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.

[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.

[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.

Medication management among home-dwelling older patients with chronic diseases: possible roles for community pharmacists.

OBJECTIVE: To describe medication management among home-dwelling older adults. These data should allow us to identify potential problems and to indicate target areas for community pharmacist intervention. DESIGN: Cross-sectional observational study. SETTING: Community pharmacies (n=86) in Belgium. PARTICIPANTS: Home-dwelling older adults using at least one chronic medicine (n=338). MEASUREMENTS: Data on drug use were taken from the electronic pharmacy databases, while drug adherence was measured by pill count, self-report and estimation by GP and pharmacist. Drug knowledge and practical drug management capacity were assessed by patient interview and questionnaire, respectively. RESULTS: The study population (n=338) used a median of 5 chronic drugs per patient. Half of our sample (n=169) used psychotropic medication chronically, mainly benzodiazepines. In 100 patients (29.6%) at least one drug-drug interaction of potential clinical significance was observed. The overall mean adherence per patient was very high (98.1%), but 39.6% of individuals was underadherent with at least one medication. Seventy-six % of patients had an acceptable knowledge of the indication for at least 75% of their medication. In nearly 15 % of the study population cognitive impairment was suspected by the mini-cog test. The participants reported several practical problems with drug taking: difficulties with vision (32.0%), blister opening (12.1%), tablet swallowing (14.8%), tablet splitting (29.7% [represents % of patients who have to split tablets]) and distinction between different drug packages (23.4%). CONCLUSION: This study identified the following aspects of medication management by home-dwelling older adults that could be improved by pharmaceutical care services: (i) assistance of cognitively impaired patients, (ii) management of practical drug taking problems, (iii) DDI screening, (iv) drug adherence, and (v) chronic benzodiazepine use.

[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.

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.

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.

Effectiveness of a community pharmacist intervention in diabetes care: a randomized controlled trial.

WHAT IS KNOWN AND OBJECTIVE: There is little evidence from well-designed randomized controlled trials of the impact of community pharmacist intervention on the clinical management of patients with type 2 diabetes. It is also not known how sustainable any observed effects on glycaemic control are, over time. This study was initiated to address both these issues. METHODS: A 6-month, randomized, controlled parallel-group trial in 66 community pharmacies was conducted in Belgium. Patients were randomly assigned to receive usual pharmacist care (n = 135) or a predefined pharmacist intervention (n = 153). The intervention mainly focused on correct medication use, medication adherence and healthy lifestyle promotion. Primary outcome was glycaemic control, as measured by fasting plasma glucose and HbA1c. Sustainability of changes in glycaemic control was assessed by additional glucose measurements 18 months after the end of the study. RESULTS AND DISCUSSION: The intervention significantly reduced HbA1c (between-group difference: 0·5%, P = 0.009). The largest impact on HbA1c was observed when pharmacotherapy changes (i.e., type and/or dose of hypoglycaemic agents) initiated by the physician were sustained with pharmaceutical care: HbA1c was reduced by 1·05% in the intervention group, whose medication was changed, compared with a reduction of 0·02% in the therapy-modification only, group. It was also found that the diabetes education program resulted in improved self-management and better knowledge of diabetes. Eighteen months after the end of the formal study period, the mean HbA1c of the intervention group did not differ significantly from the control group (7·4% vs. 7·2%). WHAT IS NEW AND CONCLUSION: This study provides new evidence, from a randomized controlled trial, of the beneficial effect of community pharmacist intervention in the clinical management of type 2 diabetic patients. However, questions remain about the sustainability of the observed improvements.

[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.

[Self-medication of upper gastrointestinal symptoms: a community pharmacy study]. / Automédication des troubles gastriques: étude dans les pharmacies belges.

