The Effect of Genotyping on the Number of Pharmacotherapeutic Gene-Drug Interventions in Chronic Kidney Disease Patients.

Patients with chronic kidney disease (CKD) stage 3-5 are polypharmacy patients. Many of these drugs are metabolized by cytochrome P450 (CYP450) and CYP450. Genetic polymorphism is well known to result in altered drug metabolism capacity. This study determined the added value of pharmacogenetic testing to the routine medication evaluation in polypharmacy patients with CKD. In adult outpatient polypharmacy patients with CKD3-5 disease, a pharmacogenetic profile was determined. Then, automated medication surveillance for gene-drug interactions was performed based on the pharmacogenetic profile and the patients' current prescriptions. Of all identified gene-drug interactions, the hospital pharmacist and the treating nephrologist together assessed clinical relevance and necessity of a pharmacotherapeutic intervention. The primary endpoint of the study was the total number of applied pharmacotherapeutic interventions based on a relevant gene-drug interaction. A total of 61 patients were enrolled in the study. Medication surveillance resulted in a total of 66 gene-drug interactions, of which 26 (39%) were considered clinically relevant. This resulted in 26 applied pharmacotherapeutic interventions in 20 patients. Systematic pharmacogenetic testing enables pharmacotherapeutic interventions based on relevant gene-drug interactions. This study showed that pharmacogenetic testing adds to routine medication evaluation and could lead to optimized pharmacotherapy in CKD patients.

Combining text mining with clinical decision support in clinical practice: a scoping review.

OBJECTIVE: Combining text mining (TM) and clinical decision support (CDS) could improve diagnostic and therapeutic processes in clinical practice. This review summarizes current knowledge of the TM-CDS combination in clinical practice, including their intended purpose, implementation in clinical practice, and barriers to such implementation. MATERIALS AND METHODS: A search was conducted in PubMed, EMBASE, and Cochrane Library databases to identify full-text English language studies published before January 2022 with TM-CDS combination in clinical practice. RESULTS: Of 714 identified and screened unique publications, 39 were included. The majority of the included studies are related to diagnosis (n = 26) or prognosis (n = 11) and used a method that was developed for a specific clinical domain, document type, or application. Most of the studies selected text containing parts of the electronic health record (EHR), such as reports (41%, n = 16) and free-text narratives (36%, n = 14), and 23 studies utilized a tool that had software "developed for the study". In 15 studies, the software source was openly available. In 79% of studies, the tool was not implemented in clinical practice. Barriers to implement these tools included the complexity of natural language, EHR incompleteness, validation and performance of the tool, lack of input from an expert team, and the adoption rate among professionals. DISCUSSION/CONCLUSIONS: The available evidence indicates that the TM-CDS combination may improve diagnostic and therapeutic processes, contributing to increased patient safety. However, further research is needed to identify barriers to implementation and the impact of such tools in clinical practice.

Contextualized Drug-Drug Interaction Management Improves Clinical Utility Compared With Basic Drug-Drug Interaction Management in Hospitalized Patients.

Drug-drug interactions (DDIs) frequently trigger adverse drug events or reduced efficacy. Most DDI alerts, however, are overridden because of irrelevance for the specific patient. Basic DDI clinical decision support (CDS) systems offer limited possibilities for decreasing the number of irrelevant DDI alerts without missing relevant ones. Computerized decision tree rules were designed to context-dependently suppress irrelevant DDI alerts. A crossover study was performed to compare the clinical utility of contextualized and basic DDI management in hospitalized patients. First, a basic DDI-CDS system was used in clinical practice while contextualized DDI alerts were collected in the background. Next, this process was reversed. All medication orders (MOs) from hospitalized patients with at least one DDI alert were included. The following outcome measures were used to assess clinical utility: positive predictive value (PPV), negative predictive value (NPV), number of pharmacy interventions (PIs)/1,000 MOs, and the median time spent on DDI management/1,000 MOs. During the basic DDI management phase 1,919 MOs/day were included, triggering 220 DDI alerts/1,000 MOs; showing 57 basic DDI alerts/1,000 MOs to pharmacy staff; PPV was 2.8% with 1.6 PIs/1,000 MOs costing 37.2 minutes/1,000 MOs. No DDIs were missed by the contextualized CDS system (NPV 100%). During the contextualized DDI management phase 1,853 MOs/day were included, triggering 244 basic DDI alerts/1,000 MOs, showing 9.6 contextualized DDIs/1,000 MOs to pharmacy staff; PPV was 41.4% (P < 0.01), with 4.0 PIs/1,000 MOs (P < 0.01) and 13.7 minutes/1,000 MOs. The clinical utility of contextualized DDI management exceeds that of basic DDI management.

Dabigatran trough concentrations in very elderly patients.

