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Objective: Adverse drug reactions (ADRs) are a significant healthcare concern. They are often documented as free text in electronic health records (EHRs), making them challenging to use in clinical decision support systems (CDSS). The study aimed to develop a text mining algorithm to identify ADRs in free text of Dutch EHRs. Materials and Methods: In Phase I, our previously developed CDSS algorithm was recoded and improved upon with the same relatively large dataset of 35 000 notes (Step A), using R to identify possible ADRs with Medical Dictionary for Regulatory Activities (MedDRA) terms and the related Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) (Step B). In Phase II, 6 existing text-mining R-scripts were used to detect and present unique ADRs, and positive predictive value (PPV) and sensitivity were observed. Results: In Phase IA, the recoded algorithm performed better than the previously developed CDSS algorithm, resulting in a PPV of 13% and a sensitivity of 93%. For The sensitivity for serious ADRs was 95%. The algorithm identified 58 additional possible ADRs. In Phase IB, the algorithm achieved a PPV of 10%, a sensitivity of 86%, and an F-measure of 0.18. In Phase II, four R-scripts enhanced the sensitivity and PPV of the algorithm, resulting in a PPV of 70%, a sensitivity of 73%, an F-measure of 0.71, and a 63% sensitivity for serious ADRs. Discussion and Conclusion: The recoded Dutch algorithm effectively identifies ADRs from free-text Dutch EHRs using R-scripts and MedDRA/SNOMED-CT. The study details its limitations, highlighting the algorithm's potential and significant improvements.

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Background: Ultrasound guidance increases first-pass success rates and decreases the number of cannulation attempts and complications during radial artery catheterisation but it is debatable whether short-, long-, or oblique-axis imaging is superior for obtaining access. Three-dimensional (3D) biplanar ultrasound combines both short- and long-axis views with their respective benefits. This study aimed to determine whether biplanar imaging would improve the accuracy of radial artery catheterisation compared with conventional 2D imaging. Methods: This before-and-after trial included adult patients who required radial artery catheterisation for elective cardiothoracic surgery. The participating anaesthesiologists were experienced in 2D and biplanar ultrasound-guided vascular access. The primary endpoint was successful catheterisation in one skin break without withdrawals. Secondary endpoints were the numbers of punctures and withdrawals, scanning and procedure times, needle visibility, perceived mental effort of the operator, and posterior wall puncture or other mechanical complications. Results: From November 2021 until April 2022, 158 patients were included and analysed (2D=75, biplanar=83), with two failures to catheterise in each group. First-pass success without needle redirections was 58.7% in the 2D group and 60.2% in the biplanar group (difference=1.6%; 95% confidence interval [CI], -14.0%-17.1%; P=0.84), and first-pass success within one skin break was 77.3% in the 2D group vs 81.9% in the biplanar group (difference=4.6%; 95% CI, 8.1%-17.3%; P=0.473). None of the secondary endpoints differed significantly. Conclusions: Biplanar ultrasound guidance did not improve success rates nor other performance measures of radial artery catheterisation. The additional visual information acquired with biplanar imaging did not offer any benefit. Clinical trial registration: N9687 (Dutch Trial Register).

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Hemodynamic monitoring technologies are evolving continuously-a large number of bedside monitoring options are becoming available in the clinic. Methods such as echocardiography, electrical bioimpedance, and calibrated/uncalibrated analysis of pulse contours are becoming increasingly common. This is leading to a decline in the use of highly invasive monitoring and allowing for safer, more accurate, and continuous measurements. The new devices mainly aim to monitor the well-known hemodynamic variables (e.g., novel pulse contour, bioreactance methods are aimed at measuring widely-used variables such as blood pressure, cardiac output). Even though hemodynamic monitoring is now safer and more accurate, a number of issues remain due to the limited amount of information available for diagnosis and treatment. Extensive work is being carried out in order to allow for more hemodynamic parameters to be measured in the clinic. In this review, we identify and discuss the main sensing strategies aimed at obtaining a more complete picture of the hemodynamic status of a patient, namely: (i) measurement of the circulatory system response to a defined stimulus; (ii) measurement of the microcirculation; (iii) technologies for assessing dynamic vascular mechanisms; and (iv) machine learning methods. By analyzing these four main research strategies, we aim to convey the key aspects, challenges, and clinical value of measuring novel hemodynamic parameters in critical care.

