Background: Both epicardial and tissue level parfuslon have been related to cliolcaJ outcomes in the setting of acute myocardial infarction (AMI), and the performance of adjunctive/ rescue parcutaneous intervention may alter clinical outcomes after thrombolytic administration. Objectives & Methods: The goal of this study was to develop a simple, broadly applicable method that integrates epicardial and tissue level perfusion both before and after PCI to arrive at a single angiographic risk score (ARS) in patients undergoing PCI after thrembolysis. The anglographic risk score is the arithmetic sum of the TIMI Flow Grade (0-3) added to the TIMI Myocardial Perfusion Grade (0-3) before and after PCI (total possible score of 012). This risk score was evaluated in patients from the LIMIT AMI trial of tPA monotherapy vs tPA plus rhuMAb CD18. Infarct size was assessed using 120-216 hr post-AMI SPECT Technetium-99m Sestamibi data. Results: Those patients with an anglographic risk score in the lowest group (0-6) had a risk of 30 day death or MI of 9.3% (5/54), whereas those with an ARS of 7-12 had a risk of 1.3% (1/79)(p=0.04). There were no deaths or recurrent MIs among patients with a risk score greater than 10. Likewise, larger SPECT infarct sizes were observed among patients with an ARS of 0-6 (22.6% + 20.4%, n=53) compared to those patients with an ARS of 7-12 (12.3% + 14,3%, n=71, p--0.001). In a second analysis, data from patients who did not undergo PCI was incorporated by using the final TIMI Flow Grade and the final TIMJ Myocardial Peffusion Grade on diagnostic arteriography instead of the post PCI values, and similar results were seen: the risk of 30 day death or MI was 11.7% (11/ 94) for ARS of 0-6, whereas it was 4.2% (6/143) for ARS of 7-12. SPECT infarct sizes were larger for ARS of 0-6 (21.0 + 19.0, n=84) vs ARS of 7-12 (11.8 + 15.2, n=127, p=0.0001). Conclusione: The angiographic risk score integrates indexes of epicardial and tissue level perfusion before and after PCI or at the end of diagnostic cardiac catheterization to arrive at a single risk estimate that is associated with infarct size and 30 day death or Ml. Failure to achieve an ARS of > 6 is associated with a doubling of infarct size.

To the Editor: The Chief Medical Officers Roundtable (CMOR), of which we are members, welcomes the Perspective article by Eichler et al. (Oct. 24 issue),(1) who are representatives of the European Medicines Agency (EMA), on access to patient-level trial data. CMOR formulates positions on medical topics, and its members include chief medical officers of major biopharmaceutical companies. CMOR supports a transparent, harmonized process for access to patient-level clinical trial data. Any approach to clinical trial data sharing must be in the interest of patients. Data sharing should be based on two tenets. First, principles should apply uniformly to all who ...

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal

e17532 Background: Treatment options and overall survival (OS) rates for pts with mCRC have increased markedly over the past decade. However, the variability in OS across TCs, and possible contributing factors (measured and unmeasured), remain unclear. We present an analysis from the BRiTE OCS assessing variability in OS as a function of TC, and sought to identify site factors that may predict better outcomes. Methods: BRiTE enrolled 1,953 pts with mCRC receiving a first-line BV-based regimen, from 248 U.S. sites, mostly community practices (Grothey et al. J Clin Oncol. 2008 26:5326). A Cox proportional hazard model was used to identify predictors of OS (age, PS, albumin, alkaline phosphatase, site of primary tumor) and calculate the expected number of deaths (E) compared to the observed number of deaths (O) within each TC. The ratio O/E was calculated and its distribution is presented. Sites with high O/E (top 25%) vs low O/E (lowest 25%) were titled “worst” (W) and “best” (B), respectively. B and W sites were compared by type (academic vs community, hospital vs clinic, urban vs rural), number of pts treated, choice of first-line chemotherapy, postprogression (PD) therapy, and duration of BV. TCs with ≥3 pts were included in the analysis (198). Results: Significant variation in the O/E ratio was observed across TCs ( Table ). The differences between W and B TCs were that pts at W TCs were less likely to receive a first-line oxali containing regimen (65% vs 67%), had shorter overall duration of BV (8 m vs 12 m) and were less likely to use BV following PD (33% vs 39%). Measured site, pt, and treatment variables explained ∼7% of the variability in O/E, suggesting most TC variability was due to unmeasured factors. Conclusions: Significant variability in OS exists across BRiTE TCs, which appears partly related to the specific therapies received by pts. Further work is needed to determine whether W TCs can be optimized and improve outcomes in pts with mCRC. [Table: see text] [Table: see text]

