Primecuts – This Week In The Journals

June 17, 2014

By Christopher Maulion, MD

Peer Reviewed

The last week was certainly a treat for sports fans. Thursday marked the start of the World Cup, and the month where the United States begins to care about fútbol. Martin Kaymer set a US Open record by beating the field at Pinehurst No. 2 by 8 strokes[1]. Last but not least, Lebron James and the Miami Heat’s attempt at a three-peat was thwarted by Timmy and the Spurs. As we watch these exciting events unfold, let us turn our attention to the latest and greatest in internal medicine.

CPAP vs. Weight Loss in the Treatment of Obstructive Sleep Apnea

Obstructive sleep apnea, OSA, is an often overlooked and under recognized diagnosis that is correlated with cardiac risk factors including insulin resistance, hyperlipidemia, inflammation and hypertension. This trial by Chirinos et al. in The New England Journal of Medicine sought to compare weight loss vs. CPAP vs. a combination of the two in the treatment of obstructive sleep apnea[2]. This randomized, parallel group, 24 week trial included patients with moderate-to-severe obstructive sleep apnea as defined by an AHPI of 15 or more events per hour. The study’s endpoints included serum CRP level, insulin sensitivity and dyslipidemia at 8 and 24 weeks. The study found that CRP was significantly reduced at 24 weeks in both the weight loss and combined-intervention group in comparison to the CPAP arm. Moreover, there was no significant difference between the weight loss group and the combined-intervention group. A similar trend was observed in insulin sensitivity with increases found in the weight loss and combined-intervention group. There was a significant decrease in triglyceridemia in the weight loss and combined therapy group in comparison to the CPAP group, however there were no significant changes in terms of changes in LDL or HDL among the study groups. If anything, this study highlights the importance of weight loss in the treatment of OSA and reduction of its related comorbidities.

Escalating Diabetes Treatment Beyond Metformin, Insulin vs. Sulfonylureas

Most of us have patients with diabetes that are poorly controlled on metformin alone. This recent article in JAMA sought to retrospectively compare the outcomes of patients who were initially treated with metformin and were then intensified to either the addition of insulin or a sulfonylurea[3]. This study used a retrospective cohort of veterans aged 18 and older consisting of 95% men and 70% white. Main exclusion criteria included nonadherent patients, inadequate follow up data, and therapy regimens that did not include metformin or included a nonstudy medication. The primary composite outcome included acute myocardial infarction, stroke hospitalization, or all cause death. The secondary outcome was fatal and nonfatal cardiovascular events. They found a significant difference in their primary outcome with an incidence of 42.7 vs 32.8 per 1000 person years in the insulin vs. sulfonylureas respectively. There was no significant difference observed in the secondary outcome. These results are in line with previous studies such as ACCORD and ORIGIN showing no advantage with tight glycemic control strategies in comparson to standard therapy. While these results would certainly delight our patients who have been staving off insulin therapy, these results should be taken with a grain of salt. It should be noted that the median A1C was 7.6% vs. 8.5% in the sulfonylurea and insulin groups respectively, and that poorly controlled diabetics with A1Cs greater than 10% should still warrant insulin therapy.

To Screen or Not To Screen?

Per the USPSTF, screening for colorectal cancer extends to the age of 75 years, after which it is no longer recommended to screen individuals. However, these recommendations only take into account those patient’s that have had adequate screening to the age of 75 years and not those patient that have not had any screening at all. van Hees et al. attempted to clarify this in their article in Annals[4]. These investigators utilized the Microsimulation Screening Analysis – Colon Model, an established simulation model developed at Erasmus University Medical Center in the Netherlands. Using this model they simulated a cohort of 10 million persons without previous screening and varying degrees of comorbid conditions. The screening strategies utilized in this study included 1-time colonoscopy, 1-time sigmoidoscopy, and FIT screening. Cost-effectiveness of screening took into account utility losses, cost of screening, life years with colorectal cancer, and quality adjusted life years. The study found that colonoscopy was still cost-effective up to age 83 years in patients without severe comorbidities, while sigmoidoscopy was an optimal screening strategy until age 84. FIT screening was found to be optimal from ages 85-86 years. While this study has its own limitations, it makes an argument for screening over the age of 75 years in previously unscreened patients. However, at this age group the decision to screen should still be done on a patient to patient basis.

