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1.
Medicine (Baltimore) ; 99(34): e21893, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846851

RESUMO

We examined the blood concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and citrullinated alpha enolase peptide-1 (CEP-1) antibody in sepsis patients to evaluate their potential diagnostic, classified and prognostic utility together with C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6).Sixty-nine patients admitted at the emergency department with sepsis were studied, on admission, their demographic and clinical information were recorded. Blood levels of CRP, PCT, IL-6, NGAL, and CEP-1 antibody were measured. Relationships between sequential [sepsis-related] organ failure assessment score and blood biomarkers, between acute physiology and chronic health evaluation II score and blood biomarkers were investigated. Additionally, the mutual correlation among CRP, PCT, IL-6, NGAL, and CEP-1 antibody were investigated. Diagnostic and predictive values for clinical outcomes for biomarkers were assessed by receiver operator characteristic curve.Sixty-nine participants (38 sepsis, 31 septic shock) were compared with 40 healthy controls. The levels of CRP, PCT, IL-6, and NGAL were significantly higher in sepsis patients ([59.49 ± 48.88]; 0.71, [0.13-11.72]; 60.46, [33.26-201.20]; 265.61, [185.79-500.96], respectively) compared with healthy controls ([2.05 ± 1.85]; 0.02, [0.02-0.03]; 12.08, [7.22-16.84]; 19.73, [7.66-34.39], respectively) (P < .001). CRP, PCT, IL-6, and NGAL had better discriminatory performance with an area under the receiver operator characteristic curve (AUC) of (0.98; 0.98; 0.90; 0.97, respectively), 95% confidence interval (CI) = ([0.95; 1.00]; [0.96; 1.00]; [0.84; 0.96]; [0.94; 1.00], respectively) (P < .001), with a cut off value of (8.02 mg/L [Se = 88.40%, Sp = 100.00%]; 0.06 ng/mL [Se = 94.20%, Sp = 75.00%]; 30.63 pg/mL [Se = 78.30%, Sp = 95.00%]; 95.72 ng/mL [Se = 99.00%, Sp = 92.00%], respectively). Between the sepsis group and septic shock group, PCT and NGAL were significantly higher in septic shock group (2.44, [0.49-20.36]; 294.65 [203.34-1262.47], respectively) compared with sepsis group (0.41, [0.11-2.63]; 219.94, [146.38-385.24], respectively) (P < .05). Between survivors group and nonsurvivors group, PCT was obviously elevated in nonsurvivors group (2.47, [0.70-12.49]) compare with survivors group (0.41, [0.11-8.16]) (P < .05), with an AUC of 0.69, 95% CI = (0.57; 0.81) (P < .05), while CEP-1 antibody was decreased in nonsurvivors group (14.03, [4.94-17.17]) contrast to survivors group (18.78, [8.08-39.72]) (P < .05), with an AUC of 0.67, 95% CI = (0.54; 0.80) (P < .05). Additionally, CEP-1 antibody demonstrated a negative correlation with either sequential [sepsis-related] organ failure assessment score (r = -0.31, P < .05) or PCT (r = -0.27, P < .05).As CRP, PCT, and IL-6, NGAL was valuable in sepsis diagnosis. With a classificatory value, PCT and NGAL correlated with the degree severity of sepsis. PCT and CEP-1 antibody were meaningful in sepsis prognosis. CEP-1 antibody may be a protective factor for sepsis.


Assuntos
Anticorpos/sangue , Lipocalina-2/sangue , Sepse/sangue , Sepse/diagnóstico , Choque Séptico/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Anti-Proteína Citrulinada/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos de Casos e Controles , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Fosfopiruvato Hidratase/metabolismo , Valor Preditivo dos Testes , Pró-Calcitonina/sangue , Prognóstico , Estudos Prospectivos , Sepse/classificação , Sepse/mortalidade , Choque Séptico/sangue
2.
Crit Care ; 24(1): 57, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070393

