Platelet glycoprotein inhibitors in patients with medically managed acute coronary syndrome: does the enthusiasm exceed the science?

Guidelines from the American Heart Association and the American College of Cardiology, as well as numerous review articles, have strongly and enthusiastically recommended that platelet glycoprotein IIb/IIIa inhibitors be used in patients with medically managed unstable angina or non-ST-segment myocardial infarction (UA/NSTEMI). We explore whether there is sufficient experimental evidence to justify these recommendations. We review the 4 large randomized trials of US Food and Drug Administration-approved platelet glycoprotein IIb/IIIa inhibitors that included medically managed UA/NSTEMI patients, first taking each trial's results at face value and then in the context of likely biases. The risk differences, unadjusted for potential biases, are 2.5% (0.6%, 4.4%) for the Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) study, 2.3% (-1.9%, 6.5%) for the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study (tirofiban plus heparin), 0.9% (-0.9%, 2.8%) for the Platelet Glycoprotein IIb/IIIa in Unstable Angina Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, -0.2% (-1.7%, 1.3%) for the least harmful treatment arm of the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-IV) trial, and -1.9% (-6.8%, 3.0%) for the PRISM-PLUS study (tirofiban alone) (positive numbers indicate benefit). The 95% confidence interval produced by combining the studies using a random effects model is -1.3% to 3.2% (mean 0.9%); this is consistent with drugs providing a small benefit, no benefit, or causing harm. Confounding caused by the nonrandom selection of patients for percutaneous transluminal coronary angioplasty and coronary artery bypass grafting in all trials except GUSTO-IV and problems arising from the fact that enrolled patients were much sicker than typical UA/NSTEMI patients are likely to have biased the studies away from the null and make an assertion of benefit even more tenuous. Given the equivocal results, it would appear that the authors are relying on opinion rather than evidence to formulate their conclusions. Clinicians should understand that opinion and factors other than medical evidence may influence the content of the recommendations.

Implementation of clinical guidelines through an electronic medical record: physician usage, satisfaction and assessment.

CONTEXT: We developed and evaluated the Emergency Department Expert Charting System (EDECS) to provide real-time guidance regarding the care of low back pain in adults, fever in children, and occupational exposure to blood and body fluids in health care workers, by embedding clinical guidelines within an electronic medical record. OBJECTIVE: To describe the behaviors and attitudes of physicians who used EDECS. DESIGN: Pre-post questionnaires were used to assess physician attitudes. Time studies of the intervention phase were observational, using clocks embedded in the software. PARTICIPANTS: One hundred and forty two residents and interns in emergency, pediatric, internal, and family medicine and patients with the above-mentioned complaints. MAIN OUTCOME MEASURES: Physician utilization of EDECS, time spent using EDECS, physician satisfaction and beliefs. RESULTS: Eighty four percent of the 142 eligible physicians used EDECS at least once. Five hundred and ninety one of 789 (75%) eligible cases were completed using EDECS. Median session time decreased from 12 min for session 1, to 5.5 min for sessions 16 and above. Physicians generally agreed that care with EDECS was better than standard care, particularly with respect to documentation. There was, however, considerable heterogeneity in belief among complaints. CONCLUSIONS: These data illuminate both the potentials of computer-assisted decision making and the need for context-specific approaches when attempting to implement guidelines.

Identification of risk factors for exertional heat-related illnesses in long-distance cyclists: experience from the California AIDS Ride.

