The Cost-Effectiveness of Platelet-Rich Plasma Compared With Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis.

PURPOSE: To examine the cost-effectiveness of a series (total of 3 injections) of intra-articular platelet-rich plasma (PRP) injections in comparison to that of hyaluronic acid (HA) viscosupplementation for the treatment of symptomatic knee osteoarthritis. METHODS: Outcome data regarding the use of PRP or HA injections for the treatment of symptomatic knee osteoarthritis were determined from the highest-quality data (Level I) available in the literature until 2015. Health utility values were then derived from these high-quality data. Costs were determined by examining typical charges for patients undergoing a series of either PRP or HA injections for the treatment of this condition at a large private orthopaedic practice. These health utility values and costs were used to create an expected-value decision analysis model. RESULTS: The results of the model revealed that the cost per quality-adjusted life-year (QALY) of a series of PRP injections was $8,635.23/QALY and that of a series of HA injections was $5,331.75/QALY. A series of PRP injections was associated with a higher initial cost than a series of HA injections (difference, $1,433.67); however, PRP was also more effective (higher utility value) than HA by 0.11 QALYs (0.69 vs 0.58, P = .0062) at 1 year. The incremental cost-effectiveness ratio of the use of PRP injections as opposed to HA was $12,628.15/QALY. CONCLUSIONS: Although a series of either PRP ($8,635.23/QALY) or HA ($5,331.75/QALY) injections for the treatment of symptomatic knee osteoarthritis would be considered cost-effective (cost per QALY < $50,000), PRP injections were not more cost-effective than HA injections. However, PRP was significantly more effective at 1 year, and being associated with an incremental cost-effectiveness ratio of $12,628.15/QALY when compared with HA, a series of PRP injections should be considered a reasonable and acceptable alternative to HA injections for the treatment of symptomatic knee osteoarthritis. LEVEL OF EVIDENCE: Level II, economic and decision analysis of Level I studies.

The value of missing information in severity of illness score development.

OBJECTIVE: We aim to investigate the hypothesis that using information about which variables are missing along with appropriate imputation improves the performance of severity of illness scoring systems used to predict critical patient outcomes. STUDY DESIGN AND SETTING: We quantify the impact of missing and imputed variables on the performance of prediction models used in the development of a sepsis-related severity of illness scoring system. Electronic health records (EHR) data were compiled from Christiana Care Health System (CCHS) on 119,968 adult patients hospitalized between July 2013 and December 2015. Two outcomes of interest were considered for prediction: (1) first transfer to intensive care unit (ICU) and (2) in-hospital mortality. Five different prediction models were employed. Indicators were utilized in these prediction models to identify when variables were missing and imputed. RESULTS: We observed statistically significant gains in prediction performance when moving from models that did not indicate missing information to those that did. Moreover, this increase was higher in models that use summary variables as predictors compared to those that use all variables. CONCLUSION: When developing prediction models using longitudinal EHR data, researchers should explore the incorporation of indicators for missing variables along with appropriate imputation.

Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial.

