Primecuts – This Week In The Journals

May 11, 2015

By Jessica Taff, M.D.

Peer Reviewed

As the curfew in Baltimore was lifted, the excitement of the Mayweather-Pacquiao boxing match died down, and Nepal continued on its recovery after the recent earthquake, medical literature remained relatively subdued this week as well. That is, until The New England Journal of Medicine (NEJM) grabbed national headlines with its brief report of Ebola Virus RNA isolated from aqueous humor in the eye of Dr. Ian Crozier, who was successfully treated for Ebola Virus Disease in September 2014, and subsequently presented with uveitis[1]. This finding underscores the importance of continued monitoring and reminds the public that we still know little about the epidemic virus that ravaged West Africa.

Moving toward diseases more common in the United States, the NEJM also published a trial related to coronary artery disease, evaluating the efficacy of continued dual antiplatelet therapy with aspirin and ticagrelor, a P2Y12 receptor antagonist, more than 1 year following a Myocardial Infarction (MI)[2]. The study randomized nearly 21,000 patients, 1-3 years after MI, in a double-blind fashion, to receive either ticagrelor 90mg twice daily, ticagrelor 60mg twice daily, or placebo in addition to their low-dose aspirin. Patients were followed for 33 months on average. Those receiving ticagrelor 90mg and 60mg doses had a significantly reduced rate cardiovascular death, MI, or stroke at 3 years compared to aspirin alone, with a hazard ratio of 0.85 (95% CI .75-0.96, p=0.008) and 0.85 (95%CI, 0.74-0.94, p=0.004) respectively. Despite this reduction in composite end points, there was an increase in the rate of major bleeding (defined by TIMI bleeding criteria as intracranial bleeding, overt signs of hemorrhage associated with a hemoglobin drop of >5g/dL or >15% absolute decrease in hematocrit, or fatal bleeding that directly results in death within 7 days)[3] in both the 90mg ticagrelor group (2.60%) and the 60mg ticagrelor group (1.06%) (p<0.001). Interestingly, dyspnea may be a rate-limiting side effect of ticagrelor, with 3-year event rates of 18.93% in those receiving 90mg of ticagrelor twice daily and 15.84% in those receiving 60mg twice daily, compared to 6.38% in the placebo group (P<0.001). This study adds to the growing body of literature in the risk versus benefit debate, including that from the recent Dual Antiplatelet Therapy (DAPT) study that similarly concludes P2Y12 antagonists have clear benefits but at the expense of increased risk of bleeding.

Moving on to gastroenterology, JAMA reports the results of a phase 2, randomized, double-blind, placebo-controlled study to determine optimal dosing, fecal recolonization, recurrence rate, and safety of nontoxigenic C. difficile strain M3 (NTCD-M3) for gut colonization and prevention recurrent C. difficile infection (CDI)[4]. 173 adult patients with CDI treated with metronidazole, oral vancomycin, or both, received oral liquid formations of the M3 spores in varying amounts (104 spores/day for 7 days [n=43]; 107 spores/day for 7 days [n=44]; 107 spores/day for 14 days [n=42]; or placebo for 14 days [n=44]). Of the 93% of participants who completed treatment, fewer patients receiving NTCD-M3 reported diarrhea (46% vs 60% in the placebo group) and abdominal pain (17% vs 33% in the placebo group). Those receiving NTCD-M3 also reported fewer treatment-related adverse events, 3% (95% CI 1%-8%) vs. 7% (95% CI 2%-19%), than those receiving placebo. Recurrence of CDI was significantly decreased following administration of NTCD-M3 (Odds Ratio 0.28; 95% CI, 0.11-0.69, P=0.006), with the fewest cases recurring in patients who received 107 spores/day for 7 days (OR 0.1; 95% CI, 0.0-0.6; P=0.01 compared to placebo). This new data suggests that NTCD-M3 is generally safe and tolerated by patients and may offer a new approach to current treatment with either prolonged antimicrobial treatment or fecal microbiota transplantation.

