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Browsing by Author "Jones, Alan E"
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Item 1-year mortality following contrast-induced nephropathy(2013) Mitchell, Alice M; Jones, Alan E; Tumlin, James A; Kline, Jeffrey A.Objective: The aim of this study was to determine the 1-year mortality risk subsequent to Contrast-Induced Nephropathy (CIN) following CECT imaging, relative to other well-recognized predictors of mortality. Methods: We followed a prospective, consecutive cohort of ambulatory patients who received intravenous contrast for CECT for the outcome of death from any cause within 1 year. In a multivariate analysis, we compared CIN with other predictors of mortality: active malignancy, coronary artery disease (CAD), congestive heart failure (CHF) and age ≥70 years. Anticipating that terminal cancers would account for the majority of deaths in this population, we also analyzed the subset of patients without an active malignancy at the time of enrollment. Results: We followed 633 patients and 46 died (7%, 95%CI: 5-9%) within 1 year. The incidence of CIN was 11% (95%CI: 8-14%). Active malignancy (HR 9.2, 95%CI: 5.1-16.8), CIN (HR 2.4, 95%CI: 1.3-4.6), CHF (HR 2.1, 95%CI: 1.0-4.2), CAD (HR 2.2, 95%CI: 1.0-5.5) and age ≥70 years (HR 1.8, 95%CI: 1.0-3.8) were significant predictors of all-cause mortality. Among patients without active malignancies, the mortality rate was 4% (25/580, 95%CI: 3-6%) and CIN (HR 4.0, 95%CI: 1.7-9.6) and age ≥70 years (HR 3.7, 95%CI: 1.4-9.7) were significantly associated with death, whereas CAD (HR 2.5, 95%CI: 0.8-7.7) and CHF (HR 1.8, 95%CI: 0.6-5.3) were not. Conclusions: The development of CIN following CECT is associated with an increased likelihood of death at 1 year among patients with and without active malignancies, comparable to CAD, CHF and advanced age.Item Association Between Timing of Antibiotic Administration and Mortality from Septic Shock in Patients Treated with a Quantitative Resuscitation Protocol(2011-09) Puskarich, Michael A; Trzeciak, Stephen; Shapiro, Nathan I; Arnold, Ryan C; Horton, James M; Studnek, Jonathan R; Kline, Jeffrey A.; Jones, Alan EObjective We sought to determine the association between time to initial antibiotics and mortality of septic shock patients treated with an emergency department (ED) based early resuscitation protocol. Design Pre-planned analysis of a multicenter randomized controlled trial of early sepsis resuscitation. Setting 3 urban US EDs. Patients Adult septic shock patients. Interventions A quantitative resuscitation protocol in the ED targeting 3 physiological variables: central venous pressure, mean arterial pressure and either central venous oxygen saturation or lactate clearance. The study protocol was continued until all endpoints were achieved or a maximum of 6 hours. Measurements Data on patients who received an initial dose of antibiotics after presentation to the ED were categorized based on both time from triage and time from shock recognition to initiation of antibiotics. The primary outcome was in-hospital mortality. Main Results Of 291 included patients, mortality did not change with hourly delays in antibiotic administration up to 6 hours after triage: 1 hour (OR 1.2, 0.6–2.5), 2 hours (OR 0.71, 0.4–1.3), 3 hours (OR 0.59, 0.3–1.3). Mortality was significantly increased 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 ED 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.Item Characteristics and Outcomes of Patients with Vasoplegic Versus Tissue Dysoxic Septic Shock(2013-07) Sterling, Sarah A; Puskarich, Michael A; Shapiro, Nathan I; Trzeciak, Stephen; Kline, Jeffrey A.; Summers, Richard L; Jones, Alan EBackground: The current consensus definition of septic shock requires hypotension after adequate fluid challenge or vasopressor requirement. Some patients with septic shock present with hypotension and hyperlactatemia greater than 2 mmol/L (tissue dysoxic shock), whereas others have hypotension alone with normal lactate (vasoplegic shock). Objective: The objective of this study was to determine differences in outcomes of patients with tissue dysoxic versus vasoplegic septic shock. Methods: This was a secondary analysis of a large, multicenter randomized controlled trial. Inclusion criteria were suspected infection, two or more systemic inflammatory response criteria, and systolic blood pressure less than 90 mmHg after a fluid bolus. Patients were categorized by presence of vasoplegic or tissue dysoxic shock. Demographics and Sequential Organ Failure Assessment scores were evaluated between the groups. The primary outcome was in-hospital mortality. Results: A total of 247 patients were included, 90 patients with vasoplegic shock and 157 with tissue dysoxic shock. There were no significant