Primecuts-This Week in the Journals

May 1, 2018

PrimeCuts 6 min read

Mother Spring has arrived in New York this week and she is lovely. Flowers are blooming, birds are tweeting, rodents are merrily scurrying to and fro in full view just as we humble folk have at long last emerged from our musty hovels to share the majesty of this sun-drenched city nestled between the fresh waters of the Hudson and the salty straits of the East.

With this sense of beauty and appreciation in mind, let us now turn our attention to medicine, and to the vital and virtuous work being done by colleagues around the world. The following are but a few morsels selected from this week’s piping hot batch of medical literature:

Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting.

Coronary artery bypass grafting (CABG) remains the standard for coronary revascularization in the setting of certain pathologies and co-morbidities, and saphenous veins comprise the vast majority of grafted vasculature [1, 2]. Yet the rate of saphenous vein graft (SVG) failure within one year post-CABG has been 15-20% in recent years, a remarkably high rate to which platelet activation and thrombosis has contributed [3, 4]. Therefore, determining the optimal antithrombotic regimen post-CABG is of great clinical interest.

In a study recently published in JAMA, 500 patients were randomized within 24 hours post-elective CABG to one of three groups: ticagrelor 90mg twice a day plus ASA 100mg daily; ticagrelor 90mg twice a day alone; ASA 100mg daily alone. At one year, a blinded committee reviewed all cases to determine patency [5].

At one year, 88.7% of SVGs remained patent with ticagrelor and aspirin; 82.8% remained patent with ticagrelor alone; and, 76.5% remained patent with aspirin alone. The difference between ticagrelor plus aspirin vs aspirin alone was statistically significant (12.2% [95% CI, 5.2% to 19.2%]; P < .001), while the difference between ticagrelor alone vs aspirin alone was not (6.3% [95% CI, –1.1% to 13.7%]; P = .10). Five major bleeding episodes occurred among the sample population, all of which were associated with ticagrelor use (3 with ticagrelor and aspirin; 2 with ticagrelor alone).

For patients undergoing elective CABG with SVG, ticagrelor plus aspirin demonstrated statistically significant increased patency after one year vs aspirin alone. Additional research is needed to further explore the bleeding risk among this population.

“Rising to the Level of Your Incompetence”: What Physicians’ Self-Assessment of Their Performance Reveals About the Imposter Syndrome in Medicine.

Sometimes providers are aware of their mistakes and sometimes they are not. Those who are not are known as “unconsciously incompetent,” while those who are aware of their errors are considered “consciously incompetent” [6]. Sometimes, too, providers are “unconsciously competent”; that is, their self-perception of sub-par performance does not necessarily match objective reality. The latter two groups are of particular interest because the feelings of guilt, anxiety, and self-doubt, regardless of whether they are warranted, can contribute to physician burnout [7].

For this qualitative study, researchers emailed all physician faculty (~1,000) at one unnamed Canadian academic institution and invited them to participate in individual interviews about their “experiences with underperformance” [8]. Twenty-eight faculty members participated. Interviews were coded in three stages using constant comparative analysis to identify themes.

The authors observed that self-doubt can affect providers at all stages of training and experience. These feelings were often triggered by transitions or new responsibilities. The authors speculate on subtle differences in the types of self-doubt experienced by trainees and more experienced physicians: while trainees’ self-doubt revolved around a concern that they did not know as much as they thought they knew, experienced practitioners’ self-doubt revolved around their fear that they did not know as much as others thought they did.

To optimize provider well-being and minimize burnout, medical culture must foster an environment in which provider underperformance, either real or perceived, can be discussed in safe, supportive confines.

A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome.

Recent animal studies and human observational studies have demonstrated immunomodulatory effects of statins in sepsis [9]. While RCTs investigating statin use in sepsis have not demonstrated benefit, there is increasing data to suggest that statins may have antibacterial effects [10]. This population-based cohort study sought to elucidate whether the observed antibacterial effect of statin therapy was drug- or class-specific. [11]

Drawing from the Taiwan National Health Insurance Research Database from the years 2001-2011, 52,737 patients with sepsis fulfilled the inclusion criteria. 1,855 were prescribed atorvastatin, 916 received simvastatin, and 732 were administered rosuvastatin. The primary end point was 30-day all-cause mortality [11].

Compared with patients who did not receive statins, simvastatin (HR, 0.72; 95% CI, 0.58-0.90) and atorvastatin (HR, 0.78; 95% CI, 0.68-0.90) were associated with an improved 30-day survival, whereas rosuvastatin’s effect was not statistically significant (HR, 0.87; 95% CI, 0.73-1.04).

The benefit of statins on patients with sepsis was drug-specific, with simvastatin and atorvastatin superior to rosuvastatin by a statistically significant margin. While further research is needed to validate and explain the observed findings, when presented with an indication for and choice of statins, providers might consider prescribing simvastatin to those patients at higher risk of sepsis.

Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa.

Azithromycin has been distributed throughout Sub-Saharan Africa on the order of 600 million doses in an effort to eliminate the ocular chlamydia from which trachoma arises [12, 13]. Although such wide distribution has prompted selection for macrolide-resistant infections there remains optimism that the medication might further reduce childhood mortality by preventing or mitigating the spread of non-chlamydial diseases, including malaria and infectious diarrhea.

