Evaluation of real-life dosing of oral medicines with respect to fluid and food intake in a Dutch-speaking population.

WHAT IS KNOWN AND OBJECTIVE: Oral drug administration is the most preferred route of drug administration. For some specific classes of drugs, recommendations regarding the intake of the drug product are provided by and approved in the summary of product characteristics (SmPC) after testing the oral drug product in clinical trials under strict and predefined conditions. The aim of this study was to investigate how certain classes of medicines are taken in a "real-life" setting in terms of concomitant fluid and food intake by a Dutch-speaking population in Flanders (Belgium). The outcome of this study was comprehensively discussed with literature data to evaluate the positive or negative consequences of their drug intake in daily life. METHODS: A retrospective and non-interventional study was set up by means of questionnaires completed by two different groups: children (ie 0-15 years) and (young) adults (ie 16 years and older). RESULTS AND DISCUSSION: In children, the co-administered volume increases with age because of a gradual switch from liquids to solid dosage forms. In adults, water was the most selected co-administered fluid and the preferred volume of intake was a half glass of liquid. WHAT IS NEW AND CONCLUSION: Results of the surveys clearly indicated that the majority of all participants took their medication with a sip or half glass of water. However, this was not the case for the youngest children, as their preferred formulations were liquids (eg solutions, suspensions) which do not require any extra intake of liquid. In the case of specific classes of drugs, real-life intake can still be improved, suggesting that the pharmacist's advice has an important influence on their administration of medicines.

[Adherence to chronic medication: also a frequent problem in Belgium!]. / L'observance thérapeutique des traitements chroniques: problématique pour les patients belges aussi!

Medication adherence in chronic conditions such as asthma, type 2 diabetes, heart failure, HIV and cancer appears to be a frequent problem. However, the literature on adherence in patients who use inhaled corticosteroids (ICS), oral hypoglycemic agents, drugs for heart failure, antiretrovirals or oral chemotherapy, contains little or no relevant data for Belgium. In the context of a Master thesis in Pharmaceutical care at KU Leuven, a quantitative study was performed to determine the prevalence of adherence to chronic medication in Belgium. This retrospective, cross-sectional study used a database containing refill data of a regional pharmacists' association (KLAV). Out of the 603 pharmacies affiliated with this association, all 50 pharmacies where HIV medication was delivered, were selected. Dispensing data from the selected pharmacies were collected from 01/07/2008 to 31/12/2009 for five pathologies, i.e.; asthma, type 2 diabetes, heart failure, HIV and cancer. Adherence (TT) was calculated with the Medication Refill Adherence (MRA) method. In order to determine whether there were associations between age, gender, drug class and adherence, Chi-square tests were used. Compared with the other patients, cancer patients were the most adherent in taking their drugs (median adherence rate = 88%). In addition, this was the only group in which the median adherence rate was above the set limit of 80%. The patients who were prescribed inhaled corticosteroids were the least adherent (median adherence rate = 38%). More than 50% of patients with asthma/COPD, heart failure and diabetes were classified as "under-users". Furthermore, the results showed a significant association within asthma patients between gender and adherence. In asthma, type 2 diabetes, heart failure and HIV patients there was a significant relationship between age and adherence and drug class and adherence. As the current study has some limitations, the results should be handled with caution. Nevertheless, the current study shows that also in Belgium there is a problem with medication adherence in chronic conditions, especially in asthma patients.

Incidence and drug treatment of emotional distress after cancer diagnosis: a matched primary care case-control study.

