Studying the impact of a medication use evaluation for polymedicated older patients by the community pharmacist (SIMENON): study protocol.

BACKGROUND: Aged polymedicated patients are particularly vulnerable for drug-related problems. A medication review aims to optimize the medication use of patients and improve health outcomes. In this study, the effect of a pharmacist-led medication use review is investigated for polymedicated ambulatory older patients with the aim of implementing this pharmaceutical care intervention across Belgium. METHODS: This article describes the study protocol of the SIMENON study and reports the results of the feasibility study, which aimed to test and optimize this study protocol. In the SIMENON intervention study, 75 Belgian community pharmacies each recruit 12 patients for a medication use review. For each patient, the identified drug-related problems and subsequent interventions are registered using the PharmDISC classification. In a subset of Dutch speaking patients, a pretest-posttest single group design is used to measure the impact of this review on patient related outcomes using questionnaires. The main outcome of the study is the type and number of drug-related problems and related interventions. A second outcome is the impact of the medication use review on adherence, objectively measured with dispensing data. Evolution in medication related quality of life is another outcome, measured with the Living with Medicines Questionnaire version 3. Other patient reported outcomes include adherence, self-management, patient satisfaction, fall incidents and use of emergency healthcare services. DISCUSSION: The findings of this study can provide data on the effectiveness of a medication use review in the Belgian primary care setting. Furthermore, it will provide insights in which patients benefit most of this intervention and therefore facilitate the implementation of medication review in Belgium. TRIAL REGISTRATION: ClinicalTrials.gov NCT03179722 . Retrospectively registered 7 June 2017.

Knowledge of staff members of residential care facilities for individuals with intellectual disability on medication administration via enteral feeding tube.

BACKGROUND: Guidelines for the safe administration of drugs through enteral feeding tube (EFT) are an important tool to minimise the risk of errors. This study aimed to investigate knowledge of these guidelines among staff of residential care facilities (RCF) for people with ID. METHOD: Knowledge was assessed using a 13-item self-administered questionnaire. Questions reflected key aspects of guidelines on medication administration via EFT. All staff members that administer medication through EFT in Belgian RCFs were invited to participate (n = 553). RESULTS: Nine out of 10 RCFs participated, and 356 questionnaires were collected. Almost all participants were women (96%), and most (82%) had a non-nursing educational background. Mean self-perceived knowledge of medication administration via EFT was 6.7 (on a 0-10 scale). On average, 5.7 (SD 1.9) out of 13 questions were answered correctly. A nursing degree and previous education on medication administration via EFT were associated with significantly higher scores. Guideline recommendations regarding rinsing of used medicine cups (90% correct answers) and preparation of hard gelatin capsules (89%) were known best. Those regarding the use of protective equipment when crushing toxic substances (4% correct answers), crushing of sustained release and enteric-coated dosage forms (6%), elevation of the patient's backrest (14%) and flushing of the EFT (15%) were known the least. CONCLUSION: This study identified a substantial lack of knowledge of guidelines for drug administration through EFT among staff of RCFs for people with ID. Our findings call for tailored educational programmes in order to increase knowledge on this subject.

[Medication screening by the community pharmacist in Belgium]. / Revue de la medication par le pharmacien d'officine en Belgique: pourquoi, comment et situation actuelle.

About 20% of the European population is older than 65 years. Because of multimorbidity (i.e. multiple chronic condition within a patient), older patients are often prescribed multiple drugs [i.e. polypharmacy). Both older age and polypharmacy significantly increase the risk for adverse drug events. International research showed that more or less 5% of all unplanned hospital admissions is related to the use of medication. About 70% of these drug related admissions happened in patients older than 65 years. Moreover, about half of the admissions could have been avoided. These preventable hospital admissions were caused by the intake of medication without an indication, problems with medication adherence, interactions and/or insufficient monitoring. We define this as (potential Drug Related Problems [DRPI. DRPs can occur on multiple occasions during the medication management process: prescribing, dispensing, intake and monitoring. When DRPs can be detected in an early stage, significant consequences can be avoided. To accomplish this, multiple strategies are possible. One of the possibilities is performing a periodic medication screening by the community pharmacist in patient groups at risk. During such a medication screening, the pharmacotherapy is critically evaluated in a systematic and structured way. The implementation of medication screening in first-line health care is currently limited. The community pharmacist is nevertheless ideally placed to perform this task. There is an important relation of trust between him and the patient and the community pharmacist has access to a full medication history. Furthermore, as an expert in drug-related issues, he possesses all necessary knowledge to perform the pharmacotherapeutic analysis.

