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In the last French study in 2007, the incidence of hospital admissions (HAs) related to adverse drug reactions (ADRs) was 3.6%. The objective was to assess the current ADR-HA incidence in France and to describe both its characteristics and preventability.A prospective multicentre study was conducted among randomly selected French public hospital medical wards (April-July 2018). Patients admitted during a week period were included. ADR-HA cases were collected by the French Regional Pharmacovigilance Centres network. An independent committee validated potential cases and ADR preventability.ADR-HA incidence was 8.5% (95% confidence interval [CI]: 7.6-9.4%), increasing with age (3.3% [95%CI: 1.8-5.5%] ≤16 y vs. 10.6% [95%CI: 9.3-12.0%] ≥65 y). The most common ADRs were haemorrhagic events (8.8%), haematological disorders (6.5%), acute renal failure (6.3%), fluid and electrolyte disorders (6.0%), and falls (5.2%). New drugs were involved: targeted therapies (22.8% of antineoplastics), direct oral anticoagulants (29.6% of antithrombotics) and incretin-based drugs (20.0% of antidiabetics). ADRs were preventable in 16.1% of cases because the drugs involved had not been used in accordance with monographies, package leaflets or other therapeutic guidelines. The main situations of noncompliance addressed either dose or duration of use (27.9%), warning (23.2%), use precaution (18.6%) and inappropriate self-medication or misuse by patients (11.6%).In France, ADR-HA incidence dramatically increased over the last decade. A significant proportion was related to new pharmacological classes and considered as preventable. These findings should lead to in-depth thought on preventive actions on at-risk drug classes.

Maude Laberge,1– 3 Caroline Sirois,2– 5 Carlotta Lunghi,3,6 Myriam Gaudreault,7 Yumiko Nakamura,8 Carolann Bolduc,4 Marie-Laure Laroche9,10 1Department of Operations & Decision Systems, Faculty of Administration, Université Laval, Quebec City, Quebec, Canada; 2Vitam, Centre de recherche en santé durable-Université Laval, Quebec, Canada; 3Centre de recherche du CHU de Québec-Université Laval, Quebec City, Quebec, Canada; 4Faculty of Pharmacy, Université Laval, Quebec City, Quebec, Canada; 5Institut National de santé publique du Québec, Quebec City, Quebec, Canada; 6Department of Health Sciences, Université du Québec à Rimouski, Rimouski, Quebec, Canada; 7Faculty of Administration, Université Laval, Quebec City, Quebec, Canada; 8College of Medicine, University of Florida, Gainesville, FL, USA; 9Centre de Pharmacovigilance, de Pharmacoépidémiologie et d’information sur les médicaments, Service de Pharmacologie, Toxicologie et Pharmacovigilance, CHU de Limoges, Limoges, France; 10Laboratoire Vie-Santé, Faculté de Médecine, Université de Limoges, Limoges, FranceCorrespondence: Maude LabergeDepartment of Operations & Decision Systems, Faculty of Administration, Université Laval, 2325 rue de la Terrasse, Bureau 2519, Quebec City, Québec, G1V 0A6, CanadaTel +1 418-656-2131 ext 407670Fax +1 418-656-2180Email Maude.laberge@fsa.ulaval.caPurpose: To conduct a systematic review of the economic impact of interventions intended at optimizing medication use in older adults with multimorbidity and polypharmacy.Methods: We searched Ovid-Medline, Embase, CINAHL, Ageline, Cochrane, and Web of Science, for articles published between 2004 and 2020 that studied older adults with multimorbidity and polypharmacy. The intervention studied had to be aimed at optimizing medication use and present results on costs.Results: Out of 3,871 studies identified by the search strategy, eleven studies were included. The interventions involved different provider types, with a majority described as a multidisciplinary team involving a pharmacist and a general practitioner, in the decision-making process. Interventions were generally associated with a reduction in medication expenditure. The benefits of the intervention in terms of clinical outcomes remain limited. Five studies were cost-benefit analyses, which had a net benefit that was either null or positive. Cost-utility and cost-effectiveness analyses resulted in incremental cost-effectiveness ratios that were generally within the willingness-to-pay thresholds of the countries in which the studies were conducted. However, the quality of the studies was generally low. Omission of key cost elements of economic evaluations, including intervention cost and payer perspective, limited interpretability.Conclusion: Interventions to optimize medication use may provide benefits that outweigh their implementation costs, but the evidence remains limited. There is a need to identify and address barriers to the scaling-up of such interventions, starting with the current incentive structures for pharmacists, physicians, and patients.Keywords: polypharmacy, economic evaluation, potentially inappropriate medication, cost-effectiveness, cost-utility, cost-benefit

This study aimed to describe attitudes toward deprescribing among older adults and caregivers. We recruited 110 adults 65 years and above using at least one prescribed medication for at least 3 months, and 95 unrelated caregivers (18+) of older adults with such characteristics, who answered the validated French version of the revised Patients’ Attitudes Towards Deprescribing questionnaire. More older adults (84.5%) than caregivers (70.5%) ( p = .007) would be willing to stop at least one medication if the doctor said it was possible. Conversely, 93.5% of older adults and 78.9% of caregivers were satisfied with the current medications taken ( p = .0024). The results did not vary according to age, sex, number of medications taken, education level, or residency. Thus, older adults and caregivers are disposed to undertake deprescribing, regardless of sociodemographic characteristics. However, relying solely on satisfaction with current medications may not be sufficient to identify relevant deprescribing opportunities.

