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Resume Objectif Les cancers ORL, bronchiques et œsophagiens sont principalement lies a la consommation d’alcool et/ou de tabac. L’incidence des cancers ayant les memes facteurs de risque devrait varier de facon similaire dans le temps et l’espace. Le but de cette etude etait d’identifier des groupes de cancers ayant la meme evolution spatiotemporelle. Methodes Cinquante mille neuf cent quatre-vingt cas de dix types de cancers differents ont ete recueillis entre 1982 et 2002 dans six departements francais. Les niveaux d’incidence et leur tendance evolutive ont ete analyses en utilisant un modele âge–cohorte avec un effet aleatoire qui prenait en compte l’heterogeneite entre departements. Resultats Trois groupes de cancers ayant une evolution similaire de l’incidence spatiotemporelle ont ete identifies : (1) cavite orale, oropharynx, hypopharynx, larynx, œsophage et carcinomes epidermoides bronchiques dont les incidences diminuaient uniformement ; (2) adenocarcinomes bronchiques et autres histologies bronchiques dont les incidences augmentaient uniformement ; (3) carcinomes bronchiques a grandes et a petites cellules dont l’evolution des incidences spatiotemporelles etait tres heterogene. Conclusion Par l’utilisation de methodes d’epidemiologie descriptive, differents groupes de cancers ont ete individualises. Cette diversite pourrait suggerer des latences et des sensibilites differentes vis-a-vis des carcinogenes.

French uterine cancer recordings in death certificates include 60% of "uterine cancer, Not Otherwise Specified (NOS)"; this hampers the estimation of mortalities from cervix and corpus uteri cancers. The aims of this work were to study the reliability of uterine cancer recordings in death certificates using a case matching with cancer registries and estimate age-specific proportions of deaths from cervix and corpus uteri cancers among all uterine cancer deaths by a statistical approach that uses incidence and survival data. Deaths from uterine cancer between 1989 and 2001 were extracted from the French National database of causes of death and case-to-case matched to women diagnosed with uterine cancer between 1989 and 1997 in 8 cancer registries. Registry data were considered as "gold-standard". Among the 1825 matched deaths, cancer registries recorded 830 cervix and 995 corpus uteri cancers. In death certificates, 5% and 40% of "true" cervix cancers were respectively coded "corpus" and "uterus, NOS" and 5% and 59% of "true" corpus cancers respectively coded "cervix" and "uterus, NOS". Miscoding cervix cancers was more frequent at advanced ages at death and in deaths at home or in small urban areas. Miscoding corpus cancers was more frequent in deaths at home or in small urban areas. From the statistical method, the estimated proportion of deaths from cervix cancer among all uterine cancer deaths was higher than 95% in women aged 30-40 years old but declined to 35% in women older than 70 years. The study clarifies the reason for poor encoding of uterus cancer mortality and refines the estimation of mortalities from cervix and corpus uteri cancers allowing future studies on the efficacy of cervical cancer screening.

Objectives Hospital surveillance systems have been established to monitor occupational blood exposures. We compare short-term monitoring with long-term monitoring of data analysis over 11 years and 21 institutions to identify variations in the number of reported exposures. Methods Short-term monitoring examines the current number of exposures compared to their average over previous years. Long-term monitoring detects trends over several years by various exposure characteristics (place, staff, procedure, etc) through estimating rates of change and using the best linear unbiased predictors (BLUPs) to prevent artefactual trends due to the many categories for each characteristic. Graphical representations of estimated rates help detect change and differences in rates of change. Results Annual monitoring allowed detection of significant changes in the number of reported exposures. Long-term monitoring identified moderate trends over time. The BLUP corrected the estimate of each specific annual rate of change and allowed all other rates to reduce the random variability around the mean change for more specificity. League tables showed significant increases or decreases compared to no change. League tables for two-by-two comparisons allowed reliable comparisons between estimates of the rates of change, although with spurious ranking. Funnel plots enabled quick detection of changes in trends within specified confidence intervals. Long-term trends agreed with the dominant type of annual changes over the 11 years but were not as sensitive. Conclusions The two methods have different uses. Both are helpful for assessing short-term sudden and long-term minor changes in number of exposures, possibly reflecting the success or otherwise of introducing specific safety devices or guidelines.