[Reliability of OTC advertisement Relevance and quality of cited literature]. / Quelle est la fiabilité de la publiciteé pour les produits non soumis à prescription? Pertinence et qualité de la littérature mentionée.

Introduction Pharmacist receive a lot of publicity for OTC products. Often one or more literature references are mentioned to support the advertising claims. Objective In this study we examine: [1) whether the advertising claim is consistent with what is stated in the literature references mentioned on the leaflet and [2] whether these literature references are trustworthy. Method Through 60 randomly selected community pharmacies, pharmacist-directed advertisements for OTC products I= medicines, medical devices, dietary supplements and parapharmacy) with at least one bibliographic reference, were collected. The literature references listed in these leaflets were assessed in terms of content [= is the claim consistent with the information in the reference) and technically [= evaluation of the quality of the references]. Results The 85 collected OTC advertisements made 214 claims that referred to 243 references. Of these, 128 references did not support the promotional claim. The remaining 84 references did support the corresponding claim. From 31 references no full text was obtained. Of the 84 supporting references 44 were of dubious quality. The remaining 40 references were found to be reliable. Conclusion This study shows that the literature references in advertising leaflets for OTC-products are not a reliable source of information on the advertised product. Pharmacists should deal critically with this information and should be encouraged to consult reliable scientific sources.

[Frequency and nature of drug related problems with corticosteroids in Belgian community pharmacies]. / Fréquence et nature des problems liés aux corticosteroïdes dans les officines publiques de Belgique.

Aim Aims are: 1] Identify causes of Drug Related Problems (DRPs), interventions performed by pharmacists and results of corticosteroid- related problems and 2] distinguish between problems related to inhaled and general corticosteroids. Methods During 5 days of their internship, 534 final year students of pharmaceutical sciences in six Belgian universities collected DRPs encountered in community pharmacies, as well as related interventions performed by pharmacists and the result of the intervention. The DRPs' electronic registration was done through an adapted tool for Belgium based on the classification of Pharmaceutical Care Network Europe [PCNE- v 6.2]. Findings The frequency of DRPs is 24,8%. 766 DRPs (4,8%) related to corticosteroids, of which 351 were inhaled corticosteroids. The most common causes of corticosteroid-related problems (53- 59%) were technical causes. The most represented category of clinical causes was the inappropriate choice of drug [33-41%]. Pharmacists' intervention was similar for inhaled and general corticosteroids. Pharmacists intervened orally with patients in 38-40% of total interventions, and in writing in 16% of interventions. Pharmacists did not react in 16% of corticosteroid-related problems. 81-83% of PLMS were resolved partially or completely. Conclusion In conclusion, DRPs detected in community pharmacies related to corticosteroid are infrequent (4,8% of DRPs) but 82% of detected problems have been resolved. Furthermore, the study shows the importance for the Belgian health system to introduce an official DRPs classification and software facilitating their documentation in community pharmacies.

Drug administration via enteral feeding tubes in residential care facilities for individuals with intellectual disability: an observational study.