Objective To describe the off-label medication use in a cohort of pregnant women. Material and methods We performed a multicenter prospective longitudinal observational study in the Haute-Vienne department (France) called the NeHaVi cohort ("Ne en Haute-Vienne" meaning "born in Haute-Vienne"). Women who had given birth to a viable baby in one of three maternity wards in the Haute-Vienne were included in the study after giving their informed consent. Data on the progress and outcome of pregnancies, childbirth, and drug or toxic exposure during pregnancy were collected. Drugs were classified, according to the labeling of the summary of product characteristics (SmPC) regarding the use in pregnancy, as follows: on-label, off-label at risk, and off-label contra-indicated. Results During their pregnancy, the 397 included women gave birth to 400 viable babies (209 boys, 191 girls, 3 sets of twins). All women had used at least 1 health product: 3,533 (92%) drugs, 298 (7.5%) homeopathic products, and 18 (0.5%) herb derivatives. The mean number of different drugs taken was 8.9 ± 5.3 (min 1, max 31). All pregnant women used at least 1 drug either with a license or considered as safe to take during pregnancy. Among the 2,538 (71.6%) on-label drugs, the most frequently used were analgesics (n = 611, 24.1%) (acetaminophen (n = 566)), antianemia preparations (n = 528, 20.8%), drugs for functional gastrointestinal disorder (n = 269, 10.6%), vitamins (n = 192, 7.5%), drugs for acid-related disorders (n = 148, 5.8%), and antibacterials (n = 118, 4.6%). In total, 321 (80.9%, 95% CI: 77.0 - 84.7) pregnant women used at least 1 off-label drug; and more precisely, 285 (71.8%, 95% CI: 67.4 - 76.2) used at least 1 off-label high-risk drug, and 189 (47.6%, 95% CI: 42.7 - 52.5) at least 1 contra-indicated drug. Among the 995 off-label drugs (28.2%), 760 (21.5%) were considered high-risk, including vasoprotectives (n = 156, 20.5%) (treatment of hemorrhoids (n = 147)), antithrombotic agents (n = 91, 11.6%) (heparins (n = 88)), and calcium channel blockers (n = 88, 11.6%). Lastly, 235 (6.7%) off-label drugs used were contraindicated medications (non-steroidal anti-inflammatory drugs during the 3rd trimester (n = 231)). Five babies were born with malformations not related to the drugs used during pregnancy. Conclusion We showed for the first time the magnitude of off-label prescription during pregnancy in France. Women and health professionals should be made more aware of the potential drug-induced risk during pregnancy. Drug adverse effects during pregnancy should be evaluated through an improved notification in pharmacovigilance and appropriate pharmacoepidemiologic studies in order to change SmPC labelings as early as possible, when necessary.

Purpose Successful deprescribing requires understanding the attitudes of older adults and caregivers towards this process. This study aimed to capture these attitudes in four French-speaking countries, and to investigate associated factors. Methods A multicenter cross-sectional study was conducted by administrating the French version of the revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire in Belgium, Canada, France and Switzerland. Community-dwelling or nursing home older adults ≥ 65 years taking ≥ 1 prescribed medications, and caregivers of older adults with similar characteristics were included. Multivariate logistic regressions were carried out to examine factors associated with willingness to deprescribe. Results A total of 367 older adults (79.3 ± 8.7 years, 63% community-dwelling, 54% ≥5 medications) and 255 unrelated caregivers (64.4 ± 12.6 years) of care recipients (83.4 ± 7.9 years, 52% community-dwelling, 69% ≥5 medications) answered the questionnaire. Among them, 87.5% older adults and 75.6% caregivers would be willing to stop medications if the physician said it was possible. Reluctance to stop a medication taken for a long time was expressed by 46% of both older adults and caregivers. A low score for the factor “concerns about stopping” [older adults: aOR: 0.21; 95%CI: 0.07–0.59], and a high score for the factor “involvement” [older adults: aOR: 2.66; 95%CI: 1.01–7.07; caregivers: aOR: 11.28; 95%CI: 1.48–85.91] were associated with willingness to deprescribe. Conclusions A significant proportion of older adults and caregivers of French speaking countries are open to deprescribing. Despite this apparent willingness, deprescribing conversations in clinical practice remains marginal, emphasizing the importance of optimizing the integration of existing tools such as rPATD.

BACKGROUND: Potentially inappropriate prescriptions (PIPs) in the older population remain a growing public health concern due to the many associated adverse events increasing healthcare service use and health costs. This study aimed to assess the prevalence and direct costs of PIPs in older adults aged ≥65 years in France. METHODS: A population-based cross-sectional study was conducted in 2017 using a representative sample of the French national healthcare reimbursement system database. PIPs were defined using the French REMEDI[e]S tool. Overall reimbursed direct costs and by PIP category were extrapolated to the French older population. RESULTS: The overall PIP prevalence was estimated at 56.7% (95% CI: 56.4-57.0). Medications with an unfavorable benefit/risk ratio had the highest prevalence (34.0%, 95% CI: 33.7-34.3). Direct costs associated with PIPs represented 6.3% of the total reimbursed medication costs in 2017 (€507 million). Drug duplications were the main contributors to these costs (39.2% of the total reimbursed PIP costs, €199 million) and among all PIPs, proton pump inhibitors (>8 weeks) were the most expensive PIPs (€152 million). CONCLUSIONS: PIP prevalence is still high among French older adults, with substantial direct costs. Large-scale interventions targeting the most prevalent and/or costly PIPs are needed to reduce their clinical and economic impacts.

