(De)Prescribing of proton pump inhibitors: what has changed in recent years? an observational regional study from the French health insurance database.

BACKGROUND: Proton pump inhibitors (PPIs) are one of the most widely prescribed drug classes in the community and at hospital. The significant misuse of PPIs requires the implementation for a deprescribing strategy. Numerous studies aiming at evaluating the impact of deprescribing interventions have been set up, implying a precisely known evolution of consumption of PPIs in the population studied without intervention. The main objective of the study was to study overall changes in PPI prescribing and deprescribing in a regional population of chronic consumers without intervention, according to health insurance databases. METHODS: This historical cohort study was based on the French National Health Data System databases. All adult patients living in the Pays de la Loire area and covered by the French National Health Insurance and who had at least one reimbursement for a PPI dispensing between 01 October 2016 and 31 December 2020 were included. Only chronic consumer patients were included, defined as patients who has had PPI dispensed for 3 consecutive months with a temporal coverage of at least 80%. Patients under 18 years of age and patients who received parenteral PPIs only were excluded. RESULTS: The percentage of chronic treatment discontinuation in 2017 was 12.5% and remained stable to reach 12.4% in 2020. The number of new chronic patients increased from year to year to reach 77,222 patients in 2020, with an increasing rate of 1.2 to 2% between 2017 and 2020. The prevalent patient population increased from year to year to reach 167 751 patients in 2020, with an increasing rate of 4.2 to 4.4% between 2017 and 2020. Regarding the initiation of PPI therapy, in 2020, 87.1% of treatment initiations were done by general practitioners. They renewed 2,402,263 prescriptions (89.3%) between 2017 and 2020. CONCLUSIONS: This study shows a stagnation over the last 4 years in the deprescribing of chronic PPI treatments in a French region despite the information on their inappropriate use reported by national agencies and in the literature with increasing frequency. This reinforces the interest of setting up a deprescribing project.

First step in assessment of VipGrade®, a computerized clinical decision system to assess Vipera envenomation grading: a single-center interrater reliability study.

METHODS: We conducted a retrospective review of Vipera spp. snakebite cases registered by the PCC of Bordeaux, France, between January 1, 2018, and December 31, 2020, evaluating the agreement between VipGrade® assessments, toxicologists' assessments, and current guidelines. RESULTS: 133 patients with Vipera aspis snakebites were included. There was 100% agreement in severity grading by PCC guidelines and VipGrade®. However, grading by toxicologists and VipGrade® diverged in 19 cases (85% agreement; κ = 0.80; 95% CI: 0.71 to 0.87). CONCLUSIONS: The VipGrade® tool's grading reflects current PCC guidelines, which are authoritative in France, and may allow for a more rapid and standardized determination of management and follow-up of viper-bitten patients. It should be noted, however, that the more complex and dynamic aspects of management are not included in VipGrade®. Its purpose is to supplement, not replace, the advice of the PCC's clinical toxicologists, and this advice should be sought whenever a viper bite is encountered in clinical practice.

Change in the regulatory framework for zolpidem: What is the impact on the landscape of the prescription of sedative medications? The French national ZORRO study.

AIMS: In recent years, zolpidem has been the subject of numerous reports of misuse, abuse and dependence. In view of these risks, the French drug agency (ANSM) decreed in April 2017 the implementation of secure prescription pads. The objective of this study was to evaluate the impact of this regulatory measure on the prescription of zolpidem and other sedative medications (zopiclone, benzodiazepines and antihistamines) in long-term users of zolpidem and associated factors. METHODS: We performed a historical cohort study using data from the Generalist Sample of Beneficiaries (EGB). All patients aged over 18 years old who were long-term users (at least 3 months) before the measure were enacted. We analysed the reimbursement trajectories of zolpidem, zopiclone, benzodiazepines and antihistamines (hydroxyzine and alimemazine) up to 2 years after the measure using a state sequence analysis. RESULTS: Overall, 2502 patients were analysed. A four-cluster typology was identified: continuation of zolpidem (n = 1044, 42%), discontinuation of sedative medications (n = 766, 31%), change to zopiclone (n = 537, 21%) and change to hypnotic benzodiazepines (n = 155, 6%). The most frequently prescribed hypnotic benzodiazepine was lormetazepam. We identified age, sex, treatment for psychiatric or addictive disorder and volume of zolpidem use before the measure as factors associated with different reimbursement trajectories after the regulatory change. CONCLUSION: The regulatory change for zolpidem prescriptions reduced exposure to zolpidem among long-term users and also had a broad impact on prescriptions of other sedative medications. Switching to other medications that also present a potential risk of abuse or dependence should be carefully monitored.

Adherence with brand versus generic bisphosphonates among osteoporosis patients: a new-user cohort study in the French National Healthcare Insurance database.

Several studies documented declines in treatment adherence with generic forms of oral bisphosphonates in osteoporosis compared to branded forms, while others did not support this relation. Our aim was to compare medication adherence with brand versus generic forms of oral bisphosphonates. A new-user cohort study was conducted using routinely collected administrative and healthcare data linked at the individual level extracted from a nationwide representative sample of the French National Healthcare Insurance database. We included all patients aged 50 and older, new users of oral bisphosphonates for primary osteoporosis between 01/01/2009 and 31/12/2015. Two components of adherence were measured: implementation (continuous multiple-interval measure of medication availability version 7; CMA7) and persistence (time to discontinuation). The sample was composed of 1,834 in the "brand bisphosphonate" group and 1,495 patients in the "generic bisphosphonate" group. Initiating oral bisphosphonate treatment with brand was associated with a higher risk of discontinuation within 12 months (Hazard Ratio = 1.08; 95%CI = [1.02;1.14]). The risk of good implementation (CMA7 ≥ 0.90) was significantly lower in "brand bisphosphonate" group (Risk Ratio = 0.90; 95%CI = [0.85; 0.95]). We did not find any evidence to support the hypothesis of a lower adherence to generic bisphosphonates. In fact, prescribing of generic bisphosphonates led to a higher persistence rate and to better implementation at 1 year.

