Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial

Context  Pulmonary artery catheters (PACs) have been used to guide therapy in multiple settings, but recent studies have raised concerns that PACs may lead to increased mortality in hospitalized patients. Objective  To determine whether PAC use is safe and improves clinical outcomes in patients hospitalized with severe symptomatic and recurrent heart failure. Design, Setting, and Participants  The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) was a randomized controlled trial of 433 patients at 26 sites conducted from January 18, 2000, to November 17, 2003. Patients were assigned to receive therapy guided by clinical assessment and a PAC or clinical assessment alone. The target in both groups was resolution of clinical congestion, with additional PAC targets of a pulmonary capillary wedge pressure of 15 mm Hg and a right atrial pressure of 8 mm Hg. Medications were not specified, but inotrope use was explicitly discouraged. Main Outcome Measures  The primary end point was days alive out of the hospital during the first 6 months, with secondary end points of exercise, quality of life, biochemical, and echocardiographic changes. Results  Severity of illness was reflected by the following values: average left ventricular ejection fraction, 19%; systolic blood pressure, 106 mm Hg; sodium level, 137 mEq/L; urea nitrogen, 35 mg/dL (12.40 mmol/L); and creatinine, 1.5 mg/dL (132.6 µmol/L). Therapy in both groups led to substantial reduction in symptoms, jugular venous pressure, and edema. Use of the PAC did not significantly affect the primary end point of days alive and out of the hospital during the first 6 months (133 days vs 135 days; hazard ratio [HR], 1.00 [95% confidence interval {CI}, 0.82-1.21]; P = .99), mortality (43 patients [10%] vs 38 patients [9%]; odds ratio [OR], 1.26 [95% CI, 0.78-2.03]; P = .35), or the number of days hospitalized (8.7 vs 8.3; HR, 1.04 [95% CI, 0.86-1.27]; P = .67). In-hospital adverse events were more common among patients in the PAC group (47 [21.9%] vs 25 [11.5%]; P = .04). There were no deaths related to PAC use, and no difference for in-hospital plus 30-day mortality (10 [4.7%] vs 11 [5.0%]; OR, 0.97 [95% CI, 0.38-2.22]; P = .97). Exercise and quality of life end points improved in both groups with a trend toward greater improvement with the PAC, which reached significance for the time trade-off at all time points after randomization. Conclusions  Therapy to reduce volume overload during hospitalization for heart failure led to marked improvement in signs and symptoms of elevated filling pressures with or without the PAC. Addition of the PAC to careful clinical assessment increased anticipated adverse events, but did not affect overall mortality and hospitalization. Future trials should test noninvasive assessments with specific treatment strategies that could be used to better tailor therapy for both survival time and survival quality as valued by patients.      

Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy

Context  Drug intervention in placebo-controlled trials has been beneficial in isolated systolic hypertension. Objective  To test the hypothesis that losartan improves outcome better than atenolol in patients with isolated systolic hypertension and electrocardiographically documented left ventricular hypertrophy (ECG-LVH). Design  Double-blind, randomized, parallel-group study conducted in 1995-2001. Setting and Participants  A total of 1326 men and women aged 55 through 80 years (mean, 70 years) with systolic blood pressure of 160 to 200 mm Hg and diastolic blood pressure of less than 90 mm Hg (mean, 174/83 mm Hg) and ECG-LVH, recruited from 945 outpatient settings in the Nordic countries, the United Kingdom, and the United States. Interventions  Patients were randomly assigned to receive once-daily losartan (n = 660) or atenolol (n = 666) with hydrochlorothiazide as the second agent in both arms, for a mean of 4.7 years. Main Outcome Measure  Composite end point of cardiovascular death, stroke, or myocardial infarction. Results  Blood pressure was reduced by 28/9 and 28/9 mm Hg in the losartan and atenolol arms. The main outcome was reduced by 25% with losartan compared with atenolol, 25.1 vs 35.4 events per 1000 patient-years (relative risk [RR], 0.75; 95% confidence interval [CI], 0.56-1.01; P = .06, adjusted for risk and degree of ECG-LVH; unadjusted RR, 0.71; 95% CI, 0.53-0.95; P = .02). Patients receiving losartan had reductions in the following without a difference in the incidence of myocardial infarction: cardiovascular mortality (8.7 vs 16.9 events per 1000 patient-years; RR, 0.54; 95% CI, 0.34-0.87; P = .01), nonfatal and fatal stroke (10.6 vs 18.9 events per 1000 patient-years; RR, 0.60; 95% CI, 0.38-0.92; P = .02), new-onset diabetes (12.6 vs 20.1 events per 1000 patient-years; RR, 0.62; 95% CI, 0.40-0.97; P = .04), and total mortality (21.2 vs 30.2 events per 1000 patient-years; RR, 0.72; 95% CI, 0.53-1.00; P = .046). Losartan decreased ECG-LVH more than atenolol (P<.001) and was better tolerated. Conclusion  These data suggest that losartan is superior to atenolol for treatment of patients with isolated systolic hypertension and ECG-LVH.      

