While walking through snowy streets of NYC, the sight of one or two innocent bystanders sliding on a patch of ice on the road is not uncommon. However, these unfortunate folks are far from being the only ones with a bruise or two: this week a widely accepted screening tool, the mammogram, received more than a few punches in the media.
The Cost of Mammography
The utility of mammography as a screening tool, questioned in a Canadian study published in the British Journal of Medicine (BMJ), is discussed in a separate article. [1,2]. This week, in the Annals of Internal Medicine, researchers gathered data from several patient surveys to assess (1) the costs of screening mammograms in the US in 2010 ($7.8 billion) and (2) to estimate how these costs would vary using different screening schedules. Guidelines by the American Cancer Society to screen women 40-84 yearly were compared with current European guidelines to screen women 50-69 biennially, and United States Preventive Services Task Force’s recommendation for risk-based screening in addition to biennial screening for women 50-74. The projected cost for mammographic screening using these guidelines were $10.1 billion/year, $2.6 billion/year and $3.5 billion/year respectively. The wide gap in these potential costs, in addition to recent studies questioning the utility of mammography as a screening tool [1, 2] raises concerns that current practices may be due for a change.
HPV Vaccines and Condyloma Incidence
In other women’s health news, the Journal of the American Medical Association (JAMA) published an observational cohort study to evaluate a possible dose-dependent effect of the HPV quadrivalent vaccine on the development of condyloma.  The study included females, ages 10-24 years in Sweden between 2006-2010, and aimed to assess an association between the number of doses of quadrivalent HPV vaccine (the full series consists of 3) and the incidence of condyloma.
The results were stratified based on age at first vaccination; comparisons were made between multiple different age groups, but the authors paid most attention to those aged 10-16 or 17-19 years. Results suggest a correlation between number of vaccination doses and Incidence Rate Reduction (IRR) for condyloma development. For individuals aged 10-16 at the time of the first vaccination, compared to those not vaccinated, after 1 dose IRR was 0.31 (95%, CI 0.20-0.49), IRR after 2 doses was 0.29 (95% CI, 0.21-0.40), and 3 doses was 0.18 (95% CI, 0.15-0.22). For women aged 17-19 after 3,2,and 1 doses the IRR was 0.23(95% CI, 0.18-0.29), 0.35 (95% CI, 0.26-0.47), and 0.35 (95% CI, 0.26-0.47) respectively. However, it should be noted that the overlap between the confidence intervals calls into question the paper’s conclusion that there is a true IRR difference based on number of doses. Further, the method of incidence collection (number of cases in the Patient Registry and number of prescriptions for podophyllotoxin and/or imiquimod) leaves out all patients who developed symptoms but did not seek medical attention and those who sought other treatments (e.g., cryotherapy, trichloroacetic acid, 5-fluorouracil/epinephrine gel).
With all of these flaws, one could argue that the relationship between number of doses and condyloma incidence will require further scrutiny before we can safely say that there is indeed a correlation between the number of vaccination dosages and condyloma development.
Viral Flu and Oseltamivir Use
Moving from women’s health to a topic affecting all genders, The Lancet Infectious Disease Journal published an article on the efficacy of oseltamivir to reduce illness duration and viral shedding in people with influenza when started within 5-days of symptom onset . This double-blind, randomized, placebo-controlled trial done in urban Bangladesh compared patients with confirmed Influenza who started treatment with Oseltamivir less than 48 hours after symptom onset to those who initiated treatment later. The primary endpoints were duration of clinical illness and viral shedding. Influenza positivity was determined by nasal washings tested with a rapid diagnostic test (QuickVue, Quidel) for Influenza A or B. Patients were then followed for duration of symptoms after initiation of oseltamivir. Viral shedding was qualified by PCR detection, virus isolation and virus titer at days 2, 4 and 7.
In the group that began treatment less than 48 hours after symptom onset, the median duration of symptoms was 3 days for oseltamivir and 4 days for placebo (p=0.01). In the group beginning treatment greater than 48 hours after symptom onset, median duration of symptoms was 3 days with both the oseltamivir and placebo groups (p=0.04). While these results are not particularly impressive, oseltamivir did significantly reduce virus isolation on day 2 (ARR 10%, NNT 10), day 4 (Absolute Risk Reduction 7%, NNT 14) and day 7 (ARR 6%, NNT 17). These results raise the question of oseltamivir’s clinical utility in controlling spread of the disease rather than individual symptom/disease management.
Sentinal Node Biopsy vs Observation in Melanoma
In oncologic news, the New England Journal of Medicine published the final report of a study comparing outcomes of sentinel node biopsy vs nodal observation in primary cutaneous melanoma . In this trial patients were randomized to wide excision plus nodal observation and lymphadenectomy for recurrence (observation group) or wide excision plus sentinel-node biopsy and immediate lymphadenectomy if metastasis was detected (biopsy group). Ten-year disease-free survival rates were stratified by melanoma thickness. In patients with intermediate thickness melanomas (1.2-3.5mm deep), 10-year disease-free survival was 71.3% vs 64.7% (biopsy vs observation), with corresponding ARR of 6.6%. Among patients with thick melanomas (>3.5mm), 10-year disease-free survival was 50.7% vs 40.5% (biopsy vs observation), with corresponding ARR of 10.2%. Although current recommendations for management of melanoma include elective complete lymphadenectomy regardless of nodal metastasis, this new data suggests an increased rate of disease-free survival in patients undergoing less aggressive surgical diagnostic treatment. Sentinel node biopsy is a minimally invasive procedure that carries with it a lesser risk of morbidity than complete lymphadenectomy, potentially contributing to reduced morbidity and mortality.
