Primecuts – This Week In The Journals

October 25, 2010

By Chris Tully, MD

Faculty Peer Reviewed

As New York City begins to feel less and less like summer, and more and more like fall, Primecuts is here to welcome the fall foliage with another edition.

 Making headlines across the major media Health sections were long-term follow-up studies on two common cancers, breast and colon cancer.  Publishing in JAMA [1], the Women’s Heath Initiative investigators (WHI) reported on the 11-year follow-up of the initial study that examined the health outcomes in post-menopausal women receiving estrogen and progestin supplementation.  While the initial study was stopped after an average of 5.6 years after an increased risk of invasive breast cancer and delayed breast cancer diagnosis was noted, this study attempted to assess the longer-term implication of the initial therapy.  Unfortunately, investigators noted women who received combination therapy continued to have an increased risk of lymph node positive invasive breast cancer.  They also noted a trend, although not statistically significant, toward increased breast cancer mortality.  Although clinical practice regarding post-menopausal hormone supplementation has largely been abandoned given the results of the Women’s Health Initiative, the results of the 11-year follow-up remind us of the need for rigorous evaluation of medical interventions as well as diligent follow up to avoid any unintended adverse affects.

Similarly studding the headlines was the follow-up of the long-term effect of low-dose aspirin on colon cancer.  Previous studies noted a decreased risk of colon adenomas in setting of treatment with aspirin and/or COX-2 inhibitors.  At that time treatment was not recommended because of multiple complicating factors: high dose requirements with gastrointestinal side affects, vascular side affects and short study time course.  In an effort to further support treatment with aspirin, researchers publishing in Lancet [2] examined a pooled analysis during which patients received lower dose aspirin (<500 mgs daily) for an average of 18.3 years.  The analysis revealed a reduction in the long-term incidence and mortality from colorectal cancer at in patients receiving at least aspirin 75mg daily for on average of at least 5 years.  While on first glance these results appear to be a promising given the already widespread use of aspirin for primary and secondary prevention of cardiovascular disease, a number of points need to be raised regarding the applicability of the results.  As referenced in the accompany commentary by Benamouzig and Uzzan [3], the fact that colorectal cancer was not the primary outcome in any of the trials, and that digestive-tract bleeding complications and its influence on trial results were not formally addressed each could confound potential results.  Irrespective, the trial does add considerable information to the question of colorectal cancer prevention and fuels further discussion for a trial to address the issue of primary prevention of colorectal cancer.

 Building on last week’s Primecuts discussion on the role of beta blockers in the prevention of migraines, researchers also publishing in the British Medical Journal further explore the medical management of headaches as they examine the role of tricyclic antidepressants (TCAs) in migraine, tension and mixed headache prevention. [4] Their systematic review and meta-analysis found that TCAs reduced the number of tension headaches and migraines compared to placebo and that their effectiveness increased with longer duration of treatment.  TCAs were also noted to be superior to selective serotonin reuptake inhibitors (SSRIs) for headache control and reduction of symptoms although there was an increased side affect profile with tricyclics.   There was a clinically significant increase in dry mouth, drowsiness, and weight gain without an increased dropout rate.  Although largely underutilized in the United States, TCAs represent an effective, inexpensive and largely tolerable treatment option in the management of chronic migrainous and tension headaches.

 Equally important to the changing world of medical science are the changes occurring in medical training, especially duty hour regulations. This topic re-surfaced in 2008 with the Institute of Medicine (IOM) report, Resident duty hours: enhancing sleep, supervision, and safety, the current concern with resident hours and medical errors, which was an update of the initial work duty guidelines established in 2003.  In the current edition of the New England Journal of Medicine, John K. Iglehart updates us on the recently enacted ACGME reforms regarding PGY-1 work hour limits. [5] Under the new standards, PGY-1 residents must not exceed 16 hours per shift or 80 hours per week, averaged over 4 weeks.  Senior residents will continue to be able to work a maximum of 24 continuous hours in the teaching setting.  The new modification allows only an additional 4 hours for handing off patients as opposed to the current 6 hours, which clearly represents another major change in housestaff education.  While common sense supports the idea that less sleep equals a greater risk of error, there is also the inevitable reality of medicine in our society and the requirements placed on residency programs.  We are increasingly placing more requirements on housestaff as hospitals close, condensing healthcare and increasing patient loads to the still viable institutions.  At the same time, the knowledge required to remain an effective medical provider continues to increase.  While duty hour reform is clearly an unstoppable force, great care needs to be placed in ensuring we are not compromising the medical knowledge our future providers will require.  This debate will obviously continue into the future, and so will Primecuts.  See you next week. 

Dr. Tully is a third-year resident at NYU Langone Medical Center

Peer reviewed by Deborah Shapiro,  MD,  wife of Neil Shapiro, MD Editor-in-Chief, Clinical Correlations.

Image courtesy of Wikimedia Commons.


[1] Chlebowski, RT et al. Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in Postmenopausal Women.  JAMA. 2010; 305(15):1684-1692.  Print.

 [2] Rothwell, PM et al.  Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials.  The Lancet.  Published online on October 22, 2010. Web.

 [3] Benamouzig, Robert and Uzzan Bernard. Aspirin to prevent colorectal cancer: time to act? The Lancet. Published online on October 22, 2010. Web.

 [4] Jackson JL et al. Tricyclic antidepressants and headaches: systematic review and meta-analysis.  British Medical Journal. 2010;341:c5222. Web.

 [5] Iglehart, John K.  The ACGME’s Final Duty-Hour Standards – Special PGY-1 Limits and Strategic Napping.  New England Journal of Medicine. 2010 Oct; 21 363 (17): 1589-1591. Print.