Effect of Prolonged Methylprednisolone Therapy in Unresolving Acute Respiratory Distress Syndrome: A Randomized Controlled Trial

Context.— No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%. Objective.— To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS. Design.— Randomized, double-blind, placebo-controlled trial. Setting.— Medical intensive care units of 4 medical centers. Participants.— Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure. Interventions.— Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment. Main Outcome Measures.— Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections. Results.— Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO₂ to fraction of inspired oxygen (FIO₂), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO₂ to FIO₂ (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever. Conclusions.— In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.      

Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial

Context  Despite many therapeutic advances, mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) remains high. The role of additional antithrombotic agents is unclear, especially among patients not receiving reperfusion therapy. Objective  To evaluate the effect of fondaparinux, a factor Xa inhibitor, when initiated early and given for up to 8 days vs usual care (placebo in those in whom unfractionated heparin [UFH] is not indicated [stratum 1] or unfractionated heparin for up to 48 hours followed by placebo for up to 8 days [stratum 2]) in patients with STEMI. Design, Setting, and Participants  Randomized double-blind comparison of fondaparinux 2.5 mg once daily or control for up to 8 days in 12 092 patients with STEMI from 447 hospitals in 41 countries (September 2003-January 2006). From day 3 through day 9, all patients received either fondaparinux or placebo according to the original randomized assignment. Main Outcome Measures  Composite of death or reinfarction at 30 days (primary) with secondary assessments at 9 days and at final follow-up (3 or 6 months). Results  Death or reinfarction at 30 days was significantly reduced from 677 (11.2%) of 6056 patients in the control group to 585 (9.7%) of 6036 patients in the fondaparinux group (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.77-0.96; P = .008); absolute risk reduction, 1.5%; 95% CI, 0.4%-2.6%). These benefits were observed at 9 days (537 [8.9%] placebo vs 444 [7.4%] fondaparinux; HR, 0.83; 95% CI, 0.73-0.94; P = .003, and at study end (857 [14.8%] placebo vs 756 [13.4%] fondaparinux; HR, 0.88; 95% CI, 0.79-0.97; P = .008). Mortality was significantly reduced throughout the study. There was no heterogeneity of the effects of fondaparinux in the 2 strata by planned heparin use. However, there was no benefit in those undergoing primary percutaneous coronary intervention. In other patients in stratum 2, fondaparinux was superior to unfractionated heparin in preventing death or reinfarction at 30 days (HR, 0.82; 95% CI, 0.66-1.02; P = .08) and at study end (HR, 0.77; 95% CI, 0.64-0.93; P = .008). Significant benefits were observed in those receiving thrombolytic therapy (HR, 0.79; P = .003) and those not receiving any reperfusion therapy (HR, 0.80; P = .03). There was a tendency to fewer severe bleeds (79 for placebo vs 61 for fondaparinux; P = .13), with significantly fewer cardiac tamponade (48 vs 28; P = .02) with fondaparinux at 9 days. Conclusion  In patients with STEMI, particularly those not undergoing primary percutaneous coronary intervention, fondaparinux significantly reduces mortality and reinfarction without increasing bleeding and strokes. Trial Registration  ClinicalTrials.gov Identifier NCT00064428      

Continuous positive airway pressure for treatment of postoperative hypoxemia: a randomized controlled trial

Context  Hypoxemia complicates the recovery of 30% to 50% of patients after abdominal surgery; endotracheal intubation and mechanical ventilation may be required in 8% to 10% of cases, increasing morbidity and mortality and prolonging intensive care unit and hospital stay. Objective  To determine the effectiveness of continuous positive airway pressure compared with standard treatment in preventing the need for intubation and mechanical ventilation in patients who develop acute hypoxemia after elective major abdominal surgery. Design and Setting  Randomized, controlled, unblinded study with concealed allocation conducted between June 2002 and November 2003 at 15 intensive care units of the Piedmont Intensive Care Units Network in Italy. Patients  Consecutive patients who developed severe hypoxemia after major elective abdominal surgery. The trial was stopped for efficacy after 209 patients had been enrolled. Interventions  Patients were randomly assigned to receive oxygen (n = 104) or oxygen plus continuous positive airway pressure (n = 105). Main Outcome Measures  The primary end point was incidence of endotracheal intubation; secondary end points were intensive care unit and hospital lengths of stay, incidence of pneumonia, infection and sepsis, and hospital mortality. Results  Patients who received oxygen plus continuous positive airway pressure had a lower intubation rate (1% vs 10%; P = .005; relative risk [RR], 0.099; 95% confidence interval [CI], 0.01-0.76) and had a lower occurrence rate of pneumonia (2% vs 10%, RR, 0.19; 95% CI, 0.04-0.88; P = .02), infection (3% vs 10%, RR, 0.27; 95% CI, 0.07-0.94; P = .03), and sepsis (2% vs 9%; RR, 0.22; 95% CI, 0.04-0.99; P = .03) than did patients treated with oxygen alone. Patients who received oxygen plus continuous positive airway pressure also spent fewer mean (SD) days in the intensive care unit (1.4 [1.6] vs 2.6 [4.2], P = .09) than patients treated with oxygen alone. The treatments did not affect the mean (SD) days that patients spent in the hospital (15 [13] vs 17 [15], respectively; P = .10). None of those treated with oxygen plus continuous positive airway pressure died in the hospital while 3 deaths occurred among those treated with oxygen alone (P = .12). Conclusion  Continuous positive airway pressure may decrease the incidence of endotracheal intubation and other severe complications in patients who develop hypoxemia after elective major abdominal surgery.      

