Primecuts – This Week In The Journals

July 5, 2011

Jeffrey Shyu, MD

Faculty Peer Reviewed

As the debt ceiling debate continues to rage stateside and as Greece’s financial bailout negotiations take up international headlines, this past week also proved to be a very active and exciting one for medical research.

This edition of Primecuts begins with controversy amongst experts in the spine field. A group of leading researchers submitted a scathing editorial to Spine Journal, blasting industry-sponsored research on recombinant bone morphogenetic protein-2 (rhBMP-2), a bone growth product popular in spinal fusion surgeries [1]. Medtronic, the maker of rhBMP-2 (trade name Infuse), has sponsored trials comparing the product to bone grafts, and according to its critics, the industry-sponsored studies frequently downplayed the risk of complications such as inflammation, osteolysis, cancer, infection, and male sterility. In a literature review published in the same issue, the authors found that the level of adverse events was downplayed 10 to 50-fold, with many of the prior authors having financial ties to the maker of the product [2]. For what it’s worth, Medtronic’s Chairman and CEO Omar Ishrak insists that the product is “safe” [3]. I for one applaud the editors and authors of this Spine Journal issue, and more disclosure and criticism of industry-sponsored research should be had in all fields of medicine.

The value of imaging for cancer screening was another major topic this past week, as two high-profile studies were published demonstrating a mortality benefit in the use of imaging to detect cancer. In Radiology, a three-decade long trial of over 133,000 women in Sweden who were randomized to mammography screening versus usual care found an absolute long-term benefit to mammography [4]. The study had previously reported a 30% reduction in breast cancer mortality among 40-74 year old women [5], and study participants were now followed for a longer period of time. In the current study, the number of women needed to screen for a period of 7 years to prevent one breast cancer death ranged from 414 to 519. Moreover, most of the deaths that were prevented would have occurred in the first 10 years of screening. This new study will surely create additional confusion about the benefit of mammography, especially regarding when a woman should start getting the exams, given that the US Preventive Services Task Force recommended in 2009 that mammography screening for most people should begin at age 50 instead of 40 [6]. Unfortunately, this study did not specifically look at the benefit of screening for people between 40 and 50.

Also, the New England Journal of Medicine published the final report came of a study whose results were first announced last year.  This study found a 20% relative mortality risk reduction for high-risk subjects when using chest CT compared to conventional x-ray (p 0.004) [7]. 53,454 people were enrolled in this prospective, multi-center study, and eligible subjects included people between 55 and 74 years of age who had at least 30 pack years of smoking history. Subjects were randomized to three low-dose CTs versus conventional chest x-rays. The survival benefit was attributed to detection of cancers at an earlier stage. However, as one might expect, the rate of positive screening results was substantially higher in the CT group compared to x-ray (24.2% versus 6.9%), and false positives were 96.4% and 94.5%, respectively. Given the increased number of positive results (the vast majority false positive), many subjects underwent further diagnostic workup including further imaging; some had invasive procedures, though adverse events from invasive procedures were rare in both groups. Although the mortality benefit to CT screening is real, many more people are likely to experience the anxiety that comes with a possible (though unlikely) cancer diagnosis if this screening test becomes widely adopted.

Also in the New England Journal, a randomized, multicenter trial with over 4600 patients looked at the timing of starting parenteral nutrition for critically ill patients who cannot obtain sufficient nutrition enterally [8]. Patients either had parenteral nutrition started within 48 hours after ICU admission (early group), or it was not initiated until after day 8 (late group). The researchers found that with late initiation, patients were 6.3% more likely to be discharged alive earlier from the ICU (p = 0.04) and from the hospital (p = 0.04). They also had fewer infections compared to the early group (22.8% versus 26.2%), although death rates in the hospital and at 90 days were similar. Previously, many had thought that early feeding (enteral or parenteral) was desirable. The authors also speculate that the increased risk of complications may be due to early parenteral nutrition causing delayed autophagy and inadequate clearance of microorganisms and cell damage.

