Potential lung cancer screening outcomes using different age and smoking thresholds in the ANRS-CO4 French Hospital Database on HIV cohort.

OBJECTIVES: In most lung screening programmes, only subjects ≥ 55 years old and smoking ≥ 30 pack-years are eligible to undergo chest low-dose computed tomography. Whether the same criteria should apply to people living with HIV (PLHIV) is uncertain, given the increased lung cancer risks associated with immunodeficiency and high rates of smoking. We assessed different outcomes obtained from simulating one round of lung cancer screening in PLHIV using different age and smoking thresholds for eligibility. METHODS: Data from the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS)-CO4 French Hospital Database on HIV (FHDH) cohort of PLHIV and a national representative survey of PLHIV in care in 2011 (the ANRS-VESPA2 [enquête sur les personnes atteintes] study) were used to estimate the maximum proportion of incident lung cancers occurring between 2012 and 2016 that would have potentially been detected by screening in 2011. Secondary outcomes were numbers of eligible subjects in the cohort and numbers of subjects needed to screen (NNS) to detect one lung cancer. RESULTS: Among 77819 PLHIV in 2011 (median age 46 years; 66% men), 285 subjects subsequently developed lung cancer. Adoption of the US Preventive Services Task Force (USPSTF) recommendations (55-80 years; ≥ 30 pack-years) would have detected 31% of lung cancers at most. Lowering the minimum age to 50 and 45 years would have detected 49% and 60% of cancers, respectively, but would have greatly increased the number of eligible subjects and the NNS to detect one case of lung cancer. CONCLUSIONS: Use of the USPSTF criteria would have detected only a minority of lung cancers in a large French cohort of PLHIV in 2011. Screening PLHIV at younger ages (45 or 50 years) and/or the use of lower smoking thresholds (20 pack-years) may be beneficial, despite the consequently higher numbers of eligible subjects and NNS to detect one case of lung cancer, and should be evaluated in future studies.

Men from Sub-Saharan Africa Living in Worker Hostels in France: A Hidden Population with Poor Access to HIV Testing.

Delayed presentation to care among HIV-infected individuals continued to be frequent in France. Migrants are at high risk for late presentation. This cross-sectional study investigated barriers to HIV testing in the specific population of men from sub-Saharan Africa living in four migrant worker hostels in Paris, France. Factors associated with never having been tested for HIV were examined using logistic regression. In all, 550 men participated, coming mainly from Mali and Senegal, with 31 % having lived in France for less than 5 years, and 25 % without any health insurance. Only 37 % have ever been tested for HIV. Not having health insurance was the main risk factor for never-testing [adjusted odds ratio (aOR) 2.4; 95 % confidence interval (CI) 1.4-4.0]. Despite free and anonymous HIV testing available at dedicated public screening centers, 63 % of men living in migrant worker hostels had never been tested for HIV.

Soluble biomarkers of immune activation and inflammation in HIV infection: impact of 2 years of effective first-line combination antiretroviral therapy.

OBJECTIVES: The aim of the study was to assess the impact of rapid and sustained viral control produced by combination antiretroviral therapy (cART) on HIV-associated immune activation and inflammation. METHODS: In this longitudinal observational study, we examined changes in interleukin-6 (IL-6), interferon-γ-inducible protein-10 (IP-10), monokine induced by interferon-γ (MIG) and soluble CD14 (sCD14) levels during 2 years of effective first-line cART. Biomarker levels before and after cART were compared with those observed in healthy subjects, using the Wilcoxon signed rank test. Elevated biomarker levels were defined with respect to values for healthy subject (mean + 2 standard deviations). Factors associated with persistently elevated biomarker levels after 2 years of cART were identified by logistic regression. RESULTS: We included in the study 139 patients with a median HIV-1 RNA level of 4.8 log10 HIV-1 RNA copies/mL and a median CD4 cell count of 294 cells/µL at cART initiation [day 0 (D0)]. At D0, all biomarker levels were higher than in healthy subjects (P < 0.05). After 2 years of cART, IL-6, IP-10 and MIG levels fell significantly, by a median of 0.54, 420 and 1107 pg/mL, respectively (all P < 0.001), and were no longer elevated in > 75% of patients. In contrast, sCD14 levels did not change significantly (0.18 × 10(6) pg/mL; P = 0.102) and remained elevated. Older age was associated with elevated levels of IP-10 [odds ratio (OR) 1.60 per 10 years older; P = 0.047] and MIG (OR 1.92 per 10 years older; P = 0.007) after 2 years of cART. CONCLUSIONS: The rapid and sustained viral suppression produced by first-line cART reduced IL-6, IP-10 and MIG to normal levels, while sCD14, a marker of monocyte activation, remained elevated. High levels of IP-10 and MIG tended to persist in older patients.

