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.

Invasive cervical cancer in HIV-infected women: risk and survival relative to those of the general population in France. Results from the French Hospital Database on HIV (FHDH)-Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS) CO4 cohort study.

OBJECTIVES: We examined trends in the incidence rates of invasive cervical cancer (ICC) and in the rate of survival after ICC among women living with HIV (WLHIV) in France and compared them to those of the general population. METHODS: Histologically validated incident cases of ICC in the period 1992-2009 from the French Hospital Database on HIV (FHDH-ANRS CO4) were included in the study. Age-standardized incidence rates were estimated for FHDH and the general population in France for 1992-1996 [pre-combination antiretroviral therapy (cART) period], 1997-2000 (early cART period), 2001-2004 (intermediate cART period), and 2005-2009 (late cART period). Age-standardized incidence ratios (SIRs) were calculated. Five-year survival was compared with that of the general population for ICC diagnosed in 2005-2009 after standardization for age. RESULTS: Among 28 977 WLHIV, 60 incident ICCs were histologically validated. There was a nonsignificant decreasing trend for the incidence across the cART periods (P = 0.07), from 60 to 36/100 000 person-years. The risk of ICC was consistently significantly higher in WLHIV than in the general population; the SIR was 5.4 [95% confidence interval (CI) 3.0-8.9] during the pre-cART period and 3.3 (95% CI 2.2-4.7) in 2005-2009. Survival after ICC did not improve across periods (log-rank P = 0.14), with overall estimated 5-year survival of 78% (95% CI 0.67-0.89%). Five-year survival was similar for WLHIV and the general population for women diagnosed with ICC in 2005-2009, after standardization (P = 0.45). CONCLUSIONS: ICC risk is still more than three times higher in WLHIV than in the general population. Survival after ICC did not improve over time and was similar to that of the general population during the most recent period. Such results call for promotion of the uptake of screening in WLHIV.

Impaired sperm motility in HIV-infected men: an unexpected adverse effect of efavirenz?

STUDY QUESTION: Are antiretroviral therapies associated with semen alterations in HIV-infected men? SUMMARY ANSWER: Antiretroviral regimens that included the non-nucleosidic reverse transcriptase inhibitor efavirenz were associated with a significant impairment of sperm motility, whereas regimens without efavirenz were not associated with significant semen changes. WHAT IS KNOWN ALREADY: Semen alterations including decreased ejaculate volume and sperm motility have been reported in HIV-infected men. The hypothesis ascribing reduced sperm motility to damages induced in sperm mitochondria by nucleosidic (or nucleotidic) reverse transcriptase inhibitors (NRTIs) has not been confirmed in HIV-infected patients and the effects of antiretroviral treatments on semen parameters remain unclear. STUDY DESIGN, SIZE, DURATION: This case-control study compared semen characteristics across 378 HIV-1 infected patients receiving different antiretroviral regimens or never treated by antiretroviral drugs, in whom an initial semen analysis was done between 2001 and 2007. PARTICIPANTS/MATERIALS, SETTING, METHODS: The patients were partners from serodiscordant couples requesting medical assistance to procreate safely. Their status with regard to antiretroviral therapy at the time of semen analysis was categorized as follows: 1/ never treated patients (n = 66); 2/ patients receiving NRTIs only (n = 49); 3/ patients receiving a NRTIs + protease inhibitor (PI) regimen (n = 144); 4/ patients receiving a NRTIs + non-nucleosidic reverse transcriptase inhibitor (NNRTI) regimen (n = 119). Semen parameters were assessed through standard semen analysis. Additional analyses included measurement of sperm motion parameters using computer-assisted semen analysis, seminal bacteriological analysis, seminal biochemical markers and testosterone plasmatic levels. All analyses were performed in the Cochin academic hospital. The data were analyzed through multivariate analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Sperm motility was the only semen parameter which significantly varied according to treatment status. The median percentage of rapid spermatozoa was 5% in the group of patients receiving a regimen including efavirenz versus 20% in the other groups (P < 0.0001). Accordingly, sperm velocity was reduced by about 30% in this group (P < 0.0001). The role of chance was minimized by the strict definition and the size of the study population, which included a large enough group of never treated patients, the controlled conditions of semen collection and analysis, the multivariate analysis, the specificity and the high significance level of the observed differences. LIMITATIONS, REASONS FOR CAUTION: The design of the study did not allow demonstrating a causal link between exposure to efavirenz and sperm motility. WIDER IMPLICATIONS OF THE FINDINGS: As efavirenz is widely used in current antiretroviral therapy, these findings may concern many HIV-infected men wishing to have children. This justifies further assessment of the consequences on fertility of the exposure to efavirenz. Moreover, the possibility of common cellular impacts underlying adverse effects of efavirenz in sperm cells and neurons deserved investigation. STUDY FUNDING/COMPETING INTERESTS: No external funding was used for this study. None of the authors has any conflict of interest to declare.