Sirolimus-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stents: the SISR randomized trial

Context  Although vascular brachytherapy is the only approved therapy for restenosis following bare-metal stent implantation, drug-eluting stents are now being used. Data on the relative merits of each are limited. Objective  To determine the safety and efficacy of the sirolimus-eluting stent compared with vascular brachytherapy for the treatment of patients with restenosis within a bare-metal stent. Design, Setting, and Patients  Prospective, multicenter, randomized trial of 384 patients with in-stent restenosis who were enrolled between February 2003 and July 2004 at 26 academic and community medical centers. Data presented represent all follow-up as of June 30, 2005. Interventions  Vascular brachytherapy (n = 125) or the sirolimus-eluting stent (n = 259). Main Outcome Measure  Target vessel failure (cardiac death, myocardial infarction, or target vessel revascularization) at 9 months postprocedure. Results  Baseline patient characteristics were well matched. Lesion length was similar between vascular brachytherapy and sirolimus-eluting stent patients (mean [SD], 16.76 [8.55] mm vs 17.22 [7.97] mm, respectively; P = .61). Procedural success was 99.2% (124/125) in the vascular brachytherapy group and 97.3% (250/257) in the sirolimus-eluting stent group (P = .28). The rate of target vessel failure was 21.6% (27/125) with vascular brachytherapy and 12.4% (32/259) with the sirolimus-eluting stent (relative risk [RR], 1.7; 95% confidence interval [CI], 1.1-2.8; P = .02). Target lesion revascularization was required in 19.2% (24/125) of the vascular brachytherapy group and 8.5% (22/259) of the sirolimus-eluting stent group (RR, 2.3 [95% CI, 1.3-3.9]; P = .004). At follow-up angiography, the rate of binary angiographic restenosis for the analysis segment was 29.5% (31/105) for the vascular brachytherapy group and 19.8% (45/227) for the sirolimus-eluting stent group (RR, 1.5 [95% CI, 1.0-2.2]; P = .07). Compared with the vascular brachytherapy group, minimal lumen diameter was larger in the sirolimus-eluting stent group at 6-month follow-up (mean [SD], 1.52 [0.63] mm vs 1.80 [0.63] mm; P<.001), reflecting greater net lumen gain in the analysis segment (0.68 [0.60] vs 1.0 [0.61] mm; P<.001) due to stenting and no edge restenosis. Conclusion  Sirolimus-eluting stents result in superior clinical and angiographic outcomes compared with vascular brachytherapy for the treatment of restenosis within a bare-metal stent. Trial Registration  ClinicalTrials.gov Identifier: NCT00231257      

Burden, features, and outcome of neurological involvement in acute falciparum malaria in Kenyan children

Context  Plasmodium falciparum appears to have a particular propensity to involve the brain but the burden, risk factors, and full extent of neurological involvement have not been systematically described. Objectives  To determine the incidence and describe the clinical phenotypes and outcomes of neurological involvement in African children with acute falciparum malaria. Design, Setting, and Patients  A review of records of all children younger than 14 years admitted to a Kenyan district hospital with malaria from January 1992 through December 2004. Neurological involvement was defined as convulsive seizures, agitation, prostration, or impaired consciousness or coma. Main Outcome Measures  The incidence, pattern, and outcome of neurological involvement. Results  Of 58 239 children admitted, 19 560 (33.6%) had malaria as the primary clinical diagnosis. Neurological involvement was observed in 9313 children (47.6%) and manifested as seizures (6563/17 517 [37.5%]), agitation (316/11 193 [2.8%]), prostration (3223/15 643 [20.6%]), and impaired consciousness or coma (2129/16 080 [13.2%]). In children younger than 5 years, the mean annual incidence of admissions with malaria was 2694 per 100 000 persons and the incidence of malaria with neurological involvement was 1156 per 100 000 persons. However, readmissions may have led to a 10% overestimate in incidence. Children with neurological involvement were older (median, 26 [interquartile range {IQR}, 15-41] vs 21 [IQR, 10-40] months; P<.001), had a shorter duration of illness (median, 2 [IQR, 1-3] vs 3 [IQR, 2-3] days; P<.001), and a higher geometric mean parasite density (42.0 [95% confidence interval {CI}, 40.0-44.1] vs 30.4 [95% CI, 29.0-31.8] x 10³/µL; P<.001). Factors independently associated with neurological involvement included past history of seizures (adjusted odds ratio [AOR], 3.50; 95% CI, 2.78-4.42), fever lasting 2 days or less (AOR, 2.02; 95% CI, 1.64-2.49), delayed capillary refill time (AOR, 3.66; 95% CI, 2.40-5.56), metabolic acidosis (AOR, 1.55; 95% CI, 1.29-1.87), and hypoglycemia (AOR, 2.11; 95% CI, 1.31-3.37). Mortality was higher in patients with neurological involvement (4.4% [95% CI, 4.2%-5.1%] vs 1.3% [95% CI, 1.1%-1.5%]; P<.001). At discharge, 159 (2.2%) of 7281 patients had neurological deficits. Conclusions  Neurological involvement is common in children in Kenya with acute falciparum malaria, and is associated with metabolic derangements, impaired perfusion, parasitemia, and increased mortality and neurological sequelae. This study suggests that falciparum malaria exposes many African children to brain insults.      

Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials

Context  Heart failure causes more than 1 million US hospitalizations yearly, mostly related to congestion. Tolvaptan, an oral, nonpeptide, selective vasopressin V₂-receptor antagonist, shows promise in this condition. Objective  To evaluate short-term effects of tolvaptan when added to standard therapy in patients hospitalized with heart failure. Design, Setting, and Patients  Two identical prospective, randomized, double-blind, placebo-controlled trials at 359 sites in North America, South America, and Europe were conducted during the inpatient period of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) between October 7, 2003, and February 3, 2006. A total of 2048 (trial A) and 2085 (trial B) patients hospitalized with heart failure and congestion were studied. Intervention  Patients were randomized to receive either tolvaptan (30 mg/d) or matching placebo, within 48 hours of admission. Main Outcome Measures  Primary end point was a composite of changes in global clinical status based on a visual analog scale and body weight at day 7 or discharge if earlier. Secondary end points included dyspnea (day 1), global clinical status (day 7 or discharge), body weight (days 1 and 7 or discharge), and peripheral edema (day 7 or discharge). Results  Rank sum analysis of the composite primary end point showed greater improvement with tolvaptan vs placebo (trial A, mean [SD], 1.06 [0.43] vs 0.99 [0.44]; and trial B, 1.07 [0.42] vs 0.97 [0.43]; both trials P<.001). Mean (SD) body weight reduction was greater with tolvaptan on day 1 (trial A, 1.71 [1.80] vs 0.99 [1.83] kg; P<.001; and trial B, 1.82 [2.01] vs 0.95 [1.85] kg; P<.001) and day 7 or discharge (trial A, 3.35 [3.27] vs 2.73 [3.34] kg; P<.001; and trial B, 3.77 [3.59] vs 2.79 [3.46] kg; P<.001), whereas improvements in global clinical status were not different between groups. More patients receiving tolvaptan (684 [76.7%] and 678 [72.1%] for trial A and trial B, respectively) vs patients receiving placebo (646 [70.6%] and 597 [65.3%], respectively) reported improvement in dyspnea at day 1 (both trials P<.001). Edema at day 7 or discharge improved significantly with tolvaptan in trial B (P = .02) but did not reach significance in trial A (P = .07). Serious adverse event frequencies were similar between groups, without excess renal failure or hypotension. Conclusion  In patients hospitalized with heart failure, oral tolvaptan in addition to standard therapy including diuretics improved many, though not all, heart failure signs and symptoms, without serious adverse events. Trial Registration  clinicaltrials.gov Identifier: NCT00071331      

Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial

Context  Enoxaparin has demonstrated advantages over unfractionated heparin in low- to moderate-risk patients with non–ST-segment elevation acute coronary syndromes (ACS) treated with a conservative strategy. Objectives  To compare the outcomes of patients treated with enoxaparin vs unfractionated heparin and to define the role of enoxaparin in patients with non–ST-segment elevation ACS at high risk for ischemic cardiac complications managed with an early invasive approach. Design, Setting, and Participants  The Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial was a prospective, randomized, open-label, multicenter, international trial conducted between August 2001 and December 2003. A total of 10 027 high-risk patients with non–ST-segment elevation ACS to be treated with an intended early invasive strategy were recruited. Interventions  Subcutaneous enoxaparin (n = 4993) or intravenous unfractionated heparin (n = 4985) was to be administered immediately after enrollment and continued until the patient required no further anticoagulation, as judged by the treating physician. Main Outcome Measures  The primary efficacy outcome was the composite clinical end point of all-cause death or nonfatal myocardial infarction during the first 30 days after randomization. The primary safety outcome was major bleeding or stroke. Results  The primary end point occurred in 14.0% (696/4993) of patients assigned to enoxaparin and 14.5% (722/4985) of patients assigned to unfractionated heparin (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.86-1.06). No differences in ischemic events during percutaneous coronary intervention (PCI) were observed between enoxaparin and unfractionated heparin groups, respectively, including similar rates of abrupt closure (31/2321 [1.3%] vs 40/2364 [1.7%]), threatened abrupt closure (25/2321 [1.1%] vs 24/2363 [1.0%]), unsuccessful PCI (81/2281 [3.6%] vs 79/2328 [3.4%]), or emergency coronary artery bypass graft surgery (6/2323 [0.3%] vs 8/2363 [0.3%]). More bleeding was observed with enoxaparin, with a statistically significant increase in TIMI (Thrombolysis in Myocardial Infarction) major bleeding (9.1% vs 7.6%, P = .008) but nonsignificant excess in GUSTO (Global Utilization of Streptokinase and t-PA for Occluded Arteries) severe bleeding (2.7% vs 2.2%, P = .08) and transfusions (17.0% vs 16.0%, P = .16). Conclusions  Enoxaparin was not superior to unfractionated heparin but was noninferior for the treatment of high-risk patients with non–ST-segment elevation ACS. Enoxaparin is a safe and effective alternative to unfractionated heparin and the advantages of convenience should be balanced with the modest excess of major bleeding.      

Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial

Context  Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results. Objective  To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups. Design, Setting, and Patients  Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year. Intervention  Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative -blockers. Main Outcome Measure  Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day. Results  Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative -blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative -blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality. Conclusion  Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration  ClinicalTrials.gov Identifier: NCT00251706      

Survival from in-hospital cardiac arrest during nights and weekends

Mary Ann Peberdy, MD; Joseph P. Ornato, MD; G. Luke Larkin, MD, MSPH, MS; R. Scott Braithwaite, MD; T. Michael Kashner, PhD, JD; Scott M. Carey; Peter A. Meaney, MD, MPH; Liyi Cen, MS; Vinay M. Nadkarni, MD, MS; Amy H. Praestgaard, MS; Robert A. Berg, MD; for the National Registry of Cardiopulmonary Resuscitation Investigators

JAMA. 2008;299(7):785-792.

Context  Occurrence of in-hospital cardiac arrest and survival patterns have not been characterized by time of day or day of week. Patient physiology and process of care for in-hospital cardiac arrest may be different at night and on weekends because of hospital factors unrelated to patient, event, or location variables.

Objective  To determine whether outcomes after in-hospital cardiac arrest differ during nights and weekends compared with days/evenings and weekdays.

Design and Setting  We examined survival from cardiac arrest in hourly time segments, defining day/evening as 7:00 AM to 10:59 PM, night as 11:00 PM to 6:59 AM, and weekend as 11:00 PM on Friday to 6:59 AM on Monday, in 86 748 adult, consecutive in-hospital cardiac arrest events in the National Registry of Cardiopulmonary Resuscitation obtained from 507 medical/surgical participating hospitals from January 1, 2000, through February 1, 2007.

Main Outcome Measures  The primary outcome of survival to discharge and secondary outcomes of survival of the event, 24-hour survival, and favorable neurological outcome were compared using odds ratios and multivariable logistic regression analysis. Point estimates of survival outcomes are reported as percentages with 95% confidence intervals (95% CIs).

Results  A total of 58 593 cases of in-hospital cardiac arrest occurred during day/evening hours (including 43 483 on weekdays and 15 110 on weekends), and 28 155 cases occurred during night hours (including 20 365 on weekdays and 7790 on weekends). Rates of survival to discharge (14.7% [95% CI, 14.3%-15.1%] vs 19.8% [95% CI, 19.5%-20.1%], return of spontaneous circulation for longer than 20 minutes (44.7% [95% CI, 44.1%-45.3%] vs 51.1% [95% CI, 50.7%-51.5%]), survival at 24 hours (28.9% [95% CI, 28.4%-29.4%] vs 35.4% [95% CI, 35.0%-35.8%]), and favorable neurological outcomes (11.0% [95% CI, 10.6%-11.4%] vs 15.2% [95% CI, 14.9%-15.5%]) were substantially lower during the night compared with day/evening (all P values < .001). The first documented rhythm at night was more frequently asystole (39.6% [95% CI, 39.0%-40.2%] vs 33.5% [95% CI, 33.2%-33.9%], P < .001) and less frequently ventricular fibrillation (19.8% [95% CI, 19.3%-20.2%] vs 22.9% [95% CI, 22.6%-23.2%], P < .001). Among in-hospital cardiac arrests occurring during day/evening hours, survival was higher on weekdays (20.6% [95% CI, 20.3%-21%]) than on weekends (17.4% [95% CI, 16.8%-18%]; odds ratio, 1.15 [95% CI, 1.09-1.22]), whereas among in-hospital cardiac arrests occurring during night hours, survival to discharge was similar on weekdays (14.6% [95% CI, 14.1%-15.2%]) and on weekends (14.8% [95% CI, 14.1%-15.2%]; odds ratio, 1.02 [95% CI, 0.94-1.11]).

Conclusion  Survival rates from in-hospital cardiac arrest are lower during nights and weekends, even when adjusted for potentially confounding patient, event, and hospital characteristics.

     

E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators

Context  Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not. Objective  To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis. Design  A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses. Setting  Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals. Patients  Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection. Intervention  Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552). Main Outcome Measures  The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation. Results  The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo. Conclusions  Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted.      

Certificate of need regulations and use of coronary revascularization after acute myocardial infarction

