Caroline Lions

Methadone Induction in Primary Care for Opioid Dependence: A Pragmatic Randomized Trial (ANRS Methaville)

Objective Methadone coverage is poor in many countries due in part to methadone induction being possible only in specialized care (SC). This multicenter pragmatic trial compared the effectiveness of methadone treatment between two induction models: primary care (PC) and SC. Methods In this study, registered at ClinicalTrials.Gov (NCT00657397), opioid-dependent individuals not on methadone treatment for at least one month or receiving buprenorphine but needing to switch were randomly assigned to start methadone in PC (N = 155) or in SC (N = 66) in 10 sites in France. Visits were scheduled at months M0, M3, M6 and M12. The primary outcome was self-reported abstinence from street-opioids at 12 months (M12) (with an underlying 15% non-inferiority hypothesis for PC). Secondary outcomes were abstinence during follow-up, engagement in treatment (i.e. completing the induction period), retention and satisfaction with the explanations provided by the physician. Primary analysis used intention to treat (ITT). Mixed models and the log-rank test were used to assess the arm effect (PC vs. SC) on the course of abstinence and retention, respectively. Results In the ITT analysis (n = 155 in PC, 66 in SC), which compared the proportions of street-opioid abstinent participants, 85/155 (55%) and 22/66 (33%) of the participants were classified as street-opioid abstinent at M12 in PC and SC, respectively. This ITT analysis showed the non-inferiority of PC (21.5 [7.7; 35.3]). Engagement in treatment and satisfaction with the explanations provided by the physician were significantly higher in PC than SC. Retention in methadone and abstinence during follow-up were comparable in both arms (p = 0.47, p = 0.39, respectively). Conclusions Under appropriate conditions, methadone induction in primary care is feasible and acceptable to both physicians and patients. It is as effective as induction in specialized care in reducing street-opioid use and ensuring engagement and retention in treatment for opioid dependence. Trial registration Number Eudract 2008-001338-28; ClinicalTrials.gov: NCT00657397; International Standard Randomized Controlled Trial Number Register ISRCTN31125511

Eating at the university canteen. Associations with socioeconomic status and healthier self-reported eating habits in France

French university canteens offer structured meals at a fixed moderate price. We examined whether eating regularly at university canteens was associated with socioeconomic status (SES) or dietary practices. The study data came from a cross-sectional study of a random sample of 1723 students aged 18-24 years, in their first year of university in 2005-2006, enrolled in the universities of southeastern France (response rate=71%). Self-reported dietary practices were collected with a behavioral questionnaire. Adjusted logistic regressions showed that eating regularly at university canteens was less frequent among students with less than € 300 monthly resources and not living with their families (OR=0.68 [95%CI: 0.49-0.94]). It was also positively associated, regardless of SES, with the consumption of at least five servings of fruit/vegetables daily (OR=1.42 [1.05-1.92]) and one serving of meat/fish daily (OR=1.41 [1.13-1.76]) but not with either restricting fatty food (OR=1.04 [0.81-1.33]) or never/rarely adding salt to food (OR=1.06 [0.85-1.32]). Eating regularly at university canteens was less frequent among less well-off students and was positively associated with some healthier self-reported dietary habits. Further research is needed to confirm these results in the overall student population in France and to understand the determinants of university canteen utilization.

Association between elevated coffee consumption and daily chocolate intake with normal liver enzymes in HIV-HCV infected individuals: Results from the ANRS CO13 HEPAVIH cohort study

