Fred H. P. De Koning

Pharmacist-Based Medication Review Reduces Potential Drug-Related Problems in the Elderly The SMOG Controlled Trial

AbstractBackground: The high prevalence of drug-related problems (DRPs) in the elderly, occurring as a result of multiple drug use combined with age-related changes in pharmacokinetics and pharmacodynamics, is a well known phenomenon. However, effective intervention strategies are uncommon. Objective: A pharmacy-based controlled trial (SMOG [Screening Medicatie Oudere Geneesmiddelgebruiker; Screening Medications in the Older Drug User]) was performed to investigate whether a community pharmacist-led intervention reduces the number of potential DRPs in patients aged ≥65 years using six or more drugs concomitantly. Methods: This intervention study was conducted from June 2002 until June 2003 in 16 community pharmacies in the Netherlands. Medication assessment was undertaken in elderly patients aged ≥65 years using six or more drugs concomitantly on the date of inclusion. Ten types of potential DRPs were determined and grouped into the following three categories: (i) patient-related potential DRPs: non-compliance; (ii) prescriber-related potential DRPs: expired indication, therapeutic duplication, inappropriate dosage (over- and under-dosage), off-label use, undertreatment, inconvenience of use; and (iii) drug-related potential DRPs: contraindications, drug-drug interactions, drug treatment of adverse drug reactions.A list of recommended changes in medication was compiled by the pharmacist for the patients in the intervention group. Recommendations for medication change were discussed with the general practitioner (GP). Four months after the date of inclusion, the medications of each patient were again reviewed and screened for potential DRPs. The primary outcome corresponded to the change in the number of potential DRPs; the secondary outcome was related to the change in number of used medications between the intervention group and the control group at baseline and 4 months later. Results: A total of 174 patients were analysed: 87 patients in the intervention arm and 87 patients in the usual care arm. After a 4-month period, we observed a significant reduction in the mean number of DRPs per patient (mean difference −16.3%; 95% CI −24.3, −8.3). The mean number of drugs per patient was not significantly reduced (mean difference −4.7%; 95% CI −9.6, 0.2). Conclusion: This study showed a positive influence of the community pharmacist in reducing potential DRPs in the elderly. Future interventions should also focus on actual outcomes, including quality of life, morbidity and mortality.

The association between antidepressant use and disturbances in glucose homeostasis: evidence from spontaneous reports.

ObjectivesDepression is common in patients with diabetes, and the use of antidepressants may impair glycaemic control. We assessed the association between antidepressant use and hyper- and hypoglycaemia.MethodsBased on spontaneous reports listed in the World Health Organization (WHO) Adverse Drug Reaction Database, a case-control study was conducted. The study base consisted of all adverse drug reactions (ADRs) ascribed to antidepressants, antipsychotics and benzodiazepines between 1969 and 2005. Cases were defined as reported ADRs classified as hyper- or hypoglycaemia and separated in different study populations. All other reports were considered as controls. Exposure to antidepressants was the primary determinant investigated. Benzodiazepines and antipsychotics were chosen as reference groups. Potential confounding factors, namely, age, gender, use of antidiabetic medication, use of hyper- or hypoglycaemia-inducing comedication and reporting year, were determined on the index date. Multivariate logistic regression was used to evaluate the strength of the association, which was expressed as reporting odds ratios (RORs) with 95% confidence intervals (95% CI).ResultsOverall, the use of antidepressants was associated with hyperglycaemia [ROR 1.52 (95% CI: 1.20–1.93)] and of hypoglycaemia [ROR 1.84 (95% CI: 1.40–2.42)]. The association with hyperglycaemia was most pronounced for antidepressants with affinity for the 5-HT2c receptor, histamine-1 receptor and norepinephrinic (NE) reuptake transporter. The association with hypoglycaemia was most pronounced for antidepressants with affinity for the serotonin reuptake transporter.ConclusionThe results of this study strengthen the findings in individual case reports that the use of antidepressants is associated with disturbances in glucose homeostasis.