Prolonged or recurrent illness, along with a multitude of stressors, can contribute to episodes of major depression (MD) in many patients. A causal relationship between early stressful life events and later MD is long established, laying the groundwork for current studies of stress’ molecular signature in patients with MD. A newly published study in Current Biology[5] recruited 5864 women with recurrent MD and 5783 matched controls, and measured their lifetime stressful events, sexual abuse in childhood, telomere length, and amounts of mitochondrial DNA (mtDNA). Analysis demonstrated a highly significant association between MD and the amount of mtDNA (OR 1.33, 95% CI= 1.29-1.37; P=9.00x 10-42) and telomere length (OR 0.85, 95% CI, 0.81-0.89; P=2.84×10-14). This difference was even more pronounced when participants were stratified by number of lifetime adverse events. Women with recurrent MD had shorter telomeres and more mtDNA than those without MD, a finding that supports the role of MD in altering these biologic markers. Additional experiments reported also suggest a causal role of glucocorticoids, which reproduced similar results when administered to mice.

Now to a lighter subject; Proceedings of the National Academy of Sciences of the United States of America[6] this week published the results of an experiment comparing fructose and glucose in dietary behaviors. Twenty-four volunteers were randomized in a double-blinded, random-order cross-over design to receive a cherry-flavored juice containing either fructose or glucose. The patients then underwent functional magnetic resonance imaging (fMRI) sessions, during which they viewed blocks of high-calorie food items or nonfood items and rated their hunger, desire for food, and willingness to give up delayed monetary compensation in exchange for immediate high-calorie foods. Patients reported greater hunger, desire for food, and willingness to give up monetary compensation (mean difference in willingness to pay +/- Standard Error: 1.45 +/- 0.45 dollars, Z = 2.305, P= 0.015) after ingesting the fructose drink compared to the glucose drink. More objectively, fMRI also showed greater activation of the brain to food cues in the visual cortex and left orbital cortex of patients receiving fructose. Measured levels of insulin showed smaller increases in response to fructose as well, while other hormones active in feeding behavior (leptin and grehlin) did not differ significantly between the two groups. This article raises concern that the ubiquity of high fructose additives suppresses appetite to a lesser degree than glucose and promotes obesity via increased feeding behavior.

Also in the news:

The CDC’s Morbidity and Mortality Weekly Report[7] shows that screening rates for colorectal, breast, and cervical cancers have not improved since 2010 and remain approximately 10% below the Healthy People 2020 targets[8]. Only 58% of people ages 50-75 reported recent colorectal cancer screening, 73% of women 50-74 reportedly received a mammography, and 81% of women ages 21-65 had a recent pap test.

A viewpoint piece in The Lancet discuses the promising future of personalized medicine[9]. Utilizing a health simulation model, the authors estimate billions of dollars of cost savings with improved screening for cancer, diabetes, heart disease, hypertension, lung disease, and stroke as a result of personalization.

Clinical Infectious Disease released a report of antibiotic overuse rates in the US in 2011, showing that 8 in 10 Americans received antibiotic prescriptions that year[10]. Highest rates were seen among infants, children to age 9, and adults over age 65, with more than one antibiotic prescribed per these individuals. Of these antibiotics, amoxicillin was the most commonly prescribed for children/teenagers and azithromycin was most common for adults.

Dr. Jessica Taff is an Associate Editor, Clinical Correlations

Peer reviewed by Mark H. Adelman, MD, Associate Editor, Clinical Correlations

Image courtesy of Wikimedia Commons


1. Varkey JB, Shantha JG, Crozier I, et al. Brief Report: Persistence of Ebola Virus in Ocular Fluid during Convalescence. N Engl J Med 2015; May 7 2015. Epub ahead of print.

2. Bonaca MP, Bhatt DL, Cohen M, et al. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med 2015;372:1791-1800.

3. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011;123:2736-47.

4. Gerding DN et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C difficile infection: A randomized clinical trial. JAMA 2015 May 5; 313:1719.

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5. Cai N et al. Molecular signatures of major depression. Curr Biol 2015 May 4; 25(9):1146.

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6. Luo S, Monterosso JR, Sarpelleh K, Page KA. Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards. PNAS 2015; published ahead of print May 4, 2015.

7. Sabatino SA, White MC, Thompson TD, Klabunde CN. Cancer Screening Test Use – United States, 2013. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention. May 8 2015.

8. US Department of Health and Human Services Office of Disease Prevention and Health Promotion. Healthy people 2020. Available at

9. Dzau V, Ginsburg G, Van Nuys K, et al. Viewpoint: Aligning incentives to fulfill the promise of personalized medicine. The Lancet. Published online May 6 2015.

10. Hicks LA et al. US outpatient antibiotic prescribing variation according to geography, patient population, and provider specialty in 2011. Clin Infect Dis 2015 May 1; 60:1308.

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