Real-world insights into risk of developing cardiovascular disease following GnRH agonists versus antagonists for prostate cancer: a methodological protocol to a study using five European databases

International audienc

New metrics for assessing linkage quality in deterministic record linkage of health databases

Linking several datasets is becoming increasingly important for epidemiological research. However, assessing linkage quality can be challenging. This paper introduces a deterministic record linkage strategy that focuses on assessing linkage quality using new quality metrics. We developed a deterministic linkage strategy that systematically considers all combinations of individual identifiers. An exhaustive exploration of all variable combinations makes it possible to compute a new metric, referred to as robustness, and to generate a linkage cartography that precisely summarizes the linked pair characteristics. This cartography is central to our approach and makes it possible for the expert to easily accept/reject groups of linked pairs. The approach was tested on synthetic datasets staging a variety of possible linkage scenarios, and on two real-world studies (a registry database and a clinical trial).Dataset simulations demonstrated very good accuracy with a limited impact of different factors (datasets size/ratio, overlap, and errors), scalability, and encouraging runtimes. Minima were greater than 0.95 for recall and greater than 0.99 for precision, whatever the scenario. Feasibility on real datasets was verified with good results: among 3985 patients from the registry, the algorithm found 3850 single linked pairs and 135 proposals with multiple candidates out of 504,795 candidates. After reviewing the linkage cartography, the expert validated 3783 linked pairs and a manual review of multiple candidates added 20 pairs, reaching a linkage rate of 95.4%. For the trial, only 2 records out of 129 were not linked among 22,426 candidates, as a result of early withdrawal (no information in the trial database), giving a linkage rate of 98.4%. The novelty of our approach is twofold: first, the linkage cartography provides a new way of classifying and comparing deterministic rules from the set of all possible rules and second, the approach is by design resilient to data corruption and can reach better recall than standard deterministic linkage strategies. Finally, good performance and scalability open the door to the linkage of very large datasets

Androgen deprivation therapy prescription, blood and bone-density testing in a French population-based study exploring adherence to the French prostate cancer guidelines

International audienceThe safety profile of androgen deprivation therapy (ADT) is well known, and cardiovascular and osteoporosis risk factors should be assessed before ADT initiation. In order to examine whether the French Committee of Urologic Oncology prostate cancer (PCa) guidelines were properly followed by clinicians, including urologists, oncologists and radiotherapists, we used a nationwide comprehensive cohort of prostate cancer patients, who were new ADT users in 2011 and were followed up to 2013. Reimbursements for biological examinations and prescribers were identified, as well as PCa specialist consultations at drug initiation. Our results in this French cohort showed that the proportions of patients resorting to specialised care between one year and 3 months before ADT initiation and in the 6 months following was around 40 % for fasting glucose and 30 % for lipid assessments. Bone densitometry was performed on around 1% of patients. In the 12 months after ADT initiation, 75% of the patients were seen by a urologist and around 47% by an oncologist or a radiotherapist. Overall, there is still room for improvement in terms of ADT monitoring by clinicians and in the information provided to general practitioners and patients regarding the expected adverse effects of this treatment

Safety of abiraterone and enzalutamidein French real-world experience

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Use of 5α-reductase inhibitors for benign prostate hypertrophy and risk of high-grade prostate cancer A French population-based study

International audienceObjective - To assess the association between 5α-reductase inhibitor (5-ARI) use and high grade (Gleason score 8-10) prostate cancer. Patients and methods - We conducted a population-based nested matched case-control study using the French national health insurance database linked to data from all pathology laboratories in Brittany, France. Among 74 596 patients with ≥1 drug reimbursement for symptomatic benign prostate hypertrophy (BPH) between 1 January 2010 and 31 December 2011, 767 incident prostate cancer cases between 1 January 2012 and 31 December 2013 were matched according to age and delay between the first observed delivery of drug for BPH (5-ARIs, α-blockers or phytotherapy) and diagnostic date of the case to five control patients, using an incidence density sampling design. Results - A total of 963 patients (153 cases, 810 controls) had been exposed to 5-ARIs. A significant heterogeneity (P = 0.005) was detected across cancer grades when estimating the association between prostate cancer and long-term (≥2 years) 5-ARI use vs no 5-ARI exposure: adjusted conditional odds ratio 1.76 (95% confidence interval [CI] 0.97-3.21) for Gleason score ≥8 and 0.64 (95% CI 0.44-0.93) for Gleason score 2 years with 5-ARIs should be informed about the increased risk of development of high grade disease

Changes in prostate cancer screening practice by blood PSA testing between 2011 and 2017, a French population-based study

