Impact of frailty status on the cost of drugs and dietary supplements prescribed to nursing home residents: the SENIOR cohort.

BACKGROUND: The financial impact associated with drug consumption has been poorly investigated among frail subjects and, specifically, in nursing home settings. AIMS: To determine the association of the average monthly cost of the drugs and dietary supplements consumed by nursing home residents with their frailty status. METHODS: This is an analysis of the first follow-up year of the SENIOR cohort. All participants were classified into "frail" or "non-frail" categories according to Fried's criteria at baseline. Monthly bills from the pharmacy were analysed to determine the association between the average monthly cost of the drugs and dietary supplements consumed and frailty status. RESULTS: A sample of 87 residents (83.8 ± 9.33 years and 75.9% women) from the SENIOR cohort was included. The prevalence of frailty was 28%. The median number of medications consumed each day was 9 (6-12) (no difference between frail and non-frail subjects; p = 0.15). The overall median monthly cost was € 109.6, of which 49% was covered by Belgian social security and the remaining balance was paid by the patient. When comparing the drug expenses of the frail subjects and the non-frail subjects, the overall average monthly cost did not differ between the 2 groups (p = 0.057). Nevertheless, the expenditure remaining to be paid by the residents, after the Belgian social security intervention, was significantly higher among the frail residents (€ 65.7) than among the non-frail residents (€ 47.6; p = 0.017). CONCLUSIONS: Frailty status has an impact on the expenditures related to the consumption of drugs.

Step-down of inhaled corticosteroids in non-eosinophilic asthma: A prospective trial in real life.

BACKGROUND: While non-eosinophilic asthmatics are usually considered poorly responsive to inhaled corticosteroids (ICSs), studies assessing a step-down of ICS in this specific population are currently lacking. OBJECTIVES: To assess the proportion of non-eosinophilic asthmatics in whom ICS may be withdrawn without any clinical degradation and to determine the predictive markers of a failure to stop treatment with ICS. METHODS: This prospective study was completed by 36 non-eosinophilic asthmatics, defined by sputum eosinophils <3% and blood eosinophils <400/µL. In these patients, whichever the baseline asthma control level, the dose of ICS was gradually reduced every 3 months until they met the failure criteria or successfully discontinued ICS for 6 months. The failure criteria were an ACQ score ≥1.5 with an increase from baseline >0.5 or a number of severe exacerbations during the study which was greater than the number during the year prior to the baseline visit. Receiver-operating characteristic (ROC) curves were constructed to assess predictors of a failure to stop ICS. This study is registered with ClinicalTrials.gov, number NCT02169323. RESULTS: In 14 patients (39%), ICSs were completely withdrawn, and in 10 further patients (28%), ICS were stepped-down to a reduced ICS dose without any deterioration of asthma control and exacerbation rate. Baseline predictors of a failure to stop ICS were a greater age (area under ROC curve [ROC AUC] and [95% CI]: 0.77 [0.62-0.93]) and elevated blood eosinophils (ROC AUC [95% CI]: 0.77 [0.61-0.93]). After the first step-down of ICS, the best predictor was an elevated blood eosinophil count (ROC AUC [95% CI]: 0.85 [0.72-0.99]). CONCLUSIONS & CLINICAL RELEVANCE: Withdrawing or reducing the dose of ICS is feasible in two-thirds of non-eosinophilic asthmatics irrespective of baseline asthma control. An elevated blood eosinophil count may predict the failure to stop ICS.

Quality of documentation on antibiotic therapy in medical records: evaluation of combined interventions in a teaching hospital by repeated point prevalence survey.

This study aimed to improve the quality of documentation on antibiotic therapy in the computerized medical records of inpatients. A prospective, uncontrolled, interrupted time series (ITS) study was conducted by repeated point prevalence survey (PPS) to audit the quality of documentation on antibiotic therapy in the medical records before and after a combined intervention strategy (implementation of guidelines, distribution of educational materials, educational outreach visits, group educational interactive sessions) from the antimicrobial stewardship team (AST) in the academic teaching hospital (CHU) of Liège, Belgium. The primary outcome measure was the documentation rate on three quality indicators in the computerized medical records: (1) indication for treatment, (2) antibiotics prescribed, and (3) duration or review date. Segmented regression analysis was used to analyze the ITS. The medical records of 2306 patients receiving antibiotics for an infection (1177 in the pre-intervention period and 1129 in the post-intervention period) were analyzed. A significant increase in mean percentages in the post-intervention period was observed as compared with the pre-intervention period for the three quality indicators (indication documented 83.4 ± 10.4 % vs. 90.3 ± 6.6 %, p = 0.0013; antibiotics documented 87.9 ± 9.0 % vs. 95.6 ± 5.1 %, p < 0.0001; and duration or review date documented 31.9 ± 15.4 % vs. 67.7 ± 15.2 %, p < 0.0001). The study demonstrated the successful implementation of a combined intervention strategy from the AST. This strategy was associated with significant changes in the documentation rate in the computerized medical records for the three quality indicators.

