[Evaluation of the lifetime of nail markings during polio vaccinations in Chad]. / Évaluation de la durée de vie des marquages sur l'ongle pendant les vaccinations polio au Tchad.

BACKGROUND: SID (Supplemental Immunization Days) is a special strategy intended to accelerate eradication of poliomyelitis in countries where it is still endemic (India, Afghanistan, and Pakistan in Asia, and Nigeria in Africa). This strategy is also applied in Nigeria's neighbours (Cameroon, Chad, Niger and Benin). Since the poliomyelitis virus was imported from Nigeria in 2001, Chad has reported cases of poliomyelitis every year. After 30 SIDs in Chad and the inaccurate or false attribution of side-effects to polio vaccines, some groups persistently refuse polio vaccination. To ascertain the true coverage of SID, the Ministry of Health and several partners (WHO, UNICEF and Rotary) conduct external coverage evaluations, to identify the under-vaccinated areas where population may be refusing immunization. The nails of the children receiving vaccinations are marked with indelible ink and those markings are the best indicator of the area's actual SID coverage. When coverage investigators arrive and propose vaccination to all children not immunized during SID, mothers who wish to refuse vaccination may claim that the children's markings disappeared after a few days, due to bathing. WHO experts have found that markings applied to their own nails with the WHO-recommended markers persist a few weeks, but others suggested that the markings may disappear much faster among children living in a traditional tropical environment. Until now, the lifetime of these markings has not been tested among children in Africa. OBJECTIVES: To determine the lifetime of the fingernail markings after SID and factors that influence this lifetime in children young than 5 years old in Chad. MATERIALS AND METHODS: This prospective cohort study of 200 children (aged 0 to 59 months) took place from March to May 2009 in Milezi, a health zone north of Ndjamena, the capital of Chad, in central Africa. These children received nail markings on their left little finger with an indelible marker pen provided by WHO. The finger was monitored for 35 days, visually and by photographs, to determine the factors associated with the lifetime of the markings. Kaplan-Meier and log-rank methods were applied to estimate their survival curve and the variables significant for their lifetime; the Cox proportional hazard model was used to determine multivariable-adjusted hazard ratios. RESULTS: Of the 184 children surveyed through the end of the study, the markings disappeared after 35 days of follow-up for 35% of them. The average lifetime of markings on these children was 28 days (SD: 4.95) and was associated, according to the Cox model, with 3 variables: the quality of the marking (RR = 0.335, 95% CI: 0.182-0.617, p < 0.001), playing with soil or mud (RR = 0.38, 95% CI: 0.208-0.697, p = 0.002), and living in different blocks, after stratification for the variable of application of chemical products on the nail. The latter could not be included in the Cox model because it made the markings disappear instantly. CONCLUSION: WHO experts were right in stating that the lifetime of the markings was sufficient to estimate coverage accurately when external evaluation takes place one or two weeks after SID. The only action found to make markings disappear rapidly was the application of chemical products. Mothers who tell SID attendance evaluation teams that the marking disappeared with bathing are expressing a tacit refusal of vaccination. These evaluations, which take place well before the disappearance of markings, help to determine the precise coverage of SID.

Deprivation and mass screening: Survival of women diagnosed with breast cancer in France from 2008 to 2010.

BACKGROUND: Some studies have investigated the role of socio-demographic inequalities in the association between screening and survival. However, in France, no study has been conducted to describe the socio-demographic characteristics and survival of women with breast cancer based on their participation to mass screening. The aim of this study was to assess the impact of socio-demographic inequalities on the association between participation in mass screening program and survival of women with breast cancer. METHODS: Data for 2,244 women aged 50-74 years diagnosed with breast cancer over the period 2008-2010 were obtained from the cancer registry and the screening structure of Gironde. We used the aggregated European Deprivation Index (EDI) to define the deprivation level of women. Net survival rates were estimated with the Pohar-Perme method, with and without correcting for lead-time bias. RESULTS: Survival rates were lower for non-attenders than for screen-detected women (83.8% vs 97.3%, p < 0.0001), even after correcting for lead-time bias. Among the most deprived women, the survival rate was significantly different between non-attenders and screen-detected women (78.1% vs 95.6%, p = 0.0002), suggesting an important effect of mass screening in this group. CONCLUSION: The introduction of incentive actions in deprived areas could play a key role in the adherence of women to mass screening and in improving their survival in case of a breast cancer diagnosis.

Arterial stiffness predicts severe progression in systemic sclerosis: the ERAMS study.

