Devices for securing and administering pediatric compounded oral liquids: survey results from French university hospitals.

Oral liquid forms, either commercial or compounded, are preferred in pediatrics due to their suitability for weight-based dosing and acceptability for children. The choice of dosing delivery devices associated with oral liquid forms is important to ensure accurate dosing, ease of administration, and patient safety. Given the prevalence of compounding in pediatric settings, this study aimed to investigate the practices among French university hospitals concerning the selection of dosing delivery devices associated with compounding oral liquid forms for children. An online survey was distributed to pharmacists involved in compounding in French university hospitals. The survey covered aspects such as the presence of child-resistant caps, types of dosing devices, the presence of bottle adapters, and the type of bottle adapters used. Among the 36 hospital pharmacies contacted, 24 responded to the survey. One pharmacy employed child-resistant caps for compounded liquid forms. Enteral syringes emerged as the primary dosing device (71%), with a minority using luer/luer-lock syringes (21%). Spoon and measuring cup usage was reported by none. Approximately two-thirds of the pharmacies (67%) used a bottle adapter in conjunction with the sampling device.   Conclusion: The study highlighted diversity in the practices of French university hospitals regarding dosing delivery devices associated with compounding oral liquid forms for pediatric patients. The findings underscored the need for standardized guidelines to streamline practices and enhance safety and precision in compounded medication administration for children. What is Known: • Administration devices are important to ensure the correct administration of the required dose of oral liquids in pediatrics. • For compounded oral liquid forms, the selection and supply of administration devices are managed by compounding pharmacies from those available on the market. What is New: • The study highlighted the variability of administration devices associated with compounded liquids for oral use in French hospital pharmacies.

Economic impact of a clinical pharmacist in the orthopaedic sector: a review of the literature.

OBJECTIVES: This review of the literature aimed to evaluate the economic impact of a clinical pharmacist in the orthopaedic sector. METHODS: The review followed the PRISMA recommendations. A bibliographic search was conducted on 23 June 2023 using PubMed, Cochrane Library and Web of Science. All articles in French or English with economic data on clinical pharmacy activities in orthopaedics were included. Articles not mentioning the term 'orthopaedics' and those published prior to 1990 were excluded. Data from the studies were compiled in an Excel table. A bias analysis using the ROBINS-I Cochrane tool was performed. The methodology of the studies was compared and weighted using the CHEERS and STROBE checklists. RESULTS: Among 529 articles initially identified, 10 were included in the review. The cost-benefit ratio of a clinical pharmacist in orthopaedics ranged from 0.47:1 to 28:1. The maximum savings reached US$73 410 /year in the American study and €1 42 356 /year in the French study. For three studies, the cost of a clinical pharmacist was not evaluated. Eight studies showed a positive economic impact. The Dutch study showed a balance and the Danish study showed a negative economic impact of €3442/month. CONCLUSIONS: This literature review has shown an economic benefit of a clinical pharmacist in the orthopaedic sector despite several biases and methodological limitations. The two studies that did not confirm this benefit only evaluated a limited number of expected benefits. Nevertheless, the economic impact of the clinical pharmacist in the orthopaedic sector seems positive and undervalued.

An observational study of haemophilia A patients without inhibitors using the French national claims (SNDS) database.

OBJECTIVES: To describe clinical characteristics, factor consumption, and events of interest in patients with haemophilia A without inhibitors receiving prophylaxis in France, and the clinical impact of switching to Elocta® in this population. METHODS: This retrospective, observational study using the Système National des Données de Santé database, analysed data from patients with haemophilia A without inhibitors using prophylactic factor VIII (FVIII) replacement therapy during 2016-2019. Clinical characteristics, treatment patterns and switches, factor consumption, and rate of events of interest were determined. In a sub-cohort of patients treated with Elocta®, clinical characteristics, factor consumption, and rate of events of interest before and after switching to Elocta® were compared. RESULTS: For 545 patients, with mean age (standard deviation [SD]) 25.4 (17.8) years, Elocta® was the most used treatment. Bleeding events and articular non-bleeding events leading to hospitalization occurred in 15.4% and 13.9% of patients, respectively, and 9.9% of patients had surgeries or procedures related to haemophilic arthropathy. The mean (SD) FVIII product consumption was 344 (93) IU/kg/month for extended half-life treatment, and 331 (98) IU/kg/month for standard half-life products. For the sub-cohort of 146 patients, bleeding events (SD) decreased from 0.32 (2.2) to 0.09 (0.42) events/patient/year (p = 0.227) after switching to Elocta®. There was no statistically significant difference in rates of factor consumption or articular non-bleeding events before and after initiation of Elocta®. CONCLUSION: This study provides real-world insights that advance the understanding of treatment patterns and events of interest in patients with haemophilia A on prophylactic regimens in France.

