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.

Strain on Scarce Intensive Care Beds Drives Reduced Patient Volumes, Patient Selection, and Worse Outcome: A National Cohort Study.

OBJECTIVES: Strain on ICUs during the COVID-19 pandemic required stringent triage at the ICU to distribute resources appropriately. This could have resulted in reduced patient volumes, patient selection, and worse outcome of non-COVID-19 patients, especially during the pandemic peaks when the strain on ICUs was extreme. We analyzed this potential impact on the non-COVID-19 patients. DESIGN: A national cohort study. SETTING: Data of 71 Dutch ICUs. PARTICIPANTS: A total of 120,393 patients in the pandemic non-COVID-19 cohort (from March 1, 2020 to February 28, 2022) and 164,737 patients in the prepandemic cohort (from January 1, 2018 to December 31, 2019). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Volume, patient characteristics, and mortality were compared between the pandemic non-COVID-19 cohort and the prepandemic cohort, focusing on the pandemic period and its peaks, with attention to strata of specific admission types, diagnoses, and severity. The number of admitted non-COVID-19 patients during the pandemic period and its peaks were, respectively, 26.9% and 34.2% lower compared with the prepandemic cohort. The pandemic non-COVID-19 cohort consisted of fewer medical patients (48.1% vs. 50.7%), fewer patients with comorbidities (36.5% vs. 40.6%), and more patients on mechanical ventilation (45.3% vs. 42.4%) and vasoactive medication (44.7% vs. 38.4%) compared with the prepandemic cohort. Case-mix adjusted mortality during the pandemic period and its peaks was higher compared with the prepandemic period, odds ratios were, respectively, 1.08 (95% CI, 1.05-1.11) and 1.10 (95% CI, 1.07-1.13). CONCLUSIONS: In non-COVID-19 patients the strain on healthcare has driven lower patient volume, selection of fewer comorbid patients who required more intensive support, and a modest increase in the case-mix adjusted mortality.

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.

Adverse drug events caused by three high-risk drug-drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study.

AIMS: Knowledge about adverse drug events caused by drug-drug interactions (DDI-ADEs) is limited. We aimed to provide detailed insights about DDI-ADEs related to three frequent, high-risk potential DDIs (pDDIs) in the critical care setting: pDDIs with international normalized ratio increase (INR+ ) potential, pDDIs with acute kidney injury (AKI) potential, and pDDIs with QTc prolongation potential. METHODS: We extracted routinely collected retrospective data from electronic health records of intensive care units (ICUs) patients (≥18 years), admitted to ten hospitals in the Netherlands between January 2010 and September 2019. We used computerized triggers (e-triggers) to preselect patients with potential DDI-ADEs. Between September 2020 and October 2021, clinical experts conducted a retrospective manual patient chart review on a subset of preselected patients, and assessed causality, severity, preventability, and contribution to ICU length of stay of DDI-ADEs using internationally prevailing standards. RESULTS: In total 85 422 patients with ≥1 pDDI were included. Of these patients, 32 820 (38.4%) have been exposed to one of the three pDDIs. In the exposed group, 1141 (3.5%) patients were preselected using e-triggers. Of 237 patients (21%) assessed, 155 (65.4%) experienced an actual DDI-ADE; 52.9% had severity level of serious or higher, 75.5% were preventable, and 19.3% contributed to a longer ICU length of stay. The positive predictive value was the highest for DDI-INR+ e-trigger (0.76), followed by DDI-AKI e-trigger (0.57). CONCLUSION: The highly preventable nature and severity of DDI-ADEs, calls for action to optimize ICU patient safety. Use of e-triggers proved to be a promising preselection strategy.

Conservative versus Liberal Oxygenation Targets in Intensive Care Unit Patients (ICONIC): A Randomized Clinical Trial.

