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Background: eConsults are increasingly used worldwide to reduce specialist referrals and increase access to medical care. An additional benefit of using an eConsult tool is a reduction of health care costs while improving the quality of health care and patient participation. Currently, shared decision making is increasingly implemented and preferred by patients. eConsults are also a promising tool to improve access to the hospital pharmacist. Patients often have questions about their medication. When medication is started during a hospital admission or outpatient visit, community pharmacists are not always sufficiently informed to answer patient questions. Direct contact with hospital pharmacists may be more appropriate and efficient. This contact is facilitated through the eConsult feature in the hospital's patient portal., Objective: This study aims to evaluate the prevalence and contents of the eConsults sent by patients to hospital pharmacists., Methods: A first retrospective descriptive study was conducted at the Leiden University Medical Center in the Netherlands. Patients who sent at least one eConsult to a hospital pharmacist between March 2017 and December 2021 were included. Patient characteristics and the number of medications taken were extracted from electronic health records. The content of eConsults was analyzed and grouped into different subjects. Time of sending of the eConsults was analyzed. A comparison was made between the number of eConsults sent to the hospital pharmacy and the number sent to the medical center. Finally, the appropriateness for evaluation by the hospital pharmacist was assessed in all eConsults., Results: During the study period, 983 eConsults (from 808 patients) were sent to the hospital pharmacist. The average patient age was 56 (SD 15.9) years, and 51.4% (415/808) were male; 47.8% (386/808) of the patients used 0 to 4 medications, 33.0% (267/808) used 5 to 9 medications, and 19.2% (155/808) used ≥10 medications. Of the eConsults, 10.9% (107/983) were excluded due to not being medication-related or not intended for the hospital pharmacist. Patients being treated in 31 medical specialties sent eConsults to the hospital pharmacist. The most common medical specialty was cardiology with 22.5% (197/876) of the eConsults. Most eConsults were sent during office hours (614/876, 70.2%). eConsult subjects were medication verification (372/876, 42.5%), logistics (243/876, 27.7%), therapeutic effect and adverse events (100/876, 11.4%), use of medication (87/876, 9.9%), and other subjects (74/876, 8.4%)., Conclusions: Introducing eConsults allows patients to ask medication-related questions directly to hospital pharmacists. Our study shows that patients send medication reconciliation-related eConsults most often. Use of the eConsult tool leads to fast, direct, and documented communication between patient and hospital pharmacist. This can reduce medication-related errors, improve patient empowerment, and increase access to the hospital pharmacist., (©Vera Weinberg, Eva van Haren, Kim B Gombert-Handoko. Originally published in JMIR Formative Research (https://formative.jmir.org), 27.01.2023.)

Introduction : Nivolumab (N), pembrolizumab (P), and dabrafenib plus trametinib (D + T) have been registered as adjuvant treatments for resected stage III and IV melanoma since 2018. Electronic health records (EHRs) are a real-world data source that can be used to review treatments in clinical practice. In this study, we applied EHR text-mining software to evaluate the real-world tolerability, safety, and efficacy of adjuvant melanoma treatments. Methods : Adult melanoma patients receiving adjuvant treatment between January 2019 and October 2021 at the Leiden University Medical Center, the Netherlands, were included. CTcue text-mining software (v3.1.0, CTcue B.V., Amsterdam, The Netherlands) was used to construct rule-based queries and perform context analysis for patient inclusion and data collection from structured and unstructured EHR data. Results: In total, 122 patients were included: 54 patients treated with nivolumab, 48 with pembrolizumab, and 20 with D + T. Significantly more patients discontinued treatment due to toxicity on D + T (N: 16%, P: 6%, D + T: 40%), and X 2 (6, n = 122) = 14.6 and p = 0.024. Immune checkpoint inhibitors (ICIs) mainly showed immune-related treatment-limiting adverse events (AEs), and chronic thyroid-related AE occurred frequently (hyperthyroidism: N: 15%, P: 13%, hypothyroidism: N: 20%, P: 19%). Treatment-limiting toxicity from D + T was primarily a combination of reversible AEs, including pyrexia and fatigue. The 1-year recurrence-free survival was 70.3% after nivolumab, 72.4% after pembrolizumab, and 83.0% after D + T. Conclusions: Text-mining EHR is a valuable method to collect real-world data to evaluate adjuvant melanoma treatments. ICIs were better tolerated than D + T, in line with RCT results. For BRAF+ patients, physicians must weigh the higher risk of reversible treatment-limiting AEs of D + T against the risk of long-term immune-related AEs.

