Julie Dupouy

Benzodiazepines and risk of death: Results from two large cohort studies in France and UK

Benzodiazepines are widely prescribed for the treatment of anxiety or insomnia, but their impact on mortality is still debated. This study investigated the impact of benzodiazepine use on short term mortality. Exposed-unexposed cohorts were constructed with the Clinical Practice Research Datalink (CPRD) in the UK and with the General Sample of Beneficiaries (EGB) in France. Benzodiazepine incident users were matched to incident users of antidepressants/non-benzodiazepine sedatives and to controls (non-users of antidepressants or anxiolytics/hypnotics) according to age and gender in both sources (and practice for the CPRD only). Survival at one year was studied using Cox regression model. In the CPRD, the final population comprised 94 123 patients per group (57 287 in the EGB). In the CPRD, adjusted HR was 3.73 in benzodiazepine users (95% CI, 3.43-4.06), and 1.61 (1.47-1.76) in antidepressant/non-benzodiazepine users compared to controls. When considering benzodiazepine use as a time-dependent covariate, adjusted HR for current use at 12 months was 1.70 (1.36-2.12). In the EGB, adjusted HR was 1.26 in benzodiazepine users (95% CI, 1.08-1.48), and 1.07 (95% CI, 0.91-1.27) in antidepressant/non-benzodiazepine users. When considering benzodiazepine use as a time-dependent covariate, adjusted HR for current use at 12 months was 1.03 (0.74-1.44). Using two nationally representative databases, we found a significant while moderate increase in all-cause mortality in relation to benzodiazepines, in a population of incident and mostly occasional users. This issue need to be monitored given the extensive use of these drugs.

Does urine drug abuse screening help for managing patients? A systematic review.

BACKGROUND In the field of addiction, assessment of psychoactive substance use is a key element. Nevertheless, self-reports and clinical examination underestimate the use of psychoactive substances. The implementation of urine drug screening tests (UDS) should improve this assessment. While the diagnostic value of UDS is well demonstrated, the consequences of carrying out UDS on medical management have not been established. Our aim was to summarize the evidence pertaining to the efficacy of UDS for medical management. METHODS A systematic review of clinical trials, quasi-randomized and observational studies was performed using PubMed, Cochrane database of systematic review, Cochrane central register of controlled trials, PsycINFO, National Institute on Drug Abuse, ISI Web of Science. The methodological quality was assessed with the score developed by Starrels et al.; the report quality using the CONSORT and the STROBE checklists. The main outcome was medical management or consequences of management for patients in terms of psychoactive substance consumption and its complications, be they medical, social or professional. RESULTS Eight studies met the inclusion criteria: one randomized clinical trial, two quasi-randomized studies, one cohort, and four cross-sectional studies. The methodological quality was judged to be poor, with the exception of the randomized clinical trial (fair quality). The value of UDS in managing patients was not clearly indicated in these studies. CONCLUSIONS Few studies, with poor quality, have assessed the value of UDS in managing patients using psychoactive substances; though with insufficiency to demonstrate the interest of carrying out UDS. Therefore, pragmatic intervention studies are necessary.

Effectiveness of drug tests in outpatients starting opioid substitution therapy

We aimed to assess the effectiveness of drug tests for treatment retention in outpatients starting opioid substitution therapy. A retrospective cohort was created from the data of the French health insurance system database for the Midi-Pyrenees region. Patients starting opioid substitution treatment (OST) were included and followed for 18 to 30 months. Two groups of patients were defined: the drug test group (at least one drug test reimbursement) and a control group (no drug test reimbursement). The cohort included 1507 patients. During follow-up, 39 subjects (2.6%) had at least one drug test reimbursement. Mean treatment retention was 207 days in the control group and 411 days in the drug test group (p < 0.001). With a multivariate Cox model, drug tests were associated with treatment retention: hazard ratio 0.55 (95% CI: 0.38-0.80). Use of a drug test in follow-up of opioid substitution treatment, although rarely prescribed, significantly improved treatment retention.

Pregabalin use disorder and secondary nicotine dependence in a woman with no substance abuse history.

This is an addictovigilance report of a pregabalin use disorder case in a young female patient who secondarily presented a tobacco use disorder after smoking initiation combined with pregabalin intake. Pregabalin was first prescribed for anxiety. Concomitant use of pregabalin with tobacco led to a synergic effect of both substances. She presented a craving behavior for pregabalin, with a tolerance phenomenon and a withdrawal syndrome between pregabaline intakes. The patient had a history of depressive disorder, personality disorder and anorexia, but never had any history of substance use disorder. This case report is noteworthy for 3 reasons: 1: this is one of the first report of pregabalin use disorder in a patient without any substance abuse disorder (licit or illicit), with the exception of a personal vulnerability factors to substance abuse; 2: the patient presented characteristics of pregabalin use disorder at usual dose (below 300mg per day), with drug-seeking behavior, tolerance phenomenon and intense craving with these moderate doses; 3: concomitant use of pregabalin with tobacco led to a synergic effect of both substances.

Which Adverse Events Are Related to Health Care during Hospitalization in Elderly Inpatients

Background: Adverse events result in longer hospital stays and increase costs and mortality. We aimed to assess incidence of adverse events occurring during hospitalization in a post-emergency unit and to describe their characteristics. Methods: All adverse events occurring in patients during their hospitalization in a post-emergency unit in a French university hospital (20 beds) were systematically and consecutively recorded from September 2009 to February 2011. Patients with adverse events were compared to up to three control patients, matched for date of admission +/- age in the same unit. Results: We identified 56 patients with 64 adverse events, giving an incidence of 3.0/100 patients admitted/year. Fifty-one adverse events were drug-related. Patients had a median age of 82.5 years with a male/female ratio of 1/1.4. They presented a median Charlson score of 1 and the median number of medications was 6. The drugs most frequently involved in drug-related events were nervous system drugs (47%) and anti-infectives (22%). In multivariate analysis, a Charlson score ≥ 2 was associated with the occurrence of adverse events (OR 0.4; 95% CI [0.21 - 0.80]). Conclusions: Systematic recording showed that adverse events were not rare in a post-emergency unit. Patients with comorbid conditions were less likely to present an adverse event, possibly because of greater precautions taken by the medical team.