differences in age, race, or sex between the vasoplegic and tissue dysoxic shock groups. The group with vasoplegic shock had a lower initial Sequential Organ Failure Assessment score than did the group with tissue dysoxic shock (5.5 vs. 7.0 points; P = 0.0002). The primary outcome of in-hospital mortality occurred in 8 (9%) of 90 patients with vasoplegic shock compared with 41 (26%) of 157 in the group with tissue dysoxic shock (proportion difference, 17%; 95% confidence interval, 7%–26%; P < 0.0001; log-rank test P = 0.02). After adjusting for confounders, tissue dysoxic shock remained an independent predictor of in-hospital mortality. Conclusions: In this analysis of patients with septic shock, we found a significant difference in in-hospital mortality between patients with vasoplegic versus tissue dysoxic septic shock. These findings suggest a need to consider these differences when designing future studies of septic shock therapies.Item Cost-Effectiveness of an Emergency Department Based Early Sepsis Resuscitation Protocol(2011-06) Jones, Alan E; Troyer, Jennifer L; Kline, Jeffrey A.Background Guidelines recommend that sepsis be treated with an early resuscitation protocol, such as early goal directed therapy (EGDT). Our objective was to assess the cost-effectiveness of implementing EGDT as a routine protocol. Design Prospective before and after study. Setting Large urban hospital ED with >110,000 visits/year. Patients The target population was patients with consensus criteria for septic shock. We excluded those with age <18 yrs, no aggressive care desired, or need for immediate surgery. Interventions Clinical and cost data were prospectively collected on two groups: 1) patients from 1 yr before and 2) 2 yrs after implementing EGDT as standard-of-care. Before phase patients received nonprotocolized care at attending discretion. The primary outcomes were one year mortality, discounted life expectancy, and quality adjusted life years (QALYs). Using costs and QALYs, we constructed an incremental cost-effectiveness ratio and performed a net monetary benefit (NMB) analysis, producing the probability that the intervention was cost-effective given different values for the willingness to pay for a QALY. Results 285 subjects, 79 in the before and 206 in the after phases, were enrolled. Treatment with EGDT was associated with an increased hospital cost of $7028 and an increase in both discounted sepsis-adjusted life expectancy and QALYs of 1.5 and 1.3 yrs, respectively. EGDT use was associated with a cost of $5397 per QALY gained and the NMB analysis indicates a 98% probability (p = .038) that EGDT is cost-effective at a willingness to pay of $50,000 per QALY. Conclusion Implementation of EGDT in the ED care of severe sepsis patients is cost effective.Item D-Dimer and Exhaled CO2/O2 to Detect Segmental Pulmonary Embolism in Moderate-Risk Patients(2010-09) Kline, Jeffrey A.; Hogg, Melanie M; Courtney, D Mark; Miller, Chadwick D; Jones, Alan E; Smithline, Howard A; Klekowski, Nicole; Lanier, RandyRationale: Pulmonary embolism (PE) decreases the exhaled end-tidal ratio of carbon dioxide to oxygen (etCO2/O2). Objectives: To test if the etCO2/O2 can produce clinically important changes in the probability of segmental or larger PE on computerized tomography multidetector-row pulmonary angiography (MDCTPA) in a moderate-risk population with a positive D-dimer. Methods: Emergency department and hospitalized patients with one or more predefined symptoms or signs, one or more risk factors for PE, and 64-slice MDCTPA enrolled from four hospitals. D-dimer greater than 499 ng/ml was test(+), and D-dimer less than 500 ng/ml was test(−). The median etCO2/O2 less than 0.28 from seven or more breaths was test(+) and etCO2/O2 greater than 0.45 was test(−). MDCTPA images were read by two independent radiologists and the criterion standard was the interpretation of acute PE by either reader. PE size was then graded. Measurements and Main Results: We enrolled 495 patients, including 60 (12%) with segmental or larger, and 29 (6%) with subsegmental PE. A total of 367 (74%) patients were D-dimer(+), including all 60 with segmental or larger PE (posterior probability 16%). The combination of D-dimer(+) and etCO2/O2(+) increased the posterior probability of segmental or larger PE to 28% (95% confidence interval [CI] for difference of 12%, 3.0–22%). The combination of D-dimer(+) and etCO2/O2(−) was observed in 40 patients (8%; 95% CI, 6–11%), and none (0/40; 95% CI, 0–9%) had segmental or larger PE on MDCTPA. No strategy changed the prevalence of subsegmental PE. Conclusions: In moderate-risk patients with a positive D-dimer, the et etCO2/O2 less than 0.28 significantly increases the probability of segmental or larger PE and the etCO2/O2 greater than 0.45 predicts the absence of