Patterns of Methylphenidate Use and Assessment of Its Abuse among the General Population and Individuals with Drug Dependence.

PURPOSE: The aim of this study was to describe the extent of methylphenidate (MPH) abuse and characterize its patterns by following several cases involving intravenous administration of crushed MPH tablets. METHODS: First, a drug reimbursement database (covering 4 million inhabitants) was explored to assess the magnitude of MPH abuse among the general population, and second, a specific study based on individuals with drug dependence was performed to describe abusers' characteristics (n = 64), patterns of abuse and clinical implications. RESULTS: From 2005 to 2011, the number of patients who were dispensed MPH at least once increased by 166%. The patients with 'deviant' patterns of MPH consumption were mainly male adults with opiate maintenance treatment reimbursements. MPH abusers had precarious living conditions. Half of them consumed MPH daily by intravenous route and reported amphetamine-like effects (cardiovascular events, weight loss, psychiatric adverse events). CONCLUSION: Given the increase of MPH use, it is important to warn the scientific community about possible MPH abuse, especially in individuals with drug dependence. This study has facilitated public health intervention and dissemination of information related to MPH abuse among health care professionals at local and national levels.

Triptans use and overuse: A pharmacoepidemiology study from the French health insurance system database covering 4.1 million people.

INTRODUCTION: The objective of this study was to estimate and to characterize the actual patterns of triptan use and overuse in France using a drug reimbursement database. METHODS: We included all people covered by the French General Health Insurance System (GHIS) from the Provence-Alpes-Côte-d'Azur (PACA) and Corsica administrative areas who had at least one dispensed dose of triptans between May 2010 and December 2011. All dispensed doses of triptans, migraine prophylactic treatment and psychotropic medications were extracted from the GHIS database. Triptan overuse was defined as triptan use >20 defined daily doses (DDD) per month on a regular basis for more than three consecutive months. Risk of overuse was assessed using logistic regression adjusted for gender and age. RESULTS: We included 99,540 patients who had at least one prescription of a triptan over the 20 months of the study. Among them, 2243 patients (2.3%) were identified as overusers and received 20.2% of the total DDD prescribed. Twelve percent of overusers and 6.9% of non-overusers were aged more than 65 years (OR: 1.81). Overusers did not have a greater number of prescribers and pharmacists than non-overusers. They were more frequently prescribed a prophylactic medication for migraine treatment (56.8% vs 35.9%, OR: 2.36), benzodiazepines (69.9% vs 54.7%, OR: 1.93) and antidepressants (49.4% vs 30.2%, OR: 2.33). CONCLUSIONS: This work suggests that triptan overuse may be due to insufficient prescriber awareness of appropriate prescribing. The off-label prescription of triptans among the elderly necessitates investigating their cardiovascular risk profile in this sub-group.

[Antipsychotic use in the cohort PACA-Alz in patients with Alzheimer's disease and other dementia in 2010]. / Consommation d'antipsychotiques chez les sujets atteints de maladie d'Alzheimer et maladies apparentées de la cohorte PACA-Alz 2010.

AIM: The aim of the study was to identify and to characterize patients with Alzheimer's disease or related dementia describing antipsychotics and other psychotropic expositions. METHODS: The study was performed, in 2010, based on Provence-Alpes-Côte d'Azur region (PACA)-Corse Alz cohort included patients with dementia, with chronic condition 'Alzheimer disease or related disease' and/or had at least one delivery of Alzheimer's specific treatment, registered in the General Health Care System. Psychotropic drugs were extracted according anatomical, therapeutical and chemical code. Chronic exposure defined as more than 3 consecutive deliveries. RESULTS: Among 34 696 included patients, 26.9% were men and 68.8% were 80 years old and more. Among them, 26% received at least one antipsychotic medication, with a chronic exposition estimated around 61.3%. Antidepressant and anxiolytic were consumed respectively by 47% and 45.3% of patients. Risperidone was the most used antipsychotic (11.2%). The Health care use (hospitalizations, nurses and physicians visits) was significantly higher among patients with antipsychotics. CONCLUSION: Antipsychotics use in patients with dementia remains high. The follow up of this regional cohort would be helpful to identify the impact of guidelines on the prescription and the care of patients with dementia.