[Overview of the implementation of pharmaceutical interviews in pharmacies in France: Analysis of responses to a questionnaire]. / État des lieux de la mise en place en France des entretiens pharmaceutiques en officine : analyse des réponses issues d'un questionnaire.

OBJECTIVE: To evaluate the development of pharmaceutical interviews in pharmacies in France, in order to understand the organization implemented, any limitations and the expansion of eligible pathologies. METHOD: A dematerialized questionnaire was designed and distributed between November 2022 and February 2023 to pharmacists and pharmacy students in France (mainland and overseas) via a link to a Google Form. RESULTS: Ninety-four pharmacists from 8 different regions of France responded to the survey. The 94 responses showed that 56% of pharmacists practiced pharmaceutical interviews. Among pharmacists who practiced interviews, pharmacy owners practiced significantly more interviews than other statuses within the pharmacy (67% vs. 38% P=0.014). No other factor, such as dispensary size or geographical area of practice, had a significant impact on whether or not pharmaceutical interviews were carried out. These talks are often carried out at the patient's request, and 89% of them are accompanied by documents for the patient's attention. For pharmacists who do not carry out interviews, time, staffing and remuneration are the 3 main blocking factors found in both quantitative and verbatim variables. Whether or not pharmacists carry out pharmaceutical interviews, this activity received 87% approval from the 94 respondents, and 84% of them would like to include more chronic disease themes. CONCLUSION: The survey shows that pharmacists approve of the pharmaceutical interviewing activity, but it also highlights obvious logistical obstacles linked to a lack of resources. Thus, even among pharmacists who carry out pharmaceutical interviews, this activity is still carried out relatively infrequently on a routine basis, and often by the incumbent pharmacist, who takes on the responsibility of carrying out this activity.

Cost effectiveness of using trastuzumab biosimilars compared to trastuzumab original drugs to treat breast cancer in a hospital setting.

INTRODUCTION: Subcutaneous (SC) drug administration, such as the Herceptin® in an oncology day hospital reduces the administration time of trastuzumab. In the context of combination therapy administration, this time-saving may be called into question. The challenge posed by the deployment of much less expensive IV biosimilar forms raises questions about the cost-effectiveness of SC administration. METHODS: Using data from a french Diagnostic Related Groups regarding prescriptions of intravenous Herceptin® (HIV), Herceptin® biosimilar IV (BSIV), and Herceptin® subcutaneous (HSC), we conducted two simulations. This simulation involved replacing all HSC with BSIV in combination therapy administration (Simulation 1) and subsequently substituting IV forms with SC forms only when prescribed as monotherapy (Simulation 2). A cost-benefit analysis was conducted based on these two simulations, from the hospital's perspective, for Normandy's population over a 1-year timeframe. RESULTS: In Simulation 1, there was an average cost-saving of €12 per patient per year, but it resulted in a loss of 10140 min, equivalent to 10 min per patient per year when compared to the current situation. Simulation 2 yielded average cost-savings for the hospital amounting to €51 per patient per year, along with a time-saving of 67 min per patient per year compared to the current situation. CONCLUSIONS: The development of a program aimed at optimizing the prescription of Trastuzumab holds the potential to deliver significant cost-savings to hospitals while enhancing the quality of service provided to the patients. This optimization involves using H SC in monotherapy and BS IV in combination therapy administration.

Evaluation of the care pathway in the context of the dispensing of emicizumab (Hemlibra) in community and hospital pharmacies in France: A patient satisfaction survey.