Objective: The present retrospective cohort study compares the long-term functional outcome, improvement or deterioration, of patients considered in a vegetative state (VS) or a minimally conscious state (MCS) 1 year after coma onset, then yearly for up to 5 years. Methods: We reviewed the clinical courses of 12 patients in VS and 39 in MCS. The outcomes were assessed at 2, 3, 4, and 5 years after injury using the 5 categories of the Glasgow Outcome Scale plus an additional category for patients in MCS. A logistic regression analysis investigated the relationships between each outcome and 10 predictor variables. Four of these variables were auditory evoked potentials recorded at the early stage of coma. Results: None of the patients in VS improved during the follow-up period: 1 was lost to follow-up, 9 died, and 2 remained in VS. Among patients in MCS, 3 were lost to follow-up, 14 died, 9 remained in MCS, and 13 emerged from MCS with severe disabilities. VS, age >39 years, and bilateral absence of cortical components of middle-latency auditory evoked potentials were significantly associated with deterioration. Conclusions: In contrast to patients in VS, a third of patients in MCS improved more than 1 year after coma onset. This emphasizes the need to define reliable boundaries between VS and MCS using repeated clinical evaluations and all imaging and neurophysiologic tools available today.

To determine the prevalence of problems with treatment adherence among type-2 diabetic patients with regards to medication, dietary advice, and physical activity; to identify the associated clinical and psychosocial factors; and to investigate the degree of agreement between patient-perceived and GP-perceived adherence.Consecutive patients were solicited during visits to 39 GPs. In total, 521 patients self-reported on treatment adherence, anxiety and depression, and disease perception. The GPs reported clinical and laboratory data and patients' adherence. A multivariate analysis identified the factors associated with adherence problems.Problems of adherence to medication, dietary advice, and physical activity recommendations were reported by 17%, 62%, and 47% of the patients, respectively. Six independent factors were found associated with adherence problems: young age, body-mass index (BMI)30 kg/m(2), glycosylated haemoglobin (HbA(1c))8%, single life, depression, and perception of medication as a constraint. Agreement between patients' and GPs' assessments of treatment problems reached 70%.In type 2 diabetes, problems with dietary advice or physical activity are far more frequent than problems with medication, and not all physicians are fully aware of patients' problems. More active listening and shared decision-making should enhance adherence and improve outcomes.

Aims Our aim was to examine intellectual development in children with congenital hemiplegia from early childhood to adolescence. Method Full-scale IQ (FIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores were measured in 32 participants (19 males, 13 females) with congenital hemiplegia at mean ages of 4 years 6 months (SD 7mo; 31 participants), 7 years (SD 6mo; 23 participants), and 14 years (SD 1y 5mo; 26 participants). Results The FIQ and VIQ scores did not change with age, but the PIQ declined significantly (0.7 points per year; p=0.004). The estimated mean (95% confidence intervals) scores in males born at term with right-sided lesions without epilepsy were FIQ 106.5 (95.29–117.74), VIQ 105.9 (95.57–116.24), and PIQ 103.7 (93.19–114.31). Those means were negatively associated with preterm birth. PIQ was negatively associated with epilepsy. VIQ increased more quickly in males and in children with right-sided lesions. Interpretation The results confirm previous findings of FIQ stability, PIQ decline, the impact of epilepsy, and the status of females with left-sided lesions, and also reveal the effect of gestational age at birth. They underline the importance of management focused on nonverbal functions and further the debate about the early lateralization of language, the ‘crowding effect’, and the difference in brain plasticity between males and females.

To illustrate the advantages of structural equation models in biomedical research using the complex example of cystic fibrosis.595 blood samples from 312 patients were tested. The model studied the effects of age, BMI and clinical condition on seven major latent variables: pulmonary function, lipid oxidation status, vitamins A and E, glutathione, carotenoids, two essential fatty acids and arachidonic acid.The model confirmed previous associations: positive (fatty acids, arachidonic acid, carotenoids and vitamins with pulmonary function and with lipid oxidation) and negative (glutathione with pulmonary function). It also verified the decrease in fatty acids during bronchial exacerbation and the increase in fatty acids and lipid oxidation after antibiotic treatment. Above all, the model revealed new positive associations between lipid oxidation and carotenoid levels and between lipid oxidation and vitamin A and E levels.Structural equations dealt easily with the great number of outcome variables of the example. They deserve a central place in biomedical issues involving too many correlated factors to help physicians and statisticians conceive biological models that best represent reality.

