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Summary: We studied the characteristics of patients prescribed osteoporosis medication and patterns of use in European databases. Patients were mostly female, older, had hypertension. There was suboptimal persistence particularly for oral medications. Our findings would be useful to healthcare providers to focus their resources on improving persistence to specific osteoporosis treatments. Purpose: To characterise the patients prescribed osteoporosis therapy and describe the drug utilization patterns. Methods: We investigated the treatment patterns of bisphosphonates, denosumab, teriparatide, and selective estrogen receptor modulators (SERMs) in seven European databases in the United Kingdom, Italy, the Netherlands, Denmark, Spain, and Germany. In this cohort study, we included adults aged ≥ 18 years, with ≥ 1 year of registration in the respective databases, who were new users of the osteoporosis medications. The study period was between 01 January 2018 to 31 January 2022. Results: Overall, patients were most commonly initiated on alendronate. Persistence decreased over time across all medications and databases, ranging from 52–73% at 6 months to 29–53% at 12 months for alendronate. For other oral bisphosphonates, the proportion of persistent users was 50–66% at 6 months and decreased to 30–44% at 12 months. For SERMs, the proportion of persistent users at 6 months was 40–73% and decreased to 25–59% at 12 months. For parenteral treatment groups, the proportions of persistence with denosumab were 50–85% (6 month), 30–63% (12 month) and with teriparatide 40–75% (6 month) decreasing to 21–54% (12 month). Switching occurred most frequently in the alendronate group (2.8–5.8%) and in the teriparatide group (7.1–14%). Switching typically occurred in the first 6 months and decreased over time. Patients in the alendronate group most often switched to other oral or intravenous bisphosphonates and denosumab. Conclusion: Our results show suboptimal persistence to medications that varied across different databases and treatment switching was relatively rare. [ABSTRACT FROM AUTHOR]

Introduction: Non-steroidal anti-inflammatory drugs are associated with a dose and duration-dependent coronary risk. There is little information concerning analgesic-dose ibuprofen, among the most widely used drugs worldwide.Objective: Our objective was to measure the risks of acute coronary syndrome (ACS) after dispensing of ibuprofen, versus paracetamol.Methods: Propensity score 1:2-matched cohorts of ibuprofen or paracetamol treatment episodes (TEs) in Echantillon Généraliste de Bénéficiaires (EGB), the 1/97 sample of Système National des Données de Santé (SNDS), the French nationwide claims database, from 2009 to 2014, were compared. Outcomes were hospital admissions for ACS during the 3 months after the dispensing of ibuprofen or paracetamol. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated overall and stratified on low-dose aspirin dispensing.Results: A total of 315,269 ibuprofen TEs in 168,400 persons were matched to 630,457 paracetamol TEs in 395,952 patients. Event rates were 50-100 times higher in low-dose aspirin users (27 vs 0.28 per 1000 patient years). Overall there was no difference in risk of ACS at 3 months (HR 0.94, 95% CI 0.74-1.20) despite a transient increase in the first 2 weeks in ibuprofen users (HR 1.70, 95% CI 1.11-2.59). In the stratified analysis, this short-term risk was only found in aspirin users (5% of population, HR 1.84, 95% CI 1.24-3.24), but not in non-aspirin users (HR 1.09, 95% CI 0.40-2.94).Conclusions: There was no evidence for an increased risk of ACS in patients dispensed ibuprofen compared to paracetamol. [ABSTRACT FROM AUTHOR]

