Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study.

BACKGROUND: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. AIMS: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. METHODS: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. RESULTS: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m2, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m2, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. CONCLUSION: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m2, which are achieved by smaller dose reductions.

Documentation of the Patient Characteristics Morbid Obesity and Bariatric Surgery in the Hospital Information System and the Influence on the Number of Medication-Related Problems.

BACKGROUND: As a result of pharmacokinetic changes, individuals with morbid obesity and/or with bariatric surgery may require dose adjustments, additional monitoring or medication should be avoided. Clinical decision support (CDS) may provide automated alerts enabling correct prescribing but requires documentation of these patient characteristics in the Hospital Information System (HIS) to prevent medication-related problems (MRPs). OBJECTIVE: The primary objective is to determine the proportion of patients with documentation of the patient characteristics morbid obesity and bariatric surgery in the HIS. The secondary objective is to compare the proportion of patients with an MRP in the group with versus without documentation. Also, the type and severity of MRPs and the medication involved are determined. METHODS: A prospective cohort study was performed. Patients admitted to the hospital were identified as morbidly obese and/or with bariatric surgery. In the identified patients, the proportion of patients with documentation of the patient characteristics in the HIS was evaluated as primary outcome. Subsequently, patient records were reviewed for MRPs, which were categorized and associated medication was registered. For the primary objective, descriptive statistics was used. For the secondary outcome, the Fisher's exact test was used. RESULTS: In 43 (21.4%, 95% confidence interval [CI]: 15.7%-27.1%) of 201 included patient (113 morbid obesity, 70 bariatric surgery and 18 both), the patient characteristics were documented. An MRP occurred in 2.3% versus 13.9% (P = 0.032) of patients with and without documentation, respectively. The most common MRP was underdosing in morbid obesity, while in patients with bariatric surgery it was prescription of contra-indicated medication. CONCLUSION AND RELEVANCE: The proportion of patients with documentation of the patient characteristics bariatric surgery and/or morbid obesity in the HIS is low, which appears to be associated with more MRPs. To improve medication safety, it is important to document these patient characteristics.

The effect of a transitional pharmaceutical care program on the occurrence of ADEs after discharge from hospital in patients with polypharmacy.

INTRODUCTION: Transitional care programs (i.e. interventions delivered both in hospital and in primary care), could increase continuity and consequently quality of care. However, limited studies on the effect of these programs on Adverse Drug Events (ADEs) post-discharge are available. Therefore, the aim of this study was to investigate the effect of a transitional pharmaceutical care program on the occurrence of ADEs 4 weeks post-discharge. METHODS: A multicentre prospective before-after study was performed in a general teaching hospital, a university hospital and 49 community pharmacies. The transitional pharmaceutical care program consisted of: teach-back to the patient at discharge, a pharmaceutical discharge letter, a home visit by a community pharmacist and a clinical medication review by both the community and the clinical pharmacist, on top of usual care. Usual care consisted of medication reconciliation at admission and discharge by pharmacy teams. The primary outcome was the proportion of patients who reported at least 1 ADE 4 weeks post-discharge. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: In total, 369 patients were included (control: n = 195, intervention: n = 174). The proportion of patients with at least 1 ADE did not statistically significant differ between the intervention and control group (general teaching hospital: 59% vs. 67%, ORadj 0.70 [95% CI 0.38-1.31], university hospital: 63% vs 50%, OR adj 1.76 [95% CI 0.75-4.13]). CONCLUSION: The transitional pharmaceutical care program did not decrease the proportion of patients with ADEs after discharge. ADEs after discharge were common and more than 50% of patients reported at least 1 ADE. A process evaluation is needed to gain insight into how a transitional pharmaceutical care program could diminish those ADEs.

Medication-Related Hospital Readmissions Within 30 Days of Discharge: Prevalence, Preventability, Type of Medication Errors and Risk Factors.