OBJECTIVE: The ERAMS study addressed the value of arterial stiffness in predicting the severity of systemic sclerosis. METHODS: ERAMS was a prospective multicentre cohort study including patients with definite systemic sclerosis. Arterial stiffness was measured by the standardized non-invasive QKd 100-60 method. Clinical evaluation, biological measurements, functional respiratory tests and cardiac Doppler echography were performed at inclusion then each year until 3 years' follow-up was completed. Progression was defined as mild (articulations, muscle, oesophagus or skin involvement) or severe (lung, heart or kidney involvement) by a critical event committee. The prediction of severe progression was studied for QKd 100-60 as well as clinical and biological data at baseline by univariate and multivariate analysis. RESULTS: Ninety-nine patients were included (81 women, 18 men, mean age 57 years, standard deviation 12.5). Although their blood pressure profile was normal, half the patients had increased arterial stiffness (QKd 100-60<200 ms). There was a significant relationship between age-adjusted arterial stiffness and decrease in carbon dioxide diffusion (P<0.03) or haemoglobin rate (P<0.01). By univariate analysis, severe progression after 3 years was predicted by age (P=0.04), lung involvement (P=0.04), diffusion of lung carbon oxide (DLCO) (P<0.01), skin score (P=0.02), haemoglobin (P<0.01) and baseline Qkd 100-60 divided into two classes according to the median (P<0.01). By multivariate analysis, only haemoglobin rate [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.2-0.9] and QKd 100-60 (OR 19.6, 95% CI 1.2-308.2) predicted severe progression of systemic sclerosis. CONCLUSION: The measurement of arterial stiffness by the QKd method is a useful objective method for assessing the prognosis of systemic sclerosis independently from other data.

Evidence-based medicine: basic principles / Principes de l'evidence-based medicine

Evidence-based medicine : basic principles. The clinical judgment of health professionals is improving over the time of experience, but they need to keep their medical knowledge up to date. Yet, practitionners are inundated by an exponentially increasing biomedical literature, whom quality is questioned. Evidence-based medicine (EBM) provides a useful framework by integrating the best available clinical evidence from systematic research with individual clinical expertise and the patient's values and situation for the sake of clinical decision making. The practice of EBM involves five steps. The first one starts from a real case and aims at formulating a simple clinical question structured in the « PICO ¼ format: patient (P) profile, intervention (I), comparator (C) and outcome (O) of interest. The second step consists in locating the available evidence through a literature search focusing primarily on pre-evaluated articles or synthesis (Cochrane). The third step is a critical appraisal of the best available evidence for validity, importance and usefulness of the results for the current patient. The fourth step combines the evidence with the clinical judgment and patient's values and preferences. Once the exercise is completed for a specific patient, the fifth step consists in rating one's performance to keep updated. Clinical questions can be formulated in 4 main areas of case management: diagnosis, treatment, prognostic or etiology. This article presents an example in the area of treatment. The EBM approach is important for the development of practitionners' abilities to find, critically appraise and incorporate the best scientific evidence for the benefit of their patients.

Principes de l'evidence-based medicine. Le jugement clinique s'améliore avec l'expérience, mais les connaissances de chaque praticien doivent être régulièrement mises à jour. Or la quantité d'articles biomédicaux publiés continue de croître à un rythme très soutenu, alors que leur qualité suscite de sévères critiques. L' evidence-based medicine (EBM), ou, en français, « la médecine fondée sur les faits ¼, consiste à intégrer les meilleures données de la littérature biomédicale, à la compétence et l'expérience cliniques du praticien et aux valeurs et à la situation du patient, pour prendre une décision clinique. La pratique complète de l'EBM comprend 5 étapes. La première étape consiste à formuler une question clinique en précisant 4 composantes : le patient, l'intervention, le comparateur, et l'événement clinique d'intérêt. La deuxième étape consiste à trouver les meilleures données disponibles, en particulier les articles pré-évalués ou les synthèses (Cochrane). La troisième étape procède à une analyse critique du meilleur article identifié, à l'évaluation de l'importance des résultats et de son utilité pour le patient. La quatrième étape combine les meilleures données au jugement clinique et aux valeurs et préférences du patient. Une fois la démarche d'EBM terminée pour un patient spécifique, la cinquième étape consiste, pour le praticien, à évaluer ses propres performances. Pour résoudre un cas clinique, un praticien formule de nombreuses questions nécessitant des informations valides dans 4 champs principaux : le diagnostic, le traitement, le pronostic ou l'étiologie. Un exemple dans le champ thérapeutique illustre la démarche. La démarche d'EBM est importante pour permettre aux praticiens de développer leurs aptitudes à trouver, analyser de manière critique, et inclure dans leurs pratiques les meilleures données scientifiques disponibles, au bénéfice des patients.

Association of apolipoproteins C3 and E with metabolic changes in HIV-infected adults treated with a protease-inhibitor-containing antiretroviral therapy.