Background: The revised Patients’ Attitudes Towards Deprescribing (rPATD) questionnaire allows capture of the beliefs and attitudes of older adults and caregivers towards deprescribing. Objectives: To translate and validate the rPATD questionnaire into French. Methods: The French rPATD was translated using forward-backward translation. Psychometric properties were evaluated in both older adults ≥65 years living in the community or in institutions and who were taking at least one chronic medication and in caregivers of older adults with similar characteristics. Participants were recruited in four French-speaking countries (Belgium, Canada, France and Switzerland). Face and content validity were assessed during the translation process. Construct validity (exploratory factor analysis (EFA)) and internal consistency (Cronbach's alpha) were investigated in questionnaires without missing data. Test-retest reliability was evaluated using intra-class correlation coefficient (ICC) in a sample of participants. Results: In total, 320 questionnaires from older adults and 215 questionnaires from caregivers were included to evaluate construct validity and internal consistency. EFA extracted four factors in the older adults' and caregivers' versions of the questionnaire consistent with the English rPATD. The extracted factors related to the perceived burden of medication taking, the beliefs in appropriateness of medications, concerns about stopping medications and the level of involvement in making decisions and of knowledge of medications. Internal consistency was satisfactory for three factors for both versions (Cronbach's alpha >0.70), with lower internal consistency in the concerns about stopping factor. Test-retest reliability was overall good for all factors in the caregivers' version (ICC > 0.75) while for the older adults' version, moderate (ICC range: 0.75–0.50) to good ICC values were found. Conclusions: The French rPATD presents globally good psychometric properties and can be used to explore attitudes towards deprescribing in French-speaking older adults and caregivers. Refereed/Peer-reviewed

Objectives The aims of the study were to describe medication errors (MEs) involving older adults reported to the French Medication Error Guichet and to compare them with MEs in younger adults, in each of the hospital and community settings. Methods Retrospective secondary data analysis of MEs reported throughout 2013 to 2017 was performed. Descriptive and multivariate analyses were performed to compare actual and potential ME reports between older adults (aged ≥60 y) and younger adults (aged ≥18, Results We analyzed 4979 reports. In older adults, both in hospital (n = 1329) and community (n = 1264) settings, antithrombotic agents were frequently reported in MEs and were significantly more likely to be associated with reported MEs in older adults compared with younger adults. In hospital setting, antibacterials for systemic use (adjusted odds ratio [aOR] = 1.87, 95% confidence interval [CI] = 1.19-2.93) and antineoplastic agents (aOR = 2.22, 95% CI = 1.34-3.69), whereas in community setting, psycholeptics (aOR = 1.43, 95% CI = 1.04-1.98) and drugs used in diabetes (aOR = 6.01, 95% CI = 3.21-11.2) were more likely to be associated with reported MEs in older adults. In both settings, wrong dose and wrong drug were the most frequently reported error types in older adults; however, wrong technique error type (aOR = 2.06, 95% CI = 1.30-3.28) in hospital setting and wrong patient (aOR = 2.17, 95% CI = 1.30-3.60) in community setting were more likely to be associated with reported MEs in older adults. Conclusions We identified specific ME patterns for older adults, including antithrombotic agents in both settings; antibacterials for systemic use, antineoplastic agents, and wrong technique in hospital setting; and psycholeptics, drugs used in diabetes, and wrong patient in community setting. These findings inform future studies investigating population-specific medication safety strategies.

The use of multiple medications is common in older adults but is associated with negative health outcomes. However, polypharmacy is not uniformly defined, and there is scant data on how the variety of definitions and their limitations hinder the development of sound scientific knowledge. The article intends to illustrate the challenges of this exposure definition. The array of thresholds for defining polypharmacy renders comparisons between results difficult. Few studies take into account the fact that polypharmacy is a changing exposure over time. In addition, although studies tend to recognize the confounding effect of multimorbidity, residual bias remains a concern. Current studies in polypharmacy often ignore basic epidemiological principles for defining exposure. Future research should integrate time-varying exposure and methods to better control confounding bias. This will help determine the positive/negative impacts of polypharmacy and help establish if polypharmacy conveys information beyond being a marker of health status.

Background: The high burden of disease-oriented drugs among older adults with limited life expectancy raises important questions about the potential futility of care. Aim: To describe the use of drugs of questionable clinical benefit during the last 3 months of life of older adults who died from life-limiting conditions. Design: Longitudinal, retrospective cohort study of decedents. Death certificate data were linked to administrative and healthcare registries with national coverage in Sweden. Setting: Older adults (≥75 years) who died from conditions potentially amenable to palliative care between 1 January and 31 December 2015 in Sweden. We identified drugs of questionable clinical benefit from a set of consensus-based criteria. Results: A total of 58,415 decedents were included (mean age, 87.0 years). During their last 3 months of life, they received on average 8.9 different drugs. Overall, 32.0% of older adults continued and 14.0% initiated at least one drug of questionable clinical benefit (e.g. statins, calcium supplements, vitamin D, bisphosphonates, antidementia drugs). These proportions were highest among younger individuals (i.e. aged 75–84 years), among people who died from organ failure and among those with a large number of coexisting chronic conditions. Excluding people who died from acute and potentially unpredictable fatal events had little influence on the results. Conclusion: A substantial share of older persons with life-limiting diseases receive drugs of questionable clinical benefit during their last months of life. Adequate training, guidance and resources are needed to rationalize and deprescribe drug treatments for older adults near the end of life.

