Primecuts – This Week In The Journals

September 26, 2016

Oh_these_Autumn_days___By Chio Yokose, M.D.

Peer Reviewed

This week, Keith L. Scott was shot to death by police in Charlotte, North Carolina while his wife recorded the scene. The footage was broadcast widely and re-ignited the intense discussion about race relations and law enforcement in America. While the police allege that he had a weapon and posed an imminent threat, his family members report that he was holding a book, not a gun, as he prepared to pick up a child from school. Along with many other details of the case, whether Mr. Scott possessed or brandished a weapon at officers remains unclear. Protests erupted in Charlotte, resulting in one fatality and injuries to protestors and law enforcement officers alike.

In medical-related news this week…

Effect of Wearable Technology Combined with a Lifestyle Intervention on Long-term Weight Loss: the IDEA Randomized Clinical Trial 

The obesity epidemic continues to pose a significant public health threat in the United States. This week in JAMA, the IDEA (Innovative Approaches to Diet, Exercise, and Activity) randomized clinical trial reports the effect of a technology-enhanced weight loss intervention over 24 months of follow-up [1].

The study enrolled 471 adult participants age 18-35 with BMI between 25-40 and randomized patients to a technology enhanced or a standardized behavioral intervention targeting weight loss. The study participants were predominantly female (71.1%) and white (77.2%). All participants received a standard behavioral weight loss intervention for 6 months. After 6 months, those in the standard intervention group initiated self-monitoring of diet and exercise while those in the enhanced intervention group were provided wearable technology to monitor physical activity and diet. The primary outcome was weight change at 24 months.

Interestingly, the standard intervention group achieved a 2.4 kilogram higher estimated mean weight loss at 24 months than those in the enhanced intervention group (95% CI 1.0-3.7, p=0.002) despite similar improvements in body composition, fitness, physical activity, and diet. While this study was unable to demonstrate a clear role of wearable technology for the initiation and maintenance of weight loss, the standardized behavioral intervention used in this program resulted in substantially more weight loss than previous reports and warrants further investigation.

Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults 

The US Preventive Services Task Force updated its 1996 recommendations regarding targeted screening and treatment of latent tuberculosis infection (LTBI) in the primary care setting. They issued a grade B recommendation in support of LTBI screening in populations at increased risk. A review of the available evidence used to inform the USPSTF in issuing this recommendation was published in JAMA [2].

The search included MEDLINE, Cochrane Library, and trial registries through August 2015 to yield English-language studies of LTBI screening, LTBI treatment with recommended pharmacotherapy, or accuracy of the tuberulin skin test (TST) or interferon-gamma release assays (IGRAs). 72 such studies were included in the review. The investigators identified no studies that evaluated benefits and harms of screening compared with no screening. The pooled estimates for sensitivity of the TST at both 5-mm and 10-mm induration thresholds were 0.79 (5-mm 95% CI 0.69-0.89, 10-mm 95% CI 0.71-0.87). The sensitivity of IGRAS ranged from 0.77-0.90. A randomized clinical trial of 24 weeks of isoniazid in more than 20,000 individuals without pulmonary fibrotic lesions and LTBI found a reduction in absolute risk of active TB at 5 years from 1.4% to 0.5% (RR 0.35, 95% CI 2.03-10.39) for 24 weeks of daily isoniazid compared to placebo. This translates to a number needed to treat of roughly 111. In comparison, the number needed to harm in regards to hepatotoxicity while on isoniazid is roughly 250. While this data may not persuade clinicians to screen all-comers in a primary care setting, it does support screening and treatment in those who have risk factors for LTBI.

CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea 

Given the previously reported association between obstructive sleep apnea and cardiovascular events, particularly cerebrovascular events, CPAP has received attention as an additional therapeutic modality for secondary prevention of such events. The results of the SAVE (Sleep Apnea Cardiovascular Endpoints), designed to address this question, was recently reported in the New England Journal of Medicine [3].

In this randomized clinical trial, 2,717 eligible adults between 45-75 years of age with moderate-to-severe obstructive sleep apnea and coronary or cerebrovascular disease were randomized to receive CPAP plus usual care or usual care alone. The primary composite end point was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for unstable angina, heart failure, or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health-related quality of life, snoring symptoms, daytime sleepiness, and mood.