Background: Hospital readmission rates are increasingly used as a measure of healthcare quality. Medicines are the most common therapeutic intervention but estimating the contribution of adverse drug events as a cause of readmissions is difficult. Objectives: To assess the prevalence and preventability of medication-related readmissions within 30 days after hospital discharge and to describe the risk factors, type of medication errors and types of medication involved in these preventable readmissions. Design: A cross-sectional observational study. Setting: The study took place across the cardiology, gastroenterology, internal medicine, neurology, psychiatry, pulmonology and general surgery departments in the OLVG teaching hospital, Netherlands. Participants: Patients with an unplanned readmission within 30 days after discharge from an earlier hospitalization (index hospitalization: IH) were reviewed. Measurements: The prevalence and preventability of medication-related readmissions were assessed by residents in multidisciplinary meetings. A senior internist and hospital pharmacist reassessed the prevalence and preventability of identified cases. Generalized estimating equation with logistic regression was performed to identify risk factors of potentially preventable medication-related readmissions. Results: Of 1,111 included readmissions, 181 (16%) were medication-related, of which 72 (40%) were potentially preventable. The number of medication changes at IH (Adjusted odds ratio [ORadj]: 1.14; 95% CI: 1.05-1.24) and having ≥3 hospitalizations 6 months before IH (ORadj: 2.11; 95% CI: 1.12-3.98) were risk factors of a preventable medication-related readmission. Of these preventable readmissions, 35% were due to prescribing errors, 35% by non-adherence and 30% by transition errors. Medications most frequently involved were diuretics and antidiabetics. Conclusion: This study shows that 16% of readmissions are medication-related, of which 40% are potentially preventable. If the results are confirmed in larger multicentre studies, this may indicate that more attention should be paid to medication-related harm in order to lower the overall readmission rates.

The Effect of Medication Reconciliation via a Patient Portal on Medication Discrepancies: A Randomized Noninferiority Study.

BACKGROUND: Medication reconciliation has become standard care to prevent medication transfer errors. However, this process is time-consuming but could be more efficient when patients are engaged in medication reconciliation via a patient portal. OBJECTIVES: To explore whether medication reconciliation by the patient via a patient portal is noninferior to medication reconciliation by a pharmacy technician. DESIGN (INCLUDING INTERVENTION): Open randomized controlled noninferiority trial. Patients were randomized between medication reconciliation via a patient portal (intervention) or medication reconciliation by a pharmacy technician at the preoperative screening (usual care). SETTING AND PARTICIPANTS: Patients scheduled for elective surgery using at least 1 chronic medication were included. MEASURES: The primary endpoint was the number of medication discrepancies compared to the electronic nationwide medication record system (NMRS). For the secondary endpoint, time investment of the pharmacy technician for the medication reconciliation interview and patient satisfaction were studied. Noninferiority was analyzed with an independent t test, and the margin was set at 20%. RESULTS: A total of 499 patients were included. The patient portal group contained 241 patients; the usual care group contained 258 patients. The number of medication discrepancies was 2.6 ± 2.5 in the patient portal group and 2.8 ± 2.7 in the usual care group. This was not statistically different and within the predefined noninferiority margin. Patients were satisfied with the use of the patient portal tool. Also, the use of the portal can save on average 6.8 minutes per patient compared with usual care. CONCLUSIONS AND IMPLICATIONS: Medication reconciliation using a patient portal is noninferior to medication reconciliation by a pharmacy technician with respect to medication discrepancies, and saves time in the medication reconciliation process. Future studies should focus on identifying patient characteristics for successful implementation of patient portal medication reconciliation.

The added value of H2 antagonists in premedication regimens during paclitaxel treatment.

BACKGROUND: Ranitidine, a histamine 2 blocker, is the standard of care to prevent hypersensitivity reactions (HSRs) caused by paclitaxel infusion. However, the added value of ranitidine in this premedication regimen is controversial. Therefore, we compared the incidence of HSRs during paclitaxel treatment between a standard regimen including ranitidine and a regimen without ranitidine. METHODS: This prospective, pre-post interventional, non-inferiority study compared the standard premedication regimen (N = 183) with dexamethasone, clemastine and ranitidine with a premedication regimen without ranitidine (N = 183). The primary outcome was the incidence of HSR grade ≥3. Non-inferiority was determined by checking whether the upper bound of the two-sided 90% confidence interval (CI) for the difference in HSR rates excluded the +6% non-inferiority margin. RESULTS: In both the pre-intervention (with ranitidine) and post-intervention (without ranitidine) group 183 patients were included. The incidence of HSR grade ≥3 was 4.4% (N = 8) in the pre-intervention group and 1.6% (N = 3) in the post-intervention group: difference -2.7% (90% CI: -6.2 to 0.1). CONCLUSIONS: As the upper boundary of the 90% CI does not exceed the predefined non-inferiority margin of +6%, it can be concluded that a premedication regimen without ranitidine is non-inferior to a premedication regimen with ranitidine. CLINICAL TRIAL REGISTRATION: www.trialregister.nl ; NL8173.

