Prescription Sequence Symmetry Analysis (PSSA) to assess prescribing cascades: a step-by-step guide.

Prescribing cascades occur when patients are prescribed medication to treat the adverse drug reaction of previously prescribed medication. Prescription sequence symmetry analysis (PSSA) can be used to assess the association between two medications in prescription or dispensing databases and thus the potential occurrence of prescribing cascades. In this article, a step-by-step guide is presented for conducting PSSA to assess prescribing cascades. We describe considerations for medication data collection and setting time periods for relevant parameters, including washout window, exposure window, continued exposure interval and blackout period. With two examples, we illustrate the impact of changes in these parameters on the strengths of associations observed. Given the impact seen, we recommend that researchers clearly specify and explain all considerations regarding medication included and time windows set when studying prescribing cascades with PSSA, and conduct subgroup and sensitivity analyses.

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.

Implementation of a pharmacist-led transitional pharmaceutical care programme: Process evaluation of Medication Actions to Reduce hospital admissions through a collaboration between Community and Hospital pharmacists (MARCH).

WHAT IS KNOWN AND OBJECTIVE: The recently conducted Medication Actions to Reduce hospital admissions through a collaboration between Community and Hospital pharmacists (MARCH) transitional care programme, which aimed to test the effectiveness of a transitional care programme on the occurrence of ADEs post-discharge, did not show a significant effect. To clarify whether this non-significant effect was due to poor implementation or due to ineffectiveness of the intervention as such, a process evaluation was conducted. The aim of the study was to gain more insight into the implementation fidelity of MARCH. METHODS: A mixed methods design and the modified Conceptual Framework for Implementation Fidelity was used. For evaluation, the implementation fidelity and moderating factors of four key MARCH intervention components (teach-back, the pharmaceutical discharge letter, the post-discharge home-visit and the transitional medication review) were assessed. Quantitative data were collected during and after the intervention. Qualitative data were collected using semi-structured interviews with MARCH healthcare professionals (community pharmacists, clinical pharmacists, pharmacy assistants and pharmaceutical consultants) and analysed using thematic analysis. RESULTS AND DISCUSSION: Not all key intervention components were implemented as intended. Teach-back was not always performed. Moreover, 63% of the pharmaceutical discharge letters, 35% of the post-discharge home-visits and 44% of the transitional medication reviews were not conducted within their planned time frames. Training sessions, structured manuals and protocols with detailed descriptions facilitated implementation. Intervention complexity, time constraints and the multidisciplinary coordination were identified as barriers for the implementation. WHAT IS NEW AND CONCLUSION: Overall, the implementation fidelity was considered to be moderate. Not all key intervention components were carried out as planned. Therefore, the non-significant results of the MARCH programme on ADEs may at least partly be explained by poor implementation of the programme. To successfully implement transitional care programmes, healthcare professionals require full integration of these programmes in the standard work-flow including IT improvements as well as compensation for the time investment.

The effect of Patient's Own Medication use on patient's self-reported medication knowledge during hospitalisation: a pre-post intervention study.

BACKGROUND: Improving patient's medication knowledge and consequently medication use is essential for optimal treatment outcomes. As patient knowledge about medication is currently suboptimal, interventions to optimise medication knowledge are necessary. Implementation of Patient's Own Medication (POM) in which patients bring their outpatient medication to the hospital, and nurses administer these during admission, may increase medication knowledge. The aim of this study is to explore the impact of POM use on self-reported medication knowledge of hospitalised patients compared to standard care. Patient's sense of medication safety, attitude to the provision of information, and to inpatient medication use were studied in both standard care and during POM use too. METHOD: In this nationwide intervention study perceived medication knowledge was assessed with a questionnaire pre and post implementing POM use. The questionnaire assessed perceived medication knowledge at admission and discharge, medication safety during hospitalisation, the provision of information during hospitalisation and at discharge, and inpatient medication use during hospitalisation. Patients' answers were categorised into positive and negative/neutral. The proportion of patients with adequate medication knowledge, in the standard care and POM use group at hospital admission and discharge, were calculated and compared with adjustment for potential confounders. RESULTS: Among the 731 patients (393 received standard care and 338 POM) who completed the questionnaire (80.2%), POM use seemed to be positively associated with self-reported knowledge on how to use medication at discharge (adjusted OR: 3.22 [95% CI 2.01-5.16]). However, for the other two knowledge related statements POM use was not associated. Medication knowledge at admission was the most important variable associated with perceived medication knowledge at discharge. The majority perceived POM use to be safer (52.9% of standard care patients versus 74.0% POM users; P <  0.01), POM users knew better which medicines they still used during hospitalisation (85.8% versus 92.3% resp.; P = 0.01), and most patients preferred POM use regardless of having experienced it (68.2% versus 82.2% resp.; P <  0.01). CONCLUSION: POM use positively affects patient's medication knowledge about how to use medication and patients' perception of medication safety. With POM use more patients have a positive attitude towards the provision of information. The majority of patients prefer POM use. In conclusion, POM use seems a valuable intervention and requires further investigation.