Heart Failure with Recovered Ejection Fraction, Characterizing a Third Phenotype of Heart Failure

While ejection fraction may not have a direct correlation with exercise tolerance or level of function, it does have important prognostic and therapeutic implications. A study by Basuray et al. attempted to characterize a population of patients with previously depressed ejection fraction[5]. The study population was the Penn Heart Failure Study prospective cohort, which included patients referred to outpatient heart failure specialty clinics at the University of Pennsylvania, Case Western Reserve University, and University of Wisconsin. Patients were classified into 3 categories: heart failure with preserved EF (HF-PEF), heart failure with reduced EF (HF-REF), and heart failure recovered (HF-Recovered). HF-Recovered patients were found to have less severe symptoms, with greater number of patients with NYHA class I or II symptoms in comparison to the other groups. In addition, HF-Recovered patients were found to have higher mean blood pressures in comparison to HF-REF, however lower than HF-PEF. Biochemical profiling of these patients showed reduced level of cardiac risk markers (i.e BNP, urate, myeloperoxidase, CRP, and novel markers) in comparison to HF-REF and HF-PEF patients. In terms of clinical outcomes, the hazard ratio for all cause death, cardiac transplantation, or VAD placement was 4.1 and 2.3 for HF-REF and HF-PEF respectively in comparison to HF-Recovered. These results show distinct differences between the three phenotypes, and calls for further investigation into those patients with recovered ejection fractions.

Other notable publications this week

Treatment of Psoriatic arthritis with novel Anti-IL17 biologic, Brodalumab, a phase 2, randomized control trial[6].

The saga of rate vs. rhythm control continues in this great summation of atrial fibrillation treatment[7].

Genetic profiling of small cell lung cancer through isolation and characterization of circulating tumor cells. A potential step into the possibilities of personalized cancer treatment[8].

Dr. Christopher Maulion is a 2nd year internal medicine resident at NYU Langone Medical Center

Peer reviewed by Mark H. Adelman, MD, Contributing Editor, Clinical Correlations

Image courtesy of Wikimedia Commons

References

1. Ferguson D. Martin Kaymer Sets US Open Record at Pinehurst. ABCNews.com. Published June 13, 2014. http://abcnews.go.com/Sports/wireStory/yep-bunch-60s-us-open-24116316

2. Chirinos JA, et al. CPAP, Weight Loss, or Both for Obstructive Sleep Apnea. N Engl J Med 2014;370:2265-2275.  http://www.nejm.org/doi/full/10.1056/NEJMoa1306187

3. Roumie CL, et al. Association Between Intensification of Metformin Treatment with Insulin vs Sulfonylureas and Cardiovascular Events and All-Cause Mortality Among Patients with Diabetes. JAMA 2014;311(22):2288-2296  http://jama.jamanetwork.com/article.aspx?articleid=1878717

4. van Hees F, et al. Should Colorectal Cancer Screening be Considered in Elderly Persons without Previous Screening?: A Cost Effectiveness Analysis. Ann Intern Med 2014;160(11)750-759 http://annals.org/article.aspx?articleid=1877018http://

5. Basuray A, et al. Heart Failure with Recovered Ejection Fraction: Clinical Description, Biomarkers, and Outcomes. Circulation 2014;129:2380-2387. http://circ.ahajournals.org/content/129/23/2380

6. Mease PJ, et al. Brodalumab, an Anti-IL17RA Monoclonal Antibody, in Psoriatic Arthritis. N Engl J Med 2014;370:2295-2306 http://www.nejm.org/doi/full/10.1056/NEJMoa1315231

7. Al-Khatib SM, et al. Rate and Rhythm Control Therapies in Patients with Atrial Fibrillation: A Systemic Review. Ann Intern Med 2014;160(11):760-773 http://annals.org/article.aspx?articleid=1877019

8. Hodgkinson CL et al. Tumorigenicity and genetic profiling of circulating tumor cells in small-cell lung cancer. Nature Med 2014. Epub ahead of print June 1, 2014 http://www.nature.com/nm/journal/vaop/ncurrent/

 

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