BACKGROUND: Emotional distress is common in cancer patients. This study aimed to describe, in the year after a cancer diagnosis: the incidence of anxiety, depression and excessive alcohol use; the pattern of these diagnoses and treatment over time; and the nature and duration of the prescribed treatment. METHODS: A matched case-control study was conducted using routinely collected primary care data from 173 Scottish general practices. A presumptive diagnosis of emotional distress (anxiety, depression and/or excessive alcohol use) was based on prescription data or diagnostic code. Prescriptions for psychotropic drugs were described in terms of drug class, volume and treatment duration. RESULTS: In total, 7298 cancer cases and 14 596 matched-controls were identified. Overall, 1135 (15.6%) cases and 201 (1.4%) controls met criteria for emotional distress (odds ratio 13.7, 95% confidence interval 11.6-16.1). Psychotropic drugs were prescribed in the 6 months following initial cancer diagnosis for 1066 (14.6%) cases and 161 (1.1%) controls. The volume and duration of anxiolytic and antipsychotic prescribing was significantly different between cases and controls. CONCLUSION: This study quantified the higher incidence of new emotional distress in cancer patients in the first year post diagnosis. Clinicians should be aware of the possibility of emotional distress at any time in the year after cancer diagnosis.

Factors determining social distance toward people with depression among community pharmacists.

OBJECTIVE: The aim of the present study was to measure stigma among community pharmacists regarding patients with depression, using social distance as a proxy measure. Furthermore, factors influencing stigmatization were identified. METHODS: A survey consisting of questions regarding social distance, cognitive attitude components, stereotypical beliefs and behavioural tendencies towards pharmaceutical care for patients with depression was carried out. The survey was completed by 149 community pharmacists with a response rate of 82%. Multiple linear regression analysis was applied to the results of the survey. RESULTS: Most pharmacists endorsed social distance towards patients with depression. The social distance further increased the more the situation described implied "social closeness". Age, depression care attitude, the stereotypical belief "danger to others" and the level of involvement pharmacists showed towards patients with depression were found to predict social distance. The present model explains 32.3% of the variance in social distance. CONCLUSION: The results showed that community pharmacists have a stigmatizing attitude towards patients with depression. The determinants found to influence these stigmatizing attitudes might be addressed when trying to reduce stigmatization of patients with depression.

Ajuga remota Benth.: from ethnopharmacology to phytomedical perspective in the treatment of malaria.

Treatment and control of malaria have become more difficult with the spread of drug-resistant parasites and insecticide-resistant mosquito vectors. In the search for new antimalarial drugs, ethnopharmacological sources should merit more attention. Establishing the safety of traditional herbal medicines, along with identifying their active principles, are essential steps in the production of a properly standardized and accessible herbal medicine. Phytochemical characterization could also serve as a base for the development of new chemical compounds. The genus of Ajuga belongs to the family Lamiaceae and contains at least 301 species. Many of these plants have been used in traditional medicine. Ajuga remota in particular is traditionally used as a herbal remedy for fever and infections, and is prescribed for malaria by 66% of the Kenyan herbalists. A large number of compounds have already been isolated from A. remota, including ergosterol-5,8-endoperoxide (6), ajugarin-I (1), 8-O-acetylharpagide (5) and several phytoecdysteroids. In vitro pharmacological studies have been conducted on constituents of A. remota of which some of them displayed a concentration-dependent inhibition of chloroquine-sensitive and -resistant Plasmodium falciparum and Mycobacterium tuberculosis. Inhibition of parasitaemia was demonstrated in mouse models with P. berghei, supporting the traditional use of the plant against malaria. In this state-of-the-art review, A. remota as a possible therapeutic tool for malaria is discussed.

[Medicine information for patients with a major depression at hospital discharge]. / Information sur les médicaments "sur mesure" pour des patients en etat dépressif. Rapport de thèse de doctorat.

This article provides an overview of several parts of a doctoral thesis on medicine information for patients with a major depression at hospital discharge. A review of the international literature showed that medicine information can increase knowledge and adherence. Inpatients would like to receive more information on the medicines prescribed. The GIPPOZ-study showed positive results on a few economic outcomes when a differentiated approach in providing information on antidepressants was applied. Follow-up calls of participants of the GIPPOZ-study yielded interesting qualitative findings on problems and perspective after discharge from hospital. The hospital pharmacists stressed the individual approach of patients during the GIPPOZ-study. Practice and health policy suggestions were formulated. Health care professionals should provide more information to patients on their medicines. Policy makers should guarantee a structure so that health care professionals can fulfill their role as provider of medication information.

Medication information for Flemish inpatients with major depression: evaluation and construct validity of the Consumer Information Rating Form.