Context  Certificate of need regulations were enacted to control health care costs by limiting unnecessary expansion of services. While many states have repealed certificate of need regulations in recent years, few analyses have examined relationships between certificate of need regulations and outcomes of care. Objective  To compare rates of coronary revascularization and mortality after acute myocardial infarction in states with and without certificate of need regulations. Design, Setting, and Participants  Retrospective cohort study of 1 139 792 Medicare beneficiaries aged 68 years or older with AMI who were admitted to 4587 US hospitals during 2000-2003. Main Outcome Measures  Thirty-day risk-adjusted rates of coronary revascularization with either coronary artery bypass graft surgery or percutaneous coronary intervention and 30-day all-cause mortality. Results  The 624 421 patients in states with certificate of need regulations were less likely to be admitted to hospitals with coronary revascularization services (321 573 [51.5%] vs 323 695 [62.8%]; P<.001) or to undergo revascularization at the admitting hospital (163 120 [26.1%] vs 163 877 [31.8%]; P<.001) than patients in states without certificates of need but were more likely to undergo revascularization at a transfer hospital (73 379 [11.7%] vs 45 907 [8.9%]; P<.001). Adjusting for demographic and clinical risk factors, patients in states with highly and moderately stringent certificate of need regulations, respectively, were less likely to undergo revascularization within the first 2 days (adjusted hazard ratios, 0.68; 95% confidence interval [CI], 0.54-0.87; P = .002 and 0.80; 95% CI, 0.71-0.90; P<.001) relative to patients in states without certificates of need, although no differences in the likelihood of revascularization were observed during days 3 through 30. Unadjusted 30-day mortality was similar in states with and without certificates of need (109 304 [17.5%] vs 90 104 [17.5%]; P = .76), as was adjusted mortality (odds ratio, 1.00; 95% CI, 0.97-1.03; P = .90). Conclusions  Patients with acute myocardial infarction were less likely to be admitted to hospitals offering coronary revascularization and to undergo early revascularization in states with certificate of need regulations. However, differences in the availability and use of revascularization therapies were not associated with mortality.      

Effects of reviparin, a low-molecular-weight heparin, on mortality, reinfarction, and strokes in patients with acute myocardial infarction presenting with ST-segment elevation

Context  Although reperfusion therapy, aspirin, -blockers, and angiotensin-converting enzyme inhibitors reduce mortality when used early in patients with acute myocardial infarction (MI), mortality and morbidity remain high. No antithrombotic or newer antiplatelet drug has been shown to reduce mortality in acute MI. Objective  To evaluate the effects of reviparin, a low-molecular-weight heparin, when initiated early and given for 7 days in addition to usual therapy on the primary composite outcome of death, myocardial reinfarction, or strokes at 7 and 30 days. Design, Setting, and Patients  A randomized, double-blind, placebo-controlled trial (Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation [CREATE]) of 15 570 patients with ST-segment elevation or new left bundle-branch block, presenting within 12 hours of symptom onset at 341 hospitals in India and China from July 2001 through July 2004. Intervention  Reviparin or placebo subcutaneously twice daily for 7 days. Main Outcome Measure  Primary composite outcome of death, myocardial reinfarction, or stroke at 7 and 30 days. Results  The primary composite outcome was significantly reduced from 854 (11.0%) of 7790 patients in the placebo group to 745 (9.6%) of 7780 in the reviparin group (hazard ratio [HR], 0.87; 95% CI, 0.79-0.96; P = .005). These benefits persisted at 30 days (1056 [13.6%] vs 921 [11.8%] patients; HR, 0.87; 95% CI, 0.79-0.95; P = .001) with significant reductions in 30-day mortality (877 [11.3%] vs 766 [9.8%]; HR, 0.87; 95% CI, 0.79-0.96; P = .005) and reinfarction (199 [2.6%] vs 154 [2.0%]; HR, 0.77; 95% CI, 0.62-0.95; P = .01), and no significant differences in strokes (64 [0.8%] vs 80 [1.0%]; P = .19). Reviparin treatment was significantly better when it was initiated very early after symptom onset at 7 days (<2 hours: HR, 0.70; 95% CI, 0.52-0.96; P = .03; 30/1000 events prevented; 2 to <4 hours: HR, 0.81; 95% CI, 0.67-0.98; P = .03; 21/1000 events prevented; 4 to <8 hours: HR, 0.85; 95% CI, 0.73-0.99; P = .05; 16/1000 events prevented; and 8 hours: HR, 1.06; 95% CI, 0.86-1.30; P = .58; P = .04 for trend). There was an increase in life-threatening bleeding at 7 days with reviparin and placebo (17 [0.2%] vs 7 [0.1%], respectively; P = .07), but the absolute excess was small (1 more per 1000) vs reductions in the primary outcome (18 fewer per 1000) or mortality (15 fewer per 1000). Conclusions  In patients with acute ST-segment elevation or new left bundle-branch block MI, reviparin reduces mortality and reinfarction, without a substantive increase in overall stroke rates. There is a small absolute excess of life-threatening bleeding but the benefits outweigh the risks.      

Effects of systematic prone positioning in hypoxemic acute respiratory failure: a randomized controlled trial