Rationale: Supplemental oxygen is widely administered to ICU patients, but appropriate oxygenation targets remain unclear. Objectives: This study aimed to determine whether a low-oxygenation strategy would lower 28-day mortality compared with a high-oxygenation strategy. Methods: This randomized multicenter trial included mechanically ventilated ICU patients with an expected ventilation duration of at least 24 hours. Patients were randomized 1:1 to a low-oxygenation (PaO2, 55-80 mm Hg; or oxygen saturation as measured by pulse oximetry, 91-94%) or high-oxygenation (PaO2, 110-150 mm Hg; or oxygen saturation as measured by pulse oximetry, 96-100%) target until ICU discharge or 28 days after randomization, whichever came first. The primary outcome was 28-day mortality. The study was stopped prematurely because of the COVID-19 pandemic when 664 of the planned 1,512 patients were included. Measurements and Main Results: Between November 2018 and November 2021, a total of 664 patients were included in the trial: 335 in the low-oxygenation group and 329 in the high-oxygenation group. The median achieved PaO2 was 75 mm Hg (interquartile range, 70-84) and 115 mm Hg (interquartile range, 100-129) in the low- and high-oxygenation groups, respectively. At Day 28, 129 (38.5%) and 114 (34.7%) patients had died in the low- and high-oxygenation groups, respectively (risk ratio, 1.11; 95% confidence interval, 0.9-1.4; P = 0.30). At least one serious adverse event was reported in 12 (3.6%) and 17 (5.2%) patients in the low- and high-oxygenation groups, respectively. Conclusions: Among mechanically ventilated ICU patients with an expected mechanical ventilation duration of at least 24 hours, using a low-oxygenation strategy did not result in a reduction of 28-day mortality compared with a high-oxygenation strategy. Clinical trial registered with the National Trial Register and the International Clinical Trials Registry Platform (NTR7376).

Age Moderates the Effect of Obesity on Mortality Risk in Critically Ill Patients With COVID-19: A Nationwide Observational Cohort Study.

OBJECTIVES: A high body mass index (BMI) is associated with an unfavorable disease course in COVID-19, but not among those who require admission to the ICU. This has not been examined across different age groups. We examined whether age modifies the association between BMI and mortality among critically ill COVID-19 patients. DESIGN: An observational cohort study. SETTING: A nationwide registry analysis of critically ill patients with COVID-19 registered in the National Intensive Care Evaluation registry. PATIENTS: We included 15,701 critically ill patients with COVID-19 (10,768 males [68.6%] with median [interquartile range] age 64 yr [55-71 yr]), of whom 1,402 (8.9%) patients were less than 45 years. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the total sample and after adjustment for age, gender, Acute Physiology and Chronic Health Evaluation IV, mechanical ventilation, and use of vasoactive drugs, we found that a BMI greater than or equal to 30 kg/m 2 does not affect hospital mortality (adjusted odds ratio [OR adj ] = 0.98; 95% CI, 0.90-1.06; p = 0.62). For patients less than 45 years old, but not for those greater than or equal to 45 years old, a BMI greater than or equal to 30 kg/m 2 was associated with a lower hospital mortality (OR adj = 0.59; 95% CI, 0.36-0.96; p = 0.03). CONCLUSIONS: A higher BMI may be favorably associated with a lower mortality among those less than 45 years old. This is in line with the so-called "obesity paradox" that was established for other groups of critically ill patients in broad age ranges. Further research is needed to understand this favorable association in young critically ill patients with COVID-19.

Body Mass Index and Mortality in Coronavirus Disease 2019 and Other Diseases: A Cohort Study in 35,506 ICU Patients.

OBJECTIVES: Obesity is a risk factor for severe coronavirus disease 2019 and might play a role in its pathophysiology. It is unknown whether body mass index is related to clinical outcome following ICU admission, as observed in various other categories of critically ill patients. We investigated the relationship between body mass index and inhospital mortality in critically ill coronavirus disease 2019 patients and in cohorts of ICU patients with non-severe acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and multiple trauma. DESIGN: Multicenter observational cohort study. SETTING: Eighty-two Dutch ICUs participating in the Dutch National Intensive Care Evaluation quality registry. PATIENTS: Thirty-five-thousand five-hundred six critically ill patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics and clinical outcomes were compared between four cohorts (coronavirus disease 2019, nonsevere acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and multiple trauma patients) and between body mass index categories within cohorts. Adjusted analyses of the relationship between body mass index and inhospital mortality within each cohort were performed using multivariable logistic regression. Coronavirus disease 2019 patients were more likely male, had a higher body mass index, lower Pao2/Fio2 ratio, and were more likely mechanically ventilated during the first 24 hours in the ICU compared with the other cohorts. Coronavirus disease 2019 patients had longer ICU and hospital length of stay, and higher inhospital mortality. Odds ratios for inhospital mortality for patients with body mass index greater than or equal to 35 kg/m2 compared with normal weight in the coronavirus disease 2019, nonsevere acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and trauma cohorts were 1.15 (0.79-1.67), 0.64 (0.43-0.95), 0.73 (0.61-0.87), and 0.81 (0.57-1.15), respectively. CONCLUSIONS: The obesity paradox, which is the inverse association between body mass index and mortality in critically ill patients, is not present in ICU patients with coronavirus disease 2019-related respiratory failure, in contrast to nonsevere acute respiratory syndrome coronavirus 2 viral and bacterial respiratory infections.

