Incidence of heart failure following exposure to a protein kinase inhibitor, a French population-based study.

AIMS: Pharmacovigilance signals of heart failure (HF) following exposure to protein kinase inhibitors (PKIs) have been detected in recent years. Our aim was to identify the PKIs most frequently associated with the development of HF. METHODS: Using the French National Healthcare Database, all patients newly exposed to a PKI between January 2011 and June 2014 were followed up for 18 months. Specific hospitalization diagnosis and long-term HF-related disease codes were used to identify HF patients. HF incidence rate ratios (IRRs) were measured and adjusted hazard ratios (aHRs) were estimated using a Cox model. Sensitivity analyses were performed to limit the potential indication and competitive risk bias. RESULTS: Thirteen PKIs were studied. Among the 49 714 new PKI users registered during the study period, the mean IRR of HF was 3.38 per 100 person-years, with a median time to onset of 155 days. We found a significant increase in the incidence of HF for six medicinal products: pazopanib (aHR = 2.42, 95% confidence interval [CI] 1.67-3.52), dasatinib (aHR = 2.22, 95% CI 1.42-3.44), ruxolitinib (aHR = 2.11, 95% CI 1.69-2.64), crizotinib (aHR = 1.71, 95% CI 1.07-2.72), everolimus (aHR = 1.45, 95% CI 1.26-1.67) and vemurafenib (aHR = 1.37, 95% CI 1.01-1.86). Sensitivity analyses were consistent with our primary analysis. CONCLUSIONS: The current study provides knowledge on HF following exposure to a PKI. Additional studies could confirm these results for dasatinib, everolimus, pazopanib and ruxolitinib, and particularly for the two medicinal products with results slightly above the significance threshold, namely, crizotinib and vemurafenib, in our sensitivity analyses.

Impact of the COVID-19 pandemic and its control measures on cardiovascular and antidiabetic drugs use in France in 2020: a nationwide repeated cohort study.

Since pandemic start, patients may have faced difficulties in accessing to care and treatment. This study aimed at assessing the impact of COVID-19 pandemic and its control measures on the use of drugs indicated in cardiovascular prevention and diabetes mellitus in France. From 09/17/2018 to 09/20/2020, a repeated cohort analysis was performed using the French nationwide health insurance databases. The pandemic impact was assessed using time-series analyses and unobserved components model for the weekly number of patients with (i) drug dispensing, (ii) ongoing treatment, (iii) treatment initiation, (iv) treatment disruption. Overall, 14,822,132 patients with cardiovascular drug dispensings and 3,231,618 with antidiabetic ones were identified. After a sharp spike in the amount of dispensings in the week the first national lockdown was announced, the period was marked by decreased levels and trends. Altogether, the estimated impact of the pandemic on dispensings appeared limited over the lockdown period (1-3% lack in dispensings). During lockdown, the weekly numbers of treatment disruptions remained stable whereas a significant decrease in treatment initiations was observed for almost all drug classes (e.g. ß-blockers initiations: - 8.9%). Conversely, the post-lockdown period showed increases in treatment disruptions especially for antihypertensive and lipid lowering drugs (e.g. statins disruptions: + 4.9%). The pandemic and associated measures had a significant impact on cardiovascular and antidiabetic drugs use in France, mostly consisting in decreases of treatment initiations over lockdown and increases in treatment disruptions afterwards. Both could result in increased morbimortality that remains to be assessed.

Antidopaminergic antiemetics and trauma-related hospitalization: A population-based self-controlled case series study.

AIMS: The aim of this study was to evaluate the risk of trauma associated with the use of antidopaminergic antiemetics in a real-world setting. METHODS: A self-controlled case series analysis was performed using the EGB database, the representative sample of the French national healthcare insurance system database. All subjects aged 18 years and over who presented with at least 1 trauma-related hospitalization and 1 supply for domperidone, metoclopramide or metopimazine between 2009 and 2014 were included in the study. Associations were evaluated by incidence rate ratios. RESULTS: Included exposed cases were 7610 for domperidone cohort, 2189 for metoclopramide and 3911 for metopimazine. Incidence rate ratio for trauma-related hospitalization during the first 7 days of exposure period compared to unexposed period was 1.53 (95% confidence interval 1.29-1.80) for domperidone, 2.00 (1.37-2.91) for metoclopramide and 2.30 (1.71-3.09) for metopimazine. CONCLUSION: We found an increased risk of hospitalizations for traumatic injuries for the main marketed antidopaminergic antiemetics during the first days of use. The highest risk was observed for metopimazine, which could relate to its pharmacological profile and central effects.

