By Vaughan Tuohy, MD
Peer Reviewed
This week saw the beginning of March Madness [1] with major upsets by 15-seed Middle Tennessee over 2-seed (and perennial contender) Michigan State, Hawaii over California, Stephen F. Austin over West Virginia, Little Rock over Purdue, and Yale over Baylor. Although in the 30+ years of the NCAA tournament, a 16-seed has yet to defeat a 1-seed, popular statistics wizard Nate Silver determined that the Middle Tennessee victory was perhaps the third biggest tournament upset of all time. He also surmised that the 2016 Michigan State Spartans were the best team to ever lose in the first round. In other news, Donald Trump continued his seemingly unstoppable march to the G.O.P. nomination on Tuesday with wins in Florida, Illinois, and North Carolina. Marco Rubio dropped out of the race and John Kasich stayed in, although his victory in his home state of Ohio is his only win to date. Mainstream Republicans are now gathering behind closed doors to try and figure out what to do about their Donald problem, while Democrats watch Hillary Clinton methodically dismantle the Sanders “revolution.”
Apart from the madness in basketball and politics, it was a pretty interesting week in medicine.
Stents or surgery for average risk patients with asymptomatic, severe carotid artery stenosis? [2]
Published this week in the New England Journal of Medicine, the Asymptomatic Carotid Trial (ACT I), a randomized non-inferiority trial of stenting with embolic protection versus carotid endarterectomy for asymptomatic carotid stenosis. A previous trial, CREST, for which ten-year follow up data was also published in this week’s NEJM, found no difference between stenting and surgery on stroke or major cardiovascular outcomes in patients with or without symptoms. The current ACT I trial randomized patients under 80 years of age with severe carotid artery stenosis (defined as 70 to 99% by ultrasound or angiography) without prior symptoms (e.g. prior ipsilateral stroke or transient ischemic attack) at “standard” surgical risk to carotid artery stenting with embolic protection versus carotid endarterectomy. Study participants were excluded if they were considered “high risk” for surgical complications. All patients were prescribed Aspirin following intervention; Clopidogrel was administered only in the stenting group for 30 days after revascularization. The study was sponsored by Abbott Vascular, the stent manufacturers. On the primary endpoint of death, stroke, or myocardial infarction within 30 days or ipsilateral stroke within one year, stenting was noninferior to endarterectomy (event rate of 3.8% vs. 3.4% for stenting vs. surgery; p=0.01 for noninferiority based on a prespecified 3-percentage point noninferiority margin). There was a trend towards more minor strokes within 30 days in the stenting group (2.4% vs. 1.1% in stenting vs. surgery, p=0.2), but no difference in major strokes. On secondary outcomes of five-year freedom from ipsilateral stroke and stroke-free survival, there was no significant difference between the two treatment arms (97.8% vs. 97.3% for stenting vs. surgery, p=0.51; 93.1% vs. 94.7% for stenting vs. surgery, p=0.44, respectively). The authors acknowledged that the lack of a medical therapy arm in the trial was a weakness because improvements in medical therapy have led to increasingly lower rates of stroke in this population. Overall, while this study suggests that stenting is probably non-inferior to carotid endarterectomy for severe asymptomatic carotid stenosis, it does not settle the question of which of the three options (stenting, surgery, or medical therapy) is best. Therefore, decisions will likely remain individualized.
Comprehensive molecular testing for community-acquired pneumonia? [3]
Diagnostic methods identify a causative pathogen in only 30-40% of cases of community-acquired pneumonia (CAP), making empiric antimicrobial therapy the most widely applied treatment strategy. This week, a study published in Clinical Infectious Diseases compared comprehensive molecular testing (quantitative PCR testing capable of identifying a wide range of bacterial and viral antigens within 24 hours) to standard culture testing. In this study, lower respiratory tract specimens were gathered from 323 adults with CAP admitted to two hospitals in Scotland. Study participants were included if they were admitted with symptoms and radiographic findings consistent with pneumonia and could produce a sputum specimen. Patients with underlying bronchiectasis, cystic fibrosis, or meeting criteria for healthcare-associated pneumonia were excluded. Comprehensive molecular testing identified a pathogen in 87% of cases as compared to 39% of cases when only standard culture-based methods were used. Not surprisingly, the most commonly identified pathogens were H. Influenza and S. Pneumoniae. Viruses were identified in 30% of cases, most (82%) co-detected with another bacterial pathogen. While these are encouraging results, it remains to be seen whether comprehensive molecular testing can be used to tailor antimicrobial therapy in practice.