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.

Unintentional guideline deviations in hospitalized patients with two or more antithrombotic agents: an intervention study.

PURPOSE: Treatment schedules for antithrombotic therapy are complex, and there is a risk of inappropriate prescribing or continuation of antithrombotic therapy beyond the intended period of time. The primary aim of this study was to determine the frequency of unintentional guideline deviations in hospitalized patients. Secondary aims were to determine whether the frequency of unintentional guideline deviations decreased after intervention by a pharmacist, to determine the acceptance rate of the interventions and to determine the type of interventions. METHODS: We performed a non-controlled prospective intervention study in three teaching hospitals in the Netherlands. We examined whether hospitalized patients who used the combination of an anticoagulant plus at least one other antithrombotic agent had an unintentional guideline deviation. In these cases, the hospital pharmacist contacted the physician to assess whether this deviation was intentional. If the deviation was unintentional, a recommendation was provided how to adjust the antithrombotic regimen according to guideline recommendations. RESULTS: Of the 988 included patients, 407 patients had an unintentional guideline deviation (41.2%). After intervention, this was reduced to 22 patients (2.2%) (p < 0.001). The acceptance rate of the interventions was 96.6%. The most frequently performed interventions were discontinuation of an low molecular weight heparin in combination with a direct oral anticoagulant and discontinuation of an antiplatelet agent when there was no indication for the combination of an antiplatelet agent and an anticoagulant. CONCLUSION: A significant number of hospitalized patients who used an anticoagulant plus one other antithrombotic agent had an unintentional guideline deviation. Intervention by a pharmacist decreased unintentional guideline deviations.

Guidelines for mono, double and triple antithrombotic therapy.

Guidelines for antithrombotic therapy are complex, especially if a patient has several indications that require antithrombotic therapy. In general, no patient should receive lifelong double or triple antithrombotic therapy. In this overview, we outline the most common indications for mono, double and triple antithrombotic therapy; the preferred antithrombotic therapy and the recommended duration of therapy. Both antiplatelet therapy and therapeutic anticoagulation therapy with vitamin K antagonists or direct oral anticoagulants were included. European guidelines were used or, if no European guidelines were available, the Dutch guidelines were used.

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.

Drug-drug interactions with metronidazole and itraconazole in patients using acenocoumarol.

PURPOSE: Various population-based cohort studies have shown that antimicrobial agents increase the risk of overanticoagulation in patients using coumarins. In this study, we assessed this association in hospitalized patients. METHODS: We included all patients hospitalized in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands), who started using an antimicrobial agent during acenocoumarol treatment or vice versa between 1 January 2015 and 1 July 2019. Patients were followed from start of concomitant therapy until 48 h after termination of the concomitant therapy or discharge, whichever came first. We analyzed the association between the antimicrobial agents and the risk of overanticoagulation, defined as an interpolated INR above 6, using Cox regression analysis. We corrected for multiple testing with the Bonferroni correction. Patients who started using acenocoumarol and amoxicillin/clavulanic acid were used as reference group. RESULTS: In the study population, sixteen antimicrobial agents were started frequently concomitantly with acenocoumarol treatment. We included 2157 interaction episodes in 1172 patients. Patients who started using the combination of co-trimoxazole (HR 3.76; 95% CI 1.47-9.62; p = 0.006), metronidazole (HR 2.55; 95% CI 1.37-4.76; p = 0.003), or itraconazole (HR 4.11; 95% CI 1.79-9.45; p = 0.001) concomitantly with acenocoumarol treatment had an increased risk of overanticoagulation compared with patients using acenocoumarol and amoxicillin/clavulanic acid concomitantly. The associations for metronidazole (p = 0.045) and itraconazole (p = 0.015) remained statistically significant after correction for multiple testing. CONCLUSION: Co-trimoxazole, metronidazole, and itraconazole increase the risk of overanticoagulation in patients using acenocoumarol. These combinations should be avoided if possible or otherwise acenocoumarol doses should be reduced and INR measured more frequently.