Trends in Early and Late Mortality in Patients With Severe Acute Pancreatitis Admitted to ICUs: A Nationwide Cohort Study.

OBJECTIVES: To investigate national mortality trends over a 12-year period for patients with severe acute pancreatitis (SAP) admitted to Dutch ICUs. Additionally, an assessment of outcome in SAP was undertaken to differentiate between early (< 14 d of ICU admission) and late (> 14 d of ICU admission) mortality. DESIGN: Data from the Dutch National Intensive Care Evaluation and health insurance companies' databases were extracted. Outcomes included 14-day, ICU, hospital, and 1-year mortality. Mortality before and after 2010 was compared using mixed logistic regression and mixed Cox proportional-hazards models. Sensitivity analyses, excluding early mortality, were performed to assess trends in late mortality. SETTING: Not applicable. PATIENTS: Consecutive adult patients with SAP admitted to all 81 Dutch ICUs between 2007 and 2018. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Among 4,160 patients treated in 81 ICUs, 14-day mortality was 17%, ICU mortality 17%, hospital mortality 23%, and 1-year mortality 33%. After 2010 in-hospital mortality adjusted for age, sex, modified Marshall, and Acute Physiology and Chronic Health Evaluation III scores were lower (odds ratio [OR], 0.76; 95% CI, 0.61-0.94) than before 2010. There was no change in ICU and 1-year mortality. Sensitivity analyses excluding patients with early mortality demonstrated a decreased ICU mortality (OR, 0.45; 95% CI, 0.32-0.64), decreased in-hospital (OR, 0.48; 95% CI, 0.36-0.63), and decreased 1-year mortality (hazard ratio, 0.81; 95% CI, 0.68-0.96) after 2010 compared with 2007-2010. CONCLUSIONS: Over the 12-year period examined, mortality in patients with SAP admitted to Dutch ICUs did not change, although after 2010 late mortality decreased. Novel therapies should focus on preventing early mortality in SAP.

Clinical sepsis phenotypes in critically ill COVID-19 patients.

BACKGROUND: A greater understanding of disease heterogeneity may facilitate precision medicine for coronavirus disease 2019 (COVID-19). Previous work identified four distinct clinical phenotypes associated with outcome and treatment responses in non-COVID-19 sepsis patients, but it is unknown if and how these phenotypes are recapitulated in COVID-19 sepsis patients. METHODS: We applied the four non-COVID-19 sepsis phenotypes to a total of 52,274 critically ill patients, comprising two cohorts of COVID-19 sepsis patients (admitted before and after the introduction of dexamethasone as standard treatment) and three non-COVID-19 sepsis cohorts (non-COVID-19 viral pneumonia sepsis, bacterial pneumonia sepsis, and bacterial sepsis of non-pulmonary origin). Differences in proportions of phenotypes and their associated mortality were determined across these cohorts. RESULTS: Phenotype distribution was highly similar between COVID-19 and non-COVID-19 viral pneumonia sepsis cohorts, whereas the proportion of patients with the δ-phenotype was greater in both bacterial sepsis cohorts compared to the viral sepsis cohorts. The introduction of dexamethasone treatment was associated with an increased proportion of patients with the δ-phenotype (6% vs. 11% in the pre- and post-dexamethasone COVID-19 cohorts, respectively, p < 0.001). Across the cohorts, the α-phenotype was associated with the most favorable outcome, while the δ-phenotype was associated with the highest mortality. Survival of the δ-phenotype was markedly higher following the introduction of dexamethasone (60% vs 41%, p < 0.001), whereas no relevant differences in survival were observed for the other phenotypes among COVID-19 patients. CONCLUSIONS: Classification of critically ill COVID-19 patients into clinical phenotypes may aid prognostication, prediction of treatment efficacy, and facilitation of personalized medicine.

