Early diagnosis of cutaneous melanoma: revisiting the ABCD criteria

Context  The incidence of cutaneous melanoma has increased over the past several decades, making its early diagnosis a continuing public health priority. The ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) acronym for the appraisal of cutaneous pigmented lesions was devised in 1985 and has been widely adopted but requires reexamination in light of recent data regarding the existence of small-diameter (6 mm) melanomas. Evidence Acquisition  Cochrane Library and PubMed searches for the period 1980-2004 were conducted using search terms ABCD and melanoma and small-diameter melanoma. Bibliographies of retrieved articles were also used to identify additional relevant information. Evidence Synthesis  Available data do not support the utility of lowering the diameter criterion of ABCD from the current greater than 6 mm guideline. However, the data support expansion to ABCDE to emphasize the significance of evolving pigmented lesions in the natural history of melanoma. Physicians and patients with nevi should be attentive to changes (evolving) of size, shape, symptoms (itching, tenderness), surface (especially bleeding), and shades of color. Conclusions  The ABCD criteria for the gross inspection of pigmented skin lesions and early diagnosis of cutaneous melanoma should be expanded to ABCDE (to include "evolving"). No change to the existing diameter criterion is required at this time.      

Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial

Context  No specifically designed studies have addressed the role of the glycoprotein IIb/IIIa inhibitor abciximab in patients with non–ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) after pretreatment with 600 mg of clopidogrel. Objective  To assess whether abciximab is associated with clinical benefit in high-risk patients with ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. Design, Setting, and Patients  International, multicenter, randomized, double-blind, placebo-controlled study conducted from March 2003 through December 2005, enrolling 2022 patients (mean age, 66 years) with non–ST-segment elevation ACS undergoing PCI. Interventions  Patients were assigned to receive either abciximab (0.25 mg/kg of body weight bolus, followed by a 0.125-µg/kg per minute [maximum, 10 µg/min] infusion for 12 hours, plus heparin, 70 U/kg of body weight) or placebo (placebo bolus and infusion of 12 hours, plus heparin bolus, 140 U/kg). All patients received clopidogrel, 600 mg, at least 2 hours prior to the procedure, as well as 500 mg of oral or intravenous aspirin. Main Outcome Measures  The primary end point was a composite of death, myocardial infarction, or urgent target vessel revascularization occurring within 30 days after randomization; secondary end points were rates of in-hospital major and minor bleeding. Results  Of 2022 patients enrolled, 1012 were assigned to abciximab and 1010 to placebo. The primary end point was reached in 90 patients (8.9%) assigned to abciximab vs 120 patients (11.9%) assigned to placebo, a 25% reduction in risk with abciximab (relative risk [RR], 0.75; 95% CI, 0.58-0.97; P = .03). Among patients without an elevated troponin level, there was no difference in the incidence of primary end point events between the abciximab group (23/499 patients [4.6%]) and the placebo group (22/474 patients [4.6%]) (RR, 0.99; 95% CI, 0.56-1.76; P = .98), whereas among patients with an elevated troponin level, the incidence of events was significantly lower in the abciximab group (67/513 patients [13.1%]) compared with the placebo group (98/536 patients [18.3%]), which corresponds to an RR of 0.71 (95% CI, 0.54-0.95; P = .02) (P = .07 for interaction). There were no significant differences between the 2 groups regarding the risk of major and minor bleeding as well as need for transfusion. Conclusions  Abciximab reduces the risk of adverse events in patients with non–ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel. The benefits provided by abciximab appear to be confined to patients presenting with an elevated troponin level. Trial Registration  ClinicalTrials.gov Identifier: NCT00133003      

Terminal complement blockade with pexelizumab during coronary artery bypass graft surgery requiring cardiopulmonary bypass: a randomized trial