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.

Development and validation of a tool to assess the risk of QT drug-drug interactions in clinical practice.

BACKGROUND: The exact risk of developing QTc-prolongation when using a combination of QTc-prolonging drugs is still unknown, making it difficult to interpret these QT drug-drug interactions (QT-DDIs). A tool to identify high-risk patients is needed to support healthcare providers in handling automatically generated alerts in clinical practice. The main aim of this study was to develop and validate a tool to assess the risk of QT-DDIs in clinical practice. METHODS: A model was developed based on risk factors associated with QTc-prolongation determined in a prospective study on QT-DDIs in a university medical center inthe Netherlands. The main outcome measure was QTc-prolongation defined as a QTc interval > 450 ms for males and > 470 ms for females. Risk points were assigned to risk factors based on their odds ratios. Additional risk factors were added based on a literature review. The ability of the model to predict QTc-prolongation was validated in an independent dataset obtained from a general teaching hospital against QTc-prolongation as measured by an ECG as the gold standard. Sensitivities, specificities, false omission rates, accuracy and Youden's index were calculated. RESULTS: The model included age, gender, cardiac comorbidities, hypertension, diabetes mellitus, renal function, potassium levels, loop diuretics, and QTc-prolonging drugs as risk factors. Application of the model to the independent dataset resulted in an area under the ROC-curve of 0.54 (95% CI 0.51-0.56) when QTc-prolongation was defined as > 450/470 ms, and 0.59 (0.54-0.63) when QTc-prolongation was defined as > 500 ms. A cut-off value of 6 led to a sensitivity of 76.6 and 83.9% and a specificity of 28.5 and 27.5% respectively. CONCLUSIONS: A clinical decision support tool with fair performance characteristics was developed. Optimization of this tool may aid in assessing the risk associated with QT-DDIs. TRIAL REGISTRATION: No trial registration, MEC-2015-368.

Factors associated with workarounds in barcode-assisted medication administration in hospitals.

AIMS AND OBJECTIVES: To identify that workarounds (defined as "informal temporary practices for handling exceptions to normal procedures or workflow") by nurses using information technology potentially compromise medication safety. Therefore, we aimed to identify potential risk factors associated with workarounds performed by nurses in Barcode-assisted Medication Administration in hospitals. BACKGROUND: Medication errors occur during the prescribing, distribution and administration of medication. Errors could harm patients and be a tragedy for both nurses and medical doctors involved. Interventions to prevent errors have been developed, including those based on information technology. To cope with shortcomings in information technology-based interventions as Barcode-assisted Medication Administration, nurses perform workarounds. Identification of workarounds in information technology is essential to implement better-designed software and processes which fit the nurse workflow. DESIGN: We used the data from our previous prospective observational study, performed in four general hospitals in the Netherlands using Barcode techniques, to administer medication to inpatients. METHODS: Data were collected from 2014-2016. The disguised observation was used to gather information on potential risk factors and workarounds. The outcome was a medication administration with one or more workarounds. Logistic mixed models were used to determine the association between potential risk factors and workarounds. The STROBE checklist was used for reporting our data. RESULTS: We included 5,793 medication administrations among 1,230 patients given by 272 nurses. In 3,633 (62.7%) of the administrations, one or more workarounds were observed. In the multivariate analysis, factors significantly associated with workarounds were the medication round at 02 p.m.-06 p.m. (adjusted odds ratio [OR]: 1.60, 95% CI: 1.05-2.45) and 06 p.m.-10 p.m. (adjusted OR: 3.60, 95% CI: 2.11-6.14) versus the morning shift 06 a.m.-10 a.m., the workdays Monday (adjusted OR: 2.59, 95% CI: 1.51-4.44), Wednesday (adjusted OR: 1.92, 95% CI: 1.2-3.07) and Saturday (adjusted OR: 2.24, 95% CI: 1.31-3.84) versus Sunday, the route of medication, nonoral (adjusted OR: 1.28, 95% CI: 1.05-1.57) versus the oral route of drug administration, the Anatomic Therapeutic Chemical classification-coded medication "other" (consisting of the irregularly used Anatomic Therapeutic Chemical classes [D, G, H, L, P, V, Y, Z]) (adjusted OR: 1.49, 95% CI: 1.05-2.11) versus Anatomic Therapeutic Chemical class A (alimentary tract and metabolism), and the patient-nurse ratio ≥6-1 (adjusted OR: 5.61, 95% CI: 2.9-10.83) versus ≤5-1. CONCLUSIONS: We identified several potential risk factors associated with workarounds performed by nurses that could be used to target future improvement efforts in Barcode-assisted Medication Administration. RELEVANCE TO CLINICAL PRACTICE: Nurses administering medication in hospitals using Barcode-assisted Medication Administration frequently perform workarounds, which may compromise medication safety. In particular, nurse workload and the patient-nurse ratio could be the focus for improvement measures as these are the most clearly modifiable factors identified in this study.