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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.

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STUDY OBJECTIVE: The three-dimensional shape of the ultrasound beam produces a thicker scan plane than most users assume. Viewed longitudinally, a needle placed lateral to a vessel just outside the central scanning plane can be displayed incorrectly in the ultrasound image as if placed intravascularly. This phenomenon is called the beam width artefact, also known as the elevation or slice thickness artefact. The goal of this study was to demonstrate the potential negative effect of the beam width artefact on the performance of in-plane ultrasound-guided vascular access procedures, and to provide a solution. DESIGN: Randomized, double-blinded study SETTING: Department of anaesthesiology and intensive care of a teaching hospital PARTICIPANTS: 31 experienced (anesthesiologists and intensivists) and 36 inexperienced (anesthetic nurses) ultrasound users INTERVENTIONS: We developed an acoustic lens that narrows the scan plane to reduce the beam width artefact. The lens was tested in a simulated vascular access study. MEASUREMENTS: The primary endpoint was first pass success. Secondary endpoints were the number of punctures and needle withdrawals, procedure time, needle visibility and operator satisfaction. MAIN RESULTS: First pass success was highly enhanced using the acoustic lens, with a success rate of 92.5% versus 68.7% without the lens (difference 23.8, 95% confidence interval 11.0-35.3, p < 0.001). The total number of punctures needed to obtain intravenous access was also reduced using the lens (1.10 versus 1.38, difference 0.27, 95% CI 0.11-0.43, p = 0.002). Procedure time, needle withdrawals, needle visibility and satisfaction were similar. Both inexperienced and experienced users benefited from the acoustic lens. CONCLUSIONS: The beam width artefact has a significant effect on the performance of ultrasound-guided needle-based procedures. The efficacy of in-plane superficial vascular access procedures can be enhanced by narrowing the imaging plane using an acoustic lens.

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The blood pressure (BP) cuff can be used to modulate blood flow and propagation of pressure pulse along the artery. In our previous work, we researched methods to adapt cuff modulation techniques for pulse transit time vs. BP calibration and for measurement of other hemodynamic indices of potential interest to critical care, such as arterial compliance. A model characterized the response of the vasculature located directly under the cuff, but assumed that no significant changes occur in the distal vasculature.This study has been tailored to gain insights into the response of distal BP and pulse transit time to cuff inflation. Invasive BP data collected downstream from the cuff demonstrates that highly dynamic processes occur in the distal arm during cuff inflation. Mean arterial pressure increases in the distal artery by up to 20 mmHg, leading to a decrease in pulse transit time of up to 20 ms. Clinical Relevance: Such significant changes need to be taken into account in order to improve non-invasive BP estimations and to enable inference of other hemodynamic parameters from vasculature response to cuff inflation. A simple model is developed in order to reproduce the observed behaviors. The lumped-parameter model demonstrates opportunities for cuff modulation measurements which can reveal information on parameters such as systemic resistance, distal arterial, venous compliances and artery-vein interaction.

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BACKGROUND: We examined whether a context and process-sensitive 'intelligent' checklist increases compliance with best practice compared with a paper checklist during intensive care ward rounds. METHODS: We conducted a single-centre prospective before-and-after mixed-method trial in a 35 bed medical and surgical ICU. Daily ICU ward rounds were observed during two periods of 8 weeks. We compared paper checklists (control) with a dynamic (digital) clinical checklist (DCC, intervention). The primary outcome was compliance with best clinical practice, measured as the percentages of checked items and unchecked critical items. Secondary outcomes included ICU stay and the usability of digital checklists. Data are presented as median (interquartile range). RESULTS: Clinical characteristics and severity of critical illness were similar during both control and intervention periods of study. A total of 36 clinicians visited 197 patients during 352 ward rounds using the paper checklist, compared with 211 patients during 366 ward rounds using the DCC. Per ICU round, a median of 100% of items (94.4-100.0) were completed by DCC, compared with 75.1% (66.7-86.4) by paper checklist (P=0.03). No critical items remained unchecked by the DCC, compared with 15.4% (8.3-27.3) by the paper checklist (P=0.01). The DCC was associated with reduced ICU stay (1 day [1-3]), compared with the paper checklist (2 days [1-4]; P=0.05). Usability of the DCC was judged by clinicians to require further improvement. CONCLUSIONS: A digital checklist improved compliance with best clinical practice, compared with a paper checklist, during ward rounds on a mixed ICU. CLINICAL TRIAL REGISTRATION: NCT03599856.