This cluster randomized trial investigated whether mass distribution of azithromycin would reduce mortality in children ages 1-59 months. 1,533 communities in Tanzania, Malawi, and Niger, consisting of 190,238 children in total, were randomly assigned to azithromycin (~20mg/kg dosing) vs. placebo coverage over four twice-yearly medication distributions [14]. The vital status of each patient was recorded every six months during the study.

Overall annual mortality rate was 14.6 deaths per 1000 person-years among the communities receiving azithromycin vs 16.5 deaths per 1000 person-years among those receiving placebo. Children ages 1-5 months demonstrated the greatest benefit from azithromycin (24.9% lower mortality than with placebo; 95% CI, 10.6 to 37.0). No clear adverse events were detected.

Statistically significant decrease in mortality rate was observed in children ages 1-59 months who received azithromycin vs those who received placebo. Although not performed here, assessment of the development of antimicrobial resistance resulting from efforts such as these is vital to truly evaluate their short- and long-term efficacy.

Minicuts

And, lastly, here are links to a few more exciting reports:

Increased connectivity between engram cells across adjacent brain regions is associated with stronger memory [15].

Oxygen therapy above SpO2 94-96% may increase mortality among acutely ill adults [16].

According to a recent study in Circulation, lifetime risks for heart failure vary significantly by sex, race, and history of MI [17].

Dr. Daren J. Simkin is a 1st year internal medicine resident at NYU Langone Health 

Peer reviewed by Amar Parikh, MD, Associate Editor of Clinical Correlations and Chief Resident of Internal Medicine at NYU Langone Health 

Image courtesy of Wikimedia Commons.

References:

  1. Alexander JH, Smith PK. Coronary-artery bypass grafting. N Engl J Med. 2016;374(20):1954-1964.
  2. Aldea GS, Bakaeen FG, Pa lJ, et al; Society of Thoracic Surgeons. The Society of Thoracic Surgeons clinical practice guidelines on arterial conduits for coronary artery bypass grafting. Ann Thorac Surg. 2016;101(2):801-809.
  3. Halabi AR, Alexander JH, Shaw LK, et al. Relation of early saphenous vein graft failure to outcomes following coronary artery bypass surgery. Am J Cardiol. 2005;96(9):1254-1259.
  4. Gaudino M, Antoniades C, Benedetto U, et al; ATLANTIC (Arterial Grafting International Consortium) Alliance. Mechanisms, consequences, and prevention of coronary graft failure. Circulation. 2017;136(18):1749-1764.
  5. Zhao et al. Effect of Ticagrelor Plus Aspirin, Ticagrelor Alone, or Aspirin Alone on Saphenous Vein Graft Patency 1 Year After Coronary Artery Bypass Grafting. JAMA. 2018;319(16):1677-1686. doi:10.1001/jama.2018.3197
  6. Hays RB, Jolly BC, Caldon LJ, et al. Is insight important? Measuring capacity to change performance. Med Educ. 2002;36:965–971.
  7. Sirriyeh R, Lawton R, Gardner P, Armitage G. Coping with medical error: A systematic review of papers to assess the effects of involvement in medical errors on healthcare professionals’ psychological well-being. Qual Saf Health Care. 2010;19:e43.
  8. LaDonna, K et al. “Rising to the Level of Your Incompetence”: What Physicians’ Self-Assessment of Their Performance Reveals About the Imposter Syndrome in Medicine. Academic Medicine: May 2018: 93 (5): 763-768
  9. Gao F, Linhartova L, Johnston AM, Thickett DR. Statins and sepsis. Br J Anaesth. 2008;100(3):288-298.
  10. Crisby M. Modulation of the inflammatory process by statins. Timely Top Med Cardiovasc Dis. 2005;9:E3.
  11. Lee, CC et al. A Population-Based Cohort Study on the Drug-Specific Effect of Statins on Sepsis Outcome. Chest. April 2018, 153 (4): 805-815.
  12. Taylor HR, Burton MJ, Haddad D, West S, Wright H. Trachoma. Lancet 2014; 384:2142-52.
  13. Emerson PM, Hooper PJ, Sarah V. Progress and projections in the program to eliminate trachoma. PLoS Negl Trop Dis 2017;11(4):e0005402.
  14. Keenan et al. Azithromycin to Reduce Childhood Mortality in Sub-Saharan Africa. N Engl J Med 2018; 378: 1583-1592.
  15. Choi JH, Sim SE, Kim JI, Choi DI, Oh J, Ye S, Lee J, Kim T, Ko HG, Lim CS, Kaang BK. Interregional synaptic maps among engram cells underlie memory formation. Science. Apr 27;360(6387):430-435.
  16. Chu DK, Kim LHY, Young PJ, Zamiri N, Almenawer SA, Jaescke R, Szczeklik W, Schunemann HJ, Neary JD, Alhazzani W. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018;391:1693-705.
  17. Pandey A, Omar W, Ayers C, LaMonte M, Klein, L, Allen NB, Kuller LH, Greenland P, Eaton CB, Gottdiener JS, Lloyd-Jones DM, Berry JD. Sex and race differences in lifetime risk of heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. Circulation. 2018 Apr 24;137(17):1814-1823.