Primecuts-This Week in the Journals

August 19, 2013

By: Kelly Forrester, MD

At Fenway Park on Sunday, after hitting a 6th inning home run that led the Yankees to a victory against the Red Sox, Alex Rodriguez made the ultimate statement to angry officials and fans that he is not going to give in.  Rodriguez has been under fire since January because of his ties to the Biogenesis baseball scandal where he was accused of using performance-enhancing drugs.  On August 5th, Rodriguez was suspended for 211 games, although he is allowed to play during his appeal process.  Last week, Rodriguez’s lawyer, Joseph Tacopina, claimed that the baseball commissioner is trying to wrongfully use Rodriguez as the “poster boy” for doping.  He also claimed that the Yankees are working with the commissioner to try to nullify Rodriguez’s contract.  Moving from the ballpark to the field of medicine…

“The resident 15”: A fear of every new intern as the dreaded consequence of long work hours and new stressors.  Unfortunately, a recent Nature Communications article proves what we have always suspected, that sleep deprivation increases the desire for high-calorie foods by altering the central nervous system’s regulation of dietary intake.  After deprivation of one night of sleep, study participants rated the desirability of 80 different food options and were told that they would subsequently be given whichever item they rated the highest.  While making their choices, functional magnetic resonance imaging (fMRI) scans measured their brain activity.  The study was then repeated seven days later using the same participants after receiving multiple nights of well-rested sleep averaging 8.2 hours a night.  The results showed that sleep deprivation diminishes activity in the regions of the frontal cortex and insular cortex involved in appetite evaluation while increasing activity in the amygdala.  The frontal and insular cortex are involved in assigning stimulus value and integrating food features that govern preferences, while the amygdala controls the motivation to eat, especially when the food is more desirable.  Participants also rated high-calorie food items more attractive after the night of sleep deprivation.  When correlating the fMRI results with the increased desire for weight-promoting food items in sleep-deprived participants, the findings suggest that weight gain associated with sleep deprivation is a result of decreased activity in the frontal cortex and excess activity in subcortical limbic regions.  Therefore, the next time you are on night float, try to elicit the help of your frontal cortex in choosing a salad over a pizza (1).

In other news this week, a New England Journal article re-analyzed the data from the 2003 Prostate Cancer Prevention Trial (PCPT) and found interesting results concerning the use of finasteride to prevent prostate cancer.  In the 2003 article, finasteride was found to reduce the relative risk of prostate cancer by 24% compared to placebo (2). However, finasteride also increased the rate of high-grade prostate cancer.  Despite subsequent analyses that showed that this increase was potentially caused by detection bias, the fear of increasing high-grade tumors has eliminated the use of finasteride in prostate cancer prevention.  The new study compared the risk of death among men treated with finasteride with men treated with placebo.  The assumption was that if finasteride actually increases the rate of high-grade prostate cancers, then there should be increased mortality in the finasteride group during long-term follow up.  The results showed that the 15-year rate of survival between the two groups was relatively similar and that there was no increase in the risk of death among men receiving finasteride (3). Although at first glance this makes finasteride seem like a wonderful primary prevention strategy, both groups in the study were regularly being screened for prostate cancer.  Given the recommendation from the United States Preventive Services Task Force (USPSTF) against screening for prostate cancer with prostate specific antigen (PSA), finasteride would have an undefined role in reducing the morbidity associated with the disease.  In addition, the study proved that it also has no role in decreasing mortality.  Perhaps the only use of finasteride is in men who choose to continue PSA testing despite current recommendations.

A recent article in The Lancet addressed another ubiquitous fear of healthcare workers: Clostridium difficile.  The study examined whether the probiotics lactobacilli and bifidobacteria help in prevention of antibiotic-associated diarrhea as well as its subset, C. difficile diarrhea, in older inpatients (the PLACIDE trial).  The results of previous meta-analyses, which have mostly supported the use of probiotics in preventing antibiotic-associated diarrhea, are controversial because of the variations in individual study designs and small sample sizes (4). The PLACIDE trial is a multicenter, randomized, double-blinded, placebo controlled trial with a sample size of 2,941 patients.  Patients aged 65 or older who had been treated with one or more oral or intravenous antibiotics in the previous seven days were given either a high-dose microbial preparation containing Lactobacillus acidophilus and bifidobacterium or a placebo pill.  The patients were then followed for 12 weeks.  Interestingly, the study found that there was no difference in antibiotic-associated diarrhea (including C. difficile associated diarrhea) between the two groups (95% CI 0.84-1.28, p=0.71) (5). Although probiotics do not appear to be useful in the prevention of antibiotic-associated diarrhea, clinicians may still decide to use them given their small risk of harm.