Low immunogenicity of seasonal trivalent influenza vaccine among patients receiving docetaxel for a solid tumour: results of a prospective pilot study.

BACKGROUND: Patients receiving cytotoxic therapy for solid tumours are at risk of severe influenza. However, few data are available regarding the immunogenical efficacy of influenza vaccine in these patients. METHODS: In this prospective study, 25 patients with breast (n=13) or prostate (n=12) cancer received a trivalent inactivated influenza vaccine along with docetaxel (Taxotere) administration. The influenza virus type A and B antibody titres were measured using haemagglutinin inhibition (Garten et al, 2009) before and 21 days after the vaccination. Seroconversion rate was defined as the percentage of patients with an increase in the serum titres ≥ 4 after vaccination. RESULTS: Median age was 65 years (range: 33-87 years); 52% were females. Seroconversion rates were low: 28% (95% CI: 23.1-33.3) for H1N1, 8% (95% CI: 7.7-8.3) for H3N2 and 16% (95% CI: 7.7-25) for the B strain. The geometric mean titres ratios were 2.16 (H1N1), 1.3 (H3N2) and 1.58 (B). No serious adverse event (AE) related to the vaccine was reported. All the reported AE were from mild-to-moderate intensity. CONCLUSION: In the patients receiving docetaxel for solid tumours, influenza vaccine triggers an immune response in only one third. Strategies using more immunogenic influenza vaccines must be evaluated in such patients.

Outcomes of endoscopic ultrasound-guided biliary drainage: A systematic review and meta-analysis.

Background: Success and event rates of endoscopic ultrasound (EUS)-guided biliary drainage vary with techniques, and results from different studies remain inconsistent. Objective: We conducted a proportion meta-analysis to evaluate the efficacy and safety of EUS-guided biliary drainage and compare the outcomes of current procedures. Methods: We searched MEDLINE, Embase, Cochrane and Web of knowledge to identify studies reporting technical success, clinical success and complication rates of EUS-guided biliary drainage techniques to estimate their clinical and technical efficacy and safety. Results: We identified 17 studies including a total of 686 patients. The overall clinical success and technical success rates were respectively 84% confidence interval (CI) 95% (80-88) and 96% CI 95% (93-98) for hepaticogastrostomy, and respectively 87% CI 95% (82-91) and 95% CI 95 (91-97) for choledochoduodenostomy. Reported adverse event rates were significantly higher (p = 0.01) for hepaticogastrostomy (29% CI 95% (24-34)) compared to choledochoduodenostomy (20% CI 95% (16-25)). Compared with hepaticogastrostomy, the pooled odds ratio for the complication rate of choledochoduodenostomy was 2.01 (1.25; 3.24) (p = 0.0042), suggesting that choledochoduodenostomy might be safer than hepaticogastrostomy. Conclusion: The available literature suggests choledochoduodenostomy may be a safer approach compared to hepaticogastrostomy. Randomized controlled trials with sufficiently large cohorts are needed to compare techniques and confirm these findings.

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.