Opportunities for changes in the drug product design to enhance medication safety in older people: Evaluation of a national public portal for medication incidents.

AIMS: Medication safety requires urgent attention in hospital pharmacy. This study evaluated the medication-related problems/errors as reported to the Dutch medication incident registry and disseminated for information to pharmacists. Through analysis by an expert panel we aimed to better understand which problems could have been mitigated by the drug product design. Additionally, the (wider) implications of the problems for current hospital/clinical practice were discussed. METHODS: Items were extracted from the public Portal for Patient Safety. Items were included if relevant for older people and connected with the drug product design and excluded if they should reasonably have been intercepted by compliance to routine controls or well-known professional standards in pharmaceutical care. To explore any underreporting of well-known incidents, it was investigated if different medication-related problems could be observed in a regional hospital practise over a 1-month period. For 6 included items (cases), the implications for hospital/clinical practise were discussed in an expert panel. RESULTS: In total, 307 items were identified in the Portal for Patient Safety; all but 14 were excluded. Six cases were added from daily hospital practice. These 20 cases commonly related to confusing product characteristics, packaging issues such as the lack of a single unit package for an oncolytic product, or incorrect or incomplete user instructions. CONCLUSION: Medication registries provide important opportunities to evaluate real-world medication-related problems. However, underreporting of well-known problems should be considered. The product design can be used as an (additional) risk mitigation measure to support medication safety in hospital practice.

Patients' and providers' perspectives on medication relatedness and potential preventability of hospital readmissions within 30 days of discharge.

BACKGROUND: Hospital readmissions are increasingly used as an indicator of quality in health care. One potential risk factor of readmissions is polypharmacy. No studies have explored the patients' perspectives on the medication relatedness and potential preventability of their readmissions. OBJECTIVE: To compare the patients' perspectives on the medication relatedness and potential preventability of their readmissions with the providers' perspectives. METHODS: Patients unplanned readmitted within 30 days after discharge at one of the participating departments of OLVG Hospital in Amsterdam were interviewed during their readmission. Patients' perspectives regarding medication relatedness of their readmissions, the potential preventability, possible preventable interventions, and satisfaction with medication information were examined. Health-care providers also reviewed files of these readmitted patients. Primary outcome was the percentage of medication-related and potentially preventable readmissions according to the patient vs the provider. Descriptive data analysis was used. RESULTS: According to patients, 36 of 172 (21%) readmissions were medication-related, and of these, 21 (58%) were potentially preventable. According to providers, 26 (15%) readmissions were medication-related and 6 (23%) of these were potentially preventable. Patients and providers agreed on the medication relatedness in 11 of the 172 readmissions, and in two of these, agreement on the potential preventability existed. According to patients, preventive interventions belonged mostly to the hospital level, followed by the primary care level and patient level. CONCLUSION: Patients and providers differ substantially on their perspectives regarding the medication relatedness and preventability of readmissions. Patients were more likely to view medication-related readmissions as preventable.

Ketogenic diet treatment as adjuvant to standard treatment of glioblastoma multiforme: a feasibility and safety study.