BACKGROUND: Post-partum depression is a serious mood disorder in women that might be triggered by peripartum fluctuations in reproductive hormones. This phase 2 study investigated brexanolone (USAN; formerly SAGE-547 injection), an intravenous formulation of allopregnanolone, a positive allosteric modulator of γ-aminobutyric acid (GABAA) receptors, for the treatment of post-partum depression. METHODS: For this double-blind, randomised, placebo-controlled trial, we enrolled self-referred or physician-referred female inpatients (≤6 months post partum) with severe post-partum depression (Hamilton Rating Scale for Depression [HAM-D] total score ≥26) in four hospitals in the USA. Eligible women were randomly assigned (1:1), via a computer-generated randomisation program, to receive either a single, continuous intravenous dose of brexanolone or placebo for 60 h. Patients and investigators were masked to treatment assignments. The primary efficacy endpoint was the change from baseline in the 17-item HAM-D total score at 60 h, assessed in all randomised patients who started infusion of study drug or placebo and who had a completed baseline HAM-D assessment and at least one post-baseline HAM-D assessment. Patients were followed up until day 30. This trial is registered with ClinicalTrials.gov, number NCT02614547. FINDINGS: This trial was done between Dec 15, 2015 (first enrolment), and May 19, 2016 (final visit of the last enrolled patient). 21 women were randomly assigned to the brexanolone (n=10) and placebo (n=11) groups. At 60 h, mean reduction in HAM-D total score from baseline was 21·0 points (SE 2·9) in the brexanolone group compared with 8·8 points (SE 2·8) in the placebo group (difference -12·2, 95% CI -20·77 to -3·67; p=0·0075; effect size 1·2). No deaths, serious adverse events, or discontinuations because of adverse events were reported in either group. Four of ten patients in the brexanolone group had adverse events compared with eight of 11 in the placebo group. The most frequently reported adverse events in the brexanolone group were dizziness (two patients in the brexanolone group vs three patients in the placebo group) and somnolence (two vs none). Moderate treatment-emergent adverse events were reported in two patients in the brexanolone group (sinus tachycardia, n=1; somnolence, n=1) and in two patients in the placebo group (infusion site pain, n=1; tension headache, n=1); one patient in the placebo group had a severe treatment-emergent adverse event (insomnia). INTERPRETATION: In women with severe post-partum depression, infusion of brexanolone resulted in a significant and clinically meaningful reduction in HAM-D total score, compared with placebo. Our results support the rationale for targeting synaptic and extrasynaptic GABAA receptors in the development of therapies for patients with post-partum depression. A pivotal clinical programme for the investigation of brexanolone in patients with post-partum depression is in progress. FUNDING: Sage Therapeutics, Inc.

Improving Infusion Pump Safety Through Usability Testing.

With the recognition that the introduction of new technology causes changes in workflow and may introduce new errors to the system, usability testing was performed to provide data on nursing practice and interaction with infusion pump technology. Usability testing provides the opportunity to detect and analyze potentially dangerous problems with the design of infusion pumps that could cause or allow avoidable errors. This work will reduce preventable harm through the optimization of health care delivery.

Investigating Informatics Activity, Control, and Training Needs in Large, Medium, and Small Health Departments.

INTRODUCTION: A recent National Association of City & County Health Officials survey shed light on informatics workforce development needs. Local health departments (LHDs) of various jurisdictional sizes and control over informatics may differ on training needs and activity. Understanding the precise nature of this variation will allow stakeholders to appropriately develop workforce development tools to advance the field. OBJECTIVE: To understand the informatics training needs for LHDs of different jurisdictional sizes. METHODS: Survey responses were analyzed by comparing training needs and LHD population size. RESULTS: Larger health departments consistently reported having greater informatics-related capacity and informatics-related training needs. Quantitative data analysis was identified as a primary need for large LHDs. In addition, LHDs that report higher control of informatics/information technology were able to engage in more informatics activities. CONCLUSION: Smaller LHDs need additional resources to improve informatics-related capacity and engagement with the field.

Heparin-Binding Protein Measurement Improves the Prediction of Severe Infection With Organ Dysfunction in the Emergency Department.

OBJECTIVES: Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting. DESIGN: A prospective international multicenter cohort study. SETTING: Seven different emergency departments in Sweden, Canada, and the United States. PATIENTS: Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (>30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve=0.80). The performance of heparin-binding protein was confirmed in the validation cohort. CONCLUSION: In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.

Factors associated with treatment failure in vertebral osteomyelitis requiring spinal instrumentation.

