Primecuts – This Week In The Journals

January 7, 2013

By Cassia Wells, MD

Faculty Peer Reviewed

This week as the world said goodbye to 2012 and welcomed the new year, the economic “fiscal cliff” dominated the US news cycles. A deal was eventually reached that, among other things, prevented a 27% decrease in Medicare reimbursements for doctors for another year. Overall 2012 was a big year for healthcare reform as it featured prominently in the presidential election in November and the US Supreme Court deemed the Affordable Care Act constitutional in June. Healthcare reform will likely continue to be a central issue in the media this year as we move toward the 2014 implementation of many of the Affordable Care Act’s major provisions.

With the start of 2013 many will be embarking on a New Year’s resolution to lose weight. A study published in JAMA last week, however, suggests that weight loss goals need not be too extreme. In a systematic review and meta-analysis, Flegal et al examined the relationship of all-cause mortality and BMI [1]. A total of 97 studies were used in their analysis, with a sample size of more than 2.88 million individuals and more than 270,000 deaths. All-cause mortality hazard ratios for overweight (BMI of 25-30), obesity (BMI of >30), grade 1 obesity (BMI of 30-35), and grades 2 and 3 obesity (BMI of >35) were calculated relative to normal weight (BMI of 18.5-25). They found that being overweight was significantly associated with reduced mortality (HR 0.94, 95% CI 0.91-0.96). All grades combined obesity was associated with an increase in mortality (HR 1.18, 95% CI 1.12-1.25), but grade 1 obesity did not show increased mortality (HR 0.95, 95% CI, 0.88-1.01), whereas grades 2 and 3 did (HR 1.29, 95% CI 1.18-1.41). While this large analysis does not provide an explanation for these associations or take into account body fat distribution or other chronic medical conditions, it does highlight that BMI should not be used in isolation, but rather as one of many indicators for recommending weight loss.

This week in the NEJM, Villanueva et al compared the efficacy and safety of a restricted (7g/dl) vs. liberal (9g/dl) hemoglobin transfusion threshold strategy for upper GI bleeds [2]. This randomized controlled trial enrolled 921 patients hospitalized with severe upper GI bleeding in Barcelona and further stratified them by the presence of cirrhosis. Probability of survival was found to be significantly higher at 45 days in the restrictive-strategy group than in the liberal-strategy group (95% and 91% respectively, p=0.02). Patients in the restricted strategy group also were significantly less likely to re-bleed or require additional rescue therapy, spent significantly fewer days in the hospital, and had fewer adverse transfusion related-events. Previous studies have suggested a lower transfusion threshold was at least equally effective, but were conducted on critically ill patients and excluded those with an active bleed [3]. This study, although limited to upper GI bleeds, again supports a lower transfusion threshold, even in active bleeding and provides evidence of an overall mortality benefit.

Switching to women’s health, the Annals of Internal Medicine published the updated U.S. Preventive Services Task Force (USPSTF) recommendations on hormone therapy for the primary prevention of chronic conditions in postmenopausal women [4]. Hormone replacement with combined estrogen-progesterone in post-menopausal women or estrogen alone in women who have undergone a hysterectomy had previously been thought to help prevent osteoporosis, CHD and dementia. The USPSTF examined the evidence from the Woman’s Health Initiative (WHI) trial and found that while hormone replacement did reduce fractures, it increased the risk of stroke, DVT, pulmonary embolus, invasive breast cancer (estrogen-progesterone only), gallbladder disease, urinary incontinence and dementia. Taken together the USPSTF recommended against the use of hormone replacement therapy for primary prevention in post-menopausal women (Grade D recommendation). While these are strong recommendations, they are only for primary prevention and do not factor in use for post-menopausal symptoms. As always, clinicians must take into account individual patient characteristics and preferences when making final decisions, however the risks of hormone replacement therapy remain considerable.

In Circulation last week, Larsen et al described six cases of atrial giant cell myocarditis (aGCM), which they claim is a distinct clinicopathologic entity from the better-known ventricular giant cell myocarditis (vGCM) [5]. Like vGCM, aGCM is characterized microscopically by myocardial infiltration with lymphocytes, multinucleated giant cells, eosinophils and cardiomyocyte necrosis/fibrosis. Also like vGCM, aGCM appears to be associated with autoimmune disorders. However aGCM has a better prognosis as it can present with different clinical features: atrial fibrillation/flutter, severe atrial dilatation, mural thrombus, and MR/TR. It also has distinct radiologic features of atrial wall thickening and edema with ventricular sparing. These cases bring the total number reported up to 13, though making an accurate estimate of prevalence is not yet possible as many were discovered incidentally. While further studies are needed to determine prevalence, etiology and whether there is a role for treatment with immunosuppressants as with vCGM, aGCM is certainly an entity worth knowing about when evaluating atrial dysfunction given its more favorable prognosis

Other articles of interest this week:

1. McKittrick Net al. Improved Immunogenicity With High-Dose Seasonal Influenza Vaccine in HIV-Infected Persons: A Single-Center, Parallel, Randomized Trial. http://annals.org/article.aspx?articleid=1487780

This randomized controlled trial, conducted on HIV positive adults, found that rates of influenza seroprotection were higher after receiving a high-dose influenza vaccine compared to a standard dose vaccine.

2. Marchioli R, et al. Cardiovascular Events and Intensity of Treatment in Polycythemia Vera. http://www.nejm.org/doi/full/10.1056/NEJMoa1208500

Reports on a randomized controlled trial which found that patients with JAK2-positive polycythemia vera who had a treatment target hematocrit of <45% had significantly lower rates of cardiovascular death and major thrombosis compared to those with a treatment target hematocrit of 45-50%.

3. Khan,AM, et al. Low Serum Magnesium and the Development of Atrial Fibrillation in the Community: The Framingham Heart Study. http://circ.ahajournals.org/content/127/1/33.abstract

A prospective cohort study as part of the Framingham Offspring Study, conducted over 20 years, found a moderate association with hypomagnesium and the development of atrial fibrillation in people without known cardiovascular disease.

4. Lasalvia A, et al. Global pattern of experienced and anticipated discrimination reported by people with major depressive disorder: a cross-sectional survey. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961379-8/abstract

As barriers to mental health treatment continue to be in the spotlight, this article presents cross-sectional data on depression and discrimination from over 1000 participants suffering from depression in 35 countries, highlighting the global need to reduce stigma associated with depression.

Dr. Cassia Wells is a 1st year resident at NYU Langone Medical Center

Faculty Peer reviewed by Megha Shah, MD, Contributing Editor, Clinical Correlations

References:

1. Flegal KM, et al. Association of All-Cause Mortality With Overweight and Obesity Using Standard Body Mass Index Categories: A Systematic Review and Meta-analysis. JAMA. 2013;309(1):71-82.  http://jama.jamanetwork.com/article.aspx?articleid=1555137

2. Villanueva C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368:11-21. http://www.nejm.org/doi/full/10.1056/NEJMoa1211801

3. Hebert PC, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-417. http://www.nejm.org/doi/full/10.1056/NEJM199902113400601

4. Moyer, VA. Menopausal Hormone Therapy for the Primary Prevention of Chronic Conditions: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2013 Jan;158(1):47-54.  http://annals.org/article.aspx?articleid=1384872

5. Larsen BT, et al. Atrial Giant Cell Myocarditis: A Distinctive Clinicopathologic Entity. Circulation. 2013;127:39-47.  http://circ.ahajournals.org/content/127/1/39.abstract

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