OBJECTIVE: To examine the relationship between plasma levels of apolipoproteins C3 (APOC3) and E (APOE) and the presence of lipid and carbohydrate metabolism abnormalities or clinical signs of lipodystrophy in HIV-1-infected patients started with a protease-inhibitor-containing antiretroviral therapy. METHODS: The Aproco (Antiproteases Cohort) Study enrolled 1,181 HIV-1-infected adults in 47 French healthcare centres from May 1997 to June 1998. From December 1998 through July 1999, the APROCO-Metabolic Complications (APROCO-MC) cross-sectional study was performed at the month 20 visit for those patients enrolled in 1997 and at the month 12 visit for those enrolled in 1998. The current analysis presents results from a subset of patients who had undergone additional tests to measure APOC3 and APOE in order to study their relationship with metabolic syndrome (n=157) and abnormal results in an oral glucose tolerance test (n=135). RESULTS: Increases in triglycerides and non-high-density lipoprotein (HDL) cholesterol were associated with significantly higher levels of APOC3, in both Lp B (lipoproteins containing apolipoprotein B) and Lp non-B (lipoproteins free of apolipoprotein B), and a significant higher level of APOE Lp B. APOC3 and APOC3 Lp non-B were increased when glucose metabolism abnormalities were more severe. The presence of a metabolic syndrome was associated with increased plasma APOC3, APOC3 Lp B and APOC3 Lp non-B levels. In a multiple regression analysis, high levels of APOC3 in Lp B and APOC3 Lp non-B were associated with the presence of clinical signs of lipodystrophy, even after adjustment for triglycerides and HDL-cholesterol levels. CONCLUSIONS: Lipid and/or glucose metabolism abnormalities in treated HIV-1-infected patients are associated with increased levels of APOC3 and, to a lesser extent, APOE plasma concentrations. Increased values are also related to clinical signs of insulin resistance and lipodystrophy.

Is hepatitis C virus co-infection associated with survival in HIV-infected patients treated by combination antiretroviral therapy?

OBJECTIVE: To study whether hepatitis C virus (HCV) co-infection or the severe elevation of transaminases is associated with survival after the initiation of antiretroviral combination therapy. DESIGN: Prospective hospital-based cohort (Aquitaine Cohort). METHODS: HIV-infected adults started on an antiretroviral combination before 30 June 1999. HCV infection was defined as antibody detection or positive HCV RNA. Severe elevation of transaminases was defined as a value of aspartate or alanine aminotransferase (AST, ALT) above five times the upper limit of normal values. Survival was studied using a Cox model, including at least baseline HCV status and transaminases as a time-dependent covariate. RESULTS: Overall, 995 patients were analysed, including 576 HCV-positive individuals (58%). At baseline, HCV-positive patients were younger, more often injecting drug users and women, and had more frequently elevated transaminases. A shorter survival was associated with AIDS stage [hazard ratio (HR) versus non-AIDS 1.67; 95% confidence interval (CI) 1.03; 2.68], lower CD4 cell count (HR for 50 cells/mm3 lower 1.33; CI 1.17; 1.51), lower haemoglobin (HR for 1 g/dl lower 1.20; CI 1.07; 1.35), lower platelet count (HR for 10 000 cells/mm3 lower 1.04; CI 1.01; 1.07), and AST during follow-up (HR for > or = 200 IU/l 2.30; CI 1.32; 4.03). HCV co-infection (HR 1.20; CI 0.75; 1.92) was not statistically associated with survival. CONCLUSION: The occurrence of a severe elevation of transaminases was associated with poorer survival, although HCV was not. If liver toxicity may be treatment induced, plasma drug concentrations could guide dosage adjustments of antiretroviral treatments currently prescribed to optimize their use.

Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy.

Morphologic and metabolic changes associated with protease inhibitor (PI) therapy have been reported since the introduction of PIs for treatment of human immunodeficiency virus infection. These changes were measured 12-20 months after initiation of PI therapy in a cross-sectional study involving 614 patients from the Antiprotéases Cohorte (APROCO) Study (Agence Nationale de Recherches sur le Sida-EP11). The prevalence was 21% for isolated peripheral atrophy, 17% for isolated fat accumulation, 24% for mixed syndrome, 23% for glucose metabolism alterations, 28% for hypertriglyceridemia (triglyceride level, > or =2.2 mM), and 57% for hypercholesterolemia (cholesterol level, > or =5.5 mM). Age was significantly associated with different phenotypes of lipodystrophy and metabolic alterations, but body-mass index, CD4(+) cell count, and type of nucleoside reverse-transcriptase inhibitor or PI received were not constantly associated with these changes. Furthermore, in all models tested, exposure to stavudine was associated with lipoatrophy and exposure of ritonavir was associated with hypertriglyceridemia. Detection and management of these disorders should be implemented to prevent further complications.

Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population.

The distribution of risk factors for cardiovascular disease in patients aged 35-44 years who were treated for human immunodeficiency virus type 1 (HIV-1) infection was compared with that for a population-based cohort. HIV-1-infected men treated with a protease inhibitor-containing regimen (n=223), compared with HIV-1-uninfected men (n=527), were characterized by a lower prevalence of hypertension, a lower mean high-density lipoprotein cholesterol level, a higher prevalence of smoking, a higher mean waist-to-hip ratio, and a higher mean triglyceride level. No difference was found for total plasma or low-density cholesterol levels, nor for the prevalence of diabetes. Similar trends were observed among female subjects. The predicted risk of coronary heart disease was greater among HIV-1-infected men (relative risk [RR], 1.20) and women (RR, 1.59; P<10(-6) for both), compared with the HIV-1-uninfected cohort. The estimated attributable risks due to smoking were 65% and 29% for HIV-1-infected men and women, respectively. Because most HIV-1-infected people will ultimately need antiretroviral therapy, risk factors for cardiovascular disease should be determined at the initiation of treatment, and interventions should be considered for all patients who have them.