The management of pharmacological therapy in older patients is challenging in clinical practice. Older subjects experience age-related changes that influence pharmacokinetics and pharmacodynamics of drugs, they also usually have multiple diseases, i.e., multimorbidity, and are often cared for, and hence, prescribed by a number of physicians over a long period of time. Therefore, it is not surprising that polypharmacy, literally the use of multiple drugs, is extremely common in older patients and is increasing over time, at least in developed countries. Appropriate geriatric pharmacotherapy, global assessment of patients’ clinical and functional parameters, and integration of skills from different healthcare professionals are needed to address the medical complexity of older adults. In this special issue, the most relevant aspects of geriatric pharmacotherapy are presented and critically discussed. The optimal management of drugs in older patients is a corner stone of the practice of geriatric medicine and one of the most important contributions to the evolution of health care in the direction of adapting contemporary clinical practice to the specific needs of older patients. However, while the tasks are clear, i.e., tailoring drug therapy according to the personal preferences and characteristics, increase patient safety by reducing adverse drug reactions, achieve the most favorable risk benefit ratio for each patient, periodically reviewing pharmacological therapy including deprescribing, as appropriate, the implementation in practice is often difficult, particularly when health care professionals are not geriatricians or clinical pharmacists.

International audience; 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.

To analyze the process from the prescription of the drug to the health outcome, from a medical and pharmaceutical perspective, to prevent the occurrence of drug-related problems (DRPs) in older adults. A mapping of a logical process of drug use from the perspective of physicians, pharmacists, and patients has been established, but many fields remain unexplored (e.g. off-label use, substance use disorders, therapeutic failure), especially in some settings (e.g. home-dwelling) as little data is available in older adults. Prevention of DRPs imperatively requires taking into account the opinions of all healthcare professionals as well as those of patients and their caregivers. To lay the fundamentals of drug-related problems (DRPs) in older adults, and to organize them according to a logical process conciliating medical and pharmaceutical approaches, to better identify the causes and consequences of DRPs. A narrative overview. The causes of DRPs may be intentional or unintentional. They lie in poor prescription, poor adherence, medication errors (MEs) and substance use disorders (SUD). Poor prescription encompasses sub-optimal or off-label drug choice; this choice is either intentional or unintentional, often within a polypharmacy context and not taking sufficiently into account the patient’s clinical condition. Poor adherence is often the consequence of a complicated administration schedule. This review shows that MEs are not the most frequent causes of DRPs. SUD are little studied in older adults and needs to be more investigated because the use of psychoactive substances among older people is frequent. Prescribers, pharmacists, nurses, patients, and caregivers all play a role in different causes of DRPs. The potential deleterious outcomes of DRPs result from adverse drug reactions and therapeutic failures. These can lead to a negative benefit-risk ratio for a given treatment regimen. Interdisciplinary pharmacotherapy programs show significant clinical impacts in preventing or resolving adverse drug events and, suboptimal responses. New technologies also seem to be interesting solutions to prevent MEs. Better communication between healthcare professionals, patients and their caregivers would ensure greater safety and effectiveness of treatments.

Summary Aims To investigate the risk of intestinal obstruction associated with incretin-based drugs by performing a disproportionality analysis of adverse reaction reports in a global pharmacovigilance database. Methods We conducted a case/non-case analysis using VigiBase, the World Health Organization's adverse drug reactions (ADR) database, to assess intestinal obstruction reporting associated with incretin-based drugs (glucagon-like peptide 1 analogues [GLP-1a] and dipeptidyl peptidase 4 inhibitors [DPP-4i]. Cases were defined as reports of gastrointestinal stenosis and obstruction (MedDRA High Level Group Term) and non-cases were all other reactions recorded. Disproportionality analysis were performed by computing reporting odds ratios (ROR) with their 95% confidence interval (95%CI) within all ADR reports concerning diabetes drugs from January 2007 to January 2018 and in a restricted sample including only serious reports. Results A total of 501,244 ADR with diabetes drugs were reported in VigiBase during the study period. We identified 452 intestinal obstructions involving an incretin-based drug. In disproportionality analyses, intestinal obstructions were more than 4.5 times more frequently reported with incretin-based drugs than with other diabetes drugs (ROR 4.52, 95% CI: 3.87–5.28) with a higher signal for serious cases and for DPP-4i (ROR 8.66, 95% CI: 7.27–10.32) compared to GLP-1a (ROR 3.05, 95% CI: 2.54–3.66). Conclusions We identified a pharmacovigilance signal that suggests a risk of potentially serious intestinal obstruction associated with incretin-based drugs, as a class and with a greater signal for DPP4-i. Other studies are needed to confirm and better understand the potential risk of intestinal obstruction associated with incretin-based drugs.

