The effect of computerised decision support alerts tailored to intensive care on the administration of high-risk drug combinations, and their monitoring: a cluster randomised stepped-wedge trial.

BACKGROUND: Drug-drug interactions (DDIs) can harm patients admitted to the intensive care unit (ICU). Yet, clinical decision support systems (CDSSs) aimed at helping physicians prevent DDIs are plagued by low-yield alerts, causing alert fatigue and compromising patient safety. The aim of this multicentre study was to evaluate the effect of tailoring potential DDI alerts to the ICU setting on the frequency of administered high-risk drug combinations. METHODS: We implemented a cluster randomised stepped-wedge trial in nine ICUs in the Netherlands. Five ICUs already used potential DDI alerts. Patients aged 18 years or older admitted to the ICU with at least two drugs administered were included. Our intervention was an adapted CDSS, only providing alerts for potential DDIs considered as high risk. The intervention was delivered at the ICU level and targeted physicians. We hypothesised that showing only relevant alerts would improve CDSS effectiveness and lead to a decreased number of administered high-risk drug combinations. The order in which the intervention was implemented in the ICUs was randomised by an independent researcher. The primary outcome was the number of administered high-risk drug combinations per 1000 drug administrations per patient and was assessed in all included patients. This trial was registered in the Netherlands Trial Register (identifier NL6762) on Nov 26, 2018, and is now closed. FINDINGS: In total, 10 423 patients admitted to the ICU between Sept 1, 2018, and Sept 1, 2019, were assessed and 9887 patients were included. The mean number of administered high-risk drug combinations per 1000 drug administrations per patient was 26·2 (SD 53·4) in the intervention group (n=5534), compared with 35·6 (65·0) in the control group (n=4353). Tailoring potential DDI alerts to the ICU led to a 12% decrease (95% CI 5-18%; p=0·0008) in the number of administered high-risk drug combinations per 1000 drug administrations per patient, after adjusting for clustering and prognostic factors. INTERPRETATION: This cluster randomised stepped-wedge trial showed that tailoring potential DDI alerts to the ICU setting significantly reduced the number of administered high-risk drug combinations. Our list of high-risk drug combinations can be used in other ICUs, and our strategy of tailoring alerts based on clinical relevance could be applied to other clinical settings. FUNDING: ZonMw.

Emergency Department Triage, Transfer Times, and Hospital Mortality of Patients Admitted to the ICU: A Retrospective Replication and Continuation Study.

OBJECTIVES: This study aimed to provide new insights into the impact of emergency department (ED) to ICU time on hospital mortality, stratifying patients by academic and nonacademic teaching (NACT) hospitals, and considering Acute Physiology and Chronic Health Evaluation (APACHE)-IV probability and ED-triage scores. DESIGN, SETTING, AND PATIENTS: We conducted a retrospective cohort study (2009-2020) using data from the Dutch National Intensive Care Evaluation registry. Patients directly admitted from the ED to the ICU were included from four academic and eight NACT hospitals. Odds ratios (ORs) for mortality associated with ED-to-ICU time were estimated using multivariable regression, both crude and after adjusting for and stratifying by APACHE-IV probability and ED-triage scores. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 28,455 patients were included. The median ED-to-ICU time was 1.9 hours (interquartile range, 1.2-3.1 hr). No overall association was observed between ED-to-ICU time and hospital mortality after adjusting for APACHE-IV probability (p = 0.36). For patients with an APACHE-IV probability greater than 55.4% (highest quintile) and an ED-to-ICU time greater than 3.4 hours the adjusted OR (ORsadjApache) was 1.24 (95% CI, 1.00-1.54; p < 0.05) as compared with the reference category (< 1.1 hr). In the academic hospitals, the ORsadjApache for ED-to-ICU times of 1.6-2.3, 2.3-3.4, and greater than 3.4 hours were 1.21 (1.01-1.46), 1.21 (1.00-1.46), and 1.34 (1.10-1.64), respectively. In NACT hospitals, no association was observed (p = 0.07). Subsequently, ORs were adjusted for ED-triage score (ORsadjED). In the academic hospitals the ORsadjED for ED-to-ICU times greater than 3.4 hours was 0.98 (0.81-1.19), no overall association was observed (p = 0.08). In NACT hospitals, all time-ascending quintiles had ORsadjED values of less than 1.0 (p < 0.01). CONCLUSIONS: In patients with the highest APACHE-IV probability at academic hospitals, a prolonged ED-to-ICU time was associated with increased hospital mortality. We found no significant or consistent unfavorable association in lower APACHE-IV probability groups and NACT hospitals. The association between longer ED-to-ICU time and higher mortality was not found after adjustment and stratification for ED-triage score.