Safety profile of drugs for advanced melanoma: A report based on 2008-2018 US Food and Drug Administration Data.

We describe the safety profiles of all drug classes used for the treatment of advanced melanoma from the US Food and Drug Administration Adverse Event Reporting System over 2008-2018. Adverse reactions reported in 25 900 pharmacovigilance cases are described for chemotherapies, immunomodulators, targeted therapies and immunotherapies. There was a sharp increase in the number of cases over time, with peaks associated with the launch of new treatments. The adverse reactions diversified over time; notably, skin (alopecias, dermatitis) and retinal disorders were frequently associated with targeted therapies and endocrine disorders (hypothalamus, thyroid and adrenal dysfunctions) with immunotherapies. Less well-known reactions were also detected, such as neuropsychiatric disorders with targeted therapies and gastrointestinal ulcers, pneumothorax and pleural effusions with immunotherapies. The findings highlight the need for various health professionals (including medical specialists or trained nurses) to enhance management of complications.

Medicine misuse: A systematic review and proposed hierarchical terminology.

AIMS: Although medicine misuse is a public health issue, it has multiple meanings in the medical literature. This study aimed to characterize, classify and identify the most appropriate definitions of medicine misuse. METHODS: A systematic review was performed in Medline, ISI Web of Science, SocINDEX, PsycInfo, PsycArticles and Psychological and Behavioral Sciences Collection, using keywords related to "misuse", "appropriateness" and "medicine" between 1 November 2008 and 25 August 2020. Additional searches were conducted in websites of regulatory agencies and public health institutions. Two authors independently selected studies providing both definitions and examples of misuse, while a third resolved disagreements. Definitions were used to propose a hierarchical classification based on initiator, intent, purpose and context of medicine misuse. The study is registered on PROSPERO: CRD42018115789. RESULTS: Of 3404 identified records, 51 were included. A total of 71 definitions and 74 examples of misuse were retrieved. When the prescriber is initiator and according to intent, potential medicine misuse referred to "intentional or unintentional prescribing not in line with clinical evidence". Based on context, they could prescribe medicines not clinically justified, i.e. overprescribing, or prescribe indicated medicines incorrectly, i.e. misprescribing. Among other groups of definitions, those overlapping with drug abuse or medication use errors were considered out-of-scope. CONCLUSION: This systematic review provides a comprehensive overview of the terms and definitions used to characterize medicine misuse and could serve as a basis for a terminology that makes clear distinctions between misuse, abuse and errors.

Effectiveness of first-line cetuximab in wild-type RAS metastatic colorectal cancer according to tumour BRAF mutation status from the EREBUS cohort.

AIMS: Poor efficacy has been reported for patients with BRAF mutations for metastatic colorectal cancer (mCRC). METHODS: EREBUS is a French cohort study of wild-type (wt) KRAS unresectable mCRC patients initiating a first-line treatment with cetuximab from 2009 to 2010, followed for two years (five years for vital status). Molecular genetics platforms have provided additional RAS and BRAF mutation testing results. Progression-free survival (PFS) and overall survival (OS) were assessed according to tumour mutation (mt) status: RASmt/BRAFany, RASwt/BRAFmt and RASwt/BRAFwt. Multivariate Cox analyses were used to evaluate association between mutation status and death or progression. RESULTS: A total of 389 patients were included in 65 centres and with a known tumour mutation status: 64 RASmt/BRAFany (21%), 33 RASwt/BRAFmt (13%) and 213 RASwt/BRAFwt (87%). Respective baseline characteristics were: median age 65, 64 and 63 years, male gender 63%, 64% and 69%, Eastern Cooperative Oncology Group performance status ≤ 1 75%, 76% and 79%, and liver-only metastases 39%, 33% and 40%. Median progression-free survival was 8.0 months [5.9-9.3] for patients with RASmt/BRAFany, 6.0 months [2.3-7.2] for patients with RASwt/BRAFmt, and 10.4 months [9.5-11.0] for patients with RASwt/BRAFwt. Respectively, median overall survival was 18.4 months [10.9-23.3], 9.7 months [6.9-16.6] and 29.3 months [26.3-36.1]. In multivariate analyses, progression (HR = 2.71 [1.79-4.10]) and death (HR = 2.79 [1.81-4.30]) were more likely for RASwt/BRAFmt vs RASwt/BRAFwt patients. CONCLUSIONS: BRAF mutations were associated with markedly poorer outcomes in initially unresectable RASwt mCRC patients treated by cetuximab in first-line treatment.