Context  A recent trial showed that placing patients with acute lung injury in the prone position did not increase survival; however, whether those results hold true for patients with hypoxemic acute respiratory failure (ARF) is unclear. Objective  To determine whether prone positioning improves mortality in ARF patients. Design, Setting, and Patients  Prospective, unblinded, multicenter controlled trial of 791 ARF patients in 21 general intensive care units in France using concealed randomization conducted from December 14, 1998, through December 31, 2002. To be included, patients had to be at least 18 years, hemodynamically stable, receiving mechanical ventilation, and intubated and had to have a partial pressure of arterial oxygen (PaO₂) to fraction of inspired oxygen (FIO₂) ratio of 300 or less and no contraindications to lying prone. Interventions  Patients were randomly assigned to prone position placement (n = 413), applied as early as possible for at least 8 hours per day on standard beds, or to supine position placement (n = 378). Main Outcome Measures  The primary end point was 28-day mortality; secondary end points were 90-day mortality, duration of mechanical ventilation, incidence of ventilator-associated pneumonia (VAP), and oxygenation. Results  The 2 groups were comparable at randomization. The 28-day mortality rate was 32.4% for the prone group and 31.5% for the supine group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.79-1.19; P = .77). Ninety-day mortality for the prone group was 43.3% vs 42.2% for the supine group (RR, 0.98; 95% CI, 0.84-1.13; P = .74). The mean (SD) duration of mechanical ventilation was 13.7 (7.8) days for the prone group vs 14.1 (8.6) days for the supine group (P = .93) and the VAP incidence was 1.66 vs 2.14 episodes per 100-patients days of intubation, respectively (P = .045). The PaO₂/FIO₂ ratio was significantly higher in the prone group during the 28-day follow-up. However, pressure sores, selective intubation, and endotracheal tube obstruction incidences were higher in the prone group. Conclusions  This trial demonstrated no beneficial outcomes and some safety concerns associated with prone positioning. For patients with hypoxemic ARF, prone position placement may lower the incidence of VAP.      

Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial

Context  Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons. Objective  To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women. Design, Setting, and Participants  In the Women’s Health Study conducted between 1992 and 2004, 39 876 apparently healthy US women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial design, and were followed up for an average of 10.1 years. Intervention  Administration of 600 IU of natural-source vitamin E on alternate days. Main Outcome Measures  Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer. Results  During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95% confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects on the incidences of myocardial infarction (RR,  1.01; 95% CI, 0.82-1.23; P = .96) or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95% CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (636 in the vitamin E group and 615 in the placebo group; RR, 1.04; 95% CI, 0.93-1.16; P = .53). Conclusions  The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women.      

Noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis

Context  In patients with acute cardiogenic pulmonary edema noninvasive ventilation may reduce intubation rate, but the impact on mortality and the superiority of one technique over another have not been clearly established. Objective  To systematically review and quantitatively synthesize the short-term effect of noninvasive ventilation on major clinical outcomes. Data Sources  MEDLINE and EMBASE (from inception to October 2005) and Cochrane databases (library issue 4, 2005) were searched to identify relevant randomized controlled trials and systematic reviews published from January 1, 1988, to October 31, 2005. Study Selection and Data Extraction  Included trials were all parallel studies comparing noninvasive ventilation to conventional oxygen therapy in patients with acute pulmonary edema. Comparisons of different techniques, either continuous positive airway pressure (CPAP) or bilevel noninvasive pressure support ventilation (NIPSV), were also included. Data Synthesis  Fifteen trials were selected. Overall, noninvasive ventilation significantly reduced the mortality rate by nearly 45% compared with conventional therapy (risk ratio [RR], 0.55; 95% confidence interval [CI], 0.40-0.78; P = .72 for heterogeneity). The results were significant for CPAP (RR, 0.53; 95% CI, 0.35-0.81; P = .44 for heterogeneity) but not for NIPSV (RR, 0.60; 95% CI, 0.34-1.05; P = .76 for heterogeneity), although there were fewer studies in the latter. Both modalities showed a significant decrease in the "need to intubate" rate compared with conventional therapy: CPAP (RR, 0.40; 95% CI, 0.27-0.58; P = .21 for heterogeneity), NIPSV (RR, 0.48; 95% CI, 0.30-0.76; P = .24 for heterogeneity), and together (RR, 0.43; 95% CI, 0.32-0.57; P = .20 for heterogeneity). There were no differences in intubation or mortality rates in the analysis of studies comparing the 2 techniques. Conclusions  Noninvasive ventilation reduces the need for intubation and mortality in patients with acute cardiogenic pulmonary edema. Although the level of evidence is higher for CPAP, there are no significant differences in clinical outcomes when comparing CPAP vs NIPSV.      

Discussion of medical errors in morbidity and mortality conferences

Context  Morbidity and mortality conferences in residency programs are intended to discuss adverse events and errors with a goal to improve patient care. Little is known about whether residency training programs are accomplishing this goal. Objective  To determine the frequency at which morbidity and mortality conference case presentations include adverse events and errors and whether the errors are discussed and attributed to a particular cause. Design, Setting, and Participants  Prospective survey conducted by trained physician observers from July 2000 through April 2001 on 332 morbidity and mortality conference case presentations and discussions in internal medicine (n = 100) and surgery (n = 232) at 4 US academic hospitals. Main Outcome Measures  Frequencies of presentation of adverse events and errors, discussion of errors, and attribution of errors. Results  In internal medicine morbidity and mortality conferences, case presentations and discussions were 3 times longer than in surgery conferences (34.1 minutes vs 11.7 minutes; P = .001), more time was spent listening to invited speakers (43.1% vs 0%; P<.001), and less time was spent in audience discussion (15.2% vs 36.6%; P<.001). Fewer internal medicine case presentations included adverse events (37 [37%] vs 166 surgery case presentations [72%]; P<.001) or errors causing an adverse event (18 [18%] vs 98 [42%], respectively; P = .001). When an error caused an adverse event, the error was discussed as an error less often in internal medicine (10 errors [48%] vs 85 errors in surgery [77%]; P = .02). Errors were attributed to a particular cause less often in medicine than in surgery conferences (8 [38%] of 21 medicine errors vs 88 [79%] of 112 surgery errors; P<.001). In discussions of cases with errors, conference leaders in both internal medicine and surgery infrequently used explicit language to signal that an error was being discussed and infrequently acknowledged having made an error. Conclusions  Our findings call into question whether adverse events and errors are routinely discussed in internal medicine training programs. Although adverse events and errors were discussed frequently in surgery cases, teachers in both surgery and internal medicine missed opportunities to model recognition of error and to use explicit language in error discussion by acknowledging their personal experiences with error.      

Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. The ARDS Network

Context  Three clinical studies have suggested that ketoconazole, a synthetic imidazole with anti-inflammatory activity, may prevent the development of acute respiratory distress syndrome (ARDS) in critically ill patients. However, the use of ketoconazole as treatment for acute lung injury (ALI) and ARDS has not been previously studied. Objective  To test the efficacy of ketoconazole in reducing mortality and morbidity in patients with ALI or ARDS. Design  Randomized, double-blind, placebo-controlled trial conducted from March 1996 to January 1997. Setting  Twenty-four hospitals associated with 10 network centers in the United States, constituting the ARDS Network. Patients  A total of 234 patients with ALI or ARDS. Intervention  Patients were randomly assigned to receive ketoconazole, 400 mg/d (n=117), or placebo (n=117), initiated within 36 hours of fulfilling study entry criteria and given enterally for up to 21 days. Main Outcome Measures  Primary outcome measures were the proportion of patients alive with unassisted breathing at hospital discharge and the number of days of unassisted breathing (ventilator-free days) during 28 days of follow-up. Secondary outcome measures included the proportion of patients achieving unassisted breathing for 48 hours or more, the number of organ failure–free days, and changes in plasma interleukin 6 (IL-6) and urinary thromboxane A₂ metabolites (thromboxane B₂ [TXB₂] and 11-dehydro-TXB₂). Results  In-hospital mortality (SE) was 34.1% (4.3%) for the placebo group and 35.2% (4.3%) for the ketoconazole group (P=.85). The median number of ventilator-free days within 28 days of randomization was 9 in the placebo group and 10 in the ketoconazole group (P=.89). There were no statistically significant differences in the number of organ failure–free days, pulmonary physiology, or adverse events between treatment groups. The median serum ketoconazole level was 1.25 µg/mL and serum levels greater than 0.5 µg/mL were detected in 96% of patients assayed. Plasma IL-6, urinary TXB₂, and 11-dehydro-TXB₂ levels were unaffected by ketoconazole. Conclusions  In these patients with ALI or ARDS, ketoconazole was safe and bioavailable but did not reduce mortality or duration of mechanical ventilation or improve lung function. These data do not support the use of ketoconazole for the early treatment of ALI or ARDS.      

Comprehensive discharge planning with postdischarge support for older patients with congestive heart failure: a meta-analysis

Context  Comprehensive discharge planning plus postdischarge support may reduce readmission rates for older patients with congestive heart failure (CHF). Objective  To evaluate the effect of comprehensive discharge planning plus postdischarge support on the rate of readmission in patients with CHF, all-cause mortality, length of stay (LOS), quality of life (QOL), and medical costs. Data Sources  We searched MEDLINE (1966 to October 2003), the Cochrane Clinical Trials Register (all years), Social Science Citation Index (1992 to October 2003), and other databases for studies that described such an intervention and evaluated its effect in patients with CHF. Where possible we also contacted lead investigators and experts in the field. Study Selection  We selected English-language publications of randomized clinical trials that described interventions to modify hospital discharge for older patients with CHF (mean age =" BORDER="0">55 years), delineated clearly defined inpatient and outpatient components, compared efficacy with usual care, and reported readmission as the primary outcome. Data Extraction  Two authors independently reviewed each report, assigned quality scores, and extracted data for primary and secondary outcomes in an unblinded standardized manner. Data Synthesis  Eighteen studies representing data from 8 countries randomized 3304 older inpatients with CHF to comprehensive discharge planning plus postdischarge support or usual care. During a pooled mean observation period of 8 months (range, 3-12 months), fewer intervention patients were readmitted compared with controls (555/1590 vs 741/1714, number needed to treat = 12; relative risk [RR], 0.75; 95% confidence interval [CI], 0.64-0.88). Analysis of studies reporting secondary outcomes found a trend toward lower all-cause mortality for patients assigned to an intervention compared with usual care (RR, 0.87; 95% CI, 0.73-1.03; n = 14 studies), similar initial LOS (mean [SE]: 8.4 [2.5] vs 8.5 [2.2] days, P = .60; n = 10), greater percentage improvement in QOL scores compared with baseline scores (25.7% [95% CI, 11.0%-40.4%] vs 13.5% [95% CI, 5.1%-22.0%]; n = 6, P = .01), and similar or lower charges for medical care per patient per month for the initial hospital stay, administering the intervention, outpatient care, and readmission (-$359 [95% CI, -$763 to $45]; n = 4, P = .10 for non-US trials and -$536 [95% CI, -$956 to -$115]; n = 4, P = .03, for US trials). Conclusion  Comprehensive discharge planning plus postdischarge support for older patients with CHF significantly reduced readmission rates and may improve health outcomes such as survival and QOL without increasing costs.