Primecuts – This Week In The Journals

December 16, 2015

PrimeCuts 6 min read

Golden_GlobesBy David Pineles, MD

Peer Reviewed 

On Sunday, December 6th, President Barack Obama addressed the nation from the Oval Office following the horrific mass shooting in San Bernardino, California which left 14 people dead and the recent discovery that the perpetrators were indeed radicalized terrorists [1]. In his speech, the president discussed our nation’s fight against terrorism since 9/11 and the steps our country is taking to fight the current threat of ISIS [2]. In other news, Donald Trump continues his surprising run for presidency with the polls showing his strongest position yet despite controversial comments this week where he proposed temporarily barring Muslims from entering the United States. Even with his flare for the dramatics and numerous controversial opinions, the latest New York Times/CBS News nationwide poll has Mr. Trump commanding the support of 35% of Republican primary voters [3]. It will surely be an interesting race leading up to the Presidential election in 2016. In the entertainment world, the nominations for the 73rd Golden Globe Awards were announced on December 10th with titles such as Spotlight, Room, Carol, and The Revenant making their mark in the movie category and titles such as Transparent, Mr. Robot, Game of Thrones, and Narcos [4]. 

In medical news this week:

Which antiplatelet strategy is preferred in patients with new ischemic stroke while taking aspirin?

Aspirin is used for both primary and secondary prevention of ischemic vascular events. However, optimal antiplatelet therapy for patients with new ischemic vascular events while taking aspirin is unclear. Kim et al. conducted a prospective analysis of a multicenter stroke registry database from 14 hospitals in South Korea over 5 years to elucidate whether switching aspirin to another antiplatelet agent, or adding antiplatelet agents to aspirin, could prevent future vascular events [5]. Over 1,000 patients were divided into 3 groups according to the antiplatelet therapy strategy pursued: maintaining aspirin monotherapy, switching aspirin to non-aspirin antiplatelet agents, and adding another antiplatelet agent to aspirin. Clopidogrel was the most commonly used alternative antiplatelet agent. The primary end point was the composite of stroke (ischemic/hemorrhagic), MI, and vascular death up to one year after stroke onset. Compared to the aspirin monotherapy group, there was a reduction in composite vascular events in the non-aspirin monotherapy group (hazard ratio, 0.50; 95% confidence interval, 0.27–0.92; P=0.03) and in the dual antiplatelet therapy group (hazard ratio, 0.40; 95% confidence interval, 0.24–0.66; P<0.001). This study suggests that dual antiplatelet therapy is preferred for patients with a new ischemic stroke on aspirin therapy, which differs from findings from prior studies that did not demonstrate superiority of dual antiplatelet therapy. However, the authors did not record or discuss major bleeding events in the current study. Providers must consider this risk compared to the overall benefit prior to escalating treatment in patients.

The smartphone-based Stroop EncephalApp has good sensitivity for minimal hepatic encephalopathy compared to existing gold standards

Minimal hepatic encephalopathy (MHE) detection can be difficult for healthcare providers due to the unavailability of point-of-care tests. Therefore, MHE, which has been shown to impair quality of life and carries an increased risk of progression to overt hepatic encephalopathy, can go undiagnosed and untreated. The Stroop EncephalApp is a test of cognitive speed and psychomotor flexibility that can be accessed on a smartphone, which has previously been validated in single-center studies to diagnose MHE [6]. Allampati et al. attempted to validate the EncephalApp for MHE diagnosis in a recent multicenter study [7]. In this study, 403 outpatient cirrhotics and 308 controls from three sites underwent EncephalApp screening as well as two gold standard screening modalities: the psychometric hepatic encephalopthy score (PHES) and the inhibitory control test (ICT). Values on the EncephalApp for the diagnosis of MHE were made based on direct norms, on ICT, and on PHES. The patients were then followed for development of overt HE. The authors then performed a separate VA-based validation arm of their study. They found that MHE was present using EncephalApp based on norms in 51%, based on PHES in 37% (sensitivity 80%), and based on ICT in 54% of patients (sensitivity 70%). In the validation cohort, the app was consistent for MHE diagnosis with >70% sensitivity. This study validates the use of a simple mobile app for healthcare providers to quickly diagnose MHE in the outpatient setting. This could potentially lead to early initiation of medications such as lactulose or rifaximin, which have been shown to improve cognitive abilities and quality of life in patients with MHE [8].