International audienceOBJECTIVE: The aim of the study was to determine the trend of first blood prostate-specific antigen (PSA) test prescription in France between 2011 and 2017, based on the assumption that prostate cancer (PCa) screening is expected to decline over the years. METHOD: Using a representative sample of the French population from the French Health Insurance database, we identified 50-52-year-old men without PCa and without any blood PSA test in the five years before 2011, 2014 and 2017 (January 1-December 31 of each year). For each of these three years, the primary outcome was the first reimbursement of a blood PSA test. We used a logistic regression model with first blood PSA test as the outcome and year as the main explanatory variable. As secondary objectives, we also identified the prescriber’s specialty, the urological consultation frequency, and the number of prostate biopsies in the year after the first blood PSA test reimbursement (only for 2011 and 2014). RESULTS: In 2011, 2014 and 2017, 5 275, 5 792 and 5 887 50-52-year-old men, respectively, were included. The percentage of patients with a first blood PSA test prescription decreased linearly from 2011 to 2017: 15.7% in 2011, 13.2% in 2014, and 12.4% in 2017 (p < .001). Blood PSA testing was mainly prescribed by general practitioners (>95%). The median interval between PSA tests was 13 months in 2011 and 14 months in 2014. Fewer than 10% of men had ≥1 consultation with an urologist during the year after the first blood PSA test. After the first blood PSA test, eight prostate biopsies were performed in 2011 and two in 2014. CONCLUSION: Our results suggest that in France, PCa screening is a primary care issue. Although PCa screening remains controversial and confusion exists about the best practice, our study showed a linear decrease of blood PSA test prescriptions for 50-52-year-old men between 2011 and 2017, although the reason for screening was unknown. As clinical information was not available, additional evidence is needed to determine the real impact of this decrease on the cancer-specific and overall mortality

Utilisation du PMSI pour la détection d'effets indésirables médicamenteux. [Use of the PMSI for the detection of adverse drug reactions].

International audienceAIM: To evaluate the performance of a query on international classification of diseases 10(th) version (ICD10) codes in the database of the programme for the medicalisation of information systems (programme de médicalisation des systèmes d'information, PMSI) to identify serious adverse drug reactions (ADR). METHODS: The query concerned hospital stays of patients discharged from the French University Hospital of Rennes in 2009. All the hospitalization summaries including a selected ICD10 code were analysed to validate ADR. RESULTS: Out of 383 cases, 142 cases were validated (37.1%). Performance of some ICD10 codes was particularly interesting, above 40% (T88.6, L27.0, J70.4, G62.0 and N14.1) and 79.5% of the ADR were detected by these five codes. During the study period, 98 ADR of the same type were spontaneously reported by physicians, 22 of which were common with the ICD10 query. CONCLUSIONS: The use of PMSI can be a tool for signal detection of serious ADR, in addition to spontaneous reporting

Major bleeding risk and mortality associated with antiplatelet drugs in real-world clinical practice. A prospective cohort study

International audienceBackground - Major bleedings other than gastrointestinal (GI) and intracranial (ICH) and mortality rates associated with antiplatelet drugs in real-world clinical practice are unknown. The objective was to estimate major bleeding risk and mortality among new users of antiplatelet drugs in real-world clinical practice. Methods and findings - A population-based prospective cohort using the French national health data system (SNIIRAM), identified 69,911 adults living within five well-defined geographical areas, who were new users of antiplatelet drugs in 2013-2015 and who had not received any antithrombotics in 2012. Among them, 63,600 started a monotherapy and 6,311 a dual regimen. Clinical data for all adults referred for bleeding was collected from all emergency departments within these areas, and medically validated. Databases were linked using common key variables. The main outcome measure was time to major bleeding (GI, ICH and other bleedings). Secondary outcomes were death, and event-free survival (EFS). Hazard ratios (HR) were derived from adjusted Cox proportional hazard models. We used Inverse Propensity of Treatment Weighting as a stratified sensitivity analysis according to the antiplatelet monotherapy indication: primary prevention without cardiovascular (CV) risk factors, with CV risk factors, and secondary prevention. We observed 250 (0.36%) major haemorrhages, 81 ICH, 106 GI and 63 other types of bleeding. Incidences were twice as high in dual therapy as in monotherapy. Compared to low-dose aspirin (≤ 100 mg daily), high-dose (> 100 up to 325 mg daily) was associated with an increased risk of ICH (HR = 1.80, 95%CI 1.10 to 2.95). EFS was improved by high-dose compared to low-dose aspirin (1.41, 1.04 to 1.90 and 1.32, 1.03 to 1.68) and clopidogrel (1.30, 0.73 to 2.3 and 1.7, 1.24 to 2.34) respectively in primary prevention with and without CV risk factors. Conclusion - The incidence of major bleeding and mortality was low. In monotherapy, low-dose aspirin was the safest therapeutic option whatever the indication. Trial registration - NCT02886533