RESUMO

BACKGROUND: Persistent critical illness is common in critically ill patients and is associated with vast medical resource use and poor clinical outcomes. This study aimed to define when patients with sepsis would be stabilized and transitioned to persistent critical illness, and whether such transition time varies between latent classes of patients. METHODS: This was a retrospective cohort study involving sepsis patients in the eICU Collaborative Research Database. Persistent critical illness was defined at the time when acute physiological characteristics were no longer more predictive of in-hospital mortality (i.e., vital status at hospital discharge) than antecedent characteristics. Latent growth mixture modeling was used to identify distinct trajectory classes by using Sequential Organ Failure Assessment score measured during intensive care unit stay as the outcome, and persistent critical illness transition time was explored in each latent class. RESULTS: The mortality was 16.7% (3828/22,868) in the study cohort. Acute physiological model was no longer more predictive of in-hospital mortality than antecedent characteristics at 15 days after intensive care unit admission in the overall population. Only a minority of the study subjects (n = 643, 2.8%) developed persistent critical illness, but they accounted for 19% (15,834/83,125) and 10% (19,975/198,833) of the total intensive care unit and hospital bed-days, respectively. Five latent classes were identified. Classes 1 and 2 showed increasing Sequential Organ Failure Assessment score over time and transition to persistent critical illness occurred at 16 and 27 days, respectively. The remaining classes showed a steady decline in Sequential Organ Failure Assessment scores and the transition to persistent critical illness occurred between 6 and 8 days. Elevated urea-to-creatinine ratio was a good biochemical signature of persistent critical illness. CONCLUSIONS: While persistent critical illness occurred in a minority of patients with sepsis, it consumed vast medical resources. The transition time differs substantially across latent classes, indicating that the allocation of medical resources should be tailored to different classes of patients.


Assuntos
Estado Terminal , Recursos em Saúde , Unidades de Terapia Intensiva , Sepse , Idoso , Estudos de Coortes , Estado Terminal/classificação , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Alta do Paciente , Estudos Retrospectivos , Sepse/classificação , Sepse/diagnóstico , Sepse/terapia
4.
Am J Emerg Med ; 38(2): 222-224, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30765276

RESUMO

The sepsis order set at our institution was created with the intent to facilitate the prompt initiation of appropriate sepsis care. Once clinical features meeting criteria for systemic inflammatory response syndrome (SIRS) are identified and an infectious source is considered, a "sepsis huddle" is concomitantly initiated. The sepsis huddle was implemented in March of 2016 in order to increase compliance with the sepsis bundles. The sepsis huddle is called via overhead paging system in the emergency department (ED) to notify all staff that there is a patient present who meets SIRS criteria with concern for sepsis requiring immediate attention. The sepsis order set is utilized for these patients and includes laboratory testing, treatment, and monitoring items to meet sepsis "bundle" compliance. In addition, it suggests antibiotic options to be administered based on the presumed source of infection. Each team member responding to a sepsis huddle has a pre-established role outlined to facilitate timely treatment. The Centers for Medicare & Medicaid Services, (CMS), is part of the Department of Health and Human Services (HHS). CMS sepsis guidelines call for periodic patient reassessment, including repeat vital signs, pertinent physical examination findings, and timed lactic acid measurement to determine a patient's response to resuscitation efforts. Our established order set has automated some of these reassessment features to facilitate compliance. Sepsis huddle initiation also triggers a department staff member to track the timing and completion of serial blood draws. Utilizing and adhering to the guidelines of this methodology in the management of these patients has enabled our hospital to improve benchmarking compliance from previously underperforming at the 31st and 49th percentiles in 2015, prior to initiation of the huddle, to a peak compliance at the 81st and 91st percentiles in 2016 and 65th and 83rd percentiles in 2017 for the 3-hour and 6-hour bundles respectively.


