New England Journal of Medicine 2015


1. Nichol G, Leroux B, Wang H et al. Trial of Continuous or Interrupted Chest Compressions during CPR. N Engl J Med. 2015 Nov 9. [Epub ahead of print].

CONCLUSIONS: In patients with out-of-hospital cardiac arrest, continuous chest compressions during CPR performed by EMS providers did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions. (Funded by the National Heart, Lung, and Blood Institute and others; ROC CCC number, NCT01372748 .). PMID: 26550795

Comment: It seems that perhaps depth of compressions is more important than continuous compressions.  But it stills seems like it's best to stay on the chest as much as possible.

2. Young P, Saxena M, Bellomo R et al. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. N Engl J Med. 2015 Oct 5. [Epub ahead of print].

CONCLUSIONS: Early administration of acetaminophen to treat fever due to probable infection did not affect the number of ICU-free days. (Funded by the Health Research Council of New Zealand and others; HEAT Australian New Zealand Clinical Trials Registry number, ACTRN12612000513819 .). PMID: 26436473

Comment: Acetaminophen didn't harm critical patients nor did it help them.

3. Parienti JJ, Mongardon N, Mégarbane B et al. Intravascular Complications of Central Venous Catheterization by Insertion Site. N Engl J Med. 2015 Sep 24;373(13):1220-9. doi: 10.1056/NEJMoa1500964.

CONCLUSIONS: In this trial, subclavian-vein catheterization was associated with a lower risk of bloodstream infection and symptomatic thrombosis and a higher risk of pneumothorax than jugular-vein or femoral-vein catheterization. (Funded by the Hospital Program for Clinical Research, French Ministry of Health; number, NCT01479153.). PMID: 26398070

Comment: Subclavian is a safe vessel for patients needing a central line.

4. Ringh M, Rosenqvist M, Hollenberg J et al. Mobile-phone dispatch of laypersons for CPR in out-of-hospital cardiac arrest. N Engl J Med. 2015 Jun 11;372(24):2316-25. doi: 10.1056/NEJMoa1406038.

CONCLUSIONS: A mobile-phone positioning system to dispatch lay volunteers who were trained in CPR was associated with significantly increased rates of bystander-initiated CPR among persons with out-of-hospital cardiac arrest. (Funded by the Swedish Heart-Lung Foundation and Stockholm County; number, NCT01789554.). PMID: 26061836

Comment: A mobile app to summon trained CPR providers to the scene gets CPR started faster, and every second counts.

5. Frat JP, Thille AW, Mercat A et al. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015 Jun 4;372(23):2185-96. doi: 10.1056/NEJMoa1503326. Epub 2015 May 17.

CONCLUSIONS: In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI number, NCT01320384.). PMID: 25981908

Comment: High flow oxygen is well tolerated and is an alternative to BiPAP.

6. Moler FW, Silverstein FS, Holubkov R et al. Therapeutic hypothermia after out-of-hospital cardiac arrest in children. N Engl J Med. 2015 May 14;372(20):1898-908. doi: 10.1056/NEJMoa1411480. Epub 2015 Apr 25.

CONCLUSIONS: In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a good functional outcome at 1 year. (Funded by the National Heart, Lung, and Blood Institute and others; THAPCA-OH number, NCT00878644.). PMID: 25913022

Comment: As in adults, probably the most important thing is to prevent post-arrest hyperthermia.

7. Jovin TG, Chamorro A, Cobo E et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.

CONCLUSIONS: Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT number,
NCT01692379.). PMID: 25882510

Comment: Yet another trial shows better outcomes for endovascular clot retrieval.

8. Saver JL(1), Goyal M, Bonafe A et al for the SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.

CONCLUSIONS: In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation, thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days. (Funded by Covidien; SWIFT PRIME number, NCT01657461.). PMID: 25882376

Comment: The evidence keeps mounting that invasive treatment for ischemic stroke is preferred.  Stent-retrievers are highly effective for removing clot.  Proper patient selection is key.

9. Postma DF(1), van Werkhoven CH, van Elden LJ et al. Antibiotic treatment strategies for community-acquired pneumonia in adults. N Engl J Med. 2015 Apr 2;372(14):1312-23. doi: 10.1056/NEJMoa1406330.

