Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case-control study.

BACKGROUND: The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D. METHODS: Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child's environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods. RESULTS: We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age. CONCLUSIONS: The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas. TRIAL REGISTRATION: Clinical-Trial.gov NCT02212522 . Registered August 6, 2014.

The causes of cancer in France.

BACKGROUND: While external factors are responsible for many human cancers, precise estimates of the contribution of known carcinogens to the cancer burden in a given population have been scarce. METHODS: We estimated the proportion of cancer deaths which occurred in France in 2000 attributable to known risk factors, based on data on frequency of exposure around 1985. RESULTS: In 2000, tobacco smoking was responsible for 23.9% of cancer deaths (33.4% in men and 9.6% in women), alcohol drinking for 6.9% (9.4% in men and 3.0% in women) and chronic infections for 3.7%. Occupation is responsible for 3.7% of cancer deaths in men; lack of physical activity, overweight/obesity and use of exogenous hormones are responsible for 2%-3% of cancer deaths in women. Other risk factors, including pollutants, are responsible for <1% of cancer deaths. Thus, known risk factors explain 35.0% of cancer deaths, and 15.0% among never smokers. CONCLUSIONS: While cancer mortality is decreasing in France, known risk factors of cancer explain only a minority of cancers, with a predominant role of tobacco smoking.

Estimation of epidemic size and incubation time based on age characteristics of vCJD in the United Kingdom.

The size of the variant Creutzfeldt-Jakob Disease (vCJD) epidemic in the United Kingdom is a major public health concern and a subject of speculation. The cases are young (mean age = 28). Assuming that the risk of developing the disease in susceptible exposed subjects decreases exponentially with age after age 15, that all infections occurred between 1980 and 1989, and that the distribution of the incubation period is lognormal, we estimate that the mean duration of the incubation period is 16.7 years [95% confidence interval (CI): 12.4 to 23.2] and that the total number of cases will be 205 (upper limit of the 95% CI: 403).

Investigating transmission in a two-wave epidemic of Chikungunya fever, Réunion Island.

An epidemic of Chikungunya fever, a mosquito-borne viral disease, spectacularly swept through Réunion Island (population 780,000) in 2005-2006. There were 3,000 cases in a first wave (March-June 2005) and more than 250,000 cases in a second (December 2005-April 2006). Adapting newly developed epidemiological tools to vector-borne diseases, we show that despite this massive difference in magnitude, the transmission potential as measured by the number of secondary cases per index case (or reproduction number), remained similar during the two consecutive waves. The best estimate for the initial reproduction number R(0) was 3.7, with a possible range from 2 to 11 depending on incubation duration and lifespan of the mosquito. We conclude that an increase in virulence between the two seasons was not necessary to explain the change in magnitude of the epidemics, and that the attack rate may be well over 50% in Chikungunya fever epidemics in the absence of intervention.

sispread: A software to simulate infectious diseases spreading on contact networks.

OBJECTIVES: We present a simulation software which allows studying the dynamics of a hypothetic infectious disease within a network of connected people. The software is aimed to facilitate the discrimination of stochastic factors governing the evolution of an infection in a network. In order to do this it provides simple tools to create networks of individuals and to set the epidemiological parameters of the outbreaks. METHODS: Three popular models of infectious disease can be used (SI, SIS, SIR). The simulated networks are either the algorithm-based included ones (scale free, small-world, and random homogeneous networks), or provided by third party software. RESULTS: It allows the simulation of a single or many outbreaks over a network, or outbreaks over multiple networks (with identical properties). Standard outputs are the evolution of the prevalence of the disease, on a single outbreak basis or by averaging many outbreaks. The user can also obtain customized outputs which address in detail different possible epidemiological questions about the spread of an infectious agent in a community. CONCLUSIONS: The presented software introduces sources of stochasticity present in real epidemics by simulating outbreaks on contact networks of individuals. This approach may help to understand the paths followed by outbreaks in a given community and to design new strategies for preventing and controlling them.

Virtual surveillance of communicable diseases: a 20-year experience in France.

