Effect of highly active antiretroviral therapy on tacrolimus pharmacokinetics in hepatitis C virus and HIV co-infected liver transplant recipients in the ANRS HC-08 study.

OBJECTIVE: To characterise the interactions between tacrolimus and antiretroviral drug combinations in hepatitis C virus-HIV co-infected patients who had received a liver transplant. DESIGN: An observational, open-label, multiple-dose, two-period, one-sequence design clinical trial in which patients received tacrolimus as an immunosuppressive therapy during the postoperative period and then had an antiretroviral drug regimen added. Tacrolimus pharmacokinetics were evaluated at steady state during these two periods. METHODS: Fourteen patients participated in the study and seven participated in the intensified pharmacokinetic protocol. Patients were included if they had undergone liver transplantation for end-stage chronic hepatitis C, absence of opportunistic infection, a CD4 cell count of >150 cells/microL and an undetectable HIV plasma viral load (<50 copies/mL) under highly active antiretroviral therapy. During the posttransplantation period, the tacrolimus dose was adjusted according to blood concentrations. When liver function and the tacrolimus dose were stable, antiretroviral therapy was reintroduced. RESULTS: When lopinavir/ritonavir were added to the tacrolimus regimen (seven patients), the tacrolimus dose was reduced by 99% to maintain the tacrolimus concentration within the therapeutic range. Only two patients were treated with nelfinavir, which led to a wide variation in inhibition of tacrolimus metabolism. When efavirenz (four patients) or a nucleoside analogue combination (one patient) was added, very little change in tacrolimus dosing was required. CONCLUSION: The lopinavir/ritonavir combination markedly inhibited tacrolimus metabolism, whereas the effect of efavirenz was small. Tacrolimus dosing must be optimised according to therapeutic drug monitoring and the antiretroviral drug combination.

Subcapsular liver haematoma after cardiopulmonary resuscitation by untrained personnel.

Although early cardiopulmonary resuscitation (CPR) is associated with increased survival of sudden cardiac arrest victims, it may also result in miscellaneous injuries. A 25-year-old inebriated man rescued from drowning in a swimming pool was apnoeic and pulseless after being pulled out of the water. Successful CPR was provided by untrained bystanders, including abdominal thrusts thought to remove water from the airways and chest compressions to provide haemodynamic support. As the patient progressively improved during his subsequent hospital stay, he complained of right upper abdominal and thoracic pain. A computed tomographic scan showed a 11 cm subcapsular haematoma contiguous to the right hepatic lobe. A favourable outcome was obtained after conservative, non-operative treatment. Subcapsular haematoma of the liver is a potentially life threatening complication that warrants consideration in survivors of cardiac arrest who have received closed chest compression and/or abdominal thrusts.

Acute hydrocarbon pneumonia after white spirit aspiration: sequential HRCT findings.

Hydrocarbon pneumonia is a very uncommon condition resulting from aspiration of mineral oil into the lung. We report the first description of early and sequential high-resolution computed tomographic (HRCT) findings of hydrocarbon pneumonia following attempted suicide by white spirit aspiration. Initial HRCT showed patchy opacities of coalescing masses with well-defined walls. They were visible in the middle lobe, lingula and lower lobes. Follow-up CT showed regression of the alveolar opacities, the presence of pneumatoceles and right asymptomatic pneumothorax. After 23 months of follow-up, the patient remained asymptomatic, and the follow-up CT scan was considered normal. The radiological features and a review of the relevant literature are briefly discussed.

Reactive hemophagocytic syndrome in adult systemic disease: report of twenty-six cases and literature review.

OBJECTIVE: To analyze specific clinical findings, underlying disorders, treatments, outcomes, and prognostic factors for reactive hemophagocytic syndrome (RHS) in systemic disease. METHODS: Data were collected using standardized forms as part of a French national survey. Adult cases without an underlying malignancy, diagnosed on bone marrow or lymph node biopsy, were included. RESULTS: Twenty-six cases (7 men, 19 women, mean age 47.4 +/- 17.7 years) were studied. Systemic diseases included systemic lupus erythematosus (n = 14), rheumatoid arthritis (n = 2), adult onset systemic Still's disease (n = 4), polyarteritis nodosa (n = 2), mixed connective tissue disease (n = 1), pulmonary sarcoidosis (n = 1), systemic sclerosis (n = 1), and Sjögren's syndrome (n = 1). RHS occurred in 2 distinct clinical settings in the course of systemic disease. RHS was associated with an active infection in 15 patients (bacterial infections, 10 cases; viral, 3 cases; tuberculosis, 1 case; and aspergillosis, 1 case) and with the onset of a systemic disease alone in 9 cases. Isolated RHS occurred in 2 cases. The overall mortality rate was 38.5%. Two factors were associated with mortality: corticosteroid treatment at the time of RHS diagnosis, and thrombocytopenia (odds ratio = 28, 95% confidence interval = 13.3-238.9). CONCLUSIONS: When RHS occurs in the course of an active systemic disease (situation only reported in cases of systemic lupus or adult Still's disease), immunosuppressive therapy should be used. In contrast, when RHS is present concomitantly with an active infection, immunosuppressive therapy needs to be lowered and antibiotic therapy should be instituted.

Contraceptive practices of non-HIV-seropositive injecting drug users.