[National and regional market penetration rates of generic's high dosage buprenorphine: its evolution from 2006 to 2008, using reimbursed drug database]. / Taux de pénétration des génériques de la buprénorphine haut dosage : principales tendances de 2006 à 2008.

OBJECTIVE: To assess the national market penetration rate (PR) of generic high-dosage buprenorphine (HDB) in 2008 and its evolution since their marketing (2006), and making a point for each dosage and at regional level. METHODS: Retrospective study over data using national and regional health reimbursement database over three years (2006-2008). RESULTS: In 2008, the generic HDB's national MPR was 31%. The PR for each dosage were 45% for 0.4 mg, 36% for 2 mg and 19% for 8 mg. The (PR) based on Defined Daily Dose (DDD) was 23% in 2008, 15% in 2007 and 4% in 2006. In 2008, at the regional level, disparities were observed in the adjusted penetration rate from 15% in Île de France to 39% in Champagne Ardennes Lorraine. CONCLUSION: The national PR of generic HDB has increased. There are differences in MPR in terms of dosage and area. However, this PR is still low (in 2008, 82% of the delivered drugs are generics).

Longitudinal cortex-wide monitoring of cerebral hemodynamics and oxygen metabolism in awake mice using multi-parametric photoacoustic microscopy.

Multi-parametric photoacoustic microscopy (PAM) has emerged as a promising new technique for high-resolution quantification of hemodynamics and oxygen metabolism in the mouse brain. In this work, we have extended the scope of multi-parametric PAM to longitudinal, cortex-wide, awake-brain imaging with the use of a long-lifetime (24 weeks), wide-field (5 × 7 mm2), light-weight (2 g), dual-transparency (i.e., light and ultrasound) cranial window. Cerebrovascular responses to the window installation were examined in vivo, showing a complete recovery in 18 days. In the 22-week monitoring after the recovery, no dura thickening, skull regrowth, or changes in cerebrovascular structure and function were observed. The promise of this technique was demonstrated by monitoring vascular and metabolic responses of the awake mouse brain to ischemic stroke throughout the acute, subacute, and chronic stages. Side-by-side comparison of the responses in the ipsilateral (injury) and contralateral (control) cortices shows that despite an early recovery of cerebral blood flow and an increase in microvessel density, a long-lasting deficit in cerebral oxygen metabolism was observed throughout the chronic stage in the injured cortex, part of which proceeded to infarction. This longitudinal, functional-metabolic imaging technique opens new opportunities to study the chronic progression and therapeutic responses of neurovascular diseases.

Alzheimer's disease: Estimating its prevalence rate in a French geographical unit using the National Alzheimer Data Bank and national health insurance information systems.

BACKGROUND: Reliable epidemiological data on Alzheimer's disease are scarce. However, these are necessary to adapt healthcare policy in terms of prevention, care and social needs related to this condition. To estimate the prevalence rate in the Alpes-Maritimes on the French Riviera, with a population of one million, we present a capture-recapture procedure applied to cases of Alzheimer's disease, based on two epidemiological surveillance systems. METHODS: To estimate the total number of patients affected by Alzheimer's disease, a capture-recapture study included a cohort of patients with Alzheimer's disease or receiving medications only eligible for use for this condition, recorded by a specific health insurance information system (Health Insurance Cohort, HIC), and those registered in the French National Alzheimer's Data Bank ("Banque Nationale Alzheimer", BNA) in 2010 and 2011. We applied Bayesian estimation of the Mt ecological model, taking into account age and gender as covariates, i.e. factors of inhomogeneous catchability. RESULTS: Overall, 5,562 patients with Alzheimer's disease were recorded, of whom only 856 were common to both information systems. Mean age and F/M sex ratio differed between BNA and HIC surveillance systems, 81 vs 84 years and 2.7 vs 3.2, respectively. A Bayesian estimation, with age and gender as covariates, yields an estimate of 15,060 cases of Alzheimer's disease [95%HPDI: 14,490-15,630] in the Alpes-Maritimes. The completeness of the HIC and BNA databases were respectively of 25.4% and 17.2%. The estimated prevalence rate among the population over 65 years old was 6.3% in 2010-2011. CONCLUSIONS: This study demonstrates that it is possible to determine the number of subjects affected by Alzheimer's disease in a geographical unit, using available data from two existing surveillance systems in France, i.e. 15,060 cases in the Alpes-Maritimes. This is the first stage of a population-based approach in view of adapting available resources to the population's needs.

