[Role of the expert when communicating during an epidemiological alert: ethical issues].
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Biomedical subjects
Publications and source records attributed to C Leport.
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BACKGROUND: Although antibiotic prophylaxis for infective endocarditis (IE) has been recommended for persons with predisposing cardiac conditions (PCCs) for many years, its efficacy, which has not been demonstrated, has been recently challenged. To assess its usefulness, we estimated the risk of developing IE after undergoing a dental procedure for which subjects would be eligible for prophylaxis, both in subjects having (protected procedure) or not having (unprotected procedure) received antibiotic prophylaxis. METHODS: The number of French persons with PCCs, the annual number of dental procedures in which subjects would be eligible for antibiotic prophylaxis, and the number of procedures that were unprotected were estimated on the basis of a survey performed on a sample of 2805 subjects aged 25-84 years. The annual number of IE cases possibly due to an unprotected procedure was estimated on the basis of a 1-year epidemiological study of IE conducted in an area inhabited by 16 million people. RESULTS: After standardization, extrapolation of results to the age-equivalent general population (39 millions subjects) indicated the following: first, 3.3% (95% confidence interval [CI], 2.6%-4%) of the subjects had PCC, 2.7 million (95% CI, 2.3-3.2 million) of whom had undergone at least 1 at-risk dental procedures within the survey year, and the procedures were unprotected in 62% of cases; second, 37 (95% CI, 18-68; 2.7%) of the 1370 annual IE cases in France were possibly related to unprotected procedures. Thus, the risks of developing IE were estimated to be 1 in 46,000 for unprotected procedures (1 in 10,700 and 1 in 54,300 for subjects with prosthetic and native valve PCC, respectively) and 1 in 150,000 for protected procedures. CONCLUSIONS: A huge number of prophylaxis doses would be necessary to prevent a very low number of IE cases.
AIM OF THE STUDY: The aim of this work is to show to what extent a psychosocial evaluation can lead bring to comprehension of the subjectivity of Quality of Life (QoL) among HIV-infected patients. Evaluation of QoL makes it possible to understand the link between the therapeutic effectiveness and the subjective evaluation of the treatment, but also to estimate more precisely how people live and take their treatment in the context of HIV infection. METHOD: This work confronts the variation of QoL with the variation of several social and psychosocial parameters identified as of the components of the system, which is the subjective evaluation, and more precisely to a specific side effect of Highly Active AntiRetroviral Therapies (HAART): lipodystrophy syndrome that consists in body fat redistribution. This side effect could consist in an accumulation of body fat, or a loss of body fat or a combination of both symptoms. The analysis was made on the data from APROCO-COPILOTE cohort composed of HIV-infected patients initiating HAART. RESULTS: Among a sample of 706 patients follow-up for three years and with available QoL data, we identified the variations of QoL according to the variation of this specific side effect and according to gender. Results show that lipodystrophy syndrome has a determinant impact on QoL different among male and female patients. Adjusted on clinical and socio-demographic characteristics, impaired women's QoL is associated with accumulation of body fat and impaired men's QoL is associated with loss of body fat. CONCLUSION: These results underline the role of body image on subjective evaluation of QoL. The analysis of empirical data made it possible to highlight the social implication of the evaluation of QoL from the role of the social support, patient-provider relationship and the social context.
During 2 periods between 1997 and 1999, the Aproco-Copilote (ANRS CO 008) cohort enrolled all HIV-infected patients who began antiretroviral therapy containing a PI in 47 French centers and who volunteered to participate (1281 patients) in order to describe and analyze their long-term clinical course and the benefits of treatment. Complete adherence (more than 95% of drugs actually taken) during the first 4 months of therapy appears crucial in maintaining virological response to therapy over time. Adherence depends on how patients experience the treatment but also on external factors such as their relationship with physicians and social workers. Virological failures were classified in two groups: those sensitive to the PI prescribed and related to poor adherence (no detectable PI) or patients with resistance related to pharmacokinetic issues (detectable but insufficient PI levels). Between April 1997 and May 2004, 118 patients died, and 188 episodes of AIDS and 1178 other severe events were recorded. Follow-up at 5 years was estimated at 90% and the probability of progression towards a new episode of AIDS 16%. Risk of AIDS onset was greatest during the first year and declined thereafter. Severe morbidity unrelated to AIDS or the side effects of treatment was frequent and gradually predominated. The only patients for whom AIDS was the most frequent severe morbidity were those who started treatment with CD4 cell counts < 50/mm3. The cumulative probability of a serious antiretroviral-induced adverse event (mainly hypertransaminasemia) was 30% at 5 years; 2/3 of these events occurred during the first 6 months of follow-up. Factors associated with the 169 events attributed to the first PI prescribed included: plasma HIV RNA >100,000 copies/ml, increased transaminase levels, creatinine clearance <70 ml/min, HCV or HBV co-infection, and prescription of indinavir. Other studies are underway on the associated factors specific to each of the events to delineate the respective roles of the virus, the treatments and other factors.