This weeks’ news cycle consisted largely of new data questioning the utility and efficacy of already available diagnostic modalities and, perhaps suggesting that aggressive prevention and treatment does not always improve outcomes. Just as uncertain as the next snowfall, we cannot predict future policies or treatments. However, we can use the new data available to question, and subsequently improve, current practices.
ALSO IN THE NEWS
Other articles circulating in this week’s medical journals include:
* A position paper from the American College of Physicians describing the public health issue of prescription drug abuse. With deaths from drug overdose now becoming the 2nd leading cause of death from unintentional injuries in the U.S. (second only to motor vehicle collisions) this position paper seeks to provide guidance on ways to address this growing problem. 
* CVS Pharmacies is planning to stop selling tobacco products. An announcement of this nature coming from a major corporation now makes international news in the medical literature with articles in both the BMJ and JAMA. [8, 9]
* The Annals of Internal Medicine published a restrospective analysis of repeated endoscopy in the Medicare population. Researchers found that nearly one half of repeat EGD’s were performed in patients who already had a diagnosis, or who had previous findings that failed to suggest the need for repeat examination, bringing into question overuse of endoscopy in this population. 
* The Journal Chemical Science published a report on Surface-enhanced Raman Spectroscopy as a new method to detect and simultaneously quantify pathogens in bacterial meningitis. This could significantly reduce waiting time as compared to standard CSF cultures and thus allow for faster delivery of targeted treatments. 
Dr. Miguel A. Saldivar is a 1st year resident at NYU Langone Medical Center
Peer reviewed by Jessica Taff, MD, 3rd year resident at NYU Langone Medical Center
Image courtesy of Wikimedia Commons
1. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. Miller, et al. BMJ 2014;348:g366 doi: 10.1136/bmj.g366. http://www.bmj.com/content/348/bmj.g366
2. Mammograms in the News, Yet Again. Miguel A Saldivar, MD. Clinical Correlations, the NYU Langone Online Journal of Medicine. February 13, 2014. http://www.clinicalcorrelations.org/?p=7352
3. Aggregate Cost of Mammography Screening in the United States: Comparison of Current Practice and Advocated Guidelines. O’Donoghue, et al. Ann Intern Med. 2014;160(3):145-153-153. doi:10.7326/M13-1217. http://annals.org.ezproxy.med.nyu.edu/article.aspx?articleid=1819118
4. Association of Varying Number of Doses of Quadrivalent Human Papillomavirus Vaccine With Incidence of Condyloma. Herweijer, et al. JAMA. 2014;311(6):597-603. doi:10.1001/jama.2014.95. http://jama.jamanetwork.com.ezproxy.med.nyu.edu/article.aspx?articleid=1829685
5. Efficacy of oseltamivir treatment started within 5 days of symptom onset to reduce influenza illness duration and virus shedding in an urban setting in Bangladesh: a randomised placebo-controlled trial. Fry, et al. The Lancet Infectious Diseases, Volume 14, Issue 2, Pages 109 – 118, February 2014. doi:10.1016/S1473-3099(13)70267-6. http://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2813%2970267-6/fulltext
6. Final Trial Report of Sentinel-Node Biopsy versus Nodal Observation in Melanoma. Morton, et al. N Engl J Med 2014; 370:599-609February 13, 2014. DOI: 10.1056/NEJMoa1310460. http://www.nejm.org.ezproxy.med.nyu.edu/doi/full/10.1056/NEJMoa1310460?query=featured_home
7. Prescription Drug Abuse: Executive Summary of a Policy Position Paper From the American College of Physicians. Kirschner, et al. Ann Intern Med. 2014;160(3):198-200-200. doi:10.7326/M13-2209. http://annals.org.ezproxy.med.nyu.edu/article.aspx?articleid=1788221
8. Major US pharmacy chain plans to stop selling cigarettes. McCarthy, Michael. BMJ 2014;348:g1442. http://www.bmj.com.ezproxy.med.nyu.edu/content/348/bmj.g1442
9. Ending Sales of Tobacco Products in Pharmacies. Brennan, et al. JAMA. Published online February 05, 2014. doi:10.1001/jama.2014.686. http://jama.jamanetwork.com.ezproxy.med.nyu.edu/article.aspx?articleid=1828530
10. Repeated Upper Endoscopy in the Medicare Population: A Retrospective Analysis. Pohl, et al. Ann Intern Med. 2014;160(3):154-160-160. doi:10.7326/M13-0046. http://annals.org.ezproxy.med.nyu.edu/article.aspx?articleid=1819119
11. Simultaneous detection and quantification of three bacterial meningitis pathogens by SERS. Gracie, et al. Chem. Sci., 2014,5, 1030-1040. DOI: 10.1039/C3SC52875H. http://pubs.rsc.org/en/content/articlelanding/2014/sc/c3sc52875h#!divAbstract