Primecuts-This Week in the Journals

May 19, 2015


By: Arvind Reddy Devanabanda, MD

This week we are reminded of the costs of over-testing and over-diagnosis in Dr. Atul Gawande’s article “Overkill” published in the New Yorker. Six years later Dr. Gawande revisits the health care costs in the city of McAllen, Texas, which was introduced in his prior article “Cost Conundrum”. Since the inception of the Affordable Care Act, cities across America, like McAlllen, have begun to see the cost of a Medicare patient flatten out. In addition, the United States’ health care inflation is at its lowest in fifteen years per Dartmouth Institute of Health Policy and Clinical Practice. [1]

What is the accuracy of a capsule colonoscopy (PillCam) testing and which patients is it appropriate for? [2]

Adaptation of the capsule endoscopy has been challenging as the first generation capsules captured photos at only 4 frames per second. The second generation capsules now capture at 35 frames per second with motion and 4 frames per second at rest, and the angle view increased from 156 degrees to 172 degrees. In a study published in Gastroenterology, second generation capsule endoscopy was used to identify polyps at least 6mm or bigger at 16 medical centers in the US and Israel

The primary endpoint of this prospective study was the diagnostic accuracy  of the capsule for detecting patients with polyps 6 mm or larger compared with conventional colonoscopy. Capsule endoscopy identified 1 or more polyps 6 mm or larger with 81% sensitivity (95% CI, 77-84%) and 93% specificity (95% CI, 91-95%) and polyps 10 mm or larger with 80% sensitivity (95% CI 74-86%) and 97% specificity (95% CI 96-98%). The study also found identification of adenomas 6 mm or larger with capsule endoscopy with 88% sensitivity (95% CI 82-93%) and 82% specificity (95% CI, 80-83%).

Thus, in an average risk screening population, capsule performance is a relatively sensitive and specific method of cancer screening for patients who cannot undergo colonoscopy or had incomplete colonoscopies.  Colonoscopy however, should still be the preferred method of detection.

A new approach to allergenic asthma presented at the meeting of the American Thoracic Society. [3]

Asthma is a chronic inflammatory and obstructive airway disease that has several clinical phenotypes and pathophysiological mechanisms. A particular mechanism seen predominantly in allergic asthma is driven by helper T cells (Th2).   In asthma,  the activation of Th2 cells leads to the production of cytokines IL- 4,5, and 13. The expression and production of these cytokines is regulated by transcriptional factor GATA-3. It has been previously shown that GATA3 overexpression is seen in lung biopsies of patients with severe asthma. This study developed a GATA3 specific DNA enzyme SB010 that has the ability to cleave GATA3.

This drug was then used in a randomized, double blinded, placebo-controlled, multicenter clinical trial in which 21 patients were assigned to receive 10 mg of SB010 and 19 received placebo. Each drug was administered by inhalation once daily for 28 days. The primary end point was late asthmatic response quantified by the area under curve (AUC) of forced expiratory volume in 1 second (FEV1). Results showed that SB010 attenuated the early and late asthmatic response by 11% and 34% respectively , while the placebo increased the early and late asthmatic response by 1% and 111% respectively. Furthermore, IL-5 levels and sputum induced eosinophilia were also attenuated in the treatment group. This is an exciting new development in asthma therapy, especially after so many years of little innovation in asthma treamtent.  Further clinical studies are required to understand if these benefits translate to benefit from persistent symptomatic asthma

A Potential New Target in the Treament of Atrial Fibrillation [5]

As we all encounter in our clinical practice, successful treatment of atrial fibrillation (AF) is challenging and the arrhythmia remains a significant risk factor for stroke, heart failure and hospitalization. Pathophysiologically, the shortening of action potential duration (APD) that occurs in atrial fibrillation promotes reentry and supports the perpetuation of the arrhythmia. While increased K+ channel current (specifically cardiac K2P3.1 channel current) is implicated in shortening APD during AF, other ion channels are poorly understood.