REview of potentially inappropriate MEDIcation pr[e]scribing in Seniors (REMEDI[e]S): French implicit and explicit criteria.

PURPOSE: To establish a consensus on both explicit and implicit criteria in order to identify potentially inappropriate prescribing (PIP) in French older people aged 75 years and over or 65 years and over with multimorbidity. METHODS: Fifteen experts in geriatrics, general practice, pharmacy, and clinical pharmacology were involved in a two-round Delphi survey to assess preliminary explicit and implicit criteria based on an extensive literature review and up-to-date evidence data. Experts were asked to rate their level of agreement using a 5-level Likert scale for inclusion of criteria and also for rationale and therapeutic alternatives. A consensus was considered as reached if at least 75% of the experts rated criteria as "strongly agreed" or "agreed." RESULTS: The new tool included a seven-step algorithm (implicit criteria) encompassing the three main domains that define PIP (i.e. overprescribing, underprescribing, and misprescribing) and 104 explicit criteria. Explicit criteria were divided into 6 tables related to inappropriate drug duplications (n = 7 criteria), omissions of medications and/or medication associations (n = 16), medications with an unfavourable benefit/risk ratio and/or a questionable efficacy (n = 39), medications with an unsuitable dose (n = 4) or duration (n = 6), drug-disease (n = 13), and drug-drug interactions (n = 19). CONCLUSION: The REMEDI[e]S tool (REview of potentially inappropriate MEDIcation pr[e]scribing in Seniors) is an original mixed tool, adapted to French medical practices, aimed at preventing PIP both at the individual level in clinical practice and the population level in large-scale studies. Therefore, its use could contribute to an improvement in healthcare professionals' prescribing practices and safer care in older adults.

Appropriateness of psychotropic drug prescriptions in the elderly: structuring tools based on data extracted from the hospital information system to understand physician practices.

BACKGROUND: The appropriateness of psychotropic prescriptions in the elderly is a major quality-of-care challenge at hospital. Quality indicators have been developed to prevent inappropriate psychotropic prescriptions. We aimed to select and automatically calculate such indicators, from the Bordeaux University Hospital information system, and to analyze the appropriateness of psychotropic prescription practices, in an observational study. METHODS: Experts selected indicators of the appropriateness of psychotropic prescriptions in hospitalized elderly patients, according to guidelines from the French High Authority for Health. The indicators were reformulated to focus on psychotropic administrations. The automated calculation of indicators was analyzed by comparing their measure to data collected from a clinical audit. In elderly patients hospitalized between 2014 and 2015, we then analyzed the evolution of the appropriateness of psychotropic prescription practices during hospital stay, using methods of visualization, and described practices by considering patients' characteristics. RESULTS: Two indicators were automated to detect overuse and misuse of psychotropic drugs. Indicators identified frequent inappropriate drug administrations, but practices tended to become more appropriate after quality-of-care improvement actions. In the majority of patients (85%), there was no inappropriate administration of psychotropic drugs during hospital stay; for the remaining 15% with at least one inappropriate administration, physicians tended to limit overuse or misuse during hospital stay. Inappropriate administrations were more frequent in patients suffering from psychiatric disorders, dependence and associated complications or morbidities. CONCLUSIONS: The automated indicators are structuring tools for the development of a drug prescription monitoring system. Inappropriate psychotropic administrations were limited by physicians during hospital stay; some inappropriate prescriptions might be explained by clinical characteristics of patients.

Antipsychotics use: 2006-2013 trends in prevalence and incidence and characterization of users.

