The Cost of Potentially Inappropriate Medications in Nursing Homes in West Occitanie.

INTRODUCTION: As of 2019, people older than 65 years represent 20% of the French population. Despite several guidelines suggesting to avoid potentially inappropriate medication (PIM) use in elderly, the prevalence of their prescription remains high (25%). Furthermore, PIM could lead to preventable adverse drug reactions (ADRs). The main objective of this study was to determine the direct cost of PIM in older persons living in residential care homes for the elderly (nursing homes). A secondary objective was to assess the potential impact of PIM deprescribing on drug-related health care costs. Methods: We undertook a multicenter, retrospective study in 19 care homes for the elderly including 1240 residents. The analysis of prescriptions was carried out according to the European EU(7) PIM list. The cost of each drug was estimated according to the French Medication Insurance database. Furthermore, patient's comorbidities were studied using Charlson's comorbidity index. In order to estimate the economic impact of PIM, we used the list of alternative appropriate drugs suggested by EU(7) PIM list and French National Health Authority. An incremental cost per patient was calculated by the difference in costs between PIMs and alternative drugs. Results: A total of 7768 lines of drug prescriptions were analyzed. The mean age was 87.6 ± 7.6 years. About 70% (n = 872) of residents received more than five drugs. We identified 959 residents (77.3%) with at least one PIM. The mean cost of PIM was 0.58 euros versus 0.48 euros for alternatives. PIM substitution by alternatives led to save 12 centimes/resident/day. The mean cost of prescription with PIM was 2.8 euros per resident per day (28% of the overall cost of prescription). According to these results, more than 25 million euros can be overall saved for aged persons living in nursing homes for the older people in France per year. Conclusion: The prevalence of PIMs among the elderly in nursing homes is high and leads to a significant cost. Deprescribing of these medications could decrease both drug misuse and cost of drug prescription. Further research is needed to estimate the overall cost of PIM exposure outcomes, taking into account the ADRs leading to hospitalization.

Drug identification by the patient: Perception of patients, physicians and pharmacists.

INTRODUCTION: Faced with the increasing number of pharmaceutical products on the market, several pharmacovigilance notifications regarding confusion between look-alike and sound-alike drugs have been reported. This study of perception among patients, family physicians and pharmacists aims to evaluate drug identification factors and the risk of errors of confusion for patients. MATERIAL AND METHODS: Patients were systematically approached in randomly selected pharmacies within the Midi-Pyrénées region in France and invited to complete a questionnaire. Two other questionnaires were respectively sent to family physicians and pharmacists in the same region asking for their opinion on patients' perception of the identification of prescribed medicines. RESULTS: Of the 768 patients interviewed, most report identifying their medications by name (brand name: 50%; generic: 21%), while a smaller number cite physical appearance (box: 16%, tablet: 7% and blister packaging: 3%). In practice the factors considered most likely to cause confusion by patients relate to drug appearance (look-alike tablets: 28%, look-alike boxes: 20% and look-alike blister packaging: 13%). In contrast, look-alike and sound-alike names (generic and brand names combined) were cited in 31% of cases. Physicians (n=345) and pharmacists (n=198) understimate that patients identify their treatment by name (physicians: 46%; pharmacists: 26% vs. patients: 71%), reporting instead that problems arise mainly from the appearance of medicines (physicians: identification: 52% and risk factors for confusion: 74%; pharmacists: identification: 74% and risk factors for confusion: 83%; versus patients: identification: 26%; risk factors for confusion: 61%). DISCUSSION: Our study highlights the critical role of medication name in identifying drugs among patients. However, confusion of look-alike tablets or pills figures prominently among fears surrounding medication errors. Despite several notifications of pharmacovigilance, this issue appears to be underestimated within the body of medical literature. Proper identification of medicines by patients is essential to improving medication safety and therapeutic compliance. Concrete measures can be undertaken to reach this goal.

Trends and Patterns of Antidepressant Use in French Children and Adolescents From 2009 to 2016: A Population-Based Study in the French Health Insurance Database.

