Primecuts – This Week In The Journals

August 26, 2013

By Brian Greet, MD

Faculty Peer Reviewed

On the twenty first of this month, rebels proclaimed that they had been attacked by the Syrian government with the use of chemical warfare. Medicins Sans Frontieres is reporting this week that they treated approximately 3,600 patients with “neurotoxic symptoms” of whom 355 had expired. Bart Janssens, MSF Director of Operations, stated “MSF can neither scientifically confirm the cause of these symptoms or establish who is responsible for the attack.” He went on to say, “However, the reported symptoms of the patients, in addition to the epidemiological pattern of the events—characterized by the massive influx of patients in a short period of time, the origin of the patients, and the contamination of medical and first aid workers—strongly indicate mass exposure to a neurotoxic agent. This would constitute a violation of international humanitarian law, which absolutely prohibits the use of chemical and biological weapons.” Per MSF, symptoms of patients included dilated pupils, convulsions and respiratory difficulty with many being treated with atropine. [1] As Washington continues to weigh its options on how to react to what’s happening in the Damascus region, many within Washington were celebrating the fiftieth anniversary of Dr. Martin Luther King Jr.’s “I Have a Dream” speech this week. Tens of thousands of people marched to the Martin Luther King Jr. Memorial and down the National Mall on Saturday in honor of Dr. King.

Marching right along from headlines to medical news, a new retrospective study in Stroke looking at “ultra-early” thrombolytic administration showed that earlier administration resulted in significantly improved outcomes. Based off a prior single center study that evaluated the outcome of lytic administration within 90 minutes of symptom onset, this new multi-center retrospective study looked to evaluate for the same in a larger cohort. Looking at 6,856 patients with ischemic stroke from ten different European stroke centers, they found that thrombolytic administration within 90 minutes in those patients with an NIH stroke scale of 7-12 had improved three month neurologic outcomes and reduced intracranial bleeding events compared to those receiving therapy after 90 minutes. Improved neurologic outcomes were defined by a Rankin scale of 0-1. Mortality, however, did not differ between groups. Such findings further emphasize the need to take early signs of stroke seriously and that patients should be brought to the closest stroke center as quickly as possible. [2]

In the world of infectious disease, a recent trial published in the Lancet looked to determine whether or not early antiretroviral therapy (ART) helps to improve outcomes in HIV-infected infants. The CHER trial was an open label randomized trial of infants less than 12 weeks that took place in two South African trial sites. 377 infants were randomized to either receive deferred ART, immediate ART for 40 weeks or immediate ART for 96 weeks, with subsequent treatment interruption. When compared to deferred treatment after a median of 5 years’ follow-up, children in the 40-week and 96-week group had their risk of death or treatment failure reduced by 40% and 50% respectively. Such findings further support the recent WHO guidelines which recommend starting ART in all infants who are suspected of having HIV. This data adds to the mounting number of clinical scenarios in which early ART in HIV appears to be favorable when compared to a delayed approach. [3]

While many interns are encountering patients with severe delirium for the first time this August, new evidence suggests that the most commonly used drug to help combat delirium may not be all that efficacious. Haloperidol, whose prior evidence was limited to small clinical trials showing reductions in duration of symptoms, has again been put to the test in this latest randomized control trial. Page et al randomized 142 patients in the ICU setting to receive either intravenous haloperidol 2.5mg every eight hours or normal saline with drug discontinuation occurring at the time of discharge, once the patient was delirium free or after a maximum of 14 days of treatment. The primary outcome assessed was number of delirium and coma-free days. Overall there was no difference in endpoint in either group, although those who received haloperidol were more likely to become over sedated. These findings suggest that within the first 14 days of treatment in an ICU setting, standing intravenous haloperidol is no better than placebo at reducing the number of delirium or coma-free days.[4]

Other interesting reads this week…

1.Csaba P. Kovesdy, Anthony J. Bleyer, Miklos Z. Molnar, Jennie Z. Ma, John J. Sim, William C. Cushman, L. Darryl Quarles, Kamyar Kalantar-Zadeh; Blood Pressure and Mortality in U.S. Veterans With Chronic Kidney DiseaseA Cohort Study. Annals of Internal Medicine. 2013 Aug;159(4):233-242.

Controlling blood pressure can be extremely difficult in those with chronic kidney disease. In a study investigating at a historical cohort from 2005 to 2012, Csaba et al showed that those with an ideal systolic blood pressure and diastolic blood pressure less than seventy mmHg had the highest mortality rates of all chronic kidney disease patients. Though not establishing causality, this study seems to suggest that the optimal blood pressure in those with chronic kidney disease may be between a systolic range of 130 to 159 and a diastolic range between 70 to 89 mmHg, with further reductions in blood pressure being associated with increased harm.

2. Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013 Aug 5. PubMed PMID: 23915096.

A new meta-analysis suggests that treating patients with oral proton pump inhibitors (PPI) in the setting of peptic ulcer bleeding may be equally as efficacious as treating with intravenous therapy. Pooled from six randomized trials, the majority of which were comprised of open labeled trials with limited sample sizes, the results showed that there was no difference in rates of recurrent bleeding, transfusion requirements, need to go to the operating room and all-cause mortality between the two therapies. Those, however, receiving oral PPI had a shorter length of hospital stay when compared to those receiving intravenous therapy. While the findings are interesting, they further support the need for a well-designed blinded randomized trial to see if oral therapy is as good as intravenous in the setting of acute peptic ulcer bleeding.

Dr. Brian Greet is the Chief Medical Resident at NYU Langone Medical Center

Peer reviewed by Matthew Vorsanger, MD, associate editor, Clinical Correlations

Image courtesy of Wikimedia Commons



[2] Strbian D, Ringleb P, Michel P, Breuer L, Ollikainen J, Murao K, Seiffge DJ,Jung S, Obach V, Weder B, Eskandari A, Gensicke H, Chamorro A, Mattle HP, Engelter S, Leys D, Numminen H, Köhrmann M, Hacke W, Tatlisumak T. Ultra-Early Intravenous Stroke Thrombolysis: Do All Patients Benefit Similarly? Stroke. 2013 Aug 22. [Epub ahead of print] PubMed PMID: 23970791.

[3] Mark F Cotton, Avy Violari, Kennedy Otwombe, Ravindre Panchia, Els Dobbels, Helena Rabie, Deirdre Josipovic, Afaaf Liberty, Erica Lazarus, Steve Innes, Anita Janse van Rensburg, Wilma Pelser, Handre Truter, Shabir A Madhi, Edward Handelsman, Patrick Jean-Philippe, James A McIntyre, Diana M Gibb, Abdel G Babiker. Early time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial. The Lancet. 2013 Aug 22. [Early Online Publication]

[4] Valerie J Page, E Wesley Ely, Simon Gates, Xiao Bei Zhao, Timothy Alce, Ayumi Shintani, Jim Jackson, Gavin D Perkins, Daniel F McAuley. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2013 Aug 21. [Early Online Publication]