Early activation of the cardiac CX3CL1/CX3CR1 axis delays ß-adrenergic-induced heart failure.

We recently highlighted a novel potential protective paracrine role of cardiac myeloid CD11b/c cells improving resistance of adult hypertrophied cardiomyocytes to oxidative stress and potentially delaying evolution towards heart failure (HF) in response to early ß-adrenergic stimulation. Here we characterized macrophages (Mφ) in hearts early infused with isoproterenol as compared to control and failing hearts and evaluated the role of upregulated CX3CL1 in cardiac remodeling. Flow cytometry, immunohistology and Mφ-depletion experiments evidenced a transient increase in Mφ number in isoproterenol-infused hearts, proportional to early concentric hypertrophy (ECH) remodeling and limiting HF. Combining transcriptomic and secretomic approaches we characterized Mφ-enriched CD45+ cells from ECH hearts as CX3CL1- and TNFα-secreting cells. In-vivo experiments, using intramyocardial injection in ECH hearts of either Cx3cl1 or Cx3cr1 siRNA, or Cx3cr1-/- knockout mice, identified the CX3CL1/CX3CR1 axis as a protective pathway delaying transition to HF. In-vitro results showed that CX3CL1 not only enhanced ECH Mφ proliferation and expansion but also supported adult cardiomyocyte hypertrophy via a synergistic action with TNFα. Our data underscore the in-vivo transient protective role of the CX3CL1/CX3CR1 axis in ECH remodeling and suggest the participation of CX3CL1-secreting Mφ and their crosstalk with CX3CR1-expressing cardiomyocytes to delay HF.

Generic drug prescriptions following hospital discharge: a prospective study in France.

AIMS: Systematic generic prescription at discharge could reduce confusion on drug-name usage, decrease commercial influence on medicine, and reduce drug-related expenditures. This study aimed to analyze generic drug prescriptions at discharge from hospital and to estimate the potential savings associated with a total substitution policy (substitution of every substitutable drug for its cheapest generic counterpart). METHODS: Drug prescriptions before admission and at discharge of all patients from three medical units of a university hospital were prospectively collected for five weeks without informing prescribers. RESULTS: Prescriptions from 85 patients were analyzed. On admission, 68 patients (80%) received 413 drugs; 141 were substitutable brand-name drugs and 23 (16%), which were directly prescribed as generics. At discharge, 488 drugs were prescribed to the 85 patients; 180 were substitutable drugs but only 5 (2.8%) were written as generics on prescription pads, a decrease of 78% (p<0.0001) compared to admission. In average, generics were 18% less expensive than brand-name drugs. Some common therapeutic classes offered even greater price difference, such as proton-pump inhibitors (42%), statins (32%), or antihypertensive agents (28%). Potential savings from a total substitution policy at discharge were estimated to €1512 per 1000 patients per week; for lifetime drugs, savings amounted to €18,960 per 1000 patients per year. CONCLUSIONS: Very few drugs are written as generics on medical forms at discharge in France. Hospital practitioners should be encouraged to prescribe generics, particularly in chronic diseases. A broad generic prescription policy at hospital discharge would result in substantial savings for health insurance.

Homelessness and high-dosage buprenorphine misuse.

AIM: To determine whether intravenous drug users (IDUs) are more likely to misuse high dosage buprenorphine (HDB) if they are homeless. DESIGN: We carried out a cross-sectional study using data collected from HDB users between 1998 and 1999. Data were collected by use of a structured questionnaire with questions about demographic characteristics, and use of HDB and other substances. IDUs were considered to be homeless if they did not live on their own or with their parents or friends. SETTING: IDUs were recruited from three centers for the treatment of drug users, three health care networks, one prison, one sleep-in, and two centers that provide psychosocial support for IDUs. PARTICIPANTS: Of the 788 eligible patients, 779 answered the questionnaire (response rate: 98.9%). RESULTS: Homeless IDUs were more likely to have injected HDB than those who were not homeless (67% vs. 47%; p<0.001), and their injection behaviors were more likely to be unsafe. The first HDB injection was more likely to result in medical complications in the homeless group than in the nonhomeless group (58% vs. 38%; p=0.001). Homeless IDUs were less likely to receive medical followed-up and were less well informed about the correct way of using HDB than nonhomeless IDUs. CONCLUSION: Homeless IDUs are more likely to misuse HDB. Thus, HDB maintenance therapy may not be the most appropriate maintenance therapy for this group.