INTRODUCTION: Since June 2021 in France, patients with haemophilia A with anti-factor VIII inhibitors and patients with severe haemophilia A without anti-factor VIII inhibitors, and treated with emicizumab (Hemlibra), have to choose the dispensing circuit community or hospital pharmacy. AIM: To evaluate satisfaction of patients whether they choose dispensation from a community pharmacy or retained dispensation from the hospital pharmacy, to understand the main motivation for choosing the community or the hospital pharmacy. METHODS: All patients living in France, regardless of age, were eligible to participate. Between September 13, 2022, and January 9, 2023, 175 respondents answered the satisfaction survey, including 123 in community pharmacy and 52 in hospital pharmacy. RESULTS: Eighteen months after availability in community pharmacies, treatment accessibility is improved for the benefit of the patient. The door-to-door travel times are significantly reduced to the community pharmacy with an average gain of 16.5 min saved from the place of residence. Patients are mostly satisfied with the new dispensing circuit especially concerning the overall satisfaction (p < .0001), the travel time (p < .0001) and the strong relationship with the pharmacist (p = .0022) compared to hospital pharmacy. CONCLUSION: Innovation in care pathways is showing its full potential in improving access to medication, made possible by the implementation of a rigorous organization accompanied by training to enable healthcare professionals involved in primary care to provide appropriate management.

[Tobacco and surgery: A survey of health professionals' practices and knowledge. A role for the community pharmacist]. / Tabac et chirurgie : enquête sur les pratiques et les connaissances des professionnels de santé. Un rôle pour le pharmacien d'officine.

OBJECTIVE: To evaluate the knowledge and management of preoperative smoking patients by different health professionals. METHOD: We conducted a survey among surgeons, anesthesiologists, and pharmacists using questionnaires. The study included 115 pharmacists and 7 physicians. RESULTS: Only 28% of pharmacists felt they had the necessary knowledge about smoking cessation before surgery and its consequences. Moreover, pharmacists were informed of the surgery less than one month before in 61% of cases, whereas physicians claimed to inform patients at least 3 months before in 57% of cases. The main reasons mentioned by the pharmacist for not informing the patient about presurgical smoking cessation were a lack of knowledge of the information to be relayed and a late knowledge of the scheduling of a surgery. Additionally, 57% of physicians stated that they never prescribed nicotine replacement products, while 42% of pharmacists felt that they never dispensed them. CONCLUSION: The study provides a clear picture of the smoking pathway before surgery and highlights areas for improvement in the management of preoperative smoking patients by different health professionals.

Pharmacist tracking and correction of medication errors: An improvement project in the observation ward of the emergency department.

OBJECTIVE: The risk of medication errors is high in emergency departments. Implementation of medication reconciliation activity complemented by pharmaceutical analysis of prescription is an effective way to reduce drug related problems. This study aimed to assess the potential clinical impact of these activities to prevent medication errors for the observation ward patients. The secondary objective was to assess these activities' cost-avoidance and benefit-to-cost ratio. MATERIAL AND METHODS: This study was conducted in a 16-bed unit, over a 5-month period. The patients' demographic and treatment details, and data from pharmaceutical activities were collected and analyzed by a pharmacist. Two pharmacists and an emergency physician assessed the potential clinical impact of medication errors. RESULTS: Medication reconciliation for 250 patients (15.7% of 1589 admitted patients) and pharmaceutical analysis of prescription for 302 patients (19%) were performed by the pharmacist. Medication reconciliation detected 752 errors in 197 patients; 19% were related to high-risk medications and 14% had a potential clinical impact assessed as major, critical or fatal. Pharmaceutical analysis of prescription revealed 159 drug related problems in 118 patients; of which 26% involved high-risk medications and 24% had a potential clinical impact assessed "at least major". In total, 16% of pharmacist interventions had a potential clinical impact assessed "at least major" in 33% of patients: this represents 1.8 pharmacist interventions formulated per day. CONCLUSION: The presence of a pharmacist in the observation ward of the emergency department is useful in detecting iatrogenic drug related problems and reducing their medical impact. The benefit-to-cost ratio is favorable for the hospital.

Impact of Clinical Pharmacist Consultations on Postoperative Pain in Ambulatory Surgery.