In Africa, HIV and feeding practices deeply affect child mortality. To prevent mother-to-child transmission, the World Health Organization recommends exclusive breastfeeding for 6 months and replacement feeding when acceptable, feasible, affordable, and sustainable. Determining the proportion and number of children saved with exclusive breastfeeding and replacement feeding is essential to design and implement crucial nationwide policies. Using data on 31 sub-Saharan countries and a decision tree for risk assessment, the authors estimated the number of children's lives potentially saved according to 6 scenarios that combine exclusive breastfeeding for 6 months or replacement feeding with 3 promotion strategies. Among all HIV-negative children born to HIV-positive mothers who die in sub-Saharan Africa per year, 52 315 (9.6%) would be saved yearly with exclusive breastfeeding versus 21 638 (4.0%) with replacement feeding. Promotion support would double these numbers (110 625 vs 45 330; ie, 20.3% vs 8.3%), and with additional prenatal group education, 132 633 versus 54 192 lives would be saved (24.3% vs 9.9%). Wherever replacement feeding is not possible, exclusive breastfeeding with promotion support and prenatal group education would save 1 of 4 exposed children. J Hum Lact . 24(2):140-149.

To study the performance of a new method designed to measure discrepancy between real prescriptions and evidence-based reference treatments.Two different indices (additive and multiplicative) are proposed to summarize deviation between prescription and reference. Deviations thought to be observed in a population of prescribers are simulated in diverse hypothetical situations in the presence or absence of evidence-based references. The performances of both indices are compared and their sensitivities to change are explored.Both indices are sensitive to variation in prescriber behaviour. The additive index allows a more accurate analysis of deviation while the multiplicative index is simpler to implement and interpret but more sensitive to change.The two deviation indices may be used as new tools in surveys or trials dealing with prescribing practices.

The present authors investigated whether cystic fibrosis is linked to a defect in fatty acids and assessed the impact of the main patients' characteristics on the levels of several fatty acids, mostly during respiratory exacerbation and after antibiotic therapy. Fatty acid phospholipid and cholesteryl ester levels were measured in stable-state patients and controls. No differences were found concerning either the fractions of palmitic and oleic acids or the cholesteryl esters of alpha-linolenic and arachidonic acids. However, phospholipids of alpha-linolenic and arachidonic acids, as well as cholesteryl esters and phospholipids of stearic and linoleic acids, were lower in patients than in controls, but fractions of dihomo-gamma-linolenic, docosatetraenoic, docosapentaenoic, palmitoleic and eicosatrienoic acids were higher. Fatty acid levels, oxidative stress markers, nutrients, body mass index and forced expiratory volume in one second (FEV(1)) were measured in patients before and after antibiotic courses for bronchial exacerbation. After adjustments, palmitic, stearic, alpha-linolenic, linoleic, arachidonic, palmitoleic and oleic acids generally decreased during exacerbation but almost all increased after antibiotic courses. Nearly all fractions increased along with FEV(1) and a positive relationship linked fatty acids to lipid hydroperoxides. There was no general drop in fatty acids. Patients' fatty acid profiles depended on the pulmonary function and the inflammation state.