[Tobacco reduction in a prison of France]. / La réduction tabagique à la maison d'arrêt de Paris-La Santé

SUBJECT: Little is known about free nicotine transdermal patch efficacy on tobacco reduction in prisoners. The objective is to study this efficacy in prison as well as motivations to reduce and influence of socioeconomic conditions and other addictions in prisoners' aspiration to stop smoking. METHODS: A prospective study was proposed to prisoners candidate to tobacco cessation. Assessment was made by questionnaires and visits to physicians working at the prison. Nicotinic patches were systematically proposed to patients with a starting 15 mg/16 h dose (or 10 mg/16 h if the dependence was low), followed by a 10 and 5 mg/16 h dose reduction. RESULTS: Prisoners motivated to smoking cessation (N=73) generally had multiaddictive behaviours and precarious socioeconomic profile. Thirty percent of prisoners self-reported a reduction of 50% of their cigarettes consumption until they left prison. Median duration of this successful treatment was 45 days. Median duration of treatment response for patients who relapsed in prison (15 %) was 75 days. No predictive factor of success was found. CONCLUSION: Tobacco reduction is possible in prison even if living conditions are not favourable.

[Prevalence and risk factors of hepatitis A infection in an HIV-infected French population]. / Prévalence et facteurs de risque de l'hépatite A au sein d'une population de patients infectés par le virus de l'immunodéficience humaine.

BACKGROUND: There are common risk factors between hepatitis A virus (HAV) and human immuno deficiency virus (HIV) infections. OBJECTIVES: We tried to evaluate if HIV-infected patients could be at risk for HAV. More over, HAV could worsen prognosis of HIV infection and HAV vaccination was then to be considered. Thus we assessed the prevalence and risk factors of HAV infection in an HIV-infected population. PATIENTS AND METHODS: Seroprevalence and risk factors for HAV were studied among 154 HIV-positive patients followed in a Parisian hospital (mean age: 42 years, male patients: 70.8%, female patients: 29.2%). They were screened for HAV antibodies and answered a questionnaire on risk factors for HAV and means of HIV contamination. RESULTS: The global prevalence was 72.7% [IC95%: 65.7-79.7]. We excluded patients who were born in highly endemic areas where seroprevalence reached 60% [IC95%: 51.2-70]. The HAV seroprevalence was almost 100% in migrants from highly endemic countries and for those born before 1946. The multivariate analysis showed that risk factors were the geographic origin [OR=20.88; IC95%: 2.40-181], age [OR = 2.33; IC95%: 1.24-4.39], and hemophilia [OR = 13.78; IC95%: 1.34-141]. CONCLUSION: Our results suggest that a screening test for HAV antibodies should be performed before vaccination, especially in HIV-infected patients born after 1946 or in non-endemic countries.

Use of observational databases to evaluate the effectiveness of antiretroviral therapy for HIV infection: comparison of cohort studies with randomized trials. EuroSIDA, the French Hospital Database on HIV and the Swiss HIV Cohort Study Groups.

OBJECTIVES: It is important to assess the extent of bias when comparing the clinical efficacy of antiretroviral regimens in observational databases because, with the current lack of planned large trials, such analyses may represent the only means of assessing the risk of serious clinical events associated with new regimens. We aimed to compare the results from observational databases with those from randomized trials. METHODS: Three treatment comparisons from randomized trials [Delta, AIDS Clinical Trials Group (ACTG) 175, Community Programs for Clinical Research on AIDS (CPCRA) 007 and ACTC 320] were mimicked in cohorts: (i) zidovudine monotherapy versus combination regimens of two nucleoside analogues; (ii) zidovudine combined with either didanosine or zalcitabine; and (iii) a dual combination versus a triple regimen including a protease inhibitor. Data for over 10 000 patients from the French Hospital Database on HIV, the EuroSIDA study and the Swiss HIV cohort study were analysed for each of the comparisons. Progression to AIDS disease or death was analysed in Cox models, adjusting for baseline differences, and results compared with randomized trials. RESULTS: For comparison (i) the adjusted relative risk estimates from cohorts were between 0.61 and 0.84, favouring combinations over monotherapy, compared with 0.57 to 0.63 for trials. For comparison (ii) relative risk estimates from cohorts ranged from 0.81 to 1.01 compared with 0.77 to 0.92 for trials. For comparison (iii), two of the cohorts showed similar results to the ACTG 320 trial but one indicated a higher risk of progression on triple therapy [relative risk 1.20, 95% confidence interval (CI) 1.01-1.441, in direct contrast to the trial result (relative risk 0.50, 95% CI 0.33-0.76). CONCLUSION: Serious biases can be present when comparing outcomes from the use of antiretroviral regimens in observational studies. However, such bias is not inevitable and careful interpretation of the results from several observational studies considered together is likely to be informative, guiding the design of new trials.