OBJECTIVES: To identify risk factors for exertional heat-related illnesses and to determine if patients who are afflicted with the human immunodeficiency virus or have acquired immunodeficiency syndrome have an increased risk of exertional heat-related illness. DESIGN: Descriptive, retrospective, matched case-control study. SETTING: Mobile community of 2,650 participants in the California AIDS Ride 3. PARTICIPANTS: Participants included 117 patients presenting for medical care with heat-related illnesses and 234 age-, gender-, and registration site-matched control subjects who did not develop a heat-related illness. METHODS: Retrospective, matched case-control study utilizing univariate and multivariate conditional logistic regression to determine if human immunodeficiency virus seropositivity, the number of chronic medical illnesses, or the number of current medications known to affect heat dissipation increased the risk of exertional heat-related illnesses. RESULTS: The multivariate model revealed that patients with a greater number of chronic medical illnesses were at a significantly increased risk of a heat-related illness (odds ratio = 1.6, 95% CI = 1.2-2.1). The number of current medications (odds ratio = 1.1, 95% CI = 0.8-1.5) and human immunodeficiency virus seropositivity (odds ratio = 0.7, 95% CI = 0.2-3.1) were not significant predictors of risk for exertional heat-related illness. CONCLUSIONS: Those riders suffering from a greater number of chronic medical illnesses were at a greater risk for developing an exertional heat-related illness. Human immunodeficiency virus seropositivity alone was not associated with increased risk of exertional heat-related illness.

Analyzing the relationship of exercise and health: methods, assumptions, and limitations.

The papers in this supplement to Medicine and Science in Sports and Exercise seek to summarize our knowledge of the dose-response relationship of exercise with a variety of health outcomes. This type of rigorous evidence summation has become quite popular in the past 10 years as health care providers and policymakers seek to distinguish interventions that are helpful--the expected benefits justify human and economic costs--from those of no or uncertain benefit (7). Proponents of "evidence-based medicine" argue that in contrast to old-style literature reviews in which the writer, typically an "expert," develops a thesis and cites only those publications that support his point of view, an evidence-based approach finds all of the evidence and objectively weighs it to determine the "truth" (20,22). Although such methods offer the promise of increased objectivity, they are not immune to bias, and readers should understand that the declaration that something is "evidence-based" is no guarantee of its veracity. In fact, because the literature virtually never includes studies that perfectly match the setting and personal circumstance of the patient under treatment, "evidence-informed medicine" would be a more honest title for care grounded in systematic reviews of the literature (23). This paper begins with a discussion of potential theoretical problems with systematic reviews and concludes by considering specific problems that members of the panel were likely to encounter when evaluating the literature on exercise and health. These concepts were presented in the initial lecture of the conference so that the 24 lecturers and 6 members of the consensus panel would be forewarned of the dangers that lay ahead.

Enabling the diagnosis of occult psychiatric illness in the emergency department: a randomized, controlled trial of the computerized, self-administered PRIME-MD diagnostic system.

STUDY OBJECTIVE: Undiagnosed mental illness is highly prevalent and produces needless morbidity. Emergency department patients with vague or longstanding complaints are at risk for occult mental illness, but are seldom diagnosed. We conducted this study to determine whether a previously validated, self-administered, computerized psychiatric interview (Primary Care Evaluation of Mental Disorders [PRIME-MD]) could increase the detection of occult psychiatric illness in the ED. METHODS: This was a randomized, controlled trial of consecutive patients enrolled during convenient times at a university teaching hospital ED with an annual census of 38,000. ED house staff and attending physicians participated. Patients were those with nonspecific complaints potentially associated with occult psychiatric illness (eg, long-standing headache, abdominal or back pain). Exclusion criteria were known psychiatric illness, complaint, or medication; and straightforward reason for the ED visit. Consenting subjects completed the PRIME-MD questionnaire in the waiting room, and were randomly assigned to either the "report" (report results given to physician) or "no-report" groups. PRIME-MD results were clipped to the front of the chart of report group patients. There was no other intervention. The main outcome measures were the percentage of all patients and percentage of patients with a PRIME-MD diagnosis who received a psychiatric diagnosis, consultation, or referral from the emergency physician. RESULTS: A total of 339 (5.1%) of all patients were approached; 230 consented to participate in the study, and 218 completed the PRIME-MD session and were randomly assigned to study groups. Ninety-two patients in the report group and 98 cases in the no-report group were analyzed. Patients were omitted for the following reasons: left without being seen (8), mistakenly enrolled (10), or unretrievable medical records (10). Seventy-nine (42%) patients received a psychiatric diagnosis from PRIME-MD and 9 (5%) from the physician. The frequencies of physician psychiatric diagnosis and referral did not differ between groups (diagnosis: report 9%, no report 9%, Delta 0%, 95% confidence interval [CI] -13, 14; referral: report 9%, no report 7%, Delta 2%, 95% CI -11, 16). CONCLUSION: ED patients willingly completed the PRIME-MD questionnaire (in a median time of 7 minutes), which frequently diagnosed psychiatric conditions. Despite this, physicians rarely diagnosed or treated these conditions regardless of whether they were provided with the PRIME-MD diagnoses.