Purpose: Chemotherapy-induced febrile neutropenia (FN) is a life-threatening and chemotherapy dose-limiting adverse event. FN can be prevented with granulocyte-colony stimulating factors (G-CSFs). Guidelines recommend primary G-CSF use for patients receiving either high (> 20%) FN risk (HR) chemotherapy, or intermediate (10-20%) FN risk (IR) chemotherapy if the overall risk with additional patient-related risk factors exceeds 20%. In this study, we applied an EHR text-mining tool for real-world G-CSF treatment evaluation in breast cancer patients., Methods: Breast cancer patients receiving IR or HR chemotherapy treatments between January 2015 and February 2021 at LUMC, the Netherlands, were included. We retrospectively collected data from EHR with a text-mining tool and assessed G-CSF use, risk factors, and the FN and neutropenia (grades 3-4) and incidence., Results: A total of 190 female patients were included, who received 77 HR and 113 IR treatments. In 88.3% of the HR regimens, G-CSF was administered; 7.3% of these patients developed FN vs. 33.3% without G-CSF. Although most IR regimen patients had ≥ 2 risk factors, only 4% received G-CSF, of which none developed neutropenia. However, without G-CSF, 11.9% developed FN and 31.2% severe neutropenia., Conclusions: Our text-mining study shows high G-CSF use among HR regimen patients, and low use among IR regimen patients, although most had ≥ 2 risk factors. Therefore, current practice is not completely in accordance with the guidelines. This shows the need for increased awareness and clarity regarding risk factors. Also, text-mining can effectively be implemented for the evaluation of patient care., (© 2022. The Author(s).)

Purpose: Drug-Related Admissions (DRAs) are a well-known problem among older patients in the Emergency Department (ED). The aim of this study was (a) to investigate the prevalence and clinical manifestations of DRAs and the responsible drugs, (b) to study the association between geriatric characteristics and DRAs, and (c) to study the predictive performance of geriatric screeners for identifying DRAs in older ED patients., Methods: Patients aged ≥ 70 hospitalized from the ED were included. Demographics, geriatric characteristics and medications were collected. The the Acutely Presenting Older Patient (APOP)-screener, the Identification of Seniors At Risk (ISAR) and the ISAR-Hospitalized Patients (ISAR-HP) were used as geriatric screeners. Potential DRAs were identified retrospectively, the association between geriatric screeners and DRAs was investigated with logistic regression and the predictive performance was assessed by calculating the Area under the Curve (AUC) of the Receiver Operator Characteristics (ROC)., Results: The mean age of patients was 78 (IQR 73-83), using an average of 6 medications. Out of 240 admissions, 77 (30%) were classified as a DRA. Independent risk factors for DRAs were polypharmacy (OR 2.42; 95% CI 1.23-4.74) and the ADL dependency (OR 1.23; 95%CI 1.05-1.44). ISAR (OR 3.27; 95%CI 1.60-6.69) and ISAR-HP (OR 1.83; 95% CI 1.02-3.27) associated with increased risk of DRAs, whereas the APOP screener did not (OR 1.56; 95% CI 0.82-2.97). The predictive performance of all geriatric screeners for predicting DRAs was poor (AUC for all screeners < 0.60)., Conclusion: DRAs are highly prevalent in older ED patients. Polypharmacy, ADL dependency and a high ISAR or ISAR-HP are associated with higher risk for DRAs, but the predictive value of geriatric screeners is insufficient., (© 2021. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

The number of treatment options for patients with metastatic renal cell carcinoma (mRCC) has significantly grown in the last 15 years. Although randomized controlled trials are fundamental in investigating mRCC treatment efficacy, their external validity can be limited. Therefore, the efficacy of the different treatment options should also be evaluated in clinical practice. We performed a chart review of electronic health records using text mining software to study the current treatment patterns and outcomes. mRCC patients from two large hospitals in the Netherlands, starting treatment between January 2015 and May 2020, were included. Data were collected from electronic health records using a validated text mining tool. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method. Most frequent first-line treatments were pazopanib (n = 70), sunitinib (n = 34), and nivolumab with ipilimumab (n = 28). The overall median PFS values for first-line treatment were 15.7 months (95% confidence interval [95%CI], 8.8-20.7), 16.3 months (95%CI, 9.3-not estimable [NE]) for pazopanib, and 6.9 months (95% CI, 4.4-NE) for sunitinib. The overall median OS values were 33.4 months (95%CI, 28.1-50.9 months), 39.3 months (95%CI, 29.5-NE) for pazopanib, and 28.1 months (95%CI, 7.0-NE) for sunitinib. For nivolumab with ipilimumab, median PFS and median OS were not reached. Of the patients who finished first- and second-line treatments, 64 and 62% received follow-up treatments, respectively. With most patients starting on pazopanib and sunitinib, these real-world treatment outcomes were most likely better than in pivotal trials, which may be due to extensive follow-up treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 van Laar, Gombert-Handoko, Groenwold, van der Hulle, Visser, Houtsma, Guchelaar and Zwaveling.)