The study found that therapy with CPAP plus usual care did not prevent cardiovascular events in these patients after 3.7 years compared to usual care alone (17% in the CPAP group vs. 15.4% in the usual care group; hazard ratio with CPAP 1.10 (95% CI 0.91 to 1.32, p=0.34). Importantly, participants in the CPAP treatment group were adherent to an average of 3.3 hours on the CPAP machine at night, which is far fewer than what is generally considered to be adequate adherence to CPAP, therefore, it is unclear at this time if CPAP with optimal adherence has the potential to prevent cardiovascular events.

Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors 

While factor Xa inhibitors have significantly simplified the lives of those that need long-term anticoagulation, one major drawback has been their lack of a clinically available reversal agent. Andexanet alfa is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy individuals. This week in the New England Journal of Medicine a multicenter, prospective, open-label, single-group study of the utility of andexanet in the setting of acute major bleeding [4] is reported.

This study included 67 patients with potentially life-threatening bleeds who had taken a dose of factor Xa inhibitor within 18 hours of presentation and who were not scheduled for emergent surgery within 12 hours of presentation. Participants were given a bolus of andexanet followed by a 2-hour infusion of the drug. As not all participants had baseline anti-Xa levels measured, the 47 patients who had had baseline anti-factor Xa activity levels of at least 75ng/mL were included in the efficacy analysis. 

After the bolus administration, median anti-factor Xa activity decreased by 89% (95% CI 58-94) in patients receiving rivaroxaban and by 93% (95% CI 87-94%) among patients receiving apixaban. 12 hours after the andexanet infusion, clinical hemostasis was adjudicated as excellent or good in 37 of 47 patients in the efficacy analysis based on predetermined criteria based on location of bleed (e.g. serial MRI in case of intracranial hemorrhage) (79%, 95% CI 64-89). Thrombotic events occurred in 12 of 67 patients (18%) during the 30-day follow-up period, including 10 deaths (15%). This descriptive analysis demonstrated that an initial bolus and subsequent 2-hour infusion of andexanet substantially reduced anti-factor Xa activity in patients with acute major bleeding associated with factor Xa inhibitors. Given the single-group nature of this study, additional randomized studies are needed to weigh the relative risk of thrombotic events after administration before it can be adopted for routine clinical use. 


A troubling report of spreading antibiotic resistance in India was reported in Clinical Infectious Disease [5]. They found unexpectedly high rates of resistance to ceftazidime-avibactam in carbapenem-resistant Enterobacteriaceae bloodstream isolates in one institution in New Delhi.

As the Affordable Care Act has expanded insurance coverage to millions, secondary barriers to care, such as access to transportation, are gaining increasing attention. This JAMA article reflects on the role that companies such as Uber and Lyft, which have transformed personal transportation, may play in the changing landscape of medical transportation as well [6].

In patients with rheumatoid arthritis whose symptoms are inadequately controlled on a TNF inhibitor, switching to a non-TNF biologic may achieve better disease activity response than the trial of a second, different TNF inhibitor [7].

Dr. Chio Yokose is a 3rd year resident at NYU Langone Medical Center

Peer reviewed by Kerrilynn Carney, MD, NYU Internal Medicine Residency Program

at NYU Langone Medical Center

Image courtesy of Wikimedia Commons


  1. Jakicic, J.M., et al., Effect of Wearable Technology Combined With a Lifestyle Intervention on Long-term Weight Loss: The IDEA Randomized Clinical Trial. JAMA, 2016. 316(11): p. 1161-1171.
  2. Kahwati, L.C., et al., Primary Care Screening and Treatment for Latent Tuberculosis Infection in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA, 2016. 316(9): p. 970-83.
  3. McEvoy, R.D., et al., CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med, 2016. 375(10): p. 919-31.
  4. Connolly, S.J., et al., Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors. N Engl J Med, 2016. 375(12): p. 1131-41.
  5. Aitken, S.L., et al., High Rates of Nonsusceptibility to Ceftazidime-avibactam and Identification of New Delhi Metallo-beta-lactamase Production in Enterobacteriaceae Bloodstream Infections at a Major Cancer Center. Clin Infect Dis, 2016. 63(7): p. 954-8.
  6. Powers, B.W., S. Rinefort, and S.H. Jain, Nonemergency Medical Transportation: Delivering Care in the Era of Lyft and Uber. JAMA, 2016. 316(9): p. 921-2.
  7. Gottenberg, J.E., et al., Non-TNF-Targeted Biologic vs a Second Anti-TNF Drug to Treat Rheumatoid Arthritis in Patients With Insufficient Response to a First Anti-TNF Drug: A Randomized Clinical Trial. JAMA, 2016. 316(11): p. 1172-1180.