Identification of Potential Drug-related Problems in the Elderly: The Role of the Community Pharmacist

Objective: The high prevalence of multiple drug use combined with age-related changes in pharmacokinetics and pharmacodynamics makes older adults more vulnerable to drug-related problems (DRPs). This pharmacy-based study was performed to identify potential DRPs from prescription records of the elderly and the role of the pharmacist in this process. Method: The study was performed from June 2002 to February 2003 in 16 community pharmacies in the Netherlands. Medication assessment of elderly patients aged 65 and over using six or more drugs concomitantly took place on the date of inclusion. Ten types of potential DRPs, grouped into three categories, were determined. The three groups were patient-related, prescriber-related or drug-related potential DRPs. We looked at the occurrence, nature and determinants of differential potential DRPs. Results: The mean number of prescriptions per patient was 8.7. In total 3.9 potential DRPs per elderly person were identified. The distribution of the potential DRPs over the three categories was: patient related 4.7%, prescriber related 55.7% and drug related 39.6%. Use of NSAIDs (OR 29.9; 95% CI 4.1–219) and digoxin (OR 15.7; 95% CI 4.9–50.5) were associated with the highest risk for potential DRPs. Conclusion: In this vulnerable group of elderly patients potential DRPs frequently occur. Community pharmacists can play an important role in the identification, assessment and prevention of potential DRPs in the elderly. It is useful to investigate which part of potential DRPs can be avoided by the intervention of the community pharmacist in collaboration with the prescriber and the patient.

Preventing hospital admissions by reviewing medication (PHARM) in primary care: design of the cluster randomised, controlled, multi-centre PHARM-study

BackgroundMedication can be effective but can also be harmful and even cause hospital admissions. Medication review or pharmacotherapy review has often been proposed as a solution to prevent these admissions and to improve the effectiveness and safety of pharmacotherapy. However, most published randomised controlled trials on pharmacotherapy reviews showed no or little effect on morbidity and mortality. Therefore we designed the PHARM (Preventing Hospital Admissions by Reviewing Medication)-study with the objective to study the effect of the total pharmaceutical care process on medication related hospital admissions and on adverse drug events, survival and quality of life.Methods/DesignThe PHARM-study is designed as a cluster randomised, controlled, multi-centre study in an integrated primary care setting. Patients with a high risk of a medication related hospital admission are included in the study with randomisation at GP (general practitioner) level. We aim to include 14200 patients, 7100 in each arm, from at least 142 pharmacy practices.The intervention consists of a patient-centred, structured, pharmaceutical care process. This process consists of several steps, is continuous and occurrs over multiple encounters of patients and clinicians. The steps of this pharmaceutical care process are a pharmaceutical anamnesis, a review of the patients pharmacotherapy, the formulation and execution of a pharmaceutical care plan combined with the monitoring and follow up evaluation of the care plan and pharmacotherapy. The patients own pharmacist and GP carry out the intervention. The control group receives usual care.The primary outcome of the study is the frequency of hospital admissions related to medication within the study period of 12 months of each patient. The secondary outcomes are survival, quality of life, adverse drug events and severe adverse drug events. The outcomes will be analysed by using mixed-effects Cox models.DiscussionThe PHARM-study is one of the largest controlled trials to study the effectiveness of the total pharmaceutical care process. The study should therefore provide evidence as to whether such a pharmaceutical care process should be implemented in the primary care setting.Trial RegistrationTrial number: NTR 2647

Association Between Hospitalization and Discontinuity of Medication Therapy Used in the Community Setting in the Netherlands