Context  Inflammation and ischemia-reperfusion injury during coronary artery bypass graft (CABG) surgery requiring cardiopulmonary bypass are associated with postoperative myocardial infarction (MI) and mortality. Objective  To determine the efficacy and safety of pexelizumab, a C5 complement inhibitor, in reducing perioperative MI and mortality in CABG surgery. Design, Setting, and Participants  A randomized, double-blind, placebo-controlled trial, including 3099 patients (=" BORDER="0"> 18 years) undergoing CABG surgery with or without valve surgery at 205 hospitals in North America and Western Europe from January 2002 to February 2003. Interventions  Patients were randomly assigned to receive intravenous pexelizumab (2.0 mg/kg bolus plus 0.05 mg/kg per hour for 24 hours; n = 1553) or placebo (n = 1546) 10 minutes before undergoing the procedure. Main Outcome Measures  The primary composite end point was the incidence of death or MI within 30 days of randomization in those undergoing CABG surgery only (n = 2746). Secondary analyses included the intent-to-treat analyses of death or MI composite at days 4 and 30 in all 3099 study patients. Results  After 30 days, 134 (9.8%) of 1373 of patients receiving pexelizumab vs 161 (11.8%) of 1359 of patients receiving placebo (relative risk, 0.82; 95% confidence interval, 0.66-1.02; P = .07) died or experienced MI in the CABG surgery only population. In the intent-to-treat analyses, 178 (11.5%) of 1547 patients receiving pexelizumab vs 215 (14.0%) of 1535 receiving placebo died or experienced MI (relative risk, 0.82; 95% confidence interval, 0.68-0.99; P = .03). The trial was not powered to detect a reduction in mortality alone. Conclusions  Compared with placebo, pexelizumab was not associated with a significant reduction in the risk of the composite end point of death or MI in 2746 patients who had undergone CABG surgery only but was associated with a statistically significant risk reduction 30 days after the procedure among all 3099 patients undergoing CABG with or without valve surgery.      

Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial

Context  Ranolazine is a novel antianginal agent that reduces ischemia in patients with chronic angina but has not been studied in patients with acute coronary syndromes (ACS). Objective  To determine the efficacy and safety of ranolazine during long-term treatment of patients with non–ST-elevation ACS. Design, Setting, and Patients  A randomized, double-blind, placebo-controlled, multinational clinical trial of 6560 patients within 48 hours of ischemic symptoms who were treated with ranolazine (initiated intravenously and followed by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching placebo (n = 3281), and followed up for a median of 348 days in the Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007. Main Outcome Measures  The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (MI), or recurrent ischemia through the end of study. The major safety end points were death from any cause and symptomatic documented arrhythmia. Results  The primary end point occurred in 696 patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P = .11). The major secondary end point (cardiovascular death, MI, or severe recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and 625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50). Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85-1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430 [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76-0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10 patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P = .84). No difference in total mortality was observed with ranolazine compared with placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91). Conclusions  The addition of ranolazine to standard treatment for ACS was not effective in reducing major cardiovascular events. Ranolazine did not adversely affect the risk of all-cause death or symptomatic documented arrhythmia. Our findings provide support for the safety and efficacy of ranolazine as antianginal therapy. Trial Registration  clinicaltrials.gov Identifier: NCT00099788      

Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke

Context  Recent studies suggest that factors other than the degree of carotid stenosis are involved in ischemic stroke pathogenesis, especially modifications of plaque composition and related complications. Objective  To examine the role of carotid plaque rupture and thrombosis in ischemic stroke pathogenesis in patients undergoing carotid endarterectomy, excluding those with possible cardiac embolization or with severe stenosis of the circle of Willis. Design, Setting, and Patients  A total of 269 carotid plaques selected from an Interinstitutional Carotid Tissue Bank were studied by histology after surgical endarterectomy between January 1995 and December 2002. A total of 96 plaques were from patients with ipsilateral major stroke, 91 plaques from patients with transient ischemic attack (TIA), and 82 plaques from patients without symptoms. Main Outcome Measures  Differences in the frequency of thrombosis, cap rupture, cap erosion, inflammatory infiltrate, and major cardiovascular risk factors between study groups. Results  A thrombotically active carotid plaque associated with high inflammatory infiltrate was observed in 71 (74.0%) of 96 patients with ipsilateral major stroke (and in all 32 plaques from patients operated within 2 months of symptom onset) compared with 32 (35.2%) of 91 patients with TIA (P < .001) or 12 (14.6%) of 82 patients who were without symptoms (P < .001). In addition, a fresh thrombus was observed in 53.8% of patients with stroke operated 13 to 24 months after the cerebrovascular event. An acute thrombus was associated with cap rupture in 64 (90.1%) of 71 thrombosed plaques from patients with stroke and with cap erosion in the remaining 7 cases (9.9%). Ruptured plaques of patients affected by stroke were characterized by the presence of a more severe inflammatory infiltrate, constituted by monocytes, macrophages, and T lymphocyte cells compared with that observed in the TIA and asymptomatic groups (P = .001). There was no significant difference between groups in major cardiovascular risk factors. Conclusion  These results demonstrate a major role of carotid thrombosis and inflammation in ischemic stroke in patients affected by carotid atherosclerotic disease.      