Patients with vertebral osteomyelitis may require instrumentation for spinal stabilization. Determining the optimal duration and type of antimicrobial therapy for these patients is challenging. The aim of this study was to examine risk factors for treatment failure, in particular antimicrobial duration, in a cohort of patients requiring spinal instrumentation for vertebral osteomyelitis. We conducted a retrospective cohort study of all patients with vertebral osteomyelitis who had spinal instrumentation between January 2002 and January 2012 at the University of Maryland Medical Center. The primary outcome measure was treatment failure >4 weeks postoperatively. We identified 131 patients with vertebral osteomyelitis requiring spinal instrumentation, 94 of whom had >4 weeks of follow-up and were included in the primary analysis. Treatment failure occurred in 22 of the 94 patients (23%) at a median of 4 months after surgery. Among patients who failed therapy, 20 of 22 failed within 1 year of surgery. Cervical and thoracic infection sites and the presence of negative cultures were associated with fewer treatment failures. Addition of rifampin and the use of chronic suppressive antimicrobials did not affect treatment failure rate. Twenty-three percent of patients with spinal instrumentation for vertebral osteomyelitis experienced treatment failure. Treatment failure almost always occurred within the first year of spinal instrumentation.

Fibro-adipose vascular anomaly: clinical-radiologic-pathologic features of a newly delineated disorder of the extremity.

BACKGROUND: The diagnosis and management of vascular anomalies of the extremities can be challenging as these disorders are uncommon and may clinically overlap. The aim of this paper is to describe the clinical, radiologic, and histopathologic features of fibro-adipose vascular anomaly (FAVA), a previously unrecognized disorder of the limb. METHODS: The clinical, imaging, operative, and histopathologic data from patients with a unique intramuscular lesion of the extremities comprising dense fibrofatty tissue and slow-flow vascular malformations were retrospectively reviewed. RESULTS: Sixteen patients diagnosed with FAVA of the extremity (3 male and 13 female individuals) met the clinical, radiologic, and histopathologic inclusion criteria. The age at presentation ranged from the time of birth to 28 years. The locations of the lesions were: calf (n=10), forearm/wrist (n=3), and thigh (n=3). Fourteen patients presented with severe pain. Seven of the patients with calf lesions had limited ankle dorsiflexion. On imaging, the complex intramuscular lesions replaced muscle fibers with fibrofatty overgrowth and phlebectasia (dilation of the veins). The extrafascial component comprised fatty overgrowth, phlebectasia, and an occasional lymphatic malformation. The histopathologic features comprised dense fibrous tissue, fat, and lymphoplasmacytic aggregates within atrophied skeletal muscle. Adipose tissue also infiltrated skeletal muscle at the periphery of the lesion. There were large, irregular, and sometimes excessively muscularized venous channels and smaller, clustered channels. Other findings include organizing thrombi, a lymphatic component, and dense fibrous tissue-encircled nerves. CONCLUSIONS: The constellation of clinical, radiologic, and histopathologic features constitutes a distinct entity comprising fibrofatty infiltration of muscle, unusual phlebectasia with pain, and contracture of the affected extremity. The clinical and radiologic findings permit the diagnosis of FAVA with major therapeutic implications. LEVEL OF EVIDENCE: Level III.

Display and perception of risk: Analysis of decision support system display and its impact on perceived clinical risk of sepsis-induced health deterioration.

Despite acknowledging the value of clinical decision support systems (CDSS) in identifying risk for sepsis-induced health deterioration in-hospitalized patients, the relationship between display features, decision maker characteristics, and recognition of risk by the clinical decision maker remains an understudied, yet promising, area. The objective of this study is to explore the relationship between CDSS display design and perceived clinical risk of in-hospital mortality associated with sepsis. The study utilized data collected through in-person experimental sessions with 91 physicians from the general medical and surgical floors who were recruited across 12 teaching hospitals within the United States. Results of descriptive and statistical analyses provided evidence supporting the impact of display configuration and clinical case severity on perceived risk associated with in-hospital mortality. Specifically, findings showed that a high level of information (represented by the Predisposition, Infection, Response and Organ dysfunction (PIRO) score) and Figure display (as opposed to Text or baseline) increased awareness to recognizing the risk for in-hospital mortality of hospitalized sepsis patients. A CDSS display that synthesizes the optimal features associated with information level and design elements has the potential to enhance the quantification and communication of clinical risk in complex health conditions beyond sepsis.