BACKGROUND: Kaposi's sarcoma (KS) is a potentially life-threatening multifocal neoplasm. Despite the significant decline in the incidence of acquired immune deficiency syndrome (AIDS)-related KS with the use of highly active antiretroviral therapy (HAART), some patients, even those with a good immune restoration, still have aggressive disease. Liposomal anthracyclines or combination chemotherapy are widely used but adverse effects limit their utilization. OBJECTIVES: We studied the efficacy and tolerance of docetaxel in the treatment of AIDS-related KS after pretreatment with anthracycline. PATIENTS/METHODS AND MAIN OUTCOME MEASURE: A retrospective cohort study was done. Nine human immunodeficiency virus (HIV)-infected patients were treated from 1997 to 2002 with docetaxel. Tumour response was evaluated using the AIDS Clinical Trial Group (ACTG) staging criteria. Clinical and biological toxicity was evaluated. AIDS status with HIV viral load and CD4 T-cell count were measured at the beginning and at the end of the treatment. RESULTS: A major (complete or partial) response and a stabilization of the disease were demonstrated in seven and two patients, respectively. Grade 4 neutropenia and thrombocytopenia were observed in four of nine and one of nine patients, respectively. One patient died after sepsis. CONCLUSIONS: Docetaxel has a good and rapid efficacy in anthracycline-pretreated patients with severe AIDS-related KS. Phase II/III trials should be done to compare docetaxel with liposomal anthracyclines as a first-line treatment.
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To reduce the number of daily pills for improving adherence to antiretrovirals, 17 protease inhibitor-treated patients receiving toxoplasmic encephalitis (TE) standard maintenance therapy were instead given cotrimoxazole 960 mg twice daily. After a median follow-up of 31 months, one relapsed after three months, TE relapse incidence = 2.1 cases per 100 patient-years (95% confidence interval, 0.05-11.3). This strategy could be useful for patients awaiting immune reconstitution which allows the interruption of TE maintenance therapy.
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The aim of this study was to investigate factors associated with better health-related quality of life (HRQL) during the first three years after starting PI-containing antiretroviral treatment. Clinical, social and behavioural data from the APROCO cohort enabled us to analyze simultaneously the association between HRQL and patients' relationships with their health care providers. A self-administered questionnaire collected information about HRQL (MOS-SF36) and relationships with medical staff (trust and satisfaction with information). Two aggregate scores, the physical (PCS) and mental (MCS) component summaries (adjusted for baseline HRQL), were used as dependent variables in the linear regressions to identify factors associated with HRQL. We had complete longitudinal data for 360 of the 611 patients followed through M36. Factors independently associated with a high MCS were (male) gender, no more than one change in treatment, (few) self-reported symptoms and trust in the physician. Factors independently associated with high PCS levels were employment, no children, (few) self-reported symptoms and satisfaction with the information and explanations provided by the medical staff. These results underline the need to improve patient-provider relationships to optimize long-term HRQL. Socio-behavioural interventions should focus on this goal.
Whereas valacyclovir is widely used and is recommended by some authors in moderately immunocompromised HIV-infected patients, its use has not been validated by clinical studies. We report a case of herpes zoster in an HIV-infected patient for whom neurologic complication was not avoided despite valacyclovir therapy. Clinical outcome was favorable after intravenous acyclovir. This case suggests careful monitoring of valacyclovir in HIV-infected patients is necessary.