Linking Dutch Intensive Care Registry Data to Socioeconomic Status Scores.

This study aimed to gain insight into the success rate of linking the NICE registry with SES data from CBS and to examine whether the characteristics of linked and non-linked patients differ. Although clinically relevant differences were found, in total 93,4% of the admissions were successfully linked.

Assessing the use of HL7 FHIR for implementing the FAIR guiding principles: a case study of the MIMIC-IV Emergency Department module.

Objectives: To provide a real-world example on how and to what extent Health Level Seven Fast Healthcare Interoperability Resources (FHIR) implements the Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles for scientific data. Additionally, presents a list of FAIR implementation choices for supporting future FAIR implementations that use FHIR. Materials and methods: A case study was conducted on the Medical Information Mart for Intensive Care-IV Emergency Department (MIMIC-ED) dataset, a deidentified clinical dataset converted into FHIR. The FAIRness of this dataset was assessed using a set of common FAIR assessment indicators. Results: The FHIR distribution of MIMIC-ED, comprising an implementation guide and demo data, was more FAIR compared to the non-FHIR distribution. The FAIRness score increased from 60 to 82 out of 95 points, a relative improvement of 37%. The most notable improvements were observed in interoperability, with a score increase from 5 to 19 out of 19 points, and reusability, with a score increase from 8 to 14 out of 24 points. A total of 14 FAIR implementation choices were identified. Discussion: Our work examined how and to what extent the FHIR standard contributes to FAIR data. Challenges arose from interpreting the FAIR assessment indicators. This study stands out for providing a real-world example of a dataset that was made more FAIR using FHIR. Conclusion: To the best of our knowledge, this is the first study that formally assessed the conformance of a FHIR dataset to the FAIR principles. FHIR improved the accessibility, interoperability, and reusability of MIMIC-ED. Future research should focus on implementing FHIR in research data infrastructures.

Characteristics and outcome of COVID-19 patients admitted to the ICU: a nationwide cohort study on the comparison between the consecutive stages of the COVID-19 pandemic in the Netherlands, an update.

BACKGROUND: Previously, we reported a decreased mortality rate among patients with COVID-19 who were admitted at the ICU during the final upsurge of the second wave (February-June 2021) in the Netherlands. We examined whether this decrease persisted during the third wave and the phases with decreasing incidence of COVID-19 thereafter and brought up to date the information on patient characteristics. METHODS: Data from the National Intensive Care Evaluation (NICE)-registry of all COVID-19 patients admitted to an ICU in the Netherlands were used. Patient characteristics and rates of in-hospital mortality (the primary outcome) during the consecutive periods after the first wave (periods 2-9, May 25, 2020-January 31, 2023) were compared with those during the first wave (period 1, February-May 24, 2020). RESULTS: After adjustment for patient characteristics and ICU occupancy rate, the mortality risk during the initial upsurge of the third wave (period 6, October 5, 2021-January, 31, 2022) was similar to that of the first wave (ORadj = 1.01, 95%-CI [0.88-1.16]). The mortality rates thereafter decreased again (e.g., period 9, October 5, 2022-January, 31, 2023: ORadj = 0.52, 95%-CI [0.41-0.66]). Among the SARS-CoV-2 positive patients, there was a huge drop in the proportion of patients with COVID-19 as main reason for ICU admission: from 88.2% during the initial upsurge of the third wave to 51.7%, 37.3%, and 41.9% for the periods thereafter. Restricting the analysis to these patients did not modify the results on mortality. CONCLUSIONS: The results show variation in mortality rates among critically ill COVID-19 patients across the calendar time periods that is not explained by differences in case-mix and ICU occupancy rates or by varying proportions of patients with COVID-19 as main reason for ICU admission. The consistent increase in mortality during the initial, rising phase of each separate wave might be caused by the increased virulence of the contemporary virus strain and lacking immunity to the new strain, besides unmeasured patient-, treatment- and healthcare system characteristics.

