Primecuts-This Week in the Journals

November 23, 2015

By Noam Broder, MD

This week in Primecuts we take a moment to honor the victims of the recent terror attacks in Paris and the emergency response teams who cared for the wounded. According to the Wall Street Journal, Paris’s hospital authority triggered its “Plan Blanc” at about 10:30 pm local time Friday, effectively calling medical personnel to work, getting ambulances on the road, and beds readied ahead of the expected patients. American hospitals have emergency plans similar to “Plan Blanc” with strategies for dealing with mass shootings developed after the 2012 tragedy at Sandy Hook [1]. Using the acronym “THREAT”, the American College of Emergency Physicians (ACEP) consensus called for threat suppression, hemorrhage control, rapid extraction, assessment by medical providers, and transport to definitive care. Importantly, this mandate included training EMS and police forces in hemorrhage control techniques like direct pressure, tourniquet application, and the use of hemostatic agents. An effective response to a mass shooting or terrorist attack requires the coordination of law enforcement, EMS, and hospital personnel in emergency preparedness. Hopefully the lessons learned from the horrific attacks in France and the framework established by the ACEP will help mitigate morbidity and mortality should a situation arise requiring its use.

As we prepare for the possibility of emergency response activation we will continue to deliver the high-quality, patient-centered, evidence-based care our patients have come to expect. This week in the journals we take a look at therapies for hypertension, depression, and cardiac arrest from non-shockable rhythms as well as the emerging threat of a polymyxin resistant E.Coli plasmid in China.

Spironolactone is shown to be the most effective additional drug for resistant hypertension. [2]:

With the recent publication of the landmark SPRINT trial [3], achieving lower blood pressure in patients with hypertension is on many practitioners’ minds. A study reported this week in the Lancet provides new guidance on the management of resistant hypertension. The PATHWAY 2 Study was designed to investigate the efficacy of an aldosterone-antagonist, beta blocker, or alpha blocking medication as a fourth line anti-hypertensive. In this double blind placebo controlled crossover trial, 335 patients with uncontrolled hypertension defined as a systolic BP >140 mm Hg or 135 mm Hg while on three maximally dosed antihypertensive agents (including an angiotensin-converting enzyme inhibitor, calcium channel blocker and diuretic) for 3 months were randomized to the addition of spironolactone, bisoprolol, doxazosin or placebo. Blood pressure was recorded by patients at home. Patients treated with spironolactone had a statistically significant decrease in systolic BP of 14.4 mm Hg compared to 9.1, 8.4, and 4.2 mm Hg for those treated with doxazosin, bisoprolol and placebo respectively (p<.0001). Spironolactone also significantly increased the likelihood of achieving goal BP < 135 as compared to the other arms of the study. These results support the hypothesis that large portions of resistant hypertension are due to salt retention which itself may be caused by under-dosing of diuretic medication as well as the development of secondary hyperaldosteronism in patients with resistant hypertension.

Bright light treatment is effective in patients with non-seasonal major depressive disorder. [4]

As the winter season approaches, many patients with seasonal depression will seek treatment with therapeutic bright light, but an article this week in JAMA Psychiatry suggests there may be benefit to bright light therapy in the treatment of major depressive disorders. In this randomized, double blind, placebo and sham controlled study 122 patients with a primary diagnosis of major depressive disorder were randomized to treatment for eight weeks with light monotherapy, light therapy with fluoxetine, antidepressant monotherapy or a placebo consisting of a sham light box and a placebo pill. The main outcome was a score change on a depression rating scale and secondary outcomes included 50% reduction on the depression scale as well as remission of symptoms. Light box therapy alone and dual therapies were found to be superior to placebo with greater reductions in mean depression scores associated with p values of .006 and <.001 respectively. While dual therapy was superior to light box monotherapy in regards to reduction of depression scores, fluoxetine monotherapy did not significantly lower mean depression scores greater than placebo (p=.32). The authors attribute this finding to a lack of power to detect fluoxetine monotherapy’s effect.  With regards to secondary outcomes, the number needed to treat for a 50% reduction in depression score for combination therapy was 2.4. This impressive result suggests a role for light therapy in the management of non-seasonal Major Depressive Disorder. The generalizability of this study may be limited however to those patients living in the 39° to 49° north latitudes as all patients in this study were Canadian.

