Impact of medicine shortages on patients - a framework and application in the Netherlands.

BACKGROUND: Medicine shortages are often described in plain numbers, suggesting all shortages have a uniform impact. However, some shortages have a direct and serious effect on patients and need a prompt reaction from stakeholders. This study aims to create a broad framework to assess the impact of a shortage. METHOD: We identified high impact shortages and selected exemplary shortages which we considered our learning cases. From five learning cases, we identified elements that had a potentially profound impact on one or more of these cases. We tested data saturation on the elements with another five test cases. Based on these elements, we created a framework to assess impact of shortages on patients and presented practical examples how to rate these different elements. Subsequently, we visualised the impact of these five learning cases on patients in radar charts. RESULTS: The five elements which we identified as potentially having a large impact were 1) alternative product, 2) disease, 3) susceptibility, 4) costs and 5) number of patients affected. The five learning cases rated high on different elements, leading to diverse and sometimes even opposite patterns of impact. CONCLUSION: We created a framework for assessing the impact of a medicine shortage on patients by means of five key elements. By rating these elements, an indication of the impact can be obtained.

Recognizing pharmaceutical illiteracy in community pharmacy: Agreement between a practice-based interview guide and questionnaire based assessment.

BACKGROUND: Patients with limited pharmaceutical literacy are at increased risk of drug-related problems. Recognizing these patients in daily practice is difficult. The Recognition and Addressing of Limited Pharmaceutical Literacy (RALPH) interview guide was developed as practical set of questions to recognize patients with limited pharmaceutical literacy in daily pharmacy practice. OBJECTIVE: To compare agreement between pharmaceutical literacy measured with the RALPH guide and a validated general health literacy questionnaire. In addition, we provide insight into patients' pharmaceutical literacy using the RALPH interview guide. METHODS: Structured face-to-face interviews with patients who visited a community pharmacy to fill a prescription for themselves were conducted. The interview included the RALPH guide as well as the Functional Communicative Critical Health Literacy (FCCHL) questionnaire to measure general health literacy. Functional, communicative and critical skills were measured and agreement between two methods was calculated. RESULTS: Data were collected from 508 patients. Patients with limited pharmaceutical literacy, indicated by the RALPH questions, also had a lower general health literacy level according to FCCHL scores. Agreement between the RALPH guide and FCCHL questionnaire was moderate (∼60%) for the three health literacy domains. Most patients (>90%) had correct understanding of frequency and timing of medication use, but 25% did not understand warnings or precautions correctly. Finding understandable information (39%), assessing information applicability (50%) and reliability (64%) were mentioned as difficult by patients. CONCLUSION: Patients experienced difficulties with more complex skills, e.g. interpretation of warnings or precautions when using a medicine, finding and analyzing medication information. Whereas the FCCHL questionnaire is useful to assess general health literacy, the RALPH interview guide provides insight in the level of skills needed for good medication use and is more suitable for use in a medication specific context such as community pharmacy. Context specific assessment of skills is important to provide tailored pharmaceutical care.

Patient-reported common symptoms as an assessment of interventions in medication reviews: a randomised, controlled trial.

Background A 'Patient-Reported Outcome Measure, Inquiry into Side Effects' (PROMISE) instrument was developed for patients to report common symptoms in clinical medication reviews. Objective To determine changes in patient-reported drug-associated symptoms collected by PROMISE before and after community pharmacist-led clinical medication reviews compared with usual care. Setting Community pharmacies in the Netherlands. Methods Patients were randomised into an intervention group (IG) and a control group (CG). PROMISE was used to collect symptoms experienced during the previous month, and any suspected drug-associated symptoms from both groups at baseline and at follow-up after 3 months. IG patients received a one-time clinical medication review, while CG patients received usual care. Main outcome measure Mean number of drug-associated symptoms at follow-up. Results Measurements were completed by 78 IG and 67 CG patients from 15 community pharmacies. Mean numbers of drug-associated symptoms per patient at follow-up were 4.0 in the IG and 5.0 in the CG, with an incident rate ratio between the groups of 0.90 (95% CI 0.62-1.33). Mean numbers of drug-associated symptoms per patient reported at follow-up and persisting since baseline were 2.1 in the IG and 2.6 in the CG, with an incident rate ratio of 0.85 (95% CI 0.43-1.42). The lowest percentages of persisting drug-associated symptoms detected in the IG were 'palpitations' and 'stomach pain, dyspepsia' while in the CG they were 'stomach pain, dyspepsia' and 'trembling, shivering'. Conclusion PROMISE provided meaningful information on drug-associated symptoms in clinical medication reviews, however the number of drug-associated symptoms was not reduced by performing clinical medication reviews compared with usual care.