Survival after neuroAIDS: association with antiretroviral CNS Penetration-Effectiveness score.

OBJECTIVE: We examined if the CNS Penetration-Effectiveness (CPE) score of antiretroviral drugs was associated with survival after a diagnosis of HIV-related encephalopathy, progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis, or cryptococcal meningitis. METHODS: Using data from the FHDH-ANRS CO4, we compared the survival of 9,932 HIV-infected patients diagnosed with a first neurologic AIDS-defining event in the pre-combination antiretroviral therapy (cART) (1992-1995), early cART (1996-1998), or late cART (1999-2004) periods. Follow-up was subdivided (CPE < 1.5 and CPE ≥ 1.5), and relative rates (RR) of death were estimated using multivariable Poisson regression models. RESULTS: In the pre-cART and early cART periods, regimens with CPE ≥ 1.5 were associated with lower mortality after HIV-related encephalopathy (RR 0.64; 95% confidence interval [CI] 0.47-0.86 and RR 0.45; 95% CI 0.35-0.58) and after PML (RR 0.79; 95% CI 0.55-1.12 and RR 0.45; 95% CI 0.31-0.65), compared to regimens with CPE < 1.5, while in the late cART period there was no association between the CPE score and the mortality. A higher CPE score was also associated with a lower mortality in all periods after cerebral toxoplasmosis (RR 0.68, 95% CI 0.56-0.84) or cryptococcal meningitis (RR 0.50, 95% CI 0.34-0.74). Whatever the neurologic event, these associations were not maintained after adjustment on updated plasma HIV-RNA (missing, <500, ≥500 copies/mL) with RR ranging from 0.82 (95% CI 0.36-1.91) to 1.02 (0.69-1.52). CONCLUSION: At the beginning of the cART era, the CPE score was of importance for survival after severe neurologic event, while in the late cART period, the additional effect of CPE score vanished with more powerful antiretroviral regimens associated with plasma viral load control.

Viral efficacy maintained and safety parameters improved with a reduced dose of stavudine: a pilot study.

OBJECTIVES: Stavudine (d4T) is a potent but potentially toxic nucleoside reverse transcriptase inhibitor that is still widely used in developing countries. This study's aim was to determine the efficacy and safety profile of lower-dose d4T. METHODS: Multi-centre, open-label, single-arm, pilot, 48-week study in French patients weighing >60 kg with viral load <400 HIV-1 RNA copies/mL who were receiving d4T 40 mg twice daily and then switched to 30 mg twice daily. The primary endpoint was the proportion with plasma viral load <400 copies/mL at week 24. Secondary endpoints included the proportion with <50 copies/mL at weeks 24 and 48, changes in mitochondrial DNA, CD4 cell count and pharmacokinetics, and clinical and laboratory safety. RESULTS: Fifty-seven patients enrolled. Baseline CD4 count was 584 cells/microL; viral loads were <400 copies/mL and <50 copies/mL in 100% and 89%, respectively. Prior antiretroviral drug exposure was 6.9 years, d4T exposure was 6.3 years. Fifty-six out of 57 (98%) patients had viral load <400 copies/mL and 51 (89%) had viral load <50 copies/mL at week 24. Median CD4 count increased by 63 cells/microL at week 48 (P=0.006). At 48 weeks, total cholesterol decreased by 0.24 mmol (P=0.02), high-density lipoprotein cholesterol by 0.15 mmol (P=0.0001) and alanine aminotransferase by 5.74 mg/dL (P=0.01). Paired baseline DNA and week 24 RNA mutations were unchanged. Mitochondrial DNA (copies/cell) content increased from 672+/-254 to 682+/-269. d4T area under the plasma concentration time curve (AUC) decreased by 31% (P=0.003) and C(max) by 44% (P=0.004). Clinical and laboratory parameters improved or were unchanged. CONCLUSIONS: Reduced-dose d4T is effective with improved safety parameters.