Assuntos
Benchmarking/normas , Serviço Hospitalar de Emergência/tendências , Sepse/classificação , Benchmarking/métodos , Benchmarking/estatística & dados numéricos , Serviço Hospitalar de Emergência/organização & administração , Fidelidade a Diretrizes , Humanos , New York , Estudos Retrospectivos , Sepse/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/classificação , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico
5.
Crit Care ; 23(1): 408, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831072

RESUMO

BACKGROUND: To develop a mathematical model to estimate daily evolution of disease severity using routinely available parameters in patients admitted to the intensive care unit (ICU). METHODS: Over a 3-year period, we prospectively enrolled consecutive adults with sepsis and categorized patients as (1) being at risk for developing (more severe) organ dysfunction, (2) having (potentially still reversible) limited organ failure, or (3) having multiple-organ failure. Daily probabilities for transitions between these disease states, and to death or discharge, during the first 2 weeks in ICU were calculated using a multi-state model that was updated every 2 days using both baseline and time-varying information. The model was validated in independent patients. RESULTS: We studied 1371 sepsis admissions in 1251 patients. Upon presentation, 53 (4%) were classed at risk, 1151 (84%) had limited organ failure, and 167 (12%) had multiple-organ failure. Among patients with limited organ failure, 197 (17%) evolved to multiple-organ failure or died and 809 (70%) improved or were discharged alive within 14 days. Among patients with multiple-organ failure, 67 (40%) died and 91 (54%) improved or were discharged. Treatment response could be predicted with reasonable accuracy (c-statistic ranging from 0.55 to 0.81 for individual disease states, and 0.67 overall). Model performance in the validation cohort was similar. CONCLUSIONS: This prediction model that estimates daily evolution of disease severity during sepsis may eventually support clinicians in making better informed treatment decisions and could be used to evaluate prognostic biomarkers or perform in silico modeling of novel sepsis therapies during trial design. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01905033.


Assuntos
Estado Terminal/classificação , Prognóstico , Sepse/classificação , APACHE , Idoso , Estudos de Coortes , Estado Terminal/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Estudos Prospectivos , Sepse/mortalidade , Índice de Gravidade de Doença , Escala Psicológica Aguda Simplificada
6.
Crit Care ; 23(1): 384, 2019 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779663

RESUMO

BACKGROUND: Clinical and biologic phenotypes of sepsis are proposed in human studies, yet it is unknown whether prognostic or drug response phenotypes are present in animal models of sepsis. Using a biotelemetry-enhanced, murine cecal ligation and puncture (CLP) model, we determined phenotypes of polymicrobial sepsis prior to physiologic deterioration, and the association between phenotypes and outcome in a randomized trial of prompt or delayed antibiotics and fluids. METHODS: We performed a secondary analysis of male C57BL/6J mice in two observational cohorts and two randomized, laboratory animal experimental trials. In cohort 1, mice (n = 118) underwent biotelemetry-enhanced CLP, and we applied latent class mixed models to determine optimal number of phenotypes using clinical data collected between injury and physiologic deterioration. In cohort 2 (N = 73 mice), inflammatory cytokines measured at 24 h after deterioration were explored by phenotype. In a subset of 46 mice enrolled in two trials from cohort 1, we tested the association of phenotypes with the response to immediate (0 h) vs. delayed (2 to 4 h) antibiotics or fluids initiated after physiologic deterioration. RESULTS: Latent class mixture modeling derived a two-class model in cohort 1. Class 2 (N = 97) demonstrated a shorter time to deterioration (mean SD 7.3 (0.9) vs. 9.7 (3.2) h, p < 0.001) and lower heart rate at 7 h after injury (mean (SD) 564 (55) vs. 626 (35) beats per minute, p < 0.001). Overall mortality was similar between phenotypes (p = 0.75). In cohort 2 used for biomarker measurement, class 2 mice had greater plasma concentrations of IL6 and IL10 at 24 h after CLP (p = 0.05). In pilot randomized trials, the effects of sepsis treatment (immediate vs. delayed antibiotics) differed by phenotype (p = 0.03), with immediate treatment associated with greater survival in class 2 mice only. Similar differential treatment effect by class was observed in the trial of immediate vs. delayed fluids (p = 0.02). CONCLUSIONS: We identified two sepsis phenotypes in a murine cecal ligation and puncture model, one of which is characterized by faster deterioration and more severe inflammation. Response to treatment in a randomized trial of immediate versus delayed antibiotics and fluids differed on the basis of phenotype.