Association between timing of antibiotic administration and mortality from septic shock in patients treated with a quantitative resuscitation protocol.

OBJECTIVE: We sought to determine the association between time to initial antibiotics and mortality of patients with septic shock treated with an emergency department-based early resuscitation protocol. DESIGN: Preplanned analysis of a multicenter randomized controlled trial of early sepsis resuscitation. SETTING: Three urban U.S. emergency departments. PATIENTS: Adult patients with septic shock. INTERVENTIONS: A quantitative resuscitation protocol in the emergency department targeting three physiological variables: central venous pressure, mean arterial pressure, and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all end points were achieved or a maximum of 6 hrs. MEASUREMENTS AND MAIN RESULTS: Data on patients who received an initial dose of antibiotics after presentation to the emergency department were categorized based on both time from triage and time from shock recognition to initiation of antibiotics. The primary outcome was inhospital mortality. Of 291 included patients, mortality did not change with hourly delays in antibiotic administration up to 6 hrs after triage: 1 hr (odds ratio [OR], 1.2; 0.6-2.5), 2 hrs (OR, 0.71; 0.4-1.3), 3 hrs (OR, 0.59; 0.3-1.3). Mortality was significantly increased in patients who received initial antibiotics after shock recognition (n = 172 [59%]) compared with before shock recognition (OR, 2.4; 1.1-4.5); however, among patients who received antibiotics after shock recognition, mortality did not change with hourly delays in antibiotic administration. CONCLUSION: In this large, prospective study of emergency department patients with septic shock, we found no increase in mortality with each hour delay to administration of antibiotics after triage. However, delay in antibiotics until after shock recognition was associated with increased mortality.

Intranodal lymphangiography: feasibility and preliminary experience in children.

PURPOSE: To review an initial experience studying the lymphatic system using direct injection of ethiodized oil contrast medium into lymph nodes (ie, intranodal lymphangiography) in children with chylous disorders. MATERIALS AND METHODS: Children with chylous disorders who underwent intranodal lymphangiography were included in this retrospective study. Under general anesthesia, ultrasonography was used to guide the placement of a small-bore (22-25-gauge) needle into an inguinal lymph node. Ethiodized oil contrast medium was very slowly injected into the node. Opacification of the lymphatic system was documented with fluoroscopic and digital substraction imaging and videofluoroscopic clips. RESULTS: Five children (age range, 6 wk to 17 y) with chylous vaginorrhea (n = 1), postoperative chylothorax (n = 2), or spontaneous chylothorax (n = 2) underwent intranodal lymphangiography. The amount of ethiodized oil injected was 0.5-4.5 mL. Intranodal lymphangiography was successfully completed in four patients. One procedure was terminated because of patient motion and extravasation of contrast medium. Lymphangiographic findings included a spectrum of lymphatic channel disorders including incompetence, obstruction, collateralization, chylous reflux, and chylous leak. There were no complications. CONCLUSIONS: The simplified technique of injecting contrast medium into a lymph node to opacify the lymphatic system in children can be an alternative to the more elaborate conventional lymphangiography.

Pulmonary CT angiography to evaluate for pulmonary embolism in children visiting adult-centered community hospitals.

OBJECTIVE: The objective of our study was to determine the rate of pulmonary embolism (PE) on pulmonary CT angiography (CTA) in children and adolescents visiting adult-centered community hospitals. We also investigated alternative diagnoses that may account for presenting symptoms. MATERIALS AND METHODS: We identified consecutive children and adolescents (age ≤ 19 years) who underwent pulmonary CTA during a 12- and 24-month period, respectively, at two community hospitals. Staff radiologists' clinical interpretations of pulmonary CTA studies were compared with interpretations performed by a blinded, subspecialty-trained thoracic radiologist, with a third tie-breaking interpretation performed in cases of discrepancy. A systematic review of pulmonary CTA studies for possible alternative diagnoses was completed. Diagnostic rates of PE on pulmonary CTA studies in adults at these hospitals were also reviewed for comparison. RESULTS: The study population consisted of 130 individuals (32 boys and 98 girls; median age, 18 years; age range, 11-19 years) who underwent 137 examinations, 11 as inpatients and 126 as outpatients. CTA studies were positive for PE in six patients (4.6%). CTA showed an important alternative diagnosis, such as pulmonary consolidation, in 27 patients (21%). By comparison, pulmonary CTA studies in adults at these two hospitals yielded a 16% positive rate for PE. CONCLUSION: The prevalence of PE in young ambulatory patients with clinically suspected PE at adult-centered community hospitals is substantially lower than in adults. Alternative diagnoses, such as pulmonary consolidation and pneumothorax, are discovered more frequently than PE on pulmonary CTA studies. Pulmonary CTA should be used with discretion in adolescents, especially when radiography may provide the necessary diagnosis.