Influence of control selection in nested case-control studies: the example of exposure to antiretroviral treatment (ART) and the risk of myocardial infarction (MI) in the French Hospital Database on HIV (FHDH-ANRS CO4).

PURPOSE: Soon after availability of protease inhibitors (PIs), a duration-related effect relationship between PI and myocardial infarction (MI) was shown. New antiretroviral treatments (ARTs) have allowed more individualized regimens. To study their influence established risk factors of MI and additional therapeutic options such as lipid-lowering drugs will have to be taken into account. A nested case-control is an interesting alternative raising the choice of controls. With the previous full cohort analysis as reference, we investigated the influence of control selection in nested case-control studies sampled in this cohort by testing nine sampling scenarios. METHODS: During the period 1996-1999, 49 MI occurred among male patients exposed to PI and followed-up in the French Hospital Database on HIV (FHDH-ANRS CO4). For each case, controls were selected using incidence-density sampling. The influence of additional matching criteria was tested. Random sampling and analysis was repeated 100 times with varying control-case ratios. RESULTS: When controls were randomly selected among patients of the same age who were free of MI at the date MI was diagnosed in the case, we observed a duration-related effect relationship between PI and MI in agreement with the results of the full cohort analysis. The use of four controls per case was sufficient. Estimates obtained with simple sampling were more precise than those obtained when controls were also matched for year of enrollment, initial CD4 cell count and HIV transmission group. CONCLUSION: To study ARTs as MI risk factors, nested case-control using incidence-density sampling without additional matching is one appropriate option.

HIV-associated Isospora belli infection: incidence and risk factors in the French Hospital Database on HIV.

OBJECTIVE: To determine the incidence of Isospora belli infection in HIV-infected patients in France, and to study risk factors. METHODS: The French Hospital Database on HIV (FHDH) is a prospective cohort study that collects demographic, clinical and therapeutic data on patients managed in 62 hospitals. We reviewed all cases of I. belli infection recorded between 1992 and 2003. We compared the incidence in 1992-1994 [before the use of dual therapy and combination antiretroviral therapy (cART)] and in 1997-2003 (when use of cART was widespread), after stratification for CD4 cell count (< 50, 50-99, 100-199 and > 200 cells/microL). RESULTS: A total of 164 patients had I. belli infection either at enrollment (n=71) or during follow up (n=93). During the study period, I. belli infection tended to occur less frequently during follow up, and to be diagnosed mainly at database enrollment. The incidence of I. belli infection during follow up fell by 79% [relative hazard (RH) 0.21; 95% confidence interval (CI) 0.13-0.33] in the cART period compared with the pre-cART period; no such change was noted among patients with CD4 cell counts below 50 cells/microL. In multivariable analysis, the risk of I. belli infection was significantly higher among patients from sub-Saharan Africa (RH 4.3; 95% CI 2.6-7.3). After adjustment for CD4 cell count, patients receiving cotrimoxazole prophylaxis were found to be at a lower risk of I. belli infection (RH 0.3; 95% CI 0.2-0.6). CONCLUSIONS: In France, I. belli infection among HIV-infected patients is now mainly seen in patients from sub-Saharan Africa, who present at an advanced stage.

[Evaluation of compliance with antiretroviral treatment in a cohort of 200 patients in Djibouti, 2005]. / Evaluation de l'observance au traitement antirétroviral au sein d'une cohorte de 200 patients à Djibouti (2005).

We determined the rate of compliance with antiretroviral therapy and investigated the factors that influence it among 86 HIV patients. Compliance ratio (number of tablets taken/number prescribed) was assessed by tablet count. The mean ratio of compliance was 92%. By tablet count, 77% of the patients were compliant (compliance ratio > or =90%). Non-compliance was significantly associated with side-effects, degree of confidentiality of the care centre and travelling. Compliance correlated significantly with viral load. In multivariate analysis, community support and level of education protected against non-compliance. Patients having already missed a dose and those dissatisfied with confidentiality had a 4 times greater risk of non-compliance.