CONCLUSIONS: Among patients with clinically suspected CAP admitted to non-ICU wards, a strategy of preferred empirical treatment with beta-lactam monotherapy was noninferior to strategies with a beta-lactam-macrolide combination or fluoroquinolone monotherapy with regard to 90-day mortality. (Funded by the Netherlands Organization for Health Research and Development; CAP-START number, NCT01660204.). PMID: 25830421

Comment: This surprised me.  Atypical pathogens causing pneumonia severe enough to warrant admission are obviously uncommon.

10. Miller LG, Daum RS, Creech CB et al. Clindamycin versus trimethoprim-sulfamethoxazole for uncomplicated skin infections. N Engl J Med. 2015 Mar 19;372(12):1093-103. doi: 10.1056/NEJMoa1403789.

CONCLUSIONS: We found no significant difference between clindamycin and TMP-SMX, with respect to either efficacy or side-effect profile, for the treatment of uncomplicated skin infections, including both cellulitis and abscesses. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, National Institutes of Health; number, NCT00730028.) PMID: 25785967

Comment: I always held to the adage that cellulitis could be staph or strep and TMP-SMX was not the best therapy for strep, but this study shows that either clindamycin or TMP-SMX can treat either cellulitis or abscess with suspicion of MRSA.

11. Mouncey PR, Osborn TM, Power GS et al. Trial of early, goal-directed resuscitation for septic shock. N Engl J Med. 2015 Apr 2;372(14):1301-11. doi: 10.1056/NEJMoa1500896. Epub 2015 Mar 17.

CONCLUSIONS: In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.). PMID: 25776532

Comment: This UK study found no difference in mortality for early goal-directed therapy (EGDT) vs. usual care in septic shock patients. Mortality was around 29% in both groups. EGDT was more costly.

12. Douglas PS(1), Hoffmann U, Patel MR et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015 Apr 2;372(14):1291-300. doi: 10.1056/NEJMoa1415516. Epub 2015 Mar 14.

CONCLUSIONS: In symptomatic patients with suspected CAD who required noninvasive testing, a strategy of initial CTA, as compared with functional testing, did not improve clinical outcomes over a median follow-up of 2 years. (Funded by the National Heart, Lung, and Blood Institute; PROMISE number, NCT01174550.). PMID: 25773919

Comment: CTA showed no advantage over functional testing with similar radiation exposure.

13. Goyal M, Demchuk AM, Menon BK et al for the ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.

CONCLUSIONS: Among patients with acute ischemic stroke with a proximal vessel occlusion, a small infarct core, and moderate-to-good collateral circulation, rapid endovascular treatment improved functional outcomes and reduced mortality.  (Funded by Covidien and others; ESCAPE number, NCT01778335.). PMID: 25671798

Comment: Endovascular treatment for stroke has arrived.

14. Campbell BC, Mitchell PJ, Kleinig TJ et al for the EXTEND-IA  Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015  Feb 11.

CONCLUSIONS: In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic recovery, and functional outcome. (Funded by the Australian National Health and Medical Research Council and others; EXTEND-IA number, NCT01492725, and Australian New Zealand Clinical Trials Registry number, ACTRN12611000969965.). PMID: 25671797

Comment: This is stunningly successful, which surprises me after recent trials of endovascular treatment showed no benefit.  It looks like the devices have finally overcome previous flaws.

15. Berkhemer OA, Fransen PS, Beumer D et al for the MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17.

CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.) PMID: 25517348

Comments: There has been a flood of papers demonstrating the effectiveness of endovascular stroke treatment this year.

16. Packham DK, Rasmussen HS, Lavin PT et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015 Jan 15;372(3):222-31. doi: 10.1056/NEJMoa1411487. Epub 2014 Nov 21.

CONCLUSIONS: Patients with hyperkalemia who received ZS-9, as compared with those who received placebo, had a significant reduction in potassium levels at 48 hours, with normokalemia maintained during 12 days of maintenance therapy. (Funded by ZS Pharma; number, NCT01737697.) PMID: 25415807

Comment: Tretment with sodium polystyrene sulfate is not benign and has questionable efficacy.  It is good to see a new agent coming soon which will hopefully be safer and more effective.  This one causes diarrhea.  The one discussed below is constipating.

