Primecuts – This Week In The Journals

December 8, 2015

800px-Kobe_Bryant_8Jiwoon Chang, MD

Peer Reviewed 

This past week we witnessed another senseless mass shooting in San Bernardino, California that killed 14 people. The FBI is investigating this act of violence as a terror attack and the assailants’ link to ISIS [1]. On average shootings that kill or injure more than 3 people occurred once or more per day in the United States this year [2]. In other news US health spending increased by 5.3% last year to $3 trillion, likely due to expanded insurance coverage and rapid development in specialty drug spending [3]. In the world of sports, the Los Angeles Lakers shooting guard Kobe Bryant announced that he would retire at the end of this season after his 20th year in the NBA.

Now onto the latest news in medicine…

On-demand pre-exposure prophylaxis in men at high risk for HIV infection found to provide protection [4] 

According to the UN Program on HIV/AIDS, there were 2.7 million new HIV infections in 2008. In 2010 the Pre-exposure Prophylaxis Initiative (iPrex) trial demonstrated that among men at high risk of acquiring HIV, the daily use of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) resulted in a 44% reduction in the rate of HIV infection [5]. Given the moderate reduction in HIV incidence as well as the suspected low compliance with a daily regimen, a new study was conducted to evaluate the efficacy and safety of using pre-exposure prophylaxis only before and after sexual activity. In a double-blind, randomized control trial published this week in the New England Journal of Medicine, 400 HIV-negative men who have sex with men and who are were at high risk for HIV acquisition (unprotected anal sex with 2 or more partners in the last 6 months) were randomized to take a combination of TDF and FTC or placebo within 24 hours before and after sexual activity. The primary end point was the diagnosis of new HIV-1 infection, as defined by the presence of HIV antibodies or p24 antigen in the serum on a fourth-generation ELISA test, or HIV-1 RNA on PCR assay of serum samples. Participants in the TDF-FTC and placebo groups each took a median of 15 pills per month. Two subjects in the TDF-FTC group and 14 in the placebo group developed HIV-1 infection after enrollment (86% relative reduction, 95% confidence interval [CI], 40 to 98; P=0.002). Compared to the placebo group, subjects in the TDF-FTC group had increased rates of gastrointestinal adverse events (nausea, vomiting, diarrhea, abdominal pain) and elevations in serum creatinine levels. Compared to the previous iPrex trial that suggested a role for daily prophylactic antiretroviral therapy, this study showed that a sexual activity-dependent approach to antiretroviral prophylaxis may provide benefit to HIV-negative men at high-risk for HIV acquisition while allowing for increased adherence. 

Sofosbuvir-velpatasvir treatment for HCV genotype 2 and 3 infection showed superior virologic response than sofosbuvir-ribavirin (ASTRAL-2 and ASTRAL-3) [6]

With the introduction of direct-acting antiviral agents, specific treatment guidelines now exist for each hepatitis C genotype. The current recommendation is 12 to 20 weeks of sofosbuvir-ribavirin for HCV genotype 2 and 24 weeks of sofosbuvir-ribavirin for HCV genotype 3. However, the use of ribavirin is limited in some patients due to its hematologic, teratogenic, and other toxic effects. Velpatasvir is a new NS5A inhibitor that is effective against all HCV genotypes. In two randomized, open-label phase III trials, subjects with HCV genotypes 2 and 3 were randomly assigned to receive either sofosbuvir-velpatasvir for 12 weeks or sofosbuvir-ribavirin for 12 or 24 weeks (for genotypes 2 and 3, respectively). The primary endpoint was sustained virologic response 12 weeks after the completion of therapy. Among patients with HCV genotype 2, the rate of sustained virologic response was 99% (95% CI, 96 to 100) in the sofosbuvir-velpatasvir group compared to 94% (95% CI, 88 to 97) in the standard treatment group (P=0.02). In patients with HCV genotype 3, the rate of sustained virologic response was 95% (95% CI, 92 to 98) in the sofosbuvir-velpatasvir group and only 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P<0.001). The combined use of sofosbuvir and velpatasvir in patients with HCV genotype 2 or 3 showed increased rates of sustained virologic response compared to standard treatment with sofosbuvir and ribavirin. It is especially encouraging to observe higher rates of sustained virologic response in genotype 3, which has been associated with more rapid disease progression and lower response rates to treatment.