An evaluation of the graphical literacy of Annals of Emergency Medicine.

STUDY OBJECTIVE: To describe the type, quantity, and quality of graphics used to present original research in Annals of Emergency Medicine. METHODS: We performed a blinded, retrospective review of all graphics published in Annals of Emergency Medicine's original research articles from January 1998 through June 1999. We assessed the types of graphics, the use of special features to display detail, the clarity of each graphic, discrepancies within the graphic or between the graphic and text, and the efficiency of data presentation. RESULTS: Forty-six percent (68/147) of original research communications contained at least 1 graphic. Of the 128 graphics in these 68 articles, simple univariate displays predominated (53%). Only one third of graphics displayed by-subject data through the use of one-way plots, scatter plots, or other formats. Graphics generally defined all symbols and abbreviations (99%) and were self-explanatory (88%). Techniques for conveying the richness of a data set were seldom used (11% of all graphics). Forty percent (51/128) of the graphics contained internal contradictions (15%), muddled displays (19%), numeric distortion (5%), nonstandard graphing conventions (7%), and other lapses in design or execution. Inefficiencies of data presentation included internal redundancy (16%), extraneous decoration (10%), and redundancy of graphic data with other text/tables (15%). CONCLUSION: The majority of graphics in Annals of Emergency Medicine, although internally valid, failed to take full advantage of the graphic's potential and often depicted summary data when portrayal of subject-specific data was possible. To help readers fully understand research findings, authors and editors should take care to ensure that graphics efficiently and effectively portray the optimal amount of information.

Achieving graphical excellence: suggestions and methods for creating high-quality visual displays of experimental data.

Graphics are an important means of communicating experimental data and results. There is evidence, however, that many of the graphics printed in scientific journals contain errors, redundancies, and lack clarity. Perhaps more important, many graphics fail to portray data at an appropriate level of detail, presenting summary statistics rather than underlying distributions. We seek to aid investigators in the production of high-quality graphics that do their investigations justice by providing the reader with optimum access to the relevant aspects of the data. The depiction of by-subject data, the signification of pairing when present, and the use of symbolic dimensionality (graphing different symbols to identify relevant subgroups) and small multiples (the presentation of an array of similar graphics each depicting one group of subjects) to portray stratification are stressed. Step-by-step instructions for the construction of high-quality graphics are offered. We hope that authors will incorporate these suggestions when developing graphics to accompany their manuscripts and that this process will lead to improvements in the graphical literacy of scientific journals. We also hope that journal editors will keep these principles in mind when refereeing manuscripts submitted for peer review.

Revisiting the oral glucose tolerance test criterion for the diagnosis of diabetes.

