JAMA - Jornal da Associação Médica Americana

Context  A low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk group potentially amenable to preventive treatments.

Objective  To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population.

Design, Setting, and Participants  The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28 980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (≤0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events.

Interventions  Once daily 100 mg aspirin (enteric coated) or placebo.

Main Outcome Measures  The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack; and (2) all-cause mortality.

Results  After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval [CI], 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group; hazard ratio [HR], 1.03; 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years; 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the placebo group (HR, 1.71; 95% CI, 0.99-2.97).

Conclusion  Among participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events.

Trial Registration  isrctn.org Identifier: ISRCTN66587262

Context  Although hospital mortality has decreased over time in the United States for patients who receive intensive care, little is known about subsequent outcomes for those discharged alive.

Objective  To assess 3-year outcomes for Medicare beneficiaries who survive intensive care.

Design, Setting, and Patients  A matched, retrospective cohort study was conducted using a 5% sample of Medicare beneficiaries older than 65 years. A random half of all patients were selected who received intensive care and survived to hospital discharge in 2003 with 3-year follow-up through 2006. From the other half of the sample, 2 matched control groups were generated: hospitalized patients who survived to discharge (hospital controls) and the general population (general controls), individually matched on age, sex, race, and whether they had surgery (for hospital controls).

Main Outcome Measure  Three-year mortality after hospital discharge.

Results  There were 35 308 intensive care unit (ICU) patients who survived to hospital discharge. The ICU survivors had a higher 3-year mortality (39.5%; n = 13 950) than hospital controls (34.5%; n = 12 173) (adjusted hazard ratio [AHR], 1.07 [95% confidence interval {CI}, 1.04-1.10]; P < .001) and general controls (14.9%; n = 5266) (AHR, 2.39 [95% CI, 2.31-2.48]; P < .001). The ICU survivors who did not receive mechanical ventilation had minimal increased risk compared with hospital controls (3-year mortality, 38.3% [n = 12 716] vs 34.6% [n=11 470], respectively; AHR, 1.04 [95% CI, 1.02-1.07]). Those receiving mechanical ventilation had substantially increased mortality (57.6% [1234 ICU survivors] vs 32.8% [703 hospital controls]; AHR, 1.56 [95% CI, 1.40-1.73]), with risk concentrated in the 6 months after the quarter of hospital discharge (6-month mortality, 30.1% (n = 645) for those receiving mechanical ventilation vs 9.6% (n = 206) for hospital controls; AHR, 2.26 [95% CI, 1.90-2.69]). Discharge to a skilled care facility for ICU survivors (33.0%; n = 11 634) and hospital controls (26.4%; n = 9328) also was associated with high 6-month mortality (24.1% for ICU survivors and hospital controls discharged to a skilled care facility vs 7.5% for ICU survivors and hospital controls discharged home; AHR, 2.62 [95% CI, 2.50-2.74]; P < .001 for ICU survivors and hospital controls combined).

Conclusions  There is a large US population of elderly individuals who survived the ICU stay to hospital discharge but who have a high mortality over the subsequent years in excess of that seen in comparable controls. The risk is concentrated early after hospital discharge among those who require mechanical ventilation.

Context  Controversy exists about optimal management of anemia in end-stage renal disease.

Objective  To compare the mortality risk of different dialysis center–level patterns of anemia management.

Design, Setting, and Patients  Using data from Medicare's end-stage renal disease program (1999-2007), we characterized each US dialysis center's annual anemia management practice by estimating its typical use of erythropoiesis-stimulating agents (ESAs) and intravenous iron in hemodialysis patients within 4 hematocrit categories. We used Cox proportional hazards regression to correlate center-level patterns of ESA and iron use with 1-year mortality risk in 269 717 incident hemodialysis patients.

Main Outcome Measure  One-year all-cause mortality.

Results  Monthly mortality rates were highest in patients with hematocrit less than 30% (mortality, 2.1%) and lowest for those with hematocrit of 36% or higher (mortality, 0.7%). After adjustment for baseline case-mix differences, dialysis centers that used larger ESA doses in patients with hematocrit less than 30% had lower mortality rates than centers that used smaller doses (highest vs lowest dose group: hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.90-0.97). Centers that administered iron more frequently to patients with hematocrit less than 33% also had lower mortality rates (highest vs lowest quintile, HR, 0.95; 95% CI, 0.91-0.98). However, centers that used larger ESA doses in patients with hematocrit between 33% and 35.9% had higher mortality rates (highest vs lowest quintile, HR, 1.07; 95% CI, 1.03-1.12). More intensive use of both ESAs and iron was associated with increased mortality risk in patients with hematocrit of 36% or higher. These findings persisted across a range of secondary analyses.

Conclusions  Greater ESA and iron use were associated with decreased mortality risk at lower hematocrit levels, in which mortality rates are the highest. Although the overall mortality rate was lower at higher hematocrit levels, elevated mortality risk was associated with greater use of ESAs and iron in these patients.

Context  Trials comparing higher vs lower levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury or acute respiratory distress syndrome (ARDS) have been underpowered to detect small but potentially important effects on mortality or to explore subgroup differences.

Objectives  To evaluate the association of higher vs lower PEEP with patient-important outcomes in adults with acute lung injury or ARDS who are receiving ventilation with low tidal volumes and to investigate whether these associations differ across prespecified subgroups.

Data Sources  Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (1996-January 2010) plus a hand search of conference proceedings (2004-January 2010).

Study Selection  Two reviewers independently screened articles to identify studies randomly assigning adults with acute lung injury or ARDS to treatment with higher vs lower PEEP (with low tidal volume ventilation) and also reporting mortality.

Data Extraction  Data from 2299 individual patients in 3 trials were analyzed using uniform outcome definitions. Prespecified effect modifiers were tested using multivariable hierarchical regression, adjusting for important prognostic factors and clustering effects.

Results  There were 374 hospital deaths in 1136 patients (32.9%) assigned to treatment with higher PEEP and 409 hospital deaths in 1163 patients (35.2%) assigned to lower PEEP (adjusted relative risk [RR], 0.94; 95% confidence interval [CI], 0.86-1.04; P = .25). Treatment effects varied with the presence or absence of ARDS, defined by a value of 200 mm Hg or less for the ratio of partial pressure of oxygen to fraction of inspired oxygen concentration (P = .02 for interaction). In patients with ARDS (n = 1892), there were 324 hospital deaths (34.1%) in the higher PEEP group and 368 (39.1%) in the lower PEEP group (adjusted RR, 0.90; 95% CI, 0.81-1.00; P = .049); in patients without ARDS (n = 404), there were 50 hospital deaths (27.2%) in the higher PEEP group and 44 (19.4%) in the lower PEEP group (adjusted RR, 1.37; 95% CI, 0.98-1.92; P = .07). Rates of pneumothorax and vasopressor use were similar.

Conclusions  Treatment with higher vs lower levels of PEEP was not associated with improved hospital survival. However, higher levels were associated with improved survival among the subgroup of patients with ARDS.