Factors associated with clinical and virological failure in patients receiving a triple therapy including a protease inhibitor.

OBJECTIVE: To determine the predictors of virological and clinical failure in patients receiving a protease inhibitor as part of triple therapy. METHODS: From the French Hospital Database on HIV, 1402 protease inhibitor-naive patients starting a highly active antiretroviral therapy regimen with ritonavir, saquinavir-hard gel capsule (hgc) or indinavir between July 1996 and March 1997, and with measured HIV RNA at baseline and at 12 months, were studied for progression to a new AIDS-defining event (ADE) or death. Virological failure was defined as plasma HIV RNA > 1000 copies/ml at 12 months. Multivariate analyses were performed using Cox models for clinical outcomes and logistic regression for virological outcomes. RESULTS: During a median follow-up of 14.1 months, 94 (6.7%) patients experienced an ADE or died. At 12 months, 700 patients (49.9%) had virological failure. In the multivariate analysis, baseline CD4 cell count and viral load were found to be independent predictors of both virological and clinical failure. Neither the type of the first protease inhibitor taken nor previous antiretroviral therapy experience was associated with risk of clinical progression. For virological failure, the use of saquinavir-hgc was associated with a significant 1.96-fold increase in risk compared with indinavir; pre-treated patients were at higher risk than antiretroviral therapy-naive patients. CONCLUSION: In this study with large samples of patients, the use of saquinavir-hgc was associated with higher risk of virological failure at 12 months than were ritonavir and indinavir; no differences between protease inhibitors were found for clinical progression. As biases cannot be excluded, a longer duration of follow-up will be necessary to answer the question of whether the results are really discrepant or simply reflect the delay between virological failure and clinical manifestations.

[Partial corpus callosum agenesis]. / Agénésie partielle du corps calleux de l'enfant.

PURPOSE: The diagnosis of corpus callosum agenesis (CCA) with prenatal MRI relies on indirect signs. However, they are known to be inconstant in case of incomplete CCA. The purpose of this study is to specify the frequency of indirect signs in partial CCA to approach the reliability of fetal MRI. MATERIALS AND METHODS: This retrospective study included 33 children with partial CCA. MRI were reviewed by two observers and a standardized radiological and clinical data collection was performed. Depending on the ratio CC length/anteroposterior brain diameter, two groups were statistically compared: subtotal partial CCA and mild partial CCA. RESULTS: 14% of patients had none indirect sign and 33% had only one sign. We found a significative difference of frequency for most of the indirect signs. 48% of patients had other cerebral anomalies. Clinical correlation showed no statistical difference between the two groups. CONCLUSION: This series shows that indirect signs are inconstant in partial CCA and related to the CC length. In contrast, mild and subtotal CCA have a similar neurological outcome. These data suggest that greatest care has to be taken in the interpretation of fetal MRI.

[Sun exposure behavior of children between 3-15 years of age living in Montpellier]. / Comportements d'exposition solaire des enfants de 3 à 15 ans domiciliés à Montpellier.

OBJECTIVE: Increasing prevalence of skin cancer over the past few decades and their relationship with childhood sun exposure, show that educational campaigns on sun protection are urgently needed. The aim of this study is to estimate the degree of children's sun exposure in the south of France (43 degrees latitude north) and to study sun protection behaviors according to phenotypic characteristics. POPULATION AND METHODS: The population was a randomly selected sample of 573 schoolchildren between 3 and 15 years of age living in Montpellier. The questionnaire provided information about sociodemographic characteristics, summer sun exposure and sun protection. Phenotypic characteristics, reactivity to sunlight and number of sunburns since birth were also reported. RESULTS: Exposure time was very high: half of children spend over 6 hours per day outside in summer. The youngest children were the most protected either by sunscreen, or by shirt. On the beach, sunscreens were used more than half of the time of exposure by 70 p. 100 of the children. At the swimming pool, sunscreens were used by 45 p. 100 of the children and only by 14 p. 100 of them during other outdoor activities. A tee-shirt was only wore by 50 p. 100 of the children when playing on the beach, and by 75 p. 100 of them at the swimming pool. In addition, the application of sunscreen varied by body site. The adolescents, although they were exposed less than the youngest children, were very poorly protected. Light skinned children who do not tan easily had highest risk of sunburns, although they were generally more protected. CONCLUSION: The parents are able to identify highly sensitive children according to phenotype, but in practice the use of sunscreens and tee-shirt is very low. Parents and adolescents must be the target population but also insufficiently protected children. Health education at school must be an important measure for prevention.