Resume Introduction Les inhibiteurs de la pompe a protons (IPP) sont frequemment prescrits par les medecins generalistes (MG), qui les considerent comme surs. Cependant, de plus en plus d’effets indesirables (EI) associes aux IPP sont decrits. Objectif Determiner le niveau de connaissance et l’attitude des MG vis-a-vis des EI des IPP utilises chez les adultes. Methode Les MG de Nouvelle-Aquitaine et les chefs ou anciens chefs de clinique des 35 departements universitaires de medecine generale de France ont ete interroges en ligne sur une liste de 12 EI etablie a partir d’une revue semi-systematique de la litterature (neutropenie, thrombopenie, anemie, hypomagnesemie, augmentation des enzymes hepatiques, insuffisance renale, pneumopathie, reactions cutanees, fracture, polype gastrique, colite microscopique, colite a Clostridium difficile) et sur leur attitude vis-a-vis de ces EI. Resultat Sur les 232 MG participants, 38,4 % avaient ete confrontes aux EI des IPP (essentiellement digestifs) au cours des 6 derniers mois. Ces EI n’avaient ete rapportes a la pharmacovigilance que dans 2,3 % des cas. Aucun EI n’etait connu par plus de 70 % des MG. Pour les MG qui les connaissaient, l’attitude etait majoritairement l’arret de l’IPP. Aucune difference de connaissance n’a ete constatee entre les maitre de stage et les non-maitres de stage universitaire. Enfin, 74,7 % des MG ont declare avoir besoin d’informations sur les EI des IPP et 80,4 % etaient prets a les « deprescrire ». Conclusion Les EI lies aux IPP, hormis ceux d’ordre digestif, sont mal connus des MG. Ceux qui les connaissent ont une attitude appropriee en les arretant. L’information souhaitee par les MG sur les risques des IPP a toute sa place en particulier dans une demarche de prescription appropriee des IPP, qui passe aussi par savoir les « deprescrire ».

Aims To assess the 1-year persistence of potentially inappropriate medication (PIM) use and identify associated factors in community-dwelling older adults in Quebec, Canada. Methods A population-based cohort study was conducted using the Quebec Integrated Chronic Disease Surveillance System. Individuals insured by the public drug plan and aged ≥66 years who initiated a PIM between 1 April 2014 and 31 March 2015 were followed-up for 1 year. PIMs were identified using the 2015 Beers criteria. One-year persistence of PIM use was defined as continuous treatment with any PIM, without interruption for more than 60 days between prescriptions refills. Poisson regression models were performed to identify factors associated with 1-year persistence of any PIM. Results In total, 25.1% of PIM initiators were persistent at 1 year. In non-persistent individuals, the median time to PIM discontinuation was 31 days (interquartile range 21-92). Individuals were more persistent at 1 year with antipsychotics (43.9%), long-duration sulphonylureas (40.2%), antiarrhythmics/immediate-release nifedipine (36.5%) and proton pump inhibitors (36.0%). Factors significantly associated with persistence were an increased age, being a man and having a high number of medications and chronic diseases, especially dementia, diabetes and cardiovascular diseases. Conclusions One-quarter of community-dwelling older adults are continuously exposed to PIMs. To optimize medication prescribing in the older population, further interventions are needed to limit the use of PIMs most likely to be continued, especially in individuals most at risk of being persistent and also particularly vulnerable to adverse events.

Background Numerous studies have pointed out the need for better training of healthcare professionals in drug-drug interactions management in order to minimize adverse drugs reactions impacts on patients. The aim of this study was to evaluate the benefits of a blended learning strategy based on peer evaluation (PE) for teaching drug-drug interactions to undergraduate pharmacy students. Methods Third-year pharmacy students (n = 72) from the University of Limoges were involved in a hybrid teaching using the Moodle platform (2.9 version). After the theoretical lectures, an online activity was proposed to students. Each student submitted a report addressing a clinical case for peer evaluation. Students evaluated the pedagogical approach using an online survey. Quantitative benefits were assessed from students randomly assigned into two groups: PE in pharmacodynamics items (PE-PD) or PE in pharmacokinetics items (PE-PK). During this activity, three marks were given: one from peers for their evaluation work and two from teachers for oral group presentation of the clinical cases and for the final written examination. Statistics were performed using two-tailed unpaired t-test and significance was set for p Results Only a few students (n = 14, 20.6%) were aware of the peer evaluation principle and even less, only one student (n = 1, 1.5%), had already encountered it. Students considered that they benefited from this evaluation (n = 65, 95.6%); from their work being reviewed (n = 62, 91.2%) and that they participated in improving their classmates understanding (n = 59, 86.8%). Peers’ allocated marks were similar in the two PE groups (PE-PD = 17.4 ± 1.4; PE-PK = 17.3 ± 1.4). Teachers’ marks for oral presentation were significantly lower for pharmacodynamics than for pharmacokinetics items (PE-PD = 15.2 ± 1.2; PE-PK = 16.1 ± 2.1; p Conclusions Besides the fact that a major short-term quantitative improvement was not detected, our teaching approach was qualified as being a positive and stimulating learning tool by students.