Inserm has developed, since 1984, an information system based on a computer network of physicians in France. It allows for constitution of large databases on diseases, with individual description of cases, and to explore some aspects of the mathematical theory of communicable diseases. We developed user-friendly interfaces for remote data entry and GIS tools providing real-time atlas of the epidemiologic situation in any location. The continuous and ongoing surveillance network is constituted of about 1200 sentinel voluntary and unpaid investigators. We studied their motivation, reasons for either withdrawal or compliance using survival analyses. We implemented early warning systems for outbreak detection and for time-space forecasting. We conducted epidemiological surveys for investigating outbreaks. Large available time and space series allowed us to calibrate and explore synchronism of influenza epidemics, to test the assumption of panmixing in susceptibles-infectious-removed type models and to study the role of closing school in influenza morbidity and mortality in elderly. More than 250 000 cases of influenza, 150 000 cases of acute diarrheas, 35,000 patients for whom HIV tests have been prescribed by general practitioners and 25,000 cases of chickenpox have been collected. Detection of regional influenza or acute diarrhea outbreaks and forecasting of epidemic trends three weeks ahead are currently broadcasted to the French media and published on Sentiweb on a weekly basis. Age-cohort-period models assessed field effectiveness of mass immunization strategies against measles and influenza in the country. Case-control studies with more than 1200 sets of cases of acute diarrheas and their matched controls showed the role of calicivirus and rotavirus as probable major causes of gastroenteritis during recurrent widespread outbreaks in winter in France. An age-specific model for chickenpox showed the probable role of children in disease transmission to their susceptible parents or grandparents. High level of synchronism between influenza epidemics has been demonstrated, either at a regional level (in France) or between France and the USA. The designation of our lab as a WHO collaborating center for electronic disease surveillance stimulates the development of global monitoring of diseases. We developed operational systems that are now available for the global monitoring of influenza (FluNet), and human and animal rabies (RABNET). Extension of electronic syndromic surveillance is needed in the world for improving surveillance capacities and real-time response against emerging diseases.

Can a second wave of new variant of the CJD be discarded in absence of observation of clinical non Met-Met cases?

BACKGROUND: Presently, all patients with clinical variant Creutzfeldt-Jakob disease in the United Kingdom have been Met-Met at codon 129 of the PrP gene. There is much worry about the possibility of a second wave of the epidemic in the 60% of the United Kingdom population which are not Met-Met. METHODS: A mathematical model of a putative United Kingdom variant Creutzfeldt-Jakob disease epidemic that could occur in non Met-Met is derived. The risk of infection is assumed to parallel the Met-Met risk which has been previously modelled. The reason for the present absence of clinical non Met-Met cases is assumed to be a longer incubation period in these subjects than in others. The incubation period is assumed to be lognormally distributed. The means and coefficients of variation compatible with the present absence of clinical cases are systematically searched. RESULTS: We show that the present absence of clinical cases of variant Creutzfeldt-Jakob disease in the Met-Val or Val-Val population can be compatible with a second wave only if the mean incubation period is more than 25 years. The best estimates of the size of the second wave are always below 250. A fraction of these cases however will never be observed, as they will die from other causes before the onset of the new variant. CONCLUSION: The mean incubation period values compatible with the absence of non Met-Met clinical cases that we found are not implausible, and the possibility of a second wave cannot yet be ruled out. However, should this second wave occur, it would be below 250 in the worst hypothesis.

[Risk-benefit assessment of hepatitis B vaccination in France, 2006]. / Evaluer le rapport bénéfices/risques de la vaccination contre l'hépatite B en France en 2006.