[Buprenorphine abuse: high dose intravenous administration of buprenorphine]. / Substitution et mésusage: l'injection intraveineuse de buprénorphine haut dosage.

BACKGROUND: In France, actually, around 70 000 drug addicts are treated with buprenorphine available as sublingual tablets. Clinical studies have demonstrated the clinical efficacity of buprenorphine for opiate addiction. But, it has been reported that some of them injected buprenorphine. Some inquiries have suggested measured with 10% to 40% injectors. To use buprenorphine tablets for injections have had heavy sanitary consequences (4). OBJECTIVES: To know the use buprenorphine context in our population and to analyse the circumstances and outcomes of buprenorphine injection for drug addicts. METHOD: In 1998-1999, we conducted a cross-sectional survey using a structured questionnaire. Information wax collected during a 30-minute face-to-face interview through an 69-item structured questionnaire administered by trained investigators. The questionnaire was composed of questions about social demographic data, the drugs taken before the first use of buprenorphine, the circumstances of the first buprenorphine experiment, the reasons for the first buprenorphine injection into drug addicts, the other substances used in the same time, the risks behaviors, the sensations seeking, the medical consequences. The questionnaire was first tested in a pilot study through ten patients. Drug addicts were followed-up in 8 drug abuse treatment centres among which 2 networks of general practitioners in Paris region, in Strasbourg region and in Nice region. The investigators were general practitioners, psychologists, psychiatrists, educators, nurses. All drugs addict which reported use buprenorphine were seen in treatment centre and were 18 years old or older, were eligible. Drugs addict with severe mental disorders, unable to answer the questions were excluded. Respondents received an assurance of confidentiality and informed consent was obtained. Standard descriptive statistics were used to analyse subjects characteristics: frequency, standard deviation. The study was funded by the Observatoire Français des Drogues et des Toxicomanies (OFDT). RESULTS: Of the 779 consecutive drug addicts interviewed, 770 completed the questionnaire. The study has shown that the majority of subjects were male (77.2%), mean age was 31.3 (SD: 5.98). Most of them were unmarried (67.5%). They had no real employment (56.5%). The mean age at the first use opiate was 19.5 (SD: 4.5). The mean age at the first heroin injection was 20.7 (SD: 4.6). At the time of interview, most of drugs addict used more than two types of drugs (42.6%). Many associations with buprenorphine are described particularly associations to alcohol (41.2%), benzodiazepines (40%), cocaine (12.4%), heroin (7.8%), crack (7.2%); most of these subjects getting buprenorphine without any medical prescription. Most drug addicts had asked themselves for using buprenorphine (61.0%). Near fifty per cent (49.5%) injected buprenorphine. Among them, 39.6% injected this substance the first time they used it. Curiosity (72.8%), need for injection (69.0%), sensation seeking (49.0%) were reasons given by drug addicts for buprenorphine injection. Others reasons were given: an inadequate dosage of sublingual buprenorphine, to find buprenorphine in black market. Buprenorphine injection took place in the secure environment (57.5%). Drug addicts were not alone when they injected (53.6%). The introducer was an buprenorphine user (57%). The first buprenorphine injection sensation was not pleasant (61%), although injection of buprenorphine is usually performed by 80% of them. However, 93% had been informed that buprenorphine injection was contra-indicated. CONCLUSION: Since six years, many French patients have received a treatment for opiate addiction. High dosage buprenorphine is actually the principal treatment for substitution medication in France. Some misappropriations and wrong uses have been seen, the most frequent and sever being using tablets for injections. The prevalence of buprenorphine injection is high among drug addicts. The results of the study show that the first buprenorphine Injection takes places place a few time after the first buprenorphine use. The codependance to other substances is one of risk markers for intravenous use of buprenorphine tablets and the dangers of polyintoxication were known. Curiosity, need for injection favour buprenorphine injection. But, the sensation seeking brings on the drug addict too. The rather loose frame of prescription, a lack of training among general practitioners, the fragility of the specialises network, the complexities in the care of drug users which not resumed by a substitution must take into consideration. The drug addict's career, the subject's environment and the circumstances of the buprenorphine injection have not been previously described. However their knowledge are of prime necessity to prevent this abnormal use and to find the best treatment for drug addicts.