Pulmonary edema is a life-threatening complication of critical illness. Identification of the underlying mechanisms of pulmonary edema is a prerequisite for the development of adequate treatment. The initial description of fluid transportation across capillaries (Starling's law) while of critical importance, did not provide full insight into the underlying pathophysiology of vascular leakage. Pulmonary edema can be differentiated into two distinct categories based on the Starling theory; the high-permeability type is attributed to inflammatory changes occurring in conditions such as the adult respiratory distress syndrome (ARDS) and the cardiogenic type is characterized by an imbalance in the Starling hydrostatic forces and occurs in acute or decompensated heart failure. However, it has long been recognized that there is significant overlap between the various types of pulmonary edema, raising important questions regarding the role of novel mechanisms that may contribute to the development of interstitial and alveolar leakage. Recently, several studies on VEGF, an angiogenic growth factor which affects endothelial permeability, have identified this molecule as a potential regulator of vascular leakage and repair in pulmonary edema. We review here the underlying the mechanisms by which VEGF may do this and will discuss the still unanswered questions regarding vascular pharmacology in the setting of pulmonary edema.

The calculation of the expected net present value of a clinical development program involves the integration of future outcomes with their timing, cash flows, and associated probabilities, both subjective and relative frequency. As applied to clinical trials, the outcomes are the clinical trial results, typically timed at the completion of the trial. When the trial design includes interim analyses with the possibility of early trial stopping with an efficacy or futility conclusion, we show that the expected net present value of the program can be meaningfully influenced through the inclusion of early stopping times and probabilities in the expected net present value calculations. This approach can be applied prior to the start of the trial, and it can also be applied during the course of the trial. In the latter case, given thai interim analyses have been passed, the trial-stopping probabilities change, with resulting effects on the expected net present value. In both cases, the improved expected net present value figures should lead to better portfolio decisions.

BackgroundAppropriate utilization of acute reperfusion therapy is not a national performance measure for ST-elevation myocardial infarction at this time, and the extent of its contemporary use among ideal patients is unknown.MethodsFrom the National Registry of Myocardial Infarction, we identified 238,291 patients enrolled from June 1994 to May 2003 who were ideally suited for acute reperfusion therapy with fibrinolytic therapy or primary percutaneous coronary intervention. We determined rates of not receiving therapy across 3 time periods (June 1994-May 1997, June 1997-May 2000, June 2000-May 2003) and evaluated factors associated with underutilization.ResultsThe proportion of ideal patients not receiving acute reperfusion therapy decreased by one half throughout the past decade (time period 1: 20.6%; time period 2: 11.4%; time period 3: 11.6%; P <.001). Utilization remained significantly lower in key subgroups in the most recent time period: those without chest pain (odds ratio [OR] 0.29; 95% confidence interval [CI], 0.27-0.32); those presenting 6 to 12 hours after symptom onset (OR 0.57; 95% CI, 0.52-0.61); those 75 years or older (OR 0.63 compared with patients <55 years old; 95% CI, 0.58-0.68); women (OR 0.88; 95% CI, 0.84-0.93); and non-whites (OR 0.90; 95% CI, 0.83-0.97).ConclusionsUtilization of acute reperfusion therapy in ideal patients has improved over the last decade, but more than 10% remain untreated. Measuring and improving its use in this cohort represents an important opportunity to improve care.

The aim of the present study was to predict which patients with severe or difficult-to-treat asthma are at highest risk for healthcare utilisation can be predicted so as to optimise clinical management. Data were derived from 2,821 adults with asthma enrolled in The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. Multiple potential predictors were assessed at baseline using a systematic algorithm employing stepwise logistic regression. Outcomes were asthma-related hospitalisations or emergency department (ED) visits within 6 months following baseline. Overall, 239 subjects (8.5%) reported hospitalisation or ED visits at follow-up. Predictors retained after multivariate analysis were as follows: younger age; female sex; non-white race; body mass index ≥35 kg·m-2; post-bronchodilator per cent predicted forced vital capacity <70%; history of pneumonia; diabetes; cataracts; intubation for asthma; and three or more steroid bursts in the prior 3 months. A final risk score derived from the logistic regression model ranged from 0–18 and was highly predictive (c-index: 0.78) of hospitalisation or ED visits. This tool was re-tested in a prospective validation using outcomes at 12- to 18-months follow-up among the same cohort (c-index: 0.77). The risk score derived is a clinically useful tool for assessing the likelihood of asthma-related hospitalisation or emergency department visits in adults with severe and difficult-to-treat asthma.