BACKGROUND: The administration of oral medication to patients with an enteral feeding tube (EFT) is challenging. Compliance to guidelines concerning medication administration via EFT has been investigated extensively in the hospital setting. However, studies in residential care facilities (RCFs) for individuals with intellectual disability (ID) are very limited. Therefore, the present study aimed to collect direct observational data on drug administration practices to residents with EFT in multiple RCFs. METHOD: This cross-sectional, observational study was conducted in six Belgian RCFs for individuals with ID. Observations of medication preparation and administration through EFT were carried out in two randomly selected units per participating RCF, on 2 days per unit during all daytime drug rounds, using a direct observation method. Afterwards, the recorded observations were compared with international guidelines on drug preparation and administration through EFT. RESULTS: In total, 862 drug preparations and 268 administrations in 48 residents with EFT were witnessed. Mixing together multiple drugs, not diluting liquid formulations with at least an equal amount of water, not shaking suspensions/emulsions before use, and not selecting the most appropriate dosage form were the most common deviations from medication preparation guideline recommendations. For medication administration, not flushing the EFT with at least 15 mL water was the most common deviation. We also observed high variability in working methods regarding medication preparation and administration via EFT, even between staff members of the same unit. CONCLUSION: This study found that current guidelines concerning medication preparation and administration through EFT are often not followed in Belgian RCFs for individuals with ID. Further research aimed at understanding why current guidelines are not followed seems warranted.

[Effectiveness of pharmaceutical care for patients with COPD: translated review of the recently published PHARMACOP trial]. / Efficacité des soins pharmaceutiques auprès de patients atteints de BPCO: compte-rendu de l'etude PHARMACOP récemment publiée.

BACKGROUND AND AIM: Few well-designed randomized controlled trials (RCT) regarding the impact of community pharmacist interventions on pharmacotherapeutic monitoring of patients with Chronic Obstructive Pulmonary Disease [COPD) have been conducted. We assessed the effectiveness of a pharmaceutical care program for patients with COPD. METHODS: The PHARMACOP-trial was a single-blind 3-month RCT, conducted in 170 community pharmacies in Belgium, enrolling patients prescribed daily COPD medication, aged > or = 50 years, and with a smoking history > or = 10 pack-years. A computer-generated randomization sequence allocated patients to intervention (n = 371), receiving protocol-defined pharmacist care, or control group (n = 363), receiving usual pharmacist care 11:1 ratio, stratified by center). Interventions, focusing on inhalation technique and adherence to maintenance therapy, were carried out at start of the trial and at one month follow-up. Primary outcomes were inhalation technique and medication adherence. Secondary outcomes were exacerbation rate, dyspnea, COPD specific and generic health status and smoking behavior. RESULTS: From December 2010 to April 2011, 734 patients were enrolled. 42 patients (5.7%) were lost to follow-up. At the end of the trial, inhalation score (Mean estimated difference [delta], 13.5%; 95% Confidence Interval [CI], 10.8-16.1; P < .0001] and medication adherence [(delta, 8.51%; 95% CI, 4.63-12.4; P < .0001) were significantly higher in the intervention group compared to the control group. In the intervention group, a significantly lower hospitalization rate was observed (9 vs 35 hospitalizations; Rate Ratio, 0.28; 95% CI, 0.12-0.64; P = .003). No other significant between-group differences were observed. CONCLUSION: The PHARMACOP-trial demonstrates that pragmatic pharmacist care programs improve both inhalation technique and medication adherence in patients with COPD and could reduce hospitalization rates. The protocolled intervention used in this trial was specifically designed for and evaluated in (Belgian) community pharmacies. This may facilitate future implementation in the Belgian context.

[Drug related problems in Belgian community pharmacies]. / Les problèmes liés aux médicaments dans les officines belges.