Increased television viewing and decreased physical activity in early adulthood were associated with worse processing speed and executive function [7]

In a prospective study published in JAMA Psychiatry this week, investigators sought to evaluate the effect of television viewing and physical activity on midlife cognition. A total of 3245 young adults aged 18 to 30 were assessed at repeat visits over a 25-year period using a validated questionnaire.  Watching more than 3 hours of television per day in more than two-thirds of the visits was categorized as a 25-year pattern of high television viewing. A 25-year pattern for low physical activity was defined as activity levels below the lower quartile in more than two-thirds of the visits. Cognitive function was evaluated at year 25 using various tests. High television viewing and low physical activity were associated with poor cognitive performance at year 25. This study demonstrates that these risky behaviors during childhood and early adulthood are associated with worse midlife cognitive function and suggests targets for prevention. It would be interesting to correlate a 25-year pattern of television viewing and physical activity with cognitive and behavioral disorders later in life.

Early administration of intravenous acetaminophen did not affect the number of ICU-free days or 90-day mortality in ICU patients with suspected infection [8] 

Fever is commonly thought to cause additional physiologic stress in hospitalized patients with suspected infections, and as a result acetaminophen is frequently administered as an adjunct to fluids and antimicrobial agents. In a prospective randomized trial, 700 ICU patients with fever and probable infection were randomly assigned to receive either 1g of intravenous acetaminophen or placebo every 6 hours until ICU discharge, resolution of fever, discontinuation of antibiotics, or death. The primary endpoint was the number of days alive and free from the need for intensive care from randomization to day 28. Researchers found no significant difference between the two groups with regards to the number of ICU free days, ICU length of stay, hospital length of stay, or overall mortality at 28 or 90 days. Patients who received intravenous acetaminophen had a lower body temperature than those in the placebo group but did not differ in adverse events. One potential drawback of this study is that most patients’ ICU stay was relatively short, and therefore the absence of any benefit from acetaminophen administration may not apply to patients who require a longer ICU stay.


In a prospective study of more than 4800 US adults aged 18 to 30 years, higher baseline fitness level and improvement in fitness are associated with lower risks for CVD and mortality [9].

In a randomized trial of adults with proliferative diabetic retinopathy, treatment with ranibizumab intravitreous injection was non-inferior to pan-retinal photocoagulation [10].

In a randomized double-blind phase II trial, andexanet, a recombinant factor Xa decoy protein, demonstrated rapid reversal of factor Xa inhibitor anticoagulant activity among healthy older adults without thrombotic or other serious adverse events [11].

In a randomized, single-blind trial, a long-term Mediterranean diet supplemented with extra-virgin olive oil was considered the most beneficial diet in the primary prevention of breast cancer among women aged 60 to 80 years at high cardiovascular disease risk [12]. 

Dr. Jiwoon Chang is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Jennifer Mulliken, MD, Internal Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons


  1. Richard A. Serrano, Brian Bennett, and Soumya Karlamangla. FBI probes Islamic State, terror links to San Bernardino massacre. The Los Angeles Times. 2015 Dec 5.


  1. Sharon LaFraniere, Sarah Cohen, and Richard A. Oppel Jr. How Often Do Mass Shootings Occur: On Average, Every Day, Records Show. The New York Times. 2015 Dec 2.


  1. Chad Terhune. U.S. health spending hits $3 trillion as Obamacare and rising drug costs kick in. The Los Angeles Times. 2015 Dec 2.


  1. Molina J, Capitant C, Spire, B et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med. 2015; 373(23):2237-46.


  1. Grant RM, Lama JR, Anderson PL, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010; 363:2587-99.


  1. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med. 2015 [Epub ahead of print].


  1. Hoang TD, Reis J, Zhu N, et al. Effect of early adult patterns of physical activity and television viewing on midlife cognitive function. JAMA Psychiatry. 2015 [Epub ahead of print].


  1. Young P, Saxena M, Bellomo R, et al. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. N Engl J Med. 2015; 373(23):2215-24.


  1. Shah RV, Murthy VL, Colangelo LA, et al. Association of fitness in young adulthood with survival and cardiovascular risk: the coronary artery risk development in young adults (CARDIA) study. 2015 [Epub ahead of print].


  1. Gross JG, Glassman AR, Jampol LM, et al. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. 2015; 314(20):2137-46.


  1. Siegal DM, Curnutte JT, Connolly SJ, et al. Andexanet Alfa for the reversal of factor Xa inhibitor activity. 2015 [Epub ahead of print].


  1. Toledo E, Salas-Salvado J, Donat-Vargas C, et al. Mediterranean diet and invasiave breast cancer risk among women at high cardiovascular risk in the PREDIMED trial: a randomized clinical trial. 2015; 175(11):1752-60.