OBJECTIVES: To develop a scoring model for stratifying patients with acute respiratory distress syndrome into risk categories (Stratification for identification of Prognostic categories In the... Show moreOBJECTIVES: To develop a scoring model for stratifying patients with acute respiratory distress syndrome into risk categories (Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score) for early prediction of death in the ICU, independent of the underlying disease and cause of death. DESIGN: A development and validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: One-thousand three-hundred one patients with moderate-to-severe acute respiratory distress syndrome managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study followed Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines for prediction models. We performed logistic regression analysis, bootstrapping, and internal-external validation of prediction models with variables collected within 24 hours of acute respiratory distress syndrome diagnosis in 1,000 patients for model development. Primary outcome was ICU death. The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score was based on patient's age, number of extrapulmonary organ failures, values of end-inspiratory plateau pressure, and ratio of Pao(2) to Fio(2) assessed at 24 hours of acute respiratory distress syndrome diagnosis. The pooled area under the receiver operating characteristic curve across internal-external validations was 0.860 (95% CI, 0.831-0.890). External validation in a new cohort of 301 acute respiratory distress syndrome patients confirmed the accuracy and robustness of the scoring model (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.829-0.911). The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score stratified patients in three distinct prognostic classes and achieved better prediction of ICU death than ratio of Pao(2) to Fio(2) at acute respiratory distress syndrome onset or at 24 hours, Acute Physiology and Chronic Health Evaluation II score, or Sequential Organ Failure Assessment scale. CONCLUSIONS: The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score represents a novel strategy for early stratification of acute respiratory distress syndrome patients into prognostic categories and for selecting patients for therapeutic trials. Show less
Background and Aims: Inflammatory bowel disease [IBD] phenotypes are very heterogeneous between patients, and current clinical and molecular classifications do not accurately predict the course... Show moreBackground and Aims: Inflammatory bowel disease [IBD] phenotypes are very heterogeneous between patients, and current clinical and molecular classifications do not accurately predict the course that IBD will take over time. Genetic determinants of disease phenotypes remain largely unknown but could aid drug development and allow for personalised management. We used genetic risk scores [GRS] to disentangle the genetic contributions to IBD phenotypes.Methods: Clinical characteristics and imputed genome-wide genetic array data of patients with IBD were obtained from two independent cohorts [cohort A, n= 1097; cohort B, n= 2156]. Genetic risk scoring [GRS] was used to assess genetic aetiology shared across traits and IBD phenotypes. Significant GRS-phenotype (false-discovery rate [FDR] corrected p<0.05) associations identified in cohort A were put forward for replication in cohort B.Results: Crohn's disease [CD] GRS were associated with fibrostenotic CD [R-2= 7.4%, FDR = 0.02] and ileocaecal resection [R-2 = 4.1%, FDR = 1.6E-03], and this remained significant after correcting for previously identified clinical and genetic risk factors. Ulcerative colitis [UC] GRS [R-2 = 7.1%, FDR = 0.02] and primary sclerosing cholangitis [PSC] GRS [R-2 . 3.6%, FDR = 0.03] were associated with colonic CD, and these two associations were largely driven by genetic variation in MHC. We also observed pleiotropy between PSC genetic risk and smoking behaviour [R-2 = 1.7%, FDR = 0.04].Conclusions: Patients with a higher genetic burden of CD are more likely to develop fibrostenotic disease and undergo ileocaecal resection, whereas colonic CD shares genetic aetiology with PSC and UC that is largely driven by variation in MHC. These results further our understanding of specific IBD phenotypes. Show less