Coxibs: evolution of prescription's behaviour in France.

The aim of the present study was, first to characterize profiles of coxibs' prescribers [general practitioners (GPs) and rheumatologists] in 2002 in France and, secondly, to identify factors associated with modification of this profile 1 year later. All GPs and rheumatologists from Midi-Pyrenees, Aquitaine, Languedoc-Roussillon and Pays de Loire areas (South of France: 11 050 000 inhabitants) were included in the study. For each practitioner, we used data concerning all non-steroidal anti-inflammatory drugs (NSAIDs) including coxibs reimbursed during period 1 (P1; January-March 2002) and period 2 (P2; January-March 2003). The ratio between the number of coxibs' prescriptions and the total number of NSAIDs' prescriptions (including coxibs) was used to define the two profiles of prescribers, one with a low level of coxibs' prescriptions and another one with a high level of coxibs' prescriptions. Characteristics of practitioners and characteristics of their practices were compared according to this profile. In the second step, we investigated the characteristics (of practitioners and practices) associated with an increase in the level of coxibs' prescriptions in P2 for practitioners with a low level of coxibs' prescriptions in P1. Results are expressed as odds ratio with their 95% confidence intervals. A positive statistical link was found between a high level of coxibs' prescriptions, the speciality of rheumatologist or extra costs for consultation. In contrast, a negative association was observed with female gender or age below 44 years. No relationship was found with the status of referent. Concerning practices' characteristics of practitioners, there was a positive statistical link between a high ratio of coxibs' prescriptions and high co-prescriptions of gastroprotective agents and a negative association with a high number of acts, a high proportion of patients with chronic disabling diseases (CDD) or a high number of patients between 15 and 64 years. There was no statistical link with proportion of patients covered by Universal Medical Coverage (UMC) or aged more than 65 years. Among the factors involved in the increase in the ratio (between P1 and P2), no relationship was found with practitioners' characteristics. In contrast, some factors related to practices (level of gastroprotective co-prescriptions, number of acts, number of CDD patients) were related to a change in coxibs' prescriptions between P1 and P2. This study allowed to discuss some relationships between coxibs' prescription and practitioners' (age, gender, medical speciality or extra costs for consultation) or practices' (level of medical practice, patients' age, number of CDD patients or level of gastroprotective prescriptions) characteristics. In contrast, some other factors like the referent status or the number of patients with UMC are not related. Physicians, initially low prescribers of coxibs and increasing their coxibs' prescriptions during the period of our study, were those with a high level of gastroprotective prescriptions, a low number of acts or a small proportion of CDD patients.

Long-term use of antipsychotics in community-dwelling dementia patients: prevalence and profile accounting for unobservable time bias because of hospitalization.

The aim of this study was to assess the prevalence of long-term antipsychotic (AP) use in community-dwelling patients with dementia considering hospitalization periods as AP exposure or not. A retrospective study was carried out from 2009 to 2012 on a PACA-Alzheimer cohort (which included 31 963 patients in 2009 and 36 442 in 2012 from 5 million inhabitants). Three groups of patients were identified according to the longest exposure to APs without interruption: nonusers, short-term users (≤3 successive months without discontinuation), and long-term users. Sensitivity analyses on hospitalization periods were carried out. The percentage of patients with at least one AP dispensing was stable over the study period (25.6% in 2009 vs. 26.5% in 2012). In 2012, 27.6% were AP long-term users. This increased to 46.7% when hospitalization periods were counted as AP exposure. In comparison with nonusers, AP users took more benzodiazepines and antidepressants. Short-term users were men [odds ratio (OR)=1.2, 95% confidence interval (CI) (1.1-1.3)] older than 85 years old [OR=1.2, 95% CI (1.1-1.2)]. Long-term users were more exposed to benzodiazepines [OR=1.2, 95% CI (1.1-1.4)]. This study showed that long-term use of AP remained frequent in community-dwelling patients with dementia. It also showed that the prevalence of long-term users almost doubled when hospitalization periods were counted as AP exposure. This underlines the need to consider hospitalization periods when assessing medication exposure in populations with frequent periods of hospitalization.