OBJECTIVE: The Expert Committee on the Diagnosis and Classification of Diabetes retained the 2-hour glucose concentration on an oral glucose tolerance test of >/=11.1 mmol/L (200 mg/dL) as a criterion to diagnose diabetes. Since glycated hemoglobin levels have emerged as the best measure of long-term glycemia and an important predictor of microvascular and neuropathic complications, we evaluated the distribution of hemoglobin A1C (Hb A1C) levels in individuals who had undergone an oral glucose tolerance test to determine how well 2-hour values could identify those with normal versus increased Hb A1C levels. DESIGN: A cross-sectional analysis of 2 large data sets was performed. We cross-tabulated 2-hour glucose concentrations on an oral glucose tolerance test separated into 4 intervals (<7.8 mmol/L [140 mg/dL], 7.8-11.0 mmol/L [140-199 mg/dL], 11.1-13.3 mmol/L [200-239 mg/dL], and >/=13.3 mmol/L [240 mg/dL]) with Hb A1C levels separated into 3 intervals (normal; <1% above the upper limit of normal; and greater than or equal to the upper limit of normal + 1%). RESULTS: Approximately two thirds of patients in both data sets with 2-hour glucose concentrations of 11.1 to 13.3 mmol/L (200-239 mg/dL) had normal Hb A1C levels. In contrast, 60% to 80% of patients in both data sets with 2-hour glucose concentrations >/=13.3 mmol/L (240 mg/dL) had elevated Hb A1C levels. CONCLUSION: Since Hb A1C levels are the best measures presently available that reflect long-term glycemia, we conclude that the 2-hour glucose concentration criterion on an oral glucose tolerance test for the diagnosis of diabetes should be raised from >/= 11.1 mmol/L (200 mg/dL) to >/= 13.3 mmol/L (240 mg/dL) to remain faithful to the concept that diagnostic concentrations of glucose should predict the subsequent development of specific diabetic complications (e.g., retinopathy).

Detection of early CT signs of >1/3 middle cerebral artery infarctions : interrater reliability and sensitivity of CT interpretation by physicians involved in acute stroke care.

BACKGROUND AND PURPOSE: This study had 2 goals: (1) to assess interrater reliability of academic neuroradiologists when classifying acute infarction by CT scan as >1/3 middle cerebral artery (MCA) involvement, <1/3 MCA involvement, or no infarction and (2) to determine the sensitivity of physicians potentially involved in acute stroke treatment in detecting >1/3 MCA acute infarctions. Studies of tissue plasminogen activator show an association between early signs of major infarction and poor outcome. The American Academy of Neurology and the American Heart Association recommend avoiding thrombolysis if early signs of major infarction are present. METHODS: We presented 25 scans (normals, acute infarctions, and old infarctions) to 3 academic neuroradiologists. A scoring sheet based on Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS)/CT Summit criteria was used to determine >1/3 MCA territory involvement. Nine of the 25 scans were presented again to assess intrarater reliability. We recalculated results of our previous study in which physicians interpreted infarction scans, now designating the scans as >1/3 MCA, <1/3 MCA, or normal, as determined by the neuroradiologists. RESULTS: All 3 neuroradiologists agreed on no infarction, <1/3 MCA, and >1/3 MCA on 64% of the scans. Neuroradiologist test-retest agreement was 96% for >1/3 MCA territory. Overall sensitivity for emergency physicians, neurologists, and general radiologists for detecting the presence of infarction in scans rated as >1/3 MCA was 78%. CONCLUSIONS: Neuroradiologists can achieve moderate agreement in detecting >1/3 MCA infarction. The emergency physicians, neurologists, and general radiologists tested were reasonably skilled at detecting >1/3 MCA acute infarction. However, their performance did not reliably identify all patients who have early CT infarct signs that place them at increased risk for cerebral hemorrhage after thrombolytic therapy.

Implementation of clinical guidelines via a computer charting system: effect on the care of febrile children less than three years of age.

OBJECTIVE: The authors have shown that clinical guidelines embedded in an electronic medical record improved the quality, while lowering the cost, of care for health care workers who incurred occupational exposures to body fluid. They seek to determine whether this system has similar effects on the emergency department care of young children with febrile illness. DESIGN: Off-on-off, interrupted time series with intent-to-treat analysis. SETTING: University hospital emergency department. SUBJECTS: 830 febrile children less than 3 years of age and the physicians who treated them. INTERVENTIONS: Implementation of an electronic medical record that provides real-time advice regarding the content of the history and physical examination and recommendations regarding laboratory testing, treatment, diagnosis, and disposition. MEASUREMENTS: Documentation of essential items in the medical record and after-care instructions; compliance with guidelines regarding testing, treatment, and diagnosis; charges. RESULTS: The computer was used in 64 percent of eligible cases. Mean percentage documentation of 21 essential history and physical examination items increased from 80 percent during the baseline period to 92 percent in the intervention phase (13 percent increase; 95 percent CI, 10-15 percent). Mean percentage documentation of ten items in the after-care instructions increased from 48 percent at baseline to 81 percent during the intervention phase (33 percent increase; 95 percent confidence interval, 28-38 percent). All documentation decreased to baseline when the computer system was removed. There were no demonstrable improvements in appropriateness of care, nor was there evidence that appropriateness worsened. Mean charges were not changed by the intervention. CONCLUSION: The intervention markedly improved documentation, had little effect on the appropriateness of the process of care, and had no effect on charges. Results for the febrile child module differ from those for the module for occupational blood and body fluid exposure (a more focused and straightforward medical condition), underscoring the need for implementation methods to be tailored to specific clinical complaints.

