Primecuts – This Week In The Journals

June 28, 2016

PrimeCuts 6 min read

Banknotes_(4897267054)By Katherine Nixon, MD

Peer Reviewed 

This week the United Kingdom (UK) had a national vote on whether to stay in or leave the European Union (E.U.). On Thursday June 23rd, the nation voted to leave the E.U. with a win of just 52% [1]. The push for movement out of the E.U. was started when the nation saw a large influx of immigrants, and fears ensued. In the E.U., citizens are allowed to move and live freely within the participating countries. With over 330,000 people who immigrated to the UK in 2015, many of the British citizens felt that their borders were not regulated enough and that they needed to “take control” [1]. The large influx of people was putting strain on their public services such as schools and health care. The supporters of the “Leave” side felt that a “Brexit” as they call it, would give their country more power [1]. Immediate repercussions, including economic downturn, the resignation of British Prime Minister David Cameron, and turmoil between various regions of the UK are being seen. While we continue to watch the future of the newly independent UK evolve, we can take a look at this week’s noteworthy items in the medical literature.

Screening for Colorectal Cancer: US Preventative Services Task Force Recommendation Statement 

Colorectal cancer is a major cause of morbidity and mortality in the United States. In the US, 5% of people at average risk will develop it. Death rates are declining in the US, and our country has one of the highest survival rates from colorectal cancer [2]. This is due, in large part, to screening.

The Unites States Preventative Services Task Force (USPSTF) has published new guidelines, updated from their 2008 recommendations, on screening for colorectal cancer [3]. The USPSTF has compared the data for various screening methods including guaiac-based fecal occult blood test (gFOBT), fecal immunochemical tests (FITs), flexible sigmoidoscopy, colonoscopy, multitargeted stool DNA testing (FIT-DNA), methylated SEPT9 DNA blood test, and computed tomography (CT) colonography.

The updated USPSTF recommends that beginning at age 50, patients should be screened for colorectal cancer, and screening should continue until age 75 (grade A recommendation). Screening in patients age 76-85 should be individualized based on the patient’s history (grade C recommendation). The test used for screening can be chosen based on risks and benefits as well as input from the patient on his/her preference. There are multiple studies showing different levels of effectiveness for each, but there are no empirical data to show that any screening entity is of greater benefit. This is a marked changed from preceding guidelines which recommended screening with specific tests; previously the USPSTF recommended colonoscopy every 10 years, annual FIT, annual high-sensitivity FOBT, or flexible sigmoidoscopy every 5 years combined with high-sensitivity FOBT every 3 years. 

Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load 

Transmission of the Hepatitis B virus from mothers to their infants is very high (up to 90%) without any treatment. Fortunately, administration of immunoglobulin in addition to the Hepatitis B vaccine is able to decrease the rate of transmission significantly. However, transmission still occurs, most frequently in mothers positive for hepatitis B e antigen (HBeAg) and in mothers with high viral load [4].

A randomized control trial was published in the New England Journal of Medicine examining the use of tenofovir in HBeAg positive pregnant women with an HBV DNA level >200,000 IU/ml to prevent transmission of the virus to their infants [5]. Results show that mothers treated with tenofovir had a statistically significant lower rate of mother-to-child transmission of Hepatitis B as compared to the control group, who received usual care with immunoglobulin and the HBV vaccine only. Number needed to treat (in the intention-to-treat analysis) is 7.7. There were no significant differences between the treatment group and the control group in terms of fetal development or congenital deformity. Clinicians should consider treating their HBeAg-positive pregnant patients that have a high viral load with tenofovir in the future to prevent vertical transmission of the virus to their newborns.

RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers 

Women with the BRCA gene mutation are at a higher risk for breast cancer than the average patient; data has shown that for women with the BRCA1 mutation, the risk for developing breast cancer is 65% by age 70 [6]. Given the very high risk, finding a preventative measure for these patients is of great interest.

Nature Medicine journal published a study in which the drug denosumab, a monoclonal antibody that binds RANK ligand (RANKL), was studied for prevention of breast cancer [7]. By studying the breast tissue of women with and without BRCA1 mutations, the authors of this study first found RANKL and its associated receptor are strongly associated with mammary neoplasm formation. Because of these findings, the authors then attempted to target this ligand for the prevention of cancer cell formation. Genetically-engineered mice subjects deficient in the BRCA1 gene were injected with pre-neoplastic cells and then randomized to receive either an antibody to RANKL vs. control antibody. Results showed a significant delay in tumor formation in mice treated with the RANKL antibody as compared to control. Also in this report, three women were treated with denosumab as part of a pilot study, and histologic examination showed that inhibition of RANKL reduced breast epithelial cell proliferation. The data is encouraging for denosumab as a preventative drug for women at high-risk for breast cancer. Further clinical studies are needed to assess the efficacy and safety in human subjects. 

A randomized controlled trial of gabapentin for chronic low back pain with and without a radiating component 

Low back pain is an issue that affects many; 80% of adults will suffer from back pain at some point in their lifetimes [8]. Clinicians are frequently tasked with trying various treatment options for those affected by the condition.