Better specification of triggers to reduce the number of drug interaction alerts in primary care.

OBJECTIVE: Drug interaction alerts (drug-drug and drug-disease interaction alerts) for chronic medications substantially contribute to alert fatigue in primary care. The aim of this study was to determine which events require (re)assessment of a drug interaction and whether using these events as triggers in clinical decision support systems (CDSSs) would affect the alert rate. METHODS: Two random 5% data samples from the CDSSs of 123 community pharmacies were used: dataset 1 and 2. The top 10 of most frequent drug interaction alerts not involving laboratory values were selected. To reach consensus on events that should trigger alerts (e.g. first time dispensing, dose modification) for these drug interactions, a two-step consensus process was used. An expert panel of community pharmacists participated in an online survey and a subsequent consensus meeting. A CDSS with alerts based on the consensus was simulated in both datasets. RESULTS: Dataset 1 and 2 together contained 1,672,169 prescriptions which led to 591,073 alerts. Consensus on events requiring alerts was reached for the ten selected drug interactions. The simulation showed a reduction of the alert rate of 93.0% for the ten selected drug interactions (comparable for dataset 1 and 2), corresponding with a 28.3% decrease of the overall drug interaction alert rate. CONCLUSION: By consensus-based better specification of the events that trigger drug interaction alerts in primary care, the alert rate for these drug interactions was reduced by over 90%. This promising approach deserves further investigation to assess its consequences and applicability in daily practice.

Evaluation of Potentially Drug-Related Patient-Reported Common Symptoms Assessed During Clinical Medication Reviews: A Cross-Sectional Observational Study.

INTRODUCTION: Healthcare professionals tend to consider common non-alarming drug-related symptoms to be of little clinical relevance. However, such symptoms can have a substantial impact on the individual patient. Insight into patient-reported symptoms could aid pharmacists to identify improvements in medication treatment, for instance in the patient interview at the start of a clinical medication review (CMR). OBJECTIVE: The objectives of this study were to describe the numbers and types of patient-reported symptoms assessed during a CMR and to elucidate their potential association with the drugs in use. METHODS: This observational study was performed using data from a clinical trial on patient-reported outcomes of CMRs. Patients taking at least five drugs and who were eligible for a CMR were selected by 15 community pharmacies. Patients were asked to fill in a structured instrument, the Patient Reported Outcome Measure, Inquiry into Side Effects (PROMISE). Among other domains, this instrument offers a list of 22 symptom categories to report symptoms and their relationship with the drugs in use. The results of the PROMISE instrument together with information on patients' actual drug use were available for analysis. Besides descriptive analysis, associations with side effects as listed in the summary of product characteristics (SPC) of the drugs in use were assessed with logistic regression analysis. RESULTS: Of the 180 patients included, 168 patients (93.3%) reported at least one symptom via the PROMISE instrument, which could be discussed with the pharmacist during the patient interview. In total, the patients reported 1102 symptoms in 22 symptom categories. Of these patients, 101 (56.1%) assumed that at one or more of the symptoms experienced were related to the drugs in use and 107 (59.4%) reported at least one symptom that corresponded to a 'very common' side effect listed in the SPC of a drug in use. Each additional drug in use with a specific symptom listed as a 'very common' side effect in its SPC statistically significantly increased the probability of a patient reporting the symptoms of 'dry mouth/thirst, mouth complaints', 'constipation', 'diarrhoea' and 'sweating'. CONCLUSION: Many patient-reported symptoms and symptoms potentially related to drugs in use were identified by administering the PROMISE instrument to users of at least five drugs being taking long-term. This information can be used in CMRs to improve patients' drug therapy.