INTRODUCTION: The identification, the management and if possible the prevention of drug related problems (DRP), are the main responsibilities of pharmacists. AIM: The aims of the study were 1/to investigate the frequency and nature of drug related problems detected by community pharmacists, 2/to inventories the frequency and nature of the interventions by community pharmacists on prescribed medicines, and 3/to evaluate whether there is a difference between DRP detection at the moment of dispensing versus in a quiet setting (a posteriori detection). METHOD: All trainees of the participating universities of Belgian were asked to contribute to a observational study. Participating pharmacists quantified DRP's and their interventions on prescribed medicines for 5 days. Registrations were made by using a web tool based on an adapted version of the classification list of PCNE. The registration took place in two phases, at the time of delivery as well as in an a posteriori verification of the prescriptions with the pharmaceutical record file of the patients. RESULTS: The study was conducted from November 2012 to April 2013 in 534 community-pharmacies with internship. During this period 9.869 prescriptions (15%) with at least one DRP were detected on a total of 64.962 prescriptions treated by tutor pharmacists. Since there could be more than one problem on a prescription, 15.952 DRP's were registered. 2.597 of the DRP's were detected by a posteriori verification. 75% of all problems had a technical cause and 37% were clinical in nature. Under the technical causes an incomplete prescription was the most common. The most frequently registered clinical causes were a drug interaction, an inopportune time of intake, a too high or too low dose and an unsuitable drug. Participating pharmacists solved almost 3 of the 4 detected DRP's. In more than half of the DRP's, the patient was verbally and/or written informed. In 44% of the a posteriori discovered problems, the pharmacist intervened. CONCLUSION: Pharmacist detected one or more DRP's with 15% of the prescriptions. Analysis of a prescription prior to dispensing the medicines therefore appears necessary. The active intervention of the pharmacist in 83% of the problems indicates that he contributes to the optimization of drug therapy with a potential increase in the quality of life of the patient and a reduction in the cost of healthcare. The a posteriori discovered DRP's demonstrate the need for pharmacist lead meditation reviews possibly together with the physician and/or patient.

Hepatic and intestinal CYP3A expression and activity in broilers.

Cytochrome P450 is involved in drug metabolism. Subfamily CYP3A shows a degree of similarity across different animal species. However, little information is available about its expression and activity in broiler chickens. A RT-PCR method was developed for the quantification of CYP3A37 expression in the liver and small intestine of broilers. A higher expression in the jejunum was observed compared with that in the ileum. In the liver, a significantly lower expression compared with that in the jejunum was noticed. Thus, the role of the small bowel in drug metabolism cannot be neglected in broilers. CYP3A activity was studied in vitro using midazolam as a substrate. Two protocols for the preparation of intestinal microsomes were compared. Mincing of the tissues before ultracentrifugation seemed to be more appropriate than a protocol based on ethylenediaminetetra-acetic acid separation. CYP3A activity revealed to be the highest in the duodenum with a decreasing trend towards the ileum. Activity in liver was comparable to duodenal activity.

[Development of a protocol for counseling patients starting with oral hypoglycemic agents]. / Développement d'un protocole pour l'accompagnement de la première délivrance des antidiabétiques oraux.

INTRODUCTION: Counseling of patients filling a first prescription is an essentiaL aspect of pharmaceutical care. The use of a protocol summarizing all relevant counseling aspects can be a useful tool to standardize pharmaceutical care and to promote impLementation. AIM: (1) To develop a protocol for counseling of patients starting with oral hypoglycaemic agents (OHA), and (2) to investigate current provision of counseling for these patients in Belgian community pharmacies. METHOD: Based on literature, a consensus meeting with community pharmacists and consultation with physicians, we developed a protocol for counseling patients starting OHA. Additionally, an observational study of current provision of counseling for patients starting OHA was performed in 90 community pharmacies. RESULTS: All pharmacists reported to provide the most important item of our protocol, i.e. dose and timing of OHA intake. All other protocol items were provided by a smaller proportion of pharmacists: indication (by 64.4% of pharmacists), mechanism of action (30.0%), what to do if a dose is missed (3.3%), side effects (34.4%), hypoglycaemia (24.4%) and Lifestyle advice (68.9%). About 45% of pharmacists reported to give written drug information to patients starting OHA. Reduction of the administrative workload was most frequently mentioned as measure to spend more time on patient counseling. The majority of pharmacists considered our protocol as feasible and appLicabLe in daily pharmacy practice. CONCLUSION: This study found that current counseLing practices for patients starting OHA can be improved. Our protocol could be a useful and feasible tool to facilitate implementation of first prescription counseling.

