Primecuts – This Week In The Journals

March 9, 2016

479px-Pink_tulip_flowerBy: Alexandra Price, MD

Peer Reviewed

This past Super Tuesday made clear that Donald Trump and Hilary Clinton are dominating the race to the White House, with both candidates winning a total of 7 out of 11 states. Ted Cruz is trailing behind Trump as the 2nd place Republican nominee, with 3 campaign wins in Alaska, Oklahama, and his home state of Texas. Marco Rubio is in 3rd place with his win in Minnesota. Dr. Ben Carson dropped out of the race after his Super Tuesday losses.1 And now onto some more clinically relevant news in this week’s Primecuts…

The association between Zika virus and Guillain-Barré Syndrome

With Zika virus rapidly spreading across the Americas, we are just beginning to understand the signs and symptoms of the disease. Interestingly, a closer look at one of the largest Zika virus outbreaks in French Polynesia between 2013-2014 revealed a concomitant rise in the incidence of Guillain-Barré syndrome (GBS).2 A case control study delved into further into this observation and found an association. Serologic evidence suggests that Zika virus can lead to GBS. In the study, 98% of patients with GBS had anti-Zika IgM or IgG antibodies, compared to 36% in the control group (OR 59.7, p<0.001). Moreover 100% of patients with GBS had neutralizing antibodies against Zika virus, compared to 56% in the control group (OR 34.1, p<0.0001). Most patients with GBS had a recent history of a viral syndrome, manifested most commonly by rash, arthralgia, and fever, a median of 6 days before the onset of neurological symptoms. 38% of patients were admitted to ICUs and 29% required respiratory support, but the clinical outcome was generally favorable. All patients survived and 3 months after discharge, 57% were able to walk without assistance. With the rising incident of Zika virus infections in America, clinicians should be aware of this association when approaching patients with viral illness or neurologic symptoms.

Use of procalcitonin level guided duration of antibiotic therapy offers mortality benefit in critically ill patients 

Antibiotic treatment, while saving so many lives from bacterial infections, when prolonged, has the potential to lead to antimicrobial resistance and adverse outcomes. As of now, there are no specific markers to guide length of antibiotic therapy with most physicians relying on established guidelines or clinical gestalt. A groundbreaking multicenter, randomized, controlled trial showed the value of procalcitonin in guiding the duration of antibiotic therapy in critically ill patients.3 Patients were randomly assigned to receive antibiotic therapy by standard-of-care protocols versus a procalcitonin-guided protocol. In the procalcitonin-guided group, procalcitonin level was measured daily as close to study enrollement as possible. In this group it was advised to discontinue antibiotics if procalcitonin concentration had decreased by 80% or more of its peak value or to 0.5 μg/L or less. In the standard-of-care group, length of antibiotic therapy was determined by local antibiotic protocols. Patients in the procalcitonin-guided group had reduced duration of antibiotic therapy compared to the standard of care-group (p<0.0001). Importantly, this reduction in treatment duration in the procalcitonin-guided group was associated with a significant decrease in mortality, resulting in a 5% improvement in mortality at 28 days by intention-to-treat analysis. The mortality benefit at 28 days in the per-protocol analysis was even higher at 7%. The study also found a 7% decrease in mortality at 1 year in the procalcitonin-guided group. All of these results were statistically significant.

This study shows that procalcitonin can safely and effectively be used to guide antibiotic therapy in critically ill patients. The mortality difference seen with procalcitonin guidance may not be fully explained by antibiotic related adverse events. Instead, the mortality difference could also be from prompt recognition of other diagnosis afford by the use of procalcitonin levels.

Efficacy of Prevention Strategies for Contrast-Induced Nephropathy 

Iodine contrast has provided a major advancement in diagnostic imaging but comes at the risk of contrast-induced nephropathy (CIN). To date, several interventions have been postulated to reduce CIN with conflicting results. Finally, a systematic review and meta-analysis analyzed the relative effectiveness of various interventions.4 The study analyzed 54 randomized controlled trials (RCTs) on N-acetylcysteine, 19 RCTs on IV sodium bicarbonate, 7 RCTs on N-acetylcysteine vs sodium bicarbonate, 13 studies on statins, and 8 RCTs on ascorbic acid. The primary outcome was CIN, defined as an increase in serum creatinine levels of greater than 25% or 0.5 mg/dL within 3 days of receiving IV contrast. The greatest reduction in CIN was achieved with low-dose N-acetylcysteine in patients receiving low-osmolar contrast (RR, 0.69, CI 0.58 to 0.84) and with statins plus N-acetylcysteine (RR 0.52, CI, 0.29 to 0.93). While these findings were clinically important and statistically significant, the strength of evidence was low-to-moderate due to limitations in the quality of the studies and inconsistency in results. Other comparisons which were clinically important but not statistically significant included: sodium bicarbonate versus IV saline in patients receiving LOCM, statins plus IV saline versus IV saline, and ascorbic acid versus IV saline. Importantly, most studies involved patients receiving intra-arterial contrast, thereby making the results difficult to extrapolate to patients receiving intravenous contrast. 