BACKGROUND AND OBJECTIVES: Evaluating the quality of written medication information is a major topic of concern when patient pamphlets are developed. The objective of this study is to evaluate a patient pamphlet on selective serotonin reuptake inhibitors (SSRIs) by calculating Flesch-Douma readability scores and by applying the Consumer Information Rating Form (CIRF) to Flemish inpatients with major depression taking SSRIs. METHODS: The pamphlet was evaluated by calculating Flesch-Douma readability scores. The study enrolled patients with major depression taking SSRIs. Patient received a SSRI pamphlet and completed a self-administered structured questionnaire consisting of the adapted CIRF and the Hospital Anxiety and Depression Scale. Construct validity was explored by means of factor analysis and Cronbach's alpha. RESULTS AND DISCUSSION: The Flesch-Douma readability scores showed that the pamphlet was easy to read, had much interest in the reader and was very popular. The sample of 96 patients consisted of doubtful/definite cases in terms of anxiety (10.65 +/- 4.90) and doubtful cases in terms of depression (8.91 +/- 5.23). Using the CIRF, patients assigned positive scores to comprehensibility, utility and design quality of the pamphlet. Factor analysis on the original CIRF confirmed the three original factors (P < 0.001). Cronbach's alpha of factors ranged from 0.69 to 0.83. CONCLUSION: The SSRI pamphlet is of good quality. Our study supported the construct validity of the CIRF to Flemish inpatients with major depression.

Pharmacotherapy of allergic rhinitis: a pharmaco-economic approach.

This article reports on a systematic literature review of the costs of allergic rhinitis (AR), the economic value of pharmacotherapy of AR, and the factors affecting costs and economic value of pharmacotherapy. Included studies had carried out a cost-of-illness analysis, cost analysis, cost-effectiveness, cost-utility or cost-benefit analysis. Allergic rhinitis imposes a substantial economic burden on society, with indirect costs of productivity loss being larger than the direct healthcare costs. Cost estimates were biased because of difficulties of diagnosis; exclusion of patients who do not seek healthcare; exclusion of over-the-counter medication; difficulties in estimating productivity loss. There is limited evidence on costs of seasonal/perennial and intermittent/persistent AR. Little is known of the economic value of pharmacotherapy of AR, although levocetirizine appears to be cost-effective as compared with placebo. Economic evaluations suffered limitations from small sample sizes, short trial duration, lack of standardized effectiveness measure, restricted scope of costs. Finally, the economic value of pharmacotherapy of AR is influenced by the perspective of the economic evaluation, relative effectiveness and costs of available drugs, patient compliance with treatment.

Clinical and economic analysis of antimicrobial therapy of chronic obstructive pulmonary disease exacerbations.

The aim of the study was to analyse the clinical and economic indicators of the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD). The study focused specifically on antimicrobial therapy and the use of fluoroquinolones in the management of exacerbations. Data on the consumption of antibiotics to treat exacerbations in ambulatory care were derived from IMS Health. Also, an observational, retrospective analysis was carried out of patients who entered the clinical pathway for COPD exacerbations in University Hospitals Leuven. IMS Health data showed that there is a trend towards the increasing use of broad-spectrum penicillins and fluoroquinolones, and decreasing use of tetracyclines in the treatment of COPD exacerbations in ambulatory care in Belgium in the first half of the 2000s. The observational analysis enrolled 267 patients who were hospitalised between October 2000 and October 2005 to manage 359 exacerbations according to the clinical pathway. Median length of stay per exacerbation amounted to 10 days. Mean quality of life associated with an exacerbation was 74 using the Chronic Respiratory Disease Questionnaire. Median costs of hospital treatment amounted to euro5514 (third-party payer reimbursement and patient co-payment) per exacerbation. Treatment costs were driven by hospital stay (75% of total costs), diagnostic and laboratory tests (20%) and medication (5%). Antibiotics played a role in the hospital management of 75% of exacerbations. Fluoroquinolones were used to treat more severe exacerbations. Treatment of acute exacerbations of COPD imposes a significant clinical and economic burden on patients, the healthcare system and the society.