[Diabetes and fasting during Ramadan. A observational study among Turkish immigrants in Belgium]. / Diabète et jeûne pendant le ramadan. Etude observationnelle parmi les migrants d'origine turque en Belgique.

AIMS: To investigate (i) Ramadan participation, (ii) provision of Ramadan related advice by healthcare providers (iii) medication use during Ramadan fasting among Turkish migrants with diabetes in Belgium. METHODS: This pilot observational study was conducted among a convenience sample of 52 Turkish migrants with diabetes in Belgium. Two questionnaires collected information on socio-demographic characteristics, diabetes related characteristics, current hypoglycaemic medication with dosing regimen, participation in the past Ramadan, reasons for (non)participation, use of hypoglycaemic medication during the past Ramadan, advice from their healthcare providers about fasting during Ramadan and follow up of this advice. RESULTS: Sixteen patients (31%) had fasted during the past Ramadan. Main reason for Ramadan participation was reinforcement of faith (12/15), while the main reason for non participation was having diabetes (34/36). About 56% of the study population had received recommendations from their healthcare provider(s) about fasting and diabetes during Ramadan. The most commonly provided advice was not to participate in Ramadan, followed by modification of drug therapy. Only 3 patients ignored the advice of their healthcare professionals. In addition, only 60% of those who actually fasted received recommendations about intake of diabetes medication during the ramadan. Most fasters continued their medication dose unchanged (87% of OHA users and 80% of the insulin users). CONCLUSIONS: This pilot study found a low prevalence of Ramadan fasting among Turkish migrants with diabetes in Belgium. We also found that provision of advice by healthcare providers could be improved. Larger scale studies are warranted to confirm these findings.

Self-medication of regular headache: a community pharmacy-based survey.

BACKGROUND: This observational community pharmacy-based study aimed to investigate headache characteristics and medication use of persons with regular headache presenting for self-medication. METHODS: Participants (n = 1205) completed (i) a questionnaire to assess current headache medication and previous physician diagnosis, (ii) the ID Migraine Screener (ID-M), and (iii) the Migraine Disability Assessment questionnaire. RESULTS: Forty-four percentage of the study population (n = 528) did not have a physician diagnosis of their headache, and 225 of them (225/528, 42.6%) were found to be ID-M positive. The most commonly used acute headache drugs were paracetamol (used by 62% of the study population), NSAIDs (39%), and combination analgesics (36%). Only 12% of patients physician-diagnosed with migraine used prophylactic migraine medication, and 25% used triptans. About 24% of our sample (n = 292) chronically overused acute medication, which was combination analgesic overuse (n = 166), simple analgesic overuse (n = 130), triptan overuse (n = 19), ergot overuse (n = 6), and opioid overuse (n = 5). Only 14.5% was ever advised to limit intake frequency of acute headache treatments. CONCLUSIONS: This study identified underdiagnosis of migraine, low use of migraine prophylaxis and triptans, and high prevalence of medication overuse amongst subjects seeking self-medication for regular headache. Community pharmacists have a strategic position in education and referral of these self-medicating headache patients.

[Self-medication of regular headache: a community pharmacy-based survey in Belgium]. / Automédication des céphalées fréquentes: étude dans les officines belges.

AIM: This observational community pharmacy-based study aimed to investigate headache characteristics and medication use of persons with regular headache presenting for self-medication. METHODS: Participants (n=1205) completed ii) a questionnaire to assess current headache medication and previous physician diagnosis, (ii) the ID Migraine Screener [ID-M] and (iii) the MIDAS questionnaire. RESULTS: Forty-four % of the study population (n=528) did not have a physician diagnosis of their headache, and 225 of them (225/528, 42.6%) were found to be ID-M positive. The most commonly used acute headache drugs were paracetamol (used by 62% of the study population), NSAIDs (39%) and combination analgesics (36%). Only 12% of patients physician-diagnosed with migraine used prophylactic migraine medication, and 25% used triptans. About 24% of our sample (n=292) chronically overused acute medication, which was combination analgesic overuse (n=166), simple analgesic overuse (n=130), triptan overuse (n=19), ergot overuse (n=6) and opioid overuse (n=51). Only 14.5% was ever advised to limit intake frequency of acute headache treatments. CONCLUSIONS: This study identified underdiagnosis of migraine, low use of migraine prophylaxis and triptans, and high prevalence of medication overuse among subjects seeking self-medication for regular headache. Community pharmacists have a strategic position in education and referral of these self-medicating headache patients.