Association between gifts from pharmaceutical companies to French general practitioners and their drug prescribing patterns in 2016: retrospective study using the French Transparency in Healthcare and National Health Data System databases

International audienceObjective To evaluate the association between gifts from pharmaceutical companies to French general practitioners (GPs) and their drug prescribing patterns.Design Retrospective study using data from two French databases (National Health Data System, managed by the French National Health Insurance system, and Transparency in Healthcare).Setting Primary care, France.Participants 41 257 GPs who in 2016 worked exclusively in the private sector and had at least five registered patients. The GPs were divided into six groups according to the monetary value of the received gifts reported by pharmaceutical, medical device, and other health related companies in the Transparency in Healthcare database.Main outcome measures The main outcome measures were the amount reimbursed by the French National Health Insurance for drug prescriptions per visit (to the practice or at home) and 11 drug prescription efficiency indicators used by the National Health Insurance to calculate the performance related financial incentives of the doctors. Doctor and patient characteristics were used as adjustment variables. The significance threshold was 0.001 for statistical analyses.Results The amount reimbursed by the National Health Insurance for drug prescriptions per visit was lower in the GP group with no gifts reported in the Transparency in Healthcare database in 2016 and since its launch in 2013 (no gift group) compared with the GP groups with at least one gift in 2016 (−€5.33 (99.9% confidence interval −€6.99 to −€3.66) compared with the GP group with gifts valued at €1000 or more reported in 2016) (P<0.001). The no gift group also more frequently prescribed generic antibiotics (2.17%, 1.47% to 2.88% compared with the ≥€1000 group), antihypertensives (4.24%, 3.72% to 4.77% compared with the ≥€1000 group), and statins (12.14%, 11.03% to 13.26% compared with the ≥€1000 group) than GPs with at least one gift between 2013 and 2016 (P<0.001). The no gift group also prescribed fewer benzodiazepines for more than 12 weeks (−0.68%, −1.13% to −0.23% compared with the €240-€999 group) and vasodilators (−0.15%, −0.28% to −0.03% compared with the ≥€1000 group) than GPs with gifts valued at €240 or more reported in 2016, and more angiotensin converting enzyme (ACE) inhibitors compared with all ACE and sartan prescriptions (1.67%, 0.62% to 2.71%) compared with GPs with gifts valued at €1000 or more reported in 2016 (P<0.001). Differences were not significant for the prescription of aspirin and generic antidepressants and generic proton pump inhibitors.Conclusion The findings suggest that French GPs who do not receive gifts from pharmaceutical companies have better drug prescription efficiency indicators and less costly drug prescriptions than GPs who receive gifts. This observational study is susceptible to residual confounding and therefore no causal relation can be concluded.This article has a correction. Please see: https://www.bmj.com/content/367/bmj.l661

Isotretinoin and risk factors for suicide attempt: a population-based comprehensive case series and nested case-control study using 2010-2014 French Health Insurance Data

International audienceBACKGROUND: Although the causal role of isotretinoin in suicidal behaviour is controversial, suicide attempts (SA) do occur among patients taking isotretinoin.OBJECTIVES: To describe patient profiles and the management of isotretinoin among patients who committed or attempted suicide under treatment. To assess the risk factors for SA under isotretinoin.METHODS: We performed a comprehensive case series of suicides and SAs under isotretinoin, and a case-control study, using Nationwide French Health Insurance database. The main analysis compared cases (subjects with a SA during a course of isotretinoin) to controls, individually matched for age, gender and rank of the current course; controls were to be exposed to isotretinoin at the index date (date of SA for the corresponding cases). The patients' psychiatric history at isotretinoin initiation was studied. In a secondary analysis, patients who continued their isotretinoin treatment after their SA were compared to patients who discontinued it.RESULTS: In all, 328 018 subjects started a course of isotretinoin between 1 January 2010 and 31 December 2014 and 184 patients were hospitalized for a SA; half of them had a psychiatric history at initiation. In the multivariate analysis, psychiatric history and history of anxiety alone were risk factors for SA [Odds ratio (OR), 18.21; 95% confidence interval (CI), 9.96-33.30 and 4.78; 95% CI, 2.44-9.33, respectively]. Among 176 cases of SA with sufficient follow-up, 103 (58.5%) carried on with their treatment after their SA. Treatment initiation by a dermatologist was inversely associated with the continuation of the treatment after a SA (OR, 0.38; 95% CI, 0.18-0.80).CONCLUSIONS: Suicide attempts under isotretinoin are rare events, and our results suggest that most of the patients concerned have a risk-prone profile detectable at the time of treatment initiation. The risk-benefit ratio of continuing isotretinoin after a SA warrants further careful evaluation