Aims This study aimed to describe the real-life incidence of bleeding, arterial thrombotic events and death during vitamin K antagonist (VKA) treatment in atrial fibrillation (AF). Methods This was a cohort study in Echantillon Généraliste de Bénéficiaires, the 1/97 sample of the French national healthcare claims and hospitalization database, of new VKA users with definite or probable AF and no other indication, and of patients without AF, from 2007 to 2011. Prespecified outcomes were all-cause death, hospitalization for bleeding, arterial thrombotic event (ATE), or acute coronary syndrome (ACS) or any of the above (composite outcome). Results Of 8894 new VKA users, 3345 had probable or certain AF, 51.7% were male, mean age was 75.1 years, 87.1% had a CHA2DS2-VASc score ≥ 2 and 11.6% a HAS-BLED score > 3. Among AF patients, during VKA exposure the incidence rate of bleeding was 2.8 [95% confidence interval (CI) 2.2, 3.4] per 100 patient-years, including 0.6 (95% CI 0.3, 0.8) cerebral, 1.0 (95% CI 0.7, 1.3) digestive and 1.4 (95% CI 1.0, 1.7) other bleeds. There were 1.6 (95% CI 1.2, 2.0) ACS, 1.5 (95% CI 1.1, 1.8) ATE and 3.8 (95% CI 3.2, 4.4) deaths per 100 patient-years. The incidence rate of the composite outcome was 9.1 per 100 patient-years (95% CI 8.2, 10.0). When patients stopped VKA, bleeding decreased (RR 0.67, 95% CI 0.43, 1.04)), but death or thrombosis increased (RR 3.06, 95% CI 2.46, 3.81 and 1.75, 95% CI 1.14, 2.70, respectively). During VKA exposure non-AF patients had similar rates of bleeding, but fewer deaths, ACS and ischaemic events. Conclusions Real-life rates for bleeding, arterial thrombotic events, ACS and deaths in AF patients treated with VKA were similar to those observed in clinical trials. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • To our knowledge, no study has ever described the intensity of nonsteroidal anti-inflammatory drug (NSAID) utilization in an employed population by occupation. • As the use of NSAIDs carries a well-known risk of adverse effects, this risk adds to the burden of musculoskeletal disorders in employed populations. • Information on utilization of NSAIDs in this context will help to better characterize and prevent this risk. WHAT THIS STUDY ADDS • In spite of a previous history of dyspepsia, blue collar workers had the highest rate of chronic and continuous utilization of nonselective NSAIDs. • No clustering of cyclooxygenase-2 selective NSAID utilization according to a previous history of dyspepsia was observed among blue collar workers. • The association between chronicity of NSAID utilization and occupation was independent of medical indication for the prescription and other lifestyle factors. AIM The aim of this study was to compare patterns of utilization of NSAIDs for musculoskeletal disorders (MSD) by occupation in a general employed population. METHODS This was a secondary analysis of the CADEUS cohort study on 5651 actively employed patients, who submitted at least one claim for the reimbursement of a NSAID dispensation for a MSD between August 2003 and July 2004, in the French National Healthcare Insurance database. Questionnaires were sent to prescribing physicians to obtain diagnoses and the medical history, and to patients for their occupation, height and weight and smoking status. Multivariate logistic regression was used to study the determinants of a heavy use of NSAIDs defined as ‘over four dispensations in one year with less than two months between any two’. RESULTS Factors associated with heavy use of NSAIDs were age (Odds ratio (OR): 1.8 (ten years), 95% confidence interval (CI): 1.6–1.9), osteoarthritis (versus back pain) (OR: 1.8, 95% CI: 1.5–2.1), body mass index (superior to 30) (OR: 1.8, 95% CI: 1.5–2.2), and occupation (blue collar versus white collar workers) (OR: 1.4, 95% CI: 1.2–1.6). Blue collar workers also had a 20% higher prevalence of 5-year history of dyspepsia. No difference was observed between sexes or in the use of COX-2 selective inhibitors between occupations. CONCLUSION Factors associated with occupational constraints that contribute to the severity of MSDs, may explain the heavier use of NSAIDs among blue collar workers in spite of a concurrent and past medical history of adverse reactions to this type of medication. [ABSTRACT FROM AUTHOR]

Background: Clinical trials have indicated that the direct-acting oral anticoagulants dabigatran and rivaroxaban have better risk/benefit profiles than do vitamin K antagonists (VKAs) for stroke prevention in non-valvular atrial fibrillation (NVAF). Objective: Our objective was to compare the 1-year real-life risk of major clinical events with dabigatran or rivaroxaban versus VKAs for NVAF. Methods: This was a high-dimensional propensity score (hdPS)-matched cohort study of new users of dabigatran, rivaroxaban or VKAs for NVAF in the French national healthcare systems database in 2013 followed-up for 1 year [22]. Hazard ratios (HRs) with 95% confidence intervals (CIs) for clinical events and death were determined during exposure. Results: In 2013, a total of 103,101 new anticoagulant users had definite NVAF: 44,653 VKA, 27,060 dabigatran, and 31,388 rivaroxaban. In matched populations, HRs were as follows for dabigatran versus VKAs (20,489 per group): stroke and systemic embolism (SSE) 0.75 (95% CI 0.63–0.88), clinically relevant bleeding (CRB) 0.58 (95% CI 0.51–0.66), hemorrhagic stroke (HS) 0.22 (95% CI 0.14–0.36), gastrointestinal bleeding (GIB) 0.98 (95% CI 0.80–1.19), acute coronary syndrome (ACS) 0.79 (95% CI 0.65–0.95), death 0.74 (95% CI 0.67–0.82), composite (any of the above) 0.71 (95% CI 0.66–0.76). For matched rivaroxaban versus VKA (23,053 per group) HRs were as follows: SSE 0.98 (95% CI 0.85–1.14), CRB 0.83 (95% CI 0.75–0.92), HS 0.65 (95% CI 0.49–0.87), GIB 1.08 (95% CI 0.90–1.30), ACS 0.84 (95% CI 0.71–1.00), death 0.77 (95% CI 0.71–0.84), composite 0.84 (95% CI 0.79–0.89). Numbers needed to treat to observe one fewer death were 49 ± 0.05 with dabigatran or rivaroxaban versus VKAs. Conclusion: Consistent with results from clinical trials and other observational studies, dabigatran and rivaroxaban were at least as effective and safer than VKAs for the prevention of thromboembolic events in NVAF over 1 year in the French population. Study registration: European Medicines Agency EUPAS 13017 (www.encepp.eu) Clinicaltrials.gov id NCT02785354. [ABSTRACT FROM AUTHOR]

