGROUND: An important part of the research effort on male reproductive health focus on two important questions: on the one side, that of the temporal deterioration of male reproductive health and, on the other head, that of the influence of exposure to environmental chemicals during intra-uterine life on health during childhood and adulthood. The concepts on endocrine disruption and testicular dysgenesis syndrome make a link between these two questions. METHODS: This work examines knowledge cumulated over the last couple of years concerning geographical and temporal variations in male reproductive health and the testicular dysgenesis syndrome. Recent results concerning the concept of endocrine disruption and on the environmental influences on male reproduction are presented, as well as on the transgenerational effects on environmental factors on the health of male children. CONCLUSIONS: Based on clinical and epidemiological data, and with the use of in vitro animal models as well as observations in wildlife, research in this field has enabled progress in the elucidation of mechanisms of action and characterization of environmental influences on male reproductive health.