Does prasugrel lower the incidence of vaso-occlusive crises in sickle cell patients?

Platelet activation plays a significant role in the pathogenesis of vaso-occlusive crises in sickle cell patients [9]. Heeney et al. performed a phase 3 double-blinded, placebo-controlled trial (DOVE trial) to assess the efficacy of prasugrel in reducing the rate of vaso-occlusive crisis in sickle cell patients [10]. The primary end point of the DOVE trial was the rate of vaso-occlusive crisis, a composite of painful crisis or acute chest syndrome. The secondary end points of the trial were the rate of sickle cell–related pain and the intensity of pain, which were assessed daily with the use of pain diaries. Over 300 patients, ages 2-17 years were randomized to receive prasugrel or placebo for a minimum of 9 months and a maximum of 24 months. The rate of vaso-occlusive crisis events per person-year was 2.30 in the prasugrel group and 2.77 in the placebo group (rate ratio, 0.83; 95% confidence interval, 0.66 to 1.05; P=0.12). The authors also found no significant differences between the groups in terms of secondary end points as well. Of note, there was no significant difference between the two arms in the incidence of hemorrhagic events requiring medical intervention. The authors discussed the possibility that the lack of effect may have been due to the fact that they aimed for modest platelet inhibition and chose a narrower target range (231 to 136 PRU’s, 30-60% platelet inhibition) than the range used in studies of adults with acute chest syndrome (235 to 95 PRU’s). This study demonstrated that prasugrel does not appear to lower the rate of vaso-occlusive events in sickle cell patients.

Is peripheral eosinophilia a predictor of COPD exacerbations?

Previous studies have demonstrated eosinophilic airway inflammation during both chronic, stable COPD and during COPD exacerbations. Vedel-Krogh et al. sought to determine whether elevated eosinophil levels are associated with an increased risk of exacerbations among COPD patients [11]. The authors used the Copenhagen Population Study cohort to prospectively analyze 7,225 individuals with COPD. Blood eosinophil levels were recorded at baseline and during COPD exacerbations, which were defined as moderate (requiring a short-course treatment of systemic corticosteroids) or severe (requiring hospitalization). Among the participants with COPD, blood eosinophil levels above 0.34∙109 cells/L had a multivariable adjusted incidence rate ratio of 1.76 (95% CI: 1.56-1.99) for severe exacerbations and of 1.15 (1.05-1.27) for moderate exacerbations. This study demonstrated that high total numbers of serum eosinophils are associated with increased risk of COPD exacerbations. Perhaps we should be paying closer attention to COPD patients’ CBC? Peripheral eosinophilia may help providers identify higher risk patients in the outpatient setting and may warrant more aggressive management to prevent exacerbations.

Other articles of note this week:

Dhabangi et al. published a study assessing if longer-storage RBC units are not inferior to shorter-storage RBC units for tissue oxygenation as measured by reduction in blood lactate levels and improvement in cerebral tissue oxygen saturation among children with severe anemia [12].

Imhann et al. published a fascinating article investigating the influence of proton pump inhibitor use on the gut microbiome [13].

In a study published in Annals of Internal Medicine this week, Cleynen et al. studied the characteristics of skin lesions associated with anti-tumor necrosis factor therapy in patients with IBD [14].

David Pineles, MD is a first year resident at NYU Langone Medical Center

Peer reviewed by Karin Katz, MD, internal medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References:

