Primecuts – This Week in the Journals

August 6, 2018

PrimeCuts 7 min read

By Vicky Chiang, MD

Peer Reviewed

While New Yorkers are finally enjoying the first section of the Second Ave Subway after nearly a century of waiting, our friends in California have decided to move forward with their own ambitious public transportation project–a $100 billion high-speed rail from Los Angeles to San Francisco. If successful, the new rail is projected to create 450,000 new jobs, reduce greenhouse emissions by 300 thousand metric tons of carbon dioxide a year, and traverse the distance between SF and LA in less than 2 hours and 40 minutes [1,2]. It is scheduled for completion in 2033.  Though construction began two weeks ago, its future remains uncertain as a mere 30 billion dollars have only been raised so far.

Now moving on to recent news in the medical literature:

Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection

Previous studies done in Europe have found that procalcitonin levels are useful in guiding antibiotic therapy with an overall reduction in use of antibiotics with no apparent harm [3,4]. However, this has not been studied in the United States which likely has different antibiotic prescribing patterns. In this multi-center, randomized control study done in the U.S., 1656 adult patients with diagnoses of lower respiratory tract infections were randomized to a procalciton-protocol group or a usual-care group in order to investigate whether a procalcitonin level based protocol for prescribing antibiotics would result in lower antibiotic exposure without an increased rate of adverse events [5]. The primary outcome was total number of antibiotic days within 30 days of enrollment in the trial with a primary safety outcome of a composite of adverse outcomes attributable to withholding antibiotics in lower respiratory tract infections. This study ultimately found that there was no significant difference between the two groups, with mean antibiotic-days of 4.2 in the procalcitonin group and 4.3 in the usual-care group (difference -0.05 day; 95% CI, -0.6 to 0.5; p=0.87). The rates of serious adverse events also did not defer between the two groups. These findings are different from previous studies, possibly due to lower clinician adherence to the procalcitonin-based protocol in this study.

The Bottom Line: Using procalcitonin levels to guide antibiotic therapy (in the U.S.) likely does not decrease the use of antibiotics for lower respiratory tract infections.

Clopidogrel and Aspirin in Acute Ischemic Stroke and High-Risk TIA

A prior trial showed a 32% lower risk of stroke recurrence in Chinese patients treated with dual antiplatelet therapy (aspirin and clopidogrel) within 24 hours after a minor ischemic stroke or transient ischemic attack compared to aspirin alone [6]. However, the generalizability of this data has been questioned given the restricted ethnic population. Thus, in this multicenter, randomized, double-blind, placebo-controlled trial, adult patients from ten countries were randomized to clopidogrel plus aspirin or placebo plus aspirin [7]. Inclusion criteria were patients over the age of 18 within 12 hours of an acute ischemic stroke with a score of 3 or less on the National Institutes of Health Stroke Scale, or a high-risk TIA (defined as a score of 4 or more on the ABCD scale). Patients who had received thrombolysis or were candidates for thrombolysis, endovascular therapy, and endarterectomy were excluded, as well as patients with isolated numbness, visual changes, or dizziness as their main TIA symptoms. This trial found that major ischemic events (defined as ischemic stroke, myocardial infarction, or death from ischemic vascular causes) at 90 days was lower in the clopidogrel and aspirin group compared to aspirin and placebo (5.0% and 6.5% respectively, hazard ratio, 0.75; 95% CI, 0.59 to 0.95; p=0.02). Ultimately, this trial had to be stopped early as major hemorrhage at 90 days was higher in the dual antiplatelet group (0.9%) compared to the aspirin group (0.4%, HR, 2.32; 95% CI, 1.10 to 4.87; p=0.02).

The Bottom Line: Though the combination of aspirin and clopidogrel after a minor ischemic stroke or high-risk TIA results in a lower risk of major ischemic events over the next 90 days, there is a higher risk of major hemorrhage.