PURPOSE/BACKGROUND: Over the last decade, the use of antidepressants (ATDs) in children and adolescents has markedly increased in several occidental countries, but recent data in French children are missing. This study aimed to assess trends of ATD use in French children (6-11 years) and adolescents (12-17 years) and to characterize changes in ATD prescribing patterns from 2009 to 2016. METHODS: Using data from the French Health Insurance Database, annual prevalence and incidence of ATD use and changes in ATD prescribing patterns were analyzed. RESULTS: Overall ATD prevalence of use rose slightly from 0.51% in 2009 to 0.53% in 2016 (+3.9%), with a decrease in children (0.18%-0.11%; -38.9%) and an increase in adolescents (0.86%-0.98%; +14.0%) and an overall female preponderance (56.7% in 2009; 58.7% in 2016). Serotonin reuptake inhibitor prevalence of use increased from 0.24% to 0.34%, whereas tricyclic ATD use decreased (from 0.20% to 0.16%). Similar trends were obtained with overall incidence of use, from 0.39% in 2009 to 0.36% in 2016 (-7.7%). Sertraline was the most frequently prescribed in adolescents (2009: 22.2% of all ATD prescriptions; 2016: 32.9%), whereas amitriptyline was the most prescribed in children (2009: 42.7% and 2016: 41.2%). Off-label use decreased in adolescents (from 48.4% to 34.8%) but increased in children (from 10.0% to 26.5%). IMPLICATIONS/CONCLUSIONS: Antidepressant level of use in French children and adolescents was stable in recent years and lower than that observed in other European countries and the United States.

Infectious risk of biological drugs vs. traditional systemic treatments in moderate-to-severe psoriasis: a cohort analysis in the French insurance database.

The aim of this study was to compare the infectious risk between a group of psoriasis patients treated by biological drugs (BD) and a group treated by traditional systemic treatments (TST). We built a retrospective observational cohort study from the French health insurance database in the Midi-Pyrénées area (2.9 million inhabitants, southwest of France) using data from 01/01/2010 to 12/31/2013. We compared the infectious risk between 'exposed' patients treated with BD (adalimumab, etanercept, infliximab, or ustekinumab) and 'unexposed' patients treated by TST (phototherapy, acitretin, methotrexate, or cyclosporine). We realized a survival analysis on the first infectious event, defined as an anti-infective drug delivery or a hospital diagnosis of infection. We selected 101 'exposed' and 788 'unexposed' patients. In our multivariate Cox model, 'exposure' did not seem to decrease the time frame of the first infectious event compared with 'nonexposure' (HR = 0.94, P = 0.62). Among all treatment, the safest seemed to be ustekinumab while the least safe was etanercept. We found factors statistically associated with the risk of infection: gender (female vs. male), economic deprivation, chronic hepatitis B or C, history of cancer, at least one infectious event, and the number of different drugs during the 6-month period before the study. We did not find any difference of infective risk between the BD and the TST. This result enhances the recent PSONET registries conclusions.

Utilization and costs of HIV antiretroviral drugs in Europe during the last ten years: Impact of generic antiretroviral drugs on cost reduction.

INTRODUCTION: Simulation studies showed that generic antiretroviral (ARV) drug utilization could lead to significant cost reduction of HIV treatment in developed world. This study aimed to quantify ARV utilization and costs in European countries between 2006 and 2015. We also assessed the impact of generic ARV drug utilization on cost reduction in real-life. METHODS: ARV drug utilization in 14 European countries (France, Italy, Germany, Denmark, Netherlands, Norway, Sweden, Finland, Iceland, Croatia, Czech Republic, Estonia, Latvia, and Lithuania) were analysed using defined daily dose (DDD)/1000 inhabitants/year. ARV drug cost was estimated in million euro/year and euro/1000 inhabitants/year. The impact of generics on cost reduction was assessed in three countries: France, Denmark, and Czech Republic, using four parameters: expected savings, observed savings, brand price-reduction savings and overall savings. RESULTS: Between 2006 and 2015, median ARV drug utilization increased from 234 DDDs per 1000 inhabitants per year (IQR 124-388) to 385 (229-670). The median cost increased from €3751/1000 inhabitants/year (1109-4681) to €9158 (3269-10,646). Between 2013 and 2015, overall savings of €0.9, €1.6, and €33.7 million were respectively observed in Denmark, Czech Republic, and France. CONCLUSION: Overall savings observed in real-life from generic ARV drugs in Denmark were related to high rate of low-price generic utilization, contrarily to France and Czech Republic where these were more related to brand price-reduction than generic utilization itself.