Lower alert rates by clustering of related drug interaction alerts.

OBJECTIVE: We aimed to investigate to what extent clustering of related drug interaction alerts (drug-drug and drug-disease interaction alerts) would decrease the alert rate in clinical decision support systems (CDSSs). METHODS: We conducted a retrospective analysis of drug interaction alerts generated by CDSSs in community pharmacies. Frequently generated combinations of alerts were analyzed for associations in a 5% random data sample (dataset 1). Alert combinations with similar management recommendations were defined as clusters. The alert rate was assessed by simulating a CDSS generating 1 alert per cluster per patient instead of separate alerts. The simulation was performed in dataset 1 and replicated in another 5% data sample (dataset 2). RESULTS: Data were extracted from the CDSSs of 123 community pharmacies. Dataset 1 consisted of 841 572 dispensed prescriptions and 298 261 drug interaction alerts. Dataset 2 was comparable. Twenty-two frequently occurring alert combinations were identified. Analysis of these associated alert combinations for similar management recommendations resulted in 3 clusters (related to renal function, electrolytes, diabetes, and cardiovascular diseases). Using the clusters in alert generation reduced the alert rate within these clusters by 53-70%. The overall number of drug interaction alerts was reduced by 11% in dataset 1 and by 12% in dataset 2. This corresponds to a decrease of 21 alerts per pharmacy per day. DISCUSSION AND CONCLUSION: Using clusters of drug interaction alerts with similar management recommendations in CDSSs can substantially decrease the overall alert rate. Further research is needed to establish the applicability of this concept in daily practice.

Drug therapy management in patients with renal impairment: how to use creatinine-based formulas in clinical practice.

PURPOSE: The use of estimated glomerular filtration rate (eGFR) in daily clinical practice. METHODS: eGFR is a key component in drug therapy management (DTM) in patients with renal impairment. eGFR is routinely reported by laboratories whenever a serum creatinine testing is ordered. In this paper, we will discuss how to use eGFR knowing the limitations of serum creatinine-based formulas. RESULTS: Before starting a renally excreted drug, an equally effective drug which can be used more safely in patients with renal impairment should be considered. If a renally excreted drug is needed, the reliability of the eGFR should be assessed and when needed, a 24-h urine creatinine clearance collection should be performed. After achieving the best approximation of the true GFR, we suggest a gradual drug dose adaptation according to the renal function. A different approach for drugs with a narrow therapeutic window (NTW) is recommended compared to drugs with a broad therapeutic window. For practical purposes, a therapeutic window of 5 or less was defined as a NTW and a list of NTW drugs is presented. Considerations about the drug dose may be different at the start of the therapy or during the therapy and depending on the indication. Monitoring effectiveness and adverse drug reactions are important, especially for NTW drugs. Dose adjustment should be based on an ongoing assessment of clinical status and risk versus the benefit of the used regimen. CONCLUSION: When determining the most appropriate dosing regimen serum creatinine-based formulas should never be used naively but always in combination with clinical and pharmacological assessment of the individual patient.

Quick assessment of drug-related admissions over time (QUADRAT study).