BACKGROUND: High-grade glioma cells consume mainly glucose and cannot compensate for glucose restriction. Apoptosis may potentially occur under carbohydrate restriction by a ketogenic diet (KD). We explored the feasibility and safety of KD during standard treatment of chemoradiation in patients with glioblastoma multiforme. METHODS: A full liquid KD induced ketosis within 2 weeks before start of chemoradiation. After 6 weeks, the KD was modified with solid foods and medium-chain-triglyceride emulsions and used for an additional 6 weeks while maintaining ketosis. During the total study period (14 weeks), feasibility, safety, coping (both patient and partner), quality of life (QoL), neurological functioning and impairment were measured. Overall survival was analyzed with actuarial estimates. RESULTS: Eleven patients started the study protocol, nine reached ketosis and six (67%) completed the study. Severe adverse effects did not occur. The majority of coping scores ranged from 3 to 6 on a 10-point scale at all timepoints; QoL, neurological functioning, and impairment did not essentially change over time; overall survival ranged between 9.8 and 19.0 months. CONCLUSION: KD was feasible and safe as an adjuvant to standard chemoradiation treatment of glioblastoma multiforme. A supportive partner and intensive counseling were essential for coping. Future research should identify possible beneficial effects on overall survival. CLINICAL TRIAL REGISTRATION: Netherlands Trial Registry: NTR5167 (registration date 29-01-2015), http://www.trialregister.nl/trialreg/index.asp.

Prospective Validation of a Risk Prediction Model to Identify High-Risk Patients for Medication Errors at Hospital Admission.

BACKGROUND: Pharmacy-led medication reconciliation in elective surgery patients is often performed at the preoperative screening (POS). Because of the time lag between POS and admission, changes in medication may lead to medication errors at admission (MEAs). In a previous study, a risk prediction model for MEA was developed. OBJECTIVE: To validate this risk prediction model to identify patients at risk for MEAs in a university hospital setting. METHODS: The risk prediction model was derived from a cohort of a Dutch general hospital and validated within a comparable cohort from a Dutch University Medical Centre. MEAs were assessed by comparing the POS medication list with the reconciled medication list at hospital admission. This was considered the gold standard. For every patient, a risk score using the risk prediction model was calculated and compared with the gold standard. The risk prediction model was assessed with receiver operating characteristic (ROC) analysis. RESULTS: Of 368 included patients, 167 (45.4%) had at least 1 MEA. ROC analysis revealed significant differences in the area under the curve of 0.535 ( P = 0.26; validation cohort) versus 0.752 ( P < 0.0001; derivation cohort). The sensitivity in this validating cohort was 66%, with a specificity of 40%. Conclusion and Relevance: The risk prediction model developed in a general hospital population is not suitable to identify patients at risk for MEA in a university hospital population. However, number of medications is a common risk factor in both patient populations and should, thus, form the basis of an adapted risk prediction model.

Risk factors for medication errors at admission in preoperatively screened patients.

BACKGROUND: Preoperative screening (POS) may help to reduce medication errors at admission (MEA). However, due to the time window between POS and hospital admission, unintentional medication discrepancies may still occur and thus a second medication reconciliation at hospital admission can be necessary. Insight into potential risk factors associated with these discrepancies would be helpful to focus the second medication reconciliation on high-risk patients. OBJECTIVE: To determine the proportion of POS patients with MEA and to identify risk factors for MEA. METHODS: This single-centre observational cross-sectional study included elective surgical patients between October 26 and December 18, 2015. Main exclusion criteria were age younger than 18 years and daycare admissions. Medication reconciliation took place at the POS and was repeated within 30 hours of admission. Unintended discrepancies between the first and second medication reconciliation were defined as MEA. The primary outcome was the proportion of patients with one or more MEA. The association of this outcome with potential risk factors was analysed using multivariate logistic regression analysis. RESULTS: Of the 183 included patients, 60 (32.8%) patients had at least one MEA. In a multivariate model, the number of medications at POS (adjusted odds ratio 1.16 [95% confidence interval, 1.04-1.30]) and respiratory disease (4.25 [1.52-11.83]) were significantly associated with MEA. CONCLUSION: In one-third of preoperatively screened patients, an MEA was found. The number of medications and respiratory comorbidities are risk factors for MEA in preoperatively screened patients.

QTc prolongation during ciprofloxacin and fluconazole combination therapy: prevalence and associated risk factors.