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BACKGROUND: Ensuring that lung-protective ventilation is achieved at scale is challenging in perioperative practice. Fully automated ventilation may be more effective in delivering lung-protective ventilation. Here, we compared automated lung-protective ventilation with conventional ventilation after elective cardiac surgery in haemodynamically stable patients. METHODS: In this single-centre investigator-led study, patients were randomly assigned at the end of cardiac surgery to receive either automated (adaptive support ventilation) or conventional ventilation. The primary endpoint was the proportion of postoperative ventilation time characterised by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first three postoperative hours. Secondary outcomes included severe hypoxaemia (Spo2 <85%) and resumption of spontaneous breathing. Data are presented as mean (95% confidence intervals [CIs]). RESULTS: We randomised 220 patients (30.4% females; age: 62-76 yr). Subjects randomised to automated ventilation (n=109) spent a 29.7% (95% CI: 22.1-37.4) higher mean proportion of postoperative ventilation time receiving optimal postoperative ventilation after surgery (P<0.001) compared with subjects receiving conventional postoperative ventilation (n=111). Automated ventilation also reduced the proportion of postoperative ventilation time that subjects were exposed to injurious ventilatory settings by 2.5% (95% CI: 1-4; P=0.003). Severe hypoxaemia was less likely in subjects randomised to automated ventilation (risk ratio: 0.26 [0.22-0.31]; P<0.01). Subjects resumed spontaneous breathing more rapidly when randomised to automated ventilation (hazard ratio: 1.38 [1.05-1.83]; P=0.03). CONCLUSIONS: Fully automated ventilation in haemodynamically stable patients after cardiac surgery optimised lung-protective ventilation during postoperative ventilation, with fewer episodes of severe hypoxaemia and an accelerated resumption of spontaneous breathing. CLINICAL TRIAL REGISTRATION: NCT03180203.

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BACKGROUND AND OBJECTIVES: Measurement of arterial compliance is recognized as important for clinical use and for enabling better understanding of circulatory system regulation mechanisms. Estimation of arterial compliance involves either a direct measure of the ratio between arterial volume and pressure changes or an inference from the pulse wave velocity (PWV). In this study we demonstrate an approach to assess arterial compliance by fusion of these two information sources. The approach is based on combining oscillometry as used for blood pressure inference and PWV measurements based on ECG/PPG. Enabling reliable arterial compliance measurements will contribute to the understanding of regulation mechanisms of the arterial tree, possibly establishing arterial compliance as a key measure relevant in hemodynamic monitoring. METHODS: A measurement strategy, a physiological model, and a framework based on Bayesian principles are developed for measuring changes in arterial compliance based on combining oscillometry and PWV data. A simulation framework is used to study and validate the algorithm and measurement principle in detail, motivated by previous experimental findings. RESULTS: Simulations demonstrate the possibility of inferring arterial compliance via fusion of simultaneously acquired volume/pressure relationships and PWV data. In addition, the simulation framework demonstrates how Bayesian principles can be used to handle low signal - to - noise ratio and partial information loss. CONCLUSIONS: The developed simulation framework shows the feasibility of the proposed approach for assessment of arterial compliance by combining multiple data sources. This represents a first step towards integration of arterial compliance measurements in hemodynamic monitoring using existing clinical technology. The Bayesian approach is of particular relevance for such patient monitoring settings, where measurements are repeated frequently, context is relevant, and data is affected by artefacts. In addition, the simulation framework is necessary for future clinical-study design, in order to determine device specifications and the extent to which noise affects the inference process.

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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.