The effect of a pharmaceutical transitional care program on rehospitalisations in internal medicine patients: an interrupted-time-series study.

BACKGROUND: Medication errors at transition of care can adversely affect patient safety. The objective of this study is to determine the effect of a transitional pharmaceutical care program on unplanned rehospitalisations. METHODS: An interrupted-time-series study was performed, including patients from the Internal Medicine department using at least one prescription drug. The program consisted of medication reconciliation, patient counselling at discharge, and communication to healthcare providers in primary care. The primary outcome was the proportion of patients with an unplanned rehospitalisation within six months post-discharge. Secondary outcomes were drug-related hospital visits, drug-related problems (DRPs), adherence, believes about medication, and patient satisfaction. Interrupted time series analysis was used for the primary outcome and descriptive statistics were performed for the secondary outcomes. RESULTS: In total 706 patients were included. At 6 months, the change in trend for unplanned rehospitalisations between usual care and the program group was non-significant (- 0.2, 95% CI -4.9;4.6). There was no significant difference for drug-related visits although visits due to medication reconciliation problems occurred less often (4 usual care versus 1 intervention). Interventions to prevent DRPs were present for all patients in the intervention group (mean: 10 interventions/patient). No effect was seen on adherence and beliefs about medication. Patients were significantly more satisfied with discharge counselling (68.9% usual care vs 87.1% program). CONCLUSIONS: The transitional pharmaceutical care program showed no effect on unplanned rehospitalisations. This lack of effect is probably because the reason for rehospitalisations are multifactorial while the transitional care program focused on medication. There were less hospital visits due to medication reconciliation problems, but further large scale studies are needed due to the small number of drug-related visits. (Dutch trial register: NTR1519).

Anticoagulant medication errors in hospitals and primary care: a cross-sectional study.

OBJECTIVE: To assess the proportion of all medication error reports in hospitals and primary care that involved an anticoagulant. Secondary objectives were the anticoagulant involved, phase of the medication process in which the error occurred, causes and consequences of 1000 anticoagulant medication errors. Additional secondary objectives were the total number of anticoagulant medication error reports per month, divided by the total number of medication error reports per month and the proportion of causes of 1000 anticoagulant medication errors (comparing the pre- and post-guideline phase). DESIGN: A cross-sectional study. SETTING: Medication errors reported to the Central Medication incidents Registration reporting system. PARTICIPANTS: Between December 2012 and May 2015, 42 962 medication errors were reported to the CMR. INTERVENTION: N/A. MAIN OUTCOME MEASURE: Proportion of all medication error reports that involved an anticoagulant. Phase of the medication process in which the error occurred, causes and consequences of 1000 anticoagulant medication errors. The total number of anticoagulant medication error reports per month, divided by the total number of medication error reports per month (comparing the pre- and post-guideline phase) and the total number of causes of 1000 anticoagulant medication errors before and after introduction of the LSKA 2.0 guideline. RESULTS: Anticoagulants were involved in 8.3% of the medication error reports. A random selection of 1000 anticoagulant medication error reports revealed that low-molecular weight heparins were most often involved in the error reports (56.2%). Most reports concerned the prescribing phase of the medication process (37.1%) and human factors were the leading cause of medication errors mentioned in the reports (53.4%). Publication of the national guideline on integrated antithrombotic care had no effect on the proportion of anticoagulant medication error reports. Human factors were the leading cause of medication errors before and after publication of the guideline. CONCLUSIONS: Anticoagulant medication errors occurred in 8.3% of all medication errors. Most error reports concerned the prescribing phase of the medication process. Leading cause was human factors. The publication of the guideline had no effect on the proportion of anticoagulant medication errors.