Prises de risques lors de la premiere injection intraveineuse de drogue.

Aims. - The objectives of the study were to describe the circumstances surrounding the intiation of intravenous drug use, the role of the introducer and to evaluate intravenous drug users risk behaviors at the first injection of drug. Design.- In 1997, we conducted a cross-sectional survey using a structured questionnaire concerning the initiation process into intravenous drug abuse. IDUs were interviewed in four treatment drug abuse and psychosocial centers in Paris and in one prison. Participants.- Of the 152 consecutive IDUs interviewed, 143 completed the questionnaire, 83 were male. Findings. - The mean age at first opiate use and at first injection were 19 years (SD: 4.3) and 20 years (SD: 4.3). At first injection, heroin was the main used drug (91%), the subject was with others persons (91%), asked himself for injection (70%) albeit had not planned this injection (40%). The subject injected at a friend's home (31%). The introducer was an IDU (93%), mean age 23.4 (SD: 5.2). He or she was a friend (61%) or a sexual partner (14%). The preparation of the first injection and the injection were made by the introducer in 72% and 74% of cases. The injecting equipment had been borrowed (22%) from an IDU whose HIV status and HCV status were unknown in 83% and 85% of cases. Conclusion. - Our study shows novel results about the first injection, they are of prime importance for harm reduction. The introducer plays a major role in preventing risk-behavior at the first injection and for education about safe injecting practices.

HCV status knowledge and risk behaviours amongst intravenous drug users.

The aim of this study was to identify relationships between injecting and sexual risk behaviours and hepatitis C virus (HCV) status knowledge in intravenous drug users (IDUs). It was a cross-sectional survey (March 1994-June 1995) in 10 drug abuse treatment or psychosocial centres in Paris, France. We used a structured questionnaire about sexual, injecting, HIV and HCV antibody testing practices and results during the previous 6 months. Six hundred and twelve sexually active IDUs aged 18 or older who were current injecting drug users were interviewed. Of 592 respondent IDUs, 37% did not report consistent HCV testing and 34% reported being HCV-positive. HCV-positive IDUs were older than HCV-negatives and HCV-unknowns. HCV-unknowns and HCV-positives had a lower educational level than HCV-negatives. After adjusting for demographic characteristics and HIV status, the factors associated with being HCV-unknown were not using condoms (OR: 2.9; 95% CI: 1.9-4.6) as well as clean equipment (OR: 1.8; 95% CI: 1.2-3.0). Not using new equipment was negatively associated with being HCV-unknown (OR: 0.4; 95% CI: 0.2-0.6) and with being HCV-positive (OR: 0.5; 95% CI: 0.3-0.8). Our study suggests that particular sexual and injecting risk-behaviours are associated with not knowing HCV status. As HCV-unknown IDUs are likely to be at the risk of transmitting HCV or acquiring other infections. HCV testing should be encouraged and associated with sexual counselling. Special attention should be paid to disinfecting practices for HCV-positives and use of new injecting equipment should be recommended for HCV-negatives.