PURPOSE: Rare and unexpected adverse events following hepatitis B immunization have been reported. This article aims to illustrate the risk-benefit assessment of hepatitis B immunization strategies, using the available evidence in medical literature. CURRENT EVENTS: i) Hepatitis B vaccination efficacy is high in infants, children and adolescents. It may be lower in adults and at risk populations; ii) Hepatitis B descriptive epidemiological data in France are scarce, fragmental, unprecise and changing according to the studied population strata. The incidence of symptomatic cases in the general population is below 5 per 100,000 since the year 2000. In France, it is estimated that about 300,000 adults are carriers of HBs antigen, and thus able to transmit the disease; iii) The actual French pharmacovigilance signal and the epidemiological studies may suggest the hypothesis of an association between the occurrence of central nervous system demyelinating diseases and hepatitis B vaccination. If this association exists, the relative risk is probably of less than 3. PERSPECTIVES: The lack of accuracy of risks estimates complicates the risk-benefit assessment of hepatitis B vaccination. Its perception is then influenced and distorted by subjective factors, underlying the need for research in communication about benefits and risks of immunizations. Although still debated, the hypothesis of a putative role of hepatitis B vaccine in the pathophysiology of demyelinating diseases should prompt to pursue experimental and epidemiological research to better understand the links between infectious environment and inflammatory chronic diseases.

[The evaluation of health care outcomes and hospital performance indicators]. / De l'évaluation de la qualité des soins à la performance des soins.

INTRODUCTION: The assessment of the performance of health care establishments has undergone a considerable development over the past 15 years in the United States and to a lesser extent in other developed countries. BACKGROUND: The aim of measurement of performance indicators is to improve the quality of care (outcomes), patient information and the contractual arrangements with purchasers. However, this approach poses numerous methodological problems in the choice of performance indicators as well as the collection and interpretation of data. Specific structural patterns such as social and geographic environment, research and educational assignments, are often inadequately considered. In terms of public health the impact of the publication of these measurements has not been well studied. Based on the data in the literature this revue defines the measures of hospital performance and describes the main studies, their impacts and limitations. VIEWPOINT: It seems likely that the French public authorities will, in the short term, ask health care establishments to undertake this approach. CONCLUSIONS: Complimentary studies are needed to clarify the links between performance indicators and health care outcomes.

Agreement and discrepancy in the evaluation of normal and diabetic oral glucose tolerance test.

Systematic analysis with a five-hour OGTT of 340 subjects representative of people likely to be examined in a center specialized in diabetes detection was performed by multiple discriminant analysis, which provides indices of discrimination for different sets of blood glucose (BG) values. The relative sensitivity and the relative specificity of six different diagnostic methods: Fajans and Conn, Wikerson, WHO, British Diabetic Association, UGDP, and European Study Group of Diabetes Epidemiology were computed, giving a quantitative determination for the degree of discrepancy in the definition of diabetes: only 48 per cent of the subjects are classified in the same way by any of the diagnostic criteria. The time(s) of sampling and the index or indices of OGTT which are the most efficient in screening diabetes were estimated from homogeneous groups of subjects universally recognized as nondiabetic (URND) or as diabetic (URD) according to the different diagnostic methods. Better discriminating power (DP) between URD and URND compared with the maximum DP as measured by D2 of Mahalanobis from the seven BG values of the OGTT is given by the two-hour (70.2 per cent) than by the one-hour (49.5 per cent) BG value when a single value is used; the one-two-hour BG value is the best set of two times (80.7 per cent). The different indices now in use for the classification of the OGTT have been found less effective than the weighted sum of one-two-hour BG values. The difficulty in obtaining highly specific diagnostic tests is discussed in relation to the consequences on a partly automated screening in large populations.

[Prevalence and management of heart failure in France: national study among general practitioners of the Sentinelles network]. / Prévalence et prise en charge de l'insuffisance cardiaque en France: enquête nationale auprès des médecins généralistes du réseau Sentinelles.