Background: Although increased attention has been paid to sex and racial differences in the management of myocardial infarction, it is unknown whether these differences have narrowed over time.Methods: With the use of data from the National Registry of Myocardial Infarction, we examined sex and racial differences in the treatment of patients who were deemed to be "ideal candidates'' for particular treatments and in deaths among 598,911 patients hospitalized with myocardial infarction between 1994 and 2002.Results: In the unadjusted analysis, sex and racial differences were observed for rates of reperfusion therapy (for white men, white women, black men, and black women: 86.5, 83.3, 80.4, and 77.8 percent, respectively; P<0.001), use of aspirin (84.4, 78.7, 83.7, and 78.4 percent, respectively; P<0.001), use of beta-blockers (66.6, 62.9, 67.8, and 64.5 percent; P<0.001), and coronary angiography (69.1, 55.9, 64.0, and 55.0 percent; P<0.001). After multivariable adjustment, racial and sex differences persisted for rates of reperfusion therapy (risk ratio for white women, black men, and black women: 0.97, 0.91, and 0.89, respectively, as compared with white men) and coronary angiography (relative risk, 0.91, 0.82, and 0.76) but were attenuated for the use of aspirin (risk ratio, 0.97, 0.98, and 0.94) and beta-blockers (risk ratio, 0.98, 1.00, and 0.96); all risks were unchanged over time. Adjusted in-hospital mortality was similar among white women (risk ratio, 1.05; 95 percent confidence interval, 1.03 to 1.07) and black men (risk ratio, 0.95; 95 percent confidence interval, 0.89 to 1.00), as compared with white men, but was higher among black women (risk ratio, 1.11; 95 percent confidence interval, 1.06 to 1.16) and was unchanged over time.Conclusions: Rates of reperfusion therapy, coronary angiography, and in-hospital death after myocardial infarction, but not the use of aspirin and beta-blockers, vary according to race and sex, with no evidence that the differences have narrowed in recent years.

To the Editor: Hyperglycemia, with or without pre-existing diabetes mellitus, is associated with adverse outcomes in patients with acute coronary syndromes ([1][1]). Whereas blood glucose levels (BGLs) ≥200 mg/dl are associated with adverse outcomes after acute myocardial infarction (AMI), the

Background Racial differences in reperfusion therapy use among patients hospitalized with myocardial infarction (MI) have been previously reported as national phenomenon. However, it is unclear whether racial differences in treatment vary by region.Methods Using data from the National Registry of Myocardial Infarction-2 and -3, a cohort of patients hospitalized with MI in the United States between 1994 and 2000, we sought to determine whether racial differences in reperfusion therapy use varied by geographic region in patients eligible for reperfusion therapy with no clinical contraindications to treatment (n = 204230).Results Black patients had lower crude rates of reperfusion therapy than white patients (66.5% vs 69.9%, -3.3% racial difference, 99% Cl -4.4% to -2.2%) overall. However, racial differences in reperfusion therapy use varied by geographic region. Reperfusion therapy rates were similar for black patients and white patients in the Northeast (67.9% black vs 65.3% white, +2.7% racial difference, 99% Cl -0.5% to 5.8%) and statistically comparable for patients in the Midwest (68.3% black vs 69.0% white, -0.7% racial difference, 99% Cl -2.9% to 1.5%) and West (70.7% black vs 72.6% white, -1.9% racial difference, 99% Cl -5.1% to 1.2%). Racial differences in reperfusion therapy use were greatest for patients hospitalized in the South (64.5% black vs 71.7% white, -7.1% racial difference, 99% Cl -8.7% to -5.6%). Racial differences were reduced, but geographic variations in racial differences persisted after multivariable adjustment.Conclusions Lower rates of reperfusion therapy use among black patients with MI do not reflect a national pattern of racial differences in treatment, but a practice pattern predominantly attributable to the South.