Effect of Escitalopram vs Placebo Treatment for Depression on Long-term Cardiac Outcomes in Patients with Acute Coronary Syndrome

It has been well-established that depression is not only comorbid with acute coronary syndrome but also associated with increased mortality and nonfatal adverse events [8]. However, the data for ameliorating this with an antidepressant has been variable given that prior studies were limited by short follow-up periods and variable antidepressant regimens [9,10]. In this double-blind, randomized control study, 300 South Korean patients who were hospitalized with ACS in the previous 2 weeks and had a positive depression screen were randomized to either receive escitalopram or receive placebo for 24 weeks (mean dose at last visit was 7.6 mg (SD, 3.7) [11]. They were subsequently followed up for 5 to 11 years (median follow-up of 8.1 years, mean 8.4) and the study found a significant difference in all-cause mortality, myocardial infarction, and percutaneous coronary intervention (MACE).  In the escitalopram group, composite MACE incidence was 40.9% and in the placebo group it was 53.6 % (HR, 0.69; 95% CI, 0.49-0.96; p=0.03). When individual MACE components were examined, there was a significant difference in the incidence of MI with 8.7% in the escitalopram group and 15.2% in the placebo group (HR, 0.54, 95% CI, 0.27-0.96, p=0.04). Interestingly, there were no significant differences in other individual MACE components between the two groups.

The Bottom Line: Patients with depression and ACS appear to have lower risk of all-cause mortality, myocardial infarction, and percutaneous coronary intervention when treated with escitalopram for 24 weeks.

Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock

Though there is good data supporting inpatient resuscitation of hemorrhaging patients with proportionate blood components rather than crystalloids, there is a paucity of data supporting this in the prehospital setting [12]. In this multicenter, cluster randomization trial, 27 air medical bases for air transport of injured patients were randomly assigned to either administer 2 units of plasma to hemorrhaging patients in addition to practicing standard care or standard care only [13]. This resulted in a total of 501 patients analyzed in the trial. Inclusion criteria were patients with at least one episode of hypotension or tachycardia at any time before arrival at the trauma center. Patients older than 90 and younger than 18 years of age were excluded, as well as patients who had injuries unlikely to cause hemorrhagic shock (specifics outlined in detail in the paper). This trial found that mortality at 30 days was lower in the plasma group than in the standard-care group (23.2% and 33.0% respectively, difference, -9.8 percentage points; 95% CI, -18.6 to -1.05; p=0.03). However, this study was limited by its cluster design which resulted in imbalanced enrollment as well as its inability to be a double-blind trial. Furthermore, there were several differences in standard of care between the various centers.

The Bottom Line: In patients at risk for hemorrhagic shock, prehospital administration of plasma resulted in a lower 30-day mortality.

Several more interesting finds:

Minicuts

  1. Using the MELD-Na score for liver allocation appears to improve post-transplant outcomes in comparison to MELD [14].
  2. Platelet aggregation inhibitors but not anticoagulation agents are at increased risk for recurrent diverticular hemorrhage [15].
  3. Adhering to a Mediterranean diet might potentially slow the progression of moderate to severe psoriasis [16].
  4. Atorvastatin apparently reduces chronic subdural hematomas by 29 mL compared to 17 mL with placebo [17].