BACKGROUND: Epidemiological data on heart failure's epidemiology in France are scarce and mostly hospital based. The present study's objective is to estimate the prevalence of heart failure (HF) and its management, in subjects aged 60 years and older seen by the French general practitioners (GP). METHODS: A standardised questionnaire was mailed to 900 GPs of the Sentinelles network, requiring answers for any patient aged 60 years and more, seen on a randomly assigned single day of year 2002. National census and health insurance data were used to estimate prevalence. RESULTS: 434 GPs answered, reporting data for 1797 patients aged 60 years and more. The 214 patients with HF, aged 79 years on average, had been seen by a cardiologist in 95% of cases. Results of an echocardiography was available for 58% of HF patients. Compared to non-HF patients, patients with HF were significantly more dependent, more frequently requiring home visit of the GP and more frequently hospitalised (p < 0.001, age adjusted). All the 42% HF patients with a reported left ventricle ejection fraction lower than 40% were treated with an angiotensin converting enzyme inhibitor or an angiotensin receptor inhibitor. The prevalence of HF among patients aged 60 years and older was estimated at 11.9% in general practice (95% confidence interval: 10.5-13.5), and at 2.19% (1.9-2.5) in the general population. The prevalence increased with age, over 20% in persons aged 80 years and more. CONCLUSION: HF in patients aged 60 years and more seen in general practice in France is characterised by a high prevalence and medical consumption in terms of required number of hospitalisation and GP's home visit. For the GP, the diagnosis of HF relies on the cardiologist more than on an echocardiography. The therapeutic management seems to fit the actual recommendations.

Timing of mother-to-child HIV-1 transmission depends on maternal status. The HIV Infection in Newborns French Collaborative Study Group.

OBJECTIVES: To estimate when mother-to-child transmission occurs and investigate the possible role of maternal factors. DESIGN: We studied virological data obtained in the first 3 months of life of 95 infected newborns born to HIV-1-seropositive mothers included in the French Prospective Cohort Study who did not breast-feed. METHODS: Comparative Western blot analysis of sequential blood specimens from neonates and mothers with incomplete antibody patterns enabled us to detect antibody production in some infants. The results of viral investigation of neonate specimens enabled us to describe the acute phase of infection in newborns. Because the process between infection and antibody production is irreversible, we chose a Markov modelling technique, which is well suited for staged clinical processes. RESULTS: About two-thirds (65%) of the infants were considered to have been contaminated during delivery. In the remaining infants, the contamination was estimated to have occurred in utero and 95% of them had been infected less than 59 days before delivery. The association between the mother's immunological and virological status and the time of transmission was examined. The greater the degree of maternal immunodeficiency at delivery (in terms of p24 antigen and Western blot pattern) the higher the risk of in utero transmission, showing that vertical transmission is dependent on the mother's immunological status. CONCLUSIONS: These estimates should be considered when designing strategies to prevent mother-to-child transmission.

HIV antibody testing in France: results of a national survey.

Data from a knowledge, attitudes, and behavior survey conducted at the end of 1988 suggest that 13% of the population in France, aged 16 to 50 years, had been tested for HIV antibodies. Geographical differences in testing were observed, with a greater number of respondents tested in the regions where AIDS is most prevalent. Important variations in the percentage of HIV antibody-tested persons were found in relation to age, education, and occupation, but not to gender. Multiple logistic regression analysis identified significant predictors of HIV antibody testing. Behavioral predictors were multiple partners (odds ratio = 2.4), anal intercourse (odds ratio = 1.8), and drug use. A positive relationship was demonstrated between HIV testing and condom use. These correlations could indicate that the opportunity for anonymous and free testing encourages high-risk individuals to be tested.

A classification after radical cystectomy of patients with bladder cancer associated with schistosomiasis.

The aim of this study was to classify the bilharzial bladder cancer patients after radical cystectomy into several prognostic strata with increasing risk of recurrence. 310 patients through the period 1977-1983 at the National Cancer Institute of Cairo were systematically analysed for 12 variables evaluated after radical cystectomy. Eight factors were shown to have a significant influence on the recurrence-free survival curve after radical cystectomy namely: tumour stage, size, grade and location in the bladder, lymph node involvement, metastasis, renal insufficiency and urinary diversion. Using the proportional hazard model, five factors were significantly related to a lower recurrence-free survival, one major prognostic factor, tumour grade (G2 or G3) (relative risk estimate of 5.5), and four minor prognostic factors (relative risk estimates around 2), namely tumour diameter greater than 5 cm, anterior or trigonal location of the tumour, tumour stage (T3 or T4) and presence of renal insufficiency before surgery. Four prognostic strata have been defined in relation to the presence of these prognostic factors. This classification was validated on a second sample of 122 patients by comparing for each prognostic stratum, the recurrence-free survival curve observed on this sample and the corresponding predicted curve by Cox model. No statistically significant difference could be detected. This classification of bladder cancer patients appears to be adequate for bilharzial bladder cancer patients after radical cystectomy, at least in the conditions they presented and were treated for at the NIC in Cairo.