Serious adverse drug events related to non-investigational drugs in academic clinical trials: another source of safety data for risk assessment?

AIMS: Sponsors of clinical trials have to analyze serious adverse events (SAEs). Both sponsors and investigators determine the relationship between the investigational medicinal product, the investigational device or procedure and SAEs. SAEs related to another cause, such as a non-investigational medicinal product (NIMP), do not have clear pharmacovigilance reporting requirements. The aim of this study was to evaluate the amount and the nature of NIMP-related SAEs recorded by three French academic sponsors and to propose pharmacovigilance requirements for these cases. METHODS: This was a retrospective descriptive study including all cases of NIMP-related SAEs occurring in clinical trials and reported to three academic sponsors between January 2009 and October 2014. RESULTS: Among 5870 cases of SAEs, 300 (5%) were related to a NIMP in 50 clinical trials. Involved NIMPs were mainly antithrombotics, cytostatics and immunosuppressants. Some of these drugs were currently followed by a risk management plan (e.g. rivoxaban). The most frequent NIMP-related SAEs were neurological, gastrointestinal and infectious disorders. Seven NIMP-related SAEs were known as 'rare' or 'very rare' and two were 'unlabelled'. CONCLUSIONS: As far as we know, this is the first study to focus about NIMP-related SAEs occurring in clinical trials. This work highlights the potential high quality source of safety data via NIMP-related SAE collection. Globally, we propose that NIMP-related SAEs occurring in clinical trials should systematically be notified to the pharmacovigilance system of the concerned country. Clearer procedures of interactions between safety units of academic sponsors and pharmacovigilance systems are needed to allow an effective recording of NIMP-related SAEs.

Biosimilars: from technical to pharmacoeconomic considerations. 30th Rencontres Nationales de Pharmacologie et Recherche clinique pour l'Innovation et l'Evaluation des Technologies de Santé. Tables rondes.

A biosimilar is a biological medicinal product claimed to be similar to a reference biological medicinal product. Its development plan includes studies comparing it with the reference product in order to confirm its similarity in terms of quality, preclinical safety, clinical efficacy, and clinical safety, including immunogenicity. Biosimilars differ from generics both in their molecular complexity and in the specific requirements that apply to them. Since patents on many biological medicinal products will expire within the next 5 years in major therapeutic areas such as oncology, rheumatology and gastroenterology and as those products are so costly to the French national health insurance system, the availability of biosimilars would have a considerable economic impact. The round table has issued a number of recommendations intended to ensure that the upcoming arrival of biosimilars on the market is a success, in which prescribing physicians would have a central role in informing and reassuring patients, an efficient monitoring of the patients treated with biologicals would be set up and time to market for biosimilars would be speeded up.

Interactions between medical residents and drug companies: a national survey after the Mediator® affair.

