[Incidence and reasons of premature discontinuation of abacavir: results of a hospital investigation among 628 patients]. / Incidence et motifs des arrêts prématurés de l'abacavir au cours des deux premiers mois de traitement: résultats d'une enquête hospitalière chez 628 patients.

OBJECTIVE: The aim of this study was to determine the incidence of abacavir discontinuation within the first two months of treatment and the link with a true hypersensitivity reaction (HSR). PATIENTS AND METHODS: A retrospective study was made between January 1998 and January 2006 on a cohort of HIV positive patients treated by abacavir delivered by the Bordeaux Saint-André University Hospital pharmacy. RESULTS: Six hundred (and) twenty-eight patients were included. The reasons for non-renewal of abacavir prescription within the first three months of treatment were investigated. Early discontinuation for adverse effects was reported in 32 patients (5.1%): proved diagnosis of HSR (N=10), uncertain diagnosis of HSR (N=8), and no HSR (N=14). The decision for discontinuation was taken by physician after consultation in 76% of cases.

The adherence to antiretroviral treatment evaluated from a hospital pharmacy: importance of the protease inhibitors pharmacological class.

The goal of this study was to develop an evaluation method of antiretroviral treatment adherence from a hospital pharmacy and to identify one or more factors that influenced this adherence, such as patient or treatment characteristics. The HIV patients included in this study were based, for the major part, in Saint-André hospital and collected their medication from this hospital pharmacy. They were all delivered a renewable prescription that should have comprised two successive delivery stamps. A total of 186 patients was included. For the adherence analysis, the delay between two successive deliveries was measured. We have specified three different categories of patients: adherent, non-adherent and intermediate, according to a definition of adherence accepted by many authors. We have demonstrated that the only antiretroviral therapeutic class associated with poor adherence was the protease inhibitors, in particular nelfinavir, which requires food to be taken at the time of administration. This can pose difficulties for those patients who lunch at their workplace and consequently affect adherence. This study allowed us to demonstrate that a less subjective adherence evaluation can be easily carried out from a hospital pharmacy.

[Efficacy and safety of pegylated-interferon plus ribavirin in HIV-infected patients co-infected with hepatitis C virus in clinical practice: a 32 cases observational follow-up]. / Efficacité et tolérance de l'association interféron pégylé-ribavirine chez les patients co-infectés VIH-VHC en pratique clinique: étude observationnelle de 32 patients.

OBJECTIVE: To describe efficacy and safety in clinical practice of pegylated interferon plus ribavirin (INFpeg-Riba) in the treatment of hepatitis C viral infection (HCV) in HIV infected patients. METHODS: Monocentric retrospective study with inclusion of all patients who received at least once INFpeg-Riba before April 1st 2003. All patients were followed up to six months after the end of HCV therapy. RESULTS: Thirty two HIV-positive patients (23 men and 9 women) with chronic hepatitis C treated by INFpeg-Riba were included. The mean age was 43 years. Fourteen patients carried HCV genotype 2 or 3 (43 %) and 18 patients carried genotype 1 or 4 (57%). The Metavir score of fibrosis showed fibrosis F1 (N =3), F2 (N =14), F3 (N =7) and F4 - cirrhosis (N =8). Twenty six patients (81%) were naive for anti hepatitis C drugs. Thirty one per cent of patients were at AIDS stage and 84% were receiving antiretroviral drugs. The mean CD4 cell count was 469 /ml and the plasma RNA HIV was less than 50 copies /ml in 57% of the cases. Adverse events leading to reduction of dose of drugs occurred in 40% and adverse events leading to discontinuation treatment occurred in 12%. A decline of CD4 cell count <200 CD4/ml was observed in 15%. Clearance of HCV-RNA in end of treatment was seen in 46 % and sustained virological response in 34 %. The main predictors of sustained virological response were HCV genotype 2 or 3 (P =0.04) and plasma HIV RNA less than 50 copies/ml (P =0.001). The predictive value of good virological response of a CD4 cell count >350/ml before treatment was very near the statistical significancy (p =0.07). CONCLUSIONS: The efficacy of pegylated interferon plus ribavirin in HIV-HCV co-infected patients is disappointing mainly due to a poor tolerance. In addition to HCV genotype, plasma HIV RNA level and CD4 cell count were essential to predict INFpeg-Riba response and should be taken into account in the process leading to the initiation of such therapy in HIV-HCV co-infected patients.