Background: Transitions from one healthcare setting to another often parallel transitions in health status and can be associated with intentional as well as unintentional changes in patient care. Hospitalization may put patients at increased risk of discontinuity of medication use. Objective: To assess the association between hospitalization and medication therapy discontinuities. Methods: A retrospective follow-up study was conducted using data obtained from the PHARMO Record Linkage System. We randomly selected patients who had been hospitalized (index date) between July 1, 1998, and June 30, 2000. For each hospitalized patient, one nonhospitalized patient was matched for age, sex, and geographic area, and was assigned the same index date as the corresponding hospitalized patient. The primary study outcome was the incidence of one or more medication therapy discontinuities at the index date and at several control moments during a period of 18 months before and 18 months after hospital admission. We defined 4 mutually exclusive types of discontinuities: generic–brand substitution, product substitution, therapeutic switch, and stop. Results: The study population comprised 8681 hospitalized patients and an equal number of age/sex-matched nonhospitalized patients. Of all hospitalized patients on drug therapy at the index date (n = 5265) 3322 (63.1 %) had one or more medication therapy discontinuities at the index dale, compared with 1390 (33.5%) of the nonhospitalized patients taking medication at the index date (n = 4147; RR 1.82; 95% CI 1.71 to 1.94). The highest risk estimate was found for therapeutic switch (RR 5.34; 95% CI 3.93 to 7.26), followed by product substitution (RR 2.32; 95% CI 1.88 to 2.86) and stop (RR 1.98; 95% CI 1.85 to 2.13). There was no significantly increased risk for generic-brand name substitution (RR 0.87; 95% CI 0.72 to 1.06). Conclusions: Hospitalization is associated with discontinuity of drugs used in the community setting. Medication stops were observed most frequently. Hospital safety programs should focus attention on medication therapy discontinuities at times of transition to ensure continuity of care in relation to drug therapy.

The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case-control study.

Hypoglycaemia is a limiting factor for glycaemic management of diabetes with intensive insulin and/or oral antidiabetic drug (OAD) regimen. Case reports suggest that antidepressants may interfere with blood glucose metabolism in patients with diabetes mellitus potentially increasing the risk of clinically relevant hypoglycaemia. Comorbid depression treated with antidepressants could therefore further complicate glycaemic control. We have carried out a nested case–control study among diabetic patients to assess the risk of hypoglycaemia requiring hospitalisation associated with the use of antidepressants.

A pharmacy medication alert system based on renal function in older patients

BACKGROUND Delayed antibiotic prescribing is promoted as a strategy to reduce antibiotic consumption, but its use and its effect on antibiotic consumption in routine care is poorly described. AIM To quantify delayed antibiotic prescribing in adults presenting in primary care with acute cough/lower respiratory tract infection (LRTI), duration of advised delay, consumption of delayed antibiotics, and factors associated with consumption. DESIGN AND SETTING Prospective observational cohort in general practices in 14 primary care networks in 13 European countries. METHOD GPs recorded clinical features and antibiotic prescribing for adults presenting with an acute infective illness with cough as the dominant symptom. Patients recorded their consumption of antibiotics from any source during the 28-day follow up. RESULTS Two hundred and ten (6.3%) of 3368 patients with usable consultation data were prescribed delayed antibiotics. The median recommended delay period was 3 days. Seventy-five (44.4%) of the 169 with consumption data consumed the antibiotic course and a further 18 (10.7%) took another antibiotic during the study period. 50 (29.6%) started their delayed course on the day of prescription. Clinician diagnosis of upper respiratory tract/viral infection and clinicians perception of patients wanting antibiotics were associated with less consumption of the delayed prescription. Patients wanting antibiotics was associated with greater consumption. CONCLUSION Delayed antibiotic prescribing was used infrequently for adults presenting in general practice with acute cough/LRTI. When used, the effect on antibiotic consumption was less than found in most trials. There are opportunities for standardising the intervention and promoting wider uptake.BACKGROUND Patients with diabetes or cardiovascular disease are at risk of reduced renal function and frequently use drugs that interact with renal function. GPs monitor renal function in these patients. Computerised prescription systems produce alerts in patients labelled as having chronic kidney disease, but alerts are often ignored. If pharmacists use a pharmacy medication alert system (PMAS) based on renal function, they can provide the GP with therapeutic advice to optimise the medication. The extent of this advice and the feasibility in the clinical context are unknown. AIM To assess the therapeutic advice formulated by pharmacists with help of a PMAS based on the renal function of patients aged ≥70 years with diabetes or cardiovascular disease. DESIGN AND SETTING Observational study in primary health care in the Netherlands. METHOD GPs provided pharmacists with the renal function of older patients with diabetes or cardiovascular disease who were using target drugs, that is, drugs requiring therapeutic advice in patients with reduced renal function. With the help of a PMAS, pharmacists assessed the actual medication. The GP weighed the advice in relation to the clinical context of the individual patient. RESULTS Six hundred and fifty patients were prescribed 1333 target drugs. Pharmacists formulated 143 therapeutic recommendations (11% of target drugs) concerning 89 patients (13.7% of study population). In 71 recommendations in 52 patients (8.0% of study population), the GP agreed immediately. CONCLUSION The use of a PMAS resulted in therapeutic advice in 11% of the target drugs. After weighing the clinical context, the GP agreed with half of the advice.

