Primecuts – This Week In The Journals

By Michael Fingerhood, MD,  MPH

Faculty Peer Reviewed

Last week the world’s eyes were on Stockholm, Sweden and the announcement of the 2010 Nobel Prize Awards.  We here at PRIMECUTS say “Grattis” to Robert Edwards, this year’s winner of the Nobel Prize in Medicine, for his pioneering work on in-vitro fertilization. Edwards discovered how to fertilize and mature human embryos outside the womb and, along with Dr. Patrick Steptoe, perfected their insertion via laparoscopy to achieve viable implantation [1]. This award separately highlights the problems of injecting politics into science, as the Medical Research Council (The British NIH) refused to fund Edwards’ work for nearly a decade on the Malthusian notion that the world was too overpopulated. Nearly 40 years later this problem persists: federal funding for embryonic stem cell research, a field which grew out of Edwards’ work, has again been curtailed after an August court ruling rebuked legislation by the Obama administration [2]. Overshadowing this controversy is the public apology the US made this week for the recently-discovered, NIH-funded experiments on sexually transmitted diseases in Guatemala, during which hundreds of prisoners, the mentally ill and soldiers were, without consent, purposefully infected with syphilis, gonorrhea and chancroid from 1946-1948 [3]. This shameful blight on our history shows that while politics has no place in research, there will always be a need for medical ethics.

Be it our country’s checkered past with STD research, the controversy over stem cell funding, the beleaguered economy or just our own work and life responsibilities, there are many reasons to lose sleep these days. However new research in the Annals of Internal Medicine suggests that loss of sleep may prevent you from slimming down [4]. Nedeltcheva et al conducted a clinical trial of overweight adults randomized to either normal or reduced sleep, with similar levels of physical activity and diets individualized to restrict caloric intake to 90% of maintenance needs. Total/fat free body mass was calculated using a scale and dual-energy x-ray absorptiometry (DEXA) and mean body weights were compared via paired t-tests, with the results analyzed via mixed linear models to control for differences in baseline characteristics between the two groups. While there was no significant difference in total weight loss or neuro-endocrine hormones (leptin, gherrelin or cortisol), subjects randomized to sleep restriction had significantly less weight lost from fat and suffered subjectively greater feelings of hunger. Although the study was underpowered (n=10) and suffered from a limited study time (14 days),  Nedeltcheva et al have given us a lot to think about, or rather, to sleep on.

While on the subject of endocrinology, an article in The New England Journal of Medicine, by Zoungas et al reanalyzed data from ADVANCE, a large randomized controlled trial of standard versus intensive glucose control among type II diabetics, to determine if severe hypoglycemic episodes lead to adverse vascular events and death [5]. The authors examined the association between severe hypoglycemic events and risk of macrovascular events, including death, using a cox-proportional hazards model to adjust for differences in baseline covariates between the two groups. Hypoglycemia was significantly associated with non-fatal stroke and MI, cardiovascular mortality and all-cause-mortality. While the intensive control group had significantly higher rates of hypoglycemia, those episodes were less likely to be associated with death than in the standard therapy group, leading to the question of whether hypoglycemia was actually a causal factor or merely a clinical indicator of other underlying physiologic derangements that can eventually lead to death. In addition, there was no significant difference in all-cause mortality between the intensive therapy and standard therapy groups, a finding which puts the ADVANCE trial at odds with the ACCORD trial and makes the question of optimal blood glucose management for diabetics more confusing [6]. 

Now on to the heart, or rather its failure; also in The New England Journal of Medicine, a study of Rolofylline, a novel adenosine-receptor antagonist, was undertaken by Massie et al [7]. In a large double-blind, placebo-controlled trial the authors randomized patients hospitalized for acute heart failure with renal impairment to either placebo or IV Rolofylline along with optimal medical management. Outcomes were measured via intention-to-treat methodology and included both treatment success and clinical status (a composite primary endpoint which included all cause mortality) and were analyzed via cox-proprtional hazard regression. The results showed Rolofylline provided no benefit in mortality, but worsened renal impairment and increased risk of seizure (a known side-effect of adenosine-receptor antagonists). While the results of this trial are disappointing for those looking for additional options to treat their heart failure patients, it is encouraging to see research with negative results, as such studies are equally important to advance the science but are less often published.

Finally we turn our attention away from the hospital to the community at large; a new article in JAMA studied the relationship between the type of CPR performed by lay-persons (standard or compression-only [COCPR]) and their resulting survival among adults suffering out-of-hospital cardiac arrest in Arizona in light of the state’s (then-new) compression-only CPR teaching campaign [8]. In this large prospective observational cohort study, Bobrow et al used multivariate logistic regression to analyze the association between CPR type and survival while controlling for confounding variables. The results were clear and impressive; not only was COCPR associated with more than 50% increased chance of survival (adjusted) but also almost double the rate of survival with full neurologic status (unadjusted). This powerful study not only demonstrates the superiority of COCPR to conventional CPR for lay persons in the treatment of cardiac arrest, it shows that a simple population-wide educational initiative can have a major effect on clinical outcomes. That’s it for now – look for more exciting articles to come in future Primecuts!

Dr.  Fingerhood is a first year resident at NYU Langone Medical Center

Peer reviewed by Michael Poles, MD, Section Editor, Clinical Correlations

Image of  Wikimedia Commons (Bourn Hall Clinic, in the village of Bourn five miles west of Cambridge, was the world’s first ‘test-tube baby’ clinic.)

References:

1.  Nobel Prizes: Honor For Test Tube Baby Pioneer. Science. 2010 October 8 (330): pgs. 158-159. Print

 2.  Stem Cells in Court, Scientists Fear for Careers. The New York Times. 2010 October 4; Science. Web. (http://www.nytimes.com/2010/10/06/science/06stem.html?_r=1&scp=1&sq=stem%20cells%20in%20the%20courts&st=cse)

 3.  Guatemala Study from 1940’s Reflects A ‘Dark Chapter’ in Medicine. Science. 2010 October 8 (330): pg. 160. Print

 4.  Nedeltcheva AV, Kilkus JM, Imperial J et al. Insufficient Sleep Undermines Dietary Efforts to Reduce Adiposity. Ann Intern Med. 2010;153:435-441. Print

 5.  Zoungas S, Patel A, Chalmers J et al. Severe Hypoglycemia and Risks of Vascular Events and Death. N Engl J Med 2010; 363:1410-8. Print

 6.  Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptomatic, severe hypoglycemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study. BMJ 2010;340:b4909. Print

 7.  Massie, BM, O’Connor, CM, Metra M et al.  Rolofylline, an Adenosine A1−Receptor Antagonist, in Acute Heart Failure. N Engl J Med 2010;363:1419-28. Print

 8.  Bobrow BJ, Spaite DW, Berg RA et al. Chest Compression–Only CPR by Lay Rescuers and Survival From Out-of-Hospital Cardiac Arrest. JAMA. 2010;304(13):1447-1454. Print

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