Primecuts – This Week In The Journals

August 20, 2012

By Benjamin Navot, MD

Faculty Peer Reviewed

This week, with Mitt Romney’s selection of Wisconsin congressman Paul Ryan as his vice-presidential candidate on the republican ticket, there has been renewed interest in the two parties plans for the future of healthcare in America. With insurance coverage for millions of Americans at stake and government solvency questioned by our increasing healthcare costs, it is highly recommended that you take a look at both candidates’ platforms with regard to healthcare (Romney [1], Obama[2]).

On a more evidence-based note, The Lancet published the results of the DREAM trial for the treatment of severe eosinophilic asthma with a novel monoclonal antibody to IL-5 [3]. In a large, multicenter, double-blind placebo controlled trial the new anti-IL-5 antibody, Mepolizumab, was shown to reduce asthma exacerbations by nearly half compared to placebo. The 621 trial participants had severe asthma as defined by two or more exacerbations requiring corticosteroids within the last year. The eosinophilic component of their asthma was defined by either elevated sputum eosinophil count, elevated blood eosinophil counts, elevated levels of exhaled nitric oxide or by inability to tolerate steroid taper.

Patients were block-randomized to 75mg Mepolizumab, 250mg Mepolizumab, 750mg Mepolizumab or 100mL NS placebo once monthly infusion. The trial arms were formed with a 1:1:1:1 ratio. Analysis was intention to treat. The primary outcome was validated asthma exacerbations such as initiation of oral corticosteroids, ER visits, and hospitalizations. Secondary outcomes included hospital admissions, eosinophil counts in blood and sputum, patient surveys and FEV1.

The 621 patients enrolled had a total of 776 validated exacerbations. The rate of exacerbations was 2.40 per patient year for the placebo group, 1.24 in the 75mg group, 1.46 in the 250mg group and 1.15 in the 750mg group (RRR of 48%, 39% and 52% respectively). Treatment arms showed longer time to first exacerbation and had fewer hospital admissions. Adverse reactions were minimal and similar to placebo (HA and nasopharyngitits). There were no anaphylactic reactions. In conclusion, the novel anti-IL-5 antibody Mepolizumab has potential to decrease the morbidity associated with severe asthma with minimal adverse reactions. However, the patients’ surveys showed no statistical difference from placebo and the drug’s ultimate benefit might be reducing the steroid requirement in this population.

In additional news, a Chicago medical group evaluated the role for screening for domestic violence with a blinded, controlled trial [4]. 2708 Female patients at their predominantly African-American and Hispanic clinics were randomized to three groups. The control group was not screened and was not given support group information. The first treatment arm was screened for domestic violence with the “Partner Violence Screen instrument” and given support information if their screen was positive. The second treatment arm was routinely given support materials. The primary outcome was a quality of life survey at one year after intervention. There was no statistical difference in the QOL score for either physical health or mental health in either treatment group compared to the control. The authors concluded, “Among women receiving care in primary care clinics, providing a partner violence resource list with or without screening did not result in improved health.”

On a more basic science track, researchers reported a novel concept for targeting cancer in this weeks Nature. Using glioblastoma as their model, scientists showed that “passenger deletions” (housekeeping genes that are deleted when neighboring tumor suppressors are lost in the process of oncogenesis) can be used as targets for selective chemotherapy [5]. In GBM, ENO-1 (enolase) is routinely lost with an adjacent tumor suppressor but the cancer cells stay alive by relying on ENO-2 (at a different locus). Using RNAi techniques, the group suppressed ENO-2 resulting in death of GBM cell lines. They also showed ENO-2 knockout mouse was viable suggesting its inhibition may be systemically tolerated. This research opens the possibility that lost redundant housekeeping genes may become the next targets in cancer chemotherapy. They suggest work on pantothenate kinase 1 and aconitase 1 as additional targets in other cancers.

Finally, an article in the Annals of Internal Medicine sought to answer the question of whether African-Americans should be held to a different Hgb A1c cutoff for diabetes than other races. Since some data show that the relationship between blood glucose and A1c is different for African Americans and Caucasians [6], with African Amercians often showing higher A1c levels, the researchers sought to determine if the threshold A1c level for African Americans should be increased from the current 6.5% [7]. Using cross sectional analysis of data obtained from the National Health and Nutrition Examination Survey, the authors determined that retinopathy may actually occur at lower A1c levels in in the African American population (as low as 5.5-5.9%). As a cross sectional study, it is limited by the unknown time spent at the recorded A1c level.

Other notable pieces of research from the previous week include a study suggesting that judges may be more lenient to criminals if presented with genetic evidence of predispositions to violent crime.

Lisa G. Aspinwall, Teneille R. Brown, and James Tabery. The Double-Edged Sword: Does Biomechanism Increase or Decrease Judges’ Sentencing of Psychopaths? Science 17 August 2012: 337 (6096), 846-849.

A case control analysis of states and their school snack laws shows that strict school snack laws decrease the prevalence of childhood obesity.

Daniel R. Taber, Jamie F. Chriqui, Frank M. Perna, Lisa M. Powell, Frank J. Chaloupka,

Weight Status Among Adolescents in States That Govern Competitive Food Nutrition Content. Pediatrics peds.2011-3353; Published online August 13, 2012

A small randomized, double-blind, placebo controlled trial showed a benefit to the addition of azithromycin for the treatment of non-CF related bronchiectasis with a rate ratio of exacerbations of 0.38 for the treatment group.

Dr Conroy Wong, et al. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. The Lancet. Volume 380, Issue 9842, 18–24 August 2012, Pages 660–667

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

Peer reviewed by Cara Litvin, MD, Editor At Large, Clinical Correlations

Image courtesy of Wikimedia Commons




3. Ian D Pavord, Stephanie Korn, Peter Howarth, Eugene R Bleecker, Roland Buhl, Oliver N Keene, Hector Ortega, Pascal Chanez Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. The Lancet. Volume 380, Issue 9842, 18–24 August 2012, Pages 651–659

4. Joanne Klevens, MD, PhD; Romina Kee, MD, MPH; William Trick, MD; Diana Garcia, MPH; Francisco R. Angulo, MBA; Robin Jones, MD; Laura S. Sadowski, MD, MPH. Effect of Screening for Partner Violence on Women’s Quality of Life. JAMA. 2012;308(7):681-689.

5. Florian L. Muller, Simona Colla, et al. Passenger deletions generate therapeutic vulnerabilities in cancer. Nature 488, 337–342 (16 August 2012)

6. Selvin E, Steffes MW, Ballantyne CM, Hoogeveen RC, Coresh J, Brancati FL. Racial differences in glycemic markers: a cross-sectional analysis of community-based data. Ann Intern Med. 2011;154303-9

7. Yusuke Tsugawa, Kenneth J. Mukamal, Roger B. Davis, William C. Taylor, Christina C. Wee; Should the Hemoglobin A1c Diagnostic Cutoff Differ Between Blacks and Whites?A Cross-sectional Study. Annals of Internal Medicine. 2012 Aug;157(3):153-159.