Attitude of French general practitioners to the public health surveillance of communicable diseases.

BACKGROUND: The attitude of general practitioners (GPs) to public health surveillance is not well documented, even though they furnish essential information, in particular for sentinel surveillance among the general population. METHODS: The attitude of 560 French GPs to the surveillance of 17 communicable diseases was researched. Half the GPs had previous experience in public health surveillance and the other half did not. Their motivation for belonging to a public health surveillance network and some of their demographic characteristics were also investigated. Their attitude was compared with an objective evaluation of public health surveillance priorities, based on 10 criteria. RESULTS: Primarily, GPs are interested in the surveillance of uncommon and serious diseases (HIV infection, tuberculosis, meningitis), and/or preventable ones (viral hepatitis, flu' syndrome, measles, sexually transmitted diseases), which coincides with the choices made by public health decision makers. The age of the GPs, their type of practice (urban/rural), and their participation (or not) in a surveillance network modify their priorities: in general the GPs' perception of the risks to which their patients may be exposed influences their choice of which diseases should be subject to surveillance in general medicine.

When did bovine spongiform encephalopathy (BSE) start? Implications on the prediction of a new variant of Creutzfeldt-Jakob disease (nvCJD) epidemic.

BACKGROUND: Knowing the starting date of the BSE epidemic and its size at the very beginning is crucial to interpret the timing of the nvCJD cases and to forecast the nvCJD epidemic. The first cases occurred in 1985. The models devised by Anderson (back-calculation) and Dealler (age-period-cohort) led to an estimate of less than 50 cases in 1983, and none earlier. Here, we applied age-cohort models to the BSE data in order to estimate the earliest possible date of the first unrecognized BSE cases. METHODS: The numbers of confirmed BSE cases in the UK, by age group and by calendar year from 1988 to 1996, were analysed by Poisson regression. The cases' age distribution was considered as constant between the different birth cohorts. The herd's age structure was taken into account. RESULTS: According to the models, BSE cases may have occurred as early as 1980. The expected number of cases before 1990 is almost twice the number of confirmed cases and exceeds by more than 20% the expected value of Anderson's model. The scenario of first human exposure in 1980 leads to fewer future nvCJD cases than predicted by Cousens with exposure patterns starting in 1983 or 1985. CONCLUSION: The first birth cohort available, consisting of two cases older than 10 in 1988, does not allow any projections before 1980. Moreover, confidence intervals are wide and the power of the study is limited by the great dispersion of the data; the precision of the estimations would be improved by considering geographical incidence. Nevertheless, our projections are consistent with Wilesmith's survey of rendering plants relating the emergence of BSE to the dramatic fall in the proportion of meat and bone meal following solvent extraction, initiated in the late 1970s (65% in 1977 to 10% in 1983).

Monitoring the compliance of sentinel general practitioners in public health surveillance: which GPs persevere?