On-Site Drugs of Abuse Urinary Screening Tests for the Management of Opiate-Addicted Patients: A Survey among French General Practitioners

In France, opiate-addicted patients are mainly managed by general practitioners (GPs). Because on-site abuse drugs urinary screening tests (ODUTs) are now on the market, we investigated French GPs’ knowledge and practices concerning drug tests with a focus on ODUTs. We conducted a descriptive cross-sectional study in ambulatory practice. Postal questionnaires were sent to a random sample of GPs in the Midi-Pyrénées area of France in December 2009. Of the 482 GPs in the sample, 116 (24.1%) regularly treated opiate- addicted patients. Only 31 of them (26.7%) used drug tests and 4 of them (3.4%) performed ODUTs in their consultation rooms. Most of the GPs did not perform ODUTs because they were unaware of whether such tests were reliable or available. Many French GPs treating opiate-addicted patients regularly did not perform ODUTs and lacked knowledge of them.

Identifying competencies required for medication prescribing for general practice residents: a nominal group technique study

BackgroundTeaching of medication prescribing is a specific challenge in general practice curriculum. The aim of this study was to identify and rank the competencies required for prescribing medication for general practice residents in France.MethodsQualitative consensus study using the nominal group technique. We invited different stakeholders of the general practice curriculum and medication use in primary care to a series of meetings. The nominal group technique allowed for the quick development of a list of consensual and ranked answers to the following question: “At the end of their general practice curriculum, in terms of medication prescribing, what should residents be able to do?”.ResultsFour meetings were held that involved a total of 31 participants, enabling the creation of a final list of 29 ranked items, grouped in 4 domains. The four domains identified were ‘pharmacology’, ‘regulatory standards’, ‘therapeutics’, and ‘communication (both with patients and healthcare professionals)’. Overall, the five items the most highly valued across the four meetings were: ‘write a legible and understandable prescription’, ‘identify specific populations’, ‘prescribe the doses and durations following the indication’, ‘explain a lack of medication prescription to the patient’, ‘decline inappropriate medication request’. The ‘communication skills’ domain was the domain with the highest number of items (10 items), and with the most highly-valued items.ConclusionThe study results suggest a need for developing general practice residents’ communication skills regarding medication prescribing.

Mortality Associated With Time in and Out of Buprenorphine Treatment in French Office-Based General Practice: A 7-Year Cohort Study

In France, most cases of opioid use disorder are treated with buprenorphine by general practitioners in private practice. Using reimbursement data of a representative sample of the French population, Echantillon Généraliste des Bénéficiaires, we investigated mortality during periods when patients were in and out of treatment in a cohort of 713 new users of buprenorphine having a mean (SD) follow-up of 4.5 (1.5) years. The mortality rate was 0.63 per 100 person-years (95% CI, 0.40–0.85) overall. In a multivariate Cox regression model, compared with being in treatment, being out of treatment was associated with a markedly increased risk of death (hazard ratio = 29.04; 95% CI, 10.04–83.99). Buprenorphine appears to be a strong protective factor against mortality.

Immeasurable time bias due to hospitalization in medico-administrative databases: which impact for pharmacoepidemiological studies?

Drugs administered to hospitalized patients are not available within almost all health insurance databases. However, this unobservable exposure time bias is very rarely taken into account in pharmacoepidemiology. The objective was to model unobservable periods due to hospitalization and to assess their impact on risk estimates in the context of the association between benzodiazepines and mortality.

Patients’ Knowledge About Analgesic-Antipyretic Medications Purchased in Community Pharmacies: A Descriptive Study

ABSTRACT The objective of this study was to describe the level of knowledge about paracetamol (acetaminophen), ibuprofen, and aspirin of subjects who purchased nonprescription medications containing one of these drugs. We conducted this cross-sectional descriptive study in 42 community pharmacies located in southwestern France between July and November 2013. A six-item self-administered questionnaire was used. Participants were asked to identify the active ingredient contained in 14 brand-name analgesic-antipyretics, to state the maximum daily dose of paracetamol, ibuprofen, and aspirin, the recommended first-line analgesic, and precautions of use or contraindications for paracetamol, ibuprofen, and aspirin. Among 576 participants, the identification of paracetamol ranged from 58% (for Dafalgan or Efferalgan) to 90% (for Doliprane), the identification of ibuprofen from 34% (for Nureflex) to 63% (for Nurofen), and the identification of aspirin was 70% (for Aspegic). The maximum recommended daily dose of paracetamol, ibuprofen, and aspirin was known by 58.3%, 17.7%, and 19.3% of participants, respectively, whereas 6.8%, 17.2%, and 13.2% stated supratherapeutic daily doses. Paracetamol was correctly stated as the first-line analgesic-antipyretic by 76.2% of participants. Knowledge on major precautions of use or contraindications was poor (45.8% and 53.6% for ibuprofen and aspirin use during pregnancy, and 14.1% for concurrent use of anticoagulants and ibuprofen). Purchasers of nonprescription analgesic-antipyretics had poor knowledge on the medication they purchased.