Suneel Upadhye

Problems with use of composite end points in cardiovascular trials: systematic review of randomised controlled trials

Objective To explore the extent to which components of composite end points in randomised controlled trials vary in importance to patients, the frequency of events in the more and less important components, and the extent of variability in the relative risk reductions across components. Design Systematic review of randomised controlled trials. Data sources Cardiovascular randomised controlled trials published in the Lancet, Annals of Internal Medicine, Circulation, European Heart Journal, JAMA, and New England Journal of Medicine, from 1 January 2002 to 30 June 2003. Component end points of composite end points were categorised according to importance to patients as fatal, critical, major, moderate, or minor. Results Of 114 identified randomised controlled trials that included a composite end point of importance to patients, 68% (n=77) reported complete component data for the primary composite end point; almost all (98%; n=112) primary composite end points included a fatal end point. Of 84 composite end points for which component data were available, 54% (n=45) showed large or moderate gradients in both importance to patients and magnitude of effect across components. When analysed by categories of importance to patients, the most important components were associated with lower event rates in the control group (medians of 3.3-3.7% for fatal, critical, and major outcomes; 12.3% for moderate outcomes; and 8.0% for minor outcomes). Components of greater importance to patients were associated with smaller treatment effects than less important ones (relative risk reduction of 8% for death and 33% for components of minor importance to patients). Conclusion The use of composite end points in cardiovascular trials is frequently complicated by large gradients in importance to patients and in magnitude of the effect of treatment across component end points. Higher event rates and larger treatment effects associated with less important components may result in misleading impressions of the impact of treatment.

Understanding receiver operating characteristic (ROC) curves.

1conclude that serum levels of neuron-specific enolase (NSE), a biochemical marker of ischemic brain injury, may have clinical utility for the prediction of survival to hospital discharge in patients experiencing the return of spontaneous circulation following at least 5 minutes of cardiopulmonary resuscitation. The authors used a receiver operating characteristic (ROC) curve to illustrate and evaluate the diagnostic (prognostic) performance of NSE. We explain ROC curve analysis in the following paragraphs. The term “receiver operating characteristic” came from tests of the ability of World War II radar operators to determine whether a blip on the radar screen represented an object (signal) or noise. The science of “signal detection theory” was later applied to diagnostic medicine. 2

Predictive validity comparison of two five-level triage acuity scales.

Introduction Each of the two most commonly used five-level triage tools in North America, the Emergency Severity Index and the Canadian Triage and Acuity Scale have been used as a measure of emergency department resource utilization in addition to acuity. In both cases, it is believed that patients triaged as having a higher level of acuity require a greater number of emergency department resources. We compared the ability of each tool to predict the emergency department resources for each emergency department visit and associated hospital admission and in-hospital mortality rates. Methods This is an observational, cohort study of a population-based random sample of patients triaged at two emergency departments over a 4-month period. Correlational analyses were performed to examine the relationship between the triage assessment and: (i) resource utilization, (ii) hospital admission, and (iii) in-hospital mortality. Results From 486 patients, analyses revealed the greatest correlation was between Emergency Severity Index and diagnostic resources [−0.54 (95% confidence intervals: −0.58, −0.50)] and the poorest correlation was between Canadian Triage and Acuity Scale and mortality [−0.16 (95% confidence intervals: −0.20, −0.12)]. No statistically significant differences (P<0.005) were observed between each tool s ability to predict any of the outcomes measured. Conclusion No statistically significant difference was observed in the ability of Emergency Severity Index v. 3 and Canadian Triage and Acuity Scale to predict emergency department resource utilization or immediate patient outcomes. This ability is, at best, only moderate indicating that other, more accurate tools than measures of triage acuity are required for this purpose.

Acute Aortic Dissection in the Emergency Department: Diagnostic Challenges and Evidence-Based Management

Acute aortic dissection in the emergency department (ED) remains one of the riskiest clinical and medicolegal challenges facing ED physicians. The variability in clinical presentations and mimics, the unreliability of clinical assessments and initial screening tools, and the need for advanced imaging all present obstacles in making an accurate and timely diagnosis for this entity. This article reviews available information and evidence regarding pathophysiology, risk factors, clinical variations in presentation, the usefulness of different diagnostic testing modalities, and management options in the ED when considering this diagnosis. Key recommendations from recent guidelines are reviewed in the context of ED practice.

A low-fidelity simulation curriculum addresses needs identified by faculty and improves the comfort level of senior internal medicine resident physicians with inhospital resuscitation.