PURPOSE: The present study was conducted to describe antipsychotic (AP) prevalent and incident use, characteristics of AP users, and their trends in the French population. METHODS: A cross-sectional study was repeated yearly from January 1, 2007 to December 31, 2013 (for prevalence analysis) or to December 31, 2012 (for incidence analysis) using the French Health Insurance reimbursement database (Echantillon Généraliste de Bénéficiaires, EGB). For each year studied, prevalent and incident AP users were described in terms of age and gender overall, and according to the type of AP (FGAPs or SGAPs) used at index date. In addition, concurrent medications and comorbidities that a priori contraindicate the use of drugs having atropinic properties were researched. RESULTS: Prevalence and incidence remained relatively stable along the 2007-2013 period. Trends slightly decreased, from 2.07% (n = 10,252) to 2.05% (n = 11,015) for prevalence, and from 0.73% (n = 3461) to 0.66% (n = 3363) for incidence, especially in elderly, in contrast of children and adolescents (+ 39% for prevalence, from 184 to 271). The number of coprescribed drugs was found high (median = 5) and remained constant over time. In 2013, about 7% of prevalent AP users presented with a comorbidity increasing the risk of atropinic ADRs, and 36% used at least one concurrent atropinic drug. In incident AP users, these numbers were of 8 and 29%, respectively. CONCLUSIONS: The present study highlighted a marked shift from FGAPs toward SGAPs, as well as an increase in AP use in children and adolescents in France.

Antidepressant use and cognitive decline in community-dwelling elderly people - The Three-City Cohort.

BACKGROUND: Cognitive impairment is very common in late-life depression, principally affecting executive skills and information processing speed. The aim of the study was to examine the effect of antidepressant treatment on cognitive performances over a 10-year period. METHODS: The community-based cohort included 7381 participants aged 65 years and above. Five cognitive domains (verbal fluency, psychomotor speed, executive function, visuospatial skills and global cognition) were assessed up to five times over 10 years of follow-up. Treatment groups included participants under a specific antidepressant class at both baseline and the first follow-up and their follow-up cognitive data were considered until the last consecutive follow-up with a report of antidepressant use of the same class. Linear mixed models were used to compare baseline cognitive performance and cognitive decline over time according to antidepressant treatment. The models were adjusted for multiple confounders including residual depressive symptoms assessed by the Center for Epidemiologic Studies-Depression scale. RESULTS: At baseline, 4.0% of participants were taking antidepressants. Compared to non-users, tricyclic antidepressant users had lower baseline performances in verbal fluency, visual memory and psychomotor speed, and selective serotonin reuptake inhibitor users in verbal fluency and psychomotor speed. For the two other cognitive abilities, executive function and global cognition, no significant differences were found at baseline irrespective of the antidepressant class. Regarding changes over time, no significant differences were observed in comparison with non-users whatever the cognitive domain, except for a slight additional improvement over the follow-up in verbal fluency skills for tricyclic antidepressant users. CONCLUSIONS: In this large elderly general population cohort, we found no evidence for an association between antidepressant use and post-treatment cognitive decline over 10 years of follow-up in various cognitive domains.

National trends in use and costs of oral anticancer drugs in France: An 8-year population-based study.

PURPOSE: During the last decade, many oral anticancer drugs (OAcDs) have been marketed, providing interesting but potentially costly pharmaceutical alternatives to intravenous treatments. This study aims to provide updated information on their use and costs. METHODS: A cross-sectional yearly repeated study was conducted from 2006 to 2014 using the representative sample of the French national health care insurance system claims database (EGB). OAcD use was described for each year, among prevalent (ie, patients with at least 1 OAcD reimbursement) and incident users (ie, patients with no OAcD reimbursement within the prior year) and according to their pharmacological classes (Hormone Therapy [HT], Cytotoxic Therapy [CT], Targeted Therapy [TT], and others). Demographic characteristics were described for both users; comorbidities and direct medical costs were described for incident users only. RESULTS: The yearly prevalence and incidence of OAcD use, mainly represented by HT, remained stable from 2006 to 2014 (1.2%; 0.4%). Compared with users of other OAcD classes, the proportion of TT users substantially increased over the 8-year study period (+9.3%), and TT incident users had more severe comorbidities at treatment initiation. The health expenditures were the most important in TT users with median monthly medical direct costs varying from 2995€ to 4968€ per patient between 2006 and 2014. CONCLUSION: With the development of new OAcDs, the TTs use reaches a wider population of patients but is responsible for increasing health expenditures.