OBJECTIVES: This study was undertaken to develop a novel approach to measure compliance of general practitioners (GPs) in sentinel public health surveillance. More specifically, its purpose was to determine the characteristics in the SGP's profile which can be objectively associated with perseverance. METHODS: Since 1984, the French sentinel network has collected weekly data on eight communicable diseases, involving volunteer SGPs. In this study, 'compliance' was defined as the length of time during which a SGP complies with a given theoretical surveillance protocol. This left-censored variable was computed from individual SGP's connection time series. Kaplan-Meier method was used to estimate the compliances survival distribution for all the SGPs (1824 SGPs who have been part of the network, at one point, or another, since 1984). Using Cox regression model, a prospective survey on the 376 most recent recruits allowed us to select the characteristics associated with a longer compliance. Sensitivity analyses were carried out using the bootstrap method. RESULTS: According to the maximum number of silences allowed by the given theoretical protocol, median compliances varied between 11.7 (95% CI: 11.1-12.3) and 38.8 (95% CI: 35.7-40.7) months. In multivariate analyses we observed long compliances for SGPs whose main motivation for being involved in the network was an interest in epidemiology and SGPs with < or = 5 or > or = 20 years seniority. On the other hand, interest in local epidemiological surveys and previous experience with other surveillance networks were associated with short compliances. We found no statistical association between compliance and computing experience, having a medical secretary, a particular feeling of being a 'public health actor', or the desire to belong to a GPs' network. CONCLUSION: We have shown our longitudinal method to be an efficient tool for monitoring non-compliant SGPs with respect to given surveillance protocols. Furthermore, this approach allows us to select out of the SGPs' profile the characteristics which are associated with a longer compliance. This regression model could be further refined by extending the SGPs' profile. The additional variables to be taken into account in this profile could be identified through a complementary sociological approach. Our work addresses the question of understanding what determines the motivation of GPs to participate in public health surveillance. This question is essential if we hope to turn general practice information systems into genuine public health surveillance tools.

Estimation of the size of the HIV/AIDS epidemic due to blood transfusion in France.

BACKGROUND: This study presents estimates of the number of individuals contaminated by human immunodeficiency virus (HIV) via a blood transfusion received in France before the end of 1991 and those who have developed or will develop AIDS. METHODS: The computer simulation model takes into account several possible hypotheses concerning the annual number of infected blood donations collected before the introduction of HIV screening in August 1985, those collected between August 1985 and December 1991 not excluded by the testing procedure due to the seroconversion period, the number of labile blood components elaborated from one donation, the 5-year mortality rate of blood recipients, and the incubation delay. RESULTS: Results reproducing the evolution of the reported annual number of transfusion-associated AIDS cases were selected which enabled the estimation of the number of recipients infected (between 3300 and 4300) and of the number of transfusion-associated AIDS cases (between 1600 and 1800) compared with 1300 transfusion-associated AIDS cases reported by June 1993. CONCLUSION: This methodology could be used for other countries provided information required by the model is available.

Epidemiological survey of a major outbreak of nosocomial legionellosis.

Forty-seven nosocomial cases of legionellosis due to Legionella pneumophila serogroup 1 were diagnosed in one major outbreak from November 1982 to March 1983 in a 960-bed teaching hospital. Contaminated water was considered to be a possible source of infection because, during that period, monthly samples were found to be positive with averages of 10(4) CFU/l. After chlorination of hot water associated with flushing of outlets, nearly all samples taken in the next two years were found to be negative. A case-control study was performed to examine potential risk factors. Three groups of controls were randomly selected among eligible patients. In a multivariate analysis, only three clinical factors were found to be associated with legionellosis patients: malignant illness (relative risk, RR = 3.5), presence of an ultimately fatal disease (RR = 2.6), and exposure to corticosteroids prior to admission (RR = 7.9). Investigations of in-hospital exposures suggest that during this nosocomial outbreak diagnostic or therapeutic respiratory procedures had not increased the risk of illness. Although the epidemiological association between water contamination and disease remains unclear, the eradication of L. pneumophila from the identified supply seems to have been effective in preventing disease in this hospital.

Six years of public health surveillance of measles in France.

Data provided by the Sentinel General Practitioners (SGP) to the French Communicable Diseases Computer Network (FCDN) have been used to present the epidemiological characteristics of measles observed during a 6-year period in France. The estimated annual incidence rates per 100,000 population were 376 in 1985, 603 in 1986 and 983 in 1987, then declined during the following 3 years to 297, 258, and 263 per 100,000 population in 1988, 1989 and 1990 respectively. There is a marked seasonal change with a high early summer peak. The mean age among the cases for the 6 years of study varied from 5.4 to 6.0 years. There is an increase in the percentage of cases with a past history of measles vaccination, from 6.7% in 1985 to 12.8% in 1990. This increase may be interpreted as a consequence of a substantial increase of the vaccine coverage during the same period.