Laboratory tests in the clinical risk management of potential drug-drug interactions: a cross-sectional study using drug-dispensing data from 100 Dutch community pharmacies.

AbstractBackground: Patient safety and the life cycle of a drug are negatively influenced by the still increasing occurrence of potential drug-drug interactions (DDIs). Clinical risk management of potential DDIs is required in patients using drugs to influence the benefit-risk profile positively. Information about laboratory test results, in particular, may be useful in the assessment of potential DDIs for the individual patient. Objective: The objective of this study was to examine the frequency and nature of laboratory tests required for the assessment of the clinical relevance of potential DDIs in Dutch community pharmacies. In addition, the nature and clinical relevance of these potential DDIs is analysed. Methods: All patients from 100 Dutch community pharmacies using, according to dispensing information, two or more drugs concomitantly on a specified date (Wednesday, 4 April 2007), were included (n = 223 019). The anonymous dispensing data of the included patients were analysed against a list of DDIs requiring laboratory tests for the assessment of their clinical relevance. The number of patients at risk for these potential DDIs with severe adverse reactions was calculated. The frequency of potential DDIs requiring laboratory tests were stratified by age, sex and degree of polypharmacy. Results: Of the included patients, 24.4% had one or more potential DDIs (n =54 427). In 9.0% of the included patients, one or more laboratory tests for the assessment of clinical relevance of the potential DDI were required (n = 19 968). The frequency of DDIs requiring laboratory tests increased with increasing age and number of drugs, but was not related to sex. The most commonly required laboratory tests were for renal function (42.2%), electrolytes (20.1%) and coagulation (13.1%). The percentage of patients at risk for potential DDIs requiring laboratory tests with adverse reaction category F (serious, irrecoverable disablement or death) was 2.5%; category E (increased risk of failure of life-saving therapy) was 0.6%; and category D (inconvenience with residual symptom and failure of therapy concerning serious but non-fatal diseases) was 3.8%. Conclusions: A large number of patients in Dutch community pharmacies are at risk for potential DDIs requiring laboratory tests for the assessment of the clinical relevance of the interaction. There is a strong relationship between the frequency of DDIs requiring laboratory tests and age and the number of drugs concomitantly used. In the clinical risk management of potential DDIs, information about laboratory test results is of additional value. Future research is necessary in order to obtain more evidence on using laboratory tests in terms of which tests should be linked to pharmacy data, in which patients they should be done, how often and what actions should be taken when an abnormal value is found.

ADR related questions received by a telephone medicines information service and ADRs received by a spontaneous ADR reporting system: a comparison regarding patients and drugs

A telephone medicines information service (telephone service) has been available in the Netherlands since 1990. Patients can anonymously and free of charge ask a pharmacist all kinds of questions related to medication use. An analysis of the questions (n=7541) received by this service in 1994 showed that 28% of the questions predominantly related to adverse drug reactions (ADRs). A comparison was made between questions concerning ADRs received by the telephone service and suspected ADRs reported to the regionalized ADR reporting system LAREB regarding characteristics of the associated patients and medicines. In both systems approximately two out of three patients were women. LAREB received relatively more reports concerning patients of 60 years and older, whereas the telephone service received relatively more questions from patients aged 20–40 years. For most classes of medicines the observed proportion of encounters at both systems differed from the expected proportion estimated by the number of prescriptions in the same year. Antidepressants in particular were more frequently encountered at both systems than expected. There were clear differences between the telephone service and LAREB regarding the classes of medicines encountered. Reports of suspected ADRs submitted to LAREB more frequently involved antibiotics, antirheumatic products, anti‐asthmatics, antihypertensives and topical antifungals, whereas questions concerning ADRs received by the telephone service significantly more frequently concerned drugs acting on the central nervous system (anxiolytics/hypnotics/sedatives, antidepressants and antipsychotic drugs) and corticosteroids. We are setting up further studies to investigate whether telephone services can serve as an additional tool in postmarketing surveillance for identifying potential drug safety issues.