The association of near-infrared spectroscopy-derived tissue oxygenation measurements with sepsis syndromes, organ dysfunction and mortality in emergency department patients with sepsis.

INTRODUCTION: Near-infrared spectroscopy (NIRS) noninvasively measures peripheral tissue oxygen saturation (StO2). NIRS may be utilized along with a vascular occlusion test, in which limb blood flow is temporarily occluded and released, to quantify a tissue bed's rate of oxygen exchange during ischemia and recovery. The objective of this study was to test the hypothesis that NIRS-derived StO2 measures (StO2 initial, StO2 occlusion and StO2 recovery) identify patients who are in shock and at increased risk of organ dysfunction (Sequential Organ Failure Assessment (SOFA) score ≥ 2 at 24 hours) and dying in the hospital. METHODS: This prospective, observational study comprised a convenience sample of three cohorts of adult patients (age > 17 years) at three urban university emergency departments: (1) a septic shock cohort (systolic blood pressure < 90 after fluid challenge; the "SHOCK" cohort, n = 58), (2) a sepsis without shock cohort (the "SEPSIS" cohort, n = 60) and emergency department patients without infection (n = 50). We measured the StO2 initial, StO2 occlusion and StO2 recovery slopes for all patients. Outcomes were sepsis syndrome severity, organ dysfunction (SOFA score at 24 hours) and in-hospital mortality. RESULTS: Among the 168 patients enrolled, mean initial StO2 was lower in the SHOCK cohort than in the SEPSIS cohort (76% vs 81%), with an impaired occlusion slope (-10.2 and 5.2%/minute vs -13.1 and 4.4%/minute) and an impaired recovery slope (2.4 and 1.6%/second vs 3.9 and 1.7%/second) (P < 0.001 for all). The recovery slope was well-correlated with SOFA score at 24 hours (-0.35; P < 0.001), with a promising area under the curve (AUC) for mortality of 0.81. The occlusion slope correlation with SOFA score at 24 hours was 0.21 (P < 0.02), with a fair mortality AUC of 0.70. The initial StO2 was significantly but less strongly correlated with SOFA score at 24 hours (-0.18; P < 0.04), with a poor mortality AUC of 0.56. CONCLUSIONS: NIRS measurements for the StO2 initial, StO2 occlusion and StO2 recovery slope were abnormal in patients with septic shock compared to sepsis patients. The recovery slope was most strongly associated with organ dysfunction and mortality. Further validation is warranted. TRIAL REGISTRATION: NCT01062685.

Variability in imaging utilization in U.S. pediatric hospitals.

BACKGROUND: Use of medical imaging is under scrutiny because of rising costs and radiation exposure. We compare imaging utilization and costs across pediatric hospitals to determine their variability and potential determinants. MATERIALS AND METHODS: Data were extracted from the Pediatric Health Information System (PHIS) database for all inpatient encounters from 40 U.S. children's hospitals. Imaging utilization and costs were compared by insurance type, geographical region, hospital size, severity of illness, length of stay and type of imaging, all among specific diagnoses. RESULTS: The hospital with the highest utilization performed more than twice as many imaging studies per patient as the hospital with the lowest utilization. Similarly, imaging costs ranged from $154 to $671/patient. Median imaging-utilization rate was 1.7 exams/patient on the ward and increased significantly in the PICU (11.8 exams/patient) and in the NICU (17.7 exams per patient, (P < 0.001). Considerable variability in imaging utilization persisted despite adjustment for case mix index (CMI, range in variation 16.6-25%). We found a significant correlation between imaging utilization and both CMI and length of stay, P < 0.0001). However, only 36% of the variation in imaging utilization could be explained by CMI. CONCLUSION: Diagnostic imaging utilization and costs vary widely in pediatric hospitals.