Background Clinical guidance is needed to initiate, continue, and discontinue drug treatments near the end of life. Aim To identify drugs and drug classes most often adequate, questionable, or inadequate for older people at the end of life. Design Delphi consensus survey. Setting/participants Forty European experts in geriatrics, clinical pharmacology, and palliative medicine from 10 different countries. Panelists were asked to characterize drug classes as “often adequate,” “questionable,” or “often inadequate” for use in older adults aged 75 years or older with an estimated life expectancy of ≤ 3 months. We distinguished the continuation of a drug class that was previously prescribed from the initiation of a new drug. Consensus was considered achieved for a given drug or drug class if the level of agreement was ≥ 75%. Results The expert panel reached consensus on a set of 14 drug classes deemed as “often adequate,” 28 drug classes deemed “questionable,” and 10 drug classes deemed “often inadequate” for continuation during the last 3 months of life. Regarding the initiation of new drug treatments, the panel reached consensus on a set of 10 drug classes deemed “often adequate,” 23 drug classes deemed “questionable,” and 23 drug classes deemed “often inadequate”. Consensus remained unachieved for some very commonly prescribed drug treatments (e.g., proton-pump inhibitors, furosemide, haloperidol, olanzapine, zopiclone, and selective serotonin reuptake inhibitors). Conclusion In the absence of high-quality evidence from randomized clinical trials, these consensus-based criteria provide guidance to rationalize drug prescribing for older adults near the end of life. Electronic supplementary material The online version of this article (10.1007/s00228-018-2507-4) contains supplementary material, which is available to authorized users.

Resume Introduction L’utilisation des anticoagulants oraux directs (AOD) est complexe : indications, posologie, contre-indications, interactions, etc. Nous avons evalue leur mesusage et leurs effets indesirables dans un service d’urgence. Methode Il s’agissait d’une etude observationnelle prospective incluant les patients traites par AOD et admis dans le service des urgences du CHU de Limoges entre aout 2013 et avril 2014. Les criteres d’evaluation etaient le suivi des recommandations actuelles (indication, posologies, âge, adaptation a la fonction renale, etc.) et les effets indesirables. Resultats Cent quatre-vingt-dix-huit patients ont ete inclus traites par rivaroxaban (68,7 %), dabigatran (30,8 %) ou apixaban (0,5 %). Les principales indications etaient la prevention de l’accident vasculaire cerebral et de l’embolie pulmonaire dans le contexte de fibrillation auriculaire (78,7 %) et le traitement curatif de la maladie thromboembolique (17,2 %). La survenue d’un effet indesirable concernait 25,8 % d’entre eux (hemorragies 18,0 %, thromboses 7,8 %) avec 44,4 % d’hemorragies graves (criteres Haute Autorite de sante 2008). Au total, 16,2 % des patients etaient traites en dehors des recommandations ; 22 % de mauvaise indication, 78 % d’erreur posologique. Les accidents hemorragiques concernaient 36 patients et un mesusage etait retrouve dans 11,1 % des cas ; les evenements thrombotiques concernaient 15 malades, sans situation de mesusage. Conclusion Notre etude observationnelle dans un service d’urgence confirme l’existence d’un mesusage mais souligne le risque d’hemorragies spontanees.

Resume La prescription d’une specialite pharmaceutique en dehors d’une indication, d’une posologie ou chez une population particuliere peut conduire a un non-respect strict de l’autorisation de mise sur le marche (AMM) initiale, voire se situer hors AMM. Le respect de l’AMM impose des precautions et des responsabilites particulieres pour le prescripteur mais aussi, lors de la dispensation, pour le pharmacien.

Introduction Pristinamycin is an antibiotic of the streptogramin family; few adverse effects of this drug are reported, only cutaneous and digestive ones. Arthralgia and myalgia may however be observed although not mentioned in the summary of product characteristics. Objective Description and analysis of cases of pristinamycin-induced arthralgia and/or myalgia registered in the French database of pharmacovigilance. Method We carried out a targeted search of the database, selecting case patients presenting with arthralgia and muscle pain and excluding those associated with sensitivities or allergies to pristinamycin. Results We retrieved 15 case patients of pristinamycin-induced arthralgia and myalgia. Pristinamycin was the only potentially incriminated drug for seven case patients. Conclusion Although not serious, this adverse effect deserves to be better known by physicians to optimize therapeutic management.

Objectives Geriatric patients with hematologic malignancies (HMs) are prescribed targeted and supportive care treatments that add to the preexisting polypharmacy (PP). PP is associated with an increased risk of potentially inappropriate medications (PIM) and drug-drug interactions (DDI) resulting in increased hospitalization and mortality in the elderly. As very few data exist on these medication issues in the context of HMs, the objective of this study was to evaluate prevalence of PP, DDI and PIM use at baseline and 3 months among elderly patients with HMs who received baseline geriatric assessment. Methods PP, DDI and PIM use were assessed by a clinical pharmacist at two time points in patients over 75 years with HMs undergoing chemotherapy. PP was defined as the concurrent use of five or more medications. DDIs were evaluated according to the literature and prescription analysis software. PIMs were assessed according to the Laroche list. Results 122 patients (mean age 81.5; 6.6 medications) were included and after 3 months, 86 patients (5.8 medications) were available for a second assessment. Prevalence of PP, PIM and DDI at inclusion was 75.4%, 34.4% and 71.3%, respectively. PP was the only medication risk that was significantly reduced (p Conclusion This observational study highlighted that PP decreased over time but neither DDI nor PIM use were reduced. A pharmacist-led evaluation might help to manage these medication issues.

