Faculty Peer Reviewed
This week’s Clinical Correlations begins with news from across the ‘pond’ and the much-anticipated birth of Prince George of Cambridge. The third in line to crown of the English monarchy, behind his grandfather Prince Charles and father Prince William the Prince George, George Alexander Louis was born on the 22rd of July 2013. The last use of the name, commonly represented in the history of the British monarchy, was by the Queen’s father, King George VI. It is understood that the use of the name ‘George’ paid homage to the Queen’s father (1). Since the wedding of the Prince William and Kate Middleton, the popularity of the British crown has increased, representing a shift in sentiments directed towards the British monarchy both in Britain and abroad.
Returning back to the USA, a number of interesting studies were published this week. The debate about the use of digoxin in heart failure was again raised in an article published in the American Journal of Medicine (2). Researchers from the Digitalis Investigation Group (DIG) trial examined the role of digoxin in reducing hospital readmission rates for Medicare patients (>65 years old) with known systolic heart failure. Readmission rates have become particularly pertinent in this new cost-conscious climate with hospitals soon being penalized for readmissions of patients with heart failure under the Affordable Care Act.
Using the original data from the DIG trial, this double blinded, placebo-controlled randomized trial looked at the effect of digoxin in 3405 patients (mean age 72 years, 25% women and 89% white) with LV ejection fractions on average 29%, (76% of which were secondary to ischaemic cardiomyopathy). The majority (85-87%) of patients were New York Heart Association Class II or III across the control and experimental group and nearly all the studied patients were on ACE inhibitors (94%) and diuretics (82%).
The results showed that there was a statistically significant reduction in all-cause readmissions at 30 days (HR = 0.66, 95% CI 0.51-0.86, p = 0.002), cardiovascular-related readmissions at 30 days (HR = 0.53, 95% CI 0.38-0.72, p < 0.001) and heart failure readmissions at 30 days (HR = 0.4, 95% CI 0.26-0.62, p < 0.001). Of note, 30 day mortality rates (all cause, cardiovascular and heart failure specific causes) were not significant. A noticeable confounder explaining these results was the potential effect of increased healthcare involvement to monitor the effects of digoxin (including drug levels). Also, in this study use of aldosterone antagonists nor beta-blockers was not reported. Another limitation included the homogenous study sample of predominately white males, which makes it harder to extrapolate to other populations of patients.
Nonetheless, with digoxin falling out of favor with many clinicians in the treatment of heart failure, these findings remind us of the value of this drug in reducing readmission rates, if not mortality. This data suggests that the ongoing difficulty in using digoxin in patients with underlying renal dysfunction and also its monitoring should not dissuade clinicians from using this medication.
In concert with last week’s discussion in Clinical Correlations, the disparities in healthcare between races remain a regrettable but important facet of the US healthcare system. In a study examining data from the National HIV Surveillance System of the CDC and the Medical Monitoring Project, Hall et al (2) investigated the differences in HIV care, particularly the continuum of care, by sex, age, race and ethnicity over 2009
Among the population estimated to have HIV, 44% were African-American, 19% Hispanic/Latino and 33% white. 76% were male, and 52% of the male population with HIV attributed it to MSM contact. More concerning was that of those living with HIV only 66% were linked with care (defined as having at least 1 report of CD4 count or viral load within 3 months of diagnosis), 37% remained in care, 33% were prescribed antiretrovirals and 25% had a suppressed viral load. Ethnic differences were noted across the spectrum of HIV care, with African-Americans consistently less linked to care than whites, with this approaching statistically significant (white to African-American, p=0.07, white to Hispanic/Latino, p=0.51).
Patients between the age groups 25-34 years and 35-44 years were less linked with care as compared to patents between 45-54 (p <0.001). Given this data, the importance of performing HIV tests on individuals with risk factors cannot be understated, particularly in younger patient populations of Hispanic and African-American ethnic groups less likely to seek care.
