High Serum Vitamin B12 Levels Associated with C-Reactive Protein in Older Patients with Cancer.

BACKGROUND: A Comprehensive Geriatric Assessment (CGA) has been proposed to assess prognosis and to adapt oncological care in older patients with cancer. However, few biological markers are incorporated in the CGA. METHODS: This comparative study on older patients with cancer was realized before final therapeutic decision and during a CGA that included biological markers. Our objective study was to know if the serum vitamin B12-C-reactive protein index (BCI) can help to estimate early death and unplanned hospitalization. Associations between BCI and unplanned hospitalization or mortality were analyzed using ordered multivariate logistic regression. FINDINGS: We included 621 older cancer adults in outpatient care with a median age of 81 years (range, 70-98 years) from September 2015 to May 2018. In this study, 5.6% of patients died within 3 months, 8.8% had unplanned hospitalization within 1 month, and 11.4% had unplanned hospitalization within 3 months. Hypercobalaminemia was present in 83 patients (13.4%), and 34 patients (5.5%) had BCI >40,000. According to the multivariate analysis, BCI was a prognostic factor of mortality within 3 months and unplanned hospitalizations at 1 and 3 months. Impaired activities of daily living (ADL) and palliative care were also risk factors for mortality within 3 months. Impaired instrumental ADL, low albumin level, and palliative care were risk factors for unplanned hospitalization at 1 month. INTERPRETATION: BCI could be routinely added to the CGA process, as part of a pretreatment workup, in order to assess more precisely the frailties and to adapt oncological care in older patients treated for cancer. IMPLICATIONS FOR PRACTICE: Aging comes with an increase of frailties and comorbidities. To identify frailties in older patients with cancer, this study used a Comprehensive Geriatric Assessment, which allowed for the adaptation of each treatment plan in accordance with the individual needs of the patients. However, biological characteristics were not included in this assessment. This study showed that hypercobalaminemia and vitamin B12 -C-reactive protein index may be potential markers for cancer with poor prognosis, particularly in the older population. These biological markers can be used in geriatric oncology and general medicine.

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.

Use of a multi-state model in a claims database: illustration with methadone.

PURPOSE: In pharmacoepidemiology, one of the main concerns is analysis of drug exposure time. However, in real-life settings, patient's behavior is complex and characterized by drug exposure dynamics. Multi-state models allow assessing the probabilities of various patterns, instead of just continuous use and/or discontinuation. The aim of this study was to illustrate with methadone, the use of multi-state model (MSM) in a large claims database. METHODS: This study is based on the French health insurance reimbursement database. Methadone exposure is defined using four states for each period of follow-up: syrup only, capsule only, syrup-capsule and no dispensing. The model considered 12 possible transitions (including reverse transitions) from one state to another. To describe these transitions a time-homogeneous Markov model was used. RESULTS: A total of 1265 methadone users were included. When patients belonged to the syrup-capsule state, they had a 61.8% chance of moving to capsules the following month and 20.9% of moving to syrup. The probability of moving from the syrup to the non-user state was 13.6% (11.7% from capsule state to non-user state). The average length of stay was 5.9 months (CI95%: [5.5-6.4]) in capsule state, 4.9 (CI95%: [4.6-5.2]) in syrup state and 5.9 (CI95%: [5.5-6.3]) in non user state. CONCLUSION: MSM provided a good description of methadone patterns of use. It outlined behaviors which have led to a rapid spread of capsule formulation among methadone users. Therefore, it illustrates the utility of MSM for modeling multiple sequences of drug use in a large claims database.

Systematic assessment of non-medical use of prescription drugs using doctor-shopping indicators: A nation-wide, repeated cross-sectional study.