AIM(S): Ciprofloxacin and fluconazole combination therapy is frequently used as prophylaxis for, and treatment of, infections in patients with haematological malignancies. However, both drugs are known to prolong the heart rate-corrected QT (QTc) interval, which is a serious risk factor for torsade de pointes (TdP). Therefore, the aim of the current study was to assess the prevalence of QTc prolongation during ciprofloxacin and fluconazole use. The secondary objective was to determine associated risk factors of QTc prolongation in these patients. METHODS: A prospective observational study was performed in patients admitted to the Erasmus University Medical Centre and treated with ciprofloxacin and fluconazole. A 12-lead electrocardiogram (ECG) was recorded at the estimated time to peak concentration (Tmax ) for the last added drug. The main outcome was the proportion of patients with QTc prolongation during treatment. Data on the following potential risk factors were collected: patient characteristics, serum electrolyte levels, dosage of ciprofloxacin and fluconazole, renal and liver function and concomitant use of other QTc-prolonging drugs and cytochrome P450 3A4 inhibitors. RESULTS: A total of 170 patients were included, of whom 149 (87.6%) were treated for haematological malignancies. The prevalence of QTc prolongation was 4.7%. No risk factors were found to be associated with QTc prolongation. The QTc interval increased by 10.7 ms [95% confidence interval (CI) 7.2, 14.1 ms] during ciprofloxacin and fluconazole combination therapy. CONCLUSION: The prevalence of QTc prolongation in patients using ciprofloxacin and fluconazole is low compared with the prevalence in the general population, which varies from 5% to 11%. In addition, no risk factors were found. Given the low prevalence, routine ECG monitoring in patients on this therapy should be reconsidered.

Noncompliance with guidelines on proton pump inhibitor prescription as gastroprotection in hospitalized surgical patients who are prescribed NSAIDs.

BACKGROUND AND AIMS: As NSAIDs can cause serious upper gastrointestinal harm, guidelines have been established for the prescribing of proton pump inhibitors (PPIs) in high-risk patients using NSAIDs. Studies examining guideline compliance in surgical patients are scarce. Therefore, a retrospective cross-sectional database study was carried out aimed at determining the proportion of noncompliance with the Dutch guideline and determining the association of several factors with this noncompliance. MATERIALS AND METHODS: Hospital admissions of patients on surgical wards of Erasmus University Medical Center between 1 January 2013 and 1 August 2014 were included in which an NSAID was newly prescribed. Preadmission PPI use was excluded. The main outcome was the proportion of noncompliance with the guideline. As a secondary outcome, the association of several potential risk factors with noncompliance was assessed. The proportion of guideline noncompliance was calculated as the percentage of all included surgical ward admissions. For the secondary analysis, univariate and multivariable logistic regression analyses were carried out. RESULTS: A total of 409 admissions were included. The proportion of admissions in which guideline noncompliance was present was 46.6%, mostly because of incorrectly added PPIs. Coxib use [adjusted odds ratio 0.22 (95% confidence interval 0.12-0.44)], polypharmacy (the use of five or more drugs) [2.18 (1.27-3.76)], and the surgical wards orthopedics [22.32 (5.38-92.55)], plastic surgery [10.82 (2.51-46.59)], trauma surgery [5.78 (1.47-22.70)], and transplant/vascular surgery [4.45 (1.10-18.00)] were statistically significantly associated with noncompliance. CONCLUSION: Noncompliance with the guideline on NSAID use and gastroprotection is present in almost half of surgical hospital admissions and mainly involves overprescribing.

Medication review using a Systematic Tool to Reduce Inappropriate Prescribing (STRIP) in adults with an intellectual disability: A pilot study.

