By Jenna Conway, MD
Peer Reviewed
With less than a month to Election Day, we learned this week what Donald Trump deems appropriate “locker room talk” about women, while several women came forward to accuse him of inappropriately touching them. Hillary Clinton continues to deal with email leaks, including thousands published on WikiLeaks that were hacked from her campaign manager’s inbox. Other notable events range from the death of the King of Thailand to Bob Dylan becoming the first songwriter to ever win the Nobel Prize in Literature.
This was also an important week in the journals with studies looking at quality of life after prostate cancer treatment, breast cancer overdiagnosis, supplement use among Americans, and post-stroke infection, among others.
How do the different treatment options for prostate cancer affect function and quality of life?
Prostate cancer is the third most common type of cancer (after breast and lung) with approximately 1 in 7 men diagnosed with prostate cancer during their lifetime.1 Although prostate cancer is the second leading cause of death (after lung) in American men, the majority of men diagnosed with prostate cancer do not actually die from the disease, but rather with the disease.1 When considering treatment options, clinicians must account for the potential mortality from prostate cancer, the effectiveness of the treatment option in reducing mortality, and also the treatment’s impact on quality of life.
As covered previously in Primecuts on 9/19/2016, a New England Journal of Medicine (NEJM) study by Hamdy et al2 looked at 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. Although they found reduced disease progression and metastases for surgery and radiotherapy vs. monitoring, there was no significant difference in 10-year mortality among the three options.
Building on this study, another NEJM study by Donovan et al3 looked at patient-reported function and quality of life after treatment. Patients diagnosed with localized prostate cancer completed questionnaires before diagnosis, 6-12 months after randomization, and then annually that assessed function (urinary, bowel, and sexual) and effects on quality of life. Surgery had the greatest negative effect on urinary and sexual function at all time points (P<0.001), while radiotherapy had worse scores for bowel function at 6 months and more bloody stools from 2 years onward (P<0.001). Effects on quality of life mirrored the patient-reported changes in function.
These two NEJM studies reinforce the need to discuss with patients how the different treatment options for prostate cancer not only impact disease progression and mortality, but also function and quality of life. This data enables clinicians to speak more cogently with patients about the impact of the different treatment options.
Does mammography screening result in overdiagnosis of breast cancer?
From prostate cancer we now transition to breast cancer screening. Breast cancer is the most common type of cancer and the leading cause of cancer-related deaths in women.1 As in prostate cancer, breast cancer screening can lead to overdiagnosis (i.e., cancer detected on screening that would not cause symptoms or lead to increased mortality). In turn, overdiagnosis can lead to invasive tests and unnecessary treatment, each with their own risks and long-term effects.
A NEJM by Welch et al4 looked at the effects of screening mammography on breast cancer diagnosis. While tumor size is now not as important as a tumor’s biological characteristics in breast cancer prognostics, screening mammography is based on tumor size rather than functional gene expression. Given that screening mammography detects small tumors before they are large enough to cause symptoms, the authors argue that effective screening should lead to greater detection of small tumors with less large tumors detected over time. Population-based data from the Surveillance, Epidemiology, and End Results (SEER) program (1975-2012) was used to calculate tumor-size distribution and size-specific incidence of breast cancer followed by a calculation of the size-specific cancer case fatality rate for the period before widespread screening (1975-1979) and a more recent period (2000-2002). The study found that screening mammography has allowed for greater detection of small tumors (from 36% to 68%) and less large tumors have been detected (from 64% to 32%). However, based on the authors assumptions and calculations of the amount of small tumors that would be expected to become large, it was shown that women were more likely to have breast cancer that was overdiagnosed than to have earlier detection of a small tumor destined to become large. As previously suggested,5,6 the authors also found that the reduction in breast cancer mortality from large tumors after initiation of screening mammography appears to be primarily from improved treatment rather than screening.
While the authors discuss the limitations of the study including their assumptions about underlying disease burden that cannot be verified, it does add to the existing literature6,7 that points towards a real problem of overdiagnosis of breast cancer secondary to mammography screening.
How many Americans use supplements?
Dietary supplements comprise various products ranging from vitamins, minerals, and botanicals to probiotics, protein powders, and fish oils.8 Numerous studies over the past two decades have failed to show a health benefit in association with supplements, some even demonstrating adverse effects. Thus it is clinically important to understand how many of our patients continue to use supplements.9
In a study published in JAMA this week, Kantor et al10 analyzed data from the National Health and Nutrition Examination Survey, a cross-sectional survey on 37,958 noninstitutionalized civilians living in the United States, in seven 2-year cycles (1999-2000 through 2011-2012). Overall supplement usage remained unchanged during the study period, with 52% reporting use in both the first and last cycle (difference 0.0%; 95% confidence interval [CI] −3.6% to 3.6%).
The proportion of respondents reporting use of four or more supplement products also did not change significantly, with 8.7% of respondents in 1999-2000 and 9.9% in 2011-2012 (difference 1.1%; 95% CI −0.8% to 3.0%). Use of multivitamins/multiminerals, defined as products containing at least 10 vitamins/minerals, fell from 37% to 31% (difference −5.7%; 95% CI −8.6% to −2.7%). A decrease was also found in the use of some individual vitamins and minerals, specifically vitamin C, vitamin E, and selenium; however, vitamin D supplementation increased from 5.1% to 19% (difference 14%; 95% CI 12% to 17%). Non-vitamin non-mineral supplements usage increased over the course of the study, with omega-3 fatty acid supplementation (primarily fish oil) rising almost sevenfold from 1.9% during 1999-2000 to 13% during 2011-2012 (difference 11%; 95% CI 9.4% to 13%). Various socio-demographic variables were associated with supplement use, including increased age, female sex, non-Hispanic white adults, and education level.