Preoperative intensive inspiratory muscle training to prevent postoperative pulmonary complications in high-risk patients undergoing CABG surgery: a randomized clinical trial

Context  Postoperative pulmonary complications (PPCs) after coronary artery bypass graft (CABG) surgery are a major source of morbidity and mortality, and increase length of hospital stay and resource utilization. The prehospitalization period before CABG surgery may be used to improve a patient's pulmonary condition. The efficacy of preoperative inspiratory muscle training (IMT) in reducing the incidence of PPCs in high-risk patients undergoing CABG surgery has not yet been determined. Objective  To evaluate the prophylactic efficacy of preoperative IMT on the incidence of PPCs in high-risk patients scheduled for elective CABG surgery. Design, Setting, and Patients  A single-blind, randomized clinical trial conducted at the University Medical Center Utrecht, Utrecht, the Netherlands, with enrollment between July 2002 and August 2005. Of 655 patients referred for elective CABG surgery, 299 (45.6%) met criteria for high risk of developing PPCs, of whom 279 were enrolled and followed up until discharge from hospital. Intervention  Patients were randomly assigned to receive either preoperative IMT (n = 140) or usual care (n = 139). Both groups received the same postoperative physical therapy. Main Outcome Measures  Incidence of PPCs, especially pneumonia, and duration of postoperative hospitalization. Results  Both groups were comparable at baseline. After CABG surgery, PPCs were present in 25 (18.0%) of 139 patients in the IMT group and 48 (35.0%) of 137 patients in the usual care group (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.30-0.92). Pneumonia occurred in 9 (6.5%) of 139 patients in the IMT group and in 22 (16.1%) of 137 patients in the usual care group (OR, 0.40; 95% CI, 0.19-0.84). Median duration of postoperative hospitalization was 7 days (range, 5-41 days) in the IMT group vs 8 days (range, 6-70 days) in the usual care group by Mann-Whitney U statistic (z = –2.42; P = .02). Conclusion  Preoperative IMT reduced the incidence of PPCs and duration of postoperative hospitalization in patients at high risk of developing a pulmonary complication undergoing CABG surgery. Trial Registration  isrctn.org Identifier: ISRCTN17691887      

Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial

Context  The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns. Objective  To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an -glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT). Design, Setting, and Participants  International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years. Intervention  Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714). Main Outcome Measures  The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (=" BORDER="0">140/90 mm Hg). Results  Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P = .03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P = .02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P = .006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P = .02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P = .004) associated with acarbose treatment was still statistically significant. Conclusion  This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.      

Mechanical reperfusion in patients with acute myocardial infarction presenting more than 12 hours from symptom onset: a randomized controlled trial

Context  No specifically designed studies have addressed the role of primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction (STEMI) presenting more than 12 hours after symptom onset. Current guidelines do not recommend reperfusion treatment in these patients. Objective  To assess whether an immediate invasive treatment strategy is associated with a reduction of infarct size in patients with acute STEMI, presenting between 12 and 48 hours after symptom onset, vs a conventional conservative strategy. Design, Setting, and Patients  International, multicenter, open-label, randomized controlled trial conducted from May 23, 2001, to December 15, 2004, of 365 patients aged 18 to 80 years without persistent symptoms admitted with the diagnosis of acute STEMI between 12 and 48 hours after symptom onset. Interventions  Random assignment to either an invasive strategy (n=182) based predominantly on coronary stenting with abciximab or a conventional conservative treatment strategy (n=183). Main Outcome Measures  The primary end point was final left ventricular infarct size according to single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 347 patients (95.1%). Secondary end points included composite of death, recurrent MI, or stroke at 30 days. Results  The final left ventricular infarct size was significantly smaller in patients assigned to the invasive group (median, 8.0%; interquartile range [IQR], 2.0%-15.8%) vs those assigned to the conservative group (median, 13.0%; IQR, 3.0%-27.0%; P<.001). The mean difference in final left ventricular infarct size between the invasive and conservative groups was –6.8% (95% confidence interval [CI], –10.2% to –3.5%). The secondary end points of death, recurrent MI, or stroke at 30 days occurred in 8 patients in the invasive group (4.4%) and 12 patients in the conservative group (6.6%) (relative risk, 0.67; 95% CI, 0.27-1.62; P = .37). Conclusion  An invasive strategy based on coronary stenting with adjunctive use of abciximab reduces infarct size in patients with acute STEMI without persistent symptoms presenting 12 to 48 hours after symptom onset.      

Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial

Context  Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents. Objective  To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI. Design, Setting, and Patients  This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006. Interventions  Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset. Main Outcome Measures  The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90. Results  No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91). Conclusion  In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab. Trial Registration  clinicaltrials.gov Identifier: NCT00091637      

Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation

Context  Screening of patients with venous thromboembolism (VTE) for thrombophilic risk factors is common clinical practice. Because of the large number of risk factors, assessing the risk of recurrence in an individual patient is complex. A method covering multicausal thrombophilia is therefore required. Objective  To investigate the relationship between recurrence of VTE and a simple global coagulation assay measuring thrombin generation. Design, Setting, and Participants  Prospective cohort study of 914 patients with first spontaneous VTE who were followed up for an average of 47 months after discontinuation of vitamin K antagonist therapy. The study was conducted at the Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, between July 1992 and July 2005. Thrombin generation was measured by a commercially available assay system. Patients with a previous or secondary VTE; antithrombin, protein C, or protein S deficiencies; presence of lupus anticoagulant; cancer; or pregnancy were excluded. Main Outcome Measure  Objectively documented symptomatic recurrent VTE. Results  Venous thromboembolism recurred in 100 patients (11%). Patients without recurrent VTE had lower thrombin generation than patients with recurrence (mean [SD], 349.2 [108.0] nM vs 419.5 [110.5] nM, respectively; P<.001). Compared with patients who had thrombin generation greater than 400 nM, the relative risk (RR) of recurrence was 0.42 (95% confidence interval [CI], 0.26-0.67; P<.001) in patients with values between 400 nM and 300 nM; for patients with lower values, the RR was 0.37 (95% CI, 0.21-0.66; P = .001). After 4 years, the probability of recurrence was 6.5% (95% CI, 4.0%-8.9%) among patients with thrombin generation less than 400 nM compared with 20.0% (95% CI, 14.9%-25.1%) among patients with higher values (P<.001). Patients with thrombin generation less than 400 nM, representing two thirds of patients, had a 60% lower RR of recurrence than those with greater values (RR, 0.40; 95% CI, 0.27-0.60; P<.001). Conclusion  Measurement of thrombin generation identifies patients at low risk for recurrent VTE.      

Efficacy and safety of pyridoxal 5'-phosphate (MC-1) in high-risk patients undergoing coronary artery bypass graft surgery: the MEND-CABG II randomized clinical trial

Context  Coronary artery bypass graft (CABG) surgery is frequently performed and effective; however, perioperative complications related to ischemia-reperfusion injury, including myocardial infarction (MI), remain common and result in significant morbidity and mortality. MC-1, a naturally occurring pyridoxine metabolite and purinergic receptor antagonist, prevents cellular calcium overload and may reduce ischemia-reperfusion injury. Phase 2 trial data suggest that MC-1 may reduce death or MI in high-risk patients undergoing CABG surgery. Objective  To assess the efficacy and safety of MC-1 administered immediately before and for 30 days after surgery in patients undergoing CABG surgery. Design, Setting, and Participants  The MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II Trial, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, with 3023 intermediate- to high-risk patients undergoing CABG surgery with cardiopulmonary bypass enrolled between October 2006 and September 2007 at 130 sites in Canada, the United States, and Germany. Interventions  Patients received either MC-1, 250 mg/d (n = 1519), or matching placebo (n = 1504) immediately before and for 30 days after CABG surgery. Main Outcome Measures  The primary efficacy outcome was cardiovascular death or nonfatal MI, defined as a creatine kinase (CK) MB fraction of at least 100 ng/mL or new Q waves through postoperative day 30. Results  The primary efficacy outcome occurred in 140 of 1510 patients (9.3%) in the MC-1 group and 133 of 1486 patients (9.0%) in the placebo group (risk ratio, 1.04; 95% confidence interval, 0.83-1.30; P = .76). All-cause mortality was higher among patients assigned to MC-1 than placebo at 4 days (1.0% vs 0.3%; P = .03) but was similar at 30 days (1.9% vs 1.5%; P = .44). There was no difference in the 8- to 24-hour CK-MB area under the curve between the MC-1 and placebo groups (median, 270 [interquartile range, 175-492] vs 268 [interquartile range, 170-456] hours x ng/mL; P = .11). Conclusion  In this population of intermediate- to high-risk patients undergoing CABG surgery, MC-1 did not reduce the composite of cardiovascular death or nonfatal MI. Trial Registration  clinicaltrials.gov Identifier: NCT00402506      