A Systematic Tool to Reduce Inappropriate Prescribing (STRIP), which includes the Screening Tool to Alert doctors to Right Treatment (START) and the Screening Tool of Older Peoples' Prescriptions (STOPP), has recently been developed in the Netherlands for older patients with polypharmacy in the general population. Active involvement of the patient is part of this systematic multidisciplinary medication review. Although annual review of pharmacotherapy is recommended for people with an intellectual disability (ID), a specific tool for this population is not yet available. Besides, active involvement can be compromised by ID. Therefore, the objective of this observational pilot study was to evaluate the process of medication review using STRIP in adults with an ID living in a centralized or dependent setting and the identification of drug-related problems using this tool. The study was performed in three residential care organizations for ID. In each organization nine clients with polypharmacy were selected by an investigator (a physician in training to become a specialized physician for individuals with an ID) for a review using STRIP. Clients as well as their legal representatives (usually a family member) and professional caregivers were invited to participate. Reviews were performed by an investigator together with a pharmacist. First, to evaluate the process time-investments of the investigator and the pharmacist were described. Besides, the proportion of reviews in which a client and/or his legal representative participated was calculated as well as the proportion of professional caregivers that participated. Second, to evaluate the identification of drug-related problems using STRIP, the proportion of clients with at least one drug-related problem was calculated. Mean time investment was 130minutes for the investigator and 90minutes for the pharmacist. The client and/or a legal representatives were present during 25 of 27 reviews (93%). All 27 professional caregivers (100%) were involved. For every client included at least one drug-related problem was identified. In total 127 drug-related problems were detected, mainly potentially inappropriate or unnecessary drugs. After six months, 15.7% of the interventions were actually implemented. Medication review using STRIP seems feasible in adults with an ID and identifies drug-related problems. However, in this pilot study the implementation rate of suggested interventions was low. To improve the implementation rate, the treating physician should be involved in the review process. Besides, specific adaptations to STRIP to address drug-related problems specific for this population are required.

A systematic review on the accumulation of prophylactic dosages of low-molecular-weight heparins (LMWHs) in patients with renal insufficiency.

PURPOSE: Although therapeutic dosages of most low-molecular-weight heparins (LMWHs) are known to accumulate in patients with renal insufficiency, for the lower prophylactic dosages this has not been clearly proven. Nevertheless, dose reduction is often recommended. We conducted a systematic review to investigate whether prophylactic dosages of LMWH accumulate in renal insufficient patients. METHODS: A comprehensive search was conducted on 17 February 2015 using Embase, Medline, Web of Science, Scopus, Cochrane, PubMed publisher, and Google scholar. The syntax emphasized for LMWHs, impaired renal function, and pharmacokinetics. The search yielded 674 publications. After exclusion by reading the titles, abstracts, and if necessary the full paper, 11 publications remained. RESULTS: For dalteparin and tinzaparin, no accumulation was observed. Enoxaparin, on the other hand, did lead to accumulation in patients with renal insufficiency, although not in patients undergoing renal replacement therapy. Bemiparin and certoparin also did show accumulation. No data were available for nadroparin. CONCLUSIONS: In this systematic review, we show that prophylactic dosages of tinzaparin and dalteparin are likely to be safe in patients with renal insufficiency and do not need dose reduction based on the absence of accumulation. However, prophylactic dosages of enoxaparin, bemiparin, and certoparin did show accumulation in patients with a creatinine clearance (CrCl) below 30 ml/min, and therefore, dose reduction is required. The differences in occurrence of accumulation seem to depend on the mean molecular weight of LMWHs.

Identification of drug-related problems by a clinical pharmacist in addition to computerized alerts.

BACKGROUND: Both clinical pharmacists and computerized physician order entry systems with clinical decision support (CPOE/CDSS) can reduce drug-related problems (DRPs). However, the contribution of a clinical pharmacist in addition to CPOE/CDSS has not been established in a prospective study. OBJECTIVE: To determine which DRPs can be identified by a clinical pharmacist in a setting with routine use of CPOE/CDSS. SETTING: Two surgical and two neurological wards in St. Elisabeth hospital, a 600-bed teaching hospital in the Netherlands. METHODS: In this observational prospective follow-up study a clinical pharmacist reviewed the pharmacotherapy of patients admitted to surgical and neurological wards to identify DRPs (i.e. medication errors and adverse drug events) and discussed the relevance of identified problems and interventions to resolve these with the responsible physician. Acceptance of the proposed interventions and the presence of alerts in CPOE/CDSS were assessed. Primary outcome was the proportion of DRPs identified by the clinical pharmacist that also triggered a CPOE/CDSS alert. Differences between the DRPs that generated an alert and those that did not were expressed as relative risks or analyzed with Chi square statistics or Mann-Whitney U tests. MAIN OUTCOME MEASURE: The proportion of drug-related problems identified by the clinical pharmacist that also generated an alert in the CPOE/CDSS. RESULTS: During 1206 medication reviews, 442 potential DRPs were identified; 286 (65 %) DRPs were considered relevant and 247 (56 %) of the proposed interventions were accepted. A CPOE/CDSS alert was generated for 35 (8 %) of the DRPs the clinical pharmacist identified. The only difference between problems that triggered an alert and those that did not was the class of the DRP (indication 23 vs. 36 %, effectiveness 23 vs. 13 %, safety 23 vs. 10 % and pharmaceutical care issues 31 vs. 42 %, p = 0.02). CPOE/CDSS triggered 623 additional alerts that were handled during routine pharmacy service. CONCLUSIONS: As most DRPs identified by a clinical pharmacist were not detected in daily clinical practice by CPOE/CDSS, a clinical pharmacist contributes to reducing DRPs. The sensitivity of CPOE/CDSS to detect certain classes of problems should be optimized.

