Primecuts – This Week In The Journals

June 2, 2014

By Ian Henderson, MD

Peer Reviewed

In the week after honoring those who have passed while serving our country, the challenges facing our nation’s veterans have become increasingly evident. The recent controversy and frustrations with delayed care of veterans culminated on Friday with the resignation of Secretary of The Department of Veteran Affairs, Eric Shinseki [1]. After an internal audit of the department’s health system showed chronic delays in care, manipulated waiting lists, and a scheduling scandal, President Barack Obama met with the Secretary on Friday. The president acknowledged both the importance and deep seated nature of the problem saying, “There is a need for a change in culture within the VHA… and perhaps the VA as a whole that makes sure that bad news gets surfaced quickly so that things can be fixed.”

ACEIs may be more protective than ARBs in diabetics

A common medical teaching and practice is that inhibitors of the renin-angiotensin system, regardless of mechanism of action, should be used to treat diabetic patients with cardiovascular risk factors. A recent meta-analysis by Cheng et al[2] compared the effect of ACEIs to ARBs on all-cause mortality and cardiovascular deaths. The study consisted of 35 randomized controlled trials, a total of 56,444 patients, comparing ACEIs or ARBs to control treatment. The study found that treatment with ACEIs significantly reduced the risk of all-cause mortality by 13% (RR, 0.87; 95% CI, 0.78-0.98), CV deaths by 17% (0.83; 0.70-0.99) whereas treatment with ARBs did not significantly reduce the risk of either primary end point. ACEI treatment also reduced the risk of secondary end points of non-fatal MI, heart failure, and major adverse cardiac events. Both groups of studies had a low to moderate level of heterogeneity for the primary outcomes (26% for ACEI studies and 22% for ARB studies). These findings suggest that differences exist between ACEIs and ARBs in diabetics and perhaps that ACEIs provide a protective effect that ARBs do not. These findings are limited because the comparison between the two drugs was indirect in nature with only one study in the meta-analysis directly comparing an ACEI to an ARB. The studies included were also not equivalent as 23 of the 35 studies looked at ACEIs, a total of 32, 827 patients, whereas only 13, a total of 23, 867 patients, looked at ARBs. This meta-analysis raises an important question: Are ACEIs and ARBs truly equivalent? Its findings should be confirmed with prospective direct comparison studies before practice is changed.

Non-selective beta blockers can be harmful in cirrhotic patients with spontaneous bacterial peritonitis

In response to a landmark paper by Serste, et al.[3] demonstrating a deleterious effect of non-selective beta blockers (NSBB) in patients with spontaneous bacterial peritonitis (SBP), Mandorfer et al. performed a retrospective study[4] to ask the same question: are NSBB harmful to patients with SBP? The study consisted of 607 patients identified at time of first paracentesis to not have SBP from the Medical University of Vienna between 2006-2011. The patients in both NSBB treatment and no NSBB treatment group were controlled for presence of esophageal varices and Child-Pugh Score. The study showed that of the 607 patients, 182 developed SBP with about even amounts receiving NSBB treatment (86) and not (96). Patients who developed SBP and received NSBB treatment had reduced transplant free survival (hazard ratio 1.58; 95% confidence interval: 1.098–2.274; P .014). Patients that received NSBB also had an increased number of nonelective inpatient admission days, as well as a higher proportion of acute kidney injury and hepatorenal syndrome. This study, though retrospective in nature, provides support for the hypothesis of a treatment window for NSBB in cirrhosis. Whereas NSBB can decrease mortality in cirrhotics with varcies due to reduction in rates of recurrent bleeding, by the time the disease has progressed to an advanced stage with ascites and SBP, NSBBs protective effects are lost and they may in fact be harmful.

An oral vaccine for cholera outbreaks

Shifting to a more global focus, Luquero, et al.[5] looked at the effectiveness of an oral cholera vaccine, Shancol, during the most recent cholera outbreak in Guinea in 2012. In this case-control study, a suspected case was defined as acute infectious non-bloody diarrhea with more than three liquid stools in 24 hours, and was confirmed by a positive rapid diagnostic test, PCR, or stool culture. Vaccination status was established by in-person questioning and vaccine card status for all patients. A total of 40 cases and 160 controls were enrolled in the study. The vaccine, when two doses were given as recommended, had an adjusted effectiveness of 86% (95% confidence interval 56.7 to 95.8; P=0.001). The study was not powered to evaluate the effectiveness of one dose of the vaccine. The results of this study are promising as this is the first time this oral cholera vaccine has been studied for short term protection (6 months), and it proved to be very effective. This form of protection is what is desired during an acute outbreak. Though the findings are positive, there is still more work to be done on this vaccine. Ideally we would like to know the effectiveness of one oral dose.