[The use of triptan in ambulatory medicine in Midi-Pyrénées Region: clinical and pharmacological contra-indications and drug abuse]. / Prescription des triptans en médecine de ville dans la ré gion Midi-Pyrénées : indications, contre indications, abus médicamenteux.

OBJECTIVE: Evaluate triptan prescriptions in ambulatory medicine. METHODS: Collection of medical data from 301 patients treated with triptans reimbursed by the French National Health Fund in the region of Midi-Pyrenees. RESULTS: Ninety-five per cent of selected patients suffered from migraine condition according to the International Headache Society diagnosis criteria [Confidence interval (CI) 95%: 93-98]. Co-morbidity factors contra-indicating triptan therapy were present in 6% of patients (CI 95%: 3-9). 2% of patients were prescribed other medicinal products contra-indicated with their triptan therapy (CI 95%: 0-4). Twenty-six per cent of patients were taking triptan medicines more than 8 times per month over a period of three months (CI 95%: 21-31) and 8% were taking this treatment more than 12 times per month (CI 95%: 5-1 I). Eleven per cent kept written information of their migraine crises (CI 95%: 7-15). Thirty-nine per cent benefited from dedicated prophylactic treatments (CI 95%: 33-45). CONCLUSION: In a context of sustained increase in prescriptions of migraine treatments, it appears necessary to remain cautious about clinical and pharmacological contra-indications. Prevention of abuse of medicines is based on a better use of crises agendas and introduction of prophylactic therapies.

[Not Available]. / Prescription des triptans en médecine de ville dans la région Midi-Pyrénées : indications, contre indications, abus médicamenteux.

OBJECTIVE: Evaluate triptan prescriptions in ambulatory medicine. METHODS: Collection of medical data from 301 patients treated with triptans reimbursed by the French National Health Fund in the region of Midi-Pyrenees. RESULTS: Ninety-five per cent of selected patients suffered from migraine condition according to the International Headache Society diagnosis criteria [Confidence interval (CI) 95%: 93-98]. Co-morbidity factors contra-indicating triptan therapy were present in 6% of patients (CI 95%: 3-9). 2% of patients were prescribed other medicinal products contra-indicated with their triptan therapy (CI 95%: 0-4). Twenty-six per cent of patients were taking triptan medicines more than 8 times per month over a period of three months (CI 95%: 21-31) and 8% were taking this treatment more than 12 times per month (CI 95%: 5-11). Eleven per cent kept written information of their migraine crises (CI 95%: 7-15). Thirty-nine per cent benefited from dedicated prophylactic treatments (CI 95%: 33-45). CONCLUSION: In a context of sustained increase in prescriptions of migraine treatments, it appears necessary to remain cautious about clinical and pharmacological contra-indications. Prevention of abuse of medicines is based on a better use of crises agendas and introduction of prophylactic therapies.

[Patterns of non steroidal anti-inflammatory drug use in ambulatory care]. / Profil des utilisateurs d'anti-inflammatoires non stéroïdiens.

The aim of this study was to discuss the patterns of non steroidal anti-inflammatory drug (NSAID) use in general population. We identified NSAID's users from the French Health Insurance System claims database covering more of the population in the Midi-Pyrenees area (southwest of France), if they have received at least one NSAID in June 2003. We discussed this population according to the NSAID used, to their demographic characteristics and to other drugs delivered in the period. Our study shows different patterns of use according to each NSAID. For example, users of ibuprofen or tiaprofenic acid were younger and less frequently exposed to "gastroprotective" drugs, users of coxibs were older and more frequently exposed to drugs increasing the risk of bleeding. This study confirms the wide use of NSAIDs and describes their target population. It underlines the interest of Health Insurance System Database for better knowledge of drug use in ambulatory care in France.

Membership in a diabetes-care network and adherence to clinical practice guidelines for treating type 2 diabetes among general practitioners: A four-year follow-up.