AIMS: The aim of this study was to present the first nation-wide, systematic, repeated assessment of doctor-shopping (i.e. visiting multiple physicians to be prescribed the same drug) during 10 years for more than 200 psychoactive prescription drugs in the 67 million inhabitants in France. DESIGN: This was a nation-wide, repeated cross-sectional study. SETTING AND PARTICIPANTS: Data are from the French National Health Data System in 2010, 2015 and 2019 for 214 psychoactive prescription drugs (i.e. anaesthetics, analgesics, antiepileptics, anti-Parkinson drugs, psycholeptics, psychoanaleptics, other nervous system drugs and antihistamines for systemic use). MEASUREMENTS: The detection and quantification of doctor-shopping relied upon an algorithm that detects overlapping prescriptions from repeated visits to different physicians. We used two doctor-shopping indicators aggregated at population level for each drug dispensed to more than 5000 patients: (i) the quantity doctor-shopped, expressed in defined daily doses (DDD), which measures the total quantity doctor-shopped by the study population for a given drug; and (ii) the proportion doctor-shopped, expressed as a percentage, which standardizes the quantity doctor-shopped according to the use level of the drug. FINDINGS: The analyses included approximately 200 million dispensings to approximately 30 million patients each year. Opioids (e.g. buprenorphine, methadone, morphine, oxycodone and fentanyl), benzodiazepines and non-benzodiazepine hypnotics (Z-drugs) (e.g. diazepam, oxazepam, zolpidem and clonazepam) had the highest proportions doctor-shopped during the study period. In most cases, the proportion and the quantity doctor-shopped increased for opioids and decreased for benzodiazepines and Z-drugs. Pregabalin had the sharpest increase in the proportion doctor-shopped (from 0.28 to 1.40%), in parallel with a sharp increase in the quantity doctor-shopped (+843%, from 0.7 to 6.6 DDD/100 000 inhabitants/day). Oxycodone had the sharpest increase in the quantity doctor-shopped (+1000%, from 0.1 to 1.1 DDD/100 000 inhabitants/day), in parallel with a sharp increase in the proportion doctor-shopped (from 0.71 to 1.41%). Detailed results for all drugs during the study period can be explored interactively at: https://soeiro.gitlab.io/megadose/. CONCLUSIONS: In France, doctor-shopping occurs for many drugs from many pharmacological classes, and mainly involves opioid maintenance drugs, some opioids analgesics, some benzodiazepines and Z-drugs and pregabalin.

Misuse of buprenorphine maintenance treatment since introduction of its generic forms: OPPIDUM survey.

PURPOSE: The purpose of the study was to compare, using data from Observation of Illicit Psychotropic Substances or Non-medical Used Medications (OPPIDUM) surveys, first, the profile of buprenorphine users and their modalities of buprenorphine use from 2006 to 2008 and, second, two subgroups: brand-name and generic buprenorphine users in 2008. METHODS: OPPIDUM is an annual, nationwide, multicentric, cross-sectional survey, including buprenorphine users followed in specialised centres dedicated to drug dependence. The evolution of the profile during three consecutive years (2006, 2007 and 2008) was analysed using Cochran-Armitage test for trend. A multivariate regression analysis was used to identify the factors associated with the use of generic compared with brand-name buprenorphine in 2008. RESULTS: In OPPIDUM, 1311 individuals used buprenorphine in 2006, 1688 in 2007 and 1696 in 2008. The proportion of users of generic buprenorphine increased from 4.2% in 2006 to 31.7% in 2008. From 2006 to 2008, a decrease in intravenous use and higher than recommended dosage, with an increase in occupation, have been observed. According to the multivariate analysis, factors associated with being generic buprenorphine user compared with brand-name buprenorphine user in 2008 were younger age, more education, absence of use of alcohol with buprenorphine, absence of heroin and/or cocaine use and absence of nasal route for buprenorphine. CONCLUSION: Three years after the launch of the buprenorphine generic, the health professionals' and buprenorphine users' perception of generic can still change. Additionally, the long-term impact of generic medications with abuse potential has not yet been studied. Thus, continued monitoring of buprenorphine is needed.

Evolution of opioids reimbursement since 2004 from the National Database of the General Health Insurance System.

OBJECTIVE: This study aims at evaluating trends in the consumption of opioids over the last years to assess the impact of public health measures on the management of pain and opiate addiction in France. METHODS: The evolution of opioids consumption was analysed by using the national database of the General Health Insurance System in France between 2004 and 2008. RESULTS: During the study period, the reimbursed quantities of opioids used for pain management have increased by 13%, except for dextropropoxyphene that has decreased by 9%. The reimbursed quantities of opioids used for substitution maintenance treatments for opioid dependence have increased by 34%, with a 116% increase for methadone. CONCLUSION: This study suggests that consumption of opioids is globally increasing in France and reveals discrepancies concerning the evolution of the different drugs. It allows to analyse switches of consumption between different opioids and constitutes the first step for further studies targetting signals of diversion and abuse.

Doctor shopping for methylphenidate as a proxy for misuse and potential abuse in the 67 million inhabitants in France.