Post-cholecystectomy abdominal pain: endoscopic sphincterotomy is not the answer

Abdominal pain after cholecystectomy is a common issue and frequently is thought to be due to sphincter of Oddi dysfunction. In a randomized, sham procedure-controlled study, Cotton et al.[6] looked at the effectiveness of endoscopic sphincterotomy in treating abdominal pain after cholecystectomy. The study enrolled 214 patients with post-cholecystectomy abdominal pain and randomized them in a 2:1 fashion to sphincterotomy or a sham procedure. The patients randomized to sphincterotomy who were found to have elevated sphincter pressures were again randomized 1:1 to biliary or biliary and pancreatic sphincterotomies. The study found that 27 patients in the sham treatment group compared to 32 in the sphincterotomy group experienced successful treatment (adjusted risk difference, -15.6%; 95% CI, -28.0% to -3.3%; P=.01). Successful treatment was defined as a RAPID score of fewer than 6 days of lost productivity at months 9 and 12 after the procedure, did not undergo a second intervention, and did not require narcotics during months 10, 11, and 12 after the procedure. Patient outcomes were not associated with manometry results. These results show that treatment of post-cholecystectomy abdominal pain with ERCP and sphincterotomy is not beneficial in relieving patients’ pain.

Other interesting articles:

In a mouse model of hypertension-induced heart failure, CD4 cells were found to be key players in the pathologic transition from concentric hypertrophy to failing myocardium[7].

In a study of water samples in France, waste water treatment plants were found to lead to relative enrichment in the concentration of extended spectrum beta-lactamase producing E. coli in the waste water. [8]

A novel antibody to Beta-2 glycoprotein which does not fix complement offers a promising new treatment for antiphospholipid syndrome [9].

Dr. Ian Henderson is an incoming 1st year resident at NYU Langone Medical Center

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

Image courtesy of Wikimedia Commons

References

1- Oppel ,Jr. R, Shear M. VA Chief Resigns in Face of Furor on Delayed Care. http://www.nytimes.com/2014/05/31/us/politics/eric-shinseki-resigns-as-veterans-affairs-head.html.  Published 5/30/2014

2- Cheng, et al. Effect of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers on All-Cause Mortality ,Cardiovascular Deaths, and Cardiovascular Events in Patients With Diabetes Mellitus: A Meta-analysis. JAMA Intern Med. 2014 May 1;174(5):773-85. http://archinte.jamanetwork.com/article.aspx?articleid=1847572

3- Serste, T., Melot, C., Francoz, C. et al. Deleterious effects of beta-blockers on survival in patients with cirrhosis and refractory ascites. Hepatology. 2010 May 25; 52: 1017–1022 http://onlinelibrary.wiley.com/doi/10.1002/hep.23775/full

4- Mandorfer, et al. Nonselective ? Blockers Increase Risk for Hepatorenal Syndrome and Death in Patients With Cirrhosis and Spontaneous Bacterial Peritonitis. Gastroenterology. 2014 June 1; 146: 1680-1690 http://www.gastrojournal.org/article/S0016-5085(14)00306-0/full

5- Luquero, et al. Use of Vibrio cholerae Vaccine in an Outbreak in Guinea. 2014 N Engl J Med 2014; 370:2111-2120 http://www.nejm.org/doi/full/10.1056/NEJMoa1312680

6- Cotton, et al. Effect of Endoscopic Sphincterotomy for Suspected Sphincter of Oddi Dysfunction on Pain-Related Disability Following Cholecystectomy: The EPISOD Randomized Clinical Trial. JAMA. 2014;311(20):2101-2109. http://jama.jamanetwork.com/article.aspx?articleid=1874513

7- Laroumanie, et al. CD4+ T Cells Promote the Transition From Hypertrophy to Heart Failure During Chronic Pressure Overload Circulation. 2014; 129: 2111-2124. http://circ.ahajournals.org/content/129/21/2111.full

8- Brechet, et al. Wastewater Treatment Plants Release Large Amounts of Extended-Spectrum ?-Lactamase–Producing Escherichia coli Into the Environment. Clin Infect Dis. (2014) 58 (12):1658-1665. http://cid.oxfordjournals.org/content/58/12/1658.full

9- Agostinis, et al. A non–complement-fixing antibody to ?2 glycoprotein I as a novel therapy for antiphospholipid syndrome. May 29, 2014; Blood 123(22);3478-87. http://bloodjournal.org/content/123

 

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