[Risks incurred by the first intravenous drug injection]. / Prises de risques lors de la première injection intraveineuse de drogue.

AIMS: The objectives of the study were to describe the circumstances surrounding the initiation of intravenous drug use, the role of the introducer and to evaluate intravenous drug users risk behaviors at the first injection of drug. DESIGN: In 1997, we conducted a cross-sectional survey using a structured questionnaire concerning the initiation process into intravenous drug abuse. IDUs were interviewed in four treatment drug abuse and psychosocial centers in Paris and in one prison. PARTICIPANTS: Of the 152 consecutive IDUs interviewed, 143 completed the questionnaire, 83 were male. FINDINGS: The mean age at first opiate use and at first injection were 19 years (SD: 4.3) and 20 years (SD: 4.3). At first injection, heroin was the main used drug (91%), the subject was with others persons (91%), asked himself for injection (70%) albeit had not planned this injection (40%). The subject injected at a friend's home (31%). The introducer was an IDU (93%), mean age 23.4 (SD: 5.2). He or she was a friend (61%) or a sexual partner (14%). The preparation of the first injection and the injection were made by the introducer in 72 % and 74 % of cases. The injecting equipment had been borrowed (22%) from an IDU whose HIV status and HCV status were unknown in 83 % and 85 % of cases. CONCLUSION: Our study shows novel results about the first injection, they are of prime importance for harm reduction. The introducer plays a major role in preventing risk-behavior at the first injection and for education about safe injecting practices.

[Recurrent bilateral pleurisy in an 80-year-old man]. / Pleurésie bilatérale récidivante chez un homme de 80 ans.

An 80-year-old man was admitted with recurrent asphyxiating pleurisy, first attributed to heart failure. During the recurrent episodes, the patient presented fever, signs of inflammation, no signs of heart failure, and subnormal cardiac function, prompting further investigations which disclosed that the patient was a homozygous carrier of the severe type of periodic disease mutation. The patient's age at symptom onset and the clinical features of this case of periodic disease are exceptional. These points emphasize the usefulness of available genetic tests in difficult diagnostic cases. It also reflects current difficulties in trying to establish correlations between genotype and phenotype in periodic disease.

Cardiac cause of hypoxaemia in a kyphoscoliotic patient.

This report presents the case of a 73 yr-old female in whom kyphoscoliosis, osteoporotic vertebra compression fractures and sternal injury resulted in severe respiratory failure and hypoxaemia. Pulmonary function testing showed moderate restrictive pattern and rare mismatches were found on lung ventilation/perfusion scanning. Transoesophageal echocardiography with contrast studies showed abnormal anatomic mediastinal interactions which led to right-to-left interatrial shunt, through patent foremen ovale. First-intention treatment, because of orthopaedic and respiratory surgical restraints, was to close the shunt using transcatheter devices. Follow-up after 6 months demonstrated that these interauricular umbrella devices corrected arterial hypoxaemia. True right-to-left interatrial shunts can be found in kyphoscoliotic patients, as a result of thoracic deformation, and can be safely treated with percutaneous trancatheter closure.

[Risk behaviors of intravenous drug users: are females taking more risks of HIV and HCV transmission?]. / Les comportements à risque des usagers de drogues par voie intraveineuse: les femmes prennent-elles plus de risques de transmission des virus VIH et VHC?