[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.

[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.

[PERSONALIZED TREATMENT OF ASTHMA: THE ISSUE OF ANTI-INTERLEUKIN-5 ANTIBODIES]. / TRAITEMENT PERSONNALISÉ DANS L'ASTHME: le cas des anticorps monoclonaux dirigés contre l'interleukine-5.

Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia. When administered monthly by intravenous or subcutaneous injection in severe eosinophilic asthmatic patients, they reduce severe exacerbation rate by 50 %, improve asthma control and quality of life, and have an oral glucocorticoids sparing effect in those requiring oral corticoids as maintenance therapy.

[A new website with evidence-based pharmaceutical information]. / Presentation d'un nouveau site de donnèes probantes pharmaceutiques.

Aware of the difficult choices that health policy makers face and the desire to develop pharmaceutical care, the Pharmacy Practice Research Unit team from the CHU Sainte-Justine examined evidence about the role and the impact of pharmacists. This research took the form of a structured approach to review the evidence from the literature. A website was designed and programmed to ensure effective knowledge sharing (http://impactpharmacie.org). The site lists evidence of the role and impact of the pharmaceutical activities, in both inpatient and outpatient settings. The site lists twelve articles from Belgian literature for hospital and community practice. Four positive outcomes of pharmaceutical interventions were recorded. This site can help to foster reflection and action surrounding the development of clinical pharmacy in Belgium.

[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.

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.

[Therapeutic adherence in elderly]. / Observance thérapeutique en gériatrie.

Therapeutic adherence can be defined as the degree of concordance between the behaviour of a person in relation with drugs prescription and medical recommendations. It represents the ability of people to follow a treatment. Bad adherence is frequent in geriatric patients. The behaviour of the patient is important but the role of the prescriptor and distributor of the drugs should also be emphasized. A bad adherence is responsible for iatrogenic consequences, which has a great impact on the functionality of the old person, but also on the cost and organization of care. Therapeutic education, a standardised method to help the patient take care of his own treatment, must be developed. The aims and means should be clearly efined. The patient himself must be involved and human or material sources of help must be sought.

[Clinical inertia in geriatrics]. / Prescription inappropriée chez la personne agée: une forme d'inertie thérapeutique? Généralités et opportunités pour la pharmacie clinique en gériatrie.

Therapeutic inertia is a phenomenon with multiple etiologies, characterized by a "lack of initiation or modification of therapy when appropriate" and mainly affecting common chronic diseases (hypertension, diabetes, dyslipidemia). Caused by various processes including the lack of clinical evidence for the elderly, it can lead, in the elderly fragile by nature, to inappropriate prescribing. In a multidisciplinary approach, integrating the expertise of a pharmacist in the health care team improves the pharmacotherapeutic management of the geriatric patient.

Oral bioavailability in sheep of albendazole from a suspension and from a solution containing hydroxypropyl-beta-cyclodextrin.

Albendazole (ABZ) is a benzimidazole derivative with a broad spectrum of activity against human and animal helminthe parasites. ABZ has a very poor aqueous solubility. This study shows that hydroxypropyl-beta-cyclodextrin (HP-beta-CD) is able to form inclusion complexes with ABZ and that is able to increase its aqueous solubility. A synergistic effect exists between HP-beta-CD and citric acid. The combination of HP-beta-CD (200 mM) and citric acid (50 mM) allows dissolution of more than 1.5 mg of ABZ per ml. The aim of this study is the in vivo evaluation in sheep of a solution of the inclusion complex of ABZ with HP-beta-CD in comparison with a suspension of the same drug. A significant (P<0.05) increase in the relative bioavailability is obtained with the solution containing the ABZ-HP-beta-CD complex as measured by ABZSO plasma levels. The area under the curve (AUC(0--> proportional, variant )) of the solution is 37% higher than that obtained with the suspension. Likewise the peak plasma concentration (C(max)) is twice that of the solution while the time to reach C(max) (T(max)) is reduced.

Molecular modeling study of beta- and gamma-cyclodextrin complexes with miconazole.

Different authors have demonstrated the inclusion of miconazole in cyclodextrins (CD). Miconazole can be included in the CD cavity both in the neutral and in the ionized form. The present study tries to understand which fragment of the miconazole molecule is involved in the inclusion. Austin Model 1 approximate molecular orbital calculations have been performed on several complexes between beta-cyclodextrin (betaCD) or gamma-cyclodextrin (gammaCD) and miconazole in the ionized and the non-ionized forms of the two R and S enantiomers in three different orientations. We observed that betaCD is a good vehicle to transport miconazole which can be very easily released. The complexation energy between miconazole and betaCD is not very high but the entropic factor has a great incidence on the stability of the formed complex. The inclusion of the dichlorobenzene-CH(2)-O- and of the imidazole part of the S isomer gives rise to the most probable complex in acidic conditions (ionized miconazole). Nevertheless, the inclusion should be considered as a dynamic process in which different parts of the molecule could be alternatively included in betaCD. The present work demonstrates the high capability of deformation of betaCD which could easily accommodate several types of ligand. By opposite, the cycle extension in gammaCD leads to a more rigid vehicle with regards to miconazole.