Prevalence of zolpidem use in France halved after secure prescription pads implementation in 2017: A SNDS database nested cohort study.

Our objective was to quantify the impact on the use of zolpidem of the obligation implemented in France in 2017 to use secure prescription pads to prescribe it. We conducted a cohort study within the French SNDS healthcare database. Patients aged over 18 years of age were considered for inclusion. The number of prevalent users and incident episodes of zolpidem use were compared before the change in law (July 1, 2016 to January 1, 2017) and after (July 1, 2017 to January 1, 2018). A prevalent user was a patient who has been reimbursed for zolpidem at least once. An incident episode of zolpidem use was defined by a first administration of zolpidem without any prior administration within the previous six months. Regarding prevalence of zolpidem users, we observed a decrease from 2.79% (CI95%:2.75-2.83) to 1.48% (1.44-1.51), with a number of patients who stopped taking it after the change in law being approximately 4.3 times higher than the number of patients who started. We observed a negative association between the post-law change period (OR = 0.52 (0.51-0.53)) and the probability of receiving zolpidem, adjusting for sex, aging, low income and chronic disease. We observed a decrease from 183 treatment episodes per 100,000 insured months on average to 79 episodes per 100,000 insured months, with an incidence rate ratio (IRR) equal to 0.43 (0.38-0.49). The use of secure prescription pads seems to have reduced the exposure of the French population to zolpidem.

French national health insurance database analysis and field study focusing on the impact of secure prescription pads on zolpidem consumption and sedative drug misuse: ZORRO study protocol.

INTRODUCTION: In recent years, data collected by the French Addictovigilance Network have shown the potential for abuse and addiction associated with zolpidem (the most sold hypnotic drug in France). Since 10 April 2017, new regulations have come into force that require zolpidem to be prescribed on special secure prescription pads, in order to reduce the risk of abuse or misuse. This measure has far-reaching repercussions that are not only limited to the consumption of zolpidem but also extend to the usage of sedative medication on a whole. The objective of the ZOlpidem and the Reinforcement of the Regulation of prescription Orders (ZORRO) study is to evaluate the overall impact of the new regulatory framework requiring zolpidem to be prescribed on special secure prescription pads. Three axes will be evaluated: the number of consumers, the type of consumption (chronic use versus occasional use, problematic consumption versus non-problematic use) and the consumption of other sedative molecules.The study has been registered in the Protocol Registration and Results System under the number NCT03584542 at stage "Pre-results". METHODS AND ANALYSIS: The ZORRO study is an epidemiological, observational, national multicentre, non-controlled, prospective research project supported by the French National Agency for Medicines and Health Products Safety. The evaluation of the impact of the regulatory framework change relative to zolpidem will be done according to two axes: via an epidemiological study of the French National Health Insurance database and by the implementation of field studies of prescribers and consumers of zolpidem. ETHICS AND DISSEMINATION: The Nantes Research Ethics Committee (Groupe Nantais d'Ethique dans le Domaine de la Santé), the Committee for the Protection of the Population and the Committee of Expertise in Research, Studies and Evaluations in the Field of Health approved this study. Results will be presented in national and international conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03584542; Pre-results.

Impact of vitamin D supplementation on health-care use in a 25-hydroxyvitamin D-tested population in France: a population-based descriptive cohort study.

OBJECTIVE: Chronic vitamin D deficiency has been associated in some patients with diffuse musculoskeletal pain. These unspecific symptoms may partly explain why vitamin D deficiency is often diagnosed late. Our aim was to analyse health-care claims after vitamin D supplementation in patients likely to have vitamin D deficiency. DESIGN: Ambulatory health-care claims were compared before and after a vitamin D supplementation prescribed following a 25-hydroxyvitamin D assay. SETTING: Health Insurance Fund (FHIF) database of the Rhône-Alpes area, France. SUBJECTS: Among patients reimbursed for a 25-hydroxyvitamin D assay between 1 December 2008 and 31 January 2009, those supplemented with vitamin D after the assay were matched on the date of assay to patients who did not receive vitamin D. RESULTS: Among the 3023 patients who had a 25-hydroxyvitamin D assay, 935 were consequently supplemented and matched to 935 patients not supplemented. Their median age was 50·0 and 49·5 years, respectively. Patients supplemented decreased their muscle relaxant consumption whereas no change was observed in the reference group, the difference between the two groups was significant (P=0·03). Second and third Pain Relief Ladder prescriptions decreased in both groups but not significantly differently between groups (P=0·58). There was a decrease in prescriptions of biological examination in both groups with no significant difference. CONCLUSIONS: Besides a decrease in muscle relaxant prescriptions in the supplemented group, it was difficult to assess the impact of vitamin D supplementation in patients likely to have vitamin D deficiency. Prospective cohort studies and randomized trials are needed to assess the efficiency of screening and supplementing vitamin D deficiency.