Primecuts-This Week in the Journals

November 3, 2015

PrimeCuts 7 min read

https://upload.wikimedia.org/wikipedia/commons/3/39/Beautiful_view_of_Verrazano-Narrows_Bridge_cropped.jpgBy Stephanie Wu, MD

Peer Reviewed

This past weekend, we cheered for the 50,000 people who ran the NYC marathon. Jonathan Mendes, at 94 years old, tackled this marathon for his 14th time [1]. In the midst of this momentous and triumphant occasion, we witnessed the tragic loss of 224 people on board a plane that crashed in Egypt. Earlier in the week, China repealed its one-child policy that had been in place since 1979. With plenty of Halloween candy in our stomachs and an extra hour of rest with the end of Daylight Saving Time, we turn to key medical news in this week’s Primecuts.

Carcinogenicity of Red and Processed Meats

This week we start off with a topic that may be disheartening to hot dog and sausage lovers out there. A team of experts of the International Agency for Research on Cancer (IARC) recently convened to evaluate the carcinogenicity of red and processed meats using over 800 epidemiological studies [2]. Based on sufficient evidence that consumption of processed meats can cause colorectal cancer in humans, processed meats were designed as Group 1 carcinogens. Red meats were classified as Group 2A carcinogens, or agents that are probably carcinogenic to humans. Although it is not entirely clear how red or processed meats increase cancer risk, it has been hypothesized that meats contain carcinogenic chemicals that form during processing or cooking [3, 4].

While the IARC’s findings are not new, their announcement as a highly reputable organization can carry significant public health implications. The IARC’s evaluation shifts attention back to the risks of cancer, obesity, and cardiovascular disease associated with significant meat consumption. At the same time, it is important to note that the IARC carcinogenic classifications designate the strength of the scientific evidence supporting a substance’s carcinogenicity, rather than the nature or severity of the carcinogenic risk. There has been substantial media coverage on the data obtained from a 2011 meta-analysis which found that a 50 gram portion of processed meat eaten daily, or approximately two strips of bacon, can increase one’s risk of colorectal cancer by 18% % (95% confidence interval [CI] 1.10 to 1.28) [5]. Although this information sounds very alarming, the data represent relative rather than absolute risk. Further research is needed to evaluate what quantity of meat consumption can be considered safe. In the meantime, it is sensible to at least be mindful of our consumption of red and processed meats.

Wearable Defibrillator Deemed Safe and Helpful in Risk Stratification for Implantable Cardioverter Defibrillators

Although the implantable cardioverter defibrillator (ICD) is associated with improved survival for patients at risk for sudden cardiac death (SCD), there are situations where ICD implantation must be deferred. In these cases, the wearable cardioverter defibrillator (WCD) can be used to provide automatic defibrillation. Using data from 2000 patients who were prescribed a LifeVest WCD and enrolled in the prospective WEARIT-II Registry, researchers sought to assess the safety and efficacy of the WCD [6]. During the median follow-up time of 90 days, there was a high rate of sustained ventricular tachyarrhythmias (120 events) with 54% of patients receiving appropriate WCD shock. The delivery of appropriate WCD shock was used to risk stratify patients and facilitated decisions to implant an ICD, as 85% of patients who had a ventricular tachyarrhythmia and a WCD shock were implanted with an ICD compared with only 39% of patients who had no arrhythmias.

This study demonstrated that the WCD is safe to use in high-risk cardiac patients, as less than 1% of patients received inappropriate WCD therapy and there were no deaths related to use of the vest. Furthermore, the authors highlighted the WCD’s ease of use as patients had high compliance to WCD (median daily use of 22.5 hours). There are ongoing efforts to collect longer-term follow-up data from WEARIT-II participants. It would be helpful in this follow-up study to better define baseline patient characteristics. For example, it is unclear how the authors designated patients with ischemic cardiomyopathy as high risk for SCD. Of note, the VEST trial, designed to study the impact of WCD on mortality, is still recruiting participants [7]. Future studies could evaluate cost-effectiveness of the WCD, as initial costs may be offset by savings from avoiding unnecessary ICD implantation.

Buffered Crystalloid Solution Not Found to Alter Risk for Acute Kidney Injury When Compared to Normal Saline

Normal saline is the most widely used resuscitation fluid but can contribute to acute kidney injury (AKI) with its high chloride content. As an alternative, low-chloride buffered crystalloid solution may be considered instead. To evaluate the effects of a buffered crystalloid solution compared to normal saline on the development of AKI in intensive care unit (ICU) patients, the authors of the SPLIT trial designed a double-blind, double-crossover trial. In alternating 7-week treatment blocks, participating ICU’s used either normal saline or buffered crystalloid (Plasma-Lyte 148) [8]. Between the 2 treatment groups, there were no significant differences in the incidence of AKI within 90 days of enrollment (9.6% for buffer crystalloid versus 9.2% for saline; relative risk [RR] 1.04 with 95% CI 0.80 to 1.36, p = 0.77), rates of renal replacement therapy, or in-hospital mortality. The study’s validity is strengthened by its high rates of patient inclusion and follow-up. However, as noted in an accompanying editorial, it is not feasible to demonstrate hazard with either fluid when the study population was at low risk for AKI and only required a small median fluid volume of 2 liters [9]. The authors also did not report serum chloride data, thereby limiting our ability to assess whether there was a physiologically significant hyperchloremic effect between the treatment groups.