Comparison of the IV pharmacokinetics in sheep of miconazole-cyclodextrin solutions and a micellar solution.

The pharmacokinetics of miconazole were studied after intravenous administration to six sheep (4 mg/kg) of three aqueous solutions: a marketed micellar solution containing polyoxyl-35 castor oil (Daktarin IV(R)) was compared with two solutions both containing 50 mM lactic acid and a cyclodextrin derivative (100 mM HP-betaCD or 50 mM SBE7-betaCD). The aim of this work was to demonstrate that these cyclodextrin derivatives (CDs) have no effect on the pharmacokinetics of miconazole by comparison with the micellar solution. The plasma concentration time curves have shown that there is no significant difference between the three solutions.

Inclusion of piroxicam into beta-cyclodextrin by means of supercritical carbon dioxide: thermal, spectroscopic and physicochemical studies.

The preparation of a piroxicam-beta-cyclodextrin inclusion compound using supercritical CO2 was investigated. The solubility piroxicam in supercritical CO2 was determined. The influence of the temperature, the pressure and the time of exposure on the inclusion rate were studied and a complete inclusion was achieved by keeping a physical mixture of piroxicam and beta-cyclodextrin (1:2.5 mol/mol) for 6 hours at 150 degrees C and 150 bar of CO2. This complex was characterised by Differential Scanning Calorimetry and Fourier Transform Infrared Spectrometry. Supercritical carbon dioxide may prove to be a novel useful complexation method of non-polar drugs into beta-cyclodextrin.

A comparative study of the antimycotic activity of a miconazole HP-beta cyclodextrin solution and a surfactant solution.

The antimycotic activity of a new parenteral solution containing miconazole was compared to that of a marketed solution (Daktarin IV solution). This solution has been withdrawn from the belgian market probably because of the toxic effects related to the presence of polyoxyl 35 castor oil. We propose a new formulation containing 10 mg of miconazole per ml (as the marketed solution), in combination with HP-beta cyclodextrin and lactic acid. The MIC of these two solutions were determined by broth microdilution method (following the NCCLS guidelines) against 15 yeasts and 16 filamentous fungi isolates. This study showed that MIC obtained with these two solutions are not significantly different. In vitro, the cyclodextrin solution has the same antimycotic activity as the Daktarin IV solution and can be proposed as a safe and effective parenteral solution to replace the previous surfactant solution.

Application of supercritical carbon dioxide for the preparation of a piroxicam-beta-cyclodextrin inclusion compound.

PURPOSE: Piroxicam is a poorly soluble NSAID, whose solubility is enhanced when included into beta-cyclodextrin. The preparation of a piroxicam-beta-cyclodextrin inclusion compound using supercritical CO2 was investigated. METHODS: The solubility and the stability of piroxicam in supercritical CO2 were determined. Then, the influence of the temperature, the pressure and the time of exposure on the inclusion rate was studied. RESULTS: The solubility of piroxicam varied over a wide range depending on the temperature and pressure (from 0.006 to 1.500 mg/g of CO2). The temperature and the time of exposure had a great influence on the inclusion yield, while pressure did not and a complete inclusion was achieved by keeping a physical mixture of piroxicam and beta-cyclodextrin (1:2.5 mol/mol) for 6 hours at 150 degrees C and 15 MPa of CO2. This complex was characterized by Differential Scanning Calorimetry, differential solubility and Fourier Transform Infrared Spectrometry. CONCLUSIONS: Supercritical carbon dioxide may prove to be a novel useful complexation method of drugs into beta-cyclodextrin.

In vitro comparison of the antimycotic activity of a miconazole-HP-beta-cyclodextrin solution with a miconazole surfactant solution.

The antimycotic activity of a new parenteral solution containing miconazole was compared with that of a marketed solution (Daktarin IV solution). This solution has been withdrawn from the Belgian market, probably because of toxic effects related to the presence of polyoxyl 35 castor oil. We propose a new formulation containing miconazole (10 mg/mL) (like the marketed solution), in combination with hydroxypropyl-beta-cyclodextrin and lactic acid. The MICs of these two solutions were determined by a broth microdilution method (based on NCCLS guidelines) for 67 yeasts and 50 filamentous fungi isolates. This study shows that the MICs obtained with these two solutions are not significantly different.