Doctor shopping enables subjects to receive more than the prescribed dose out of any medical management, which suggests a search for high doses and makes doctor shopping a relevant proxy for misuse and potential abuse. Therefore, this study aimed to identify and characterize profiles of subjects with doctor-shopping behavior for methylphenidate in the entire French population. This study is a cross-sectional study of doctor-shopping behavior for methylphenidate in France, in 2016, using the Système national des données de santé, and accounting for overlapping prescriptions. Subjects who obtained >840 mg by doctor shopping were defined as subjects with heavy doctor-shopping behavior, and subjects who obtained >0 mg and ≤840 mg by doctor shopping were defined as subjects with light doctor-shopping behavior. A total of 63 739 subjects were included, and received 339.6 kg of methylphenidate. Among them, 216 (0.3%) subjects had heavy doctor-shopping behavior, and 313 (0.5%) subjects had light doctor-shopping behavior. Compared with subjects with light doctor-shopping behavior, subjects with heavy doctor-shopping behavior were older (64% of 30- to 49-year-old subjects vs. 77% of ≤17-year-old subjects; P < 0.001), received more concomitant dispensings of antipsychotics (37% vs. 26%; P = 0.008) and opioid maintenance treatments (50% vs. 6%; P < 0.001), and had more prescribers (4 [IQR = 2-5] vs. 2 [IQR = 2-3]; P < 0.001). In the French context where prescription and dispensing of methylphenidate are highly regulated and methylphenidate is much less used than in other countries, these results are a warning signal to avoid trivializing methylphenidate in adults.

Early Detection of Prescription Drug Abuse Using Doctor Shopping Monitoring From Claims Databases: Illustration From the Experience of the French Addictovigilance Network.

Opioid analgesics and maintenance treatments, benzodiazepines and z-drugs, and other sedatives and stimulants are increasingly being abused to induce psychoactive effects or alter the effects of other drugs, eventually leading to dependence. Awareness of prescription drug abuse has been increasing in the last two decades, and organizations such as the International Narcotics Control Board has predicted that, worldwide, prescription drug abuse may exceed the use of illicit drugs. Assessment of prescription drug abuse tackles an issue that is hidden by nature, which therefore requires a specific monitoring. The current best practice is to use multiple detection systems to assess prescription drug abuse by various populations in a timely, sensitive, and specific manner. In the early 2000's, we designed a method to detect and quantify doctor shopping for prescription drugs from the French National Health Data System, which is one of the world's largest claims database, and a first-class data source for pharmacoepidemiological studies. Doctor shopping is a well-known behavior that involves overlapping prescriptions from multiple prescribers for the same drug, to obtain higher doses than those prescribed by each prescriber on an individual basis. In addition, doctor shopping may play an important role in supplying the black market. The paper aims to review how doctor shopping monitoring can improve the early detection of prescription drug abuse within a multidimensional monitoring. The paper provides an in-depth overview of two decades of development and validation of the method as a complementary component of the multidimensional monitoring conducted by the French Addictovigilance Network. The process accounted for the relevant determinants of prescription drug abuse, such as pharmacological data (e.g., formulations and doses), chronological and geographical data (e.g., impact of measures and comparison between regions), and epidemiological and outcome data (e.g., profiles of patients and trajectories of care) for several pharmacological classes (e.g., opioids, benzodiazepines, antidepressants, and methylphenidate).

Evolution of doctor shopping for oxycodone in the 67 million inhabitants in France as a proxy for potential misuse or abuse.

ABSTRACT: This nationwide study aimed to compare use of oxycodone and doctor shopping for oxycodone in 2010 and 2016, and to quantify doctor shopping for oxycodone by sex, age, formulation, and dosage in 2010 and 2016. This study is a cross-sectional comparative analysis of doctor shopping based on all dispensings of oxycodone in France, in 2010 and 2016. Dispensings of oxycodone were extracted from the Système national des données de santé, which covers the 67 million inhabitants in France. Quantification of doctor shopping relies on an algorithm accounting for overlapping prescriptions, which is a proxy for potential misuse or abuse. The number of subjects who received oxycodone increased by 214% from 67,838 subjects in 2010 to 212,753 subjects in 2016, and the number of subjects with doctor-shopping behavior increased by 197%, from 1066 subjects in 2010 to 3163 subjects in 2016. For 30- to 44-year-old men, the total quantity of oxycodone obtained by doctor shopping increased by 391%, from 4582 defined daily doses in 2010 to 22,517 defined daily doses in 2016. By formulation and dosage, the total quantity of oxycodone obtained by doctor shopping increased with the dosage for both immediate-release and extended-release tablets in 2010 and 2016. The widespread extent of doctor shopping and its 3-fold increase in line with population exposure is a strong signal in the French context. These results are another argument to avoid trivializing oxycodone to prevent misuse, potential abuse, and potential oxycodone-related deaths, but it requires caution to prevent compromising effective treatment of pain.