Post-operative pain is a common symptom of ambulatory surgery. The objective of this study was to evaluate a pain management protocol integrating a pharmacist consultation. We conducted a quasi-experimental, single center, before-after study. The control group was recruited between 1 March and 31 May 2018 and the intervention group between 1 March and 31 May 2019. Outpatients in the intervention group received a pharmacist consultation, in addition to the usual anesthesiologist and nurse consultations. Pharmacist consultations were conducted in two steps: the first step consisted of general open-ended questions and the second step of a specific and individualized pharmaceutical interview. A total of 125 outpatients were included in each group. There were 17% (95% CI 5 to 27%, p = 0.022) fewer patients with moderate to severe pain in the pharmaceutical intervention group compared with the control group, which corresponded to a decrease in the mean pain level of 0.9/10 (95% CI -1.5/10; -0.3/10; p = 0.002). The multivariate analysis did not reveal any confounding factors, showing that only the pharmaceutical intervention could explain this result. This study demonstrates a positive impact of pharmacist consultations on postoperative pain in ambulatory surgery.

Development of an Oral Liquid Formulation of Nicardipine Hydrochloride Compounded with Simple Excipients for the Treatment of Pediatric Hypertension.

Nicardipine hydrochloride is an anti-hypertensive drug that is used off-label to treat hypertension in children. A previous oral formulation of nicardipine hydrochloride was developed using a commercial vehicle as an excipient. However, ready-to-use vehicles are prone to supply shortages, and their composition may undergo substantial modifications. The aim of this study was to propose a new oral formulation of nicardipine hydrochloride 2 mg/mL using simple excipients. The formulation included hydroxypropylmethylcellulose, simple syrup, polysorbate 80, sodium saccharin, citrate buffer, strawberry flavor and 0.2% potassium sorbate. The uniformity of content was maintained before and after agitation. Nicardipine hydrochloride concentration assessed by HPLC-MS/MS remained above 90% for 365 days before opening and for 28 days after opening. pH and osmolality were maintained throughout the study, and no microbial contamination was observed. The uniformity of mass of the delivered doses was evaluated using four different devices. A new oral formulation of nicardipine hydrochloride 2 mg/mL was developed using simple and safe excipients. Pharmacological and clinical parameters remain to be assessed and compared with those of the previous formulation.

Clinical Pharmacist Intervention Reduces Potentially Inappropriate Prescriptions in a Geriatric Perioperative Care Unit Dedicated to Hip Fracture.

INTRODUCTION: Clinical pharmacist (CP) intervention improves drug prescription by identifying potentially inappropriate prescriptions (PIPs). Geriatric perioperative care units (UPOGs) provide enhanced care for patients with hip fracture, including drug prescription. However, it is not known whether adding a CP intervention in a UPOG decreases the number of PIPs. This study aimed to evaluate the effect of a CP intervention, combining an implicit and an explicit method, on the number of PIPs in a UPOG. METHODS: This single centre before-after-control-impact study recruited patients aged over 75 years admitted to a UPOG for a hip fracture. The "control group" ("before period") received usual care including two medication reconciliations, one at admission and one at discharge. The "intervention group" ("after period") received usual care and a CP intervention including two medication reconciliations, a medication review with two tools, STOPP/START and Medication Appropriateness Index, and a meeting between a CP and geriatricians. PIPs were assessed in both groups by STOPP/START and Medication Appropriateness Index and compared from hospital admission to discharge. RESULTS: A total of 209 patients were included, 150 in the control group and 59 in the intervention group (mean age: 87.2 ± 5.9 years). The number of PIPs decreased in both groups from hospital admission to discharge (p < 0.001). The number of PIPs, potentially inappropriate medications, and potential prescribing omissions decreased more in the intervention group than in the control group (adjusted intervention effect: -2.46 (95% CI: -2.63; -2.24); -1.13 (95% CI: -1.27; -0.98); and -1.35 (95% CI: -1.52; -1.18), respectively, p < 0.001 for all). DISCUSSION/CONCLUSION: A CP intervention with an explicit and implicit method improved prescriptions in a UPOG. Further randomized studies are necessary to evaluate the effect of a CP intervention on adverse drug events, health costs, and mortality.

A Methodological Approach Using rAAV Vectors Encoding Nanobody-Based Biologics to Evaluate ARTC2.2 and P2X7 In Vivo.