Common SNPs of AmelogeninX (AMELX) and dental caries susceptibility.

Genetic approaches have shown that several genes could modify caries susceptibility; AmelogeninX (AMELX) has been repeatedly designated. Here, we hypothesized that AMELX mutations resulting in discrete changes of enamel microstructure may be found in children with a severe caries phenotype. In parallel, possible AMELX mutations that could explain resistance to caries may be found in caries-free patients. In this study, coding exons of AMELX and exon-intron boundaries were sequenced in 399 individuals with extensive caries (250) or caries-free (149) individuals from nine French hospital groups. No mutation responsible for a direct change of amelogenin function was identified. Seven single-nucleotide polymorphisms (SNPs) were found, 3 presenting a high allele frequency, and 1 being detected for the first time. Three SNPs were located in coding regions, 2 of them being non-synonymous. Both evolutionary and statistical analyses showed that none of these SNPs was associated with caries susceptibility, suggesting that AMELX is not a gene candidate in our studied population.

Can C-reactive protein, procalcitonin and mid-regional pro-atrial natriuretic peptide measurements guide choice of in-patient or out-patient care in acute pyelonephritis? Biomarkers In Sepsis (BIS) multicentre study.

Whereas C-reactive protein (CRP), procalcitonin (PCT) and mid-regional pro-atrial natriuretic peptide (ANP) may be of use at the bedside in the management of adult patients with infectious disorders, their usefulness has not been established in the setting of acute pyelonephritis. To assess the effectiveness of CRP, PCT and ANP measurements in guiding emergency physicians' decisions whether to admit to hospital patients with acute pyelonephritis, we conducted a multicentre, prospective, observational study in 12 emergency departments in France; 582 consecutive patients were included. The reference standard for admission was defined by experts' advice combined with necessity of admission or death during the 28-day follow-up. Baseline CRP, PCT and ANP were measured and their accuracy in identifying the necessity of admission was analysed using area under curves (AUC) of receiver-operating characteristic (ROC) plots. According to the reference standard, 126 (22%) patients required admission. ANP (AUC 0.75, 95% CI 0.69-0.80) and PCT (AUC 0.75, 95% CI 0.71-0.80) more accurately predicted this than did CRP (AUC 0.69, 95% CI 0.64-0.74). The positive and negative likelihood ratios for each biomarker remained clinically irrelevant whatever the threshold. Our results did not support the use of these markers to help physicians in deciding about admission of patients experiencing acute pyelonephritis in daily practice.

Effects of candidaemia on outcome of burns.

AIM: To evaluate the diversity and antifungal susceptibilities of Candida isolates from wounds and blood of burn victims, and the associated mortality rates compared with those of controls without candidaemia. METHODS: We performed a nested case-control study within a database of clinical data for all patients admitted to our burn unit from January 2001 to December 2005. Each candidaemic patient was compared with two matched controls. Bloodstream cultures were performed if the core temperature was >39 degrees C, and three sites were cultured weekly for fungal identification (burn wound, pharynx, urinary tract). RESULTS: At least one episode of candidaemia was diagnosed among 20 of 851 persons admitted during the study period. Isolates in bloodstream infection were Candida albicans (65%), C. parapsilosis (25%) and C. tropicalis (10%). The median time between admission and onset of candidaemia was greater with C. albicans infection (42.6+/-31 days) than with infection by other yeasts (18+/-12 days). Candidaemia was associated with more extensive burn and longer duration of hospital stay but with similar mortality, compared with controls. CONCLUSION: Candidaemia in burn cases is mostly due to fluconazole-susceptible C. albicans and is not associated with increased mortality.

