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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. [ABSTRACT FROM AUTHOR]

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. β-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Metastatic colorectal cancer (mCRC) is increasingly treated using targeted therapies. Post-marketing safety of these agents is understudied, especially in the elderly.Objective: This study aimed to compare, according to age, the adverse drug reactions (ADRs) of targeted therapies used for mCRC in real life.Patients and Methods: An extraction of VigiBase, which contains World Health Organization individual case safety reports (ICSRs), was performed. All ADR reports with aflibercept, bevacizumab, cetuximab, panitumumab, or regorafenib used in CRC were considered. For all drugs, chi-square tests were used to compare frequencies of serious ADRs between patients aged ≥75 and <75 years. For selected ADRs and each drug, the drug-ADR association compared to other anticancer drugs was estimated through the proportional reporting ratio (PRR) in both age groups.Results: There were 21,565 ICSRs included, among which 74% were serious and 11% were fatal. Median age was 64 years (Inter Quartile Range = 56-71) and 15% of patients were aged ≥75; 57% were male. Serious ICSRs accounted for 47,292 ADRs. Neutropenia was not more reported in elderly for all drugs while diarrhea was more reported in elderly for panitumumab. Cardiac disorders were more reported in elderly patients, in particular heart failure, especially for bevacizumab, cetuximab, and regorafenib, as were respiratory, thoracic, and mediastinal disorders. Most of PRR were not different between the two groups, except encephalopathies, which were significantly associated with bevacizumab in the elderly only.Conclusions: ADRs related to targeted therapies used for mCRC treatment were different across age groups; yet, not systematically more reported or worse in elderly patients. Selected elderly patients could, therefore, be treated with these targeted therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Resection of metastases after chemotherapy improves survival outcomes of patients with initially inoperable metastatic colorectal cancer (mCRC), yet little data is available for those treated in the first-line setting with bevacizumab plus irinotecan. To provide data on this, the present study described the subgroup of the ETNA cohort who underwent metastases surgery.Methods: The population of operated patients was described according to metastatic site (exclusively hepatic, non-exclusively hepatic, and non-hepatic). Factors associated with overall survival (OS) and progression-free survival (PFS) were evaluated using multivariable Cox analysis.Results: A total of 76 patients (21.1 % of the ETNA cohort) underwent metastases resection: 50 % male, median age 61.9 years, 85.5 % ECOG  ≤ 1, and median duration of bevacizumab use 7.2 months. No surgery-related deaths were observed and 30.6 % of patients had at least one post-operative complication, mainly infections (11.8 % of resections), bleeding complications (3.5 %), or delayed wound healing (2.4 %). Complete remission was higher for those with exclusively hepatic metastases (22/32, 68.8 %) than those with non-exclusively hepatic metastases (12/24, 50.0 %), or non-hepatic metastases (12/20, 60.0 %). Among operated patients, 52.6 % had died after 5 years of follow-up. In multivariable analysis at 2 years of follow-up, death (HR 0.09 [95 % CI 0.02-0.35]) and progression (HR 0.35 [95 % CI 0.23-0.56]) were less likely for patients with complete remission (CR) after surgery R0-R1 or radiofrequency ablation (RFA) [CR RFA] compared with those who were not resected or with R2 resection.Conclusion: In real-life practice, bevacizumab with irinotecan in first-line therapy for mCRC allows secondary resection of metastases and survival is more favourable in those with complete remission (R0-R1/CR RFA). [ABSTRACT FROM AUTHOR]

Although the real-life benefits of bevacizumab may differ from clinical trials, observational data are rare. In this cohort study, the effectiveness of bevacizumab in first-line treatment of metastatic colorectal cancer was investigated. Patients initiating bevacizumab between January 2006 and December 2007 were identified in 28 French centres. Outcomes were investigated in the whole cohort and in those with irinotecan-based treatment that was used in the pivotal clinical trial; patients were stratified using inclusion/exclusion criteria of the pivotal clinical trial (PCT) ( eligible for the PCT, not eligible or unclassifiable). The Kaplan-Meier method estimated progression-free survival (PFS) and overall survival (OS). A total of 411 patients were included: 57 % male, median age 65.1 years, 78 % Eastern Cooperative Oncology Group performance status ≤1, 88 % irinotecan-based regimen, median duration of bevacizumab use 5.5 months, median OS = 25.3 months (95 % confidence interval, CI [23.3; 27.0]) and median PFS = 10.1 months (95 % CI [9.5; 11.0]). Among the 360 patients who received irinotecan-based chemotherapy, 144 would have been eligible for the PCT, 194 not eligible and 22 unclassifiable. Median OS in those considered eligible was 29.1 (95 % CI [25.4; 33.6]) and in those considered not eligible this was 24.9 months (95 % CI [21.3; 26.9]); median PFS was respectively 11.5 months (95 % CI [10.3; 12.0]) and 9.4 months (95 % CI [8.8; 10.3]). The effectiveness of bevacizumab was found to be similar to that found in other studies including clinical trials which is reassuring. [ABSTRACT FROM AUTHOR]

Background: Since its introduction in France, ketoprofen for topical use has been associated with a large number of cutaneous adverse effect reports. Therefore, the French Medicine Agency progressively introduced warnings and contraindications to its use. Despite this, serious adverse drug reactions (ADRs) still occur. Objective: To describe clinical patterns and estimate costs of spontaneously reported cutaneous ADRs of topical ketoprofen. Methods: All cases of cutaneous ADRs of topical ketoprofen reported to the Bordeaux regional pharmacovigilance center between January 1989 and December 2006 were included. Clinical patterns, in respect of adherence to recommendations, causality, seriousness, and direct costs incurred by the ADRs, were assessed. Results: A total of 136 cases were reported (median age: 42 years, 55.9% women). Proper use of topical ketoprofen regarding indications, warnings, and contraindications was not respected by one-third of the patients. Almost all cases occurred during sunny months. Symptoms consisted predominantly of bullous eruptions (29.4%) or contact dermatitis (27.2%). Generalized lesions were observed in 37.5% of patients. Causality was considered at least possible for most of the cases (92.6%). These ADRs induced hospital admission in 15 cases (11.0%). The total estimated cost was h42 962 ($US66 559), corresponding to h316 per case. This mean cost was nine times higher for serious ADRs. Conclusion: Topical ketoprofen is used to treat benign symptoms but can be associated with serious and costly cutaneous ADRs. Furthermore, the number of cases and the calculated costs may have been greatly under-estimated in the present study. [ABSTRACT FROM AUTHOR]