A JAMA article this week compared medical management versus early surgical intervention on the outcomes of asymptomatic mitral regurgitation from flail mitral valve leaflets.  Current controversy exists regarding the correct treatment choice for those without the American Heart Association guideline class I triggers, meaning no or minimal symptoms and no left ventricular dysfunction.  European recommendations favor medical management, or watchful waiting until a distinct event is encountered, whereas North American recommendations are in favor of early surgical intervention.  The primary endpoint of the study was all-cause mortality, and the secondary endpoints were heart failure and new-onset atrial fibrillation.  The study found that early surgical intervention, meaning within three months of diagnosis, was not associated with increased mortality or heart failure.  It was, however, associated with a small increase in new-onset atrial fibrillation.  Long-term results showed that early surgical correction was associated with a significant survival benefit and a decrease in heart failure risk (6). There was no difference in late-onset atrial fibrillation.  As for clinical decision making, it is still prudent to only refer patients to surgery if the surgical risk is low and the likelihood of valve repair success is high.

Other interesting articles:

1.  DeCamp, M., T. Koenig, and M. Chisolm. Social Media and Physicians’ Online Identity Crisis. JAMA.  August 14, 2013.  310(6): 581-582.

http://jama.jamanetwork.com/article.aspx?articleid=1728725

This editorial discusses how it is impossible for physicians to separate their professional and social media identities.  It rebels against the recommendations of the majority of medical organizations to maintain strict patient-physician boundaries online.  The article claims that it is not only operationally impossible, but it also induces psychological burden on physicians, is inconsistent with the wishes of active physician social media users, and it potentially instills patient distrust in their physicians.

2.  US Burden of Disease Collaborators.  The State of US Health, 1990-2010: Burden of Diseases, Injuries, and Risk Factors.  JAMA.  August 14, 2013.  310(6): 591-608.

http://jama.jamanetwork.com/article.aspx?articleid=1710486

In this study, researchers compared health outcomes in the USA with those of 34 other countries using data from the Global Burden of Disease Study 2010 (GBD 2010).  From 1990 to 2010, the US rank among the 34 other countries for age-standardized death rate changed from 18th to 27th.  The life expectancy at birth rank changed from 20th to 27th, and the healthy life expectancy (HALE) changed from 14th to 26th.  The age-specific rates of years lived with disability remained stable.

3.  Hsu-Wen, C., J. Wang, C. Chang, et al.  Risk of Severe Dysglycemia Among Diabetic Patients Receiving Levofloxacin, Ciprofloxacin, or Moxifloxacin in Taiwan.  Clinical  Infectious Disease.  August 14, 2013.

http://cid.oxfordjournals.org/content/early/2013/07/23/cid.cit439.abstract

Outpatient diabetic patients newly prescribed levofloxacin, ciprofloxacin, moxifloxacin, cephalosporins, and macrolides were monitored for dysglycemia for 30 days after initiation of antibiotic therapy.  The study found that diabetics are at increased risk for dysglycemia when using oral fluoroquinolones.  The risk of hypoglycemia was higher in those using moxifloxacin compared to levofloxacin and ciprofloxacin.

Kelly Forrester, MD is a first year internal medicine resident at NYU Langone Medical Center

Peer Reviewed by Matthew Vorsanger, MD, Associate Editor, Clinical Correlations

References:

1.  Greer, S., A. Goldstein, and M. Walker. The impact of sleep deprivation on food desire in the human brain. Nature Communications.  August 6, 2013.  4:2259.

2.  Thompson, I., P. Goodman, C. Tangen, et al.  The influence of finasteride on the development of prostate cancer.  The New England Journal of Medicine.  2003.  349:215-24.

3.  Thompson, I., P. Goodman, C. Tangen, et al. Long term survival of participants in the prostate cancer prevention trial. The New England Journal of Medicine.  August 15, 2013.  369:7.

4.  McFarland, LV.  Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease.  American Journal of Gastroenterology.  2006.  101: 812–22.

5.  Allen, S., K. Wareham, D. Wang et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet. August 8, 2013. Epub ahead of print.

6.  Suri, R., J. Vanoverschelde, F. Grigioni et al. Association Between Early Surgical Intervention vs. Watchful Waiting and Outcomes for Mitral Regurgitation Due to Flail Mitral Valve Leaflets. JAMA.  August 14, 2013.  310(6):609-616.

 

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