The effect of treatment and clinical course during Emergency Department stay on severity scoring and predicted mortality risk in Intensive Care patients.

BACKGROUND: Treatment and the clinical course during Emergency Department (ED) stay before Intensive Care Unit (ICU) admission may affect predicted mortality risk calculated by the Acute Physiology and Chronic Health Evaluation (APACHE)-IV, causing lead-time bias. As a result, comparing standardized mortality ratios (SMRs) among hospitals may be difficult if they differ in the location where initial stabilization takes place. The aim of this study was to assess to what extent predicted mortality risk would be affected if the APACHE-IV score was recalculated with the initial physiological variables from the ED. Secondly, to evaluate whether ED Length of Stay (LOS) was associated with a change (delta) in these APACHE-IV scores. METHODS: An observational multicenter cohort study including ICU patients admitted from the ED. Data from two Dutch quality registries were linked: the Netherlands Emergency department Evaluation Database (NEED) and the National Intensive Care Evaluation (NICE) registry. The ICU APACHE-IV, predicted mortality, and SMR based on data of the first 24 h of ICU admission were compared with an ED APACHE-IV model, using the most deviating physiological variables from the ED or ICU. RESULTS: A total of 1398 patients were included. The predicted mortality from the ICU APACHE-IV (median 0.10; IQR 0.03-0.30) was significantly lower compared to the ED APACHE-IV model (median 0.13; 0.04-0.36; p < 0.01). The SMR changed from 0.63 (95%CI 0.54-0.72) to 0.55 (95%CI 0.47-0.63) based on ED APACHE-IV. Predicted mortality risk changed more than 5% in 321 (23.2%) patients by using the ED APACHE-IV. ED LOS > 3.9 h was associated with a slight increase in delta APACHE-IV of 1.6 (95% CI 0.4-2.8) compared to ED LOS < 1.7 h. CONCLUSION: Predicted mortality risks and SMRs calculated by the APACHE IV scores are not directly comparable in patients admitted from the ED if hospitals differ in their policy to stabilize patients in the ED before ICU admission. Future research should focus on developing models to adjust for these differences.

Diagnosis clarification by generalization to patient-friendly terms and definitions: Validation study.

BACKGROUND: Now that patients increasingly get access to their healthcare records, its contents require clarification. The use of patient-friendly terms and definitions can help patients and their significant others understand their medical data. However, it is costly to make patient-friendly descriptions for the myriad of terms used in the medical domain. Furthermore, a description in more general terms, leaving out some of the details, might already be sufficient for a layperson. We developed an algorithm that employs the SNOMED CT hierarchy to generalize diagnoses to a limited set of concepts with patient-friendly terms for this purpose. However, generalization essentially implies loss of detail and might result in errors, hence these generalizations remain to be validated by clinicians. We aim to assess the medical validity of diagnosis clarification by generalization to concepts with patient-friendly terms and definitions in SNOMED CT. Furthermore, we aim to identify the characteristics that render clarifications invalid. RESULTS: Two raters identified errors in 12.7% (95% confidence interval - CI: 10.7-14.6%) of a random sample of 1,131 clarifications and they considered 14.3% (CI: 12.3-16.4%) of clarifications to be unacceptable to show to a patient. The intraclass correlation coefficient of the interrater reliability was 0.34 for correctness and 0.43 for acceptability. Errors were mostly related to the patient-friendly terms and definitions used in the clarifications themselves, but also to terminology mappings, terminology modelling, and the clarification algorithm. Clarifications considered to be most unacceptable were those that provide wrong information and might cause unnecessary worry. CONCLUSIONS: We have identified problems in generalizing diagnoses to concepts with patient-friendly terms. Diagnosis generalization can be used to create a large amount of correct and acceptable clarifications, reusing patient-friendly terms and definitions across many medical concepts. However, the correctness and acceptability have a strong dependency on terminology mappings and modelling quality, as well as the quality of the terms and definitions themselves. Therefore, validation and quality improvement are required to prevent incorrect and unacceptable clarifications, before using the generalizations in practice.