17. Weir MR, Bakris GL, Bushinsky DA et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015 Jan 15;372(3):211-21. doi: 10.1056/NEJMoa1410853. Epub 2014 Nov 21.

CONCLUSIONS: In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemia. (Funded by Relypsa; OPAL-HK number, NCT01810939.). PMID: 25415805

Comment: Another oral potassium binder is making progress.  This one causes constipation.  Now you can pick an agent based on desired stool consistency!


1. Kaukonen KM, Bailey M, Pilcher D et al. Systemic inflammatory response syndrome criteria in defining severe sepsis. N Engl J Med. 2015 Apr 23;372(17):1629-38. doi: 10.1056/NEJMoa1415236. Epub 2015 Mar 17.

CONCLUSIONS: The need for two or more SIRS criteria to define severe sepsis excluded one in eight otherwise similar patients with infection, organ failure, and substantial mortality and failed to define a transition point in the risk of death. (Funded by the Australian and New Zealand Intensive Care Research Centre.). PMID: 25776936

Comment: SIRS negative sepsis occurred frequently in this study.  To have severe sepsis requires at least 2 SIRS criteria plus proven or suspected infection and organ failure.  The point of this study is to not have overly stringent definitions of severe sepsis when patients meet the other criteria but have less than 2 SIRS criteria.  Patient outcomes were the same with SIRS positive and SIRS negative sepsis.


1. Moritz ML, Ayus JC. Maintenance Intravenous Fluids in Acutely Ill Patients. N Engl J Med. 2015 Oct;373(14):1350-60. doi: 10.1056/NEJMra1412877.

Comment: PMID: 26422725

2. Nable JV, Tupe CL, Gehle BD, Brady WJ. In-Flight Medical Emergencies during Commercial Travel. N Engl J Med. 2015 Sep 3;373(10):939-45. doi: 10.1056/NEJMra1409213.

Comment: PMID: 26332548

3. Brunham RC, Gottlieb SL, Paavonen J. Pelvic inflammatory disease. N Engl J Med. 2015 May 21;372(21):2039-48. doi: 10.1056/NEJMra1411426.

Comment: PMID: 25992748

4. Raymond EG, Cleland K. Clinical practice. Emergency contraception. N Engl J Med. 2015 Apr 2;372(14):1342-8. doi: 10.1056/NEJMcp1406328.

Comment: PMID: 25830424

5. Ropper AH, Zafonte RD. Sciatica. N Engl J Med. 2015 Mar 26;372(13):1240-8. doi: 10.1056/NEJMra1410151.

Comment: PMID: 25806916

6. Adalja AA, Toner E, Inglesby TV. Clinical management of potential bioterrorism-related conditions. N Engl J Med. 2015 Mar 5;372(10):954-62. doi: 10.1056/NEJMra1409755.

CONCLUSIONS: The agents most likely to be used in bioterrorism attacks are reviewed, along
with the clinical syndromes they produce and their treatment. PMID: 25738671


7. Kamel KS, Halperin ML. Acid-base problems in diabetic ketoacidosis. N Engl J Med. 2015 Feb 5;372(6):546-54. doi: 10.1056/NEJMra1207788.

Comment: PMID: 25651248

8. LeWinter MM. Clinical practice. Acute pericarditis. N Engl J Med. 2014 Dec 18;371(25):2410-6. doi: 10.1056/NEJMcp1404070.

Comment: PMID: 25517707

9. Kraut JA, Madias NE. Lactic acidosis. N Engl J Med. 2014 Dec 11;371(24):2309-19. doi: 10.1056/NEJMra1309483.

Comment: PMID: 25494270

10. Schuckit MA. Recognition and management of withdrawal delirium (delirium tremens). N Engl J Med. 2014 Nov 27;371(22):2109-13. doi: 10.1056/NEJMra1407298.

Comment: PMID: 25427113

Clinical Prediction Rules


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