BACKGROUND. In adult acute lymphoblastic leukemia, treatment results generally are expressed in terms of overall survival or disease-free survival at 3 years. In this investigation, the authors attempted to express the results in terms of the proportion of long-term disease-free survivors and in terms of lifetime in patients who developed recurrent disease or died. METHODS. Univariate and multivariate analyses were used to assess the influence of different covariates on the 2 result criteria in 922 participants in the Adult Acute Lymphoblastic Leukemia-94 multicenter trial. RESULTS. The proportion of long-term survivors was 21.5% (95% confidence interval [95% CI], 18.1–25.4%) and was higher in women than in men. The proportion decreased with increasing age, white blood cell count, and lactate dehydrogenase level. The lowest proportion was observed in patients ages 44 years to 55 years (11.4%; 95% CI, 7–17.9%) and in patients with the t(9;22) BCR-ABL karyotype (13.4%; 95% CI, 8.8–19.8%), and the highest proportion was observed in patients with the t(4;11) MLL-AF4 karyotype (31.3%; 95% CI, 18.2–48.3%). The mean expected lifetime of patients who were not cured was 11.4 months (95% CI, 9.1–14.1 months). It was longer in men than in women and was shorter with increasing age, performance status, hemoglobin level, and white blood cell count. CONCLUSIONS. The results of this study highlighted and specified the importance of some classic prognostic factors in patients with acute lymphoblastic leukemia. Cancer 2007. © 2007 American Cancer Society.

Introduction L’uveite est la manifestation oculaire la plus frequente de la sarcoidose (jusqu’a 30 % des patients). Peu d’etudes se sont focalisees specifiquement sur les uveites sarcoidosiques. L’objectif de cette etude etait de determiner les caracteristiques epidemiologiques et cliniques des uveites sarcoidosiques ainsi que la valeur diagnostique des examens biologiques et de l’imagerie. Patients et methodes Etude retrospective des donnees cliniques et paracliniques des patients presentant une uveite sarcoidosique (confirmee histologiquement), pris en charge dans 2 services de medecine interne des Hospices Civils de Lyon, entre avril 2004 et mars 2014. Resultats Les donnees de 83 patients (sexe feminin : 75 % ; caucasiens : 75 % ; âge > 50 ans : 45 %) ont ete analysees. La duree moyenne d’evolution de la sarcoidose etait de 4,8 ans (1–300 mois). L’uveite revelait la maladie dans 86 % des cas. Les caracteristiques des uveites etaient les suivantes : uveite anterieure et/ou intermediaire (37 %), posterieure (11 %), panuveite (52 %) ; uveite granulomateuse (57 %) ; uveite bilaterale (75 %) ; uveite chronique (65 %), aigue (27 %). L’etude des sous-groupes revelait que : – les caucasiens presentaient une uveite plus tardive (âge moyen : 58 vs. 41 ans ; p = 0,001) et d’evolution plus souvent chronique (78,3 vs. 43,8 % ; p = 0,01) ; – l’œdeme maculaire chronique etait plus frequent chez la femme (48,3 % vs. 14,3 % ; p = 0,01) ; – il n’existait aucune difference statistique entre les sujets âges de plus ou moins de 50 ans. Concernant les outils diagnostiques : les taux d’enzyme de conversion de l’angiotensine (ECA) et de lysozyme etaient superieurs a la normale dans 62 % et 84 % des cas testes, respectivement. La radiographie et le scanner thoracique etaient evocateurs d’une sarcoidose dans 63 % et 91 % des cas, respectivement. L’association d’au moins un test biologique a au moins un test d’imagerie permettait de porter le diagnostic de sarcoidose dans 100 % des cas. La cytoponction des adenopathies mediastinales, guidee par echographie, contribuait au diagnostic chez 7 patients dont les biopsies de glandes salivaires et transbronchique etaient negatives. Conclusion Nous rapportons ici une large serie d’uveites dans un contexte de sarcoidose histologiquement prouvee. Nos resultats confirment les differences precedemment rapportees dans les etudes americaines : les uveites sarcoidosiques etant plus volontiers granulomateuses et localisees au segment anterieur chez les sujets jeunes non-caucasiens alors que les formes chroniques posterieures sont plus frequentes chez les femmes caucasiennes, plus âgees. Les patients atteints d’uveite sarcoidosique ont au moins un test biologique (ECA ou lysozyme) ou un examen d’imagerie compatible avec le diagnostic de sarcoidose. L’indication des explorations invasives pourrait donc etre limitee aux patients qui presentent ces anomalies.