BACKGROUND: There is evidence to suggest a pharmacokinetic-pharmacodynamic relationship in HIV-infected patients receiving protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART); however, the effective trough PI plasma concentrations achieved have not been precisely determined. METHODS: The relationship between HIV viral load and concomitant PI trough plasma concentration (C(trough)) was evaluated in 101 patients receiving at least 4 months of thrice daily indinavir (IDV)-containing (n=68) or nelfinavir (NFV)-containing (n=33) HAART. The more discriminating C(trough) efficacy thresholds were determined statistically for each PI by using the raw C(trough) and the time-corrected C(trough), using the precise delay since the last PI intake and the half-life of each PI. RESULTS: For IDV (P=0.002) and NFV (P=0.019) median C(trough) levels were higher in patients with undetectable viral load [0.23 mg/L (n=30) and 2.3 mg/L (n=16) respectively] than in patients with detectable viral load [0.11 mg/L (n=38) and 0.6 mg/L (n=17) respectively]. C(trough) levels of IDV (r=-0.45; P<0.0001) and NFV (r=-0.43; P=0.011) were correlated with the concomitant viral load. The more discriminating C(trough) efficacy thresholds were estimated statistically as 0.12 mg/L for IDV and 0.5 mg/L for NFV. When C(trough) values were time-corrected, the C(trough) efficacy thresholds, 8 h after the last intake, were 0.15 mg/L for IDV and 0.65 mg/L for NFV. CONCLUSIONS: These results support the importance of achieving minimal effective C(trough) to improve the virological efficacy of PI-containing HAART, and specify the target concentrations for IDV and NFV.
New French recommendations on infective endocarditis (IE) prevention were recently published and mark a turning point in the history of antibiotic prophylaxis. Endocarditis is an evolving disease, and its clinical and microbiological profile dramatically changes over time. The French surveys that were conducted in 1991 and 1999 showed variations in underlying heart disease with a decrease in native valvular disease and an increase of IE in patients without previously known heart disease. Moreover, the distribution of responsible microorganisms dramatically changed over time, with a marked decrease of oral streptococci. In addition, some dogmas are now challenged. First of all, the part of responsibility of dental procedures is debated, as dental bacteraemia possibly responsible of endocarditis are more likely due to daily manoeuvres such as tooth brushing or chewing gum than to occasional dental procedures. Moreover, as suggested by case-control studies, efficacy--or lack of efficacy--of antibiotic prophylaxis is far from being clinically proved. For all these reasons, the proportion of theoretically avoidable endocarditis seems very low, and the benefit of largely and systematically applied antibiotic prophylaxis may be discussed, not only in terms of financial cost but also in terms of microbiological threat of emergence of antibiotic resistant bacteria. So, the general idea of those new recommendations was to maintain the principle and the modalities of antibiotic prophylaxis, but to limit its indications to situations at high benefit to risk ratio, i.e. procedures at high risk in patients at high risk. Depending on the situation, antibiotic prophylaxis may be either recommended or become optional and decision-making factors are defined. Furthermore, the importance of general prophylaxis was emphasised, concerning more specifically oral and cutaneous hygiene, and patients and practitioners' education, such as, for example, recommendations on blood cultures to be performed before any antibiotic treatment in case on fever occurring in a patient at risk during the 3 months following a procedure at risk.
BACKGROUND: We examined whether the initial virological and immunological response to highly active antiretroviral treatment (HAART) is prognostic in patients with HIV-1 who start HAART. METHODS: We analysed 13 cohort studies from Europe and North America including 9323 adult treatment-naive patients who were starting HAART with a combination of at least three drugs. We modelled clinical progression from month 6 after starting HAART, taking into account CD4 count and HIV-1 RNA measured at baseline and 6 months. FINDINGS: During 13408 years of follow-up 152 patients died and 874 developed AIDS or died. Compared with patients who had a 6-month CD4 count of fewer than 25 cells/microL, adjusted hazard ratios for AIDS or death were 0.55 (95%CI 0.32-0.96) for 25-49 cells/microL, 0.62 (0.40-0.96) for 50-99 cells/microL, 0.42 (0.28-0.64) for 100-199 cells/microL, 0.25 (0.16-0.38) for 200-349 cells/microL, and 0.18 (0.11-0.29) for 350 or more cells/microL at 6 months. Compared with patients who had a 6-month HIV-1 RNA of 100000 copies/mL or greater, adjusted hazard ratios for AIDS or death were 0.59 (0.41-0.86) for 10000-99999 copies/mL, 0.42 (0.29-0.61) for 500-9999 copies/mL, and 0.29 (0.21-0.39) for 6-month HIV-1 RNA of 500 copies/mL or fewer. Baseline CD4 and HIV-1 RNA were not associated with progression after controlling for 6-month concentrations. The probability of progression at 3 years ranged from 2.4% in the patients in the lowest-risk stratum to 83% in patients in the highest-risk stratum. INTERPRETATION: At 6 months after starting HAART, the current CD4 cell count and viral load, but not values at baseline, are strongly associated with subsequent disease progression. Our findings should inform guidelines on when to modify HAART.