One-year Mortality of Cancer Patients with an Unplanned ICU Admission: A Cohort Analysis Between 2008 and 2017 in the Netherlands.

Introduction: A decrease in short-term mortality of critically ill cancer patients with an unplanned intensive care unit (ICU) admission has been described. Few studies describe a change over time of 1-year mortality. Therefore, we examined the 1-year mortality of cancer patients (hematological or solid) with an unplanned ICU admission and we described whether the mortality changed over time. Methods: We used the National Intensive Care Evaluation (NICE) registry and extracted all patients with an unplanned ICU admission in the Netherlands between 2008 and 2017. The primary outcome was 1-year mortality, analyzed with a mixed-effects Cox proportional hazard regression. We compared the 1-year mortality of cancer patients to that of patients without cancer. Furthermore, we examined changes in mortality over the study period. Results: We included 470,305 patients: 10,401 with hematological cancer, 35,920 with solid cancer, and 423,984 without cancer. The 1-year mortality rates were 60.1%, 46.2%, and 28.3% respectively (P< .01). Approximately 30% of the cancer patients surviving their hospital admission died within 1 year, this was 12% in patients without cancer. In hematological patients, 1-year mortality decreased between 2008 and 2011, after which it stabilized. In solid cancer patients, inspection showed neither an increasing nor decreasing trend over the inclusion period. For patients without cancer, 1-year mortality decreased between 2008 and 2013, after which it stabilized. A clear decrease in hospital mortality was seen within all three groups. Conclusion: The 1-year mortality of cancer patients with an unplanned ICU admission (hematological and solid) was higher than that of patients without cancer. About one-third of the cancer patients surviving their hospital admission died within 1 year after ICU admission. We found a decrease in 1-year mortality until 2011 in hematology patients and no decrease in solid cancer patients. Our results suggest that for many cancer patients, an unplanned ICU admission is still a way to recover from critical illness, and it does not necessarily lead to success in long-term survival. The underlying type of malignancy is an important factor for long-term outcomes in patients recovering from critical illness.

Comparison of patient characteristics and long-term mortality between transferred and non-transferred COVID-19 patients in Dutch intensive care units: A national cohort study.

BACKGROUND: COVID-19 patients were often transferred to other intensive care units (ICUs) to prevent that ICUs would reach their maximum capacity. However, transferring ICU patients is not free of risk. We aim to compare the characteristics and outcomes of transferred versus non-transferred COVID-19 ICU patients in the Netherlands. METHODS: We included adult COVID-19 patients admitted to Dutch ICUs between March 1, 2020 and July 1, 2021. We compared the patient characteristics and outcomes of non-transferred and transferred patients and used a Directed Acyclic Graph to identify potential confounders in the relationship between transfer and mortality. We used these confounders in a Cox regression model with left truncation at the day of transfer to analyze the effect of transfers on mortality during the 180 days after ICU admission. RESULTS: We included 10,209 patients: 7395 non-transferred and 2814 (27.6%) transferred patients. In both groups, the median age was 64 years. Transferred patients were mostly ventilated at ICU admission (83.7% vs. 56.2%) and included a larger proportion of low-risk patients (70.3% vs. 66.5% with mortality risk <30%). After adjusting for age, APACHE IV mortality probability, BMI, mechanical ventilation, and vasoactive medication use, the hazard of mortality during the first 180 days was similar for transferred patients compared to non-transferred patients (HR [95% CI] = 0.99 [0.91-1.08]). CONCLUSIONS: Transferred COVID-19 patients are more often mechanically ventilated and are less severely ill compared to non-transferred patients. Furthermore, transferring critically ill COVID-19 patients in the Netherlands is not associated with mortality during the first 180 days after ICU admission.

Association Between an Increase in Serum Sodium and In-Hospital Mortality in Critically Ill Patients.