PURPOSE: To develop a computerized prescreening procedure for the identification of possible/probably Hospital Admissions potential Related to Medications (HARMs). METHOD: Pairs of drugs and reasons for hospitalization (generated automatically from the PHARMO record linkage database by using two data mining techniques) were assessed manually to determine whether they represented pharmacologically plausible adverse drug events (PP-ADEs). Two crude samples of these PP-ADEs (from 2005 and 2008) were examined manually to establish causality and preventability on the basis of hospital discharge letters plus medication dispensing data. The results were used to calculate the positive predictive value (PPV) of the crude causality PP-ADEs, the net percentage of possible/probably HARMs, and their potential preventability. RESULTS: Data mining by Gamma Poisson Shrinkage and trend analysis produced 1330 and 2941 significant drug-event pairs, respectively. After manual assessment, 307 different PP-ADEs remained. The annual prevalence of these PP-ADEs was stable at approximately 8% throughout 2000-2009. Manual assessment of two samples of crude PP-ADEs showed that their causality PPV was 53.7% (95%CI: 52.7%-54.7%) in 2005 and 47.9% (95%CI: 46.9%-49.0%) in 2008. The net contribution of possible/probably HARMs to all acute admissions was 4.6% (95%CI: 4.5%-4.8%) in 2005 and 3.9% (95%CI: 3.8%-4.0%) in 2008. The potential preventability of all possible/probably HARMs in the two samples was 19.3% (95%CI: 18.5-20.1). CONCLUSION: Automated pre-selection of PP-ADEs is an efficient way to monitor crude trends. Further validation and manual assessment of the automatically selected hospitalizations is necessary to get a more detailed and precise picture.

Evaluation of quality indicators for Dutch community pharmacies using a comprehensive assessment framework.

BACKGROUND: In 2008, the Dutch Health Care Transparency Programme (Zichtbare Zorg) was set up to develop and apply quality indicators (QIs) for health care. These QIs serve a range of purposes and can be categorized into those for internal use--for meeting quality standards and to continuously measure improvement (formative)--and external use--to enable patients and health insurance companies to distinguish between health care providers (summative). In order to assess the validity of QIs, a comprehensive Indicator Assessment Framework (IAF) was developed. This framework specifies the following criteria for validation: content validity, absence of selection bias, absence of measurement bias, and statistical reliability. Because of the intended summative use, the IAF was used for structural assessment of the QIs set for Dutch community pharmacists. OBJECTIVE: To assess the validity of the current set of 52 QIs for community pharmacies using the IAF. METHODS: An expert panel applied the IAF criteria to the set of QIs collected in 1,807 Dutch community pharmacies on their performance in 2011. The QIs were judged as meeting, partly meeting, or not meeting the requirements regarding these criteria. The judgments were evaluated for QI type (structure, process, or outcome) and for predefined domains. RESULTS: Thirteen QIs (25%) were judged as meeting the requirements for all criteria. Among them were 12 structure indicators and 1 process indicator. For process indicators, the criterion for measurement bias poorly met the requirements, and content validity was unsatisfactory for outcome indicators. The 13 overall valid QIs covered 6 out of 10 predefined domains: continuity of care, clinical risk management, compounding, dispensing of medication, management, and quality management. CONCLUSIONS: When subjecting the QI set for community pharmacies to the requirements of the IAF, only a quarter of the QIs met all requirements. To increase the number of valid process and outcome indicators, meaningful aspects for the outcome of pharmaceutical care have to be defined, and uniform measurement of relevant processes has to be implemented.

NSAID-antihypertensive drug interactions: which outpatients are at risk for a rise in systolic blood pressure?