BACKGROUND: Upper gastrointestinal (GI) symptoms are a common reason for self-treatment with over-the-counter (OTC) medication. However, data on the typology of GI complaints for which individuals seek self-medication and, more importantly, on the prevalence of alarm symptoms in this population are scarce. OBJECTIVE: This study aimed to investigate: (i) the nature of GI symptoms people intend to self-medicate, (ii) prevalence of alarm symptoms, (iii) compliance with referral advice given by the pharmacist, and (iv) self-reported efficacy and frequency of use of OTC medication for minor complaints. METHODS: This descriptive study was performed in 63 community pharmacies. Participants (n=592, aged 18-80 y) completed a questionnaire to assess symptom characteristics and previous medical consulting. Based on this information, the pharmacist referred subjects to a physician or advised self-treatment. Four weeks later, participants were presented a follow-up questionnaire, evaluating compliance with referral advice or efficacy of self-treatment. RESULTS: The most frequently reported GI complaints were burning retrosternal discomfort (49.2%), acid regurgitation (53.2%) and bothersome postprandial fullness (51.2%). At least 1 alarm symptom was present in 22.4% of the individuals, difficulty in swallowing being the most prevalent one (15.4%). Although twenty-one percent of the customers were referred, only 51.7% of these actually contacted a physician. Almost all of the remaining customers who were advised self-treatment reported symptom relief with the obtained OTC drug (95.1%). CONCLUSIONS: Mild GI symptoms will mostly resolve with self-treatment. Yet, the value of pharmacist counselling on OTC treatment should be recognized, as community pharmacists can play an important role in

Effectiveness of pharmacist intervention for asthma control improvement.

Education on optimal medication use is an essential strategy to improve asthma control. The current authors investigated whether pharmacist interventions, focused on appropriate use of asthma medication and tailor-made to the patient's current asthma control, would improve asthma control in adult patients. A 6-month randomised, controlled, parallel-group trial was conducted in 66 community pharmacies in Belgium. Patients were randomly assigned to receive usual pharmacist care (n = 94) or a pre-defined pharmacist intervention (n = 107). This intervention mainly focused on improving inhalation technique and medication adherence. Primary outcome was the level of asthma control, as assessed by the Asthma Control Test (ACT). Mean ACT scores did not change from baseline for both study groups. However, a pre-defined subgroup analysis of patients having insufficiently controlled asthma at baseline showed that the intervention had significantly increased the ACT score after 6 months compared with usual care. The intervention also reduced, for the complete study group, reliever medication use and the frequency of night-time awakenings due to asthma. Inhalation technique and adherence to controller medication were significantly better in the intervention group. In conclusion, pragmatic community pharmacy-based programmes can significantly improve therapeutic outcomes in adult asthma patients.

Medication use and disease control of asthmatic patients in Flanders: a cross-sectional community pharmacy study.

The aim of this study was to describe medication use and disease management of asthmatic patients and to evaluate the usefulness of the Asthma Control Test (ACT) in community pharmacies. In 54 Flemish community pharmacies 166 asthmatic patients were included in the study. At inclusion, the study persons completed a survey to assess subject characteristics, symptoms and asthma attacks, and peak expiratory flow (PEF) was measured. Furthermore, the actual level of asthma control was assessed by ACT, a clinically validated measure of asthma control. Prescribed medicine data of the patients were 1 year retrospectively analysed from the prescriptions. Mean age of the sample was 36.8 year, 23% were smokers. As maintenance treatment, 63% of the patients used a combination product containing an inhaled corticosteroid and a long-acting beta2-agonist in a single inhaler. According to ACT, 49.1% of the patients were insufficiently controlled. Only 4.9% of the patients had a maximal ACT score of 25, indicating complete asthma control; 46.0% of the study population obtained an ACT score between 20 and 24, meaning that their asthma is well controlled. In contrast, 30.7% of the patients had a score between 15 and 19, indicating uncontrolled asthma. In all, 18.4% obtained ACT scores of less than 15, meaning that their asthma was seriously out of control and necessitating referral to their general practitioner or lung specialist. Importantly, the correlation between the self-perceived level of asthma control and the objective assessment of the asthma control level was poor: 82.3% of the patients believed their asthma to be totally or well controlled, while this was the fact for only 50.9% of the patients. In conclusion, the ACT appears to be a useful tool to determine rapidly and accurately the level of asthma control in patients presenting at community pharmacies.