Dr. Vicky Chiang, is a 3rd year resident at NYU Langone Health

Reviewed by David Kudlowitz, MD, NYU Langone Health

Image courtesy of Wikimedia Commons

References

  1. Nagourney, Aaron. “A $100 Billion Train: The Future of California or a Boondoggle?” New York Times. 30 July 2018. A9. Web. 30 July 2018.  http://inlandpolitics.com/blog/2018/07/30/a-100-billion-train-the-future-of-california-or-a-boondoggle/
  2. Environmental Report: October 2013. ca.gov. 30 July 2018
  3. Assicot, M., Bohuon, C., Gendrel, D., Raymond, J., Carsin, H., & Guilbaud, J. (1993). High serum procalcitonin concentrations in patients with sepsis and infection. The Lancet, 341(8844), 515-518. https://www.ncbi.nlm.nih.gov/pubmed/8094770
  4. Müller, B., Harbarth, S., Stolz, D., Bingisser, R., Mueller, C., Leuppi, J., … & Christ-Crain, M. (2007). Diagnostic and prognostic accuracy of clinical and laboratory parameters in community-acquired pneumonia. BMC infectious diseases, 7(1), 10.
  5. Huang, D. T., Yealy, D. M., Filbin, M. R., Brown, A. M., Chang, C. C. H., Doi, Y., … & Holst, J. M. (2018). Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection.New England Journal of Medicine.
  6. Wang, Y., Wang, Y., Zhao, X., Liu, L., Wang, D., Wang, C., … & Jia, J. (2013). Clopidogrel with aspirin in acute minor stroke or transient ischemic attack.New England Journal of Medicine, 369(1), 11-19.  https://www.ncbi.nlm.nih.gov/pubmed/23803136
  7. Johnston, S. C., Easton, J. D., Farrant, M., Barsan, W., Conwit, R. A., Elm, J. J., … & Palesch, Y. Y. (2018). Clopidogrel and aspirin in acute ischemic stroke and high-risk TIA.New England Journal of Medicine.
  8. Thombs, B. D., De Jonge, P., Coyne, J. C., Whooley, M. A., Frasure-Smith, N., Mitchell, A. J., … & Soderlund, K. (2008). Depression screening and patient outcomes in cardiovascular care: a systematic review.Jama, 300(18), 2161-2171.  https://www.ncbi.nlm.nih.gov/pubmed/19001627
  9. Berkman, L. F., Blumenthal, J., Burg, M., Carney, R. M., Catellier, D., Cowan, M. J., … & Kaufmann, P. G. (2003). Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial.JAMA: Journal of the American Medical Association.
  10. Kim, J. M., Stewart, R., Bae, K. Y., Kang, H. J., Kim, S. W., Shin, I. S., … & Yoon, J. S. (2015). Effects of depression co-morbidity and treatment on quality of life in patients with acute coronary syndrome: the Korean depression in ACS (K-DEPACS) and the escitalopram for depression in ACS (EsDEPACS) study.Psychological medicine, 45(8), 1641-1652.
  11. Kim, J. M., Stewart, R., Lee, Y. S., Lee, H. J., Kim, M. C., Kim, J. W., … & Hong, Y. J. (2018). Effect of Escitalopram vs Placebo Treatment for Depression on Long-term Cardiac Outcomes in Patients With Acute Coronary Syndrome: A Randomized Clinical Trial.JAMA, 320(4), 350-358.
  12. Holcomb, J. B., Tilley, B. C., Baraniuk, S., Fox, E. E., Wade, C. E., Podbielski, J. M., … & Cohen, M. J. (2015). Transfusion of plasma, platelets, and red blood cells in a 1: 1: 1 vs a 1: 1: 2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial.Jama, 313(5), 471-482. https://www.ncbi.nlm.nih.gov/pubmed/25647203
  13. Sperry, J. L., Guyette, F. X., Brown, J. B., Yazer, M. H., Triulzi, D. J., Early-Young, B. J., … & Claridge, J. A. (2018). Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock.New England Journal of Medicine, 379(4), 315-326.
  14. Nagai, S., Chau, L. C., Schilke, R. E., Safwan, M., Rizzari, M., Collins, K., … & Moonka, D. (2018). Effects of Allocating Livers for Transplantation Based on Model for End-stage Liver Disease-Sodium Scores on Patient Outcomes.Gastroenterology.
  15. Vajravelu, R. K., Mamtani, R., Scott, F. I., Waxman, A., & Lewis, J. D. (2018). Incidence, Risk Factors, and Clinical Effects of Recurrent Diverticular Hemorrhage: A Large Cohort Study.Gastroenterology.
  16. Phan, Céline, et al. “Association Between Mediterranean Anti-inflammatory Dietary Profile and Severity of Psoriasis: Results From the NutriNet-Santé Cohort.”JAMA dermatology (2018).
  17. Jiang R, Zhao S, Wang R, et al. Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese PatientsA Randomized ClinicalTrial.JAMA Neurol. Published online July 30, 2018. doi:10.1001/jamaneurol.2018.2030