Financial incentives for exercise in overweight and obese adults? [4]
You may not want to exercise, but what if money were on the line? A randomized trial published in Annals of Internal Medicine this week studied three different financial incentive strategies aimed at encouraging physical activity. Included were 281 employees with BMI greater than 27 at the University of Pennsylvania. All participants were given a goal of achieving 7,000 steps per day. Step counts were tracked using a smart phone application. To be tracked, participants simply had to install the application and carry their phone. Participants were randomized to one of three intervention groups or a control group. All four groups received daily feedback about their 7,000-step goal for 26 weeks. The three intervention groups received one of the following during the first 13 weeks: 1) $1.40 for each day the goal was met; 2) $1.40 framed as a loss (taken from a monthly stipend each day the goal was not met); 3) a daily lottery with up to a $50 payout with an expected value of $1.40. The control group received only the daily feedback with no financial incentive. The mean proportion of participant-days achieving the goal was 0.30 (95% CI: 0.22-0.37) in the control group, 0.35 (CI: 0.28-0.42) in the gain-incentive group, 0.36 (CI: 0.29-0.43) in the lottery group, and 0.45 (CI, 0.38-0.52) in the loss-incentive group. Only the loss-incentive group had a significantly greater proportion of participant-days achieving the goal than controls. If only Mayor Bloomberg was still around…
Two articles were published in Science this week on Ebola virus neutralization using human antibodies. The first described the structural and molecular basis for Ebola virus neutralization, and the second described a specific monoclonal antibody effective against the Ebola virus. In the second article, [6]monoclonal antibodies were obtained from a survivor of the 1995 Kikwit Ebola outbreak. The monoclonal antibody (mAb114) neutralized recent and previous outbreak variants of Ebola virus by mediating antibody-dependent cell-mediated cytotoxicity in vitro. When given to macaques, monotherapy with mAb114 was protective against a lethal inoculum of Ebola virus as late as five days after exposure. All macaques given the monoclonal antibodies within five days survived (n=7) and were symptom-free, whereas control macaques that did not receive the monoclonal antibodies (n=2) died from Ebola infection. Later administrations of neutralizing monoclonal antibody were not studied. Indeed, this raises hope that a cure for Ebola may one day be discovered.
Alcohol and cardiovascular events: short-term risks, long-term benefits? [7]
A systematic review was published this week in Circulation on the immediate risks of alcohol consumption on cardiovascular events. The review included 23 studies. In the meta-analysis, they found that moderate alcohol consumption was associated with an immediately higher cardiovascular risk that attenuated over 24 hours and was generally protective within one week. In contrast, heavy alcohol consumption was associated with higher cardiovascular risk within 24 hours and remained elevated after one week. Overall, the study suggests that alcohol has a time-dependent effect on cardiovascular health.
Risk of recurrent MI in medically managed ACS? [8]
An article published this week in the Journal of the American College of Cardiology analyzed data from the TRILOGY ACS trial to characterize the risk of recurrent myocardial infarction in those who have unstable angina or NSTEMI that is medical managed (i.e. do not undergo revascularization). 10.7% had a recurrent myocardial infarction within 30 months. The strongest predictors of recurrent MI were older age, NSTEMI rather than unstable angina, diabetes, and higher serum creatinine. This information could be used help further risk stratify patients presenting with NSTEMI or unstable angina.
Neurologic consequences of chronic hyponatremia? [9]
This week in the Journal of the American Society of Nephrology, a new study challenged the notion that chronic hyponatremia is an asymptomatic condition. Recent studies have linked chronic hyponatremia to attention deficits, gait disturbances, fall risk, and cognitive impairment, but it is unclear to what extent this may be due to the underlying causes of low serum sodium (e.g. cirrhosis, heart failure). Using an SIADH rat model, this study found that a sustained reduction in serum sodium was associated with multiple neurologic deficits (using special rat tests of gait disturbance, cognitive impairment, etc.). In vivo analysis showed elevated extracellular glutamate concentrations in the hippocampus and decreased glutamate uptake by astrocytes in the chronically hyponatremic rats, suggesting a mechanism for the neurologic effects. Furthermore, when the serum sodium was corrected, the neurologic performance of the hyponatremic rats improved and was equivalent to controls. If this data applies to humans, perhaps careful correction of serum sodium could improve neurologic function and quality of life in patients with chronic hyponatremia.