Trends in incident use of benzodiazepines and Z-drugs in France from 2006 to 2012: a population-based study.

PURPOSE: To study trends in incident use of benzodiazepines in France between 2006 and 2012. METHODS: A cross-sectional study repeated yearly was conducted using data from the French national healthcare insurance system. New benzodiazepine users were defined as users without any benzodiazepine dispensing in the year prior to the first dispensing of benzodiazepine in each year. Relative changes in incidence of use were calculated with the year 2006 as reference; confidence intervals for changes were estimated using the bootstrap method. RESULTS: Over the study period, the incident use of benzodiazepines decreased from 6.2% to 5.9%; this corresponded to a 5.1% decrease (95%CI: -6.8% to -4.2%) for 2012 compared to 2006. The decrease mainly concerned hypnotics (-15.5%; -21.2% to -15.3%) and appeared more pronounced in people aged 18-44 years. Incident use of anxiolytics remained stable overall during the period (4.0% of the population). Within anxiolytics, incident use of long half-life benzodiazepines (bromazepam, prazepam) decreased in favor of short half-life benzodiazepines (alprazolam, oxazepam). This change concerned patients aged 65-79 and patients aged 80 years and over. Nevertheless, in 2012, nearly one third of incident users aged 65 years and over started a treatment with a long half-life benzodiazepine, mostly bromazepam. CONCLUSIONS: A limited decrease in incident benzodiazepine use was observed in France between 2006 and 2012 that concerned only hypnotics. Although congruent with recommendations, this improvement appears insufficient with regard to the level of exposure to these drugs in France. New actions especially targeting anxiolytic benzodiazepine use should be undertaken to consolidate these results. Copyright © 2016 John Wiley & Sons, Ltd.

Real-life patterns of use, safety and effectiveness of sunitinib in first-line therapy of metastatic renal cell carcinoma: the SANTORIN cohort study.

PURPOSE: To investigate sunitinib in the real-life first-line treatment of metastatic renal cell carcinoma (mRCC). METHODS: SANTORIN is a French observational multicentre cohort. Patients initiating sunitinib in first-line mRCC therapy were included (January 2008 to April 2010) and followed for 24 months. Data were collected from medical files. The outcomes were 24-month overall survival (OS) and progression-free survival (PFS), response and safety. RESULTS: Three hundred two patients were included: median age, 64.8 years; male, 73.2%; clear cell mRCC, 83.1%; prior nephrectomy, 85.4%; >1 metastatic sites, 64.2%; brain metastases, 6.3%; ECOG-PS ≥ 2, 9.9%. Median duration of first-line therapy with sunitinib was 10.7 months. Initial sunitinib dose was 50 mg/day for 83.4% of patients; dose reduction occurred in 65.2%. Sunitinib was discontinued in 73.2% of the patients: for progression (61.1%), death (31.2%) or adverse events (6.8%). More than half (58.3%) had grade ≥3 adverse events, mainly hypertension (12.6%) and hand-foot syndrome (12.3%). The 24-month OS and PFS rates [95%CI] were 49.5% [43.7;55.0] and 16.4% [12.5;20.9], respectively. Median OS was 23.6 months [20.2;-] and median PFS 8.4 months [7.6;9.9]. Overall best response rate was 31.1%. CONCLUSIONS: Results from this large observational study suggest that effectiveness of sunitinib in first-line mRCC as predicted by clinical trials is maintained in real-life clinical practice. The expected benefit in poor-prognosis patients that were not evaluated in the pivotal clinical trial remains; however, questionable and long-term safety monitoring is still warranted. Copyright © 2017 John Wiley & Sons, Ltd.

Comorbidities and concurrent medications increasing the risk of adverse drug reactions: prevalence in French benzodiazepine users.