OBJECTIVES: In critically ill patients, dysnatremia is common, and in these patients, in-hospital mortality is higher. It remains unknown whether changes of serum sodium after ICU admission affect mortality, especially whether normalization of mild hyponatremia improves survival. DESIGN: Retrospective cohort study. SETTING: Ten Dutch ICUs between January 2011 and April 2017. PATIENTS: Adult patients were included if at least one serum sodium measurement within 24 hours of ICU admission and at least one serum sodium measurement 24-48 hours after ICU admission were available. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A logistic regression model adjusted for age, sex, and Acute Physiology and Chronic Health Evaluation-IV-predicted mortality was used to assess the difference between mean of sodium measurements 24-48 hours after ICU admission and first serum sodium measurement at ICU admission (Δ48 hr-[Na]) and in-hospital mortality. In total, 36,660 patients were included for analysis. An increase in serum sodium was independently associated with a higher risk of in-hospital mortality in patients admitted with normonatremia (Δ48 hr-[Na] 5-10 mmol/L odds ratio: 1.61 [1.44-1.79], Δ48 hr-[Na] > 10 mmol/L odds ratio: 4.10 [3.20-5.24]) and hypernatremia (Δ48 hr-[Na] 5-10 mmol/L odds ratio: 1.47 [1.02-2.14], Δ48 hr-[Na] > 10 mmol/L odds ratio: 8.46 [3.31-21.64]). In patients admitted with mild hyponatremia and Δ48 hr-[Na] greater than 5 mmol/L, no significant difference in hospital mortality was found (odds ratio, 1.11 [0.99-1.25]). CONCLUSIONS: An increase in serum sodium in the first 48 hours of ICU admission was associated with higher in-hospital mortality in patients admitted with normonatremia and in patients admitted with hypernatremia.

Contextual property detection in Dutch diagnosis descriptions for uncertainty, laterality and temporality.

BACKGROUND: Accurate, coded problem lists are valuable for data reuse, including clinical decision support and research. However, healthcare providers frequently modify coded diagnoses by including or removing common contextual properties in free-text diagnosis descriptions: uncertainty (suspected glaucoma), laterality (left glaucoma) and temporality (glaucoma 2002). These contextual properties could cause a difference in meaning between underlying diagnosis codes and modified descriptions, inhibiting data reuse. We therefore aimed to develop and evaluate an algorithm to identify these contextual properties. METHODS: A rule-based algorithm called UnLaTem (Uncertainty, Laterality, Temporality) was developed using a single-center dataset, including 288,935 diagnosis descriptions, of which 73,280 (25.4%) were modified by healthcare providers. Internal validation of the algorithm was conducted with an independent sample of 980 unique records. A second validation of the algorithm was conducted with 996 records from a Dutch multicenter dataset including 175,210 modified descriptions of five hospitals. Two researchers independently annotated the two validation samples. Performance of the algorithm was determined using means of the recall and precision of the validation samples. The algorithm was applied to the multicenter dataset to determine the actual prevalence of the contextual properties within the modified descriptions per specialty. RESULTS: For the single-center dataset recall (and precision) for removal of uncertainty, uncertainty, laterality and temporality respectively were 100 (60.0), 99.1 (89.9), 100 (97.3) and 97.6 (97.6). For the multicenter dataset for removal of uncertainty, uncertainty, laterality and temporality it was 57.1 (88.9), 86.3 (88.9), 99.7 (93.5) and 96.8 (90.1). Within the modified descriptions of the multicenter dataset, 1.3% contained removal of uncertainty, 9.9% uncertainty, 31.4% laterality and 9.8% temporality. CONCLUSIONS: We successfully developed a rule-based algorithm named UnLaTem to identify contextual properties in Dutch modified diagnosis descriptions. UnLaTem could be extended with more trigger terms, new rules and the recognition of term order to increase the performance even further. The algorithm's rules are available as additional file 2. Implementing UnLaTem in Dutch hospital systems can improve precision of information retrieval and extraction from diagnosis descriptions, which can be used for data reuse purposes such as decision support and research.

Quality indicators for patients with traumatic brain injury in European intensive care units: a CENTER-TBI study.