BACKGROUND: This work was aimed at identifying differences in HIV and HCV risk behaviors among intravenous drug users (IDUs) according to the gender and their determinants. METHODS: IDUs over 18 years, having had sexual intercourse and able to answer the questionnaire were interviewed in 10 drug abuse treatment centers or social institutions using a questionnaire adapted from the one used in the survey of sexual lifestyle in France. RESULTS: Over 612 eligible IDUs, 595 completed the questionnaire (women: 29%);37% had multiple partners with no difference according to the gender; 14% of the women and 7% of the men reported trading sex. More women reported inconsistent condom use (46% vs. 55%) and inconsistent clean equipment use (65% vs. 73%). A younger age, independently associated to sharing equipment (men: OR = 0.94; 95% CI = 0.90-0.99; women: OR = 0.92; 95% CI = 0.85-0.99) and inconsistent HIV serology testing, independently associated to inconsistent condom use (men: OR = 3.36; 95% CI = 2.02-5.60; women: OR = 10.72; 95% CI = 3.18-36.18), were the only risk markers common to both genders. For women, being HIV negative increased the risk of inconsistent condom use. Low educational level increased the risk of inconsistent clean equipment use. No risk marker among those analyzed was associated to having had multiple partners. For men, low socioeconomic status markers, a steady sexual partner or not living in couple and educational level were associated with sexual risk behaviors (inconsistent condom use and having multiple partners); low socioeconomic status markers were associated with injecting risk behaviors (inconsistent clean equipment use and sharing). CONCLUSIONS: Women were more likely to have both sexual and injecting risk behaviors; their significant risk markers are less numerous thus harm reduction could be more difficult than for men.

Patterns of sexual and injecting risk behaviours in French intravenous drug users not reporting HIV and hepatitis C virus seropositivities.

AIMS: To characterize and identify determinants of risk behaviour patterns of intravenous drug users (IDUs) independently of changes due to knowledge of HIV or hepatitis C Virus (HCV) seropositivity. DESIGN: A cross-sectional survey using a structured questionnaire concerning sexual, injecting and HIV and HCV antibody testing practices. SETTING: IDUs were interviewed in the Paris region at 10 treatment or psychosocial centres. PARTICIPANTS: Six hundred and twelve consecutive sexually active IDUs over 18 years able to answer the questionnaire. MEASUREMENTS: Five hundred and ninety-five IDUs completed the questionnaire. The risk-behaviour patterns of the 328 IDUs not reporting HIV or HCV seropositivity were analysed by phi correlation. Risk factors for each risk behaviour were determined by regression logistic models yielding odds ratios (OR) and their 95% confidence intervals (95% CI). FINDINGS: Several risk behaviour patterns were suggested: (1) lending, borrowing; (2) not or inconsistently testing HIV and HCV serology and not or inconsistently using condoms; (3) having multiple partners and prostitution; and (4) not using clean equipment. Alcohol abuse was independently and specifically associated with lending (OR = 3.8; 95% CI: 2.1-7.0) and borrowing (OR = 3.3; 95% CI: 1.8-6.1); homelessness with injecting risk behaviours and with prostitution (OR = 2.7; 95% CI: 1.2-6.1); low educational level and having children with not or inconsistently using condom and serology testing; and cocaine use with not or inconsistently using condoms (OR = 0.4; 95% CI: 0.3-0.7) and serology testing and not using clean equipment (OR = 0.4; 95% CI: 0.2-0.8). Having multiple partners and prostitution had no common risk factors. CONCLUSIONS: Identifying specific risk factors could help to target drug harm reduction programmes for each risk behaviour pattern among IDUs not reporting HIV and HCV seropositivity.

[Withdrawal in opiate addicts in an internal medicine hospital unit]. / Sevrage des toxicomanes dépendant des opiacés, dans une unité hospitalière de médecine interne.

Withdrawal of opiates drug addicts in Internal Medicine is unusual in France. Four main preliminary conditions are requested: 1--Drug addict preparation and self motivation, 2--Inter and intra institution team collaboration, 3--Opening the hospital towards community agencies, 4--Hospital staff recruited on volunteer basis. Within two years (1992-1993), 210 opiates drug addicts were hospitalized for withdrawal. Two third were males, median age was 27, median years of addiction was 7. Thirty percent were seropositive for HIV, 70% for HCV. Hospitalisation lasted 7 days for heroin addicts and 10 days for morphin, codein or buprenorphin addicts. Successful withdrawn was observed for 70% patients but six months after withdrawal, only 15% remained abstinent.