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JAMA. 2007;298:1129.

Effects of Homocysteine Lowering in Renal Disease
High homocysteine levels are a risk factor for vascular complications and mortality in patients with chronic and end-stage renal disease. In a randomized placebo-controlled trial, Jamison and colleagues (SEE ARTICLE) investigated whether treatment to lower homocysteine levels with a combination of high-dose folic acid and vitamins B₆ and B₁₂ is associated with a reduction in mortality, cardiovascular events, or amputations in patients with advanced renal disease. The authors report significant reductions in homocysteine levels among patients in the intervention group but no improvement in all-cause survival or incidence of vascular disease compared with patients receiving placebo. In an editorial, Baigent and Clarke (SEE ARTICLE) discuss the evidence linking elevated homocysteine levels to vascular disease risk and possible reasons that reductions in homocysteine levels have not been associated with improved outcomes.

Carvedilol in Pediatric Heart Failure
In the prospective, randomized Pediatric Carvedilol Study, investigators assessed the effect of adding carvedilol vs placebo to conventional treatment of children and adolescents with symptomatic systolic heart failure. Shaddy and colleagues (SEE ARTICLE) writing for the trial investigators report that in contrast to the documented benefits of -blockers in adults with heart failure, there was no significant difference in a composite measure of heart failure outcomes between the children and adolescents randomly assigned to carvedilol vs placebo. In an editorial, Gidding (SEE ARTICLE) discusses the importance of clinical trials in pediatric cardiology and lessons from this study for the design of future investigations.

Thiazolidinediones and Cardiovascular Event Risks
The thiazolidinediones pioglitazone and rosiglitazone are effective in improving glycemic control among patients with type 2 diabetes mellitus, but recent evidence has suggested a possible increased risk of cardiovascular events associated with these drugs. Two articles in this issue provide additional data to assess these risks. Lincoff and colleagues (SEE ARTICLE) analyzed pooled data from 19 randomized clinical trials of pioglitazone and found that compared with patients receiving placebo or a comparator drug, patients who received pioglitazone had a significantly lower risk of death, myocardial infarction, or stroke but experienced an increased risk of serious heart failure. Singh and colleagues (SEE ARTICLE) analyzed pooled data from 4 randomized trials of rosiglitazone and found that patients receiving rosiglitazone for at least 12 months had a significantly increased risk of myocardial infarction and heart failure compared with patients receiving a placebo or comparator drug. In an editorial, Solomon and Winkelmayer (SEE ARTICLE) discuss these findings in the context of measures to improve drug safety.

CLINICIAN'S CORNER
Intractable Nausea and Vomiting
Perspectives on Care at the Close of Life

Mr Q, a 50-year-old man with metastatic esophageal cancer treated with palliative chemotherapy, was admitted to the hospital with intractable nausea and vomiting. Wood and colleagues discuss the pathophysiology of intractable nausea and vomiting and present a mechanism-based approach to the evaluation and treatment of this symptom complex.

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A Piece of My Mind
"Perhaps it is reverence for knowledge that has fostered so many of my happy years of teaching medicine." From "On Knowledge."

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Medical News & Perspectives
Evidence that electroconvulsive therapy is an effective and safe treatment for severe major depression is helping to overcome inaccurate perceptions of the technique that have stigmatized its use.

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Applying Trial Data to Individuals
Multivariate risk-stratified analysis of clinical trial data can identify important treatment differences among patients with varying levels of baseline risk.

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Author in the Room Teleconference
Join Douglas R. Lowy, MD, on September 19 from 2 to 3 PM eastern time to discuss human papillomavirus vaccine among young women with preexisting infection. To register, go to http://www.ihi.org/AuthorintheRoom.

Audio Commentary
Dr DeAngelis summarizes and comments on this week's issue. Go to http://jama.ama-assn.org/misc/audiocommentary.dtl.

JAMA Patient Page
For your patients: Information about chronic kidney disease.

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