[Evaluation of compliance with antiretroviral treatment of HIV patients in Djibouti, 2005]

We determined the rate of compliance with antiretroviral therapy and investigated the factors that influence it among 86 HIV patients. Compliance ratio [number of tablets taken/number prescribed] was assessed by tablet count. The mean ratio of compliance was 92%. By tablet count, 77% of the patients were compliant [compliance ratio >/=90%]. Non-compliance was significantly associated with side-effects, degree of confidentiality of the care centre and traveling. Compliance correlated significantly with viral load. In multivariate analysis, community support and level of education protected against non-compliance. Patients having already missed a dose and those dissatisfied with confidentiality had a 4 times greater risk of non-compliance

[Immunofixation compared to isoelectric focusing in the detection of oligoclonal bands in cerebrospinal fluid of multiple sclerosis patients]. / Comparaison de l'immunofixation après électrophorèse sur gel d'agarose avec la focalisation isoélectrique dans la détection des bandes oligoclonales d'IgG du liquide céphalo-rachidien de patients atteints de sclérose en plaques.

INTRODUCTION: Intrathecal immunoglobulins (Ig) synthesis, reflected by oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is observed in up to 90 percent of patients with clinically definite Multiple Sclerosis (MS). The gold standard laboratory test to establish the presence of OCBs in CSF of MS patients is isoelectric focusing (IEF). However, a quicker and less expensive method has been developed: immunofixation (IF). METHODS: The aim of this study was to compare these two methods carried out 74 CSF/serum pairs of MS, 103 CSF/serum pairs of subject controls and to determine their sensitivity and specificity. RESULTS: The agreement between results from IEF and IF was excellent (Kappa = 0.84). IEF sensitivity (78 percent) was not significantly different from that of IF (74 percent) (p = 0.3). Similarly, the specificity of IEF (93 percent) was not significantly different from that of IF (95 percent) (p = 0.2). CONCLUSION: IF is a semi automated method which is easier to perform than IEF and which appears to be as efficient as IEF.

Serum adiponectin and metabolic parameters in HIV-1-infected patients after substitution of nevirapine for protease inhibitors.

BACKGROUND: In the context of HIV infection and antiretroviral therapy, adiponectin concentrations have been shown to be related to lipodystrophy, metabolic alterations and HIV-protease inhibitor (PI) use. The replacement of PI by nevirapine has improved the lipid profile of patients under antiretroviral therapy. The aim of the present study was to examine whether adiponectin concentration or insulin sensitivity level correlate with the modifications of lipid parameters after the switch of PI by nevirapine. MATERIAL AND METHODS: The evolution of metabolic parameters before and after 6 months of substitution of nevirapine for protease inhibitors was evaluated in a cohort of 55 HIV-1 infected patients. Adiponectin concentration, insulin sensitivity, lipid profile, cholesterol ester transfer protein (CETP) mass concentration and triglyceride enrichment of HDL were determined before and after the replacement of PI by nevirapine. Insulin sensitivity was evaluated by the HOMA model assessment. RESULTS: Twenty-four weeks of treatment with nevirapine improved significantly the lipid profile with a significant reduction of apoB (from 0.98 to 0.92 g L(-1); P = 0.005) and triglyceride (from 2.02 to 1.66 mmol L(-1); P = 0.02). HDL cholesterol and apoA1 increased significantly (from 0.99 to 1.19 mmol L(-1); P = 0.001 and from 1.40 to 1.57 g L(-1); P < 0.001, respectively). The triglyceride enrichment of HDL significantly decreased after the replacement of PI by nevirapine (from 0.248 +/- 0.092 to 0.213 +/- 0.093; P = 0.003). At baseline, and after 24 weeks of nevirapine treatment, we observed significant correlations between adiponectin level and lipid parameters [(HDL-cholesterol (r = 0.66, P = 0.001 and r = 0.69, P = 0.001); triglycerides (r = -0.42, P = 0.002 and r = -0.57, P = 0.001), and triglyceride enrichment of HDL (r = -0.43, P = 0.005 and r = -0.53, P = 0.005)]. Twenty-four weeks of treatment with nevirapine did not significantly change adiponectin concentrations (from 984 to 1086 micro g L(-1), P = 0.22), CETP mass and insulin sensitivity. CONCLUSION: This study shows that even though a strong correlation was found between adiponectin and some metabolic parameters at baseline and after 24 weeks of treatment by nevirapine, the improvement of lipid profile observed after the replacement of PI by nevirapine was not in relation to the change of plasma adiponectin concentration. The significant decrease of triglyceride enrichment of HDL after the replacement of PI by nevirapine probably leads to a decreased catabolism of HDL lipoprotein, and consequently explains the increase of plasma HDL concentration observed in this study.