Prescription errors in older individuals with an intellectual disability: prevalence and risk factors in the Healthy Ageing and Intellectual Disability Study.

Prescribing pharmacotherapy for older individuals with an intellectual disability (ID) is a complex process, possibly leading to an increased risk of prescription errors. The objectives of this study were (1) to determine the prevalence of older individuals with an intellectual disability with at least one prescription error and (2) to identify potential risk factors for these prescription errors (age, gender, body mass index (BMI), frailty index, level of intellectual disability and living situation). The study population consisted of 600 older (≥ 50 years) individuals with an ID using one or more drugs who were randomly selected from the study cohort of the Healthy Ageing and Intellectual Disability (HA-ID) Study. The medication used at the time of measurement was screened for errors by a hospital pharmacist/clinical pharmacologist and a Master's student pharmacy using consensus methodology. Participants with one or more prescription errors were compared to participants without prescription errors by multivariate logistic regression to identify potential risk factors. The prevalence of individuals with one or more prescription errors was 47.5% (285 of 600 individuals; 95% confidence interval (CI) 43-52%). Relevant errors, defined as errors that actually do require a change of pharmacotherapy, were identified in 26.8% of the individuals (161 of 600 individuals; 95% CI 23-30%). Higher age (adjusted odds ratio (OR adj) 1.03; 95% CI 1.01-1.06), less severe intellectual disability (moderate: OR adj 0.48; 95% CI 0.31-0.74 and severe: OR adj 0.56; 95% CI 0.32-0.98), higher BMI (OR adj 1.04; 95% CI 1.01-1.08), higher frailty index (0.39-0.54: OR adj 2.4; 95% CI 1.21-4.77 and ≥ 0.55: OR adj 3.4; 95% CI 1.03-11.02), polypharmacy (OR adj 8.06; 95% CI 5.59-11.62) and use of medicines acting on the central nervous system (OR adj 3.34; 95% CI 2.35-4.73) were independently associated with the occurrence of prescription errors. Interventions targeted to high risk patients should be designed and implemented to improve pharmacotherapy in older individuals with an intellectual disability.

Thrombocytopenia in adult cancer patients receiving cytotoxic chemotherapy: results from a retrospective hospital-based cohort study.

