Genetic association studies in critically ill patients:protocol for a systematic review

Introduction: Patients in the intensive care unit (ICU) are highly heterogeneous in characteristics, their clinical course, and outcomes. Genetic variability may partly explain the variability and similarity in disease courses observed among critically ill patients and may identify clusters of subgroups. The aim of this study is to conduct a systematic review of all genetic association studies of critically ill patients with their outcomes. Methods and analysis: This systematic review will be conducted and reported according to the HuGE Review Handbook V1.0. We will search PubMed, Embase, and the Cochrane Library for relevant studies. All types of genetic association studies that included acutely admitted medical and surgical adult ICU patients will be considered for this review. All studies will be selected according to predefined selection criteria, evaluated and assessed for risk of bias independently by two reviewers. Risk of bias will be assessed according to the HuGE Review Handbook V1.0 with some modifications reflecting recent insights. We will provide an overview of all included studies by reporting the characteristics of the study designs, the patients included in the studies, the genetic variables, and the outcomes evaluated. Ethics and dissemination: We will use data from peer-reviewed published articles, and hence, there is no requirement for ethics approval. The results of this systematic review will be disseminated through publication in a peer-reviewed scientific journal.</p

Right ventricular strain measurements in critically ill patients: an observational SICS sub-study

Background: Right ventricular (RV) dysfunction is common in critically ill patients and is associated with poor outcomes. RV function is usually evaluated by Tricuspid Annular Plane Systolic Excursion (TAPSE) which can be obtained using critical care echocardiography (CCE). Myocardial deformation imaging, measuring strain, is suitable for advanced RV function assessment and has widely been studied in cardiology. However, it is relatively new for the Intensive Care Unit (ICU) and little is known about RV strain in critically ill patients. Therefore, the objectives of this study were to evaluate the feasibility of RV strain in critically ill patients using tissue-Doppler imaging (TDI) and explore the association between RV strain and conventional CCE measurements representing RV function. Methods: This is a single-center sub-study of two prospective observational cohorts (Simple Intensive Care Studies (SICS)-I and SICS-II). All acutely admitted adults with an expected ICU stay over 24 h were included. CCE was performed within 24 h of ICU admission. In patients in which CCE was performed, TAPSE, peak systolic velocity at the tricuspid annulus (RV s’) and TDI images were obtained. RV free wall longitudinal strain (RVFWSL) and RV global four-chamber longitudinal strain (RV4CSL) were measured during offline analysis. Results: A total of 171 patients were included. Feasibility of RVFWSL and RV4CSL was, respectively, 62% and 56% in our population; however, when measurements were performed, intra- and inter-rater reliability based on the intraclass correlation coefficient were good to excellent. RV dysfunction based on TAPSE or RV s’ was found in 56 patients (33%) and 24 patients (14%) had RV dysfunction based on RVFWSL or RV4CSL. In 14 patients (8%), RVFWSL, RV4CSL, or both were reduced, despite conventional RV function measurements being preserved. These patients had significantly higher severity of illness scores. Sensitivity analysis with fractional area change showed similar results. Conclusions: TDI RV strain imaging in critically ill patients is challenging; however, good-to-excellent reproducibility was shown when measurements were adequately obtained. Future studies are needed to elucidate the diagnostic and prognostic value of RV strain in critically ill patients, especially to outweigh the difficulty and effort of imaging against the clinical value

Right ventricular strain measurements in critically ill patients:an observational SICS sub-study

Background: Right ventricular (RV) dysfunction is common in critically ill patients and is associated with poor outcomes. RV function is usually evaluated by Tricuspid Annular Plane Systolic Excursion (TAPSE) which can be obtained using critical care echocardiography (CCE). Myocardial deformation imaging, measuring strain, is suitable for advanced RV function assessment and has widely been studied in cardiology. However, it is relatively new for the Intensive Care Unit (ICU) and little is known about RV strain in critically ill patients. Therefore, the objectives of this study were to evaluate the feasibility of RV strain in critically ill patients using tissue-Doppler imaging (TDI) and explore the association between RV strain and conventional CCE measurements representing RV function. Methods: This is a single-center sub-study of two prospective observational cohorts (Simple Intensive Care Studies (SICS)-I and SICS-II). All acutely admitted adults with an expected ICU stay over 24 h were included. CCE was performed within 24 h of ICU admission. In patients in which CCE was performed, TAPSE, peak systolic velocity at the tricuspid annulus (RV s’) and TDI images were obtained. RV free wall longitudinal strain (RVFWSL) and RV global four-chamber longitudinal strain (RV4CSL) were measured during offline analysis. Results: A total of 171 patients were included. Feasibility of RVFWSL and RV4CSL was, respectively, 62% and 56% in our population; however, when measurements were performed, intra- and inter-rater reliability based on the intraclass correlation coefficient were good to excellent. RV dysfunction based on TAPSE or RV s’ was found in 56 patients (33%) and 24 patients (14%) had RV dysfunction based on RVFWSL or RV4CSL. In 14 patients (8%), RVFWSL, RV4CSL, or both were reduced, despite conventional RV function measurements being preserved. These patients had significantly higher severity of illness scores. Sensitivity analysis with fractional area change showed similar results. Conclusions: TDI RV strain imaging in critically ill patients is challenging; however, good-to-excellent reproducibility was shown when measurements were adequately obtained. Future studies are needed to elucidate the diagnostic and prognostic value of RV strain in critically ill patients, especially to outweigh the difficulty and effort of imaging against the clinical value

External Validation of Mortality Prediction Models for Critical Illness Reveals Preserved Discrimination but Poor Calibration

OBJECTIVES: In a recent scoping review, we identified 43 mortality prediction models for critically ill patients. We aimed to assess the performances of these models through external validation. DESIGN: Multicenter study. SETTING: External validation of models was performed in the Simple Intensive Care Studies-I (SICS-I) and the Finnish Acute Kidney Injury (FINNAKI) study. PATIENTS: The SICS-I study consisted of 1,075 patients, and the FINNAKI study consisted of 2,901 critically ill patients. MEASUREMENTS AND MAIN RESULTS: For each model, we assessed: 1) the original publications for the data needed for model reconstruction, 2) availability of the variables, 3) model performance in two independent cohorts, and 4) the effects of recalibration on model performance. The models were recalibrated using data of the SICS-I and subsequently validated using data of the FINNAKI study. We evaluated overall model performance using various indexes, including the (scaled) Brier score, discrimination (area under the curve of the receiver operating characteristics), calibration (intercepts and slopes), and decision curves. Eleven models (26%) could be externally validated. The Acute Physiology And Chronic Health Evaluation (APACHE) II, APACHE IV, Simplified Acute Physiology Score (SAPS)-Reduced (SAPS-R)‚ and Simplified Mortality Score for the ICU models showed the best scaled Brier scores of 0.11‚ 0.10‚ 0.10‚ and 0.06‚ respectively. SAPS II, APACHE II, and APACHE IV discriminated best; overall discrimination of models ranged from area under the curve of the receiver operating characteristics of 0.63 (0.61-0.66) to 0.83 (0.81-0.85). We observed poor calibration in most models, which improved to at least moderate after recalibration of intercepts and slopes. The decision curve showed a positive net benefit in the 0-60% threshold probability range for APACHE IV and SAPS-R. CONCLUSIONS: In only 11 out of 43 available mortality prediction models, the performance could be studied using two cohorts of critically ill patients. External validation showed that the discriminative ability of APACHE II, APACHE IV, and SAPS II was acceptable to excellent, whereas calibration was poor