Assuntos
Fenótipo , Sepse/terapia , Fatores de Tempo , Análise de Variância , Animais , Antibacterianos/uso terapêutico , Ceco/anormalidades , Ceco/cirurgia , Estudos de Coortes , Modelos Animais de Doenças , Hidratação/métodos , Ligadura/efeitos adversos , Ligadura/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pennsylvania , Sepse/classificação , Sepse/fisiopatologia
8.
J Emerg Med ; 57(4): 453-460.e2, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31500993

RESUMO

BACKGROUND: Early recognition of sepsis remains a major challenge. The clinical utility of the Quick Sepsis-Related Organ Failure Assessment (qSOFA) score is still undefined. Several studies have tested its prognostic value. However, its ability to diagnose sepsis is still unknown. OBJECTIVE: Our aim was to compare the performance of qSOFA, systemic inflammatory response syndrome (SIRS) criteria, National Early Warning Score (NEWS), and formal triage with the Emergency Severity Index (ESI) algorithm to identify patients with sepsis and predict adverse outcomes on arrival in an emergency department (ED) all-comer cohort. METHODS: We included all patients presenting consecutively to the ED during a 3-week period. We used vital signs recorded at triage to calculate the study scores. Two independent assessors retrospectively assigned the primary outcome of sepsis according to Third International Consensus Definitions for Sepsis and Septic Shock criteria in a chart review process. RESULTS: There were 2523 cases included in the analysis and 39 (1.6%) had the primary outcome of sepsis. The area under the curve for sepsis was 0.79 (95% confidence interval [CI] 0.71-0.86) for qSOFA, 0.81 (95% CI 0.73-0.87) for SIRS, 0.85 (95% CI 0.77-0.92) for NEWS, and 0.77 (95% CI 0.70-0.83) for ESI. CONCLUSIONS: qSOFA offered high specificity for the prediction of sepsis and adverse outcomes. However, its low sensitivity does not support widespread use as a screening tool for sepsis. NEWS outperformed qSOFA for prediction of adverse outcomes and screening for sepsis.


Assuntos
Programas de Rastreamento/normas , Sepse/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Criança , Estudos de Coortes , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/normas , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Curva ROC , Estudos Retrospectivos , Sepse/diagnóstico , Resultado do Tratamento , Triagem
9.
PLoS One ; 14(6): e0218714, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31233529

RESUMO

Infectious disease and sepsis represent a serious problem for all, but especially in early life. Much of the increase in morbidity and mortality due to infection in early life is presumed to relate to fundamental differences between neonatal and adult immunity. Mechanistic insight into the way newborns' immune systems handle infectious threats is lacking; as a result, there has only been limited success in providing effective immunomodulatory interventions to reduce infectious mortality. Given the complexity of the host-pathogen interactions, neonatal mouse models can offer potential avenues providing valuable data. However, the small size of neonatal mice hampers the ability to collect biological samples without sacrificing the animals. Further, the lack of a standardized metric to quantify newborn mouse health increases reliance on correlative biomarkers without a known relationship to 'clinical' outcome. To address this bottleneck, we developed a system that allows assessment of neonatal mouse health in a readily standardized and quantifiable manner. The resulting health scores require no special equipment or sample collection and can be assigned in less than 20 seconds. Importantly, the health scores are highly predictive of survival. A classifier built on our health score revealed a positive relationship between reduced bacterial load and survival, demonstrating how this scoring system can be used to bridge the gap between assumed relevance of biomarkers and the clinical outcome of interest. Adoption of this scoring system will not only provide a robust metric to assess health of newborn mice but will also allow for objective, prospective studies of infectious disease and possible interventions in early life.