This study in the journal Pain looked at gabapentin (titrated up to 3600mg daily) for the treatment of chronic low back pain (>/6 months) both with and without associated radiation [9]. They found that after twelve weeks of treatment with gabapentin vs. placebo, pain levels, measured with the Descriptor Differential Scale, decreased in both the gabapentin and control arm of the study without any statistical significance between the two. In addition, there was not a statistically significant difference between the treatment arms in patients with or without radiating pain. Plasma levels of gabapentin had no correlation with pain levels. Finally mood was reported as improved at the end of the 12 weeks in both treatment and control groups with no significant difference between treatment and control arms. In terms of side effects, six symptoms were associated with the gabapentin treatment arm; these included fatigue, dry mouth, difficulties with mental concentration, memory, or visual accommodation, and loss of balance. According to this RCT, gabapentin is not useful in the treatment of chronic low back pain, and because of the side effect profile, the risks may outweigh any benefits for using this drug for the treatment of chronic low back pain, even if there is a radiating component.

Additional Articles:

“Use of Plant-Based Therapies and Menopausal Symptoms. A Systematic Review and Meta-Analysis”

Women going through menopause often look to supplements to help cope with their symptoms. This study examined the efficacy of various interventions in symptoms and found that phytoestrogen supplementations helped with hot flashes and vaginal dryness but not night sweats [10].

“Breast cancer screening with tomosynthesis (3D mammography) with acquired or synthetic 2D mammography compared with 2D mammography alone (STORM-2): a population-based prospective study”

Women are advised to get mammograms to detect breast cancer. This study looks at the benefit vs. risks of 3D vs 2D mammography for detection of breast cancer [11].

“Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood”

This study found that a BMI in 50th to 74th percentiles, which is currently considered normal, during adolescence is associated with increased cardiovascular and all-cause mortality over the next 40 years [12].

“Protection against malaria at 1 year and immune correlates following PfSPZ vaccination”

This study examines the durability of the malaria vaccine and found that the vaccine is still protective up to at least 59 weeks, and higher doses may be of greater benefit [13]. 

Dr. Katherine Nixon is a 1st year resident at NYU Langone Medical Center

Reviewed by David Kudlowitz, MD, Chief Resident Internal Medicine, NYU Langone Medical Center

Image courtesy of Wikimedia Commons 

References:

  1. Erlanger S. Britain votes to leave E.U.; Cameron plans to step down. The New York Times 23 June 2016. http://www.nytimes.com/2016/06/25/world/europe/britain-brexit-european-union-referendum.html?action=click&pgtype=Homepage&clickSource=story-heading&module=span-abc-region&region=span-abc-region&WT.nav=span-abc-region&_r=0 
  2. Macrae FA. Colorectal Cancer: Epidemiology, risk factors, and protective factors. https://www-uptodate-com.ezproxy.med.nyu.edu/contents/colorectal-cancer-epidemiology-risk-factors-and-protective-factors?source=search_result&search=colorectalcancer&selectedTitle=3~150 
  3. Bibbins-Domingo K. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2016;315(23):2564-2575. http://jama.jamanetwork.com.ezproxy.med.nyu.edu/article.aspx?articleid=2529486.
  4. Lee H, Lok AS. Hepatitis B and pregnancy. https://www-uptodate-com.ezproxy.med.nyu.edu/contents/hepatitis-b-and-pregnancy?source=search_result&search=hepatitis b pregnancy&selectedTitle=1~150 
  5. Pan CQ, Duan Z, Dai E, Zhang S, Han G, Wang Y, Jiang,H, et al. Tenofovir to Prevent Hepatitis B Transmission in Mothers with High Viral Load. NEJM. 2016;374:2324-2334. http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMoa1508660#t=article. 
  6. Antoniou, A, Easton DF, et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet. 2003 Sep;73(3):709. http://www-ncbi-nlm-nih-gov.ezproxy.med.nyu.edu/pubmed?term=12677558.
  7. Nolan E, Vaillant F, Branstetter D, Pal B, Giner G, Whitehead L, Lindeman, GJ, et al. Rank ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers. Nature Medicine. 2016. http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4118.html 
  8. “Back PainFact Sheet”, NINDS, NIH Publication No. 15-5161. http://www.ninds.nih.gov/disorders/backpain/detail_backpain.htm
  9. Atkinson JH, Slater M, Capparelli E, Patel S, Wolfson T, Gamst A, Garfin S, et al. A randomized controlled trial of gabapentin for chronic low back pain with and without a radiating component. Pain. 2016;157(7),1499-1507. http://ovidsp.tx.ovid.com.ezproxy.med.nyu.edu/sp-3.20.0b/ovidweb.cgi?&S=DIELFPHNIEDDDJNONCIKFHLBDFFFAA00&Link+Set=S.sh.22.23.26%7c16%7csl_1.
  10. Franco O, et al. Use of Plant-Based Therapies and Menopausal Symptoms. A Systematic Review and Meta-Analysis. JAMA. 2016;315(23):2554-2563. http://jama.jamanetwork.com/article.aspx?articleid=2529629
  11. Bernardi D, et al. Breast cancer screening with tomosynthesis (3D mammography) with acquired or synthetic 2D mammography compared with 2D mammography alone (STORM-2): a population-based prospective study. The Lancet. 2016. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30101-2/abstract
  12. Twig G, et al. Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood” NEJM. 2016; 374:2430-2440. http://www.nejm.org/doi/full/10.1056/NEJMoa1503840?query=featured_home
  13. Ishizuka A, et al. Protection against malaria at 1 year and immune correlates following PfSPZ vaccination” Nature Medicine. 2016; 22:614-623. http://www.nature.com/nm/journal/v22/n6/abs/nm.4110.html