BACKGROUND & AIMS We used longitudinal data from the ANRS CO13 HEPAVIH cohort study of HIV-HCV co-infected individuals to investigate whether polyphenol rich food intake through coffee and/or daily chocolate consumption could play a role in reducing liver enzymes levels. METHODS Longitudinal data collection included self-administered questionnaires and medical data (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) liver enzymes). Two analyses were performed to assess the association between coffee (≥3 cups a day) and daily chocolate intake and abnormal values of AST and ALT (AST or ALT >2.5 × upper normal limit (UNL)) (N=990) over time, after adjustment for known correlates. Logistic regression models based on generalized estimating equations were used to take into account the correlations between repeated measures and estimate adjusted odds ratio. RESULTS After adjustment, patients reporting elevated coffee consumption and daily chocolate intake were less likely to present abnormal ALT (OR=0.65; p=0.04 and OR=0.57; p=0.04, for coffee and chocolate respectively), while only patients reporting elevated coffee consumption were less likely to have abnormal AST values (p=0.05). Nevertheless, the combined indicator of coffee and chocolate intake was most significantly associated with approximately 40% reduced risk of abnormal liver enzymes (p=0.003 for AST; p=0.002 for ALT). CONCLUSIONS Elevated coffee consumption and daily chocolate intake appear to be associated with reduced levels of liver enzymes in HIV-HCV co-infected patients. Further experimental and observational research is needed to better understand the role that polyphenol intake or supplementation can play on liver disease and liver injury.

Predictors of non-prescribed opioid use after one year of methadone treatment: An attributable-risk approach (ANRS-Methaville trial)

BACKGROUND The effectiveness of methadone as an opioid maintenance treatment (OMT) for opioid dependence has been widely demonstrated. However many patients continue to use other opioids while on methadone treatment. Studies assessing avoidable cases of continued non-prescribed opioid use during methadone treatment are sparse. METHODS At 12 months of treatment (M12), 158 subjects had available data on opioid use, measured using the Opiate Treatment Index. We identified variables associated with non-prescribed opioid use at M12, using a univariate logistic regression and two multivariate models, one incorporating only pre-treatment variables, the second adding the in-treatment variables. We also calculated attributable fractions for risk factors. RESULTS At M12, 32.3% of the patients had used non-prescribed opioids during the previous month. A good patient-physician relationship was the most influential factor associated with not using non-prescribed opioids after one year. Living with a heroin user after one year of treatment, using cocaine during treatment and hazardous alcohol consumption at enrolment were all associated with an increased risk of non-prescribed opioid use at M12. Analysis of attributable fractions indicated that living with a heroin user at M12 accounted for 21% of patients reporting non-prescribed opioid use at M12, while the lack of a good relationship with the physician accounted for 26%. CONCLUSIONS The attributable risk approach suggests that continued non-prescribed opioid use by a considerable proportion of individuals could potentially be reduced by improving patient-physician relationships, enhancing care for co-dependent patients and encouraging patients to modify their social network.

Papillomavirus vaccine coverage and its determinants in South-Eastern France.

OBJECTIVES We wanted: (i) to assess vaccine coverage (VC) for papillomavirus (HPV) (one and three doses of the vaccine, VC1 and VC3) and compliance with the recommended vaccination regimen (3rd dose within 1 year after the 1st dose) among 14-16 year-old girls; and (ii) to identify the factors independently associated with VC and compliance with the recommended vaccination regimen. METHODS We conducted a descriptive longitudinal study, using the National Health Insurance reimbursement database, for years 2007 to 2009, in South-Eastern France. We performed a multivariate analysis (Cox proportional hazards model). RESULTS VC1 was 35.5%, with 68.8% of those who started vaccination having completed the 3-dose regimen, 64.1% within one year. VC1 and VC3 were positively associated with the girls age. Girls covered by the complementary social welfare healthcare program and those living in rural areas had lower VC1 and VC3. Being covered by the complementary social welfare healthcare program was also associated with lower compliance with the recommended vaccination regimen. VC1 and VC3 were positively associated with the number of medical consultations during the study period. Important geographical variations were noted regarding VC1. CONCLUSIONS Our study confirms that VC for HPV is insufficient in our region, and that there are socio-economic and geographical inequalities. Even though the vaccine is reimbursed for all girls, efforts must be made to improve VC, particularly for girls covered by the complementary social welfare healthcare program and those living in rural areas.