Evaluation of three state-of-the-art metabolite prediction software packages (Meteor, MetaSite, and StarDrop) through independent and synergistic use.

The aim of this study was to evaluate three different metabolite prediction software packages (Meteor, MetaSite, and StarDrop) with respect to their ability to predict loci of metabolism and suggest relative proportions of metabolites. A chemically diverse test set of 22 compounds, for which in vivo human mass balance studies and metabolic schemes were available, was used as basis for the evaluation. Each software package was provided with structures of the parent compounds, and predicted metabolites were compared with experimentally determined human metabolites. The evaluation consisted of two parts. First, different settings within each software package were investigated and the software was evaluated using those settings determined to give the best prediction. Second, the three different packages were combined using the optimized settings to see whether a synergistic effect concerning the overall metabolism prediction could be established. The performance of the software was scored for both sensitivity and precision, taking into account the capabilities/limitations of the particular software. Varying results were obtained for the individual packages. Meteor showed a general tendency toward overprediction, and this led to a relatively low precision (∼35%) but high sensitivity (∼70%). MetaSite and StarDrop both exhibited a sensitivity and precision of ∼50%. By combining predictions obtained with the different packages, we found that increased precision can be obtained. We conclude that the state-of-the-art individual metabolite prediction software has many advantageous features but needs refinement to obtain acceptable prediction profiles. Synergistic use of different software packages could prove useful.

Factors associated with medication adherence to oral hypoglycaemic agents in different ethnic groups suffering from type 2 diabetes: a systematic literature review and suggestions for further research.

AIMS: To synthesize knowledge regarding the different factors that may influence adherence to oral hypoglycaemic agents in different ethnic groups through a systematic review of the literature. METHODS: Thirteen databases were searched and 1201 articles were screened by two authors independently from each other. Different quantitative study designs were included if the study population included at least one ethnic group other than White people, medication adherence was a dependent variable and a clear description was given of the method used to measure medication adherence. RESULTS: Demographic, disease-related and treatment-related, socio-economic and cultural factors were associated with medication adherence in the populations that were studied. However, to synthesize results, the number of studies was too small and the included studies differed too much with respect to their study designs and the ethnic groups that were studied. We discuss several methodological challenges with respect to measuring medication adherence, measuring ethnicity and study designs that need to be resolved to make future studies comparable. We propose methodological improvements for future research. CONCLUSION: Although medication adherence is an essential part of the diabetic regimen, little is known about the association between ethnicity and medication adherence and the underlying factors that could explain this association. More research is needed in which important methodological challenges will have to be faced.

[Management of COPD in community pharmacy]. / Traitement de la BPCO: quel est le rôle du pharmacien d'officine?

BACKGROUND: This observational study aimed to provide a detailed description of (i) drug therapy, (ii) drug adherence, (iii) inhalation technique, and (iv) health status of COPD patients recruited via community pharmacies. Based on these results, problem areas can be detected and targeted pharmacist interventions for improvement of COPD management could be developed. METHOD: We conducted a cross-sectional, observational study in 93 pharmacies (Belgium). Participants (n = 555) completed a questionnaire collecting personal characteristics, smoking history, influenza vaccination, COPD medication and side effects. Adherence to COPD maintenance medication was analysed 1 year-retrospectively through prescription refill rates. Inhalation technique was scored using a checklist. RESULTS: The COPD patients had a mean age of 68.6 yr, 73.7% were men and 37.2% were current smokers. The influenza vaccination status was significantly lower in patients aged < 65 yr (65.7%) than in patients aged > or = 65 years (86.2%) (p < 0.001). Fixed combinations of inhaled corticosteroids and long-acting beta2-agonists were the most frequently used COPD medications (75.4%). About 48% of patients was underadherent (< 80% adherence), 47% was adherent (80-120% adherence) and 5% was overadherent (> 120% adherence). Twenty-one % of patients made major inhalation technique errors with rescue medication; these were all errors in handling pressurized metered dose inhalers (pMDI's). CONCLUSION: This study on COPD management in primary care highlights 4 main aspects which could be improved: (i) drug adherence, (ii) inhalation technique with pMDI's, (iii) influenza vaccination in COPD patients < yr and (iv) smoking cessation.