Short-term prognosis after emergency department diagnosis of TIA

Context  Management of patients with acute transient ischemic attack (TIA) varies widely, with some institutions admitting all patients and others proceeding with outpatient evaluations. Defining the short-term prognosis and risk factors for stroke after TIA may provide guidance in determining which patients need rapid evaluation. Objective  To determine the short-term risk of stroke and other adverse events after emergency department (ED) diagnosis of TIA. Design and Setting  Cohort study conducted from March 1997 through February 1998 in 16 hospitals in a health maintenance organization in northern California. Patients  A total of 1707 patients (mean age, 72 years) identified by ED physicians as having presented with TIA. Main Outcome Measures  Risk of stroke during the 90 days after index TIA; other events, including death, recurrent TIA, and hospitalization for cardiovascular events. Results  During the 90 days after index TIA, 180 patients (10.5%) returned to the ED with a stroke, 91 of which occurred in the first 2 days. Five factors were independently associated with stroke: age greater than 60 years (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1-2.7; P = .01), diabetes mellitus (OR, 2.0; 95% CI, 1.4-2.9; P<.001), symptom duration longer than 10 minutes (OR, 2.3; 95% CI, 1.3-4.2; P = .005), weakness (OR, 1.9; 95% CI, 1.4-2.6; P<.001), and speech impairment (OR, 1.5; 95% CI, 1.1-2.1; P = .01). Stroke or other adverse events occurred in 428 patients (25.1%) in the 90 days after the TIA and included 44 hospitalizations for cardiovascular events (2.6%), 45 deaths (2.6%), and 216 recurrent TIAs (12.7%). Conclusions  Our results indicate that the short-term risk of stroke and other adverse events among patients who present to an ED with a TIA is substantial. Characteristics of the patient and the TIA may be useful for identifying patients who may benefit from expeditious evaluation and treatment.      

Relation between operator and hospital volume and outcomes following percutaneous coronary interventions in the era of the coronary stent

Context  Studies have found an association between physician and institution procedure volume for percutaneous coronary interventions (PCIs) and patient outcomes, but whether implementation of coronary stents has allowed low-volume physicians and centers to achieve outcomes similar to their high-volume counterparts is unknown. Objective  To assess the relationship between physician and hospital PCI volumes and patient outcomes following PCIs, given the availability of coronary stents. Design, Setting, and Participants  Analysis of data from Medicare National Claims History files for 167 208 patients aged 65 to 99 years who had PCIs performed by 6534 physicians at 1003 hospitals during 1997. Of these procedures, 57.7% involved coronary stents. Main Outcome Measures  Rates of coronary artery bypass graft (CABG) surgery and 30-day mortality occurring during the index episode of care, stratified by physician and hospital PCI volume. Results  Overall unadjusted rates of CABG during the index hospitalization and 30-day mortality were 1.87% and 3.30%, respectively. After adjustment for case mix, patients treated by low-volume (<30 Medicare procedures) physicians had an increased risk of CABG vs patients treated by high-volume (>60 Medicare procedures) physicians (2.25% vs 1.55%; P<.001), but there was no difference in 30-day mortality rates (3.25% vs 3.39%; P = .27). Patients treated at low-volume (<80 Medicare procedures) centers had an increased risk of 30-day mortality vs patients treated at high-volume (>160 Medicare procedures) centers (4.29% vs 3.15%; P<.001), but there was no difference in the risk of CABG (1.83% vs 1.83%; P = .96). In patients who received coronary stents, the CABG rate was 1.20% vs 2.78% for patients not receiving stents, and the 30-day mortality rate was 2.83% vs 3.94%. Among patients who received stents, those treated at low-volume centers had an increased risk of 30-day mortality vs those treated at high-volume centers, whereas those treated by low-volume physicians had an increased risk of CABG vs those treated by high-volume physicians. Conclusion  In the era of coronary stents, Medicare patients treated by high-volume physicians and at high-volume centers experience better outcomes following PCIs.      

An international study of patient compliance with hemodialysis

Context  International differences in compliance of patients undergoing hemodialysis are poorly characterized and could contribute to international survival differences. Objective  To compare international differences in patient compliance with hemodialysis treatments. Design  A prospective observational study of patients undergoing hemodialysis in 1995 and a cross-sectional survey of health care professionals caring for hemodialyzed patients in 1996. Setting and Patients  Four dialysis centers in the southeastern United States with 415 patients undergoing hemodialysis, 1 center in Sweden with 84 patients, and 4 centers in Japan with 194 patients participated in the prospective observational study. In the cross-sectional survey, nurses and nephrologists from the United States (n=49), Japan (n=21), and Sweden (n=16) responded to questions regarding the compliance of their patients undergoing hemodialysis. Main Outcome Measures  Percentage of patients who miss a dialysis treatment and number of missed dialysis treatments. Results  Of 415 US patients, 147 missed 699 treatments over a 6-month period (28.1 missed treatments per 100 patient-months or 2.3% of all prescribed treatments). During a 3-month period, there were 0 missed treatments per 100 patient-months for patients from Japan and 0 missed treatments per 100 patient-months for patients from Sweden (P<.001). In the cross-sectional survey, the mean (SD) estimated percentage of patients missing a treatment per month was 4% (3%) for the United States, 0% for Japan, and 0.1% (3%) for Sweden (P<.001). Conclusions  Noncompliance is much more common in US patients undergoing hemodialysis than Swedish and Japanese patients. The implications of these results for international differences in survival deserve further study.      

Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial

Context  The effect of antihypertensive drugs on cardiovascular events in patients with coronary artery disease (CAD) and normal blood pressure remains uncertain. Objective  To compare the effects of amlodipine or enalapril vs placebo on cardiovascular events in patients with CAD. Design, Setting, and Participants  Double-blind, randomized, multicenter, 24-month trial (enrollment April 1999-April 2002) comparing amlodipine or enalapril with placebo in 1991 patients with angiographically documented CAD (>20% stenosis by coronary angiography) and diastolic blood pressure <100 mm Hg. A substudy of 274 patients measured atherosclerosis progression by intravascular ultrasound (IVUS). Interventions  Patients were randomized to receive amlodipine, 10 mg; enalapril, 20 mg; or placebo. IVUS was performed at baseline and study completion. Main Outcome Measures  The primary efficacy parameter was incidence of cardiovascular events for amlodipine vs placebo. Other outcomes included comparisons of amlodipine vs enalapril and enalapril vs placebo. Events included cardiovascular death, nonfatal myocardial infarction, resuscitated cardiac arrest, coronary revascularization, hospitalization for angina pectoris, hospitalization for congestive heart failure, fatal or nonfatal stroke or transient ischemic attack, and new diagnosis of peripheral vascular disease. The IVUS end point was change in percent atheroma volume. Results  Baseline blood pressure averaged 129/78 mm Hg for all patients; it increased by 0.7/0.6 mm Hg in the placebo group and decreased by 4.8/2.5 mm Hg and 4.9/2.4 mm Hg in the amlodipine and enalapril groups, respectively (P<.001 for both vs placebo). Cardiovascular events occurred in 151 (23.1%) placebo-treated patients, in 110 (16.6%) amlodipine-treated patients (hazard ratio [HR], 0.69; 95% CI, 0.54-0.88 [P = .003]), and in 136 (20.2%) enalapril-treated patients (HR, 0.85; 95% CI, 0.67-1.07 [P = .16]. Primary end point comparison for enalapril vs amlodipine was not significant (HR, 0.81; 95% CI, 0.63-1.04 [P = .10]). The IVUS substudy showed a trend toward less progression of atherosclerosis in the amlodipine group vs placebo (P = .12), with significantly less progression in the subgroup with systolic blood pressures greater than the mean (P = .02). Compared with baseline, IVUS showed progression in the placebo group (P<.001), a trend toward progression in the enalapril group (P = .08), and no progression in the amlodipine group (P = .31). For the amlodipine group, correlation between blood pressure reduction and progression was r = 0.19, P = .07. Conclusions  Administration of amlodipine to patients with CAD and normal blood pressure resulted in reduced adverse cardiovascular events. Directionally similar, but smaller and nonsignificant, treatment effects were observed with enalapril. For amlodipine, IVUS showed evidence of slowing of atherosclerosis progression.      

Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials

Context  Although Chlamydia pneumoniae infection has been associated with the initiation and progression of atherosclerosis, results of clinical trials investigating antichlamydial antibiotics as adjuncts to standard therapy in patients with coronary artery disease (CAD) have been inconsistent. Objective  To conduct a meta-analysis of clinical trials of antichlamydial antibiotic therapy in patients with CAD. Data Sources  The MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from 1966 to April 2005 for English-language trials of antibiotic therapy in patients with CAD. Bibliographies of retrieved articles were searched for further studies. Presentations at major scientific meetings (2003-2004) were also reviewed. Search terms included antibacterial agents, myocardial infarction, unstable angina, and coronary arteriosclerosis. Study Selection  Eligible studies were prospective, randomized, placebo-controlled trials of antichlamydial antibiotic therapy in patients with CAD that reported all-cause mortality, myocardial infarction, or unstable angina. Of the 110 potentially relevant articles identified, 11 reports enrolling 19 217 patients were included. Data Extraction  Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, and end points. End points of interest included all-cause mortality, myocardial infarction (MI), and a combined end point of MI and unstable angina. Data Synthesis  Event rates were combined using a random-effects model. Antibiotic therapy had no impact on all-cause mortality among treated vs untreated patients (4.7% vs 4.6%; odds ratio [OR], 1.02; 95% confidence interval [CI], 0.89-1.16; P = .83), on the rates of MI (5.0% vs 5.4%; OR, 0.92; 95% CI, 0.81-1.04; P = .19), or on the combined end point of MI and unstable angina (9.2% vs 9.6%; OR, 0.91; 95% CI, 0.76-1.07; P = .25). Conclusion  Evidence available to date does not demonstrate an overall benefit of antibiotic therapy in reducing mortality or cardiovascular events in patients with CAD.      

Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review,meta-analysis,and meta-regression

Context  The long-term renal prognosis of patients with diarrhea-associated hemolytic uremic syndrome (HUS) remains controversial. Objectives  To quantify the long-term renal prognosis of patients with diarrhea-associated HUS and to identify reasons for different estimates provided in the literature. Data Sources  We searched MEDLINE and Experta Medica (EMBASE) bibliographic databases and conference proceedings, and we contacted experts until February 2003. We also searched the Institute for Scientific Information index and reference lists of all studies that fulfilled our eligibility criteria. The search strategy included the terms hemolytic-uremic syndrome, purpura, thrombotic thrombocytopenic, Escherichia coli O157, longitudinal studies, kidney diseases, hypertension, and proteinuria Study Selection  Any study that followed up 10 or more patients with primary diarrhea-associated HUS for at least 1 year for renal sequelae. Data Extraction  Two authors independently abstracted data on study and patient characteristics, renal measures, outcomes, and prognostic features. Disagreements were resolved by a third author or by consensus. Data Synthesis  Forty-nine studies of 3476 patients with a mean follow-up of 4.4 years (range, 1-22 years at last follow-up) from 18 countries, 1950 to 2001, were summarized. At the time of recruitment, patients were aged 1 month to 18 years. In the different studies, death or permanent end-stage renal disease (ESRD) ranged from 0% to 30%, with a pooled incidence of 12% (95% confidence interval [CI], 10%-15%). A glomerular filtration rate lower than 80 mL/min per 1.73 m², hypertension, or proteinuria was extremely variable and ranged from 0% to 64%, with a pooled incidence of 25% (95% CI, 20%-30%). A higher severity of acute illness was strongly associated with worse long-term prognosis. Studies with a higher proportion of patients with central nervous system symptoms (coma, seizures, or stroke) had a higher proportion of patients who died or developed permanent ESRD at follow-up (explaining 44% of the between-study variability, P = .01). Studies with a greater proportion of patients lost to follow-up also described a worse prognosis (P = .001) because these patients were typically healthier than those followed up. One or more years after diarrhea-associated HUS, patients with a predicted creatinine clearance higher than 80 mL/min per 1.73 m², no overt proteinuria, and no hypertension appeared to have an excellent prognosis. Conclusions  Death or ESRD occurs in about 12% of patients with diarrhea-associated HUS, and 25% of survivors demonstrate long-term renal sequelae. Patients lost to follow-up contribute to worse estimates in some studies. The severity of acute illness, particularly central nervous system symptoms and the need for initial dialysis, is strongly associated with a worse long-term prognosis.      

Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials

Context  Implantable cardioverter defibrillator (ICD) therapy is effective in primary and secondary prevention of sudden cardiac death among patients with prior myocardial infarction and depressed ejection fraction. However, conclusive evidence of survival benefit in patients with nonischemic cardiomyopathy (NICM) is still lacking. Objective  To determine whether ICD therapy reduces all-cause mortality in patients with NICM. Data Sources  MEDLINE (1966-2004), EMBASE (1991-2004), the Cochrane Central Register of Controlled Trials (through first quarter, 2004), reports presented at scientific meetings (2003-2004), and bibliographic review of secondary sources. Search terms included defibrillator, randomized controlled trials, clinical trials, andsudden death. Study Selection  Eligible studies were prospective randomized controlled trials of ICD or combined cardiac resynchronization therapy and defibrillator (CRT-D) vs medical therapy enrolling at least some individuals with NICM and reporting all-cause mortality as an outcome. Of 675 potentially relevant articles screened initially, 8 reports of randomized trials enrolling a total of 2146 patients with NICM were included. Data Extraction  Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, primary end point, mortality of ICD cohort, and mortality of control cohort. Data Synthesis  Five primary prevention trials enrolling 1854 patients with NICM were identified; pooled analysis suggested a significant reduction in total mortality among patients randomized to ICD or CRT-D vs medical therapy (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.55-0.87; P = .002). Mortality reduction remained significant even after elimination of CRT-D trials. Two of the 3 secondary prevention trials presented subgroup estimates for ICD efficacy in NICM. Pooled analysis of these secondary prevention trials (n = 256 patients with NICM) indicated an equivalent but nonsignificant mortality reduction with ICD therapy (RR, 0.69; 95% CI, 0.39-1.24; P = .22). Analysis of all 7 trials combined demonstrated a statistically significant 31% overall reduction in mortality with ICD therapy (RR, 0.69; 95% CI, 0.56-0.86; P = .002). Conclusion  ICD therapy appears to significantly reduce mortality in selected patients with NICM.      