Impact of HCV treatment and depressive symptoms on adherence to HAART among coinfected HIV-HCV patients: results from the ANRS-CO13-HEPAVIH cohort.

BACKGROUND The additional burden of HCV infection in HIV-HCV-coinfected individuals may have some consequences on adherence to HAART. Few studies have explored the pattern of correlates of non-adherence to HAART while simultaneously considering the impact of HCV treatment and depressive symptoms on adherence to HAART. We used longitudinal data to assess factors associated with non-adherence to HAART. METHODS The French national prospective cohort ANRS-CO13-HEPAVIH is a multicentrer cohort, which recruited 1,175 HIV-HCV-coinfected patients in 17 hospital outpatient units delivering HIV and HCV care in France between October 2006 and June 2008. For this analysis, we selected participants on HAART with self-reported data for adherence to HAART (n=727 patients, 1,190 visits). Data were collected using self-administered questionnaires and medical records. A mixed logistic regression model based on an exchangeable correlation matrix was used to identify factors associated with non-adherence to HAART. RESULTS Patients reported non-adherence to HAART in 808 (68%) of the 1,190 visits. Four variables remained associated with non-adherence to HAART after multivariate analysis: hazardous alcohol consumption, cocaine use and depressive symptoms, regardless of whether treatment for depression was being received. Finally, patients being treated for HCV infection were less likely to be non-adherent to HAART. CONCLUSIONS Besides the problem of polydrug use, two other dimensions deserve special attention when considering adherence to HAART in HIV-HCV-coinfected patients. Access to HCV treatment should be encouraged as well adequate treatment for depression in this population to improve adherence and response to HAART.

Drug-specific quality indicators assessing outpatient antibiotic use among French general practitioners.

Quality indicators assessing the use of antibiotics among general practitioners (GPs) would be useful to target antibiotic stewardship interventions. We adapted to an individual GP level a set of 12 drug-specific quality indicators of outpatient antibiotic use in Europe developed by the European surveillance of antimicrobial consumption project. We performed a cross-sectional study analysing reimbursement data on outpatient antibiotic prescriptions in adults in south-eastern France in 2009. Substantial heterogeneity in antibiotic prescribing among French GPs was observed, and opportunity to improve antibiotic prescribing can be identified.

Suicidal risk among patients enrolled in methadone maintenance treatment: HCV status and implications for suicide prevention (ANRS Methaville).

BACKGROUND Suicide is a critical issue among opioid users. The aim of this study was to assess the relationship between HCV status and suicidal risk in patients receiving methadone treatment. METHODS We used data from Methaville, a multicenter, pragmatic randomized trial designed to evaluate the feasibility of methadone induction in primary care compared with induction in specialized centers. Suicidal risk was assessed at enrollment and after one year of methadone treatment using the suicidality module in the MINI International Neuropsychiatric Interview. Socio-demographic characteristics, drug and alcohol consumption, behavioral and personality factors, history of drug use and health indicators were also assessed. RESULTS A total of 195 individuals were enrolled from January 2009 to December 2010. Suicidal risk assessment was available at month 0 (M0) and M12 for 159 (72%) and 118 (73%) individuals, respectively. Forty-four (28%) were at risk of suicide at M0 and 17 (14%) at M12 (p=0.004). One patient attempted suicide by overdose during the one-year follow-up. The following three factors were associated with suicidal risk: hepatitis C virus (HCV) positive status (OR [95%CI]=17.25 [1.14-161.07]; p=0.04), receiving food assistance (OR [95%CI]=0.05 [0.00-1.05]; p=0.05) and a higher number of health problems (OR [95%CI]=1.24 [1.08-1.44]; p=0.003). CONCLUSIONS Special attention should be given to HCV-positive patients through suicidal risk prevention strategies and routine suicide assessment as part of a comprehensive approach to prevention and care for opioid users. Our results represent a new and powerful argument for the expansion of access to HCV treatment to drug users with chronic infection.