Comparing causal random forest and linear regression to estimate the independent association of organisational factors with ICU efficiency.

PURPOSE: Parametric regression models have been the main statistical method for identifying average treatment effects. Causal machine learning models showed promising results in estimating heterogeneous treatment effects in causal inference. Here we aimed to compare the application of causal random forest (CRF) and linear regression modelling (LRM) to estimate the effects of organisational factors on ICU efficiency. METHODS: A retrospective analysis of 277,459 patients admitted to 128 Brazilian and Uruguayan ICUs over three years. ICU efficiency was assessed using the average standardised efficiency ratio (ASER), measured as the average of the standardised mortality ratio (SMR) and the standardised resource use (SRU) according to the SAPS-3 score. Using a causal inference framework, we estimated and compared the conditional average treatment effect (CATE) of seven common structural and organisational factors on ICU efficiency using LRM with interaction terms and CRF. RESULTS: The hospital mortality was 14 %; median ICU and hospital lengths of stay were 2 and 7 days, respectively. Overall median SMR was 0.97 [IQR: 0.76,1.21], median SRU was 1.06 [IQR: 0.79,1.30] and median ASER was 0.99 [IQR: 0.82,1.21]. Both CRF and LRM showed that the average number of nurses per ten beds was independently associated with ICU efficiency (CATE [95 %CI]: -0.13 [-0.24, -0.01] and -0.09 [-0.17,-0.01], respectively). Finally, CRF identified some specific ICUs with a significant CATE in exposures that did not present a significant average effect. CONCLUSION: In general, both methods were comparable to identify organisational factors significantly associated with CATE on ICU efficiency. CRF however identified specific ICUs with significant effects, even when the average effect was nonsignificant. This can assist healthcare managers in further in-dept evaluation of process interventions to improve ICU efficiency.

Quality improvement of Dutch ICUs from 2009 to 2021: A registry based observational study.

PURPOSE: To investigate the development in quality of ICU care over time using the Dutch National Intensive Care Evaluation (NICE) registry. MATERIALS AND METHODS: We included data from all ICU admissions in the Netherlands from those ICUs that submitted complete data between 2009 and 2021 to the NICE registry. We determined median and interquartile range for eight quality indicators. To evaluate changes over time on the indicators, we performed multilevel regression analyses, once without and once with the COVID-19 years 2020 and 2021 included. Additionally we explored between-ICU heterogeneity by calculating intraclass correlation coefficients (ICC). RESULTS: 705,822 ICU admissions from 55 (65%) ICUs were included in the analyses. ICU length of stay (LOS), duration of mechanical ventilation (MV), readmissions, in-hospital mortality, hypoglycemia, and pressure ulcers decreased significantly between 2009 and 2019 (OR <1). After including the COVID-19 pandemic years, the significant change in MV duration, ICU LOS, and pressure ulcers disappeared. We found an ICC ≤0.07 on the quality indicators for all years, except for pressure ulcers with an ICC of 0.27 for 2009 to 2021. CONCLUSIONS: Quality of Dutch ICU care based on seven indicators significantly improved from 2009 to 2019 and between-ICU heterogeneity is medium to small, except for pressure ulcers. The COVID-19 pandemic disturbed the trend in quality improvement, but unaltered the between-ICU heterogeneity.