EnglishIn France, the missions of regional pharmacovigilance centres are to monitor, assess and prevent potential or proven medication risks and to promote the correct use of medicines. These organisations also play a role in informing and training health professionals whose involvement, by reporting adverse effects, is essential for the proper functioning of the national pharmacovigilance system. francaisEn France, les centres regionaux de pharmacovigilance ont pour missions de surveiller, evaluer et prevenir les risques medicamenteux potentiels ou averes et de promouvoir le bon usage du medicament. Ces structures ont aussi un role d’information et de formation des professionnels de sante. L’implication de ces derniers, via les notifications, est indispensable au fonctionnement du systeme national de pharmacovigilance.

Resume Le pharmacien d’officine est bien souvent un acteur de sante de premier recours pour la personne âgee face a son traitement. Comprendre les principaux facteurs de risque de survenue des effets indesirables chez les seniors permet d’ameliorer le bon usage des medicaments dans cette population.

An inappropriate immunologic response has been suggested to play a role in the pathogenesis of hidradenitis suppurativa (HS). Adalimumab was the first TNF-α inhibitor approved for moderate to severe HS. We report on a case of HS (Hurley stage 2) in a 39-year-old man, who had received fusidic acid and isotretinoin treatments without evident benefit during the last 8 years. The patient noticed a reduction in the number of lesions and quality of life (DLQI from 27 to 6) in the 2 months following verapamil initiation for cluster headache. When verapamil was stopped, the lesions recurred within 1.5 months. The patient resumed taking verapamil as before and a remission occurred. Verapamil has been shown to inhibit TNF-α and IL-1β in vitro and in vivo. We hypothesize that verapamil inhibits the inflammatory process through the TNF-α/IL-1 pathway involved in the HS physiopathology. Compared to biologic agents as anti-TNF-α (adalimumab) and anti-IL1 (anakinra), verapamil is safer and cheaper. Given its possible role on TNF-α/IL-1, verapamil may represent an alternative therapeutic option in mild and moderate HS.

Resume Chaque individu vieillit a son rythme, a sa maniere et a partir d’un âge qu’il est impossible de preciser. Le sujet âge presente des caracteristiques bien particulieres susceptibles d’aggraver la iatrogenie : deshydratation, denutrition, modifications des principales fonctions et organes, pathologies specifiques. Il convient de bien differencier les problemes lies au simple vieillissement physiologique des troubles generes par des maladies acquises.

BackgroundNon-optimal medication use among older adults is a public health concern. A concrete picture of potentially inappropriate medication (PIM) use is imperative to ensure optimal medication use.ObjectiveTo assess the prevalence of PIMs in community-dwelling older adults and identify associated factors.MethodsA retrospective population-based cohort study was conducted using the Quebec Integrated Chronic Disease Surveillance System (QICDSS). The QICDSS includes data on drug claims for community-dwelling older adults with chronic diseases or at risk of developing chronic diseases aged ≥65 years who are insured by the public drug insurance plan. Individuals aged ≥66 years who were continuously insured with the public drug plan between 1 April 2014 and 31 March 2016 were included. PIMs were defined using the 2015 Beers criteria. We conducted multivariate robust Poisson regression analyses to explore factors associated with PIM use.ResultsA total of 1 105 295 individuals were included. Of these, 48.3% were prescribed at least one PIM. The most prevalent PIMs were benzodiazepines (25.7%), proton-pump inhibitors (21.3%), antipsychotics (5.6%), antidepressants (5.0%) and long-duration sulfonylureas (3.3%). Factors associated with PIM exposure included being a woman [rate ratio (RR): 1.20; 95% confidence interval (CI): 1.20–1.21], increased number of medications and having a high number of chronic diseases, especially mental disorders (RR: 1.50; 95% CI: 1.49–1.51).ConclusionAlmost one out of two community-dwelling older adults use a PIM. It is imperative to reduce the use of PIMs, by limiting their prescription and by promoting their deprescribing, which necessitates not only the active involvement of prescribers but also patients.

With the intensification of chronical disease within older people, concurrent use of different drugs (polypharmacy) is becoming increasingly frequent. However, there is no established manner to determine whether polypharmacy is appropriate or not. We propose an original method of classifying polypharmacy using a Delphi survey results and multi-criteria decision-aid methods. To do this, we provided clinicians with a list of drugs that could be potentially prescribed to the typical elderly person suffering from three diseases (diabetes, chronic obstructive pulmonary disease, and heart failure). Clinicians expressed their opinions on a 5-point Likert scale, allowing for hesitation between two or more answers. They evaluated risks, benefits, and impacts of each drug on the patient’s quality of life. We then aggregated these evaluations in order to obtain, for each drug, a multi-criteria evaluation vector representing the collective opinion of the clinicians consulted. Subsequently, ELECTRE Tri-C and ELECTRE Tri multi-criteria sorting methods were used to evaluate and assign the polypharmacy to one of the following three categories: appropriate, more or less appropriate, or not appropriate. The proposed approach is innovative and enables the integration of a variety of conflicting criteria in the evaluation of polypharmacy quality. It also allows clinicians to express their opinion, and their hesitation where relevant, linguistically.