Abstract Background and aims We aimed to compare the effectiveness of ticagrelor vs. clopidogrel or prasugrel on recurrence of acute coronary syndromes (ACS) in real-life conditions, as requested by regulatory authorities at the time of marketing. Methods We performed a cohort study in SNDS, the French national healthcare database. All patients with a hospital admission for ACS in 2013 were followed one year. Patients on ticagrelor, clopidogrel or prasugrel were matched 1:1 using age, gender, index ACS type, and high-dimensional propensity scores (hdPS). Outcomes were ACS, stroke, all-cause death, and major bleeding, compared within matched groups using Cox proportional hazards models analysis during treatment. Results 54,048 ACS were hospitalized in 2013. At discharge, 19,796 were dispensed clopidogrel, 8242 prasugrel, and 13,916 ticagrelor. Per group, 9224 ticagrelor vs. clopidogrel, 6752 ticagrelor vs. prasugrel, and 4676 prasugrel vs. clopidogrel patients were matched. Compared to clopidogrel, ticagrelor was associated with a lower hazard ratio of death 0.73 [0.59–0.90] and composite criterion (0.88, 95% CI [0.79–0.99] but not ACS 0.92 [0.80–1.06], stroke (0.96 [017-5.53]) or major bleeding (1.02 [0.82–1.26]). Prasugrel was not different from ticagrelor or clopidogrel for any outcome, in matched patients. Conclusions Ticagrelor in real-life conditions in matched populations was associated with a lower risk of all-cause death than clopidogrel, and a lower risk of composite outcome, as in the main pivotal clinical trial. Ticagrelor and prasugrel were not different, nor were prasugrel and clopidogrel. Graphical abstract Image 1 Highlights • In real-life, clopidogrel was used in older patients compared with ticagrelor or prasugrel. • Prasugrel was used mostly after percutaneous intervention. • There were fewer deaths in ticagrelor users than in matched clopidogrel users. • There was no difference between ticagrelor and matched prasugrel users, or between clopidogrel and matched prasugrel users. [ABSTRACT FROM AUTHOR]

Aims: We compared the 1‐year safety and effectiveness of dabigatran 110 mg (D110) or 150 mg (D150) twice daily to vitamin K antagonists (VKA) in patients with nonvalvular atrial fibrillation. Methods: New user cohort study of patients dispensed D110 or D150 vs. VKA in 2013 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million persons). D110 and D150 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing and high‐dimensional propensity score. Hazard ratios [HR (95% confidence intervals)] for stroke and systemic embolism (SSE), major bleeding (MB) and death were computed using Cox proportional hazards or Fine and Gray models during exposure. Results: In 14 442 matched D110 and VKA patients, mean age 79, 49% male, 91% with CHA2DS2‐VASc ≥2 and 8% with HAS‐BLED score >3, incidence rates of SSE were 1.9% and 2.6% person‐years [HR 0.69 (0.56–0.84)], MB 1.8% and 2.9% [0.62 (0.51–0.76)], death 7.2% and 8.6% [0.84 (0.76–0.94)]. In 8389 matched D150 and VKA patients, mean age 67, 67% male, 65% with CHA2DS2‐VASC ≥2; < 5% HAS‐BLED >3, incidence rates were for SSE 1.4% and 1.9% [0.76 (0.56–1.04)], MB 0.6% and 1.9% [0.30 (0.20–0.46)], death 1.6% and 3.6% [0.46 (0.35–0.59)]. Numbers needed to treat to observe one fewer death were 78 for D110, 88 for D150. Conclusion: In real life D110 and D150 were at least as effective, and safer than VKA. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Centaurium erythraea Rafn (CE), Artemisia herba-alba Asso (AHA) and Trigonella foenum-graecum L. (TFG) are traditionally used to treat type 2 diabetes in Algeria, previous studies have found that extracts of these plants were effective to treat or prevent experimental diabetes induced by high-fat diet (HFD). Aim of the study Describe the additional effects of these extracts on lipid tissue deposition in HFD. Materials and methods Male C57BL/6J mice were fed with HFD to induce type 2 Diabetes. Groups of mice were given plant extracts orally at 2 g/kg/bodyweight daily for 20 weeks during establishment of diabetes, or for 18 weeks after confirmation of diabetes at the 17th week. Liver and other tissue samples were stained with Oil Red O. Results Liver steatosis was confirmed with HFD. CE, AHA and TFG extracts improved liver steatosis by the end of the preventive (20 weeks) and curative periods (35 weeks). This was most marked for CE extract ( p <0.05), less so with TFG and AHA. No steatosis was found in other tissues. Conclusion CE extract had a clear hepatoprotective effect in this mouse model of diet-induced type 2 diabetes. AHA and TFG had a minimal or no significant effect on steatosis. Beyond its effect as an antidiabetic agent, CE may also be promising to prevent or treat non-alcoholic liver steatosis. [ABSTRACT FROM AUTHOR]