Emergence of Klebsiella pneumoniae carbapenemase-producing bacteria.

Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are a group of emerging highly drug-resistant Gram-negative bacilli causing infections associated with significant morbidity and mortality. Once confined to outbreaks in the northeastern United States (US), they have spread throughout the US and most of the world. KPCs are an important mechanism of resistance for an increasingly wide range of Gram-negative bacteria and are no longer limited to K pneumoniae. KPC-producing bacteria are often misidentified by routine microbiological susceptibility testing and incorrectly reported as sensitive to carbapenems; however, resistance to the carbapenem antibiotic ertapenem is common and a better indicator of the presence of KPCs. Carbapenem antibiotics are generally not effective against KPC-producing organisms. The best therapeutic approach to KPC-producing organisms has yet to be defined; however, common treatments based on in vitro susceptibility testing are the polymyxins, tigecycline, and less frequently, aminoglycoside antibiotics. The purpose of this review is to identify the various challenges that KPC-producing bacteria present to clinicians. These include the need for special techniques for microbiological detection, the potential for nosocomial transmission, and therapeutic challenges related to limited, relatively unproven antimicrobial treatment options.

Bone presence between the central peg's radial fins of a partially cemented pegged all poly glenoid component suggest few radiolucencies.

BACKGROUND: Cement penetration problems and/or cement-induced bone necrosis may contribute to glenoid component failures. An all polyethylene component was developed that promotes biologic fixation between radial fins of its central peg and utilizes minimal cement fixation for its peripheral pegs, but it has little published data. We hypothesized better bone presence between the radial fins would be associated with less overall radiolucencies. This study's purpose was to utilize computed tomography (CT) and plain films to assess for bone between the central peg's radial fins and to assess overall component radiolucencies. MATERIALS AND METHODS: Thirty-five of 48 consecutively performed total shoulder arthroplasties (TSA) for primary glenohumeral osteoarthritis were in patients able to participate a minimum 2 years after surgery. All had reamed humeral head bone packed between radial fins of the central peg and minimal cement for the peripheral pegs. Thin cut (0.625 mm) CT scans, standardized plain films, Simple Shoulder Tests (SST), and Constant scores were obtained. A musculoskeletal radiologist calculated Yian CT scores, bone presence between fins on CT, and Lazarus radiolucency scores. RESULTS: At a mean of 43 months, by CT: 1) better Yian scores correlated with more bone between fins, and 2) bone was present in 6/6 inter-fin compartments in 23/35 shoulders, averaging 4.5/6 overall. Mean Lazarus radiolucency score was 0.45. Mean SST and Constant scores were 10.3 and 81.3, respectively. CONCLUSION: TSA utilizing autologous bone in inter-fin compartments of the central peg and minimal peripheral peg cement maintained bone presence a minimum 2 years post-op. More bone imparted fewer overall component radiolucencies.

Proximity of Cellular and Physiological Response Failures in Sepsis.

Sepsis is a devastating multi-stage health condition with a high mortality rate. Its complexity, prevalence, and dependency of its outcomes on early detection have attracted substantial attention from data science and machine learning communities. Previous studies rely on individual cellular and physiological responses representing organ system failures to predict health outcomes or the onset of different sepsis stages. However, it is known that organ systems' failures and dynamics are not independent events. In this study, we identify the dependency patterns of significant proximate sepsis-related failures of cellular and physiological responses using data from 12,223 adult patients hospitalized between July 2013 and December 2015. The results show that proximate failures of cellular and physiological responses create better feature sets for outcome prediction than individual responses. Our findings reveal the few significant proximate failures that play the major roles in predicting patients' outcomes. This study's results can be simply translated into clinical practices and inform the prediction and improvement of patients' conditions and outcomes.