Factors able to predict overall survival in adult patients with acute lymphoblastic leukaemia were assessed according to the period since initiation of the treatment using a Cox proportional hazards model. This period covers successively an initial period during the induction treatment and a consolidation period during the postinduction treatment. From 1994 to 2002, 922 patients with acute lymphoblastic leukaemia (excluding French-American-British L3 subtype) were enrolled in a multicentre protocol and followed, with a mean follow up of 58 months. A multivariate time-segmented analysis was performed on 658 patients. Analyses of the initial (before 100 d) and the late phases were realised after stratification on the type of induction treatment and on the different treatment strategies respectively. Age was the sole factor that influenced survival during the initial phase (hazard ratio 1.48 per 10-yr increase; P

A 67-year-old man presented with myalgia, muscle atrophy, and a history of seronegative polyarthritis. Blood tests showed inflammation but no hematologic or immunologic abnormalities. Muscle biopsy revealed no vasculitis or myositis but Tropheryma whipplei was detected by polymerase chain reaction in muscle, blood, and duodenum specimens; this was confirmed by immunohistochemistry. Ceftriaxone led to clinical improvement. Although rare, Whipple's disease should be considered in the differential diagnosis of diffuse myopathy. Muscle Nerve, 2006

The objective was to design a method that considers, on clinical arguments, the likely existence of patient subgroups with different evolution profiles. The method is applied in familial adenomatous polyposis to predict the proportion of patients that would develop duodenal cancer. A subject-specific linear mixed-effects model was elaborated to explicitly model heterogeneity in regression parameters. The estimates of the parameters were obtained by Bayesian inference using Gibbs sampling. The application concerned two potential polyposis subgroups: stable-state and progressive. Each patient's score was expressed in function of his putative subgroup, the reference subgroup mean score (intercept), the rate of change (slope), and time. The estimated proportion of stable-state patients was 35%. In progressive-state patients, the estimated annual score increase was 0.38 (95% CI: 0.27-0.48). The regression model predicted that the proportion of patients with a scoreor = 9 is near 43% at age 60 (36-50%) and 50% at 70 (43-57%). The method indicates the evolution profile of each subject, which facilitates therapeutic decisions. The modelling may be extended to other more complex situations with several subgroups, with different change rates, or with various genetic or therapeutic profiles.

Steroids are nowadays routinely used as a long-term treatment in Duchenne muscular dystrophy (DMD). Their effects on body composition were assessed using Dual X-ray absorptiometry. The study followed over two years 29 genetically confirmed DMD patients: 21 in the steroid-treated group and 8 in the steroid-naive group. After two years of steroid treatment, the lean tissue mass values increased significantly ( p p =0.94) in comparison with the initial visit. In the steroid-naive patients, there were no significant increases in the lean tissue mass but deterioration in body composition confirmed by a significant increases in the percentage of body fat mass. Besides, significant negative correlations were found between the percentage of body fat mass and the MFM total score ( R =−0.79, n =76, p

International audience; OBJECTIVE: The early events of human immunodeficiency virus infection seem critical for progression toward disease and antiretroviral therapy initiation. We wanted to clarify some still unknown prognostic relationships between inoculum size and changes in various immunological and virological markers. Feline immunodeficiency virus infection could be a helpful model. METHODS: Viremia and T-cell markers (number of CD4, CD8, CD8β(low)CD62L(neg) T-cells, CD4/CD8 ratio, and percentage of CD8β(low)CD62L(neg) cells among CD8 T-cells) were measured over 12 weeks in 102 cats infected with different feline immunodeficiency virus strains and doses. Viremia and T-cell markers trajectory groups were determined and the dose-response relationships between inoculum titres and trajectory groups investigated. RESULTS: Cats given the same inoculum showed different patterns of changes in viremia and T-cell markers. A statistically significant positive dose-response relationship was observed between inoculum titre and i) viremia trajectory-groups (r = 0.80, p