Assuntos
Sepse/mortalidade , Animais , Animais Recém-Nascidos , Carga Bacteriana , Modelos Animais de Doenças , Feminino , Indicadores Básicos de Saúde , Humanos , Recém-Nascido , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reflexo de Endireitamento , Sepse/classificação , Sepse/microbiologia
10.
J Emerg Med ; 57(2): 216-226, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31229302

RESUMO

BACKGROUND: Pediatric oncology patients may be at a higher risk of complications and mortality from sepsis compared with their nononcology counterpart. OBJECTIVES: The aim of this study is to compare characteristics, treatment, and sepsis-related mortality between oncology and nononcology patients presenting to the emergency department (ED). METHODS: This is a retrospective single-center cohort study including patients <18 years old with a diagnosis of sepsis, severe sepsis, septic shock, or bacteremia presenting to an academic ED between January 2009 and January 2015. A total of 158 patients were included with 53.8% having an underlying malignancy. The primary outcome of the study was in-hospital mortality. Secondary outcomes included ED vital signs, resuscitation parameters, laboratory work, infection site, general practitioner unit, intensive care unit length of stay, and hospital length of stay. RESULTS: Oncology patients had a higher in-hospital mortality (5.9% vs. 2.7%), however, it did not meet statistical significance (p = 0.45). On presentation, oncology patients had a lower respiratory rate (24.33 ± 9.48 vs. 27.45 ± 7.88; p = 0.04). There was a significant increase in the white blood count in oncology patients (4.011 ± 4.965 vs. 17.092 ± 12.806; p < 0.001) with this cohort receiving more intravenous fluids. In the first 6 hours (33.0 ± 27.7 mL/kg vs. 24.9 ± 16.1 mL/kg; p = 0.029) as well as having a higher percentage of vasopressor administration (15.3% vs. 1.4%; p = 0.002). Antibiotics were initiated at an earlier stage in the oncology cohort (1.25 ± 1.95 vs. 3.33 ± 1.97 hours; p < 0.0001). Cancer-free patients had a significantly higher rate of lung infections compared with cancer patients (68.5% vs. 32.9%; p < 0.0001). In terms of infection characteristics, cancer patients had a higher percentage of bacteremia (27.1% vs. 4.1%; p < 0.001). CONCLUSION: There was no statistical significance regarding mortality between the 2 cohorts. Pediatric cancer patients were found to have a higher incidence of bacteremia and received more aggressive treatment.


Assuntos
Neoplasias/classificação , Sepse/classificação , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Neoplasias/epidemiologia , Neoplasias/mortalidade , Medicina de Emergência Pediátrica/tendências , Estudos Retrospectivos , Sepse/epidemiologia , Sepse/mortalidade , Resultado do Tratamento
11.
Tidsskr Nor Laegeforen ; 139(9)2019 May 28.
Artigo em No | MEDLINE | ID: mdl-31140244

RESUMO

BACKGROUND: In 2017, Acute Admissions at Oslo University Hospital, Ullevål, introduced a specific protocol for evaluating patients with suspected sepsis on arrival. Patients with suspected sepsis, and all those who fulfilled at least two of three criteria in the Quick Sequential Organ Failure Assessment (qSOFA) screening tool, were to undergo a structured evaluation by a dedicated sepsis team. We have examined whether this initiative improved compliance with national recommendations to initiate antibiotics within one hour in cases of sepsis. MATERIAL AND METHOD: Adult patients with suspected sepsis who underwent a structured team evaluation on arrival in Acute Admissions in the period 15 May to 15 November 2017 were included. A retrospective review was used to determine whether or not those included did in fact have sepsis. RESULTS: Antibiotics were administered for suspected sepsis following 216 structured evaluations in Acute Admissions (172 by sepsis teams and 44 by general medical teams). In all, 175 (81 %) patients received antibiotics within one hour of arrival in Acute Admissions. Median time from arrival to initiation of antibiotics was 35 minutes. Use of qSOFA alone captured 80 (71 %) of the 112 patients who were subsequently classified as having sepsis. INTERPRETATION: Following the introduction of a structured evaluation for patients with suspected sepsis, antibiotic treatment was generally initiated within one hour.