For patients with rheumatoid arthritis (RA), the drug methotrexate remains the cornerstone of treatment. In the event that this alone should fail, often clinicians use biological agents such as TNF alpha inhibitors to augment treatment over other drug-modifying anti-rheumatoid arthritis drugs (DMARDs). However the cost of TNF alpha medications remains an issue. Furthermore, a comparison of other immunosuppressive agents with biological in methotrexate-treatment failure RA has not been undertaken. To assess this, this week’s New England Journal of Medicine published an article by O’Dell et al (4) comparing the two types of treatment. The researchers compared the triple therapy of methotrexate, sulfasalazine (maximum 2g daily) and hydrochloroquine (400mg daily) to the double therapy etanercept (weekly)/methotrexate in a double-blinded non-inferiority trial comparing over 48 weeks in 353 patients who failed methotrexate therapy with 15-25mg weekly for at least 12 weeks.
The primary outcome used to assess for non-inferiority was a change in the Disease Activity Score for 28 joints (a standardized score representing composite number of physical examination findings, pain scores and lab values such as ESR) at 48 weeks. Using a non-inferiority margin of less than 0.6 point difference in DA28 score, at 48 weeks the triple therapy was found to be non-inferior compared with the double therapy of etanercept/methotrexate (p for non-inferiority = 0.002) according to a per-protocol analysis.
Twelve patients discontinued all therapy in the triple therapy group, whereas 5 discontinued in the double therapy group, and there were more serious infections in the double therapy group (12, with one death) compared to the triple therapy group (4, no deaths). Major limitations of the study include the use of a conservative non-inferiority margin, owing in part to the lack of enrolment, which in turn limited the power of the study. In addition there was a the large number of men, who are thought to have a better biological response to treatment compared with women. While this data suggests there is no significant difference between the triple and double therapy for methotrexate-failed RA, clinicians need to be mindful of the risk of infection with TNF-alpha combinations, given the risk of serious immunosuppression.
With almost 19 cents in every dollar spent going to healthcare in the United States, controlling the cost of care remains an important goal. With this in mind, physicians’ views about cost control and physician responsibility were assessed in a study published by JAMA this week (5). 2556 physicians were surveyed for their views around three major topics: 1) the perceived role of the physician in controlling costs; 2) enthusiasm for cost-containment strategies and 3) the professional role in cost containment
Of note, respondents noted that most major stakeholders (health insurance companies, hospitals, patients) had a role in reducing costs, while noted than 36% thought physicians had a major role in reducing health costs. Furthermore, enthusiasm to reduce costs was high amongst physician respondents, (75% very enthusiastic) but there was a schism between adherence to clinical guidelines to reduce costs (76%) and ‘being solely devoted to…patient’s best interests, even if that is expensive’ (78%). This data underlines the fundamental tension between the social responsibilities of physicians to contain costs with the individual responsibility to deliver optimal care to their patients
Other articles of note:
Jacobson MF, Havas S, McCarter R. Changes in sodium levels in processed and restaurant foods, 2005 to 2011. JAMA Intern Med. 2013;173(14):1285-91
This retrospective cross-sectional analysis looked at sodium content in processed and restaurant foods according to the data from the Center for Science in the Public Interest. It was noted that there was a 3.5% decline in sodium content in processed food whereas in fast-food restaurants, sodium content increased by 2.6%
Baron E, Miller M, Weinstein M et al. A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of American (IDSA) and the American Society for Microbiology (ASM). Clin Inf Dis 2013;57(4):485-488
This report released by the Infectious Disease Society of America outlines the common pitfalls and issues with collection microbiological data, including many common sense interventions such as appropriate and accurate labeling of microbiological tests and specimen collection prior to antibiotic administration.