Finally, in non-human medical news, for the second time in history a disease has been eradicated from the face of the earth [9, 10]. The first was smallpox, which most of our readers surely know about. This one is rinderpest, which is (was) a relative of measles and an ancient scourge of cattle and other cloven-hoofed animals, killing as much as 95% of afflicted creatures. Despite being noninfectious to humans, given our reliance on domesticated organisms, the virus has had a role in bringing down Rome and starting revolutions in France and Russia. But with vaccines, new diagnostic tests, and aggressive outreach to faraway lands, veterinarians have now conquered the “cattle plague”. This event should give us human doctors some optimism for eradicating our own ancient adversaries like polio or measles, although given the skepticism that some people hold towards vaccines these days, we may still have a long road ahead of us.

Dr. Jeffrey Shyu recently completed his preliminary year internal medicine residencyat NYU Langone Medical Center

Peer reviewed by Neil Shapiro, MD, Editor-In-Chief, Clinical Correlations

Image courtesy of Wikimedia Commons

 References:

 1. Carragee EJ, Ghanayem AJ, Weiner BK, Rothman DJ, Bono CM. A challenge to integrity in spine publications: years of living dangerously with the promotion of bone growth factors. The Spine Journal 2011; 11: 463-468. http://www.spine.org/Pages/ConsumerHealth/NewsAndPublicRelations/NewsReleases/2011/pressrelease1_062811.aspx

 2. Carragee EJ, Hurwitz EL, Weiner BK. A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: emerging safety concerns and lessons learned. The Spine Journal 2011; 11: 471-491. http://www.spine.org/Pages/ConsumerHealth/NewsAndPublicRelations/NewsReleases/2011/pressrelease1_062811.aspx

 3. Medtronic CEO Omar Ishrak statement on rhBMP-2 articles in Spine Journal. July 28, 2011. http://wwwp.medtronic.com/Newsroom/NewsReleaseDetails.do?itemId=1309287256363&lang=en_US

 4. Tabár L, Vitak B, Chen TH, Yen AM, Cohen A, Tot T, Chiu SY, Chen SL, Fann JC, Rosell J, Fohlin H, Smith RA, Duffy SW. Swedish Two-County Trial: impact of mammographic screening on breast cancer mortality during 3 decades. Radiology 2011. Published online before print June 28, 2011. http://radiology.rsna.org/content/early/2011/06/15/radiol.11110469.abstract

 5. Tabár L, Gad A, Holmberg LH, Ljungquist U, Kopparberg County Project Group, Fagerberg CJG, Baldetorp L, Gröntoft O, Lundström B, Mànson JC, Östergötland County Project Group, Eklund G, Day NE, Pettersson F. Reduction in mortality from breast cancer after mass screening with mammography: randomized trial from the Breast Cancer Screening Working Group of the Swedish National Board of Health and Welfare. The Lancet 1985: 325 (8433). 829-832. http://www.sciencedirect.com/science/article/pii/S0140673685922044

 6. US Preventive Services Task Force: Screening for breast cancer. 2009 recommendations. http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrca.htm

 7. The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. New England Journal of Medicine 2011. Published online ahead of print June 29, 2011. http://www.nejm.org/doi/full/10.1056/NEJMoa1102873?query=featured_homehttp://www.nejm.org/doi/full/10.1056/NEJMoa1104621

 8. Casaer MP, Mesotten D, Hermans G, Wouters PJ, Schetz M, Meyfroidt G, Van Cromphaut SV, Ingels C, Meersseman P, Muller J, Vlasselaers D, Debaveye Y, Desmet L, Dubois J, Van Assche A, Vanderheyden S, Wilmer A, Van den Berghe G. Early versus late parenteral nutrition in critically ill adults. New England Journal of Medicine 2011. Published online ahead of print June 29, 2011. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1102662

 9. “Rinderpest, scourge of cattle, is vanquished”. Donald J. McNeil Jr. New York Times, June 27, 2011. http://http://www.nytimes.com/2011/06/28/health/28rinderpest.html

 10. Declaration of global freedom from rinderpest and implementation of follow-up measures to maintain world freedom from rinderpest. Draft resolution, Thirty-seventh session of the Food and Agriculture Organization of the United Nations. Rome, June 25 – July 2 2011. http://www.fao.org/docrep/meeting/022/mb363e.pdf

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