Development of a clinical prediction model for an international normalised ratio ≥ 4·5 in hospitalised patients using vitamin K antagonists.

Vitamin K antagonists (VKAs) used for the prevention and treatment of thromboembolic disease, increase the risk of bleeding complications. We developed and validated a model to predict the risk of an international normalised ratio (INR) ≥ 4·5 during a hospital stay. Adult patients admitted to a tertiary hospital and treated with VKAs between 2006 and 2010 were analysed. Bleeding risk was operationalised as an INR value ≥4·5. Multivariable logistic regression analysis was used to assess the association between potential predictors and an INR ≥ 4·5 and validated in an independent cohort of patients from the same hospital between 2011 and 2014. We identified 8996 admissions of patients treated with VKAs, of which 1507 (17%) involved an INR ≥ 4·5. The final model included the following predictors: gender, age, concomitant medication and several biochemical parameters. Temporal validation showed a c statistic of 0·71. We developed and validated a clinical prediction model for an INR ≥ 4·5 in VKA-treated patients admitted to our hospital. The model includes factors that are collected during routine care and are extractable from electronic patient records, enabling easy use of this model to predict an increased bleeding risk in clinical practice.

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.

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 QTc interval prolongation.

PURPOSE: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In this study, we quantified the effect of these risk factors on the length of the QTc interval. METHODS: We analyzed all ECGs that were taken during routine practice between January 2013 and October 2016 in the Spaarne Gasthuis, a general teaching hospital in the Netherlands. We collected laboratory values in the week before the ECG recording and the drugs prescribed. For the identification of risk factors, we used multilevel linear regression analysis to correct for multiple ECG recordings per patient. RESULTS: We included 133,359 ECGs in our study, taken in 40,037 patients. Patients using one QT-prolonging drug had a 11.08 ms (95% CI 10.63-11.52; p < 0.001) longer QTc interval. Patients using two QT-prolonging drugs had a 3.04 ms (95% CI 2.06-4.02; p < 0.001) increase in the QTc interval compared to patients using one QT-prolonging drug. Women had a longer QTc interval compared to men (16.30 ms 95% CI 14.59-18.01; p < 0.001). The QTc interval increased with increasing age, but the difference between men and women diminished. Other independent risk factors that significantly prolonged the QTc interval with at least 10 ms were hypokalemia, hypocalcemia, and the use of loop diuretics. CONCLUSION: We identified and quantified various risk factors for QTc interval prolongation.

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.

The effect of prescriber education on medication-related patient harm in the hospital: a systematic review.

AIMS: Educating prescribers is a strategy to reduce prescription errors in hospitals. The present systematic review gives an overview of original research papers on the education of prescribers and reporting outcomes on (potential) patient harm. METHODS: A search of the databases Embase and Medline, using the Ovid interface, was performed. Research on the effect of physician education in order to prevent medication-related problems in inpatients, and on reporting original data and outcomes on prescribing errors and/or (potential) patient harm, was included. The assessment of methodological quality and risk of bias was performed using the Methodological Index for Non-Randomized studies (MINORS) checklist and the suggested risk of bias criteria for Effective Practice and Organization of Care (EPOC) reviews. RESULTS: Eight studies investigated an intervention on education alone, and in seven studies education was the main part of a multifaceted intervention. All studies were small and had short follow-up periods. The educational programmes varied and were given to physicians of different specialties and levels of experience. Most studies reported intermediate process parameters as the outcome. The risk of performance and reporting bias were high. CONCLUSION: All included studies suffered from poor methodology. The majority, especially studies in which education was part of a multifaceted intervention, reported effectiveness on intermediate outcome markers as prescription errors and potential adverse drug events. However, we found no firm evidence that educating prescribers in the hospital leads to a decrease in patient harm. Further work is needed to develop educational programmes, accompanied by more high-quality research with outcomes on the improvement of patient care.