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Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia - results from the prospective observational PROGRESS study.

ABSTRACT: BACKGROUND:CAP (Community acquired pneumonia) is frequent, with a high mortality rate and a high burden on health care systems. Development of predictive biomarkers, new therapeutic concepts, and epidemiologic research require a valid, reproducible, and quantitative measure describing CAP severity. METHODS:Using time series data of 1532 patients enrolled in the PROGRESS study, we compared putative measures of CAP severity for their utility as an operationalization. Comparison was based on ability to correctly identify patients with an objectively severe state of disease (death or need for intensive care with at least one of the following: substantial respiratory support, treatment with catecholamines, or dialysis). We considered IDSA/ATS minor criteria, CRB-65, CURB-65, Halm criteria, qSOFA, PSI, SCAP, SIRS-Score, SMART-COP, and SOFA. RESULTS:SOFA significantly outperformed other scores in correctly identifying a severe state of disease at the day of enrollment (AUC?=?0.948), mainly caused by higher discriminative power at higher score values. Runners-up were the sum of IDSA/ATS minor criteria (AUC?=?0.916) and SCAP (AUC?=?0.868). SOFA performed similarly well on subsequent study days (all AUC?>?0.9) and across age groups. In univariate and multivariate analysis, age, sex, and pack-years significantly contributed to higher SOFA values whereas antibiosis before hospitalization predicted lower SOFA. CONCLUSIONS:SOFA score can serve as an excellent operationalization of CAP severity and is proposed as endpoint for biomarker and therapeutic studies. TRIAL REGISTRATION:clinicaltrials.gov NCT02782013 , May 25, 2016, retrospectively registered.

SUBMITTER: Ahnert P

PROVIDER: S-EPMC6450002 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia - results from the prospective observational PROGRESS study.

Ahnert Peter P Creutz Petra P Horn Katrin K Schwarzenberger Fabian F Kiehntopf Michael M Hossain Hamid H Bauer Michael M Brunkhorst Frank Martin FM Reinhart Konrad K Völker Uwe U Chakraborty Trinad T Witzenrath Martin M Löffler Markus M Suttorp Norbert N Scholz Markus M

Critical care (London, England) 20190404 1

<h4>Background</h4>CAP (Community acquired pneumonia) is frequent, with a high mortality rate and a high burden on health care systems. Development of predictive biomarkers, new therapeutic concepts, and epidemiologic research require a valid, reproducible, and quantitative measure describing CAP severity.<h4>Methods</h4>Using time series data of 1532 patients enrolled in the PROGRESS study, we compared putative measures of CAP severity for their utility as an operationalization. Comparison was ...[more]

PMID: 30947753

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Project description:BackgroundCommunity acquired pneumonia (CAP) is a high incidence disease resulting in about 260,000 hospital admissions per year in Germany, more than myocardial infarction or stroke. Worldwide, CAP is the most frequent infectious disease with high lethality ranging from 1.2 % in those 20-29 years old to over 10 % in patients older than 70 years, even in industrial nations. CAP poses numerous medical challenges, which the PROGRESS (Pneumonia Research Network on Genetic Resistance and Susceptibility for the Evolution of Severe Sepsis) network aims to tackle: Operationalization of disease severity throughout the course of disease, outcome prediction for hospitalized patients and prediction of transitions from uncomplicated CAP to severe CAP, and finally, to CAP with sepsis and organ failure as a life-threatening condition. It is a major aim of PROGRESS to understand and predict patient heterogeneity regarding outcome in the hospital and to develop novel treatment concepts.MethodsPROGRESS was designed as a clinical, observational, multi-center study of patients with CAP requiring hospitalization. More than 1600 patients selected for low burden of co-morbidities have been enrolled, aiming at a total of 3000. Course of disease, along with therapy, was closely monitored by daily assessments and long-term follow-up. Daily blood samples allow in depth molecular-genetic characterization of patients. We established a well-organized workflow for sample logistics and a comprehensive data management system to collect and manage data from more than 50 study centers in Germany and Austria. Samples are stored in a central biobank and clinical data are stored in a central data base which also integrates all data from molecular assessments.DiscussionWith the PROGRESS study, we established a comprehensive data base of high quality clinical and molecular data allowing investigation of pressing research questions regarding CAP. In-depth molecular characterization will contribute to the discovery of disease mechanisms and establishment of diagnostic and predictive biomarkers. A strength of PROGRESS is the focus on younger patients with low burden of co-morbidities, allowing a more direct look at host biology with less confounding. As a resulting limitation, insights from PROGRESS will require validation in representative patient cohorts to assess clinical utility.Trial registrationThe PROGRESS study was retrospectively registered on May 24(th), 2016 with ClinicalTrials.gov: NCT02782013.