Lipid-lowering therapy and in-hospital mortality following major noncardiac surgery

Context  Cardiovascular complications following major noncardiac surgery are an important source of perioperative morbidity and mortality. Although lipid-lowering medications are considered a key component in the primary and secondary prevention of cardiovascular disease, their potential benefit during the perioperative period is uncertain. Objective  To examine the association between treatment with lipid-lowering medications and in-hospital mortality following major noncardiac surgery. Design, Setting, and Patients  A retrospective cohort study based on hospital discharge and pharmacy records of 780 591 patients aged 18 years or older who underwent major noncardiac surgery from January 1, 2000, to December 31, 2001, at any 1 of 329 hospitals throughout the United States. Only patients who survived through at least the second hospital day were included. Lipid-lowering therapy was defined as use during the first 2 hospital days. Propensity matching was used to adjust for numerous baseline differences. Main Outcome Measure  In-hospital mortality. Results  Of the 780 591 patients, 77 082 patients (9.9%) received lipid-lowering therapy perioperatively and 23 100 (2.96%) died during the hospitalization. Treatment with lipid-lowering agents was associated with lower crude mortality (2.13% vs 3.05%, P<.001). In an analysis using matching by propensity score, 1595 patients (2.18%) treated with lipid-lowering medications died compared with 4158 patients (3.15%) who did not receive therapy or in whom treatment was initiated after the second day (P<.001). After adjusting for residual differences in the propensity matched groups using conditional logistic regression, risk of mortality remained lower among treated patients (adjusted odds ratio [OR], 0.62; 95% confidence interval [CI], 0.58-0.67). Based on this adjusted OR, the number needed to treat to prevent a postoperative death in the propensity matched cohort was 85 (95% CI, 77-98) and varied from 186 among patients at lowest risk to 30 among those with a revised cardiac risk index score of 4 or more. In a further analysis using the entire study cohort and adjusting for quintile of propensity, a significant effect of treatment persisted (adjusted OR, 0.71; 95% CI, 0.67-0.75). Conclusions  Treatment with lipid-lowering agents may reduce risk of death following major noncardiac surgery. Clinical trials are required to confirm this observation.      

Primary care outcomes in patients treated by nurse practitioners or physicians: a randomized trial

Context  Studies have suggested that the quality of primary care delivered by nurse practitioners is equal to that of physicians. However, these studies did not measure nurse practitioner practices that had the same degree of independence as the comparison physician practices, nor did previous studies provide direct comparison of outcomes for patients with nurse practitioner or physician providers. Objective  To compare outcomes for patients randomly assigned to nurse practitioners or physicians for primary care follow-up and ongoing care after an emergency department or urgent care visit. Design  Randomized trial conducted between August 1995 and October 1997, with patient interviews at 6 months after initial appointment and health services utilization data recorded at 6 months and 1 year after initial appointment. Setting  Four community-based primary care clinics (17 physicians) and 1 primary care clinic (7 nurse practitioners) at an urban academic medical center. Patients  Of 3397 adults originally screened, 1316 patients (mean age, 45.9 years; 76.8% female; 90.3% Hispanic) who had no regular source of care and kept their initial primary care appointment were enrolled and randomized with either a nurse practitioner (n = 806) or physician (n = 510). Main Outcome Measures  Patient satisfaction after initial appointment (based on 15-item questionnaire); health status (Medical Outcomes Study Short-Form 36), satisfaction, and physiologic test results 6 months later; and service utilization (obtained from computer records) for 1 year after initial appointment, compared by type of provider. Results  No significant differences were found in patients' health status (nurse practitioners vs physicians) at 6 months (P = .92). Physiologic test results for patients with diabetes (P = .82) or asthma (P = .77) were not different. For patients with hypertension, the diastolic value was statistically significantly lower for nurse practitioner patients (82 vs 85 mm Hg; P = .04). No significant differences were found in health services utilization after either 6 months or 1 year. There were no differences in satisfaction ratings following the initial appointment (P = .88 for overall satisfaction). Satisfaction ratings at 6 months differed for 1 of 4 dimensions measured (provider attributes), with physicians rated higher (4.2 vs 4.1 on a scale where 5 = excellent; P = .05). Conclusions  In an ambulatory care situation in which patients were randomly assigned to either nurse practitioners or physicians, and where nurse practitioners had the same authority, responsibilities, productivity and administrative requirements, and patient population as primary care physicians, patients' outcomes were comparable.