OBJECTIVES: To assess whether private general practitioners (GPs) belonging to a diabetes-care network adhered more closely to clinical practice guidelines for diabetes care than GPs not in such a network, for all their patients with type 2 diabetes treated with medication (patients with diabetes), regardless of whether they received care through a network (that is, whether a halo effect occurred). RESEARCH DESIGN AND MEASURES: The study, based on health insurance reimbursement databases in southeastern France, included 468 GPs in two networks and 468 non-network GPs in the same geographical area, matched one-to-one by propensity scores. We followed up their patients with diabetes (n=22,808) from 2008 through 2011, conducting multivariate time-to-event analyses (Cox models) that took the matching design into account to evaluate time from inclusion until performance of the given number of each of six recommended examinations/tests. RESULTS: GPs belonging to a diabetes-care network adhered more closely to clinical practice guidelines but our result were slightly pronounced. Hazard ratios (HR) were significantly higher for patients of network GPs for the implementation of 3 HbA1C assays (HRa=1.13; [95%CI=1.10-1.16]), or 1 microalbuminuria assay (1.4 [1.35-1.45]); they were lower for LDL-cholesterol assays (1.04 [1.01-1.07]) and ophthalmological checkups (1.07 [1.04-1.10]), and not significant for creatinemia or cardiac monitoring. CONCLUSIONS: Network GPs had better diabetes monitoring practices for all their patients with diabetes than the other GPs, especially for the most diabetes-specific tests. Further research is needed in other settings to confirm the existence of this halo effect.

Osteoporosis prevention among chronic glucocorticoid users: results from a public health insurance database.

INTRODUCTION: Long-term glucocorticoid therapy is the leading cause of secondary osteoporosis. The management of glucocorticoid-induced osteoporosis (GIOP) seems to be inadequate in many European countries. OBJECTIVE: To evaluate the rate of screening and treatment of GIOP. DESIGN: Information was collected from a national public health-insurance database in our geographic area of Provence-Alpes-Côte-d'Azur and in Corsica, from September 2009 through August 2011. PATIENTS: We identified participants aged 15 years and over starting glucocorticoid therapy (≥7.5 mg of prednisone equivalent per day during at least 90 days consecutive). This cohort was compared with an age-matched and sex-matched population that did not receive glucocorticoids. MAIN OUTCOME MEASURES: Bone mass, prescription of bone antiresorptive medication and use of calcium and/or vitamin D treatment. RESULTS: We identified 32 812 patients who were prescribed glucocorticoid therapy, yielding 1% prevalence. Incidence of glucocorticoid therapy was 2.8/1000 inhabitants/year. Males represented 44%, the mean age was 58 years. The median prednisone-equivalent dose was 11 mg/day (IQR 9-18 mg/day). 8% underwent bone mass measurement. Calcium and/or vitamin D, and bisphosphonates were prescribed in 18% and 12%, respectively. Results were lower for the control population: 3% underwent bone mass measurement and 3% received bisphosphonate therapy. The rates of osteodensitometry and treatments were higher in women over 55 years of age than in men and women 55 years of age and younger, and also when glucocorticoid therapy was initiated by a rheumatologist versus other physician specialty. CONCLUSIONS: The management of GIOP remains very inadequate, despite the availability of a statutory health insurance system. Targeted interventions are needed to improve the management of GIOP.

[Outpatient use of heparin: data from the Midi-Pyrenes Health Fund]. / Utilisation des héparines en médecine de ville: données de l'Assurance Maladie de Midi-Pyrénées.