Assuntos
Antibacterianos , Serviço Hospitalar de Emergência , Escores de Disfunção Orgânica , Sepse/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Admissão do Paciente , Estudos Prospectivos , Estudos Retrospectivos , Sepse/classificação , Sepse/diagnóstico , Sepse/mortalidade , Tempo para o Tratamento
12.
PLoS One ; 14(5): e0217146, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116772

RESUMO

BACKGROUND: The performance of a new diagnostic test is typically evaluated against a comparator which is assumed to correspond closely to some true state of interest. Judgments about the new test's performance are based on the differences between the outputs of the test and comparator. It is commonly assumed that a small amount of uncertainty in the comparator's classifications will negligibly affect the measured performance of a diagnostic test. METHODS: Simulated datasets were generated to represent typical diagnostic scenarios. Comparator noise was introduced in the form of random misclassifications, and the effect on the apparent performance of the diagnostic test was determined. An actual dataset from a clinical trial on a new diagnostic test for sepsis was also analyzed. RESULTS: We demonstrate that as little as 5% misclassification of patients by the comparator can be enough to statistically invalidate performance estimates such as sensitivity, specificity and area under the receiver operating characteristic curve, if this uncertainty is not measured and taken into account. This distortion effect is found to increase non-linearly with comparator uncertainty, under some common diagnostic scenarios. For clinical populations exhibiting high degrees of classification uncertainty, failure to measure and account for this effect will introduce significant risks of drawing false conclusions. The effect of classification uncertainty is magnified further for high performing tests that would otherwise reach near-perfection in diagnostic evaluation trials. A requirement of very high diagnostic performance for clinical adoption, such as a 99% sensitivity, can be rendered nearly unachievable even for a perfect test, if the comparator diagnosis contains even small amounts of uncertainty. This paper and an accompanying online simulation tool demonstrate the effect of classification uncertainty on the apparent performance of tests across a range of typical diagnostic scenarios. Both simulated and real datasets are used to show the degradation of apparent test performance as comparator uncertainty increases. CONCLUSIONS: Overall, a 5% or greater misclassification rate by the comparator can lead to significant underestimation of true test performance. An online simulation tool allows researchers to explore this effect using their own trial parameters (https://imperfect-gold-standard.shinyapps.io/classification-noise/) and the source code is freely available (https://github.com/ksny/Imperfect-Gold-Standard).


Assuntos
Testes Diagnósticos de Rotina/estatística & dados numéricos , Testes Diagnósticos de Rotina/normas , Modelos Estatísticos , Sepse/classificação , Sepse/diagnóstico , Simulação por Computador , Humanos , Curva ROC , Incerteza
13.
JAMA ; 321(20): 2003-2017, 2019 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-31104070

RESUMO

Importance: Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care. Objective: To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs). Design, Settings, and Participants: Retrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20 189 total patients (16 552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients and n = 31 160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n = 583), and in 3 sepsis RCTs (n = 4737). Exposures: All clinical and laboratory variables in the electronic health record. Main Outcomes and Measures: Derived phenotype (α, ß, γ, and δ) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs. Results: The derivation cohort included 20 189 patients with sepsis (mean age, 64 [SD, 17] years; 10 022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43 086 patients (mean age, 67 [SD, 17] years; 21 993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the ß phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the α phenotype; 561 of 4420 (13%) for the ß phenotype; 1031 of 4318 (24%) for the γ phenotype; and 897 of 2223 (40%) for the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P < .001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from >33% chance of benefit to >60% chance of harm). Conclusions and Relevance: In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation.


Assuntos
Sepse/classificação , Algoritmos , Biomarcadores/sangue , Análise por Conglomerados , Conjuntos de Dados como Assunto , Mortalidade Hospitalar , Humanos , Aprendizado de Máquina , Escores de Disfunção Orgânica , Fenótipo , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sepse/mortalidade , Sepse/terapia
14.
Int J Gynaecol Obstet ; 146(1): 39-42, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31037723

RESUMO

Despite major advances in the last century, particularly in high resource settings, maternal sepsis remains a common and potentially preventable cause of direct maternal death globally. A barrier to further progress has been the lack of consensus on the definition of maternal sepsis. Publications from two recent multidisciplinary consensus conferences, one on sepsis in the non-pregnant adult and the other on sepsis in the pregnant woman, concluded that the criteria for diagnosing sepsis should be clinically-based, applicable at the bedside, and should not be laboratory-based. Informed by reviews of the evidence, in 2017 WHO published a new definition of maternal sepsis based on the presence of suspected or confirmed infection. It also announced a Global Maternal and Neonatal Sepsis Initiative to identify the diagnostic criteria for the early identification, epidemiology, and disease classification of maternal sepsis. Standardizing the criteria for maternal sepsis optimizes clinical audit and research. It may facilitate the evaluation of the role of different clinical parameters and biomarkers in the diagnosis, earlier recognition and management of maternal infection and sepsis. Further work is required to develop an international consensus on the criteria for diagnosing maternal sepsis and any associated organ dysfunction.


