Primecuts-This Week in the Journals

September 25, 2018

By: Chen Fu, MD

This week’s news brought stories of potential game changers in the world at large. On Thursday, South Korean President Moon Jae-Im arrived in North Korea in a symbolic visit to Mount Paektu, a sacred site with tremendous significance for both North and South Koreans. His arrival brought with it parades and fanfare on the North Korean side, along with a renewed hope of peace in a region still embroiled in a decades-long conflict.   Meanwhile, back in the U.S., Brett Kavanaugh’s confirmation hearings take center stage as allegations of sexual misconduct threaten an appointment that may change the face of the federal Supreme Court for a generation. And with that, let’s shift gears toward some of the potential game changers from this week in the medical journals.

Opioid Prescribing in the United States Before and After the Centers for Disease Control and Prevention’s 2016 Opioid Guideline

As the opioid epidemic rages on in the United States, efforts continue to be made at both the federal and local levels to combat this enormous problem. One important tool used to curtail opioid prescriptions involves the implementation of stricter prescribing guidelines, published by the CDC as of March 2016. A recent interrupted time series analysis from the Annals of Internal Medicine questions whether the number of opioid prescriptions has been affected by the release of the updated guidelines. Researchers looked at monthly prescribing metrics from population-level retail pharmacy data between 2012 and 2017, and found that the rate of opioid prescriptions dropped significantly after the new guidelines were released. This includes the rate of high-dose opioid prescriptions, as well as the proportion of patients receiving simultaneous prescriptions for both opiate and benzodiazepine pharmacotherapy.

Bottom Line: According to national retail pharmacy data, opioid prescribing rates, which had previously been declining, have decreased even further since the release of more stringent opioid prescribing guidelines from the CDC.

Bohnert AS, Guy GP, Losby JL. Opioid Prescribing in the United States Before and After the Centers for Disease Control and Prevention’s 2016 Opioid Guideline. Ann Intern Med.169:367–375.

Effect of aspirin on all-cause mortality in the healthy elderly

A recent study examining the effect of aspirin on all-cause mortality in elderly patients garnered some attention in the New York Times as a potential shift in the way aspirin is prescribed as primary prevention. In this randomized, double-blind, placebo-controlled trial, researchers in Australia and the U.S. examined nearly 20,000 individuals aged 70 years or older who were otherwise healthy and were without overt contraindications to aspirin therapy (e.g. high-risk for bleeding). Patients were randomized to receive either aspirin or placebo, and were followed for a median of 4.7 years. This study found that neither disability-free survival nor the rate of death were significantly different in the placebo group compared to the aspirin group. Moreover, the aspirin cohort was found to have a slightly increased rate of major hemorrhage, which the investigators defined as hemorrhagic stroke, intracranial bleeding, or clinically significant bleeding that led to transfusion, hospitalization, or worse inpatient outcomes. The study was terminated early after the authors determined that there was no significant benefit from aspirin therapy.

Bottom line:The use of aspirin as primary prevention in otherwise healthy individuals over the age of 70 did not yield a significant difference in disability-free survival, and may have contributed to more major bleeding events.

McNeil JJ, Nelson MR, Woods RL, et al. Effect of aspirin on all-cause mortality in the healthy elderly. N Engl J Med. DOI: 10.1056/NEJMoa1803955.

Mutation Clearance after Transplantation for Myelodysplastic Syndrome

Allogeneic stem cell transplant (SCT) is the only established cure for patients diagnosed with myelodysplastic syndrome (MDS). However, the procedure itself not only carries a tremendous risk of complications, but also a significant rate of treatment failure. In order to better identify which patients might be at the greatest risk for failure, researchers at the Washington University in St. Louis attempted to use genetic sequencing to predict the rate of progression-free survival in patients with MDS who underwent stem cell transplantation. Prior to SCT, researchers confirmed the presence of at least one mutation associated with MDS in patient cells, and found that, while the majority of patients cleared the mutation after transplant, a proportion of these patients (37%) continued to carry at least one mutation even after SCT. These patients experienced a nearly four-fold increase in the rate of disease progression (53.1% vs. 13%; HR = 3.86; 95% CI, 1.96-7.62) with nearly half the rate of 1 year progression-free survival (31.3% vs. 59.3%; HR = 2.22; 95% CI, 1.32-3.73).

In a press interview released by Washington University School of Medicine, senior author Matthew J. Walter, MD stated his motivation for using genetic testing to predict the success rate of SCT. “A genetic analysis is a much more precise method of measuring how many blood cells are cancerous. It also lets us find abnormal cells at earlier time points after a stem cell transplant, when there are fewer cancerous cells to find. The earlier we can detect that the cancer is coming back, the more time we may have to intervene.” In the same press interview, Dr. Walter expresses the promise of these results: “Using our sequencing method, we’re identifying residual tumor cells before a pathologist could see them under the microscope and before a patient develops symptoms… At that moment, there may be time to intervene in ways that could delay the cancer from coming back or potentially prevent it completely.”

Bottom line: Persistent mutations after stem cell transplant in patients with myelodysplastic syndrome correlates with disease progression and treatment failure. Early recognition of these patients may help us identify a group at high risk of further disease progression.

Duncavage EJ, Jacoby MA, Chang GS, Miller CA. Mutation Clearance after Transplantation for Myelodysplastic Syndrome. NEJM. Sept 13, 2018.

Strait, JE. “Genetic testing helps predict disease recurrence in myelodysplastic syndrome.” Washington University School of Medicine News. [St Louis, MO]. September 12, 2018. Online

Baloxavir Marboxil for uncomplicated influenza in adults and adolescents (CAPSTONE-1 Trial)

Flu season is almost upon us again, and with growing questions about the resistance to the veteran anti-influenza drug Oseltamavir, the need for additional antiviral therapy is becoming a priority. Baloxavir, a viral cap-dependent endonuclease inhibitor, was studied in the CAPSTONE-1 trial, a phase 3 double-blind, randomized placebo- and oseltamavir-controlled trial, recently published in the New England Journal of Medicine. Nearly 1,500 patients with clinical signs and symptoms of uncomplicated influenza infection were randomized in the phase 3 study. Researchers showed that treatment with a single dose of Baloxavir was associated with a shorter time to resolution of symptoms when compared to placebo, though had similar time to resolution as the standard 5-day course of oseltamivir. Evaluation of effective viral load (EVL) showed that Baloxavir provided a more rapid decline of EVL when compared to both placebo and oseltamavir. This study did observe a rise in influenza strain resistance between phase 2 and phase 3 trials , from 2% to nearly 10%. This inspires the question: does viral resistance pose a vital threat to Baloxavir’s efficacy before it even reaches the US market?

Bottom Line:Baloxavir is a promising anti-influenza drug that has proven effective in reducing the time course of flu-like symptoms, but concern continues for growing rates of influenza strain resistance between clinical trials.


Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med 2018;379:913923.

Chen Fu, MD is a third year internal medicine resident at NYU Langone Health

Peer Reviewed by Allison Guttmann, MD Associate Editor, Clinical Correlations

Image of Mount Paektu courtesy of Wikimedia Commons