BACKGROUND: The aim of this study is to validate a previously published consensus-based quality indicator set for the management of patients with traumatic brain injury (TBI) at intensive care units (ICUs) in Europe and to study its potential for quality measurement and improvement. METHODS: Our analysis was based on 2006 adult patients admitted to 54 ICUs between 2014 and 2018, enrolled in the CENTER-TBI study. Indicator scores were calculated as percentage adherence for structure and process indicators and as event rates or median scores for outcome indicators. Feasibility was quantified by the completeness of the variables. Discriminability was determined by the between-centre variation, estimated with a random effect regression model adjusted for case-mix severity and quantified by the median odds ratio (MOR). Statistical uncertainty of outcome indicators was determined by the median number of events per centre, using a cut-off of 10. RESULTS: A total of 26/42 indicators could be calculated from the CENTER-TBI database. Most quality indicators proved feasible to obtain with more than 70% completeness. Sub-optimal adherence was found for most quality indicators, ranging from 26 to 93% and 20 to 99% for structure and process indicators. Significant (p < 0.001) between-centre variation was found in seven process and five outcome indicators with MORs ranging from 1.51 to 4.14. Statistical uncertainty of outcome indicators was generally high; five out of seven had less than 10 events per centre. CONCLUSIONS: Overall, nine structures, five processes, but none of the outcome indicators showed potential for quality improvement purposes for TBI patients in the ICU. Future research should focus on implementation efforts and continuous reevaluation of quality indicators. TRIAL REGISTRATION: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on August 06, 2014, with Resource Identification Portal (RRID: SCR_015582).

Performance of the quick SOFA in very old ICU patients admitted with sepsis.

BACKGROUND: The number of very elderly ICU patients (abbreviated to VOPs; ≥80 years) with sepsis increases. Sepsis was redefined in 2016 (sepsis 3.0) using the quick SOFA (qSOFA) score. Since then, multiple studies have validated qSOFA for prognostication in different patient categories, but the prognostic value in VOPs with sepsis is still unknown. METHODS: Retrospective cohort study including patients admitted to Dutch ICUs with sepsis, in the period 2012 to 2016, evaluating the outcome and the performance of qSOFA, an extended qSOFA model, SOFA, SAPS II, and APACHE IV for hospital mortality. RESULTS: 5969 patients were included, of which 935 VOPs. Crude hospital mortality rates were 19%, 28%, and 39% for patients aged 18-65, 65-80, and ≥80 years respectively. Discriminative performance of qSOFA for in-hospital mortality in VOPs was poor (AUC 0.596) and lower than that of SOFA, APACHE IV, and SAPS II (0.704, 0.722, and 0.780 respectively). A qSOFA model extended with several other characteristics (AUC 0.643) was non-inferior to the full SOFA, but still inferior to APACHE IV and SAPS II, for all age groups. The Hosmer-Lemeshow goodness-of-fit test showed non-significant p-values for all models. Accuracy for both qSOFA and the extended qSOFA was lower compared to APACHE IV and SAPS II (Brier scores 0.227, 0.223, 0.184, and 0.183 respectively). CONCLUSION: The qSOFA showed worse discriminative performance to predict mortality than SOFA, APACHE IV, and SAPS II in both VOPs and younger patients admitted with sepsis.

Evaluation of lexical clarification by patients reading their clinical notes: a quasi-experimental interview study.

BACKGROUND: Patients benefit from access to their medical records. However, clinical notes and letters are often difficult to comprehend for most lay people. Therefore, functionality was implemented in the patient portal of a Dutch university medical centre (UMC) to clarify medical terms in free-text data. The clarifications consisted of synonyms and definitions from a Dutch medical terminology system. We aimed to evaluate to what extent these lexical clarifications match the information needs of the patients. Secondarily, we evaluated how the clarifications and the functionality could be improved. METHODS: We invited participants from the patient panel of the UMC to read their own clinical notes. They marked terms they found difficult and rated the ease of these terms. After the functionality was activated, participants rated the clarifications provided by the functionality, and the functionality itself regarding ease and usefulness. Ratings were on a scale from 0 (very difficult) to 100 (very easy). We calculated the median number of terms not understood per participant, the number of terms with a clarification, the overlap between these numbers (coverage), and the precision and recall. RESULTS: We included 15 participants from the patient panel. They marked a median of 21 (IQR 19.5-31) terms as difficult in their text files, while only a median of 2 (IQR 1-4) of these terms were clarified by the functionality. The median precision was 6.5% (IQR 2.3-14.25%) and the median recall 8.3% (IQR 4.7-13.5%) per participant. However, participants rated the functionality with median ease of 98 (IQR 93.5-99) and a median usefulness of 79 (IQR 52.5-97). Participants found that many easy terms were unnecessarily clarified, that some clarifications were difficult, and that some clarifications contained mistakes. CONCLUSIONS: Patients found the functionality easy to use and useful. However, in its current form it only helped patients to understand few terms they did not understand, patients found some clarifications to be difficult, and some to be incorrect. This shows that lexical clarification is feasible even when limited terms are available, but needs further development to fully use its potential.