BACKGROUND: The present study aimed to describe exposure and attitudes of French medical residents towards pharmaceutical industry. The study was performed shortly after the Mediator affair which revealed several serious conflicts of interest inside the French health system. METHODS AND FINDINGS: A cross-sectional study was implemented among residents from 6 French medical faculties. Independent education in pharmacology, attitudes towards the practices of pharmaceutical sales representatives, opinions concerning the pharmaceutical industry, quality of information provided by the pharmaceutical industry, and opinions about pharmaceutical company sponsorship were investigated through a web-based questionnaire. We also assessed potential changes in resident attitudes following the Mediator affair. The mean value of exposure to drug companies was 1.9 times per month. Global opinions towards drug company information were negative for 42.7% of the residents and positive for only 8.2%. Surprisingly, 81.6% of residents claimed that they had not changed their practices regarding drug information since the Mediator affair. Multivariate analyses found that residents in anesthesiology were less likely to be exposed than others (OR = 0.17 CI95% [0.05-0.61]), exposure was significantly higher at the beginning of residence (p<0.001) and residents who had a more positive opinion were more frequently exposed to drug companies (OR = 2.12 CI95% [1.07-4.22]). CONCLUSIONS: Resident exposure to drug companies is around 1 contact every 2 weeks. Global opinion towards drug information provided by pharmaceutical companies was negative for around 1 out of 2 residents. In contrast, residents tend to consider the influences of the Mediator affair on their practice as relatively low. This survey enabled us to identify profiles of residents who are obviously less exposed to pharmaceutical industry. Current regulatory provisions are not sufficient, indicating that further efforts are necessary to develop a culture of disclosure of conflict of interest and of transparency in residents.

Are adverse drug reaction patterns different between romiplostim and eltrombopag? 2009-2013 French PharmacoVigilance assessment.

BACKGROUND: Romiplostim and eltrombopag, the two marketed thrombopoietin receptor agonists (TPO-RAs), have distinct binding sites and might have distinct pharmacodynamic mechanisms. The aim of this study was to compare their adverse drug reaction (ADR) patterns. METHODS: We selected in the French PharmacoVigilance Database all ADRs associated with TPO-RAs from TPO-RA marketing until the 31st of December 2013. Medical charts were reviewed. We conducted disproportionality analyses comparing romiplostim exposure in the reports of a given ADR pattern (thrombosis, neurological, cutaneous, gastrointestinal or hematological) to romiplostim exposure in all other TPO-RA-related ADR reports. Reporting Odds Ratios (RORs) were adjusted for age and gender. We also compared the number of reports of a given ADR pattern per million daily defined doses (DDDs) dispensed in France during the study period. RESULTS: We described 45 reports (53 ADRs) with romiplostim and 26 reports (37 ADRs) with eltrombopag. There were 19 venous thromboses. At least one other risk factor was present in 83.3% of the cases. Ten (55.6%) patients had been splenectomized previously. There were eight arterial thromboses. Another risk factor was noticed in all cases. There was no signal for an excess risk of thrombosis with romiplostim versus eltrombopag (ROR: 1.45, 95% CI [0.48-4.45]). There was a signal for a higher risk of gastrointestinal ADRs with eltrombopag (ROR: 30.28, 95% CI [3.23-383.86]) and of hematological ADRs with romiplostim (ROR: 14.36, 95% CI [1.73-119.08]). Dispensing data-adjusted comparisons led to similar results. CONCLUSIONS: This study suggests different ADR patterns between romiplostim and eltrombopag.

["Serious" adverse drug reactions with tramadol: a 2010-2011 pharmacovigilance survey in France]. / Effets indésirables « graves ¼ du tramadol : bilan 2010-2011 de pharmacovigilance en France.

OBJECTIVE: Tramadol is a weak opioid used as a step 2 analgesic, approved in France for moderate to severe pain. After dextropropoxyphene withdrawal, a national pharmacovigilance follow-up of tramadol was decided by the French Drug Agency. METHODS: All Serious Adverse Drug Reactions (SADR) notified with tramadol to the French PharmacoVigilance Centres (CRPV) and pharmaceutical companies between August 1(st), 2010 and July 31(th), 2011 were analyzed. RESULTS: During the study period, 296 cases of SADR were notified to CRPV and 59 to pharmaceutical companies. Apart from opiate-related SADR, tramadol induced serotoninergic SADR, including seizures or serotoninergic syndromes. Several « unlabelled ¼ SADR were also identified: some of them, like hyponatremia or hypoglycemia, are poorly known by health professionals. Other were never published: peripheral edema or pancreatitis. CONCLUSION: This study shows that besides well-known opioid or serotoninergic ADR, tramadol can also induce 2 other relatively unknown ADR: hypoglycemia and hyponatremia.