Objective:The purpose of this study was to describe the essential elements of in hospital resuscitation knowledge and skills for senior internal medicine resident physicians and to evaluate a low-fidelity simulation course that incorporates these elements. Design:In part 1, attending physicians were electronically surveyed using a modified Dillman method. A broad list of knowledge skills sets was gathered from recent resuscitation guidelines. In part 2, a 2-day, low-fidelity simulation, case-based curriculum was designed based on the results of part 1. Course participants were surveyed 1 month before and 1 month after the course. Setting:Four academic teaching hospitals. Participants:Attending physicians in cardiology, critical care, and internal medicine responded to the needs assessment survey. A convenience sample of internal medicine residents responded to the surveys before and after the course. Measurements:Respondents ranked items on a 6-point Likert scale for all surveys. Responses were collated using descriptive statistics. This study met the requirements of the Research Ethics Board. Main Results:In part 1, the response rate was 75% (n = 93), with the majority (52%) of respondents being internal medicine attending physicians. The top five knowledge sets were cardiac rhythm assessment, discussion of code status, delivery of bad news, management of wide complex tachycardia, and management of bradycardia. The top five skills were defibrillation, airway assessment, bag-mask ventilation, central venous access, and cardioversion. In part 2, the response rate was 93% (n = 27) before and 85% (n = 23) after course. Only 28% of residents felt prepared to lead resuscitations before the course. After the course, 45% of participants reporting using the knowledge and skills during a resuscitation. Significant changes in median confidence scores before to after the course occurred in important domains. Conclusions:The results of the needs assessment should be used to tailor resuscitation education for residents. An educational need exists for resident physicians. This low-fidelity simulation course improves self-reported confidence in resuscitation knowledge and skills.

The end of early-goal directed therapy?

Emergency medicine practitioners around the world have been confronted with the increasing challenge of managing patients in severe sepsis and septic shock. Introduction of early goal-directed therapy (EGDT) revolutionized sepsis care and was adopted worldwide. Since then, multiple randomized controlled trials have been published questioning the superiority of EGDT. The purpose of this article is to review and provide clinical commentary on the ProCESS, ARISE, and ProMISE trials, which address whether invasive, expensive interventions are needed to achieve mortality reduction goals in septic patients. This article discusses that EGDT bundled care is not necessary to achieve mortality reduction goals.

Does This Patient With Chest Pain Have Acute Coronary Syndrome

*Ischemic ECG defined as any T-wave inversion, ST depression, or Q waves. Fifty-eight articles from the 2,992 that were screened met inclusion criteria. The overall acute coronary syndrome event rate ranged from 5% to 42% (median 14%; interquartile range 10% to 20%). Substantial heterogeneity was identified for some of the decision tools (I>50%). Furthermore, many studies were confounded by incorporation and verification biases. Moreover, data pooling was limited because of the wide variation of variables tested among included studies with the intention to reduce bias from any single study (minimum 560 patients per variable tested).

Circulating biomarkers in acute myofascial pain: A case-control study.

Abstract The aims of the present study were to compare levels of circulating inflammatory biomarkers and growth factors between patients with myofascial pain syndrome (MPS) and healthy control participants, and to assess the relationship among inflammatory markers and growth factors in the two groups. Biomarkers levels were assessed in patients (n = 37) with myofascial pain complaints recruited from the hospital emergency department and non-MPS controls (n = 21), recruited via advertisements in the hospital and community. Blood levels of the cytokines, namely, interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-12 (IL-12), and the chemokine, namely, monocyte chemoattractant protein-1 (MCP-1), macrophage-derived chemokine (MDC), eotaxin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-8 (IL-8), and macrophage inflammatory proteins-1&bgr; (MIP-1&bgr;) were significantly higher in patients with MPS than controls. The results of the growth factor analyses revealed significantly higher levels of fibroblast growth factor-2 (FGF-2), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF) in MPS patients versus controls. The pattern of correlation coefficients between cytokines and growth factors differed considerably for MPS patients and controls with far fewer significant positive coefficients observed in the controls. Serum inflammatory and growth factor biomarkers were elevated in MPS patients. Inflammatory biomarkers and growth factor levels may play an important role in the onset and maintenance of MPS and therefore may be useful in the diagnosis and treatment of MPS. Understanding the mechanisms of inflammation in MPS necessitates future research.

Do Peripheral Thermometers Accurately Correlate to Core Body Temperature

Seventy-five studies (8,682 patients) were included; 42 studies (56%) were conducted with adults, 32 (43%) were conducted with children, and 1 included both groups. Most studies possessed high or unclear risks of patient selection bias (74%). Considerable heterogeneity between studies was encountered, not all of which could be explained by differences in measurement techniques, equipment, temperature thresholds, or other variables. Agreement between peripheral and central thermometers did not vary depending on study quality.

What Are the Most Useful Red Flags for Suspected Vertebral Fracture in Patients With Low Back Pain in the Emergency Department

TUDY SELECTION tudies selected provided nformation about the diagnostic ccuracy of history and physical xamination elements to determine isk of vertebral fracture. Two uthors independently screened itles and abstracts for potential nclusion, and then full publications ere reviewed for final inclusion; isagreement was resolved by onsensus. Quality Assessment of iagnostic Accuracy Studies riteria were used to assess study uality.