Major hypertriglyceridemia in HIV-infected patients on antiretroviral therapy: a role of the personal and family history.

BACKGROUND: Our aim was to identify factors predisposing HIV-infected patients on long-term antiretroviral therapy (ART) to major hypertriglyceridemia (HTG). PATIENTS AND METHODS: We conducted a retrospective, case-control study involving 76 HIV-infected patients with HTG, defined by 12-hour fasting plasma triglyceride (TG) > 4.5 mmol/l on at least one occasion, and 150 HIV-infected matched control patients with TG consistently below 1.8 mmol/l. RESULTS: Patients coinfected by the hepatitis C virus appeared to be protected from HTG. In addition to known predisposing factors for HTG in HIV-infected patients (ART and immune/viral status), patients with a history of excess body weight were twice as likely to have HTG (odds ratio [OR] 2.8, 95% confidence interval [CI]: 1.1-6.9); HTG was also more frequent in patients who had a first-degree relative with cardiovascular disease (CVD) or a major risk factor for CVD (OR = 3.6, CI: 1.3-9.9). CONCLUSION: By identifying subgroups of highly predisposed patients, appropriate lifestyle and dietary measures could be recommended on ART initiation.

Oncologic results following abdominoperineal resection for adenocarcinoma of the low rectum.

PURPOSE: The role of abdominoperineal resection for rectal cancer has changed because of advances in sphincter-preserving surgery. Our aim was to evaluate the results of this operation in the five-year period following introduction of the concept of total mesorectal excision METHODS: Data on all patients undergoing abdominoperineal resection for very low rectal cancer between 1992 and 1997 were collected prospectively. All patients had had total mesorectal excision. Curative resection was defined as absence of macroscopic disease after resection and local recurrence as any infiltration or tumor identified in the pelvis, alone or combined with distant disease. Survival and local recurrence rates were calculated using the Kaplan-Meier method and log-rank analysis. RESULTS: Of 165 abdominoperineal resections performed, 106 were for primary adenocarcinoma of the rectum. The male:female ratio was 50:56, with a median age of 65 (range, 33-85) years. There was one postoperative death. Twenty-seven patients received short-course preoperative radiotherapy (25 Gy over 1 week), whereas 22 had a longer course, with concomitant chemotherapy in 2. Postoperative chemotherapy was administered in 29, postoperative radiotherapy in 4, and combined therapy in 8. After curative resection (n = 91), survival at five years was 76 percent and differed significantly by stage. Recurrence at any site was 7 percent (3/34) for Stage I, 27 percent (6/26) for Stage II, and 53 percent (16/31) for Stage III. Nine patients presented with local recurrence, with an overall rate at five years of 10 percent. Isolated locale recurrence was observed in only 5 percent of patients CONCLUSIONS: After abdominoperineal resection and total mesorectal excision, good rates of local control may be achieved provided surgical technique is meticulous.

[Complications due to peripheral venous catheterization. Prospective study]. / Complications liées au cathétérisme veineux périphérique. Etude prospective.

OBJECTIVE: Peripheral venous catheter (PVC)-associated complications were prospectively evaluated in a 2 month-study performed in 3 different wards. METHODS: For each inserted PVC, the following complications were observed daily by an external investigator: tenderness, erythema, swelling or induration, palpable cord and purulence. PVC that were removed were systematically sent to the Microbiology department and analysed according to the semi-quantitative method described by Brun-Buisson et al. RESULTS: A total of 525 PVC (corresponding to 1,036 catheterisation-days) were included. Main clinical complications were erythema (22.1%), tenderness (21.9%), swelling or induration (20.9%), palpable cord (2.7%) and purulence (0.2%). Phlebitis, defined by 2 or more of the following signs: tenderness, erythema, swelling or induration and palpable cord, was observed in 22%. Catheter colonization (> or = 103 CFU/ml) occurred in 13%. Bacteria isolated from colonized catheters were coagulase-negative staphylococci (88.1%), Staphylococcus aureus (7.1%) and Candida sp. (4.8%). Multivariate risk factor analysis showed that age > or = 55 y. (OR = 3.16, p = 0.003), insertion on articulation site (OR = 2.94, p = 0.01) or in jugular vein (OR = 8.18, p = 0.01) and > 72 hour-catheterisation (OR = 4.74, p = 0.0003) were significantly associated with PVC colonization. Risk factors for phlebitis were skin lesions (OR = 1.88, p < 0.016), active infection unrelated to PVC (OR = 2.8, p = 0.001), "poor quality" peripheral vein (OR = 2.46, p < 0.02) and > 72 hour-catherisation (OR = 2.38, p = 0.009). CONCLUSION: Complications associated with peripheral venous catheters are frequent but remain benign. They could probably be reduced by a systematic change every 72-96 hours as recommended by different guidelines.