Risk factors for lactic acidosis in HIV-infected patients treated with nucleoside reverse-transcriptase inhibitors: a case-control study.

A case-control study was undertaken to determine risk factors for lactic acidosis in human immunodeficiency virus-infected patients treated with nucleoside reverse-transcriptase inhibitors (NRTIs). From May 1996 to June 2000, 9 patients with lactic acidosis (defined as a plasma lactic acid level of >5 mM and plasma pH of <7.38) were identified. Control patients were randomly selected from among a large cohort of patients who initiated a dual NRTI regimen in 1996 or after. Two factors were associated with an increased risk of lactic acidosis: first, a creatinine clearance of <70 mL/min before lactic acidosis (OR, 15.8 [range, 3.0-86.5], P<10(-4)), and, second, a low nadir CD4+ T lymphocyte count before the inception of NRTI therapy (OR, 8.4 [range, 1.2-infinity], P=.03). The total cumulative exposure to NRTIs was not associated with an increased risk of lactic acidosis, nor was the cumulative exposure to any of the 4 NRTIs studied. According to these results, monitoring of creatinine clearance, especially in patients with a low nadir CD4+ T lymphocyte count, could lead to modifications in antiretroviral therapy in order to diminish the risk of occurrence of lactic acidosis.

[Severe lactic acidosis in HIV-infected patients treated with nucleosidic reverse transcriptase analogs: a report of 9 cases]. / Acidose lactique sévère chez les patients infectés par le VIH traités par inhibiteurs nucléosidiques de la reverse transcriptase : 9 cas.

PURPOSE: Symptomatic lactic acidosis requiring intensive care is a rare and severe adverse event related to the mitochondrial toxicity of the nucleoside analog reverse transcriptase inhibitors (NRTIs). METHOD: We retrospectively investigated the clinical and biological features of HIV-infected patients who developed severe lactic acidosis syndrome at the University teaching hospital of Bordeaux and the regional community hospital, during 1996-2000. RESULTS: Nine patients were identified (incidence: 0,9/1000 NRTI treated patient-years), 4 men and 5 women with a median age of 36 years. They had a moderate immunodeficiency (median CD4+ T lymphocyte counts: 197/mm(3)) and only one of them presented a virological failure. The causes of hospital admission were abdominal pain (n = 6), dyspnea (n = 6), asthenia (n = 5), jaundice (n = 4), and vomiting (n = 2). Hepatomegaly was present in 6 patients. Lactic acidosis was found in all cases: median pH: 7.28, bicarbonate: 12 mmol/l, anion gap: 27 mEq/l, plasma lactic acid: 13 mmol/l. Cytolysis (n = 8), cholestasis (n = 6), hepatic failure (n = 4), rhabdomyolysis (n = 4) and pancreatitis (n = 2), were also present. Despite medical intensive care, seven patients died. The only two post-mortem examinations revealed severe hepatic steatosis. Median duration of NRTI therapy was 4 years. At presentation, five patients were receiving lamivudine, five didanosine, four stavudine and three zidovudine. Six patients were coinfected by HCV and/or HBV, four had chronic renal failure and five an immediately preceding infectious disease. CONCLUSION: The prognosis of lactic acidosis is severe. Nucleosid-analog therapy needs clinical and biological monitoring, specially in patients with comorbidities.

A cohort study of nevirapine tolerance in clinical practice: French Aquitaine Cohort, 1997-1999.