Therapeutic hypothermia found to have benefit in patients presenting with cardiac arrest from non-shockable rhythms. [5]

The original study demonstrating the neuroprotective value of therapeutic hypothermia post cardiac arrest included patients who had an out of hospital cardiac arrest with an initial shockable rhythm of pulseless ventricular tachycardia or ventricular fibrillation [6,7]. Therapeutic hypothermia in the setting of cardiopulmonary arrest from a non-shockable rhythm currently carries a IIB level of recommendation due to a lack of studies in this subgroup of patients. This week Circulation published a retrospective cohort study suggesting a benefit from hypothermia protocol in patients with non-shockable presenting rhythms. Overall, patients with initial non-shockable rhythms who received hypothermia protocol survived to hospital discharge with favorable cognitive outcomes as compared those who did not receive hypothermia (OR 3.5, 95% CI:1.8-6.6). This benefit was true for both in and out of hospital cardiac arrest. Other independent factors found to be associated with neurologic recovery included female gender, PEA arrest, witnessed arrests and relative duration of arrest. While this study was limited by its retrospective design, its encouraging result may strengthen the recommendation for therapeutic hypothermia in patients with non-shockable rhythms at the time of cardiac arrest.

Emergence of plasmid mediated polymyxin resistant E Coli in animals and humans in China. [8]

Antibiotics are used prophylactically and regularly to protect food animals from becoming sick and losing value. This practice has led to the emergence of transmissible antibiotic resistant plasmids in bacteria, but polymyxin resistance has heretofore only been found in spontaneous mutations. During a routine surveillance of the microbiome and resistance patterns of E Coli in farm animals and inpatients in China, researchers have discovered a plasmid mediated, and therefore transmissible, species of polymyxin resistant E Coli. The mechanism of this plasmid mediated resistance is through a mutation on the MCR-1 gene which is involved in the production of the lipopolysaccharides that polymyxin usually targets. E coli carrying this plasmid was found in 78 out of 523 samples of raw meat and 166 of 804 live animals, and most alarmingly 16 out of1322 inpatients with infection, suggesting that this polymyxin resistant E. Coli has already begun to transfer to humans. The emergence of E Coli resistant to polymyxin, one of the antibiotics being increasingly used to fight antibiotic resistant bacterial infections, further emphasizes the need for development of novel antibiotics and the continued judicious use of antibiotics by all medical practitioners

Other interesting reads this week….

In an analysis of three large prospective cohort trials, higher total coffee consumption was associated with a lower risk of mortality [9]

In a case control study of VA patients with Barrett’s Esophagus, statin use was associated with a decreased risk of progression of Barrett’s Esophagus to esophageal adenocarcinoma [10]

A new tuberculosis vaccination based on a genetically attenuated form of TB expressing most antigens of TB expressed in humans passed phase 1 safety trials. Immunogenicity comparisons to the BCG vaccination are under trial now, perhaps heralding a new era of reduced global TB burden [11]

Noam Broder is a second year internal medicine resident at NYU Langone Medical Center

Peer Reviewed by Kerrilynn Carney, MD, Contributing Editor, Clinical Correlations

Picture courtesy of Pourya Pashootan, MD


1) Jacobs, L. M., et al. “Active shooter and intentional mass-casualty events: the Hartford Consensus II.” Bulletin of the American College of Surgeons 98.9 (2013):18-22

2) Williams, Bryan, et al. “Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2): a randomised, double-blind, crossover trial.” The Lancet (2015).

3)Verdecchia, Paolo, Fabio Angeli, and Gianpaolo Reboldi. “The SPRINT trial.”Journal of the American Society of Hypertension 9.10 (2015): 750-753.

4) Kripke, Daniel F. “Light treatment for nonseasonal depression: speed, efficacy, and combined treatment.” Journal of affective disorders 49.2 (1998): 109-117

5) Grossestreuer, Anne V., et al. “The Utility of Therapeutic Hypothermia for Post-Cardiac Arrest Syndrome Patients with an Initial Nonshockable Rhythm.”Circulation 128.22 Supplement (2013): A1.

6) Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest. NEngl J Med. 2002;346:549-556.

7) Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. “Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia”. N Engl J Med. 2002;346:557-563.

8) Liu, Y et al, “Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study” Lancet Infectious Diseases, Online prepublication.

9) Ding, Ming, et al. “Association of Coffee Consumption with Total and Cause-specific Mortality in Three Large Prospective Cohorts.” Circulation (2015): CIRCULATIONAHA-115.

10) Nguyen, Theresa, et al. “Statin Use Reduces Risk of Esophageal Adenocarcinoma in US Veterans With Barrett’s Esophagus: A Nested Case-Control Study.” Gastroenterology 149.6 (2015): 1392-1398.

11) Spertini, F. et al “Safety of human immunisation with a live-attenuated Mycobacterium tuberculosis vaccine: a randomised, double-blind, controlled phase I trial” Lancet Respiratory Medicine, Online prepublication




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