Follow-up of antibiotic prophylaxis: impact on compliance with guidelines and financial outcomes.

In order to enhance the quality of antibiotic use, a new financial system was introduced in Belgium in 1997, which links reimbursement of antibiotic costs incurred during prophylaxis in surgery and obstetrics to compliance with evidence-based guidelines. At University Hospitals Leuven (UHL), this reimbursement scheme was supplemented with a follow-up programme in 2001 that informs physicians of their compliance with the guidelines and outlines the financial consequences of their use of prophylactic antibiotics. The aim of this paper is to evaluate the impact of the follow-up programme developed and implemented by a clinical pharmacist at UHL. The analysis drew on data on consumption and costs of antibiotics used in standard prophylaxis that were retrieved from patient invoices. Both financial outcomes and results on consumption patterns of antibiotics point to an increasing compliance with guidelines. An average annual loss of 92,353 Euro associated with prophylactic antibiotic use prior to the implementation of the follow-up programme evolved into a profit of 27,269 Euro following its introduction. The share of consumption of prophylactic antibiotics held by cefazolin and metronidazole, the two main antibiotics recommended by the guidelines, increased substantially or remained stable as a result of the follow-up programme, whereas the shares held by other antibiotics generally fell. Moreover, the range of antibiotics consumed during standard prophylaxis narrowed. This follow-up programme thus reduced antibiotic costs, improved profitability and increased physician compliance with guidelines.

Treating respiratory tract infections in ambulatory care in Belgium: fluoroquinolone consumption and resistance development.

This study analyses consumption patterns of fluoroquinolones in treating respiratory tract infections in ambulatory care in Belgium and describes susceptibility of Streptococcus pneumoniae isolates to fluoroquinolones. Consumption data were obtained from IMS Health. Pneumococcal resistance was investigated in 600 blood isolates collected from 1998 to 2003. Although consumption of fluoroquinolones has increased rapidly over the last decade, this trend does not seem to persist more recently. Fluoroquinolones were mainly used to treat urinary and lower respiratory tract infections, but rarely in the management of upper respiratory tract infections. The use of new fluoroquinolones (levofloxacin, moxifloxacin) and the ongoing use of older fluoroquinolones have not led to increased pneumococcal resistance, which remained below 1% for levofloxacin and was 0% for moxifloxacin.

[St. Mary's Thistle: an overview]. / Le Chardon Marie: un aperçu.

St. Marys Thistle has been approved for registration as a regular medicine in Belgium. The hepatotropic properties of this plant are rather difficult to evaluate objectively. Mortality rate in case of life-threatening hepatic diseases is the most objective parameter. Legalon is the only drug registered in Belgium. It has a prescription only status. The plant Silybum marianum is a thistle and as a consequence belongs to the Compositae. There is a limited production of St.-Marys Thistle in Pajottenland, west of Brussels. The seeds are exported to Italy in order to extract silymarine, a mixture of flavonolignanes with antioxidant properties. Silymarine has been tested in living animals deliberately intoxicated with mushroom toxins, medicines, heavy metals or toxic organic solvents. Preventive as well as curative activity has been confirmed. Silymarine accumulates in the liver, which is also the target organ in therapy. Silymarine improves the prognosis after accidental ingestion of the toxic Amanita phalloides. Patients infected with hepatitis B and C might benefit from Silymarine, but more data have to be generated. Silymarine given to patients with liver damages by alcohol lowers the death toll. The drug has a general safety pattern comparable to placebo.

Antimalarial activity of Ajuga remota Benth (Labiatae) and Caesalpinia volkensii Harms (Caesalpiniaceae): in vitro confirmation of ethnopharmacological use.

