Bottom line: Daily azithromycin decreases COPD exacerbations in those with a history of previous exacerbation at the cost of increased macrolide resistance and possible reversible decrements in hearing. The high degree of macrolide resistance at enrollment suggests non-antibacterial mechanisms might be responsible.
Citation: Albert RK, Connett J, Bailey WC, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689-698.
Serial Low-Dose CT Scans Decrease Lung Cancer Mortality
Clinical question: Does annual screening with low-dose CT scans reduce mortality from lung cancer in current or former heavy smokers?
Background: Lung cancer is still the top cause of cancer death in the United States, and its prevalence is increasing in the developing world. Prior trials of screening chest radiography and sputum samples have not shown a decrease in lung cancer mortality, but CT scans could help identify lung cancer at an earlier, more treatable stage.
Study design: Prospective, multicenter, randomized trial of low-dose (roughly one-fifth the radiation of traditional CT) annual CT versus annual chest radiography.
Setting: Thirty-three U.S. medical institutions.
Synopsis: The study enrolled 53,454 current or prior smokers with a history of smoking more than 30 packs a year who were randomly assigned to undergo three annual CT scans or chest X-rays. Any CT scans that showed a noncalcified nodule greater than 4 mm and chest X-rays that showed a noncalcified nodule or mass of any size were classified as “positive,” but follow-up was left to the discretion of the treating physicians. Participants were followed for 6.5 years on average.
Of those screened with CT, 40% had a positive screening test at some point, more than three times the rate of chest radiography, and 96.4% of these were false-positives, which was similar to chest radiography. Adverse events as a result of workup of eventual false positives were uncommon, occurring in around 1% of those who did not have lung cancer and in 11% of those who did. Screening reduced lung cancer mortality by 20% compared with chest radiography, with a number needed to screen to prevent one lung cancer death of 320. Cost-effectiveness and effects of radiation were not assessed.
Bottom line: Serial screening with low-dose CT reduces lung cancer mortality at the cost of a high rate of false-positives. Questions remain about cost-effectiveness and radiation exposure.
Citation: National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395-409.
One-Week Delay in Starting Parenteral Nutrition in ICU Patients Is Associated with Better Outcomes
Clinical question: In patients admitted to the ICU who are at risk for malnutrition, does supplementing enteral feeding with parenteral feeding on the day of admission improve outcomes when compared with supplementation starting on Day 8?
Background: Patients with critical illness are at risk for malnutrition, which may lead to worsened outcomes. Many are unable to tolerate enteral feeding. However, adding parenteral nutrition has risks, including overfeeding and hyperglycemia.
Study design: Prospective, multicenter, randomized controlled trial. Neither patients/families nor ICU physicians were blinded.
Setting: Two university hospitals in Belgium.
Synopsis: The study included 4,640 patients admitted to the ICU who were “at risk” for malnutrition (assessed using a Nutritional Risk Score of >3). They were randomized to early initiation of parenteral nutrition on Day 1 or late initiation of parenteral nutrition on Day 8, in both cases only if needed to supplement enteral feeding. Both groups received intensive IV insulin protocols to keep blood glucose at 80 mg/dL to 110 mg/dL. The study populations were well-matched, with similar APACHE II scores. Of the total patients, 42% were emergency admissions to the ICU (more than half of which had sepsis), while scheduled cardiac surgery patients made up the majority of the rest of the study participants.