BACKGROUND: Management guidelines for drug-drug interactions between non-steroidal anti-inflammatory drugs (NSAIDs) and antihypertensives recommend blood pressure monitoring in hypertensive patients. We measured the short-term effect of initiating NSAIDs on systolic blood pressure (SBP) in users of antihypertensives, aiming to investigate which outpatients are at risk for an increase in SBP in daily clinical practice. DESIGN: A cohort study with a nested case-control design in Dutch community pharmacies. METHODS: Patients with a drug-drug interaction alert for a newly initiated NSAID and antihypertensive were interviewed and their SBP was measured at T0, after one week (T1) and after two weeks (T2). We evaluated risk factors for exceeding a predefined limit of change (PLoC) in SBP (≥ 10 mmHg to ≥ 140 mmHg) at T1 and T2 versus T0. RESULTS: For 112 patients the SBP at T0 was measured. Two patients were excluded (T0 SBP ≥ 180 mmHg). PLoC was exceeded in 10 patients (10.4%) at T1 and in seven patients (8.0%) at T2. Patients using etoricoxib (odds ratio (OR), 21.0; 95% confidence interval (CI), 3.7-120.6) and patients using >1 defined daily dose of an NSAID (OR, 3.3; 95% CI, 1.1-10.0) were at increased risk of a rise in SBP. CONCLUSIONS: A newly initiated NSAID has an immediate clinically relevant effect on SBP in some users of antihypertensives. Management guidelines for NSAID-antihypertensive drug-drug interactions should advise SBP monitoring before and after initiation of an NSAID or intensification of NSAID therapy. Monitoring is especially relevant in patients prescribed high dosages of NSAIDs. Etoricoxib should not be used in hypertensive patients.

Medication incidents related to automated dose dispensing in community pharmacies and hospitals--a reporting system study.

INTRODUCTION: Automated dose dispensing (ADD) is being introduced in several countries and the use of this technology is expected to increase as a growing number of elderly people need to manage their medication at home. ADD aims to improve medication safety and treatment adherence, but it may introduce new safety issues. This descriptive study provides insight into the nature and consequences of medication incidents related to ADD, as reported by healthcare professionals in community pharmacies and hospitals. METHODS: The medication incidents that were submitted to the Dutch Central Medication incidents Registration (CMR) reporting system were selected and characterized independently by two researchers. MAIN OUTCOME MEASURES: Person discovering the incident, phase of the medication process in which the incident occurred, immediate cause of the incident, nature of incident from the healthcare provider's perspective, nature of incident from the patient's perspective, and consequent harm to the patient caused by the incident. RESULTS: From January 2012 to February 2013 the CMR received 15,113 incidents: 3,685 (24.4%) incidents from community pharmacies and 11,428 (75.6%) incidents from hospitals. Eventually 1 of 50 reported incidents (268/15,113 = 1.8%) were related to ADD; in community pharmacies more incidents (227/3,685 = 6.2%) were related to ADD than in hospitals (41/11,428 = 0.4%). The immediate cause of an incident was often a change in the patient's medicine regimen or relocation. Most reported incidents occurred in two phases: entering the prescription into the pharmacy information system and filling the ADD bag. CONCLUSION: A proportion of incidents was related to ADD and is reported regularly, especially by community pharmacies. In two phases, entering the prescription into the pharmacy information system and filling the ADD bag, most incidents occurred. A change in the patient's medicine regimen or relocation was the immediate causes of an incident.

Effectiveness of interventions by community pharmacists to reduce risk of gastrointestinal side effects in nonselective nonsteroidal anti-inflammatory drug users.

PURPOSE: Upper gastrointestinal (UGI) complications in elderly users of nonselective nonsteroidal anti-inflammatory drugs (ns-NSAIDs) without concomitant use of gastroprotective agents (GPAs) were a leading cause of potentially avoidable drug-related hospital admissions in the Netherlands. We aimed to determine the effectiveness of community pharmacists' interventions to improve safety in ns-NSAID use in patients at UGI risk. METHODS: In this prospective cohort study, pharmacists in participating pharmacies (intervention group, IG) received feedback on drug dispensing in ns-NSAID users of ≥60 years of age at risk for UGI damage and were instructed to select patients to improve ns-NSAID prescribing, in collaboration with primary care physicians. Ns-NSAID users from other pharmacies without concomitant GPA use were followed in parallel as a control group (CG). Changes in the UGI risk of ns-NSAID users between baseline and follow-up measurement, assessed either by the addition of GPAs or the cessation of ns-NSAIDs, were compared between the two study arms. RESULTS: At baseline, 14% of ns-NSAID users at UGI risk did not receive GPAs. Persistent ns-NSAID users from the selected IG patients had an additional 7% likelihood of reduced UGI risk at follow-up (odds ratio 0.93, 95% confidence interval 0.89-0.97) compared with CG patients. In the IG, 91% of selected IG patients at UGI risk from ns-NSAIDs at baseline were no longer at increased risk at follow-up because of cessation of ns-NSAIDS or to concomitant GPA use. CONCLUSION: Although concomitant gastroprotection use in susceptible ns-NSAID users in the Netherlands is high, pharmacist-led interventions could further improve prescribing of ns-NSAIDs.