End-of-life Healthcare Costs for Dementia Exceed Costs for Other Diseases

As the U.S. population ages, it is becoming more crucial to better understand the social and financial costs associated with end-of-life care. In a large retrospective cohort study of Medicare beneficiaries, investigators found that the average total cost of care for people with dementia in the last 5 years of life was $287,038, compared to $173,136 for heart disease and $173,383 for cancer (p < 0.001) [10]. Out-of-pocket spending accounted for the majority of this discrepancy in end-of-life healthcare expenditures, as average out-of-pocket spending for people with dementia was 81% higher than that for people with other diseases. This study demonstrates that not only do total healthcare costs for people with dementia far exceed that for other diseases, but a large portion of these expenditures are not covered by insurance (out-of-pocket spending accounted for 32% of household wealth). Importantly, the proportion of out-of-pocket spending for people with dementia was even greater for financially vulnerable demographic groups, including African Americans (84%), unmarried or widowed women (58%), and people with less than a high school degree (48%). Medicare does not currently cover healthcare expenditures integral for the care of those with dementia, including home care services and nursing home care. This study shows that dementia caregivers bear a great portion of healthcare expenditures on their own, with larger financial risk being taken on by economically disadvantaged groups. With a more concrete understanding of the financial burden associated with end-of-life care, it will be interesting to see how this data is used in future discussions of Medicare policy reform.

Quick-Cuts

A temporal analysis of mortality rates in the U.S. between 1969 and 2013 showed decreased death rates for all leading causes of death, with the exception of COPD. Of note, the rate of decrease in mortality has begun to plateau for diabetes, heart disease, and stroke [11].

The USPSTF has recommended that all overweight adults between the ages of 40 and 70 should be screened for abnormal blood glucose levels [12].

BRAF mutations are found in nearly all cases of hairy-cell leukemia. Recent clinical trials have shown that vemurafenib, a BRAF inhibitor, can lead to greater than 90% response rates in patients with hairy-cell leukemia [13].

A meta-analysis of low-fat and higher-fat diets found that low-fat diets are not any more effective than other diets for long-term weight loss [14].

Dr. Stephanie Wu is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Amar Parikh, MD, Contributing Editor, NYU Langone Medical Center

References

  1. Eversley, M., Meet the NYC marathon’s oldest runner; he’s about to turn 95, in USA Today. 2015 Oct 31. http://www.usatoday.com/story/news/2015/10/30/94-year-old-tackles-new-york-city-marathon—-again/74890406/
  2. Bouvard, V., et al., Carcinogenicity of consumption of red and processed meat. Lancet Oncol, 2015. [Epub ahead of print]. http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00444-1/abstract
  3. Cross, A.J., et al., A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cancer Res, 2010. 70(6): p. 2406-14. http://cancerres.aacrjournals.org/content/70/6/2406.full.pdf
  4. Lewin, M.H., et al., Red meat enhances the colonic formation of the DNA adduct O6-carboxymethyl guanine: implications for colorectal cancer risk. Cancer Res, 2006. 66(3): p. 1859-65. http://cancerres.aacrjournals.org/content/66/3/1859.full
  5. Chan, D.S., et al., Red and processed meat and colorectal cancer incidence: meta-analysis of prospective studies. PLoS One, 2011. 6(6): p. e20456. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0020456
  6. Kutyifa, V., et al., Use of the Wearable Cardioverter Defibrillator in High-Risk Cardiac Patients: Data From the Prospective Registry of Patients Using the Wearable Cardioverter Defibrillator (WEARIT-II Registry). Circulation, 2015. 132(17): p. 1613-9. http://circ.ahajournals.org/content/132/17/1613.abstract
  7. University of San Francisco. Vest prevention of early sudden death trial and VEST registry. 2011. https://www.clinicaltrials.gov/ct2/show/study/NCT01446965
  8. Young, P., et al., Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit: The SPLIT Randomized Clinical Trial. JAMA, 2015. 314(16): p. 1701-10. http://jama.jamanetwork.com/article.aspx?articleid=2454911
  9. Kellum, J.A. and A.D. Shaw, Assessing Toxicity of Intravenous Crystalloids in Critically Ill Patients. JAMA, 2015. 314(16): p. 1695-7. http://jama.jamanetwork.com/article.aspx?articleid=2454909
  10. Kelley, A.S., et al., The Burden of Health Care Costs for Patients With Dementia in the Last 5 Years of Life. Ann Intern Med, 2015. [Epub ahead of print]. http://annals.org/article.aspx?articleid=2466364
  11. Ma, J., et al., Temporal Trends in Mortality in the United States, 1969-2013. JAMA, 2015. 314(16): p. 1731-9. http://jama.jamanetwork.com/article.aspx?articleid=2466136
  12. Siu, A.L., Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med, 2015. [Epub ahead of print]. http://annals.org/article.aspx?articleid=2466368
  13. Tiacci, E., et al., Targeting Mutant BRAF in Relapsed or Refractory Hairy-Cell Leukemia. N Engl J Med, 2015. 373(18): p. 1733-47. http://www.nejm.org/doi/full/10.1056/NEJMoa1506583
  14. Tobias, D.K., et al., Effect of low-fat diet interventions versus other diet interventions on long-term weight change in adults: a systematic review and meta-analysis. The Lancet Diabetes & Endocrinology, 2015. [Epub ahead of print]. http://www.thelancet.com/journals/landia/article/PIIS2213-8587(15)00367-8/abstract

Picture of Verrazano-Narrows Bridge. Fergal Carr from New York, United States derivative work: MachoCarioca [CC BY 2.0 (http://creativecommons.org/licenses/by/2.0)], via Wikimedia Commons