On murine T cells, mono-ADP ribosyltransferase ARTC2.2 catalyzes ADP-ribosylation of various surface proteins when nicotinamide adenine dinucleotide (NAD+) is released into the extracellular compartment. Covalent ADP-ribosylation of the P2X7 receptor by ARTC2.2 thereby represents an additional mechanism of activation, complementary to its triggering by extracellular ATP. P2X7 is a multifaceted receptor that may represents a potential target in inflammatory, and neurodegenerative diseases, as well as in cancer. We present herein an experimental approach using intramuscular injection of recombinant AAV vectors (rAAV) encoding nanobody-based biologics targeting ARTC2.2 or P2X7. We demonstrate the ability of these in vivo generated biologics to potently and durably block P2X7 or ARTC2.2 activities in vivo, or in contrast, to potentiate NAD+- or ATP-induced activation of P2X7. We additionally demonstrate the ability of rAAV-encoded functional heavy chain antibodies to elicit long-term depletion of T cells expressing high levels of ARTC2.2 or P2X7. Our approach of using rAAV to generate functional nanobody-based biologics in vivo appears promising to evaluate the role of ARTC2.2 and P2X7 in murine acute as well as chronic disease models.

Clinical impact of a personalized pharmaceutical plan on opioid management in non-cancer pain: a pilot study.

Non-cancer pain of the locomotor apparatus is the main symptom justifying referral to a rheumatologist with potential introduction of opioids, leading to addiction if misused. The objective was to evaluate the impact of a personalized pharmaceutical plan on patients' knowledge of their opioid treatment and its duration. This prospective non-randomized pilot study was conducted during 7 months with standardized data collected in a French rheumatology department. Patients with rheumatic diseases and non-cancer pain requiring opioid treatment were included. The intervention group had a 30-min opioid-targeted pharmaceutical interview and received a full medication plan and the control group received usual care. A total of 17 patients were included in the intervention group and 18 in the control group. Among patients in the intervention group, only 6 (35%) knew that immediate-release opioids have a rapid and short action, 9 (53%) were worried about taking opioids, and 13 (76%) reported that they would refer to the information document provided if side effects occurred. A trend toward a shorter duration of treatment was observed in the study group (HR = 1.87, 95% CI 0.93 to 3.76, p = 0.08), but this trend was attenuated when adjusting on hospital duration (HR = 1.53, 95% CI 0.74 to 3.15, p = 0.25). This pilot study provides preliminary evidence on the role of the clinical pharmacist in the management of non-cancer pain with strong opioids. Clinical benefits will be assessed in a randomized study. Key Points • Knowledge of opioids is insufficient in rheumatology patients with non-cancer pain. • Pharmaceutical interviews may improve patients' knowledge of opioids.

Stability study of a compounded oral solution of nicardipine for the treatment of hypertension in children.

Nicardipine is an antihypertensive drug that may be used off-label by oral route to treat hypertension in children. Currently commercially available tablets are inappropriate for oral use in children and manufactured hard capsules are not suitable for easy dose individualization to achieve target blood pressure. We aimed to fulfill this lack of appropriate dose forms by developing an oral liquid formulation of nicardipine. We compounded an extemporaneous 2 mg/mL nicardipine solution in InOrpha® vehicle for oral use with 1% polysorbate 80. A HPLC-MS/MS stability-indicating method was developed and validated. The stability was assessed under room temperature and refrigerated storage conditions. Nicardipine concentration remained above 95% of the initial concentration for 90 days in both storage conditions, without apparition of degradation products. Organoleptic parameters, pH, osmolality, viscosity and density were assessed and remained stable throughout storage. A uniformity of content was maintained before and after agitation of the packaging bottles. Mass uniformity of delivered doses was also ensured. Finally, the formulation met the Pharmacopoeia specifications for microbiological contaminations. In this study we report a compounded formulation of nicardipine for oral use in pediatrics. This solution, which could be easily manufactured, is being used in our hospital. Pharmacological and clinical parameters including bioavailability, pharmacokinetics, efficacy and tolerance remain to be assessed.

Pharmacogenetics of Direct Oral Anticoagulants: A Systematic Review.

Dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban are direct oral anticoagulants (DOACs). Their inter-individual variability in pharmacodynamics and pharmacokinetics (transport and metabolism) is high, and could result from genetic polymorphisms. As recommended by the French Network of Pharmacogenetics (RNPGx), the management of some treatments in cardiovascular diseases (as antiplatelet agents, oral vitamin K antagonists, and statins) can rely on genetic testing in order to improve healthcare by reducing therapeutic resistance or toxicity. This paper is a review of association studies between single nucleotide polymorphisms (SNPs) and systemic exposure variation of DOACs. Most of the results presented here have a lot to do with some SNPs of CES1 (rs2244613, rs8192935, and rs71647871) and ABCB1 (rs1128503, rs2032582, rs1045642, and rs4148738) genes, and dabigatran, rivaroxaban, and apixaban. Regarding edoxaban and betrixaban, as well as SNPs in the CYP3A4 and CYP3A5 genes, literature is scarce, and further studies are needed.

Medico-economic impact of robot-assisted lung segmentectomy: what is the cost of the learning curve?

OBJECTIVES: The objective of this study was to assess the learning curve (LC) of robot-assisted lung segmentectomy and to evaluate hospital-related costs. METHODS: We conducted a retrospective study of Robot-assisted thoracic surgery (RATS) segmentectomies performed by 1 surgeon during 5 years. Perioperative and medical device data were collected. The LC, based on operating time, was assessed by Cumulative SUM analysis and an exponential model. Cost of care was estimated using the French National Cost Study method. RESULTS: One hundred and two RATS segmentectomies were included. The LC was completed at ∼30 procedures according to both models without significant difference in patients' characteristics before or after the LC. Mean operative time decreased from 136 min [95% confidence intervals (CI) 124-149] for the first 30 procedures to 97 min (95% CI 88-107) for the last 30 procedures. Mean length of stay decreased non-significantly (P = 0.10 for linear trend) from 8.1 days (95% CI 6.1-11.0) to 6.2 days (95% CI 4.9-7.9). The overall costs for the last 30 procedures as compared with the first 30 did not significantly decrease in the primary economic analysis but significantly decreased (P = 0.02) by €1271 (95% CI -2688 to +108, P = 0.02 for linear trend) after exclusion of 1 outlier (hospitalization-related costs > €10 000). After exclusion of this outlier, costs related to EndoWrist® instruments significantly decreased by €-135 (95% CI -220 to -35, P = 0.004), whereas costs related to clips decreased non-significantly (P = 0.28). CONCLUSIONS: The LC was completed at ∼30 procedures. Inexperienced surgeons may have higher procedure costs, related to consumable medical devices and operating time.

Assessment of adherence to disease-modifying anti-rheumatic drugs in rheumatoid arthritis.

OBJECTIVES: This work aimed to assess treatment adherence in rheumatoid arthritis patients with several tools and to identify factors associated with poor adherence. METHOD: Between February and December 2015, 183 patients were included in this cross-sectional study. A homemade 23-item self-questionnaire was filled by patients during an outpatient consultation or a day hospitalization stay. Morisky Medication Adherence Scale (MMAS)-4, MMAS-8 and Girerd scores were extracted from this homemade questionnaire. Medication possession ratio (MPR) was then calculated. For identification of factors associated with nonadherence, patients were divided in two groups according to MMAS-8 results differentiating patients with good or bad adherence to treatments. RESULTS: Of the 183 patients, 59% received a combination of biologic and conventional synthetic disease-modifying drugs, 22% a biological treatment alone, and 19% a conventional DMARD alone. Respectively, 3%, 10%, and 7% were considered as low adherent according to MMAS-4, MMAS-8, and Girerd scores. MPR was calculated for 84/183 patients; 23% were low adherent. The need for a help in preparing the drugs (p = 0.05; OR = 6.12; 95% CI: 0.86 to 268.90) and concomitant diabetes (p < 0.001; OR = 0.045, 95% CI: 0.001 to 0.299) was higher in patients with good adherence. Presence of a patient's relative reminding to take medications was associated with low adherence (p = 0.002; OR = 4.32, 95% CI: 1.41 to 13.11). CONCLUSIONS: This study highlighted the difficulty of assessing treatment adherence in rheumatoid arthritis patients despite four different tools. Objective measures by MPR indicated a higher proportion of poor adherent patients than self-questionnaires.Key Points• Proportion of patients considered as low adherent ranged from 3 to 27% according to the method of evaluation.• The use of a pillbox and/or the preparation of drugs by a patient's relative was associated with good adherence.• The presence of a patient's relative reminding to take medication was associated with low adherence.