In this study, we investigated the cytokine profiles of 14 treatment-naive HIV-infected patients on the initiation of highly active antiretroviral therapy (HAART). At baseline, plasma levels of TNF-alpha and its mRNA in peripheral blood mononuclear cells (PBMC) were highest in the most severely immunocompromised patients (<200 CD4+ cells/mm3). After 12 months of HAART, the virus was undetectable in the plasma of all patients (<200 copies/ml), and median CD4 T cell counts had increased (+164 cells/mm3). We also observed a gradual decrease in the number of proviral DNA copies in PBMC and in immune activation, with lower levels of IFN-gamma mRNA in PBMC associated with weaker activation of CD8+ T cells and lower levels of plasma TNF-alpha. IL-2 mRNA levels in PBMC were found to increase in parallel. The decrease in TNF-alpha and IFN-gamma levels and the increase in IL-2 production appear to be correlated with the efficacy of HAART in naive immunocompromised HIV-infected individuals.
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OBJECTIVE: We wanted to describe the epidemiological aspects of infective endocarditis (IE) in a French hospital and identify the prognostic factors. METHODS: We reviewed the clinical, echocardiographic and microbiological features, and the outcome of 89 patients (90 episodes, median age 60 years) with IE over 18 months. Logistic regression analysis was used to identify prognostic factors for death. RESULTS: A native valve was involved in 68 cases (75.5%); in 7 of these the patient was an intravenous drug user. A prosthetic valve was involved in 22 cases (24.5%); 5 of these were of early onset. Diagnosis was definite in 87% of cases. Median time to diagnosis was 3 days. Twenty-five patients (28%) were immunocompromised. A portal of entry, usually cutaneous, was identified in 65% of cases. Sixty-two percent of patients had an underlying heart disorder, usually degenerative. The infection involved the left heart in more than 75% of cases. One or more vegetations were detected in 75% of cases. The median size of vegetation was 15 mm. Isolated agents were mainly staphylococci (n=40 (44%), including 12 coagulase-negative isolates), and streptococci (n=23 (25%), including 7 enterococci). In 11 cases (12%), cultures remained negative. Nineteen episodes were nosocomial and Staphylococcus aureus was implicated in 11 of them. Fifty percent of patients had at least one complication: heart failure (n=42), kidney failure (n=44), embolism (n=35), septic shock (n=19). Surgery was performed in 49 cases (54%) due to heart failure (n=19), cerebral embolism (n=12), and/or severe valve lesions (n=27). Eighteen patients died, 10 of whom were infected with S. aureus. Nosocomial IE (P=0.0008), heart failure (P=0.004) and prosthetic valve (P=0.01), but not S. aureus were independently associated with death. CONCLUSIONS: S. aureus was the main microorganism isolated in our patients. However, it was not independently predictive of fatal outcome.
In a sample of 277 patients included in the French APROCO cohort study who were initially adherent at follow-up visit 4 months after initiation of a protease inhibitor-containing regimen, 76.4% self-reported at least one lipodystrophy-related symptom and 30.0% failed to maintain adherence behaviour 20 months after enrolment. After multiple adjustment for other related factors, such as younger age, alcohol consumption and poor housing conditions, the number of self-reported lipodystrophy symptoms was independently associated with adherence failure.
BACKGROUND: Fusobacterium septicemia with septic metastasis is a very rare and potentially serous condition when complicated by septic shock. Most cases have been described in patients with humoral immunity disorders and/or severe underlying chronic disease. CASE REPORT: A 24-year-old immunocompetent woman with a tonsil infection developed F. nucleatum septic shock with liver abscess formation. Outcome was rapidly favorable with antibiotic treatment and adapted intensive care, probably favored by the absence of an associated immune deficit. DISCUSSION: Despite its low incidence, F. nucleatum should be entertained as a possible cause of septicemia originating from a pelviperitoneal, pulmonary with abscess formation, or upper airway infection. Proper diagnosis is essential due to the risk of poor prognosis. Fusobacterium nucleatum is a commensal strictly anaerobic bacteria of the buccal cavity. It can cause dental and upper airway infections. Septicemia with secondary localization of F. nucleatum is very rare and the severity depends on the presence of associate septic shock. The immunopathological implications of these infections remain to be elucidated.