AIMS: To study the sociodemographic characteristics and sexual behaviours in contraception choices of injecting drug users (IDUs) and to compare the contraceptive practices of non-HIV-positive IDUs to those of the general population. DESIGN: Two surveys were used: a sample of IDUs attending 10 drug abuse treatment centres in the Paris region (IDU) and the Parisian subsample of the National French Survey of Sexual Behaviour (ACSF). MEASUREMENTS: Percentages of contraception practices were estimated separately for 81 IDU and 130 ACSF women, and for 175 IDU and 168 ACSF men, aged 25-34, not reporting prostitution or HIV seropositivity. FINDINGS: Most IDU (77%) and ACSF (84%) women, and IDU (73%) and ACSF (75%) men currently used a contraceptive method. Male condoms were more widely used by IDUs than by the general population (64 vs. 10% in women, 75 vs. 14% in men), for all subgroups of educational level, marital status, recent multipartnership status and sexual activity. CONCLUSIONS: Contraceptives are used as often by IDUs as by the general population aged 25-34. However, the methods employed differ, with higher condom use by IDUs, which suggest that IDUs take into account the risk of HIV contamination in their contraceptive practices.

Intravenous use of prescribed sublingual buprenorphine tablets by drug users receiving maintenance therapy in France.

BACKGROUND: In 1996, sublingual buprenorphine was authorized for prescription in France for maintenance therapy (MT). MT should facilitate the rehabilitation of opioid-dependent drug users and reduce the risks associated with injection. However, misuse and side effects have been reported. OBJECTIVES: To assess the frequency of buprenorphine injection in 404 subjects on buprenorphine MT and to determine the factors associated with the injection of buprenorphine. METHODS: A cross-sectional survey was used to collect data from subjects on buprenorphine MT seeking treatment from health care networks, specialized structures, a prison and a hostel in three different regions of France (1998-1999). Information was collected by trained interviewers using a structured questionnaire. RESULTS: About half (46.5%) of the subjects on MT (188/404) had ever injected buprenorphine; 67.2% of this subgroup had since used both injected and sublingual buprenorphine. Variables associated with buprenorphine injection were having injected a substance other than buprenorphine (odds ratio (OR): 13.18; 95% CI: 5.36-32.42), cannabis use (OR: 2.34; 95% CI: 1.51-3.63) and having a source of income other than a salary (OR: 1.58; 95% CI: 1.02-2.45) and heroin use (OR: 0.23; 95% CI: 0.09-0.61). CONCLUSIONS: To decrease buprenorphine injection, prescribers of buprenorphine should participate in networks with specialized centers, and social and professional rehabilitation programs should be implemented for subjects on buprenorphine MT.

[French nationwide survey of abstinence-oriented treatments in opiate-addicted patients. Results at 12 months]. / Observatoire national des Traitements visant à l'Abstinence d'agonistes opiacés chez les patients Dépendants (OTAD). Résultats à 12 mois.

UNLABELLED: Over the last few years, general practitioners and pharmacists in France have become more directly involved in the treatment of opiate-addicted patients with the rapid development of office-based buprenorphine and methadone maintenance programs. At the same time, demand for abstinence-oriented interventions outside established maintenance programs continues to be addressed to the primary care system. METHOD: Our prospective and multicentric survey was conducted to monitor the follow-up of such abstinence-oriented interventions during a 12 months period, by means of questionnaires investigating the psychosocial, medical and addictive status of the patients recruited. RESULTS: One hundred and sixty five general practitioners have accepted to participate in the survey. Initially, they recruited 414 patients (51% terminating a buprenorphine maintenance treatment, 5% a methadone treatment and 36% withdrawing from heroin). Naltrexone chlorhydrate was prescribed for 50% early after entry in the survey. During the 12-month follow-up period: four data collections were proposed at 1, 3, 6, and 12 months. In all, data were collected for 158 patients. No data could be collected for 63 patients who were excluded from follow-up analysis. Out of the 351 patients who attended at least one follow-up visit, 137 (one third) moved to an opiate agonist maintenance program. When naltrexone was prescribed, total duration of treatment averaged 4785 days with no significant difference in terms of heroin relapse and attendance to follow-up visits. Between the first and the last data collection, out of the 113 HCV-positive patients, 13 received/started an anti-viral treatment. No significant difference was noted according to indicators of social outcome. CONCLUSION: Our survey shows that office-base abstinence-oriented interventions in opiate-addicted patients can produce a moderate benefit. Research concerning alternative formulations for opiate antagonists (e.g., long-acting naltrexone) could be helpfully in developing new options for treatment.

Association between first injection risk behaviors and hepatitis C seropositivity among injecting drug users.

HCV infection is rapidly acquired after drug addicts first inject drug intravenously. The risk behaviors accompanying the first intravenous substance injection are not well known. We used in 1997 a structured questionnaire to investigate the relationships between risk behaviors at the first injection and current reported HCV status. We interviewed 151 injecting drug users from four treatment centers and one prison in Paris. Risk markers for reported HCV seroconversion were explored by use of logistic regression models. One hundred and forty-three injecting drug users (95%) agreed to participate in the study. At the first injection, 50% shared preparation equipment; 22% borrowed and 26% lent injecting equipment. At the time of the study, 46% reported that they were HCV-positive. Sharing preparation equipment (odds ratio=3.1; 95% confidence interval: 1.2-7.8) and lending injection equipment (odds ratio=3.0; 95% confidence interval: 1.1-8.5) during the first injection were independently associated with reported HCV seropositivity. The high-risk behaviors accompanying the first intravenous injection of drugs justifies the implementation of specific prevention measures, aimed at young drug users who have not started to inject.

Injection risk behaviors at the first and at the most recent injections among drug users.

Risk behaviors at the first intravenous substance injection are unknown. A structured questionnaire was used to investigate the circumstances of the first injection and the changes in risk behaviors between the first and the most recent injections in a group of 143 intravenous drug users (IDUs). When they first injected most subjects were not alone, the initiator was an IDU (94%) who prepared the injection (76%) and did it (79%). The proportions of IDUs sharing preparation equipment (58 vs. 14%), borrowing (23 vs. 2%) and lending injecting equipment (26 vs. 4%) decreased between the first and the most recent injection.