In Rheumatoid Arthritis Patients, HLA-DRB1*04:01 and Rheumatoid Nodules Are Associated With ACPA to a Particular Fibrin Epitope.

Objectives: Rheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5-amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein/peptide antibodies (ACPAs). Citrulline is a neutral amino acid resulting from post-translational modification of arginine involved in peptidic bounds (arginyl residue) by PeptidylArginine Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrin(ogen) (hFib) and can be specifically detected by the AhFibA assay. Five citrullinated peptides derived from hFib together represent almost all of the epitopes recognized by patients with ACPA-positive RA, namely: α36-50cit, α171-185cit, α501-515cit, α621-635cit, and ß60-74cit. The use of antibody fine specificities as markers of clinical phenotypes has become a major challenge. Our objective was to study whether RA clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against the epitopes borne by the five peptides. Methods: 184 ACPA-positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patient characteristics including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2 antibodies, AhFibA, and antibodies against the five citrullinated hFib (hFib-cit) peptides were analyzed by ELISA. Results: Anti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 - 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were associated with rheumatoid nodules (OR = 2.71 [1.00 - 7.16], p= 0.044). Conclusion: Immune complexes containing anti-α501-515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. Apheresis of these epitope-specific antibodies might be a new therapeutic opportunity for patients with rheumatoid nodules.

Beta-lactam allergy labeling in intensive care units: An observational, retrospective study.

ABSTRACT: This retrospective study aimed to describe the association between the "ß-lactam allergy" labeling (BLAL) and the outcomes of a cohort of intensive care unit (ICU) patients.Retrospective cohort study.Seven ICU of the Aix Marseille University Hospitals from Marseille in France.We collected the uses of the label "ß-lactam allergy" in the electronic medical files of patients aged 18 years or more who required more than 48 hours in the ICU with mechanical ventilation and/or vasopressors admitted to 7 ICUs of a single institution.We retrospectively compared the patients with this labeling (BLAL group) with those without this labeling (control group).The primary outcome was the duration of ICU stay. Among the 7146 patients included in the analysis, 440 and 6706 patients were classified in the BLAL group and the control group, respectively. The prevalence of BLAL was 6.2%. In univariate and multivariate analyses, BLAL was weakly or not associated with the duration of ICU and hospital stays (respectively, 6 [3-14] vs 6 [3-14] days, standardized beta -0.09, P = .046; and 18 [10-29] vs 15 [8-28] days, standardized beta -0.09, P = .344). In multivariate analysis, the ICU and 28-day mortality rates were both lower in the BLAL group than in the control group (aOR 0.79 95% CI [0.64-0.98] P = .032 and 0.79 [0.63-0.99] P = .042). Antibiotic use differed between the 2 groups, but the outcomes were similar in the subgroups of septic patients in the BLAL group and the control group.In our cohort, the labeling of a ß-lactam allergy was not associated with prolonged ICU and hospital stays. An association was found between the labeling of a ß-lactam allergy and lower ICU and 28-day mortality rates.Trial registration: Retrospectively registered.

Prognostic Value of the B12/CRP Index in Older Systemically Treatable Cancer Patients.

BACKGROUND: While comprehensive geriatric assessment (CGA) in older patients treated for cancer assesses several related domains, it does not include standardized biological tests. The present study aimed to: (1) assess the prognosis value of the B12/CRP index (BCI) in a population of systemically treatable older patients with cancer and (2) analyze the association between BCI value and pre-existing geriatric frailty. METHOD: We conducted a retrospective observational study between January 2016 and June 2020 at Marseille University Hospital. All consecutive cancer patients aged 70 years and over before initiating systemic therapy were included. RESULTS: Of the 863 patients included, 60.5% were men and 42.5% had metastatic stage cancer. Mean age was 81 years. The low-BCI group (≤10,000) had a significantly longer survival time than the mid-BCI (10,000 < BCI ≤ 40,000) and high-BCI (BCI > 40,000) groups (HR = 0.327, CI95% [0.26-0.42], p-value = 0.0001). Mid- and high-BCI (BCI > 40,000) values were associated with impaired functional status and malnutrition. CONCLUSION: A BCI > 10,000 would appear to be a good biological prognostic factor for poor survival times and pre-existing geriatric impairment in older cancer patients before they initiate systemic treatment.