Adherence to guidelines for the prescribing of double and triple combinations of antithrombotic agents.

BACKGROUND: To prevent cardiovascular complications, sometimes double and triple therapy with a vitamin K antagonist (VKA), clopidogrel and/or acetylsalicylic acid (ASA) are indicated. These combinations increase the patient's risk of serious bleeding events. Therefore, adherence to clinical guidelines is of the utmost importance when these high-risk therapies are prescribed. METHODS: We performed a retrospective cohort study of 238 cases in a community pharmacy that were treated with a combination of VKA, clopidogrel and/or ASA between January 2006 and December 2009. Hospital records and community pharmacy records were used to obtain the indication(s), the duration of combination therapy, the presence of risk-increasing and risk-decreasing co-medications and any relevant co-morbidities. The cardiologists' attitudes towards the prescribing of antithrombotic combinations and their self-reported adherence to guidelines were assessed by a brief questionnaire. RESULTS: We found there was no guideline-based indication for 22 of the 146 cases (14%) on ASA plus clopidogrel and 19 of the 82 cases (23%) on VKA plus ASA. Of the 238 cases given antithrombotic combination therapies, 77 (32%) were placed at an additional increased risk of serious gastrointestinal events, yet 43 (56%) of these did not receive adequate gastric protection. Out of the 19 of 60 cardiologists (32%) who responded to our questionnaire; 17 (90%) and 13 (68%) stated that a strict indication is very important when initiating therapy with ASA plus clopidogrel or ASA plus VKA, respectively. CONCLUSIONS: There is room to further develop adherence to guideline-based prescribing of antithrombotic combination therapies and to improve prescription of gastric protection for patients receiving these high-risk combinations.

Vietnamese traditional medicine from a pharmacist's perspective.

Traditional medicine plays an important role in the healthcare system of Vietnam. Vietnamese traditional medicine (VTM) is underpinned by the oriental philosophy and theory of healing. VTM is largely influenced by traditional Chinese medicine, but differs to a certain extent. VTM is largely not evidence-based from a clinical perspective but subclinical research data from the past decades support the traditional use of many herbal VTM drugs. For safe use, knowledge of the occurrence of adverse reactions and herb-drug interactions is necessary. The Vietnamese government supports further development of VTM in a scientific way and integration of VTM with Western medicine. This article first gives an overview of the general aspects of VTM (historical perspective, regulatory aspects, comparison with traditional Chinese medicine, philosophical background, the Vietnamese market situation, quality assurance and formulations), and subsequently focuses on its safe and effective use in Vietnamese clinical pharmacy and medical practice.

Clarity and applicability of drug-drug interaction management guidelines: a systematic appraisal by general practitioners and community pharmacists in the Netherlands.