We performed a retrospective study to evaluate, under routine circumstances, the tolerance and immunovirological changes associated with antiretroviral regimens that contain nevirapine in 137 patients (88% were antiretroviral experienced). During a mean follow-up of 11 months, 33% of patients reported side effects attributed to nevirapine, and 21% discontinued treatment because of poor tolerance. Administration of antihistamines or corticosteroids at the initiation of treatment was not protective against adverse events (relative risk, 0.82; 95% confidence interval, 0.49-1.38). The proportion of patients with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection who had alanine aminotransferase levels of >100 IU/L increased from 19.4% at baseline to 42.9% at month 12 of follow-up (P=.02). We noticed a significant increase of the proportion of patients with total cholesterol levels of >5.5 mM (P=.02). We have shown that there is a high level of discontinuation of nevirapine therapy in clinical practice and that side effects were not prevented by administration of antihistamines or corticosteroids. Coinfection with HCV or HBV increased the risk of hepatotoxicity, which lead to the cautious use of nevirapine for such patients.

Sarcoidosis-associated hepatitis C virus infection.

Although several reports of sarcoidosis have been reported in hepatitis C virus (HCV)-infected patients treated with interferon-alpha, this association has never been described in nontreated HCV patients. We report two cases of sarcoidosis associated with chronic hepatitis C infection. The patients developed multivisceral sarcoidosis (cutaneous, lungs, nodes) at two and at least six years after the presumed date of infection. One patient obtained remission of sarcoidosis with corticosteroid treatment but the other remained corticodependent. The levels of hepatic enzymes were not significantly modified throughout the course of corticosteroid therapy. In conclusion, these case reports suggest that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system. It could be of interest to test for HCV infection all patients diagnosed with sarcoidosis and to watch over every treated or nontreated hepatitis C infected patient for the development of granulomatous lesions.

Prognostic score of short-term survival in HIV-infected patients admitted to medical intensive care units.

A retrospective cohort was set up to identify prognostic factors associated with in-hospital survival in HIV-infected patients admitted to medical intensive care units (MICUs), from 1991 to 1994. Survival from MICU admission to hospital discharge (or in-hospital fatal issue) was estimated and a prognostic score at MICU admission was developed. One hundred and thirty patients were recruited of whom 20% were AIDS-free prior to admission. In-hospital mortality rate was 65%. Median survival was 20 days. The following variables were predictive of mortality: Simplified Acute Physioloy Score II (SAPS II): (hazard ratio [HR]=1.5 for 10 points higher, P<10(-3)), time between HIV diagnosis and admission >5 years (HR=2.7, P<10(-4)), hypoalbuminaemia (HR=1.2 per 5 g/l lower, P=0.03). The prognostic score developed was: SAPS II+25 (if time between HIV diagnosis and MICU admission >5 years) albuminaemia (g/l). A new prognostic score including SAPS II, prior HIV history and albuminaemia better reflected the in-hospital mortality than SAPS II alone. Our findings may still be useful to better evaluate the immediate prognosis of current HIV-infected patients admitted to MICU, particularly those naive to antiretroviral therapy or in treatment failure.

The absence of hyperbilirubinaemia is highly predictive of treatment failure in advanced HIV-infected patients treated with indinavir.

In order to determine prognostic factors associated with treatment failure (TF) in advanced HIV-infected patients treated with a regimen including indinavir, a prospective cohort study of 80 patients was set up between 1 March and 31 December 1996. TF time was calculated using the Kaplan-Meier method, from treatment induction to the first of the following events: treatment modification for adverse event or lack of significant virological and/or immunological response, AIDS-defining diagnosis or death. Date of point was 31 December 1998. Multivariate analysis was performed using a Cox model. At baseline, 60% of the patients were AIDS-free, median viral load and CD4+ count were respectively 4.8 log/ml and 79/microl. After a median follow-up of 26 months, 70% of the patients experienced a TF in a median time of 8 months. Seventy-two per cent presented an hyperbilirubinaemia (>2 mg/dl). In multivariate analysis, initial AIDS stage (hazard ratios [HR]=1.94, P=0.04) and digestive intolerance (HR=2.32, P=0.003) were predictive of TF. Conversely, hyperbilirubinaemia was associated with a better outcome (HR=0.35, P<0.0001). These 2 latter parameters very likely reflected patients' treatment compliance.