BACKGROUND: Data on the frequency and relative risk (RR) of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumours receiving chemotherapy in clinical practice are limited. OBJECTIVE: The aim of the study was to estimate the frequency and RR of thrombocytopenia in adult patients with solid tumours receiving chemotherapy treatment. METHODS: For this retrospective, hospital-based study, adult patients with solid tumours who received chemotherapy at the University Medical Center Utrecht in the period 2004-6 were identified from the Utrecht Patient Oriented Database. We examined the frequency of (i) overall thrombocytopenia (defined as platelet count <100 × 109/L) with or without other cytopenias; (ii) isolated thrombocytopenia (i.e. without other cytopenias); and (iii) the frequency and RR of overall thrombocytopenia and isolated thrombocytopenia associated with different cytotoxic agents. RESULTS: A total of 614 patients receiving one of 37 different chemotherapy regimens was included. Overall thrombocytopenia frequency was 21.8% and isolated thrombocytopenia frequency was 6.2%. The highest frequencies of thrombocytopenia were observed in patients receiving carboplatin monotherapy (81.8%) and combination therapies that included carboplatin (58.2%), gemcitabine (64.4%) or paclitaxel (59.3%). The highest RRs of thrombocytopenia, compared with cisplatin-based therapy, were observed for combination therapies of carboplatin/gemcitabine (RR 10.1; 95% CI 5.5, 18.5) and carboplatin/paclitaxel/etoposide (RR 11.8; 95% CI 6.7, 20.8). In 54% of cases, the thrombocytopenia was of grade 2-4, which are considered to be the most clinically relevant grades. The highest frequencies of isolated thrombocytopenia were found with combination therapies that included oxaliplatin (28.6%) or gemcitabine (28.9%). CONCLUSIONS: The results suggest that CIT is a relevant problem in clinical practice. Further research is necessary to investigate the clinical consequences of thrombocytopenia. The observed frequencies of thrombocytopenia were lower than those observed in older studies, but comparable with that observed in a recent US-based study. The observed increased risks for possible immune-mediated thrombocytopenia associated with exposure to oxaliplatin and gemcitabine contribute to the suspicion that these drugs can cause immune-mediated thrombocytopenia, and warrant further investigation. For clinicians, the mechanism has important consequences because in immune-mediated thrombocytopenia the drug must be avoided, while in dose-dependent thrombocytopenia a dose reduction may be sufficient.

Erroneous exchange of asparaginase forms in the treatment of acute lymphoblastic leukemia.

For the treatment of children with acute lymphoblastic leukemia (ALL), Dutch pediatric oncologists use the Dutch Childhood Oncology Group ALL 10 protocol. This protocol is complex, as it comprises many different drug regimens. One of the drugs is asparaginase which is available in different forms with different pharmacokinetics: Escherichia coli asparaginase, Erwinia asparaginase, and pegylated E. coli asparaginase [polyethylene glycol (PEG) asparaginase]. Here, we report the case of a 3-year-old patient treated with ALL who was 8 times erroneously treated with E. coli asparaginase instead of PEG asparaginase. As E. coli asparaginase was administered to the patient in the lower dosage regimen of PEG asparaginase, she was undertreated, but at the end of the treatment the patient was in complete remission. This case report describes the actual course of treatment, the reasons why it went wrong, and possible preventive measures.

The impact of type of manual medication cart filling method on the frequency of medication administration errors: a prospective before and after study.

BACKGROUND: The medication cart can be filled using an automated system or a manual method and when using a manual method the medication can be arranged either by round time or by medication name. For the manual methods, it is hypothesized that the latter method would result in a lower frequency of medication administration errors because nurses are forced to read the medication labels, but evidence for this hypothesis is lacking. OBJECTIVES: The aim of this study was to compare the frequency of medication administration errors of two different manual medication cart filling methods, namely arranging medication by round time or by medication name. DESIGN: A prospective, observational study with a before-after design. PARTICIPANTS AND SETTINGS: Eighty-six patients who stayed on an orthopaedic ward in one university medical centre in the Netherlands were included. METHODS: Disguised observation was used to detect medication administration errors. The medication cart filling method in usual care was to fill the cart with medication arranged by round time. The intervention was the implementation of the second medication cart filling method, where the medication cart was filled by arranging medicines by their names. The primary outcome was the frequency of medication administrations with one or more error(s) after the intervention compared with before the intervention. The secondary outcome was the frequency of subtypes of medication administration errors. RESULTS: After the intervention 170 of 740 (23.0%) medication administrations with one or more medication administration error(s) were observed compared to 114 of 589 (19.4%) before the intervention (odds ratio 1.24 [95% confidence interval 0.95-1.62]). The distribution of subtypes of medication administration errors before and after the intervention was statistically significantly different (p<0.001). Analysis of subtypes revealed more omissions and wrong time errors after the intervention than before the intervention. Unauthorized medication errors were detected more frequently before the intervention than after the intervention. CONCLUSION: The frequency of medication administration errors with the medication cart filling method where the medication is arranged by name was not statistically significantly different compared to the medication cart filling method where the medication is arranged by round time.