Factors associated with HCV risk practices in methadone-maintained patients: the importance of considering the couple in prevention interventions

BackgroundOne important public health issue associated with opioid use today is the risk of hepatitis C (HCV) infection. Although methadone maintenance may help to decrease HCV-related risk practices, HCV risk behaviors persist and are strongly associated with specific substance use patterns, mental status and social context. The ANRS-Methaville study gave us the opportunity to better disentangle the different relationships between these various factors and HCV risk practices.MethodsThe ANRS-Methaville multisite randomized trial was designed to assess the feasibility of initiating methadone in primary care by comparing it with methadone initiation in specialized centers. This study recruited 195 participants initiating methadone maintenance and followed up for 12 months. Longitudinal data from this trial was used to acquire a greater understanding of HCV risk practices and their pattern of correlates in this population. We selected 176 patients who had data on HCV risk practices at M0 and M12, accounting for 312 visits. HCV risk practices were defined as follows: sharing needles or syringes, sharing drug paraphernalia, getting a tattoo or having a piercing in a non-professional context, sharing toiletry items. To identify factors associated with HCV risk practices, we performed a mixed logistic regression analysis.ResultsHCV risk practices were reported by 19% and 15% of participants at baseline and M12, respectively. After adjustment for age, cocaine use and alcohol dependence as well as suicidal risk, living in a couple with a non-drug user and in a couple with a drug user were both independent predictors of HCV risk practices (OR[CI95%] = 4.16 [1.42-12.12]; OR[CI95%] = 9.85 [3.13-31.06], respectively).ConclusionsIdentifying individuals at risk of HCV transmission during methadone treatment such as stimulant users, alcohol dependent individuals, and those at suicidal risk is necessary to optimize response to treatment. Innovative prevention approaches tailored to couples are also urgently needed and could decrease HCV-risk in this population.The trial is registered with the French Agency of Pharmaceutical Products (ANSM) under the number 2008-A0277-48, the European Union Drug Regulating Authorities Clinical Trials. Number Eudract 2008-001338-28, the ClinicalTrials.gov Identifier: NCT00657397 and the International Standard Randomised Controlled Trial Number Register ISRCTN31125511.

HCV seropositivity in inmates and in the general population: an averaging approach to establish priority prevention interventions

Objectives Despite the fact that a considerable portion of hepatitis C virus (HCV) positive individuals are viraemic, the risk of transmitting HCV to others is context dependent. Prison is a particularly risky environment as HCV prevention tools are often unavailable. Using data from a cross-sectional study conducted in centres for HCV testing in southeastern France, we aimed to compare the patterns of risk factors in HCV-positive inmates with those in the general population. Setting 26 centres for HIV/HCV testing in southeastern France (23 in the general population and 3 in prison). Primary outcome measure HCV seropositivity measured with ELISA test. Methods A propensity score method to ensure that the general and inmate populations could be compared and a multimodel averaging to estimate the degree (strong, weak, none) of the association of a number of specific factors with HCV seropositivity in each group. Results Among the 52 082 participants, HCV infection prevalence was 1.5% and 5.2% in the general (n=46 125) and inmate (n=5957) populations, respectively. In both populations, ‘drug injection without snorting’ and ‘drug injection with snorting’ were very strongly associated with HCV seropositivity. Among inmates, ‘drug snorting alone’ (OR (95% CI) 2.21 (1.39 to 3.52) was also a strong correlate while tattoos, piercings (OR (95% CI) 1.22 (0.92 to 1.61)) and the sharing of toiletry items (OR (95% CI) 1.44 (0.84 to 2.47)) were weak correlates. Conclusions The pattern of risk factors associated with HCV seropositivity is different between the general and prison populations, injection and snorting practices being more prevalent in the latter. Access to prevention measures in prisons is not only a public health issue but also a human right for inmates who deserve equity of care and prevention.