Aggarwal B, Ellis SG, Lincoff AM et al. Cause of Death Within 30 Days of Percutaneous Coronary Intervention in an Era of Mandatory Outcome Reporting. J Am Coll Cardiol. 2013 May 8. doi:pii: S0735-1097(13)01787-7. 10.1016/j.jacc.2013.03.071
This article noted the findings on causes and incidence of 30-day mortality in relation to percutaneous coronary intervention (PCI) in a retrospective analysis of registry data. It showed overall prevalence of all-cause mortality of 2% (n=81) out of a total of 2078 PCIs. Of those who died, 58% were from cardiac causes (72% of which were PCI-related, most commonly periprocedural bleeding), and 42% from non cardiac causes (the most common being septic shock and stroke).
Ghofrani H, D’Armini A, Grimminger F et al. Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension. NEJM. 2013;369(4):319-329)
This was a industry-funded, placebo controlled randomized multicenter double blinded study comparing riociguat ( a souble guanylate cyclase stimulator) in patient with chronic thromboembolic pulmonary hyerptension using functional status (6 min walk test) as the primary outcome. It showed a significant decrease in the 6 min walk test compared to placebo.
Dr. Arnab Ghosh is a 2nd year resident at NYU Langone Medical Center
Peer reviewed by Neil Shapiro, MD, Editor-In-Chief, Clinical Correlations
Image courtesy of Wikimedia Commons
(1) Burn J. The Little Prince Gets a Name: George. The New York Times July 24th, 2013 http://www.nytimes.com/2013/07/25/world/europe/and-the-name-isgeorge-alexander-louis.html?_r=0
(2) Bourge R, Fleg J, Fonarow G et al. Digoxin Reduces 30-day ALL-cause Hospital Admission in Older Patients with Chronic Systolic Heart Failure. Am J Med. 2013;126(8): 701-708
(3) Hall HI, Frazier EL, Rhodes P et al. Differences in human immunodeficiency virus care and treatment among subpopulations in the United States. JAMA Intern Med. 2013;173(14):1337-44. http://archinte.jamanetwork.com/article.aspx?articleid=1697789
(4) O’Dell J, Mikuls T, Taylor T et al. Therapies for Active Rheumatoid Arthritis after Methotrexate Failure. NEJM. 2013;369(4):307-318 http://www.ncbi.nlm.nih.gov/pubmed/23755969
(5) Tilburt J, Wynia M, Sheeler R. Views of US Physicians About Controlling Health Care Costs. JAMA 2013;310(4):380-388 http://jama.jamanetwork.com/article.aspx?articleID=1719740&utm_source=Silverchair%20Information%20Systems&utm_medium=email&utm_campaign=MASTER%3AJAMALatestIssueTOCNotification07%2F23%2F2013
(6) Jacobson MF, Havas S, McCarter R. Changes in sodium levels in processed and restaurant foods, 2005 to 2011. JAMA Intern Med. 2013;173(14):1285-91 http://archinte.jamanetwork.com/article.aspx?articleid=1687516
(7) Baron E, Miller M, Weinstein M et al. A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2013 Recommendations by the Infectious Diseases Society of American (IDSA) and the American Society for Microbiology (ASM). Clin Inf Dis 2013;57(4):485-488 http://cid.oxfordjournals.org/content/early/2013/06/24/cid.cit278.full.pdf
(8) Aggarwal B, Ellis SG, Lincoff AM et al. Cause of Death Within 30 Days of Percutaneous Coronary Intervention in an Era of Mandatory Outcome Reporting. J Am Coll Cardiol. 2013 May 8. doi:pii: S0735-1097(13)01787-7. 10.1016/j.jacc.2013.03.071 https://www.ncbi.nlm.nih.gov/m/pubmed/23665371/?i=6&from=/18215596/related
(9) Ghofrani H, D’Armini A, Grimminger F et al. Riociguat for the Treatment of Chronic Thromboembolic Pulmonary Hypertension. NEJM. 2013;369(4):319-329 http://www.nejm.org/doi/full/10.1056/NEJMoa1209657