Assuntos
Complicações Infecciosas na Gravidez/diagnóstico , Sepse/diagnóstico , Adulto , Conferências de Consenso como Assunto , Diagnóstico Precoce , Feminino , Humanos , Morte Materna/prevenção & controle , Mortalidade Materna , Escores de Disfunção Orgânica , Gravidez , Complicações Infecciosas na Gravidez/classificação , Complicações Infecciosas na Gravidez/mortalidade , Medição de Risco , Sepse/classificação , Sepse/mortalidade
15.
Crit Care ; 23(1): 80, 2019 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-30850013

RESUMO

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .


Assuntos
Sepse/classificação , Sepse/fisiopatologia , Cuidados Críticos/tendências , Humanos , Unidades de Terapia Intensiva/organização & administração
16.
Artigo em Alemão | MEDLINE | ID: mdl-30620952

RESUMO

Sepsis is a common disease in intensive care units worldwide, which is associated with relevant morbidity and mortality. Although massive research efforts have been made for decades, there is no specific therapy for sepsis to date. Decisive in the treatment of sepsis is the early diagnosis, because the outcome of the treated patients can be significantly improved by early elimination of the infection focus, the fastest possible administration of a broad, calculated antibiosis as well as the stabilization of the hemodynamic situation. A definition of the clinical picture of sepsis with high diagnostic sensitivity and specificity is therefore indispensable. This article describes the previously and the currently available definition of sepsis and gives an overview of the epidemiology of this disease.


Assuntos
Sepse/classificação , Sepse/epidemiologia , Cuidados Críticos , Humanos , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/etiologia , Terminologia como Assunto
17.
Langenbecks Arch Surg ; 404(3): 257-271, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30685836

RESUMO

PURPOSE: The abdomen is the second most common source of sepsis and is associated with unacceptably high morbidity and mortality. Recently, the essential definitions of sepsis and septic shock were updated (Third International Consensus Definitions for Sepsis and Septic Shock, Sepsis-3) and modified. The purpose of this review is to provide an overview of the changes introduced by Sepsis-3 and the current state of the art regarding the treatment of abdominal sepsis. RESULTS: While Sepsis-1/2 focused on detecting systemic inflammation as a response to infection, Sepsis-3 defines sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The Surviving Sepsis Campaign (SSC) guideline, which was updated in 2016, recommends rapid diagnosis and initiating standardized therapy. New diagnostic tools, the establishment of antibiotic stewardship programs, and a host of new-generation antibiotics are new landmark changes in the sepsis literature of the last few years. Although the "old" surgical source control consisting of debridement, removal of infected devices, drainage of purulent cavities, and decompression of the abdominal cavity is the gold standard of surgical care, the timing of gastrointestinal reconstruction and closure of the abdominal cavity ("damage control surgery") are discussed intensively in the literature. The SSC guidelines provide evidence-based sepsis therapy. Nevertheless, treating critically ill intensive care patients requires individualized, continuous daily re-evaluation and flexible therapeutic strategies, which can be best discussed in the interdisciplinary rounds of experienced surgeons and intensive care medicals.