The risk of haemorrhagic complications associated with heparin therapy can be reduced by good clinical practice. The aim of this study was to describe outpatient heparin therapy by using the database of the National Health Fund. The study population consisted of affiliates of the salaried employees insured by the health fund branch of the Midi-Pyrénées region, and corresponded to 62% of the residents of that region. Analysis of treatments and biological monitoring was carried out on a 1-year period. During this period, 16,462 patients started a treatment with heparin, 92% for a single treatment. The mean age of the patients was 55 years (SD = 19.8) and the majority were women (53%). Nine percent of these patients were switched to oral anticoagulant therapy. Of the other patients, 52% received heparin for less than 10 days, 36% for between 10 days and 5 weeks, and 12% for more than 5 weeks; 33% of the last group where heparin was prescribed for more than 5 weeks corresponds to a prescription of more than 3 months. Seventy-three percent of the heparin treatment durations complied with the authorities' (l'Agence française de sécurité sanitaire des produits de santé [AFSSAPS]) recommendations. Biological monitoring comprised a platelet count, an APTT (activated partial thromboplastin time) or an anti-Xa check in 41.9%, 27.8% and 3.1% of treated patients, respectively. Creatininaemia was measured in 27% of patients aged > 75 years (a group at increased risk of adverse drug reactions). Even considering some of the differences noted between the medical prescriptions and the reimbursement data of the health fund, results from this study allowed an evaluation of medical practices and suggests that monitoring of patients receiving heparin treatments remains insufficient, thus decreasing the benefit/risk ratio of such therapies.

Social inequalities in early antidepressant discontinuation.

OBJECTIVE: This study aimed to test for social disparities in early discontinuation of antidepressant treatment and to explore associations with type of drug and composition of prescriber's clientele. METHODS: The cohort was 14,518 Marseille residents (ages 18-64 years) covered by the National Health Insurance Fund who had a new episode of antidepressant treatment (specifically, no prescription claim in the six months before the index claim) prescribed by a private general practitioner in 2008 or 2009. Factors associated with early discontinuation (prescription filled or refilled fewer than four times in the six months after the index claim) were analyzed with multilevel models that were adjusted for patient morbidity and number of consultations with private general practitioners and psychiatrists. Sensitivity analyses were conducted with different definitions of new treatment and early discontinuation. RESULTS: Low income, type of antidepressant (tricyclics versus selective serotonin reuptake inhibitors), and prescribers' clientele composition (specifically, a high proportion of socioeconomically disadvantaged patients) were independently associated with an increased risk of early antidepressant discontinuation. A significant interaction was found between low income and gender. Low-income patients were more likely than other patients to receive tricyclic antidepressants. CONCLUSIONS: These results add further evidence of inequalities in care for major depression and suggest that women are at greater disadvantage than men. Educational programs for general practitioners should focus on the risks of antidepressant discontinuation among disadvantaged patients. Enhancing therapeutic education of low-income patients may improve their treatment adherence.

Social inequalities in new antidepressant treatment: a study at the individual and neighborhood levels.

PURPOSE: To determine whether social inequalities in new antidepressant treatment exist at the individual and/or neighborhood level; and their relation to access to prescribers and/or processes of care (treatment initiation and duration). METHODS: We followed 316,412 inhabitants of Marseilles (aged 18-64 years) covered by the National Health Insurance Fund for 2.5 years. We analyzed new treatments (≥1 purchase of antidepressants and none in the 6 months before the first one), and new long treatments (≥4 within 6 months after the first purchase). We tested their associations with high individual disadvantage and census block deprivation in a multivariate, multilevel logistic model adjusted for consultations with general practitioners and psychiatrists to control for access to care. RESULTS: High individual disadvantage was not associated with the probability of new treatments, but it was with lower odds of receiving new long treatments. Residing in deprived census blocks was associated with lower odds of receiving treatment for both dependent variables. CONCLUSIONS: Our results suggest that social inequalities at the individual and neighborhood levels in new antidepressant treatment occur in access to specialty care and in treatment initiation and affect its duration. Further research is warranted to improve our understanding of their mechanisms.

Monitoring of benzodiazepine diversion using a multi-indicator approach.

Fourteen benzodiazepine (BZD) or BZD-like medications were analyzed with three data sources aiming to assess prescription drug abuse for the year 2008. After a descriptive analysis, a principal component analysis was carried out to explore correlations between seven indicators obtained by different methods using these three different data sources and to compute a composite score of diversion for these drugs. For all the indicators, flunitrazepam appears first with much higher values than the other drugs, whereas clonazepam appears in the second or third place. These methods produce globally correlated indicators and the composite score obtained from principal component analysis ranks the drugs with the highest diversion as follows: flunitrazepam, clonazepam, oxazepam, diazepam, and bromazepam. This study shows that these methods yield consistent results. Their integration into a single multi-indicator approach gives health authorities a global view of different behaviors regarding diversion of a given drug.