The Available Criteria for Different Sepsis Scoring Systems in the Emergency Department-A Retrospective Assessment.

OBJECTIVE: The goal of the study was to assess the criteria availability of eight sepsis scoring methods within 6 hours of triage in the emergency department (ED). DESIGN: Retrospective data analysis study. SETTING: ED of MedStar Washington Hospital Center (MWHC), a 912-bed urban, tertiary hospital. PATIENTS: Adult (age ≥ 18 years) patients presenting to the MWHC ED between June 1, 2017 and May 31, 2018 and admitted with a diagnosis of severe sepsis with or without shock. MAIN OUTCOMES MEASURED: Availability of sepsis scoring criteria of eight different sepsis scoring methods at three time points-0 Hours (T0), 3 Hours (T1) and 6 Hours (T2) after arrival to the ED. RESULTS: A total of 50 charts were reviewed, which included 23 (46%) males and 27 (54%) females. Forty-eight patients (96%) were Black or African American. Glasgow Coma Scale was available for all 50 patients at T0. Vital signs, except for temperature, were readily available (>90%) at T0. The majority of laboratory values relevant for sepsis scoring criteria were available (>90%) at T1, with exception to bilirubin (66%) and creatinine (80%). NEWS, PRESEP and qSOFA had greater than 90% criteria availability at triage. SOFA and SIRS consistently had the least percent of available criteria at all time points in the ED. CONCLUSION: The availability of patient data at different time points in a patient's ED visit suggests that different scoring methods could be utilized to assess for sepsis as more patient information becomes available.

A prospective multicenter cohort study of the association between global tissue hypoxia and coagulation abnormalities during early sepsis resuscitation.

OBJECTIVE: Coagulation activation is an integral part of sepsis pathogenesis. Experimental data suggest that endothelial exposure to hypoxia activates coagulation. We aimed to test the hypothesis that the quantity of exposure to global tissue hypoxia is associated with the degree of coagulation activation during early sepsis resuscitation. DESIGN: Prospective, multicenter cohort study. SETTING: Emergency department and intensive care unit of three academic hospitals. PATIENTS: Inclusion criteria were age older than 17, acute infection with two or more signs of systemic inflammation, hypotension despite fluid challenge (or lactate >4 mM), and continuous central venous oxygen saturation (Scvo2) monitoring for quantitative resuscitation. Exclusion criteria were anticoagulant or blood product administration. MEASUREMENTS AND MAIN RESULTS: We recorded central venous oxygen saturation continuously for 0 to 6 hrs of resuscitation and calculated the area under the curve for central venous oxygen saturation <70%. We defined hypoxia exposure as exceeding the median area under the curve for the entire cohort. At 0, 6, and 24 hrs, we measured conventional coagulation biomarkers plus thrombin-antithrombin complex, plasmin-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1, protein C, antithrombin, and endothelial markers (E-selectin, intracellular adhesion molecule-1, thrombomodulin). We compared changes during 0 to 6 hrs and 0 to 24 hrs in biomarkers between hypoxia exposure and nonexposure groups. We enrolled 40 patients (60% requiring vasopressors; 30% mortality). We found that exposure to hypoxia alone was not associated with a significant degree of coagulation activation. However, in secondary analyses we found that exposure to arterial hypotension induced E-selectin and thrombin-antithrombin complex, whereas concomitant exposure to both hypotension and hypoxia was associated with amplification of E-selectin and thrombomodulin, and a reduction in protein C. CONCLUSION: In this sample of patients undergoing quantitative resuscitation for sepsis, we found that exposure to global tissue hypoxia (as quantified by low central venous oxygen saturation) was not associated with major coagulation activation. Further investigation to elucidate the clinical factors that trigger or intensify the procoagulant response to sepsis is warranted.