The study demonstrates that more than half of American adults continue to use nutritional supplements and their use remained stable between 1999-2012, while multivitamin use decreased slightly during the same period. Usage by our patients persists despite the evidence in randomized clinical trials that supplements and multivitamins provide no clear health benefit and that they may even result in adverse effects. This study serves as a good reminder to ensure that we are asking our patients about vitamin and supplement usage and counseling them appropriately.
Is post-stroke infection caused by translocation of gut bacteria?
Stroke is a leading cause of morbidity and mortality and the major cause of death after stroke is infection, most commonly bacterial pneumonia. Despite the potential contribution of micro-aspiration in post-stroke pneumonia, Stanley et al in a Nature Medicine study11 found that the majority of the microorganisms detected in the patients who developed post-stroke infections comprised normal gut flora. Specifically, they found that in post-stroke patients with positive cultures (blood, urine, or sputum), more than 70% contained normal gut flora (Enterococcus spp., Escherichia coli and Morganella morganii). Using post-stroke mice, the authors demonstrated that post-stroke infection originated within the host endogenously rather than acquired from the environment exogenously and that the small intestine was the source of the bacteria forming the microbial community in the lungs of post-stroke mice. Finally, the authors also showed that stroke-induced gut barrier permeability and dysfunction preceded the dissemination of orally inoculated bacteria to peripheral tissues.
In conclusion, the authors demonstrate that stroke induces the activation of the sympathetic nervous system and triggers a series of events that increase gut permeability and impair host antibacterial and intestinal barriers to promote the translocation and dissemination of normal gut flora. Given current therapies do not address bacterial infection as a key modifiable issue in patients who have had a stroke, the identification of this novel mechanism for post-stroke infection may foster development of targeted therapies for stroke patients.
Mini-Cuts
A study published in the Lancet by Aldridge et al12 found that migrants to the UK from countries at high risk of tuberculosis (TB) and who were pre-screened for TB pose a negligible risk of transmission, despite being at increased risk of developing TB themselves. This increased risk of developing TB could potentially be prevented through treatment of those identified by the pre-entry screening program as having latent infection, which would continue the downward trend of TB incidence in the UK.
A systemic review and meta-analysis in the Annals of Internal Medicine by Bloomfield et al13 found that a Mediterranean diet with unrestricted fat intake may reduce incidence of cardiovascular events, breast cancer, and type 2 diabetes, however, it does not affect all-cause mortality relative to other diets.
Clostridium difficile (C difficile) infection is the number one cause of hospital-related diarrhea and a study in JAMA Internal Medicine by Freedberg et al14 showed that C difficile infection was increased in patients whose prior hospital bed occupants were treated with antibiotics, suggesting that antibiotics can directly affect risk for C difficile infection in patients who were not themselves treated with antibiotics.
Dr. Jenna Conway is a 1st year resident at NYU Langone Medical Center
Peer reviewed by Neil Shapiro, MD, Editor-In-Chief, Clinical Correlations
Image courtesy of Wikimedia Commons
References
1 American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society (2016). http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2016/index
2 Hamdy, Freddie C., et al. “10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer.” New England Journal of Medicine (2016). http://www.nejm.org/doi/full/10.1056/NEJMoa1606220
3 Donovan, Jenny L., et al. “Patient-reported outcomes after monitoring, surgery, or radiotherapy for prostate cancer.” New England Journal of Medicine (2016). http://www.nejm.org/doi/full/10.1056/NEJMoa1606221
4 Welch, H. G., et al. “Breast-Cancer Tumor Size, Overdiagnosis, and Mammography Screening Effectiveness.” New England Journal of Medicine 375.15 (2016): 1438-47. Print. https://www.ncbi.nlm.nih.gov/labs/articles/27732805/
5 Kalager, Mette, et al. “Effect of screening mammography on breast-cancer mortality in Norway.” New England Journal of Medicine 363.13 (2010): 1203-1210. http://www.nejm.org/doi/full/10.1056/NEJMoa1000727
6 Miller, Anthony B., et al. “Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial.” BMJ (2014): g366.
7 Bleyer, Archie, and H. Gilbert Welch. “Effect of three decades of screening mammography on breast-cancer incidence.” New England Journal of Medicine 367.21 (2012): 1998-2005. http://www.nejm.org/doi/full/10.1056/NEJMoa1206809
8 US Food and Drug Administration. “Dietary supplement health and education act of 1994.” December 1 (1995). https://ods.od.nih.gov/About/dshea_wording.aspx
9 Cohen, P. A. “The Supplement Paradox: Negligible Benefits, Robust Consumption.” Jama 316.14 (2016): 1453-54. Print.
10 Kantor, E. D., et al. “Trends in Dietary Supplement Use among Us Adults from 1999-2012.” Jama 316.14 (2016): 1464-74. Print. http://jamanetwork.com/journals/jama/fullarticle/2565748
11 Stanley, Dragana, et al. “Translocation and dissemination of commensal bacteria in post-stroke infection.” Nature Medicine (2016).
12 Aldridge, Robert W, et al. “Tuberculosis in migrants moving from high-incidence to low-incidence countries: a population-based cohort study of 519 955 migrants screened before entry to England, Wales, and Northern Ireland.” The Lancet (2016).
13 Bloomfield, Hanna E., et al. “Effects on Health Outcomes of a Mediterranean Diet With No Restriction on Fat Intake.” Annals of Internal Medicine 165.7 (2016): 491-500. http://annals.org/article.aspx?articleid=2534409
14 Freedberg, D. E., et al. “Receipt of Antibiotics in Hospitalized Patients and Risk for Clostridium Difficile Infection in Subsequent Patients Who Occupy the Same Bed.” JAMA Intern Med (2016). Print.