Assuntos
Medicina Baseada em Evidências/normas , Infecções Intra-Abdominais/terapia , Sepse/terapia , Terapia Combinada , Diagnóstico Precoce , Humanos , Infecções Intra-Abdominais/classificação , Infecções Intra-Abdominais/diagnóstico , Escores de Disfunção Orgânica , Guias de Prática Clínica como Assunto , Fatores de Risco , Sepse/classificação , Sepse/diagnóstico
18.
Med. clín (Ed. impr.) ; 152(1): 13-16, ene. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-181667

RESUMO

Antecedentes y objetivo: Tras la publicación de la nueva definición de sepsis y shock séptico, nuestro objetivo es analizar la evolución de los pacientes que ingresan en UCI por enfermedad infecciosa utilizando la definición clásica y los nuevos criterios. Material y métodos: Subanálisis de un estudio observacional y prospectivo. Incluye a 98 pacientes ingresados en UCI por enfermedad infecciosa desde Urgencias durante 18 meses. Se estudió la evolución clínica en UCI y la mortalidad hospitalaria. Resultados: El 78% de los pacientes tuvieron shock séptico con la definición Sepsis-2 y el 52% con los criterios Sepsis-3. La mortalidad hospitalaria fue del 29 y del 41%, respectivamente. El RR de mortalidad hospitalaria de los pacientes con shock séptico fue 10,3 (IC 95%: 2,8-37,5) respecto a los pacientes sin shock. La probabilidad de supervivencia a los 30 días de los pacientes con sepsis y shock séptico fue del 78 y 68%, respectivamente (long Rank < 0,001). Conclusiones: En nuestra experiencia, la incorporación de la puntuación SOFA y el lactato a la nueva definición puede mejorar la valoración del riesgo de muerte hospitalaria


Background and objectives: After the publication of the new definition for sepsis and septic shock, our objective is to analyse the evolution of patients admitted to ICU with an infection process using the previous and new recommendations. Materials and methods: This is a sub-analysis of a previous observational prospective study. We included 98 patients admitted to ICU from the emergency department due to infection during an 18-month period. We studied the clinical evolution during ICU admission and hospital mortality. Results: According to Sepsis-2 definition, 78% percent had septic shock and using Sepsis-3 criteria, 52%; hospital mortality was 29 and 41%, respectively. The RR of hospital mortality of septic shock was 10.3 (95% CI: 2.8-37.5) compared to patients without shock. The 30-day probability survival of patients with sepsis and septic shock were 78% and 68%, respectively (long rank < 0.001). Conclusions: In our experience, the incorporation of the SOFA score and lactate levels to the new definition could help improve the evaluation of risk of hospital death


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Terminologia como Assunto , Sepse/classificação , Choque Séptico , Doenças Transmissíveis/epidemiologia , Unidades de Terapia Intensiva , Estudos Prospectivos , Mortalidade Hospitalar
20.
Emerg Med Australas ; 31(3): 339-346, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30126044

RESUMO

OBJECTIVE: Use of the Sequential Organ Failure Assessment (SOFA) score has been proposed by the Third International Consensus Definitions for Sepsis and Septic Shock. The utility in the ED is not yet well established. We retrospectively studied the application of a modified SOFA (mSOFA) score, to assess its ability to predict mortality. METHODS: At our urban tertiary teaching hospital staff recorded patients with probable sepsis in the ED Information System (EDIS). Data was analysed for the year of July 2015 to June 2016. For a sample of the suspected sepsis patients, ED and inpatient clinical records were manually reviewed to ascribe an mSOFA score and assess its performance in predicting mortality, with a primary outcome of death by 30 days. RESULTS: There were 474 patients recorded over the 1 year with probable sepsis, of whom 228 were manually reviewed. The mSOFA was a significant predictor of mortality at all the time points tested. The 30 day mortality was 22/88 (25%) for those with a positive mSOFA score and 3 out of 140 (2.1%) of those with a negative mSOFA score (OR 15.2, 95% CI [4.4, 52.7]; P < 0.001). This equated to a negative predictive value of 97.9% (95% exact CI 93.9-99.6%). CONCLUSION: For ED patients thought likely to have sepsis, the mSOFA score distinguished those with a high or low mortality risk. The high negative predictive value could be practically useful. Prospective study of the mSOFA score used in ED will be needed to validate these observations.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Escores de Disfunção Orgânica , Prognóstico , Sepse/classificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Serviço Hospitalar de Emergência/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Estudos Retrospectivos , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos
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