Update, June 30-- Jann Ingmire, the director of media relations for JAMA and the Archives Journals, sent the following clarification late this afternoon: “The authors submitted the additional data in a letter just prior to publication.  That letter was submitted by the authors in response to a request for changes from the NIH program director (not the journal).” This information is helpful, but it still does not shed any light on the substance of the problems with the Archives paper or the issue concerning the last-minute timing of events, and it raises a new question about the NIH’s involvement with this study.

Over on his blogs Retraction Watch and Embargo Watch, Ivan Oransky has published statements about the mystery of the disappearing paper from the editor of the journal that pulled the paper and the first author of the paper.   Unfortunately, the statements don’t really shed a whole lot of light on the unprecedented event, in which the publication of a paper was halted only 12 minutes before its scheduled debut.

Rita Redberg, the editor of  Archives of Internal Medicine told Oransky that she did not know when (if ever) a revised version of the paper would be published: “we are awaiting a revised version that contains additional data which must be reviewed and analyzed,” she said.

In response to Oransky’s question about peer review of the study, she said:

The study was peer reviewed, as are all Archives articles, and in general peer review works well as long as all data are provided as required by Instructions to Authors. We thought we had all the data when the manuscript underwent peer review, but it turned out there was additional data to be considered.

Here is the comment Oransky received from the first author of the paper, Robert Schneider:
Click to continue reading…

Here’s something I’ve never seen: 12 minutes before the scheduled publication of a paper the journal publishing the paper announced that it had “made the decision not to publish” the paper. Here’s what happened:

Last Thursday the JAMA/Archives media team issued a press package to  accredited media about several articles scheduled for publication in Archives of Internal Medicine on Monday (today) at 4 PM ET. The package included a press release (see below) about an article, “Stress Reduction in the Secondary Prevention of Cardiovascular Disease: A Randomized Controlled Trial of Transcendental Meditation and Health Education in African Americans.” The first author was Robert Schneider, MD, from the Maharishi University of Management, Maharishi Vedic City, Iowa. Co-authors from the same institution were: Maxwell Rainforth PhD, Sanford Nidich. EdD, Carolyn Gaylord-King, PhD, John Salerno, PhD, and Charles Alexander, PhD. Two other authors, Clarence Grim and Theodore Kotchen are from the Medical College of Wisconsin in Milwaukee.

Today (Monday), at 3:48 PM ET, 12 minutes before the scheduled publication of the paper, the following message appeared in my inbox:

Subject: Important Notice from Archives of Internal Medicine — Please Open Immediately!

The editorial office of the Archives of Internal Medicine has made the decision not to publish,  “Stress Reduction in the Secondary Prevention of Cardiovascular Disease: A Randomized Controlled Trial of Transcendental Meditation and Health Education in African Americans,” by Schneider et al, and the accompanying Commentary by Mehta and Bairey Merz that was to post Online First at 3 PM central time today.

The decision is to allow time for review and statistical analysis of additional data not included in the original paper that the authors provided less than 24 hours before posting. We apologize for the short notice, but hope you will understand and not run your stories on this study today.

Sincerely,

JAMA/Archives Media Relations

Without more information it’s difficult to comment at this point, but I strongly suspect that we will hear more about this story in the future. It should be noted that the study was funded by the NHLBI. In addition, the same study was presented at the AHA Scientific Sessions in 2009. The first author, Robert Schneider, is the Dean of the College of Maharishi Consciousness Based Health Care at Maharishi University of Management and Director of the Institute for Natural Medicine and Prevention, which is funded by the NIH’s National Center for Complementary and Alternative Medicine. “Schneider is a specialist in clinical hypertension and has published extensively, including papers in the American Journal of Cardiology, Stroke, and Hypertension.

[Update: the NCCAM has written to inform me that it "does not currently fund research at Maharishi University of Management; we last provided grant funding to the institution in FY 2004." The information in the article was taken directly from the website linked above.]

For more on this story see my next post.
Click here to read the press release originally issued by JAMA/Archives…

In 2008 347 million people in the world had diabetes, more than twice the 153 million in 1980, according to estimates contained in a report in the Lancet from the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group. The papers appears in conjunction with the annual meeting of the American Diabetes Association.

Throughout  the world diabetes prevalence has risen or, at best, stayed the same over the last 30 years, the authors report. Although most of the increase was due to population growth and an increased proportion of elderly people, 30% of the increase was due to an increase in risk factors such as obesity.
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The FDA today said that it was recommending more conservative dosing of ESAs (erythropoiesis-stimulating agents) in patients with chronic kidney disease (CKD). The possible beneficial effects of the drugs to decrease the need for transfusions in CKD patients should be weighed against the increased risk of cardiovascular events, the FDA said. ESA therapy should be given at the lowest possible dose to reduce the need for transfusions. Currently available ESAs include epoetin alfa, marketed as Epogen (Amgen) and Procrit (J&J) and darbepoetin alfa, marketed as Aranesp, (Amgen).
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Pfizer and Bristol-Myers Squibb said today that their new oral direct Factor Xa drug apixaban, which will be marketed under the brand name of Eliquis, had met the primary endpoint of the ARISTOTLE study.

The Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation (ARISTOTLE) study was designed to compare the factor Xa inhibitor apixaban with warfarin for the prevention of stroke and systemic embolism in atrial fibrillation (AF) patients with additional risk factors for stroke. The primary outcome was the time to first occurrence of either stroke or systemic embolism. According to the company, apixaban met the criteria for noninferiority to warfarin in the trial.
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Although the cardiovascular benefits of statin therapy are well-characterized, recent studies have raised concerns that intensive statin therapy increases the risk of developing type 2 diabetes. Now, a new meta-analysis published in JAMA provides a more precise estimate of the risk of diabetes associated with statin therapy and also weighs that risk against the cardiovascular benefits of statins.
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The FDA said that the anti-smoking drug varenicline (Chantix) may increase the risk of cardiovascular events in people who already have cardiovascular disease. The new information will be added to the drug’s label and Medication Guide for patients.

The FDA does not recommend that people with cardiovascular disease discontinue taking varenicline, but says that physicians and patients should weigh the known benefits of varenicline with the potential risks. Pfizer, which manufactures the drug, will be required to conduct a large meta-analysis.
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(Updated with comments from Joe Ross and Steve Nissen)– In a perspective published in the New England Journal of Medicine, two FDA officials, Amy Egan and Eric Colman, explain in some detail the recent changes made by the FDA regarding simvastatin. They note that in the SEARCH trial myopathy developed in 52 (0.9%) patients in the 80 mg group compared to only 1 (0.02%) patient in the 20 mg group. There were 22 cases of rhabdomyolysis in the high dose group compared to no cases in the low dose group. Further, patients at high risk usually developed myopathy early in the course of treatment.

Click to continue reading, including comments from Joe Ross and Steve Nissen…

Approximately 40% of cardiac resynchronization therapy (CRT) devices are implanted in patients with QRS intervals below 150 msecs, but a meta-analysis published in Archives in Internal Medicine finds that these patients may not benefit from the device.

Ilke Sipahi and colleagues performed a meta-analysis that included 5 CRT clinical trials (COMPANION, CARE-HF, REVERSE, MADIT-CRT, RAFT) with designs that enabled them to examine the effect of QRS duration on outcome. Although patients with severely prolonged QRS had a 40% reduction in risk associated with CRT therapy (CI 0.53-0.67, p<.001), no benefit at all was observed in the patients with only moderately prolonged QRS. The same finding was observed in patients with class 1 and 2 heart failure as in patients with class 3 and 4 heart failure. The presence or absence of an ICD did not alter the pattern.
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A new study raises the possibility that a protein produced in the lungs may improve the prediction of cardiovascular disease. In a paper in the European Journal of Cardiology, John Hill and colleagues report on their research with surfactant protein-D (SP-D), which is produced in the lungs and whose levels are increased in the general circulation following lung injury and lung inflammation.

The researchers first measured SP-D levels in 806 patients undergoing coronary angiography in order to determine its value in predicting cardiovascular risk. In the second stage they measured SP-D levels in a replication cohort of 4,486 current and former smokers with no known history of coronary disease.
Click to continue reading, including a comment from James De Lemos…

The main results of SHARP (Study of Heart and Renal Protection) have now been published in the Lancet, following their preliminary presentation last November at the American Society of Nephrology meeting. The results are also posted online on the trial’s website.

In brief, SHARP randomized 9270 patients with chronic kidney disease (one-third of whom were on dialysis) to either placebo or the combination of simvastatin and ezetimibe. After a median followup of 4.9 years the rate of major atherosclerotic events (defined as nonfatal MI or coronary death, non-hemorrhagic stroke, or arterial revascularization excluding dialysis access procedures) was significantly reduced from 13.4% in the placebo group to 11.3% in the combination therapy group (RR 0.83, CI 0.74-0.94, p=0.0021).
Click to continue reading, including comments from James Stein and Merck…

An FDA advisory panel will review the premarket approval (PMA) application for the Sapien transcatheter aortic valve on July 20, the device’s manufacturer, Edwards, has announced. The application is based on results from the PARTNER B trial, which compared the Sapien valve to optimal medical therapy in patients with severe aortic stenosis who were not eligible for surgery.
Click to read the press release from Edwards…

The latest report on the 40,000 women enrolled in the Women’s Health Study provides further demonstration that smoking is “a potent risk factor for symptomatic PAD.” The paper by David Conen and colleagues has been published in Annals of Internal Medicine.

Here are the age-adjusted incidence rates per 1000 person-years of follow-up:
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