OBJECTIVES: The aim of this observational study was to explore dabigatran concentrations in elderly and very elderly patients in a real-life population. Patients aged >75 years receiving dabigatran have a significantly higher risk of gastrointestinal bleeding compared withthose receiving warfarin. High trough concentrations have an important impact on this bleeding risk. METHODS: We measured dabigatran trough concentrations in 75 patients with atrial fibrillation, divided into age categories <75, ≥75 to 84 and ≥85 years. The most important exclusion criteria were use of interacting medication and severe renal failure. We analysed absolute trough concentrations and concentrations normalised for dose. RESULTS: Trough concentrations were considerably higher in the highest age category. Dose-normalised medians were 0.66, 0.83 and 1.20 ng/mL/mg in the <75, ≥75-84 and ≥85 age groups, respectively (p=0.004). CONCLUSION: Clinicians should be aware of higher dabigatran concentrations in elderly patients despite dose reduction.

Clinical Decision Support System-Assisted Pharmacy Intervention Reduces Feeding Tube-Related Medication Errors in Hospitalized Patients: A Focus on Medication Suitable for Feeding-Tube Administration.

BACKGROUND: Administering medication through an enteral feeding tube (FT) is a frequent cause of errors resulting in increased morbidity and cost. Studies on interventions to prevent these errors in hospitalized patients, however, are limited. OBJECTIVE: The objective was to study the effect of a clinical decision support system (CDSS)-assisted pharmacy intervention on the incidence of FT-related medication errors (FTRMEs) in hospitalized patients. METHODS: A pre-post intervention study was conducted between October 2014 and May 2015 in Catharina Hospital, the Netherlands. Patients who were admitted to the wards of bowel and liver disease, oncology, or neurology; using oral medication; and had an enteral FT were included. Preintervention patients were given care as usual. The intervention consisted of implementing a CDSS-assisted pharmacy check while also implementing standard operating procedures and educating personnel. An FTRME was defined as the administration of inappropriate medication through an enteral FT. The incidence was expressed as the number of FTRMEs per medication administration. Multivariate Poisson regression was used to calculate the incidence ratio (IR) comparing both phases. RESULTS: Eighty-one patients were included, 38 during preintervention and 43 during the intervention phase. Incidence of FTRMEs in the preintervention phase was 0.15 (95% CI, 0.07-0.23) vs 0.02 (95% CI, 0.00-0.04) in the intervention phase, resulting in an adjusted IR of 0.13 (95% CI, 0.10-0.18). DISCUSSION: Incidence of FTRMEs, as well as the IR, is comparable to previous studies. CONCLUSION: The intervention resulted in a substantial reduction in the incidence of FTRMEs.

End-tidal to Arterial Gradients and Alveolar Deadspace for Anesthetic Agents.

BACKGROUND: According to the "three-compartment" model of ventilation-perfusion ((Equation is included in full-text article.)) inequality, increased (Equation is included in full-text article.)scatter in the lung under general anesthesia is reflected in increased alveolar deadspace fraction (VDA/VA) customarily measured using end-tidal to arterial (A-a) partial pressure gradients for carbon dioxide. A-a gradients for anesthetic agents such as isoflurane are also significant but have been shown to be inconsistent with those for carbon dioxide under the three-compartment theory. The authors hypothesized that three-compartment VDA/VA calculated using partial pressures of four inhalational agents (VDA/VAG) is different from that calculated using carbon dioxide (VDA/VACO2) measurements, but similar to predictions from multicompartment models of physiologically realistic "log-normal" (Equation is included in full-text article.)distributions. METHODS: In an observational study, inspired, end-tidal, arterial, and mixed venous partial pressures of halothane, isoflurane, sevoflurane, or desflurane were measured simultaneously with carbon dioxide in 52 cardiac surgery patients at two centers. VDA/VA was calculated from three-compartment model theory and compared for all gases. Ideal alveolar (PAG) and end-capillary partial pressure (Pc'G) of each agent, theoretically identical, were also calculated from end-tidal and arterial partial pressures adjusted for deadspace and venous admixture. RESULTS: Calculated VDA/VAG was larger (mean ± SD) for halothane (0.47 ± 0.08), isoflurane (0.55 ± 0.09), sevoflurane (0.61 ± 0.10), and desflurane (0.65 ± 0.07) than VDA/VACO2 (0.23 ± 0.07 overall), increasing with lower blood solubility (slope [Cis], -0.096 [-0.133 to -0.059], P < 0.001). There was a significant difference between calculated ideal PAG and Pc'G median [interquartile range], PAG 5.1 [3.7, 8.9] versus Pc'G 4.0[2.5, 6.2], P = 0.011, for all agents combined. The slope of the relationship to solubility was predicted by the log-normal lung model, but with a lower magnitude relative to calculated VDA/VAG. CONCLUSIONS: Alveolar deadspace for anesthetic agents is much larger than for carbon dioxide and related to blood solubility. Unlike the three-compartment model, multicompartment (Equation is included in full-text article.)scatter models explain this from physiologically realistic gas uptake distributions, but suggest a residual factor other than solubility, potentially diffusion limitation, contributes to deadspace.