Causes of the first AIDS-defining illness and subsequent survival before and after the advent of combined antiretroviral therapy.

OBJECTIVES: To analyse the impact of combined antiretroviral treatment (cART) on survival with AIDS, according to the nature of the first AIDS-defining clinical illness (ADI); to examine trends in AIDS-defining causes (ADC) and non-AIDS-defining causes (non-ADC) of death. METHODS: From the French Hospital Database on HIV, we studied trends in the nature of the first ADI and subsequent survival in France during three calendar periods: the pre-cART period (1993-1995; 8027 patients), the early cART period (1998-2000; 3504 patients) and the late cART period (2001-2003; 2936 patients). RESULTS: The three most frequent initial ADIs were Pneumocystis carinii (jirovecii) pneumonia (PCP) (15.6%), oesophageal candidiasis (14.3%) and Kaposi's sarcoma (13.9%) in the pre-cART period. In the late cART period, the most frequent ADIs were tuberculosis (22.7%), PCP (19.1%) and oesophageal candidiasis (16.2%). The risk of death after a first ADI fell significantly after the arrival of cART. Lower declines were observed for progressive multifocal leukoencephalopathy, lymphoma and Mycobacterium avium complex infection. After an ADI, the 3-year risk of death from an ADC fell fivefold between the pre-cART and late cART periods (39%vs. 8%), and fell twofold for non-ADCs (17%vs. 9%). CONCLUSIONS: The relative frequencies of initial ADI have changed since the advent of cART. Tuberculosis is now the most frequent initial ADI in France; this is probably the result of the increasing proportion of migrants from sub-Saharan Africa. After a first ADI, cART has a major impact on ADCs and a smaller impact on deaths from other causes. The risk of death from AIDS and from other causes is now similar.

[Hydroxyzine premedication does not alter bispectral index changes following etomidate induction of general anaesthesia]. / La prémédication par l'hydroxyzine ne modifie pas les variations du BIS induites par l'administration d'étomidate.

OBJECTIVE: Various drugs including hydroxyzine are preoperatively administered to facilitate the induction of general anaesthesia. We investigated the effect of hydroxyzine premedication on BIS-based etomidate induction of general anaesthesia. PATIENTS AND METHODS: Sixty-seven ASA I-II consecutive patients were randomly allocated to receive oral hydroxyzine 1.5 mg/kg or placebo, 90 min prior to inducing general anaesthesia using intravenous etomidate alone 0.3 mg/kg. BIS values were continuously recorded. The times for the BIS to decrease to 50 and to loss of eyelid reflex; the evolution of arterial pressure and heart rate; and myoclonia rate and grade were investigated and compared. RESULTS: The results for the hydroxyzine and placebo groups were similar with respect to: a) time [median (range) (seconds)] to a BIS decrease to 50 [100 (21-266) versus 113 (30-510), P=0.1] and to loss of eyelid reflex [83 (21-210) versus 97 (30-300), P=0.1]; b) myoclonia frequency (yes/no) (9/26 versus 4/28, P=0.2) and grade (P=0.3); the evolution of mean arterial pressure and heart rate (P=0.3). CONCLUSION: Oral weight-related hydroxyzine premedication does not alter BIS-based etomidate induction of GA.

Relationship between cytochrome 3A activity, inflammatory status and the risk of docetaxel-induced febrile neutropenia: a prospective study.