PURPOSE: To estimate benzodiazepine prevalence of use and to quantify, in benzodiazepine users, the prevalence of comorbidities and concurrent medications increasing the risk of adverse drug reactions (ADRs). METHODS: Cross-sectional study performed using data from the French national healthcare insurance system. The prevalence of use was estimated by considering as users, patients who had at least one benzodiazepine reimbursement during the year 2013. Patients at increased risk for benzodiazepine ADRs were those who had (i) drug-drug interactions at risk for central nervous system and respiratory depression and (ii) comorbidities at risk for adverse respiratory effects, or for falls or fractures. RESULTS: Overall, the prevalence of benzodiazepine use in 2013 was estimated to be 13.8 %; it was higher among women and increased with age. This prevalence was 10.6 % for anxiolytic benzodiazepines, and 6.1 % for hypnotic benzodiazepines. Approximately half of the benzodiazepine users (48.1 %) were at increased risk for benzodiazepine ADRs; this proportion increased with age. Drug-drug interactions represented the most prevalent condition (39.3 % of benzodiazepine users). The drugs most frequently involved were opioids: analgesics (15.9 %) and antitussives (6.8 %). Overall, 11.3 % of benzodiazepine users had comorbidities at increased risk for adverse respiratory effects (13.9 % in those aged 65-79), and 7.0 % comorbidities at increased risk for falls or fractures (13.4 % in those aged ≥80). CONCLUSIONS: This study found that benzodiazepine use remained high in France, and that roughly half of the users presented with comorbidities and concurrent medications increasing the risk of ADRs. These findings are of concern, given that benzodiazepines are frequently used, and especially among the elderly.

[Not Available]. / Comment le grand public utilise Internet pour rechercher des informations sur le médicament ?

UNLABELLED: To quantify and characterize the use of the Internet to search for information about medicines. METHODS: A random sample of subjects was interviewed in the city of Bordeaux (France) in November 2012 regarding their use of the Internet to find information on medicines. RESULTS: Among 103 interviewed subjects (median age: 38years; 53.4% of men), 48 (46.6%) reported using the Internet to find information about medicines (58.3% of women). Two-thirds (66.7%) declared visiting consumer forums. However, nearly 60% reported to first consult a health professional. Three subjects had already bought medicines on the web and half (52.0%) of those who never made a purchase on the Internet would not trust the quality of the medicine. CONCLUSION: Even if purchasing medicines on the web remains rare, this media is frequently used to find information on medicines and most often on websites of questionable quality.

[How people use the internet to find information on medicines?]. / Comment le grand public utilise Internet pour rechercher des informations sur le médicament ?

OBJECTIVE: To quantify and characterize the use of the Internet to search for information about medicines. METHODS: A random sample of subjects was interviewed in the city of Bordeaux (France) in November 2012 regarding their use of the Internet to find information on medicines. RESULTS: Among 103 interviewed subjects (median age: 38 years; 53.4% of men), 48 (46.6%) reported using the Internet to find information about medicines (58.3% of women). Two-thirds (66.7%) declared visiting consumer forums. However, nearly 60% reported to first consult a health professional. Three subjects had already bought medicines on the web and half (52.0%) of those who never made a purchase on the Internet would not trust the quality of the medicine. CONCLUSION: Even if purchasing medicines on the web remains rare, this media is frequently used to find information on medicines and most often on websites of questionable quality.

Use of the French National Health Data System (SNDS) in pharmacoepidemiology: A systematic review in its maturation phase.

AIM OF THE STUDY: The French National Health Data System (SNDS) comprises healthcare data that cover 99% of the population (over 67 million individuals) in France. The aim of this study was to present an overview of published pharmacoepidemiological studies using the SNDS in its maturation phase. METHODS: We conducted a systematic literature review of original research articles in the Pubmed and EMBASE databases from January 2012 until August 2018. RESULTS: A total of 316 full-text articles were included, with an annual increase over the study period. Only 16 records were excluded after screening because they did not involve the SNDS but other French healthcare databases. The study design was clearly reported in only 66% of studies of which 57% were retrospective cohorts and 22% cross-sectional studies. The reported study objectives were drug utilization (65%), safety (22%) and effectiveness (9%). Almost all ATC groups were studied but the most frequent ones concerned the nervous system in 149 studies (49%), cardiovascular system drugs in 104 studies (34%) and anti-infectives for systemic use in 50 studies (16%). CONCLUSION: The SNDS is of growing interest for studies on drug use and safety, which could be conducted more in specific populations, including children, pregnant women and the elderly, as these populations are often not included in clinical trials.

Drugs and the elderly: A complex interaction.