Hypoxia inducible factor 1alpha gene (HIF-1alpha) splice variants: potential prognostic biomarkers in breast cancer.

BACKGROUND: Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1alpha protein overexpression has been shown in breast cancer. The impact of HIF-1alpha alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known. METHODS: Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1alpha and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1alpha splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival. RESULTS: HIF-1alpha isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1alphaTAG) and HIF-1alpha736 mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (P = 0.009 and P = 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1alphaTAG mRNA levels (P = 0.037). Significant statistical association was found between tumour grade and HIF-1alphaTAG (P = 0.048), and total HIF-1alpha (P = 0.048) mRNA levels. HIF-1alphaTAG mRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (P = 0.005 and P = 0.033 respectively). Univariate analysis showed that high HIF-1alphaTAG mRNA levels correlated with shortened metastasis free survival (P = 0.01). CONCLUSIONS: Our results show for the first time that mRNA expression of a HIF-1alphaTAG splice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.See commentary: http://www.biomedcentral.com/1741-7015/8/45.

Preoperative simplified geriatric assessment in planned hip and knee arthroplasty.

INTRODUCTION: Hip and knee arthroplasties are the most common planned orthopedic surgical procedures in older persons. It would be useful to identify frailties before surgery to improve the outcome of older patients. PURPOSE: The objective of this work was to identify the criteria of a simplified comprehensive geriatric assessment (mini-CGA) that were associated with unplanned hospital readmission and postoperative complications within 3 months after the planned hip and/or knee arthroplasty in patients ≥ 65 years. METHODS: This prospective study was carried out in the orthopedic department of Marseille University Hospital from January to May 2019. A mini-CGA was performed preoperatively. RESULTS: One hundred four patients were included in the study. The rate of early readmission within 3 months after surgery was 12.5% and the rate of postoperative complications was 40.4%. In multivariate analysis, dependence in the activities of daily living (ADL ≤ 5) was the only factor associated with unplanned readmission (aOR = 9.9, 95% CI 1.9-50.8), and living alone was the only factor associated with postoperative complications (aOR = 3.2, 95% CI 1.2-8.8). CONCLUSIONS: We found that the ADL score was associated with the risk of unplanned readmission in older patients undergoing planned arthroplasty, and that living alone was associated with postoperative complications. A preoperative mini-CGA appears essential to limit postoperative morbidity.

Impact of a prescription monitoring program on doctor-shopping for high dosage buprenorphine.

PURPOSE: Doctor-shopping (simultaneous use of several physicians by a patient) is one of the most frequent ways of diversion for prescription drugs. A specific method was used to assess the evolution of doctor-shopping for High Dosage Buprenorphine (HDB) in a French region from 2000 to 2005 and the impact of a prescription monitoring program for HDB implemented in 2004. METHODS: Data from eight periods (semesters of years 2000, 2002, 2004, and 2005) were extracted from a prescription database. Three quantities (the delivered, the prescribed, and the doctor-shopping quantity) were computed for each patient. The total doctor-shopping quantity and the doctor-shopping ratio (percentage of buprenorphine obtained through doctor-shopping) were used to evaluate the diversion of HDB among the population. The total prescribed quantity and the number of patients treated regularly were used as indicators of the access to treatment. RESULTS: The doctor-shopping ratio increased from 1st semester 2000 to 1st semester 2004 (from 14.9 to 21.7%) and then decreased to 16.9% in 2nd semester 2005. The total doctor-shopping quantity followed the same evolution. The number of patients treated remained stable from 1st semester 2000 to 2nd semester 2005. The prescribed quantity increased from 1st semester 2000 to 2nd semester 2002, decreased in 1st semester 2004 (4163 g) and then remained stable. CONCLUSIONS: After a four-year increase of the diversion through doctor-shopping for buprenorphine the beginning of the prescription monitoring program was concomitant with a marked decrease of doctor-shopping indicators without notable impact on the access to treatment.