BACKGROUND: We hypothesized that cancer-related inflammation might increase the risk of febrile neutropenia (FN) induced by docetaxel (DCX, Taxotere), by both affecting the exposure to DCX and the tissue sensitivity. PATIENTS AND METHODS: Advanced cancer patients with normal liver function, performance status (PS)<3, were included. Cytochrome P450 3A (CYP 3A) activity was estimated before the first cycle of DCX by a single determination of midazolam plasma concentration, 4 hours after 0.015 mg/kg i.v. bolus. Following the first cycle of 75-100 mg/m2 DCX, clearance and area under the concentration versus time curve (AUC) were estimated using a limited sampling strategy. RESULTS: Among 56 assessable patients, 7 FNs occurred after first cycle (13%). In univariate analysis, high midazolam concentration and free DCX AUC were associated with severe neutropenia and FN. In addition to DCX exposure-related parameters, the risk of FN was also correlated with poor PS, baseline lymphopenia and lung cancer, while high ferritin level, indicator of an inflammatory state, reached borderline significance (P=0.07). By multivariate analysis, total DCX AUC and baseline lymphopenia were associated with FN. High midazolam concentration was correlated with elevated ferritin level (r=0.32; P=0.02). CONCLUSION: Inflammatory status and lymphocyte count should be included in the evaluation of the benefice/risk ratio before the initiation of DCX.

Clinical outcome of patients with HIV-1 infection according to immunologic and virologic response after 6 months of highly active antiretroviral therapy.

BACKGROUND: The prognostic value of discordant immunologic (CD4 cell increase) and virologic (plasma HIV RNA level decrease) responses to antiretroviral treatment is not known. OBJECTIVE: To study the relation between clinical outcome of HIV-infected patients receiving highly active antiretroviral therapy (HAART) and early immunologic and virologic responses to such therapy. DESIGN: Prospective cohort study. SETTING: 68 hospitals in France. PATIENTS: 2236 protease inhibitor-naive patients. INTERVENTION: Initiation of HAART with one protease inhibitor and two nucleoside analogues between July 1996 and March 1997. MEASUREMENTS: Immunologic and virologic response at 6 months. Multivariate Cox models were used to assess the relation between these responses and progression to a new AIDS-defining event or death. RESULTS: On the basis of 6-month immunologic and virologic responses, patients were classified into four groups: complete response (47.5%), complete nonresponse (16.2%), immunologic response only (19.0%), and virologic response only (17.3%). After month 6 and within a median of 18 months, 69 patients died and 123 experienced a new AIDS-defining event. After adjustment, complete nonresponders and those with only a virologic response had significantly higher risks for clinical progression at 6 months (relative risk, 3.38 [95% CI, 2.28 to 5.02] and 1.98 [CI, 1.26 to 3.10], respectively) than complete responders. The difference between complete responders and those with only an immunologic response at 6 months was weaker and nonsignificant (relative risk, 1.55 [CI, 0.96 to 2.50]). CONCLUSIONS: Immunologic response after 6 months of HAART indicates a favorable clinical outcome in HIV-infected patients regardless of virologic response. This suggests that both immunologic and virologic markers should be used in clinical practice to evaluate treatment response.

TSH suppression combined with carbimazole for Graves' disease: effect on remission and relapse rates.

OBJECTIVE: We studied the influence of TSH suppressive therapy combined with carbimazole (CBZ) on treatment outcome in Graves' disease. DESIGN: Open non-randomized prospective study. SETTING: University Hospital of Montpellier, France. SUBJECTS: Sixty-six consecutive patients without prior treatment were included. All the patients were treated initially with 30 mg of CBZ. After 1 month of treatment, one group continued CBZ alone (n = 23), another group received a combination of CBZ plus T3 (n = 19) and a third group received CBZ and 3,5,3'-triiodothyroacetic acid (Triac, n = 24). Therapy was stopped when remission was obtained based on clinical euthyroidism, normalization of FT4 and of early radioiodine uptake. Nine patients with medical treatment failure or major side effects requiring to stop antithyroid drugs underwent surgery or radioiodine therapy. Nine patients were lost to follow-up. The remaining 48 patients were available for analysis of both remission and relapse. RESULTS: The median duration of therapy was 18 months (range, 4-41 months). Based on clinical examination, goitre size at 4 months decreased more in the CBZ + T3 and CBZ + Triac groups than in the CBZ group (P = 0.02). The overall remission rate tended to be higher in the groups treated with CBZ + T3 and CBZ + Triac than in the group treated with CBZ alone, but the difference did not reach statistical significance (P = 0.17). No difference in the relapse rate was observed between the three groups. CONCLUSION: TSH suppression combined with CBZ has little or no effect on remission and relapse rates in Graves' disease patients.