Erythropoietin-Stimulating Agents Do Not Impact Health-Related Quality of Life 

Up until now it has been unclear whether providing erythropoietin-stimulating agents to patients with anemia of chronic kidney disease provides any benefit with regard to improving health-care related quality of life (HRQOL). A systematic review and meta-analysis tackled this question by analyzing data from 17 studies.5  In total, the studies involved 10,049 patients with chronic kidney disease (CKD). Twelve studies were in the nondialysis CKD population, 4 were in the dialysis population, and 1 was in a combined sample. The lower hemoglobin target ranged from 7.4 to 12 g/L, and the higher hemoglobin target ranged from 10.2 to 13.6 g/L. The primary measure was change in baseline and follow-up scores of HRQOL instruments, specifically the 36-item Short Form Health Survey (SF-26) and the Kidney Disease Questionnaire (KDQ). The patient follow up periods ranged from 8 weeks to 36 months. The systematic review found that randomization to a higher hemoglobin target resulted in no statistically or clinically significant differences in HRQOL. Current evidence suggests that treatment of anemia with erythropoietin-stimulating agents to higher hemoglobin targets leads to increased health care costs without improving quality of life and may even increase morbidity and mortality in patients with CKD.6,7

Other highlights from this week:

Computer-assisted stethoscopes that can both record and help to differentiate respiratory sounds (e.g. wheezes, crackles, rhonchi, rales) through data analysis algorithms are on the rise.8 Before we know it, these sounds will be uploaded and stored in patient charts on EMRs

A cohort study showed that women undergoing transcatheter aortic valve replacement had a lower mortality rate than men at 1 year, despite having more frequent postprocedural vascular and bleeding complications.9 Several plausible reasons were cited, including lower levels of cardiac fibrosis and more rapid LV remodeling in women.

A multicenter double-blind, randomized trial found oral prednisone and indomethacin had similar analgesic effectiveness among patients with acute gout, paving the way for oral corticosteroids to compete as a first-line treatment option.10

Dr. Alexandra Price is a medical intern at NYU Langone Medical Center

Peer reviewed by Ian Henderson, MD, 2nd year medicine resident at NYU Langone Medical Center

Image courtesy of Wikimedia Commons


  1. Ben Carson Suspends 2016 Campaign at CPAC. NBC News. March 4, 2016.
  2. Cao-Lormeau V-M, Blake A, Mons S, et al. Guillain-Barre Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study. The Lancet.
  3. de Jong E, van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. The Lancet Infectious Diseases.
  4. Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of Prevention Strategies for Contrast-Induced Nephropathy: A Systematic Review and Meta-analysis. Ann. Intern. Med. Feb 2 2016.
  5. Collister D, Komenda P, Hiebert B, et al. The Effect of Erythropoietin-Stimulating Agents on Health-Related Quality of Life in Anemia of Chronic Kidney Disease: A Systematic Review and Meta-analysis. Ann. Intern. Med. Feb 16 2016.
  6. Inrig JK, Barnhart HX, Reddan D, et al. Effect of hemoglobin target on progression of kidney disease: a secondary analysis of the CHOIR (Correction of Hemoglobin and Outcomes in Renal Insufficiency) trial. Am. J. Kidney Dis. Sep 2012;60(3):390-401.
  7. Lau JH, Gangji AS, Rabbat CG, Brimble KS. Impact of haemoglobin and erythropoietin dose changes on mortality: a secondary analysis of results from a randomized anaemia management trial. Nephrol. Dial. Transplant. Dec 2010;25(12):4002-4009.
  8. Ohshimo S, Sadamori T, Tanigawa K. Innovation in Analysis of Respiratory Sounds. Ann. Intern. Med. Feb 16 2016.
  9. Kodali S, Williams MR, Doshi D, et al. Sex-Specific Differences at Presentation and Outcomes Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Cohort Study. Ann. Intern. Med. Feb 23 2016:377-384.
  10. Rainer TH, Cheng CH, Janssens HJ, et al. Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial. Ann. Intern. Med. Feb 23 2016.