Sleep apnea and cardiovascular risk in the ESRD population? [10]
Finally, a shout out for my own article published last month in BMC Nephrology. Sleep-disordered breathing (e.g. obstructive sleep apnea) is a known contributor to cardiovascular disease and is highly prevalent in patients with ESRD, as 30-80% have sleep-disordered breathing when a sleep study is performed. We sought to elucidate the association between sleep-disordered breathing and cardiovascular outcomes in the ESRD population. We used Medicare claims data to identify >180,000 patients with ESRD age 67 or older. When controlling for BMI and demographic factors only, sleep-disordered breathing was associated with slightly higher risks of death and atrial fibrillation, while no significant association was found with myocardial infarction or ischemic stroke. In a larger model including multiple demographic, comorbidity, and laboratory variables, we found that sleep-disordered breathing was actually associated with slightly lower risks of death, myocardial infarction, and ischemic stroke. The major limitations of our study were the exclusion of younger patients and the use of Medicare diagnosis codes to identify patients with sleep-disordered breathing. Overall, our study suggests against any clinically significant association between sleep-disordered breathing and cardiovascular outcomes in patients with ESRD. In fact, the diagnosis of sleep-disordered breathing carried a mildly protective effect in some instances making it perhaps another risk factor with paradoxical associations in the ESRD population.
Dr. Vaughan Tuohy is a 3rd year resident at NYU Langone Medical Center
Peer reviewed by Anish B. Parikh, MD, Chief Resident, Medicine, NYU Langone Medical Center
Image courtesy of eonline.com
References
1. Silver N. Michigan State and The Biggest NCAA Tournament Upsets Ever. fivethirtyeight.com. March 18, 2016.
2. Rosenfield K et al. Randomized Trial of Stent versus Surgery for Asymptomatic Carotid Stenosis. N Engl J Med. 2016 Mar 17;374(11):1011-20. http://www.nejm.org/doi/full/10.1056/NEJMoa1515706?query=featured_home
3. Gadsby N et al. Comprehensive Molecular Testing for Respiratory Pathogens in Community-Acquired Pneumonia. Clin Infect Dis. (2016). 62 (7): 817-823. http://www.mdlinx.com/infectious-disease/medical-news-article/2016/02/04/pneumonia/6488295/?category=focus-on&page_id=1
4. Patel M et al. Framing Financial Incentives to Increase Physical Activity Among Overweight and Obese Adults: A Randomized, Controlled Trial. Ann Intern Med. 2016;164(6):385-394.
5. Miasi J et. Al. Structural and molecular basis for Ebola virus neutralization by protective human antibodies. Science. 18 Mar 2016: Vol. 351, Issue 6279, pp. 1343-1346. http://science.sciencemag.org/content/351/6279/1343
6. Davide C et. Al. Protective monotherapy against lethal Ebola virus infection by a potently neutralizing antibody. Science. 18 Mar 2016: Vol. 351, Issue 6279, pp. 1339-1342.
7. Mostofsky E et al. Alcohol and Immediate Risk of Cardiovascular Events: A Systematic Review and Dose-Response Meta-Analysis. Circulation. Published online before print March 2, 2016. http://www.ncbi.nlm.nih.gov/pubmed/26936862
8. Lopes R et al. Spontaneous MI After Non–ST-Segment Elevation Acute Coronary Syndrome Managed Without Revascularization. J Am Coll Cardiol. 2016;67(11):1289-1297 http://m.amedeo.com/26988949
9. Fujisawa H et al. Chronic Hyponatremia Causes Neurologic and Psychologic Impairments. JASN March 2016 vol. 27 no. 3 766-780 http://jasn.asnjournals.org/content/early/2015/09/16/ASN.2014121196.abstract
10. Tuohy CV et al. Sleep disordered breathing and cardiovascular risk in older patients initiating dialysis in the United States: a retrospective observational study using medicare data. BMC Nephrol. 2016; 17: 16.