segmental or larger PE on MDCTPA.Item D-dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography(2012-04) Kline, Jeffrey A.; Hogg, Melanie M; Courtney, D Mark; Miller, Chadwick D; Jones, Alan E; Smithline, Howard ABackground: Increasing the threshold to define a positive D-dimer could reduce unnecessary computed tomographic pulmonary angiography (CTPA) for a suspected pulmonary embolism (PE) but might increase rates of a missed PE and missed pneumonia, the most common non-thromboembolic diagnosis seen on CTPA. Objective: Measure the effect of doubling the standard D-dimer threshold for ‘PE unlikely’ Revised Geneva (RGS) or Wells’ scores on the exclusion rate, frequency and size of a missed PE and missed pneumonia. Methods: Patients evaluated for a suspected PE with 64-channel CTPA were prospectively enrolled from emergency departments (EDs) and inpatient units of four hospitals. Pretest probability data were collected in real time and the D-dimer was measured in a central laboratory. Criterion standard was CPTA interpretation by two independent radiologists combined with clinical outcome at 30 days. Results: Of 678 patients enrolled, 126 (19%) were PE+ and 93 (14%) had pneumonia. Use of either Wells’ ≤ 4 or RGS ≤ 6 produced similar results. For example, with RGS ≤ 6 and standard threshold (< 500 ng mL−1), D-dimer was negative in 110/678 (16%), and 4/110 were PE+ (posterior probability 3.8%) and 9/110 (8.2%) had pneumonia. With RGS ≤ 6 and a threshold < 1000 ng mL−1, D-dimer was negative in 208/678 (31%) and 11/208 (5.3%) were PE+, but 10/11 missed PEs were subsegmental and none had concomitant DVT. Pneumonia was found in 12/208 (5.4%) with RGS ≤ 6 and D-dimer < 1000 ng mL−1. Conclusions: Doubling the threshold for a positive D-dimer with a PE unlikely pretest probability could reduce CTPA scanning with a slightly increased risk of missed isolated subsegmental PE, and no increase in rate of missed pneumonia.Item Derivation and validation of a multivariate model to predict mortality from pulmonary embolism with cancer: the POMPE-C tool(2012-05) Kline, Jeffrey A.; Roy, Pierre-Marie; Than, Martin P; Hernandez, Jackeline; Courtney, D Mark; Jones, Alan E; Penazola, Andrea; Pollack Jr, Charles VBackground Clinical guidelines recommend risk stratification of patients with acute pulmonary embolism (PE). Active cancer increases risk of PE and worsens prognosis, but also causes incidental PE that may be discovered during cancer staging. No quantitative decision instrument has been derived specifically for patients with active cancer and PE. Methods Classification and regression technique was used to reduce 25 variables prospectively collected from 408 patients with AC and PE. Selected variables were transformed into a logistic regression model, termed POMPE-C, and compared with the pulmonary embolism severity index (PESI) score to predict the outcome variable of death within 30 days. Validation was performed in an independent sample of 182 patients with active cancer and PE. Results POMPE-C included eight predictors: body mass, heart rate > 100, respiratory rate, SaO2%, respiratory distress, altered mental status, do not resuscitate status, and unilateral limb swelling. In the derivation set, the area under the ROC curve for POMPE-C was 0.84 (95% CI: 0.82-0.87), significantly greater than PESI (0.68, 0.60-0.76). In the validation sample, POMPE-C had an AUC of 0.86 (0.78-0.93). No patient with POMPE-C estimate ≤ 5% died within 30 days (0/50, 0-7%), whereas 10/13 (77%, 46-95%) with POMPE-C estimate > 50% died within 30 days. Conclusion In patients with active cancer and PE, POMPE-C demonstrated good prognostic accuracy for 30 day mortality and better performance than PESI. If validated in a large sample, POMPE-C may provide a quantitative basis to decide treatment options for PE discovered during cancer staging and with advanced cancer.Item The effect of a quantitative resuscitation strategy on mortality in patients with sepsis: A meta-analysis(2008-10) Jones, Alan E; Brown, Michael D; Trzeciak, Stephen; Shapiro, Nathan I; Garrett, John S; Heffner, Alan C; Kline, Jeffrey A.Objective Quantitative resuscitation consists of structured cardiovascular intervention targeting predefined hemodynamic end points. We sought to measure the treatment effect of quantitative resuscitation on mortality from sepsis. Data Sources We conducted a systematic review of the Cochrane Library, MEDLINE, EMBASE, CINAHL, conference proceedings, clinical practice guidelines, and other sources using a comprehensive strategy. Study Selection We identified randomized control trials comparing quantitative resuscitation with standard resuscitation in adult patients who were diagnosed with sepsis using standard criteria. The primary outcome variable was mortality. Data Abstraction Three