There are numerous definitions of polypharmacy to describe the use of many medications among older adults, but there is a need to clarify if they are purposive and meaningful. By means of a systematic review, we identified definitions of polypharmacy used in multimorbid older adults (≥65 years). We evaluated if the definitions align among the domains of research, clinical practice, and public health and appraised whether concepts of polypharmacy are based on strong foundations. More than 46 definitions of polypharmacy were retrieved from 348 publications (research: n = 243; clinical practice: n = 88; public health: n = 17). Several thresholds based on the number of medications were mentioned. The majority of the publications (n = 202, 58%) used a minimal threshold of five medications. Heterogeneous qualitative definitions were identified, mostly stating that polypharmacy is “more drugs than needed”. There was no significant divergence between domains as to the type of definitions used, although qualitative definitions were more common in clinical practice. Nearly half (n = 156, 47%) of the publications provided no justification for the polypharmacy definition used. The wide variety of definitions for polypharmacy precludes comparisons, appropriate identification and management of polypharmacy in multimorbid older adults. Standardized definitions would allow more coherent judgments regarding the individual and collective stakes of polypharmacy.

Proton pump inhibitors (PPIs) are frequently prescribed by general practitioners (GPs) who consider these drugs to be safe. However, more and more adverse drug reactions (ADRs) associated with PPIs are described.To determine the level of knowledge and attitude of GPs with respect to the ADRs of PPIs in adults.The GPs of the Nouvelle-Aquitaine region and the chief residents or former chief residents of the 35 French university departments of general medicine were questioned online using a list of 12 ADRs based on a semi-systematic literature review (neutropenia, thrombocytopenia, anemia, hypomagnesemia, increased liver enzymes, renal failure, pneumonitis, skin reactions, fracture, gastric polyps, microscopic colitis, Clostridium difficile colitis) and their attitude towards these ADRs.Out of the 232 (7.5%) GPs who participated, 38.4% had come across PPI ADRs (mainly digestive) in the last 6 months. These ADRs had been reported to pharmacovigilance in only 2.3% of the cases. No ADR at all was known by more than 70% of the GPs. The attitude of the GPs who had identified them was, in the majority, to stop PPI treatement. No difference in knowledge was found between university supervisors and non-supervisors. Finally, 74.7% of GPs declared that they required more information on IPP ADRs and 80.4% were willing to "deprescribe" these drugs.Aside from digestive ADRs, GPs have a poor knowledge of IPP-related ADRs. Those who do know them have an appropriate attitude and interrupt IPP treatment. The information requested by the GPs about the risks of PPIs is pertinent, particularly in a PPI-adapted prescription procedure, which also involves knowing how to "deprescribe".

Knowledge of the benefit/risk ratio of drugs in older adults is essential to optimise medication use. While randomised controlled trials are fundamental to the process of drug development and bringing new drugs to the market, they often exclude older adults, especially those suffering from frailty, multimorbidity and/or receiving polypharmacy. Therefore, it is generally unknown whether the benefits and harms of drugs established through pre-marketing clinical trials are translatable to the real-word population of older adults. Pharmacoepidemiology can provide real-world data on drug utilisation and drug effects in older people with multiple comorbidities and polypharmacy and can greatly contribute towards the goal of high quality use of drugs and well-being in older adults. A wide variety of pharmacoepidemiology studies can be used and exciting progress is being made with the use of novel and advanced statistical methods to improve the robustness of data. Coordinated and strategic initiatives are required internationally in order for this field to reach its full potential of optimising drug use in older adults so as to improve health care outcomes. Refereed/Peer-reviewed

Background Multimorbidity and polypharmacy are common in older people. Despite the existence of quality criteria for medication use among this population, there is little guidance for managing the complex pharmacological arsenal in a multimorbidity context. Objective To establish consensus on benefits, risks and impacts on quality of life of medications used in an older adult with three chronic diseases that require complex pharmacotherapy. Setting International experts in pharmacology. Method A panel of experts responded to three rounds of a Delphi survey. They assessed the benefits, risks and positive impacts on quality of life of 50 different medications or medication classes that could be used by a hypothetical multimorbid older patient aged 65–75years, with type2 diabetes, heart failure and chronic obstructive pulmonary disease. Each aspect was evaluated on a 5-level Likert scale. Main outcome measure Percentage of agreement on each of the three aspects for all medication. Results Consensus was reached on 95% of items (166/174). Only two medication classes were associated with both the highest category of benefits and positive impacts on quality of life, and the lowest risk category: long-acting anticholinergics and long-acting beta-2-agonists. Nine other medications/classes of medications were categorized within the highest benefits level (metformin, DPP-4-inhibitors, short-acting beta-2-agonists, ACE inhibitors, beta-blockers, warfarin, non-vitamin K oral anticoagulants, nitrates and acetaminophen). Fifteen medications were included in the highest level of risks, among which warfarin and Non-vitamin K oral anticoagulants. Conclusions Medications recommended in clinical guidelines for individual diseases are generally considered positive for multimorbid older patients. Nevertheless, a non-negligible number of medications was deemed negative or very negative by our panelists. For multimorbid patients, individualizing treatment according to their preferences seems of utmost importance.