Impact of highly active antiretroviral therapy on the occurrence of bacteraemia in HIV-infected patients and their epidemiologic characteristics.

OBJECTIVE: 1. to assess the impact of highly active antiretroviral therapy (HAART) on the occurrence of bacteraemia in HIV-infected patients and their clinical and microbiological characteristics. 2. to identify risk factors for bacteraemia in this setting. METHODS: The files of all HIV-infected patients hospitalized for an episode of bacteraemia in a 28-bed infectious diseases unit between January 1995 and December 1998 were reviewed. Cases occurring during HAART were compared to cases occurring in patients not receiving HAART. Furthermore, in a case-control study, patients with bacteraemia occurring during HAART were compared with other patients receiving HAART. RESULTS: There were 74 episodes of bacteraemia in patients not receiving HAART and 31 episodes in patients receiving HAART. The occurrence of bacteraemia fell from 10.5/100 hospitalizations in 1995 to 5.5/100 in 1998 (P = 0.02 trend test). The occurence of P. aeruginosa bacteraemia fell sharply (9/398 vs 1/273, P = 0.05). A significant fall in catheter-related infections was observed between 1995 and 1998 (5.5% vs 1.8%). The two-thirds/one-third distribution of hospital-acquired and community-acquired infections remained stable throughout the period study. In patients receiving HAART, the case-control study showed by multivariate analysis, that a CD4 cell count of less than 100/ micro L [OR = 7.3 (1.9-49.7)], and the use of exogenous devices [OR = 13.3 (2.5-71)] were significantly associated with the risk of bacteraemia. CONCLUSION: The introduction of HAART has been associated with a significant fall in the occurrence of bacteraemia. However, patients with a low CD4 cell count remain at risk of bacteraemia with similar microbiological and epidemiological characteristics than in the pre-HAART era.

Postdischarge nosocomial infections in primary care.

OBJECTIVE: To study both surgical and nonsurgical nosocomial infections (NIs) seen by primary-care physicians (general practitioners [GPs]) in France. DESIGN: Ongoing surveillance of postdischarge NIs by an organized group of GPs, from August 1997 to July 1999. Both the GP who personally examined the case spontaneously presenting with NI and the responsible hospital physician or surgeon were interviewed by telephone. SETTING: 305 general practices from all French regions. RESULTS: 2,199 (29%) of 7,540 patients referred for hospitalization reconsulted the GP within 30 days of discharge. In 21 (1%) of the 2,199 cases, an NI was diagnosed by the GP and confirmed as plausible by the responsible hospital physician. We diagnosed an NI in 8 (1.3%) of the post-surgical patients and in 13 (0.8%) of the non-surgical cases within the cohort. We saw eight urinary tract infections, seven surgical-site infections, three soft-tissue infections, two respiratory tract infections, and one primary bloodstream infection. In 19 patients (90%), clinical signs of NI appeared within 7 days of discharge. Assuming that all 5,431 patients who were missed for follow-up did not experience any NI, an attack rate of 0.3 per 100 admissions may be estimated for the whole group. CONCLUSION: We diagnosed 1% of NIs following discharge from a hospital in a cohort of 2,199 patients, of which 1.3% were seen post-surgery and 0.8% following nonsurgical admissions. The percentage of postdischarge visits that were for an NI in nonsurgical patients warrants a major effort with feedback to the hospital physician to reduce infection rates.

Risk factors for diabetes mellitus and early insulin resistance in chronic hepatitis C.