BACKGROUND: Despite the availability and daily use of computerized drug-drug interaction surveillance systems, exposure to potentially relevant drug-drug interactions (DDIs) continues. DDI management guidelines are often inadequate and clear management options are lacking, which attributes to overriding of DDI signals. Although general criteria for the development and reporting of high-quality clinical practice guidelines have been identified, it appears these have not yet been applied to DDI management guidelines. OBJECTIVES: The aim of the study was to assess the clarity and applicability of guidelines for the management of potentially harmful DDIs. METHODS: We selected 13 DDIs that are potentially harmful for patients and frequently occur in community pharmacy practice in the Netherlands. The clarity and applicability of the management guidelines of these DDIs were appraised using the appropriate two domains - 'Clarity and presentation' and 'Applicability', of the validated Appraisal of Guidelines for Research and Evaluation (AGREE) Instrument. The appraisal was performed by 12 community pharmacists and 12 general practitioners. The standardized domain scores and mean item scores for 'Clarity and presentation' and 'Applicability' were compared. RESULTS: All DDI management guidelines were generally found to score well on 'Clarity and presentation', but poorly with respect to 'Applicability' (standardized domain scores 68.0 vs 26.1%). Within the domain 'Clarity and presentation', the item 'tools for application' received the lowest scores. Within the domain 'Applicability', cost implications, organizational barriers and key review criteria were all poorly documented. All guidelines presented non-directive advice using words such as 'consider' and 'regularly'. CONCLUSIONS: Developers of DDI management guidelines should take the appropriate domains of the AGREE Instrument into consideration in their development processes. The applicability of DDI management guidelines should be pretested before publishing. To improve guideline quality, more attention should particularly be paid to the available tools for applications and cost implications.

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.

BACKGROUND: 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.

Clinical risk management of interactions between natural products and drugs.

Clinical risk management offers a systematic approach to minimize healthcare-related risks by paying attention to: (1) risk identification and assessment; (2) development and execution of risk reduction strategies; (3) evaluation of risk reduction strategies. This paper reviews these key areas for the risk of interactions between natural products and drugs (NPDIs) to explore how the impact of these interactions on public health can be minimized. It argues that specific components of clinical risk management need to be evaluated, before adoption, and then actively implemented if proven valuable.

Treatment reviews of older people on polypharmacy in primary care: cluster controlled trial comparing two approaches.

BACKGROUND: Older people are prone to problems related to use of medicines. As they tend to use many different medicines, monitoring pharmacotherapy for older people in primary care is important. AIM: To determine which procedure for treatment reviews (case conferences versus written feedback) results in more medication changes, measured at different moments in time. To determine the costs and savings related to such an intervention. DESIGN OF STUDY: Randomised, controlled trial, randomisation at the level of the community pharmacy. SETTING: Primary care; treatment reviews were performed by 28 pharmacists and 77 GPs concerning 738 older people (> or =75 years) on polypharmacy (>five medicines). METHOD: In one group, pharmacists and GPs performed case conferences on prescription-related problems; in the other group, pharmacists provided results of a treatment review to GPs as written feedback. Number of medication changes was counted following clinically-relevant recommendations. Costs and savings associated with the intervention at various times were calculated. RESULTS: In the case-conference group significantly more medication changes were initiated (42 versus 22, P = 0.02). This difference was also present 6 months after treatment reviews (36 versus 19, P = 0.02). Nine months after treatment reviews, the difference was no longer significant (33 versus 19, P = 0.07). Additional costs in the case-conference group seem to be covered by the slightly greater savings in this group. CONCLUSION: Performing treatment reviews with case conferences leads to greater uptake of clinically-relevant recommendations. Extra costs seem to be covered by related savings. The effect of the intervention declines over time, so performing treatment reviews for older people should be integrated in the routine collaboration between GPs and pharmacists.

Clinical risk management in Dutch community pharmacies: the case of drug-drug interactions.