Field trips to herbalists' practices in an area about 200 miles around Nairobi (Kenya) enabled us to make a list of medicinal plant species preferentially used to treat malaria. Ajuga remota and Caesalpinia volkensii were further investigated as being the most frequently used species. Aqueous decoctions, ethanol macerates, and petroleum ether, methanol and water Soxhlet extracts of these plants were further tested for their in vitro antimalarial properties in a chloroquine sensitive (FCA/20GHA) and resistant (W2) strain of Plasmodium falciparum. The activity was assessed by the parasite lactate dehydrogenase (pLDH) assay method. There was a concentration-dependent inhibition by the vegetal extracts of both plants. The IC(50) of the most active A. remota extract (ethanol macerate) was 55 and 57 microg/ml against FCA/20GHA and W2, respectively. For C. volkensii, it was the Soxhlet-water extract which was most active against FCA/20GHA with an IC(50) of 404 microg/ml while the petroleum ether extract exhibited the most activity against W2 with an IC(50) of 250 microg/ml. Further phytochemical work is being done in order to identify the active principles.

Hypoglycemic, anticomplement and anti-HIV activities of Spathodea campanulata stem bark.

Spathodea campanulata stem bark decoction (SCD) has shown hypoglycemic activity in mice. It was separated by column chromatography into different fractions, which were evaluated for their hypoglycemic, anticomplement and anti-HIV activities. The most polar fraction exerted by far the most prominent effect in different biological models.

Renal hemodynamics and blood flow autoregulation during acute cyclooxygenase inhibition in male rats.

After the acute inhibition of prostanoid synthesis, adjustments of renal hemodynamics may not be characterized immediately. Therefore, time-related effects of indomethacin on hemodynamics and renal blood flow (RBF) autoregulation were studied in anesthetized euvolemic male rats injected intravenously with vehicle, indomethacin (3, 4, or 5 mg/kg body wt), or meclofenamate (4 or 5 mg/kg body wt). Hemodynamics and RBF autoregulation were not influenced by vehicle injection, nor by time (n = 6). In contrast, mean arterial pressure (MAP) decreased significantly from 117 +/- 4 to 103 +/- 3 mmHg, and RBF progressively and significantly increased from 8.00 +/- 0.34 to 9.17 +/- 0.50 ml/min in the 3 mg/kg body wt indomethacin group (n = 8). Treatment with the higher doses of indomethacin (n = 9) or meclofenamate (n = 6) did not change RBF, while MAP decreased by 15 mmHg. A time-dependent significant enhancement of RBF autoregulatory efficiency was found in the drug-treated rats. Changes in renal function and reductions of prostanoid excretion in urine, of plasma renin activity, or serum aldosterone were similar in the nonsteroidal antiinflammatory drug groups. In conclusion, our findings demonstrate important time-related adjustments of renal hemodynamics in male rats treated with indomethacin, especially with the lower dose (3 mg/kg body wt iv). The factor(s) responsible for the hemodynamic changes remains unknown.

In vitro effects of tremorgenic mycotoxins.

Paxilline was isolated from Penicillium paxilli (NRRL 6110). It was studied together with penitrem B and verruculogen in the electrically stimulated guinea pig ileum. All three mycotoxins enhanced the electrically induced twitch contractions, without influencing the contractions provoked by exogenous acetylcholine. The effect of the mycotoxins could be greatly diminished by hyoscine. The possible mechanism of action of these substances in this in vitro model is discussed. The electrically stimulated guinea pig ileum could be useful in the detection and estimation of the biological activity of tremorgenic mycotoxins.

Prostacyclin/thromboxane ratio in human breast cancer.

In this prospective follow-up study the prognostic value of the tumor prostacyclin/thromboxane ratio in human breast carcinoma was investigated. The stable degradation products of prostacyclin and thromboxane (6-keto-PGF1 alpha and TXB2, respectively), were measured by radio-immunoassay in homogenized primary tumours from 29 patients with primary non-metastatic breast cancer. The median follow-up was 43 months (range 24-58 months). Patients with recurrent disease or patients who died of breast cancer had a significantly higher 6-keto-PGF1 alpha/TXB2 ratio than the disease-free survivors (p = 0.018 and p = 0.047, respectively). There was no significant difference in the 6-keto-PGF1 alpha and TXB2 levels. These data indicate that the prostacyclin/thromboxane balance in the tumour might be a prognostic factor in breast cancer. Prostanoid may contribute to metastasis in breast cancer, but the problem is complex because the different prostaglandins have numerous actions that may produce both undesirable and desirable effects.