  1. Martinez M, Shoichet C, and Brown P. “San Bernardino shooting: Couple radicalized before they met, FBI says.” CNN. 2015 Dec 9. http://www.cnn.com/2015/12/09/us/san-bernardino-shooting/
  2. Barack Obama. “Transcript: President Obama’s address to the nation on the San Bernardino terror attack and the war on ISIS.” CNN. 2015 Dec 6. http://www.cnn.com/2015/12/06/politics/transcript-obama-san-bernardino-isis-address/
  3. Megan Thee-Brenan. “Donald Trump solidifies his lead, but leaves many nervous.” The New York Times. 2015 Dec 10. http://www.nytimes.com/politics/first-draft/2015/12/10/trump-solidifies-his-lead-but-leaves-many-nervous/
  4. Lauren Moraski. “Golden Globe Awards 2016 nominees list.” CBS News. 2015 Dec 10. http://www.cbsnews.com/news/2016-golden-globe-awards-nominees-list/
  5. Kim JT, Park MS, Choi KH, et al. Different Antiplatelet Strategies in Patients with New Ischemic Stroke While Taking Aspirin. Stroke. 2015 Nov 24. http://stroke.ahajournals.org/content/early/2015/11/24/STROKEAHA.115.011595.abstract
  6. Bajaj JS, Thacker LR, Heuman DM et al. The Stroop smartphone application is a short and valid method to screen for minimal hepatic encephalopathy. Hepatology. 2013 May 23. (58): 3; 1122-1132.
  7. http://7.http://onlinelibrary.wiley.com.ezproxy.med.nyu.edu/doi/10.1002/hep.26309/full
  8. Allampati S, Duarte-Rojo A, Thacker L, et al. Diagnosis of minimal hepatic encephalopathy using Stroop EncephalApp: a multicenter US-based, norm-based study. Am J Gastroenterol. 2015 Dec 8. Online publication. http://www.nature.com/ajg/journal/vaop/ncurrent/abs/ajg2015377a.html
  9. Prasad S, Dhiman RK, Duseja A, et al. Lactulose improves cognitive functions and health-related quality of life in patients with cirrhosis who have minimal hepatic encephalopathy. Hepatology. 2007;45:549–559.
  10. http://10.http://onlinelibrary.wiley.com/doi/10.1002/hep.21533/abstract
  11. Wun T, Paglieroni T, Tablin F, Welborn J, Nelson K, Cheung A. Platelet activation and platelet-erythrocyte aggregates in patients with sickle cell anemia. J Lab Clin Med. 1997; 129: 507-516. http://www.translationalres.com/article/S0022-2143%2897%2990005-6/abstract
  12. Heeney MM, Hoppe CC, Abboud MR, et al. A multinational trial of prasugrel for sickle cell vaso-occlusive events. New England Journal of Medicine. Online publication, 2015 Dec 8. http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMoa1512021#t=abstract
  13. Vedel-Krogh S, Nielsen SF, Lange P, et al. Blood eosinophils and exacerbations in COPD: the Copenhagen general population study. Am J Respir Crit Care Med. Published online 2015 Dec 7. http://www.atsjournals.org/doi/abs/10.1164/rccm.201509-1869OC
  14. Dhabangi A, Ainomugisha B, Cserti-Gazdewich C, et al. Effect of transfusion of red blood cells with longer vs shorter storage duration on elevated blood lactate levels in children with severe anemia. JAMA. Published online 2015 Dec 5. http://jama.jamanetwork.com/article.aspx?articleid=2472941
  15. Imhann F, Bonder MJ, Vila AV, et al. Proton pump inhibitors affect the gut microbiome. Gut. Published online 2015 Dec 9. http://gut.bmj.com/content/early/2015/12/09/gutjnl-2015-310376.abstract
  16. Cleynen I, Moerkercke WV, Billiet T, et al. Characteristics of skin lesions associated with anti-tumor necrosis factor therapy in patients with inflammatory bowel disease: a cohort study. Ann Intern Med. Published online 2015 Dec 8. http://annals.org/article.aspx?articleid=2474360

 

One comment on “Primecuts – This Week In The Journals”

  • Avatar of Andre Haddad
    Andre Haddad on

    A few observations about the antiplatelet/stroke prevention study mentioned here:
    It was small (including only 1172 of 26000 patients sampled).
    It involved Asian patients almost exclusively (a distinction that seemed significant in prior studies).
    It was an observational study, not a RCT (unlike MATCH or PRoFESS, which both showed contrary results).
    It had significant bias (for example, the discussion acknowledges, “Antihypertensive and statin uses at discharge were highest in the AA group, the second highest in the SA group, and lowest in the MA group.”)
    And, as mentioned, it did not include risk data.
    The 33 listed authors’ conclusion that, “compared with maintaining aspirin, switching to or adding alternative antiplatelet agents may be better in preventing subsequent vascular events” is appropriately vague. Perhaps it should’ve added, “…but may not be better”, for clarity. In fairness, they do admit their results “should be interpreted with caution and… confirmed in randomized clinical trials”.

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