[Analysis of prescriptions associated to hormone replacement therapy in Midi-Pyrénées region]. / Analyse des prescriptions associées au traitement hormonal de la ménopause en Midi-Pyrénées.

The aim of the present study was 1- to describe hormone replacement therapy (HRT) prescription in Midi-Pyrénées region (South West France) and 2- to compare the prescriptions of associated drugs to those of women who took HRT with prescriptions to women who did not take HRT. From 2004 to 2008, HRT prescription decreased for women aged 50 to 59 years in Midi-Pyrénées: 13.95% to 10.33% estradiol/progestin association consumers. During the first 6 months of 2008, 20,161 women took the association estradiol/progestin. Transdermal/percutaneous forms of estradiol (71.21%) and natural progesterone were mainly prescribed. The number of different dispensed drugs was significantly higher in the HRT group: 5.18 versus 2.82 in the control group (p < 0.0001). All classes were concerned except antineoplastic drugs and immunomodulators, drugs for diabetes and raloxifene which were more prescribed to controls. In the period of the study, 7,035 patients took estrogen alone (25.87% of HRT consumers). The same phenomena were observed in this group. Women exposed to HRT in Midi-Pyrénées, great consumers of drugs, represent a population who require particular medical supervision, because of the risks of HRT and pathologies and/or numerous associated drugs.

[Could we improve notification of adverse drugs reactions in hospital? Assessment of 5 years of network PharmacoMIP's activities]. / Peut-on améliorer la notification des effets indésirables dans les établissements hospitaliers ? Bilan de 5 ans d'activité du réseau PharmacoMIP.

BACKGROUND: Spontaneous reporting of adverse drug reactions (ADR) is fundamental to drug safety surveillance (pharmacovigilance) and assessment of benefit/risk ratio. However, under-reporting remains the limit of the system. OBJECTIVE: The aim of this study was to assess the effect of regular visits of an Assistant in Clinical Research (CRA) on the improvement of ADR reporting in non-university hospitals. METHODS: We set up an ADR report collecting system that involved regular visits in non-university hospitals, We began the visits in 2006 in 2 areas (Haute Garonne and Gers), extended to 4 other areas in 2009. We compared the reporting rate (number of reports/number of beds) of total ADRs reported by non-university hospitals in these areas before (one year) and after the start of CRA visits. RESULTS: A total 2831 of reports were collected by the CRA: 40% were "serious" including two deaths. The results suggest an increase of 100% of the rate of reporting of ADRs. CONCLUSION: This study shows that regular visits increases the number of ADRs reported by non-university hospitals. Further assessment of this procedure is necessary for long term evaluation of its effectiveness.

Laboratory monitoring of patients treated with antihypertensive drugs and newly exposed to non steroidal anti-inflammatory drugs: a cohort study.

BACKGROUND: Drug-Drug Interactions between Non Steroidal Anti-Inflammatory Drugs (NSAIDs) and Angiotensin Converting Enzyme Inhibitors (ACEIs), Angiotensin Receptor Blocker (ARBs) or diuretics can lead to renal failure and hyperkalemia. Thus, monitoring of serum creatinine and potassium is recommended when a first dispensing of NSAID occur in patients treated with these drugs. METHODS: We conducted a pharmacoepidemiological retrospective cohort study using data from the French Health Insurance Reimbursement Database to evaluate the proportion of serum creatinine and potassium laboratory monitoring in patients treated with ACEI, ARB or diuretic and receiving a first dispensing of NSAID. We described the first dispensing of NSAID among 3,500 patients of a 4-year cohort (6,633 patients treated with antihypertensive drugs) and analyzed serum creatinine and potassium laboratory monitoring within the 3 weeks after the first NSAID dispensing. RESULTS: General Practitioners were the most frequent prescribers of NSAIDs (85.5%, 95% CI: 84.3-86.6). The more commonly prescribed NSAIDs were ibuprofen (20%), ketoprofen (15%), diclofenac (15%) and piroxicam (12%). Serum creatinine and potassium monitoring was 10.7% (95% CI: 9.5-11.8) in patients treated by ACEIs, ARBs or diuretics. Overall, monitoring was more frequently performed to women aged over 60, treated with digoxin or glucose lowering drugs, but not to patients treated with ACEIs, ARBs or diuretics. Monitoring was more frequent when NSAIDs' prescribers were cardiologists or anesthesiologists. CONCLUSION: Monitoring of serum creatinine and potassium of patients treated with ACEIs, ARBs or diuretics and receiving a first NSAID dispensing is insufficiently performed and needs to be reinforced through specific interventions.