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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

For the treatment of Covid-19 patients with remdesivir, poor renal and liver function were both exclusion criteria in randomized clinical trials and contraindication for treatment. Also, nephrotoxicity and hepatotoxicity are reported as adverse events. We retrospectively reviewed renal and liver functions of Covid-19 103 patients who received remdesivir in the 15 days after treatment initiation. Approximately 20% of the patient population met randomized clinical trial exclusion criteria. In total, 11% of the patients had a decrease in estimated glomerular filtration rate >10 mL/min/1.73m 2 . Also, 25 and 35% had increased alanine transaminase and aspartate transaminase levels, respectively. However, serious adverse events were limited. Therefore, based on these preliminary results, contraindications based on kidney and liver function should not be absolute for remdesivir treatment in patients with Covid-19 if these functions are monitored regularly. A larger patient cohort is warranted to confirm our results., (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Real-world evidence can close the inferential gap between marketing authorization studies and clinical practice. However, the current standard for real-world data extraction from electronic health records (EHRs) for treatment evaluation is manual review (MR), which is time-consuming and laborious. Clinical Data Collector (CDC) is a novel natural language processing and text mining software tool for both structured and unstructured EHR data and only shows relevant EHR sections improving efficiency. We investigated CDC as a real-world data (RWD) collection method, through application of CDC queries for patient inclusion and information extraction on a cohort of patients with metastatic renal cell carcinoma (RCC) receiving systemic drug treatment. Baseline patient characteristics, disease characteristics, and treatment outcomes were extracted and these were compared with MR for validation. One hundred patients receiving 175 treatments were included using CDC, which corresponded to 99% with MR. Calculated median overall survival was 21.7 months (95% confidence interval (CI) 18.7-24.8) vs. 21.7 months (95% CI 18.6-24.8) and progression-free survival 8.9 months (95% CI 5.4-12.4) vs. 7.6 months (95% CI 5.7-9.4) for CDC vs. MR, respectively. Highest F1-score was found for cancer-related variables (88.1-100), followed by comorbidities (71.5-90.4) and adverse drug events (53.3-74.5), with most diverse scores on international metastatic RCC database criteria (51.4-100). Mean data collection time was 12 minutes (CDC) vs. 86 minutes (MR). In conclusion, CDC is a promising tool for retrieving RWD from EHRs because the correct patient population can be identified as well as relevant outcome data, such as overall survival and progression-free survival., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Medication non-adherence is one of the most important causes for shortened graft survival subsequently leading to a reduction in kidney graft survival results. Our aim was to provide an overview of its prevalence, risk factors, diagnostic methods and interventions to improve adherence in kidney transplant recipients. Therefore, we systematically searched the databases PubMed, COCHRANE Library, Web of Science and EMBASE for studies addressing "medication adherence", "compliance", "adherence", "kidney transplantation" and "life style factors". We identified 96 studies that satisfied our inclusion criteria. A problematic lack of a uniformly accepted definition for non-adherence was found, consequently leading to a wide range in non-adherence prevalence (36-55%). Using one uniformly accepted non-adherence definition should therefore be encouraged. A wide range in diagnostic methods makes it difficult to accurately detect non-adherence. Heterogeneous results of intervention studies make it difficult to select the best adherence enhancing method, challenging the battle against medication non-adherence. Literature suggests a combination of personalized interventions, based on patient-specific non-adherent behavior, to be most successful in improvement of adherence. High quality diagnostic methods and multidisciplinary, personalized interventions with focus on relevant clinical outcome are essential in overcoming medication non-adherence in kidney transplant recipients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Medication reconciliation in transitions of care can prevent medication transfer errors (MTE). MTE can cause patient harm. Since performing medication reconciliation for every patient is not always feasible, identification of potential risk factors of MTE could aid in targeting this intervention to the right patients., Objective: To establish the proportion of patients with one or more MTE in the outpatient nephrology setting. Secondary patient characteristics associated with MTE, type and potential harm, and medication groups were investigated., Methods: This retrospective observational cohort study was conducted in the Leiden University Medical Center, the Netherlands, between November 2017 and April 2018. The cohort involved patients in whom medication reconciliation was performed by a medical attendant using the electronic tool 'Medical Dashboard' prior to visiting the nephrologist. MTE were defined as unintended discrepancies between the medication in the hospital system and the result of the medication reconciliation. The proportion of patients with one or more MTE was calculated and the association of patient characteristics (age, sex, number of medications and kidney function (CKD-EPI)) with MTE was analyzed using multivariate logistic regression., Results: Of 380 patients, 235 patients (61.8%) had at least one MTE. On average patients used 10.3 medications. The number of medications per patient was significantly associated with MTE; OR 1.11 (95%CI 1.05-1.16). No association was found for age, sex, and kidney function., Conclusion: In ambulatory nephrology patients 61.8% had at least one MTE. Nephrology patients using a higher number of drugs are more prone to MTE., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

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.