Aims Most risks of nonsteroidal anti-inflammatory drugs ( NSAIDs) are pharmacological, dose and duration dependent. Usage patterns of prescription-only ( POM) or 'over-the-counter ( OTC)' NSAIDs may influence risks, but are not commonly described. Methods The Echantillon Généraliste de Bénéficiaires database, the permanent 1/97 representative sample from the French national healthcare insurance systems, was queried over 2009-2010 to identify usage patterns, concomitant chronic diseases and cardiovascular medication in OTC and POM NSAID users. Results Over 2 years, 229 477 of 526 108 patients had at least one NSAID dispensation; 44 484 patients (19%) were dispensed only OTC NSAIDs (93% ibuprofen) and 121 208 (53%) only POM NSAIDs. The OTC users were younger (39.9 vs. 47.4 years old) and more often female (57 vs. 53%); 69% of OTC users and 49% of POM users had only one dispensation. A mean of 14.6 defined daily doses ( DDD) were dispensed over 2 years for OTC vs. 53 for POM; 93% OTC vs. 60% POM patients bought ≤ 30 DDD over 2 years, and 1.5 vs. 12% bought ≥ 90 DDD. Chronic comorbidities were found in 19% of OTC users vs. 28% of POM users; 24 vs. 37% had at least one dispensation of a cardiovascular drug over the 2 years. Conclusions Most of the use of NSAIDs appears to be short term, especially for OTC-type NSAIDs, such as ibuprofen. The validity of risk estimates for NSAIDs extrapolated from clinical trials or from observational studies not including OTC-type usage may need to be revised. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Comparative Real‑Life Efectiveness and Safety of Dabigatran or Rivaroxaban vs. Vitamin K Antagonists: A High‑Dimensional Propensity Score Matched New Users Cohort Study in the French National Healthcare Data System SNDS."

Abstract: Ethnopharmacological relevance: Trigonella foenum-graecum L. (TFG) is traditionally used to treat diabetes in North Africa. we therefore tested the effects of the hydro-alcoholic extract of TFG seeds in a C57/BL6J mouse model of diabetes induced by a standardised high-fat diet (HFD). Materials and methods: Plant extracts (2g/kg daily) were administered orally by gavage at the start of HFD, or after confirmation of established diabetes (17th week), for 20 or 18 weeks, respectively, to male C57BL/6J mice. Animals were weighed; food intake and plasma glucose, lipid profile, insulin and insulin resistance were measured. Results: TFG extracts opposed the development of diabetes: compared with untreated HFD mice, TFG-treated HFD mice had lower mean (±SD) plasma glucose (129.3±39.4 vs. 183.1±19.1mg/dL, p<0.05), plasma insulin (1.3±0.8 vs. 3.1±1.8ng/mL, p<0.05) and triglycerides (18.9±12.9 vs. 48.9±12.1mg/dL, p<0.05), and less insulin resistance as estimated by the homeostasis model assessment (HOMA: 9.7±11.1 vs. 38.3±26.6, p<0.05). In mice with established diabetes, TFG reduced fasting plasma glucose (170.4±24.1 vs. 229.0±20.8mg/dL, p<0.05), plasma insulin (1.7± 1.3 vs. 3.3±14.3ng/mL, p<0.05) and insulin resistance (HOMA: TFG: 19.2±15.7 vs. HFD control: 38.5±30.3, p<0.05). In addition, administration of TFG extract also caused significant reduction in triglycerides (17.9±9.7 vs. 62.8±18.3mg/dL, p<0.05) and total cholesterol (1.30±0.20 vs. 1.80±1.10g/L, p<0.05), and an increase in HDL-cholesterol (1.6±0.2 vs. 1.2±0.1g/L). The plant extract had no effect on calorie intake or body weight. Conclusion: TFG extract opposed the development of experimental HFD diabetes in mice, and had an anti-diabetic effect in mice with established diabetes. [Copyright &y& Elsevier]