Clinical rule-guided pharmacists' intervention in hospitalized patients with hypokalaemia: A time series analysis.

WHAT IS KNOWN AND OBJECTIVE: Physicians' response to moderate and severe hypokalaemia in hospitalized patients is frequently suboptimal, leading to increased risk of cardiac arrhythmias and sudden death. While actively alerting physicians on all critical care values using telephone or electronic pop-ups can improve response, it can also lead to alert fatigue and frustration due to non-specific and overdue alerts. Therefore, a new method was tested. A clinical rule built into a clinical decision support system (CDSS) generated alerts for patients with a serum potassium level (SPL) <2.9 mmol/L without a prescription for potassium supplementation. If the alert was deemed clinically relevant, a pharmacist contacted the physician. The aim of this study was to evaluate the impact of the clinical rule-guided pharmacists' intervention compared to showing passive alerts in the electronic health records on outcome in patients who developed hypokalaemia (<2.9 mmol/L) during hospitalization. METHODS: A before (2007-2009) and after (2010-2017) study with time series design was performed. Pre-intervention, physicians were shown passive alerts for hypokalaemia in the electronic health records. During the intervention period, in addition to these passive alerts, a pharmacist provided the physician with a specific advice on patients with untreated hypokalaemia, guided by the generated alerts. Unique patients >18 years with SPL <2.9 mmol/L measured at least 24 hours after hospitalization in whom no potassium supplementation was initiated within 4 hours after measurement and normalization of SPL was not achieved within these 4 hours were included. Haemodialysis patients were excluded. The percentage of hypokalaemic patients with a subsequent prescription for potassium supplementation, time to subsequent potassium supplementation prescription, the percentage of patients who achieved normokalaemia (SPL ≥ 3.0 mmol/L), time to achieve normokalaemia and total duration of hospitalization were compared. RESULTS AND DISCUSSION: A total of 693 patients were included, of whom 278 participated in the intervention phase. The percentage of patients prescribed supplementation as well as time to prescription improved from 76.0% in 31.1 hours to 92.0% in 11.3 hours (P < .01). Time to achieve SPL ≥3.0 mmol/L improved, P < .009. No changes, however, were observed in the percentage of patients who achieved normokalaemia or time to reach normokalaemia, 87.5% in 65.2 hours pre-intervention compared to 90.2% (P = .69) in 64.0 hours (P = .71) in the intervention group. A non-significant decrease of 8.2 days was observed in the duration of hospitalization: 25.4 compared to 17.2 days (P = .29). WHAT IS NEW AND CONCLUSION: Combining CDSS alerting with a pharmacist evaluation is an effective method to improve response rate, time to supplementation and time to initial improvement, defined as SPL ≥3.0 mmol/L. However, it showed no significant effect on the percentage of patients achieving normokalaemia, time to normokalaemia or hospitalization. The discrepancy between rapid supplementation and improvement on the one hand and failure to improve time to normokalaemia on the other warrants further study.

Psychotropic Drug Prescription and the Risk of Falls in Nursing Home Residents.

BACKGROUND: Falling is a common and serious problem in the elderly. Previous studies suggest that the use of psychotropic drugs increases the risk of falling. However, the contribution of these drugs on fall risk has not been quantified on a daily basis among the general population of nursing homes until now. OBJECTIVE: To assess the association between fall incidence and the prescription of psychotropic drugs and different categories of psychotropic drugs (antipsychotics, antidepressants, and benzodiazepines) among a general nursing home population. DESIGN: Retrospective observational study, data collection per person-day. SETTING: 9 nursing homes in Eindhoven, the Netherlands. PARTICIPANTS: 2368 nursing home residents, resulting in 538,575 person-days. MAIN OUTCOME MEASURE: Association between the prescription of psychotropic drugs and falls. RESULTS: A total of 2368 nursing home residents were included, which resulted in a data set of 538,575 person-days. Prescription of at least 1 psychotropic drug per day occurred during a total of 318,128 person-days (59.1%). Scheduled prescriptions with or without an as-needed prescription were involved in a total of 270,781 person-days (50.3%). The prescription of psychotropic drugs on a scheduled basis was found to be associated with almost a 3-fold increase in fall incidence (OR 2.88; 95% CI 1.52-5.44). An increase in fall incidence was found following the prescription of antipsychotics (OR 1.97; 95% CI 1.51-2.59) and antidepressants (OR 2.26; 95% CI 1.73-2.95). This increased fall risk was found for prescriptions on a scheduled basis as well as for prescriptions on an as-needed basis. CONCLUSION: The prescription of psychotropic drugs is associated with a strongly increased risk of falling among nursing home residents. To our knowledge, this is the first study among the general nursing home population in which the association between daily falls and daily prescriptions of psychotropic drugs and groups of psychotropic drugs was specified.