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., (Copyright © 2018 John Wiley & Sons, Ltd.)

Background: Hyperkalemia is a potentially dangerous electrolyte abnormality with a reported incidence of 1-10 % in hospitals. Patients are especially at risk of developing this complication if they use a combination of potassium supplements and potassium sparing diuretics or renin-angiotensin-aldosterone-system (RAAS) inhibitors. Previous studies on the occurrence of hyperkalemia in patients who use multiple potassium influencing drugs simultaneously were either small in sample size or did not investigate the full range of drugs involved., Objective: To assess the prevalence of hyperkalemia and to identify risk factors for its development in hospitalised patients using potassium supplements, potassium-sparing diuretics and/or RAAS-inhibitors concurrently., Setting: The study was conducted at the Onze Lieve Vrouwe Hospital in Amsterdam, The Netherlands from January 2009 to May 2010., Method: A retrospective, nested case-control study included hospitalised patients who used a combination of potassium-influencing drugs. Cases were patients with serum potassium ≥ 5.5 mmol/l, controls were patients with normal serum potassium levels. Cases and controls were included in a ratio of 1:2. The following known risk factors associated with hyperkalemia were recorded and statistically analyzed: diabetes mellitus, congestive heart failure, decreased renal function, advanced age, gender and use of heparin, digoxin, non-steroidal anti-inflammatory drugs, beta-blockers, calcineurin antagonists and trimethoprim., Main Outcome Measure: Identify risk factors for the development of hyperkalemia as a result of the concurrent use of potassium supplements, RAAS inhibitors and/or potassium-sparing diuretics., Results: Of 774 patients included in this study, 52 patients developed hyperkalemia; a prevalence of 6.7 %. The only risk factor found to be significantly associated with hyperkalemia was lowered renal function, expressed as estimated glomerular filtration rate (eGFR) <50 ml/min (adjusted OR 5.08; 95 % CI 2.46-10.48). None of the other tested risk factors was identified as significant., Conclusion: This study showed that decreased renal function (eGFR <50 ml/min) was associated with a fivefold increased risk for hyperkalemia in patients using potassium-influencing drugs. While previous studies showed that hyperkalemia substantially increases below a threshold of eGFR <30 or 40 ml/min, we observed a lower threshold of eGFR <50 ml/min. It is therefore recommended that physicians should be particularly alert while monitoring the use of potassium-influencing drugs in patients with decreased renal function.

Background: Preventable adverse drug events (pADEs) are widely known to be a health care issue for hospitalized patients. Surgical patients are especially at risk, but prevention of pADEs in this population is not demonstrated before. Ward-based pharmacy interventions seem effective in reducing pADEs in medical patients. The cost-effectiveness of these preventive efforts still needs to be assessed in a comparative study of high methodological standard and also in the surgical population. For these aims the SUREPILL (Surgery & Pharmacy in Liaison) study is initiated., Methods/design: A multi-centre controlled trial, with randomisation at ward-level and preceding baseline assessments is designed. Patients admitted to the surgical study wards for elective surgery with an expected length of stay of more than 48 hours will be included. Patients admitted to the intervention ward, will receive ward-based pharmacy care from the clinical pharmacy team, i.e. pharmacy practitioners and hospital pharmacists. This ward-based pharmacy intervention includes medication reconciliation in consultation with the patient at admission, daily medication review with face-to-face contact with the ward doctor, and patient counselling at discharge. Patients admitted in the control ward, will receive standard pharmaceutical care.The primary clinical outcome measure is the number of pADEs per 100 elective admissions. These pADEs will be measured by systematic patient record evaluation using a trigger tool. Patient records positive for a trigger will be evaluated on causality, severity and preventability by an independent expert panel. In addition, an economic evaluation will be performed from a societal perspective with the costs per preventable ADE as the primary economic outcome. Other outcomes of this study are: severity of pADEs, number of patients with pADEs per total number of admissions, direct (non-)medical costs and indirect non-medical costs, extra costs per prevented ADE, number and type of pharmacy interventions, length of hospital stay, complications registered in a national complication registration system for surgery, number of readmissions within three months after initial admission (follow-up), quality of life and number of non-institutionalized days during follow-up., Discussion: This study will assess the cost-effectiveness of ward-based pharmacy care on preventable adverse drug events in surgical patients from a societal perspective, using a comparative study design., Trial Registration: Netherlands Trial Register (NTR): NTR2258.