Objective The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses. Methods We compared uncorrected survival estimates derived from routine program data with estimates obtained by applying six correction methods that use updated outcome data by a field survey targeting LFU patients in a rural HIV program in Malawi. These methods were based on double-sampling and differed according to the weights given to survival estimates in LFU and non-LFU subpopulations. We then proposed a correction of the survival regression analysis. Results Among 6,727 HIV-infected adults receiving ART, 9% were LFU after one year. The uncorrected survival estimates from routine data were 91% in women and 84% in men. According to increasing sophistication of the correction methods, the corrected survival estimates ranged from 89% to 85% in women and 82% to 77% in men. The estimates derived from uncorrected regression analyses were highly biased for initial tuberculosis mortality ratios (RR; 95% CI: 1.07; 0.76–1.50 vs. 2.06 to 2.28 with different correction weights), Kaposi sarcoma diagnosis (2.11; 1.61–2.76 vs. 2.64 to 3.9), and year of ART initiation (1.40; 1.17–1.66 vs. 1.29 to 1.34). Conclusions In HIV programs with high LFU rates, the use of correction methods based on non-exhaustive double-sampling data are necessary to minimise the bias in survival estimates and survival regressions.

Several molecules can interact with membrane receptors on mononuclear cells to increase intracellular levels of cyclic adenosine monophosphate (cAMP). We used the cholera toxin (CT), a cAMP elevating agent, to study the influence of this nucleotide on the production of interleukin 2 (IL-2) by human peripheral blood mononuclear cells stimulated by phytohemagglutinin and phorbol myristate acetate. Stimulated generation of IL-2 activity was inhibited by CT but not by its B subunit. The inhibition was potentiated by addition of theophylline. Therefore the synthesis and/or release of IL-2 is controlled by intracellular cAMP levels and may be modulated by agents active on this nucleotide system, such as bacterial toxins, glycoprotein hormones, or neurotransmitters.

International audience; First described in 1971, adult-onset Still's disease (AOSD) is a rare multisystemic disorder considered as a complex (multigenic) autoinflammatory syndrome. A genetic background would confer susceptibility to the development of autoinflammatory reactions to environmental triggers. Macrophage and neutrophil activation is a hallmark of AOSD which can lead to a reactive hemophagocytic lymphohistiocytosis. As in the latter disease, the cytotoxic function of natural killer cells is decreased in patients with active AOSD. IL-18 and IL-1β, two proinflammatory cytokines processed through the inflammasome machinery, are key factors in the pathogenesis of AOSD; they cause IL-6 and Th1 cytokine secretion as well as NK cell dysregulation leading to macrophage activation. The clinico-biological picture of AOSD usually includes high spiking fever with joint symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia with collapsed glycosylated ferritin (\textless20%), and abnormal liver function tests. According to the clinical presentation of the disease at diagnosis, two AOSD phenotypes may be distinguished: i) a highly symptomatic, systemic and feverish one, which would evolve into a systemic (mono- or polycyclic) pattern; ii) a more indolent one with arthritis in the foreground and poor systemic symptomatology, which would evolve into a chronic articular pattern. Steroid- and methotrexate-refractory AOSD cases benefit now from recent insights into autoinflammatory disorders: anakinra seems to be an efficient, well tolerated, steroid-sparing treatment in systemic patterns; tocilizumab seems efficient in AOSD with active arthritis and systemic symptoms while TNFα-blockers could be interesting in chronic polyarticular refractory AOSD.

Background Since the 1990s and since the development of humanised monoclonal antibodies in 1998, the treatment of non-Hodgkin lymphoma has undergone profound changes. Follicular lymphoma (FL) was the first to benefit from this treatment, and several clinical trials have shown a significant improvement in overall survival, but little information is available at a population level. Objective Our objective was to estimate changes in FL-specific mortality at a population level, with an appropriate methodology. Methods Two French retrospective population-based studies on FL were conducted, one from 1995 to 2004, in 1477 patients, and one from 1995 to 2010, in 451 patients. Trends in excess mortality rates (EMRs) according to age, sex, Ann Arbor stage and year of diagnosis were evaluated using the flexible model of Remontet et al. Results Trends in the EMR differed according to age at diagnosis and was higher in advanced stage (III, IV) in patients older than 65 yr. The EMR decreased linearly from 1995 to 2010. This decrease was more marked for advanced stages. Conclusion FL-specific mortality decreased over the years of diagnosis, and the difference according to the lymphoma stage diminished in more recent years. However, progress in the management of FL was not able to erase age-related differences.