BACKGROUND: The prevention of drug-drug interactions requires a systematic approach for which the concept of clinical risk management can be used. The objective of our study was to measure the frequency, nature and management of drug-drug interaction alerts as these occur in daily practice of Dutch community pharmacies. METHODS: In total, 63 Dutch pharmacies collected all drug-drug interaction alerts during 153 research days (on average 2.4 days/pharmacy), as well as variables related to these alerts, such as involved medicines, first time or recurrent drug-drug interaction, same or different prescribers, patient data (age, sex) and information about the management of drug-drug interactions by the pharmacy. The latter was discriminated into internal procedures only and external action, such as communication with the patient, the prescriber or the anticoagulation clinic and prescription modification. All drug-drug interactions were classified into categories of clinical relevance (A-F) and available evidence (0-4). RESULTS: A total of 43,129 prescription-only medicines were dispensed during the study period. On average, 16.8 interaction alerts per day per pharmacy were collected. Approximately 6% of all prescriptions generated a drug-drug interaction alert. Of all alerts (n = 2572), 31.1% occurred for the first time and with 21% two different prescribers were involved. The 20 most frequently occurring drug-drug interaction alerts accounted for approximately 76% of all alerts. Cardiovascular drugs, NSAIDs, oral contraceptives and antibacterials were most frequently involved. External action was taken in response to 27.3% of the alerts, meaning either a modification of one of the concerned prescriptions (n = 65; 9.3%), communication with the prescriber or anticoagulation clinic (n = 90; 12.8%) or communication with the patient or a relative (n = 547; 77.9%). Where there was no external action (n = 1860; 72.3%), pharmacists concluded in about two-thirds of cases that the drug-drug interaction had been managed in the past. Other reasons not to intervene externally were for instance: incorrect alert; acceptable drug-drug interaction; or outcome of the interaction considered irrelevant. Adjusted for several variables, a first alert was found to be a main determinant for external action. After stratifying for first alerts no other significant determinants were found. CONCLUSIONS: A high frequency of drug-drug interaction alerts was found. Most concerned recurrent alerts, which were the main reason not to act externally. Concerning the assessment phase in the risk-management process, drug-drug interactions with no or low evidence/relevance should be reconsidered. Concerning the management of drug-drug interactions in pharmacies, the opportunity to actively suppress alerts for a certain period of time should be studied in more detail. There are indicators that the management of patient-orientated advice could be improved and a greater degree of consistency developed for the management of first and recurrent interaction alerts.

Repeat prescribing: scale, problems and quality management in ambulatory care patients.

The reported scale of repeat prescriptions ranges from 29% to 75% of all items prescribed, depending on the definition of repeat prescribing and other variables. It is likely that a substantial part of repeat prescribing by general practitioners (GPs) occurs without direct doctor-patient contact. While this reduces the workload for the GP and is convenient for the patient, it does not provide the adequate control that is needed to ensure that every repeat prescription is still appropriate, effective and well tolerated, and that it is still being viewed upon and taken by the patient as intended. Infrequent therapy reviews may lead to failure to prevent, identify and solve drug-related problems and drug wastage, and may, thereby, have a negative impact on the effectiveness, safety or cost of the medications prescribed. Studies evaluating the repeat prescribing process have shown that GPs and medical practices vary widely in their degree of administrative and clinical control of repeat prescriptions. Contrary to the opinion that GPs cannot change prescribing behaviour when the prescription is initiated by a medical specialist, GPs have their own responsibility for controlling the repeats of such prescriptions. Intervention studies suggest that a medication review by a pharmacist can help to reduce drug-related problems with repeat prescriptions, and the effectiveness of the intervention may be increased by combining the medication review with a consultation of the patient's medical records and a patient interview. In several studies, such an intervention was relatively inexpensive and, therefore, feasible. However, these conclusions should be viewed with appropriate caution because a number of caveats pertain. There is still no evidence that these types of intervention improve health-related quality of life or reduce healthcare cost, and so far only a few trials have produced any evidence of clinical improvement. As implicit and explicit screening criteria have their own benefits and limitations, a combined application may offer a more thorough assessment but may also be more complex and time consuming. Further studies on the development and evaluation of repeat prescription management models are needed, preferably focussing on improving clinical, humanistic and economic outcomes. New studies should investigate the effects of: different types of interventions; different organisational models; different target populations; and selecting and training different types of healthcare professionals. Future studies should also assess whether results are sustained, the optimal time interval between reviews of repeat prescriptions, and the possibilities offered by new computerised support technologies.