Relationships between cholesterol, apolipoprotein E polymorphism and dementia: a cross-sectional analysis from the PAQUID study.

This study assesses the cross-sectional relationship between serum cholesterol level and dementia, controlling for apolipoprotein E (apoE) genotype, in a nested case-control study of 334 elderly French subjects aged 73 and over who participated in the PAQUID study (37 demented subjects and 297 nondemented controls). A diagnosis of dementia was established by two-step screening: (1) psychometric testing and DSM-III-R criteria and (2) neurologist's confirmation. Cholesterol, its fractions and apoE genotype were determined from a blood sample. Elevated high-density lipoprotein cholesterol was associated with a significantly decreased risk of dementia, independent of apoE status and other potential confounding variables, suggesting that cholesterol fractions could be involved in both Alzheimer's disease and vascular dementia.

Reduced parathyroid functional mass after successful kidney transplantation.

BACKGROUND: Chronic uremia is responsible for secondary hyperparathyroidism (HPT II). Parathyroid secretion usually tends to normalize after kidney transplantation (KT), but the parameters of the reversibility of HPT II remain poorly defined, particularly the intrinsic mechanisms underlying the improvement of parathyroid function. METHODS: The kinetic functional parameters of the ionized calcium (iCa)/parathormone (PTH) relationship curve were studied in 11 patients with mild to moderate HPT II one and six months after successful KT. Hypercalcemia and hypocalcemia were induced, respectively, by CaCl2 and Na2-ethylenediaminetetraacetic acid (Na2-EDTA) infusions. RESULTS: The mean glomerular filtration rate remained stable during follow-up. Basal PTH decreased from 195 +/- 54 pg/ml before KT to 70 +/- 12 pg/ml six months later (P < 0. 005). During the tests, mean PTH levels decreased significantly between the two measured times for all iCa levels, indicating an improved parathyroid function. An analysis of the kinetic parameters of the curves showed significant decreases of the mean maximal and minimal PTH levels, respectively, from 340 +/- 91 to 220 +/- 30 pg/ml (P = 0.03) and from 25 +/- 6 to 15 +/- 5 pg/ml (P = 0.005). On the other hand, no change was noted in the parathyroid-cell calcium-sensitivity parameters (slope, set point) assessed using two different approaches, either the entire curve or the limited calcium-mediated suppression curve. CONCLUSION: Improvement of the parathyroid function between the first and sixth months post-KT seems mainly attributable to a reduction of the parathyroid functional mass.

[Compliance with regulations for medical records in 15 Aquitaine public health facilities. Aquitaine DIM Physician's Group]. / Conformité à la réglementation des dossiers de soins dans 15 établissements publics de santé en Aquitaine. Groupe des médecins des DIM d'Aquitaine.

OBJECTIVE: Record keeping contributes to the quality of health care in addition to fulfilling medicolegal and accreditation regulations. We conducted an audit of patient files in 15 public hospitals in Aquitaine to determine their compliance with national laws. METHODS: One hundred patient files were randomly selected in each hospital. Their compliance with 18 criteria established in 1992 by the ANDEM was studied. These 18 criteria were updated in accordance with the latest decrees from the health ministry and precisely defined in order to achieve good reproducibility of the measurements. RESULTS: Ten percent of the files fulfilled all 18 criteria. Each component of the record was correctly identified and the name of the general practitioner, admission documents, and delivery, anesthesia and transfusion records were almost always present. Surgery reports were found in 65 to 89% of the files. Low compliance with three criteria was observed: authorization to give health care to a minor (39 to 80% of the files), identification of the physician who prescribed the drugs during hospitalization (6 to 32%) and discharge prescription (42 to 95%). We also pinpointed problems concerning archiving and retrieval, especially concerning the results of complementary exams which were not necessarily stored with the patient files. CONCLUSION: This audit allowed us to define the first steps of a quality improvement project for patient records. We were able to deduct recommendations for analyzing compliance with legal requirements and suggest that the 1992 ANDEM criteria be updated to allow for valid comparisons between health care establishment.