Relationship between fasting plasma glucose and glycosylated hemoglobin: potential for false-positive diagnoses of type 2 diabetes using new diagnostic criteria.

CONTEXT: New criteria for the diagnosis of type 2 diabetes mellitus have recently been introduced that lowered the diagnostic fasting plasma glucose (FPG) concentration from 7.8 to 7.0 mmol/L (140 to 126 mg/dL). OBJECTIVE: To determine if individuals with diabetes diagnosed by the new FPG concentration criterion would have excessive glycosylation (elevated hemoglobin [HbA1c] levels). DEFINITIONS: We determined the distribution of HbA1c levels in individuals using 4 classifications: (1) normal by the new criterion (FPG concentration <6.1 mmol/L [110 mg/dL]); (2) impaired fasting glucose by the new criterion (FPG concentration of 6.1-6.9 mmol/L [110-125 mg/dL]); (3) diabetes diagnosed solely by the new FPG concentration criterion of 7.0 through 7.7 mmol/L (126-139 mg/dL); and (4) diabetes diagnosed by the previous FPG concentration criterion of 7.8 mmol/L (140 mg/dL) or higher. DESIGN: Cross-sectional analysis of 2 large data sets (NHANES III and Meta-Analysis Research Group [MRG] on the Diagnosis of Diabetes Using Glycated Hemoglobin) that contained individuals in whom FPG concentrations, 2-hour glucose concentrations using an oral glucose tolerance test, and an HbA1c level were simultaneously measured. We cross-tabulated FPG concentrations (<6.1 mmol/L [110 mg/dL], 6.1-6.9 mmol/L [110-125 mg/dL], 7.0-7.7 mmol/L [126-139 mg/dL], and > or =7.8 mmol/L [140 mg/dL]) and HbA1c levels separated into 3 intervals: normal, less than the upper limit of normal (ULN); slightly elevated, ULN to ULN plus 1%; and high, higher than ULN plus 1%. RESULTS: Among subjects with normal FPG concentrations, HbA1c levels in the NHANES III (and the MRG) data sets were normal in 97.3% (96.2%), slightly elevated in 2.7% (3.6%), and high in 0.1% (0.2%). Among individuals with impaired fasting glucose, HbA1c concentrations were normal in 86.7% (81.4%), slightly elevated in 13.1% (16.4%), and high in 0.2% (2.2%). Among diabetic patients diagnosed by the new FPG criterion only, HbA1c levels were normal in 60.9% (59.6%), slightly elevated in 35.8% (32.8%), and high in 3.4% (7.6%). In diabetic patients diagnosed by the former FPG criterion, HbA1c levels were normal in 18.6% (16.7%), slightly elevated in 32.5% (21.0%), and high in 48.9% (62.3%). CONCLUSIONS: About 60% of the new cohort of diabetic patients in both data sets have normal HbA1c levels. We believe that diabetes should not be diagnosed in those with FPG concentrations less than 7.8 mmol/L (140 mg/dL) unless excessive glycosylation is evident. Individuals without excessive glycosylation but with moderate elevations of FPG concentrations (6.1-7.7 mmol/L [110-139 mg/dL]) should be diagnosed as having impaired fasting glucose and treated with an appropriate diet and exercise. This diagnostic labeling achieves the goal of early intervention without subjecting these persons to the potentially negative insurance, employment, social, and psychological consequences of a diagnosis of diabetes mellitus.