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OBJECTIVES: Paediatric patients receive less procedural sedation and analgesia (PSA) in the emergency department compared with adults, especially in countries where emergency medicine is at an early stage of development. The objectives of this study were to evaluate the adverse events and efficacy of paediatric PSA in a country with a recent establishment of emergency medicine and to describe which factors aided implementation. METHODS: This is a prospective, multicentre, observational study of paediatric patients undergoing PSA by the first trained emergency physicians (EPs) in The Netherlands. A standardized data collection form was used at all participating hospitals to collect data on adverse events, amnesia, pain scores, and procedure completion. A survey was used to interpret which factors had aided PSA implementation. RESULTS: We recorded 351 paediatric PSA. The mean age was 9.5 years (95% confidence interval: 9.1-10.0). Esketamine was most frequently used (42.4%), followed by propofol (34.7%). The adverse event rate was low (3.0%). Amnesia was present in 86.8%. The median pain score was 2 (out of 10) for patients without amnesia. Procedures were successfully completed in 93.9% of the cases. CONCLUSION: Paediatric PSA provided by the first EPs in The Netherlands showed appropriate levels of sedation and analgesia with a high rate of procedure completion and a low rate of adverse events. Our paper suggests that EPs provided with a proper infrastructure of mentorship, training and guidelines can implement effective paediatric PSA.

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We present RegressionExplorer, a Visual Analytics tool for the interactive exploration of logistic regression models. Our application domain is Clinical Biostatistics, where models are derived from patient data with the aim to obtain clinically meaningful insights and consequences. Development and interpretation of a proper model requires domain expertise and insight into model characteristics. Because of time constraints, often a limited number of candidate models is evaluated. RegressionExplorer enables experts to quickly generate, evaluate, and compare many different models, taking the workflow for model development as starting point. Global patterns in parameter values of candidate models can be explored effectively. In addition, experts are enabled to compare candidate models across multiple subpopulations. The insights obtained can be used to formulate new hypotheses or to steer model development. The effectiveness of the tool is demonstrated for two uses cases: prediction of a cardiac conduction disorder in patients after receiving a heart valve implant and prediction of hypernatremia in critically ill patients.

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BACKGROUND: In intensive care environments, technology is omnipresent whereby ensuring constant monitoring and the administration of critical drugs to unstable patients. A clinical decision support system (CDSS), with its widespread possibilities, can be a valuable tool in supporting adequate patient care. However, it is still unclear how decision support alerts should be presented to physicians and other medical staff to ensure that they are used most effectively. OBJECTIVE: To determine the effect of four different alert presentation methods on alert compliance after the implementation of an advanced CDSS on the intensive care unit (ICU) in our hospital. METHODS: A randomized clinical trial was executed from August 2010 till December 2011, which included all patients admitted to the ICU of our hospital. The CDSS applied contained a set of thirteen locally developed clinical rules. The percentage of alert compliance was compared for four alert presentation methods: pharmacy intervention, physician alert list, electronic health record (EHR) section and pop-up alerts. Additionally, surveys were held to determine the method most preferred by users of the CDSS. RESULTS: In the study period, the CDSS generated 902 unique alerts, primarily due to drug dosing during decreased renal function and potassium disturbances. Alert compliance was highest for recommendations offered in pop-up alerts (41%, n=68/166), followed by pharmacy intervention (33%, n=80/244), the physician alert list (20%, n=40/199) and the EHR section (19%, n=55/293). The method most preferred by clinicians was pharmacy intervention, and pop-up alerts were found suitable as well if applied correctly. The physician alert list and EHR section were not considered suitable for CDSSs in the process of this study. CONCLUSION: The alert presentation method used for CDSSs is crucial for the compliance with alerts for the clinical rules and, consequently, for the efficacy of these systems. Active alerts such as pop-ups and pharmacy intervention were more effective than passive alerts, which do not automatically appear within the clinical workflow. In this pilot study, ICU clinicians also preferred pharmacy intervention and pop-up alerts. More research is required to expand these results to other departments and other hospitals, as well as to other types of CDSSs and different alert presentation methods.

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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.

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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.

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Cardiac herniation after pneumonectomy is recognized as a rare complication. This case report describes two cases. The mortality rate of this complication remains high as reported in the literature; in early-recognized cases 50 % and in late or unrecognized cases 100 %. In the following two cases a pneumonectomy was performed as a treatment for lung cancer. Within 48 h after the initial operative treatment, the clinical situation of the patients got worse and radiographic examinations showed a strongly deviated heart. After suspicion of the diagnosis, the patients were immediately transferred to the operation theatre for emergency thoracotomy. Per-operative the diagnosis was confirmed and the heart was returned into its original position while the defect in the pericardial sac was closed with a bovine pericardial patch. Both patients survived these procedures and did not suffer from any further complication.

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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.

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