In this study, atrial tissues were obtained from patients with paroxysmal (p) or chronic (c) atrial fibrillation and from sinus rhythm (SR) controls. Ion channel expression was analyzed by PCR and Western blot. K2P3.1 subunits exhibited predominant atrial expression with K2P3.1 mRNA levels increased in cAF. By contrast K2P3.1 mRNA levels were not significantly increased in pAF. Subsequent pharmacologic inhibition of K2P3.1 channel prolonged APD in atrial myocytes from cAF patients compared to SR. In summary, the K2P3.1 channel can be considered as a novel target for pharmacologic inhibition and treatment of atrial fibrillation.

Update on renal denervation therapy for the use of drug resistant hypertension. [6]

Despite the effectiveness of conventional antihypertensive agents, about 10% of patients continue to have arterial hypertension and remain at high cardiovascular and renal risk. Renal denervation therapy is a recent development in the treatment of drug resistant hypertension that acts by decreasing the sympathetic response in hypertension. A recent study, Simplicity HTN– 3, however, failed to show reduction in blood pressure in the renal denervation group. The study was limited by the variable experience of interventionalists, the variable drug regimens, and the patients’ poor adherence to therapy prior to enrollment. A new study published in the Lancet, DENERHTN, with the same catheter used in Simplicity HTN3 study, was able to meet its primary end point with reduction of systolic blood pressure by 5.9 points compared to drug treatment group.  While Simplicity HTN-3 was a negative study, Simplicity HTN-1, Simplicity HTN-2 and DENERHTN, showed a positive impact of renal denervation therapy in drug resistant hypertension. As hypertension continues to be a major challenge due to medication adherence we look forward to further trials to clarify the role of nonpharmacologic treatments.

Also in the journals this week…

This week the meeting of the American Thoracic Society published results that in patients with non-hypercapenic, acute hypoxemic respiratory failure, treatment with high flow oxygen, standard oxygen or noninvasive ventilation did not result in significantly different intubation rates.  There was however a significant difference in favor of high flow oxygen with 90 day mortality rates. [7]

It has been shown that psychological distress is a risk factor in cardiovascular mortality. A recent metanalysis in Gastroenterology journal, looked at psychological distress in liver disease mortality. The age and sex adjusted hazard ratio was 3.48 in patients with depression, and after adjusted for health behavior, socioeconomic status, BMI, and diabetes the hazard ratio decreased to 2.59. [8] URL:

Did you know that prolonged TV viewing is associated witha  modest increase in risk for colorectal adenoma independent of leisure time physical activity and obesity? [9]

References :

  1. Gawande. A. Overkill. New Yorker. May 11, 2015
  2. Rex KD., Adler S., Aisenberg ., et al. Accuracy of Capsule Colonoscopy in detecting colorectal polyps in a screening population. Gastroenterology. May 2015, Volume 148, Issue 5, Pages 948-957.
  3. Krug N., Hohlfeld J., Kirsten A., et al. Allergen Induced Asthmatic Responses Modified by GATA3- Specific DNAzyme. New England Journal of Medicine. May 17, 2015. DOI: 10.1056/NEJMoa1411776
  4. I Cheng Ho et al. GATA3 is required for both STAT6 dependent and STAT6 independent pathways for TH2 cell differentiation. Nature Reviews Immunology. February 2009.
  5. Schmidt et al. Upregulation of K2P3.1 K+ current causes action potential shortening in patients with chronic atrial fibrillation. Circulation, May 2015. Published ahead of print
  6. Dagmara Hering. Renal Denervation superior to drug therapy in hypertension. Lancet. Volume 385, Issue 9981, Pages 1917-2014, e47-e48 (16–22 May 2015)
  7. Fratt J., Thille A., Mercatt A., et al. High flow oxygen through nasal cannula in acute hypoxemic respiratory failure. New England Journal of Medicine. Epub ahead of print. May 24, 2015
  8. Russ et al. Association between psychological distress and Liver disease mortality: A meta analysis of individual study participants. Gastroenterology. May 2015. Volume 148, issue 5, pages 958-966.
  9. Cao Y et al. Television watching and risk of colorectal adenocarcinoma. British Journal of Cancer. January 2015.

Arvind Devanabanda, MD is a first year resident at NYU Langone Medical Center
Peer Reviewer : Greg Scrhank, MD, Associate Editor, Clinical Correlations