authors independently extracted data and assessed study quality using standardized instruments; consensus was reached by conference. Preplanned subgroup analysis required studies to be categorized based on early (at the time of diagnosis) vs. late resuscitation implementation. We used the chi-square test and I2 to assess for statistical heterogeneity (p < 0.10, I2 > 25%). The primary analysis was based on the random effects model to produce pooled odds ratios with 95% confidence intervals. Results The search yielded 29 potential publications; nine studies were included in the final analysis, providing a sample of 1001 patients. The combined results demonstrate a decrease in mortality (odds ratio 0.64, 95% confidence interval 0.43–0.96); however, there was statistically significant heterogeneity (p = 0.07, I2 = 45%). Among the early quantitative resuscitation studies (n = 6) there was minimal heterogeneity (p = 0.40, I2 = 2.4%) and a significant decrease in mortality (odds ratio 0.50, 95% confidence interval 0.37–0.69). The late quantitative resuscitation studies (n = 3) demonstrated no significant effect on mortality (odds ratio 1.16, 95% confidence interval 0.60–2.22). Conclusion This meta-analysis found that applying an early quantitative resuscitation strategy to patients with sepsis imparts a significant reduction in mortality.Item Effect of Glucose–Insulin–Potassium Infusion on Mortality in Critical Care Settings: A Systematic Review and Meta-Analysis(2009-07) Puskarich, Michael A; Runyon, Michael S; Trzeciak, Stephen; Kline, Jeffrey A.; Jones, Alan EThis study seeks to measure the treatment effect of glucose—insulin—potassium (GIK) infusion on mortality in critically ill patients. A systematic review of randomized controlled trials is conducted, comparing GIK treatment with standard care or placebo in critically ill adult patients. The primary outcome variable is mortality. Two authors independently extract data and assess study quality. The primary analysis is based on the random effects model to produce pooled odds ratios (ORs) with 95% confidence intervals (CIs). The search yields 1720 potential publications; 23 studies are included in the final analysis, providing a sample of 22 525 patients. The combined results demonstrate no heterogeneity (P = .57, I2 = 0%) and no effect on mortality (OR = 1.02; 95% CI, 0.93–1.11) with GIK treatment. No experimental studies of shock or sepsis populations are identified. This meta-analysis finds that there is no mortality benefit to GIK infusion in critically ill patients; however, study populations are limited to acute myocardial infarction and cardiovascular surgery patients. No studies are identified using GIK in patients with septic shock or other forms of circulatory shock, providing an absence of evidence regarding the effect of GIK as a therapy in patients with shock.Item End expiratory oxygen concentrations to predict central venous oxygen saturation: an observational pilot study(2006-09) Jones, Alan E; Kuehne, Karl; Steuerwald, Michael; Kline, Jeffrey A.Background A non-invasive surrogate measurement for central venous oxygen saturation (ScVO2) would be useful in the ED for assessing therapeutic interventions in critically ill patients. We hypothesized that either linear or nonlinear mathematical manipulation of the partial pressure of oxygen in breath at end expiration (EtO2) would accurately predict ScVO2. Methods Prospective observational study of a convenience sample of hemodialysis patients age > 17 years with existing upper extremity central venous catheters were enrolled. Using a portable respiratory device, we collected both tidal breathing and end expiratory oxygen and carbon dioxide concentrations, volume and flow on each patient. Simultaneous ScVO2 measurements were obtained via blood samples collected from the hemodialysis catheter. Two models were used to predict ScVO2: 1) Best-fit multivariate linear regression equation incorporating all respiratory variables; 2) MathCAD to model the decay curve of EtO2 versus expiratory volume using the least squares method to estimate the pO2 that would occur at <20% of total lung capacity. Results From 21 patients, the correlation between EtO2 and measured ScVO2 yielded R2 = 0.11. The best fit multivariate equation included EtCO2 and EtO2 and when solved for ScVO2, the equation yielded a mean absolute difference from the measured ScVO2 of 8 ± 6% (range -18 to +17%). The predicted ScVO2 value was within 10% of the actual value for 57% of the patients. Modeling of the EtO2 curve did not accurately predict ScVO2 at any lung volume. Conclusion We found no significant correlation between EtO2 and ScVO2. A linear equation incorporating EtCO2 and EtO2 had at best modest predictive accuracy for ScVO2.
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