BACKGROUND Practice guidelines for acute ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) recommend similar therapies and interventions, but differences in patterns of care between MI categories have not been well described in contemporary practice. METHODS In-hospital treatments with similar recommendations from practice guidelines were compared with outcomes in 185 968 eligible patients (without listed contraindications) with STEMI (n = 53 417; 29%) vs NSTEMI (n = 132 551; 71%) from 1247 US hospitals participating in the National Registry of Myocardial Infarction 4 between July 1, 2000, and June 30, 2002. Hierarchical logistic regression modeling was used to determine adjusted differences in treatment patterns in MI categories. RESULTS Unadjusted in-hospital mortality rates were high for NSTEMI (12.5%) and STEMI (14.3%), and the use of guideline-recommended medications and interventions was suboptimal in both categories of patients with MI. The adjusted likelihood of receiving early (within 24 hours of presentation) aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors was higher in patients with STEMI. Similar patterns of care were noted at hospital discharge: the adjusted likelihood of receiving aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, lipid-lowering agents, smoking cessation counseling, and cardiac rehabilitation referral was higher in patients with STEMI. CONCLUSIONS Evidence-based medications and lifestyle modification interventions were used less frequently in patients with NSTEMI. Quality improvement interventions designed to narrow the gaps in care between NSTEMI and STEMI and to improve adherence to guidelines for both categories of patients with MI may reduce the high mortality rates associated with acute MI in contemporary practice.

OBJECTIVES:Although cross-sectional and prospective studies have shown that the white blood cell (WBC) count is associated with long-term mortality for patients with ischemic heart disease, the role of the WBC count as an independent predictor of short-term mortality in patients with acute myocardial infarction (AMI) has not been examined as extensively. The objective of this study was to determine whether the WBC count is associated with in-hospital mortality for patients with ischemic heart disease after controlling for potential confounders.METHODS:From July 31, 2000, to July 31, 2001, the National Registry of Myocardial Infarction 4 enrolled 186,727 AMI patients. A total of 115,273 patients were included in the analysis.RESULTS:WBC counts were subdivided into intervals of 1,000/mL, and in-hospital mortality rates were determined for each interval. The distribution revealed a J-shaped curve. Patients with WBC counts >5,000/mL were subdivided into quartiles, whereas patients with WBC counts <5,000/mL were assigned to a separate category labeled "subquartile" and were analyzed separately. A linear increase in in-hospital mortality by WBC count quartile was found. The unadjusted odds ratio (OR) for the fourth versus the first quartile showed strong associations with in-hospital mortality among the entire population and by gender: 4.09 (95% confidence interval [95% CI] = 3.83 to 4.73) for all patients, 4.31 (95% CI = 3.93 to 4.73) for men, and 3.65 (95% CI = 3.32 to 4.01) for women. Following adjustment for covariates, the magnitude of the ORs attenuated, but the ORs remained highly significant (OR, 2.71 [95% CI = 2.53 to 2.90] for all patients; OR, 2.87 [95% CI = 2.59 to 3.19] for men; OR, 2.61 [95% CI = 2.36 to 2.99] for women). Reperfused patients had consistently lower in-hospital mortality rates for all patients and by gender (p < 0.0001).CONCLUSIONS:The WBC count is an independent predictor of in-hospital AMI mortality and may be useful in assessing the prognosis of AMI in conjunction with other early risk-stratification factors. Whether elevated WBC count is a marker of the inflammatory process or is a direct risk factor for AMI remains unclear. Given the simplicity and availability of the WBC count, the authors conclude that the WBC count should be used in conjunction with other ancillary tests to assess the prognosis of a patient with AMI.