[Drug prescription and pharmacovigilance in spa therapy: a comparative study at a 20-year interval (1987 versus 2007)]. / Prescription médicamenteuse et pharmacovigilance en pratique thermale: étude comparative à 20 ans d'intervalle (1987 versus 2007).

OBJECTIVES: Spa therapy is often considered as a dedicated period for a global treatment of patients. However, the prescription behaviours of spa physicians remain largely unknown. METHODS: A postal questionnaire concerning drug prescriptions during spa therapy and occurrence of adverse reactions to spa therapy was sent to the 95 spa physicians of South West of France. RESULTS: Seventy physicians answered to the survey. During spa period, most of them (67%) could associate drug prescription in complement of spa therapy. Drugs most often prescribed were analgesic (80%), non steroidal anti-inflammatory (57%) and antiinfectious (37%) drugs. Fifty nine per cent of the spa physicians could suppress part of the usual drug treatment of the patients. Spa related drugs which were the most often suppressed were anti-arthrosic and veinotonic drugs. Spa physicians could also modify or suppress drugs unrelated to the purpose of spa therapy, mainly psychotropics (anxiolytics or hypnotics), statins, diuretics or hypoglycemics (in case of inefficacy or adverse drug reactions). Spa physicians modified more drug prescriptions related to spa therapy than those unrelated to the purpose of spa therapy. Most of the spa physicians (77%) did observe adverse reactions to spa treatments. For 53% of the physicians, these adverse reactions could be "serious". The 2007 results were compared to those obtained during a similar survey performed 20 years before (1987). CONCLUSION: Spa therapy is often associated with change in drug prescriptions, with mainly a decrease in the number of prescribed drugs. Adverse reactions to spa therapy are rare and mainly "unserious". However, their imputability remains difficult to establish, thus justifying the need of a specific vigilance in spa therapy ("SpaVigilance").

[Writing and dispensing of NSAID prescriptions in late pregnancy: impact of health authorities' advice]. / Prescriptions et délivrances d'anti-inflammatoires non stéroïdiens après le 6(e) mois de grossesse: impact d'une lettre d'information envoyée par les autorités de santé

OBJECTIVE: To evaluate the impact a year afterwards of a letter sent by French health authorities (AFSSAPS) to health care professionals on 12 December 2003 to remind them that late pregnancy is a contraindication to nonsteroidal antiinflammatory drugs (NSAIDs). METHODS: We used records of the general health insurance fund in the district of Haute-Garonne to study the dispensing of prescription NSAIDS during late pregnancy to women who gave birth in this district both before the letter was sent (n=3099) (before group) and afterwards (2751 women who delivered between 12 July and 12 October 2004: "early after" group) and 2859 women between 12 March and 12 June 2005: "late after" group). We performed a "before-and-after" comparison. RESULTS: In the before group, 6.6% of the pregnant women had at least one NSAID prescription written and dispensed after the beginning of the sixth month of pregnancy, while this was the case for 5.1% of the women in the "early after" group (p=0.03) and 4.4% of the women in the "late after" group (p=0.004). Moreover, prescriptions and dispensing of paracetamol increased significantly (from 26.8% of the exposed women in 2003 to 36.6% in 2005, p<0.0001). CONCLUSION: The "before-and-after" comparison does not allow us to be sure of the causal link between the recommendations and the changes observed in the writing and dispensing of NSAID prescriptions. Nevertheless, we can hypothesize that this letter contributed to the decrease observed. The reduction is encouraging, but remains insufficient: in 2005, 4.4% of pregnant women were still receiving and filling prescriptions that are potentially harmful to fetuses and neonates.