Although it can be difficult to define who should be considered an elderly person, the population aged 65 and over is experiencing the fastest demographic expansion and will represent almost one billion inhabitants of the 2030 World. Drug use increases dramatically with age and the elderly population is, by far, the highest consumer of medicines, up to 10 times more than younger adults. This consumption is in many aspects inappropriate, unjustified or sub-optimal and associated with a huge number of adverse reactions, admissions in emergency units and attributable deaths. A good part of which could be prevented if basic rules of good prescription and ad-hoc guidelines were systematically used. Even if older adults are more likely to present an adverse drug reaction, available data tend to support that the main risk factor of iatrogenesis in the elderly is the number of drugs used. Moreover, it is often irrelevant to transpose to this population the conclusions concerning the benefit-risk balance of drugs assessed in younger adults; similarly, approaches and programs classically used in pharmacovigilance and pharmacoepidemiology should be tailored to this specific population.

Impact of Cardiovascular Comorbidities on the Effectiveness and Safety of Bevacizumab in Older Patients with Metastatic Colorectal Cancer.

BACKGROUND: Cardiovascular comorbidities are not contraindications of bevacizumab for metastatic colorectal cancer. OBJECTIVE: We aimed to evaluate the impact of cardiovascular comorbidities before bevacizumab treatment on overall survival and cardiovascular safety in older patients with metastatic colorectal cancer. METHODS: A 2009-2015 cohort of patients with metastatic colorectal cancer aged ≥ 65 years administered first-line bevacizumab was extracted from the French healthcare reimbursement claims database. Baseline heart failure, hypertension, and venous/arterial thromboembolic events were identified. The 36-month overall survival rate was evaluated using the Kaplan-Meier method, and the impact of cardiovascular comorbidities on the 36-month overall survival using a time-dependent, multivariable, Cox proportional hazards model. The 36-month cumulative incidence of cardiovascular events, and the impact of cardiovascular comorbidities on the likelihood of cardiovascular events were evaluated using the Fine and Gray model, with death as a competing risk. RESULTS: We included 9222 patients (56.4% male; median age 73 years). Two-thirds (66.7%) had baseline cardiovascular comorbidities. The median 36-month overall survival was 20.4 [95% confidence interval (CI) 19.9-21.0] and 21.8 [95% CI 21.1-22.6] months in patients with and without cardiovascular comorbidities, respectively. Age ≥ 75 years, dependency in activities of daily living, radiotherapy, and another targeted therapy were identified as death risk factors, but not cardiovascular comorbidities. At 36 months, cardiovascular events had occurred in 60.2% [95% CI 58.9-61.4] and 44.1% [95% CI 42.3-45.9] of patients with and without cardiovascular comorbidities. Baseline venous thrombosis, female, three or more cardiovascular medications, another targeted therapy, and more than six bevacizumab injections were identified as risk factors for cardiovascular events. CONCLUSIONS: In clinical practice, cardiovascular comorbidities before administering bevacizumab to older patients with metastatic colorectal cancer impacted the cardiovascular safety, but not overall survival. Unless they limit functional independency, older patients with cardiovascular comorbidities should be treated with bevacizumab under close monitoring.

Engagement in leisure activities and benzodiazepine use in a French community-dwelling elderly population.

OBJECTIVE: The prevalence of benzodiazepine use among community-dwelling older persons varies between 10% and 30%. The aim of this study was to explore the association between leisure activities and the use of benzodiazepine among older persons living at home. METHODS: The study population included 4848 persons aged 65 years and over living in either of two French cities. Information was collected from a questionnaire administered to the respondents by trained psychologists during face-to-face interviews at home and from a self-administered questionnaire. Baseline examination included socio-demographic characteristics, drug use and leisure activities. We classified as benzodiazepine users subjects who reported use of at least one benzodiazepine during the month preceding the interview. The association between the use of benzodiazepine and leisure activities was assessed by logistic regression adjusted on known potential confounders. RESULTS: More than 18% of participants reported use of at least one benzodiazepine. The adjusted odds ratio (OR) of benzodiazepine use associated with no or lower participation versus participation in the following activities were as follows: OR = 1.31 (95% confidence interval (CI): 1.09 to 1.58) for mental activity; OR = 1.50 (CI: 1.12 to 2.03) for physical activity; OR = 1.28 (CI: 1.05 to 1.55) for productive activity and OR = 0.82 (CI: 0.69 to 0.97) for recreational activity. CONCLUSION: Low engagement in stimulating activities and high engagement in sedentary activities were associated with recent benzodiazepine use.