Doctor shopping of opioid analgesics relative to benzodiazepines: A pharmacoepidemiological study among 11.7 million inhabitants in the French countries.

BACKGROUND: The abuse of prescription opioids and its subsequent consequences is an important public concern particularly in the USA. The literature on opioid analgesic abuse is scarce. OBJECTIVE: We assess the extent and risk of opioid analgesics abuse relative to benzodiazepines (BZD) using the doctor shopping method, taken into account the pharmacological characteristics (dosage, route of administration, extended or immediate release). METHODS: We used SNIIRAM database covering 11.7 million inhabitants. All individuals with at least one reimbursement for non-injectable opioid analgesic or BZD in 2013 were included. Opioids for mild to moderate pain and for moderately severe to severe pain were studied. The Doctor Shopping Quantity (DSQ) is the quantity obtained by overlapping prescriptions from several prescribers. The Doctor Shopping Indicator (DSI) is the DSQ divided by the total dispensed quantity. RESULTS: The strong opioid analgesics have the highest DSI (2.79%) versus 2.06% for BZD hypnotics. Flunitrazepam ranked first according to its DSI (13.2%), followed by morphine (4%), and zolpidem (2.2%). The three-strong opioids having the highest DSI were morphine, oxycodone and fentanyl (respectively 4%, 1.7% and 1.5%). The highest DSI was observed for the highest dosages of morphine (DSI = 8.4% for 200 mg) and oxycodone (DSI = 2.8% for 80 mg). The highest DSI for fentanyl was described with nasal and transmucosal forms (4.1% and 3.3% respectively). The highest DSI for morphine was described for extended-release (4.1%). CONCLUSION: There is a need to reinforce surveillance systems to track opioid misuse and to increase awareness of healthcare professionals.

[Prescription switch studies: objectives, methods and limits]. / Etude des reports de prescription: objectifs, méthodes et limites.

Prescription switch is a phenomenon of major interest for most of current questions in pharmacoepidemiology and pharmacoeconomics. However, only a few drug utilization studies focus on prescription switch description and analysis. Prescription switch can be considered at two different levels: global (drug market changes) or individual (description of patient's treatments patterns). The objective of this article is to describe the different types of prescription switch studies, according to this distinction. Objectives, type of data needed, and limits of each type of prescription switch study are presented.

Are Ultrasound Findings Similar in Patients with Axial Spondyloarthritis and in Athlete Entheses?

OBJECTIVE: Enthesitis is the spondyloarthritis (SpA) landmark, but can also be seen after entheses overuse, such as during intensive sport. METHODS: We aimed to compare entheses ultrasound (US) findings in a prospective cross-sectional study of 30 axial SpA cases, 30 athletes, and 29 controls. RESULTS: Mean (SD) MAdrid Sonographic Enthesis Index (MASEI) score was 26.3 (13), 12.2 (7), and 10.4 (6) in patients with SpA, athletes, and non-athlete control groups, respectively (p < 0.0001). CONCLUSION: The MASEI score was significantly higher in patients with SpA compared with healthy controls, athletes, and non-athletes, and can be of value to distinguish SpA from healthy subjects, whatever their physical activity.

[Misuse of clonazepam (Rivotril): recent trends]. / Détournement d'usage du clonazépam (Rivotril): tendances récentes.

Recent observations suggest the existence of clonazepam abuse. In order to determine the importance of this practice and the characteristics of these consumers, a study has been carried out, based on data from the Provence-Alpes-Côte-d'Azur and Corsica health reimbursement system. Individuals from these regions affiliated to the French health reimbursement system, who have had a prescription of clonazepam reimbursed between January 1, 2001 and February 15, 2001, have been selected. The deliveries have been monitored over a 9 month-period. 9381 subjects have been selected. A sub-group of 1.5 per cent subjects with a deviant behaviour has been identified by factorial analysis and has been compared to the sub-group without deviant behaviour. The subjects with deviant behaviour are younger and mostly male. The dosage of clonazepam is higher (10.8 mg per day versus 2.1 mg per day) with a significantly higher proportion of benzodiazepine and high-dose buprenorphine. The number of deliveries is higher (19.4 versus 5.9) as well as the number of different physicians (4.5 versus 1.5) and pharmacies (5.9 versus 1.3). This study provides some arguments in favor of the potential of abuse and dependence of clonazepam and the necessity to reinforce its monitoring. This information requires to be relayed to health professionals.

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.