Systems that prevent unwanted represcription of drugs withdrawn because of adverse drug events: a systematic review.

Represcription of medication that was withdrawn after the occurrence of an adverse drug event (including allergy), is a recognized medication safety issue on a patient level. We performed a systematic review to identify systems (electronic and nonelectronic) that can prevent the represcription of drugs withdrawn because of an adverse drug event and the effects of these systems. The review was performed using PRISMA and Cochrane guidelines. PubMed and Embase were searched for articles describing systems that can prevent represcription of drugs that had been withdrawn for causing an adverse drug event. Information on the characteristics of the studies, systems, and if present results achieved with such systems, was extracted. The results showed that of 6793 articles screened, 137 full-text articles were assessed for eligibility. A total of 45 studies describing 33 systems (28 electronic) were included. The five nonelectronic systems used allergy bracelets or allergy labels on hospital medical records or on drug orders. Systems differed in the way adverse drug events were documented and how users were alerted to drug represcription. Most systems functioned within a specific healthcare setting. Of 12 studies that compared pre- and post-intervention periods or wards with and without intervention, 7 showed a reduction in represcription after adverse drug event. In conclusion, several systems have been developed that can prevent the represcription of drugs that elicited an adverse drug event, but the evidence that these systems are effective is limited.

An electronic system to document reasons for medication discontinuation and to flag unwanted represcriptions in geriatric patients.

BACKGROUND: Earlier studies have shown poor documentation of the reasons for medication discontinuation during hospitalization. Communication of reasons for discontinuation, e.g. adverse drug reactions (ADRs), to general practitioners and pharmacists was also found to be insufficient, leading to a rate of represcription after an ADR of 27% during the first 6 months after discharge. OBJECTIVE: The aim of this study was to develop and implement a user-friendly electronic clinical decision support system to document reasons for medication discontinuation in hospitalized geriatric patients and to flag potentially undesirable represcriptions. METHODS: The electronic clinical decision support module was developed using the Gaston framework. Pop-up windows force physicians to document reasons for medication discontinuation, and the system alerts physicians to the represcription of drugs withdrawn because of an ADR. We interviewed users regarding the acceptability of the system. RESULTS: On a 20-bed geriatric ward, the electronic system documented 2,228 medication discontinuations and the reasons for them over 11.4 months and alerted physicians to represcription of drugs associated with an ADR 20 times. The system was considered to be user-friendly. CONCLUSIONS: This clinical decision support system fulfilled its aims of documenting the reasons for medication discontinuation and alerting physicians to potentially undesirable represcription of previously withdrawn drugs. It was found to be user-friendly.

Recurrence of adverse drug reactions following inappropriate re-prescription: better documentation, availability of information and monitoring are needed.

Adverse drug reactions (ADRs) are a common, and often preventable, cause of hospital admission, especially in the elderly, and can occur during hospitalization. In this current opinion article, we present three cases of recurrence of a serious ADR due to re-prescription of a withdrawn medication that highlight the need for a system to prevent the undesirable re-prescription of medications withdrawn because of an ADR. In addition, we describe an electronic system that could help prevent undesirable re-prescription following an ADR. Such a system should document ADRs systematically at the patient level, make this information available to relevant healthcare providers and the patient, and flag re-prescription of the offending drug. The effectiveness and cost effectiveness of such a system would need to be determined.

Quantification in echocardiography.

Until recently, more than 2200 Swan Ganz catheters were used annually in the operating rooms (OR) and intensive care unit (ICU) of the Catharina Hospital in Eindhoven, The Netherlands. After cardiologists who were specialists in echocardiography (ECHO) trained anesthesiologists in ECHO, the need for these catheters in cardiac and noncardiac surgery was reduced. Initially intended as a local teaching project, an ECHO teaching compact disk (CD) was produced during the training and distributed later worldwide, thanks to a positive review in a major anesthesiology publication. By reducing the number of Swan Ganz catheters, the hospital could finance and acquire two echocardiography machines for the OR and ICU. The availability of these machines resulted in a further reduction of the number of Swan Ganz catheters. However, the need for quantification (eg, measurements of cardiac output) remained. During the creation of the ECHO teaching CD, the idea was born to apply indicator-dilution principles on injected echo contrast. This study was performed in cooperation with the Signal Processing Department of the Eindhoven University of Technology. Advanced signal processing and modelling were used to develop algorithms to enable quantification of intrapulmonary blood volume, ejection-fraction, and flow from the transesophageal echocardiography approach. These quantitative measurements, which can be performed on an outpatient basis, may become a real asset in cardiology, anesthesiology, and intensive care.