Background Both epicardial and myocardial perfusion have been associated with clinical outcomes in the setting of ST elevation myocardial infarction (STEMI), and the performance of adjunctive/rescue percutaneous coronary intervention (PCI) may further improve clinical outcomes after fibrinolytic administration.Methods The goal was to develop a simple, broadly applicable angiographic metric that takes into account indices of epicardial and myocardial perfusion both before and after PCI to arrive at a single perfusion grade in patients undergoing cardiac catheterization after fibrinolysis. The angiographic perfusion score (APS) is the sum of the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG; 0-3) added to the TIMI myocardial perfusion grade (TMPG; 0-3) before and after PCI (total possible grade, 0-12). Failed perfusion was defined as an APS of 0 to 3, partial perfusion was defined as an APS of 4 to 9, and full perfusion was defined as an APS of 10 to 12. The APS was evaluated in patients from the Double-blind, Placebo-contolled, Multicenter Angiographic Trial of Rhumab CD18 in Acute Myocardial Infarction (LIMIT-AMI; n = 394) and Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction-Thrombolysis In Myocardial Infarction (ENTIRE-TIMI) 23 trials (n = 483), and infarct size (120-216 hours after AMI SPECT Technetium-99m Sestamibi data) was assessed in the LIMIT-AMI trial.Results The APS was associated with the incidence of death or myocardial infarction (failed, 16.7% [n = 18]; partial, 2.5% [n = 155]; full, 2.4% [n = 82]; P=.039 for trend) and larger SPECT infarct sizes (failed, median 39% [n = 10]; partial, 12% [n = 79]; and full, 8% [n 35]; P =.002). No patient with full APS died, whereas the mortality rate was 11.1% in patients with a failed APS (P=.03).Conclusions The APS combines grades of epicardial and tissue level perfusion before and after PCI or at the end of diagnostic cardiac catheterization to arrive at a single angiographic variable that is associated with infarct size and the rates of 30-day death or MI. Partial or full angiographic perfusion scores are associated with a halving of infarct size, and no patients with full angiographic perfusion died.

BACKGROUND:Prior studies have suggested that young blacks with acute myocardial infarction (AMI) may have higher hospital mortality rates than whites of similar age. However, the influence of age and race on short-term death has not been explored in detail. We examined the relation of age and race on short-term death in a large AMI population and ascertained the factors that may have contributed to differences in mortality rates. METHODS:We compared the crude and adjusted hospital mortality rates stratified by age among 40,903 blacks and 501,995 whites with AMI enrolled in the National Registry of Myocardial Infarction-2 in 1482 participating US hospitals from June 1994 through March 1998. RESULTS:Overall crude mortality was lower among blacks compared with whites (10.9% vs 12.0%, P <.0001). However, blacks had a significantly higher crude mortality rate compared with the whites in the age groups <65 years (<45 years, and 5-year age groups between 45 and 64 years). There was a statistically significant interaction between age and black race on hospital death (P value for interaction <.001). Each 5-year decrement in age from 85 years was associated with 7.2% higher odds of death in blacks compared with whites (95% CI, 5.7% to 7.6%). After adjusting for differences in the baseline, clinical presentation, early treatment, and hospital characteristics, 5-year decrements in age was still associated with increases in the odds for death in blacks compared with whites (5.4%; 95% CI, 3.6% to 7.2%). This interaction between age and black race was present in both sexes but was stronger among men. CONCLUSIONS:Blacks younger than 65 years had higher hospital mortality rates compared with whites hospitalized for AMI, and decreasing age was associated with progressively higher risk of hospital death for blacks. Differences in the clinical presentation, early treatment, and hospital characteristics could only partly explain this age-race interaction.

Aims Interpreting the results and practice implications of clinical studies requires accurate characterisation of the baseline risk of the population. We evaluated the Thrombolysis in Myocardial Infarction (TIMI) risk score for STEMI as a too[ to describe and compare the risk profile of populations enrolled in three clinical trials (InTIME-II, ASSENT-2 and MAGIC) and the National Registry of Myocardial Infarction.Methods and Results The risk score was calculated for each patient (N = 1211 085) and the frequency distribution plotted for each population. The Risk Score Profiles were compared using the Kolmogorov-Smirnov test. The Risk Score Profile demonstrated a striking concordance between the baseline risk of patients in InTIME-II and ASSENT-2 (median scores in each = 3[1,4], P = 0.11). In contrast, the distributions in MAGIC (designed to enroll high risk) and NRMI (registry) were shifted significantly toward higher risk (median scores = 4[3, 5] for MAGIC and 4[2,6] in NRMI, P < 0.0001 for each vs. InTIME-II). A graded relationship between the risk score and mortality was evident in each study (P < 0.0001).Conclusions The frequency distribution of the TIMI Risk Score, or similar tools for risk assessment, may be used to quantify and readily compare the risk profile of populations enrolled in clinical studies. (C) 2004 Published by Elsevier Ltd on behalf of The European Society of Cardiology.