Detection of potentially inappropriate prescribing in older patients with the GheOP³S-tool: completeness and clinical relevance.

OBJECTIVES: The Ghent Older People's Prescriptions community Pharmacy Screening (GheOP3S-) tool was recently developed as an explicit screening method to detect Potentially Inappropriate Prescribing (PIP) in the community pharmacy. We aimed to validate the GheOP3S-tool as an effective screening method for PIP. METHODS: All patients admitted to the acute geriatric ward of the Sint-Vincentius hospital (Belgium) were consecutively screened for inclusion (≥70 years,≥5 drugs chronically). PIP prevalence was evaluated by applying the GheOP3S-tool on the complete medication history. For each PIP-item, clinical relevance of the detected item, relevance of proposed alternative and subsequent acceptance by the treating geriatrician and a general practitioner were evaluated. Additionally, contribution to the current admission and preventability was assessed by the geriatrician. The completeness of a PIP-screening with the GheOP3S-tool was evaluated through comparison with the adapted Medication Appropriateness Index (aMAI). RESULTS: We detected 250 GheOP3S-items in 57 of 60 included patients (95%) (median: four PIP-items per patient; IQR: 3-5). Both the geriatrician and the general practitioners scored the clinical relevance of the detected items 'serious' or 'significant' in over 70% of cases. Proposed alternative treatment plans were accepted for 79% of the PIP-items (n = 198). The aMAI detected 536 items, of which 145 were also detected by the GheOP3S-tool. A total of 119 PIP-items were additionally detected by the GheOP3S-tool. CONCLUSION: The clinical relevance of the PIP-items detected with the GheOP3S-tool is high, likewise the acceptance rate of proposed alternatives.

Pharmaceutical compounding of orphan active ingredients in Belgium: how community and hospital pharmacists can address the needs of patients with rare diseases.

BACKGROUND: Pharmaceutical compounding of orphan active ingredients can offer cost-effective treatment to patients when no other drug product is available for a rare disease or during periods of drug product shortages. Additionally, it allows customized therapy for patients with rare diseases. However, standardized compounding formulas and procedures, and monographs are required to ensure the patients' safety. RESULTS: Standardized formulas and compounding procedures were developed for seven orphan active ingredients (L-arginine, sodium benzoate, sodium phenylbutyrate, L-carnitine, chenodesoxycholic acid, primaquine phosphate, pyridoxal phosphate) and one non-orphan molecule (sodium perchlorate) regularly compounded by hospital pharmacists for extemporaneous use. The stability of these formulations was evaluated over 3 months at refrigerated (5 °C) and standard storage conditions (25 °C/60%RH) using HPLC-based assays and a suitable shelf life was assigned to the formulations. Additionally, suitable analytical methods for quality control of formulations of pyridoxal phosphate and sodium perchlorate were developed as monographs for these components were not available in the European Pharmacopeia or United States Pharmacopeia. CONCLUSIONS: Availability of compounding formulas and protocols, as well as stability information, for orphan active ingredients can improve patients' access to treatment for rare diseases. Such data were collected for seven orphan active ingredients to treat patients with rare diseases when no other treatment is available. More efforts are needed to develop standardized formulas and compounding procedures for additional orphan active ingredients whose clinical efficacy is well-known but which are not available as products with a marketing authorization. Additionally, a legal framework at EU level is required to enable the full potential of pharmaceutical compounding for orphan active ingredients.