Project description:Background: Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in children. Diagnosis remains challenging and there are no reliable tools to objectively risk stratify patients or predict clinical outcomes. Molecular distance to health (MDTH) is a genomic score that measures the global perturbation of the transcriptional profile and may help classify patients by disease severity. We evaluated the value of MDTH to assess disease severity in children hospitalized with CAP. Methods: Children hospitalized with CAP and matched healthy controls were enrolled in a prospective observational study. Blood samples were obtained for transcriptome analyses within 24 h of hospitalization. MDTH scores were calculated to assess disease severity and correlated with laboratory markers, such as white blood cell count, c-reactive protein (CRP), and procalcitonin (PCT), and clinical outcomes, including duration of fever and duration of hospitalization (LOS). Univariate and multivariable logistic regression were applied to assess factors associated with LOS and duration of fever after hospitalization. Results: Among children hospitalized with CAP (n = 152), pyogenic bacteria (PB) were detected in 16 (11%), Mycoplasma pneumoniae was detected in 41 (28%), respiratory viruses (RV) alone were detected in 78 (51%), and no pathogen was detected in 17 (11%) children. Statistical group comparisons identified 6,726 genes differentially expressed in patients with CAP vs. healthy controls (n = 39). Children with confirmed PB had higher MDTH scores than those with RV (p < 0.05) or M. pneumoniae (p < 0.01) detected alone. CRP (r = 0.39, p < 0.0001), PCT (r = 0.39, p < 0.0001), and MDTHs (r = 0.24, p < 0.01) correlated with duration of fever, while only MDTHs correlated with LOS (r = 0.33, p < 0.0001). Unadjusted analyses showed that both higher CRP and MDTHs were associated with longer LOS (OR 1.04 [1-1.07] and 1.12 [1.04-1.20], respectively), however, only MDTH remained significant when adjusting for other covariates (aOR 1.11 [1.01-1.22]). Conclusions: In children hospitalized with CAP MDTH score measured within 24 h of admission was independently associated with longer duration of hospitalization, regardless of the pathogen detected. This suggests that transcriptional biomarkers may represent a promising approach to assess disease severity in children with CAP.

Project description:BackgroundThe Confusion, Urea > 7 mM, Respiratory Rate ≥ 30 breaths/min, BP < 90 mm Hg (Systolic) or < 60 mm Hg (Diastolic), Age ≥ 65 Years (CURB-65) score and the Pneumonia Severity Index (PSI) are well-established clinical prediction rules for predicting mortality in patients hospitalized with community-acquired pneumonia (CAP). SARS-CoV-2 has emerged as a new etiologic agent for CAP, but the role of CURB-65 score and PSI have not been established.Research questionHow effective are CURB-65 score and PSI at predicting in-hospital mortality resulting from SARS-CoV-2 CAP compared with non-SARS-CoV-2 CAP? Can these clinical prediction rules be optimized to predict mortality in SARS-CoV-2 CAP by addition of procalcitonin and D-dimer?Study design and methodsSecondary analysis of two prospective cohorts of patients with SARS-CoV-2 CAP or non-SARS-CoV-2 CAP from eight adult hospitals in Louisville, Kentucky.ResultsThe in-hospital mortality rate was 19% for patients with SARS-CoV-2 CAP and 6.5% for patients with non-SARS-CoV-2 CAP. For the PSI score, receiver operating characteristic (ROC) curve analysis resulted in an area under the ROC curve (AUC) of 0.82 (95% CI, 0.78-0.86) and 0.79 (95% CI, 0.77-0.80) for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP, respectively. For the CURB-65 score, ROC analysis resulted in an AUC of 0.79 (95% CI, 0.75-0.84) and 0.75 (95% CI, 0.73-0.77) for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP, respectively. In SARS-CoV-2 CAP, the addition of D-dimer (optimal cutoff, 1,813 μg/mL) and procalcitonin (optimal cutoff, 0.19 ng/mL) to PSI and CURB-65 score provided negligible improvement in prognostic performance.InterpretationPSI and CURB-65 score can predict in-hospital mortality for patients with SARS-CoV-2 CAP and non-SARS-CoV-2 CAP comparatively. In patients with SARS-CoV-2 CAP, the inclusion of either D-dimer or procalcitonin to PSI or CURB-65 score did not improve the prognostic performance of either score. In patients with CAP, regardless of cause, PSI and CURB-65 score remain adequate for predicting mortality in clinical practice.

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Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia - results from the prospective observational PROGRESS study.

Publications

Sequential organ failure assessment score is an excellent operationalization of disease severity of adult patients with hospitalized community acquired pneumonia - results from the prospective observational PROGRESS study.

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