BACKGROUND/AIMS: Our aims were to investigate the host and viral specific factors associated with diabetes mellitus (DM) and insulin resistance in chronic hepatitis C patients. METHODS: One hundred and three hepatitis C virus (HCV)-infected were studied to assess the effects of HCV genotype, hepatic iron content, steatosis, hepatic fibrosis, body mass index (BMI) and family history of DM on the occurrence of DM. Insulin resistance (HOMA IR) was studied in 81 non-diabetic patients to determine the mechanism associated with insulin resistance in this subgroup. RESULTS: Sixteen of the 123 were diabetic (13.0%). The variables predictive of DM were METAVIR fibrosis score 4 (OR, 13.16; P = 0.012), family history of diabetes (OR, 16.2; P = 0.0023), BMI (OR, 1.37; P = 0.017) and age (OR, 1.09; P = 0.002). In non-diabetic HCV-infected patients, HOMA-IR of METAVIR fibrosis score 0 and 1 patients were significantly different than score 2 and score 3/4 patients. CONCLUSIONS: Our findings indicate that older age, obesity, severe liver fibrosis and family history of diabetes help identify those HCV patients who might have potential risk factors for development of DM. We observed that insulin resistance in non-diabetic HCV-infected patients was related to grading of liver fibrosis, and occurs already at an early stage in the course of HCV infection.

Postdischarge adverse drug reactions in primary care originating from hospital care in France: a nationwide prospective study.

OBJECTIVE: To describe and estimate the incidence and preventability of postdischarge adverse drug reactions (ADRs) detected in primary care in France. DESIGN: Prospective study of patients referred to hospital by participating general practitioners (GPs). These GPs reported all cases of an adverse reaction to a drug instituted in hospital among patients who consulted them within 30 days of discharge. SETTING: 305 general practices from all French regions. PATIENTS: 7540 patients referred by GPs to private or public hospitals. MAIN OUTCOME MEASURES: The incidence for postdischarge ADRs in primary care, and their preventability. RESULTS: 30 cases of postdischarge ADR were detected in 29 re-consulting patients, yielding a minimal incidence for France of 0.4 per 100 admissions (95% confidence interval 0.3 to 0.6). The ADRs were assessed as serious in 60% of cases. The main drug classes implicated were cardiovascular drugs (8 ADRs), oral anticoagulants (6), psychoactive drugs (4), antidiabetics (3), and opioid analgesics (3). Patients experiencing a postdischarge ADR were older than patients not experiencing one (median age: 77 vs 68 years; p = 0.004). Detected ADRs were considered preventable in 59% of cases. CONCLUSIONS: Physicians and patients should be aware of the possible occurrence of postdischarge ADRs. Patient information in hospital, close postdischarge follow-up of patients at risk, and appropriate transmission of information between hospital physicians and GPs can help to prevent them.

Improved efficiency of remission induction facilitates autologous BMT harvesting and improves overall survival in adults with AML: 108 patients treated at a single institution.

A hundred and eight patients less than 60 years old with de novo acute myeloid leukemia were treated between 1982 and 1994 by protocols including final intensification with a transplant using autologous bone marrow purged by mafosfamide in first remission in the absence of an HLA-matched sibling donor available for allograft. From 1989, we attempted to improve tumor control by using high-dose anthracyclines in induction, by increasing from one to two the number of consolidation courses pre-transplant and by introducing intermediate doses of cytarabine in the first consolidation course. The CR rate was 77% (33/43) before 1989 and 90% (59/65) after 1989 (P = 0.06). Forty-five out of the 59 patients (76%) who achieved CR after 1989 could undergo bone marrow grafting in CR1 vs 16/33 (48%) before 1989 (P = 0.01). In spite of the higher proportion of patients above 50 years after 1989 (32%) toxicity was mild and an adequate graft was obtained more frequently after one collection. The principal factor relating to improvement in graft feasibility was the post-1989 modification of induction and consolidation regimens. This improvement in graft feasibility was associated with a better disease-free survival (DFS) (48 +/- 7% vs 32 +/- 8%, P = 0.04) and overall survival (OS) (53 +/- 6% vs 30 +/- 7%, P = 0.007) at 5 years. By multivariate analysis four factors were associated with overall survival (OS): karyotype, white blood cell count at diagnosis, treatment regimen and bone marrow grafting in CR1. This global approach should be prospectively compared with intensive chemotherapy.