ICU Survivors Have a Substantial Higher Risk of Developing New Chronic Conditions Compared to a Population-Based Control Group.

OBJECTIVES: To describe the types and prevalence of chronic conditions in an ICU population and a population-based control group during the year before ICU admission and to quantify the risk of developing new chronic conditions in ICU patients compared with the control group. DESIGN: We conducted a retrospective cohort study, combining a national health insurance claims database and a national quality registry for ICUs. Claims data in the timeframe 2012-2014 were combined with clinical data of patients who had been admitted to an ICU during 2013. To assess the differences in risk of developing new chronic conditions, ICU patients were compared with a population-based control group using logistic regression modeling. SETTING: Eighty-one Dutch ICUs. PATIENTS: All patients admitted to an ICU during 2013. A population-based control group was created, and weighted on the age, gender, and socio-economic status of the ICU population. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICU patients (n = 56,760) have more chronic conditions compared with the control group (n = 75,232) during the year before ICU admission (p < 0.0001). After case-mix adjustment ICU patients had a higher risk of developing chronic conditions, with odds ratios ranging from 1.67 (CI, 1.29-2.17) for asthma to 24.35 (CI, 14.00-42.34) for epilepsy, compared with the control group. CONCLUSIONS: Due to the high prevalence of chronic conditions and the increased risk of developing new chronic conditions, ICU follow-up care is advised and may focus on the identification and treatment of the new developed chronic conditions.

Emergency Department to ICU Time Is Associated With Hospital Mortality: A Registry Analysis of 14,788 Patients From Six University Hospitals in The Netherlands.

OBJECTIVES: Prolonged emergency department to ICU waiting time may delay intensive care treatment, which could negatively affect patient outcomes. The aim of this study was to investigate whether emergency department to ICU time is associated with hospital mortality. DESIGN, SETTING, AND PATIENTS: We conducted a retrospective observational cohort study using data from the Dutch quality registry National Intensive Care Evaluation. Adult patients admitted to the ICU directly from the emergency department in six university hospitals, between 2009 and 2016, were included. Using a logistic regression model, we investigated the crude and adjusted (for disease severity; Acute Physiology and Chronic Health Evaluation IV probability) odds ratios of emergency department to ICU time on mortality. In addition, we assessed whether the Acute Physiology and Chronic Health Evaluation IV probability modified the effect of emergency department to ICU time on mortality. Secondary outcomes were ICU, 30-day, and 90-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 14,788 patients were included. The median emergency department to ICU time was 2.0 hours (interquartile range, 1.3-3.3 hr). Emergency department to ICU time was correlated to adjusted hospital mortality (p < 0.002), in particular in patients with the highest Acute Physiology and Chronic Health Evaluation IV probability and long emergency department to ICU time quintiles: odds ratio, 1.29; 95% CI, 1.02-1.64 (2.4-3.7 hr) and odds ratio, 1.54; 95% CI, 1.11-2.14 (> 3.7 hr), both compared with the reference category (< 1.2 hr). For 30-day and 90-day mortality, we found similar results. However, emergency department to ICU time was not correlated to adjusted ICU mortality (p = 0.20). CONCLUSIONS: Prolonged emergency department to ICU time (> 2.4 hr) is associated with increased hospital mortality after ICU admission, mainly driven by patients who had a higher Acute Physiology and Chronic Health Evaluation IV probability. We hereby provide evidence that rapid admission of the most critically ill patients to the ICU might reduce hospital mortality.