Primecuts – This Week In The Journals

November 24, 2014

By Chio Yokose, MD

Peer Reviewed

As temperatures took a noticeable dip earlier this week in New York City, prompting many of us to begrudgingly pull out our heavy down coats and boots from our closets, no place was hit harder than Buffalo, NY. Although no stranger to snow in this part of the country, even lifelong residents of Buffalo were shocked to wake up to a wall of white on Wednesday morning as a lake-effect storm, which rapidly developed over Lake Erie late Tuesday evening, dumped nearly six feet of snow in Buffalo and its surrounding suburbs [1]. In an area where the average annual snowfall is in the vicinity of eight feet, many of its residents were unprepared for this storm, expected to result in snowfall that met or surpassed this number in a matter of days [2]. Unfortunately, this record-setting storm has tragically claimed the lives of eight people already, including four who died of cardiac complications while shoveling snow [3].

In the medical journals this week…

Flu Vaccine Efficacy in Elderly Patients

As temperatures become more frigid, the looming flu season comes to the forefront of many of our minds. In a study published in Lancet Infectious Diseases this week, Darvishian et al. performed a meta-analysis of test-negative design case-control studies that assessed the effectiveness of seasonal influenza vaccine against laboratory confirmed influenza in community-dwelling elderly people over the age of 60 [4]. In a test-negative design study, the vaccine status is compared between patients who present with influenza-like symptoms who subsequently test positive for the influenza (laboratory-confirmed cases) against those who test negative (controls). This group identified 35 such studies with 53 data sets through searches of Medline, Embase, and the Cochrane library, which were included in the analysis. Interestingly, they found that during periods of local activity, the influenza vaccine was not significantly effective regardless of whether the vaccine matched or did not match the circulating strains (OR 0.62, 95% CI 0.28-1.36, p=0.2126 for matched; OR 0.83, 95% CI 0.38-1.79, p=0.6079 for mismatched). During periods of sporadic activity, the vaccine was effective only if it matched the circulating strains (OR 0.69, 95% CI 0.48-0.99, p=0.0489). During epidemic seasons, regional outbreaks, and widespread outbreaks, the influenza vaccine was significantly effective regardless of whether the vaccine matched the circulating strains or not.

Some of the limitations in the study are related to the systemic literature search, specific characteristics of the included studies, and model-related factors. For instance, some of the studies identified in the initial literature search pertained to the general population, so the information about individuals 60 years and older was sometimes incomplete or missing. Although the authors reached out to the investigators of such studies to obtain additional information, they did not always receive all the information they needed to include the study in the meta-analysis. Nevertheless, this analysis supports the notion that in elderly patients in particular, the seasonal influenza vaccine is effective against confirmed influenza during epidemic seasons.

NSAIDS – A Double-Edged Sword for Patients with Atrial Fibrillation on Anticoagulation?

The Annals of Internal Medicine published an observational study this week aiming to quantify the widely assumed increased risk bleeding and thromboembolic complications in patients with atrial fibrillation on anticoagulation and concomitant NSAID use [5]. The study included 150,900 patients with atrial fibrillation identified by the Danish National Patient Registry (exclusion criteria included presence of valvular disease). The median age was 75 years, and 47% of study participants were female. Of the patients included, 69.8% were treated with an antiplatelet agent (aspirin or clopidogrel) or oral anticoagulant (warfarin or phenprocoumon) at baseline, whereas 5% were treated with a concomitant NSAID. During follow-up, 35.6% of participants claimed at least one NSAID prescription.

The primary outcome examined in this study was serious bleeding, defined as hospitalization or death from intracranial bleeding, gastrointestinal bleeding, or bleeding from the respiratory or urinary tract or anemia caused by bleeding. The secondary outcome was hospitalization or death from thromboembolism, defined as ischemic stroke, unspecified stroke, or systemic arterial embolism. At three months, the absolute risk for serious bleeding with 14 days of continuous NSAID exposure across all patients was 3.5 events per 1000 patients vs. 1.5 events per 1000 patients without NSAID exposure, with an absolute risk different of 1.9 events per 1000 patients (95% CI, 1.6-2.3). Among patients receiving warfarin or phenprocoumon, the absolute risk difference was 2.5 (95% CI, 2.1-3.0). A similar statistically significant difference was also observed at 2 years. The hazard ratio for thromboembolism was also increased (1.36; 95% CI, 1.27-1.45) when comparing NSAID users to non-NSAID users.

Although this study is limited by its observational design, the data published further emphasize the dangers of using NSAIDs in those with atrial fibrillation on antiplatelet or anticoagulant therapy, and argue for the use of tylenol and other non-NSAID analgesics before resorting to NSAID use, especially chronic use, in such patient populations.

Beta-Blocker Use in Heart Failure with Preserved Ejection Fraction

In other news, JAMA presents a study about the use of beta-blockers in heart failure with preserved ejection fraction (HFPEF) [6]. While beta-blockers have been extensively studied and shown to improve outcomes in heart failure with reduced ejection fraction (HFREF), the data on HFPEF and beta-blockers is sparser. This cohort study initially enrolled 19,083 individuals with a diagnosis of HFPEF (15,786 treated and 3297 untreated with beta-blocker), with 8244 included in the study after propensity score matching two treated to one untreated patient. The primary outcome of the study was all-cause mortality.

In the matched HFPEF cohort, the total number of deaths per 1000 patient-years was 177 (95% CI, 170-184) among those who received beta-blockers vs. 191 (95% CI, 181-202) among those who did not (P=0.03). At 1 year, survival was 80% (95% CI, 79-81%) in the treated group vs. 79% (95% CI, 78-81%) in the untreated group. At 5 years, it was 45% (95% CI, 43-47%) in the treated group vs. 42% (95% CI, 40-45%) among those who did not. The hazard ratio throughout follow-up was 0.93 (95% CI, 0.86-0.996, P=0.04) for a number-needed-to-treat to save 1 life of 100 at 1 year and 33 at 5 years.

Enteral Feeding in Acute Pancreatitis

Shifting gears to the treatment of acute pancreatitis, a new study published in the New England Journal of Medicine this week aims to shed more light in the timing and manner of initiating enteral feeding in the setting of acute pancreatitis [7]. The PHYTHON (Pancreatitis, Very Early Compared with Selective Delayed Start of Enteral Feeding) trial was a multi-center, randomized, controlled superiority trial performed in six university medical centers and 13 large teaching hospitals of the Dutch Pancreatitis Study Group. Adult patients presenting with a first episode of acute pancreatitis, who were at high risk for complications defined as having APACHE scores of 8 or higher within 24 hours of presentation, were eligible for the study; a total of 208 such patients enrolled at 19 Dutch hospitals. The patients were then randomly assigned in 1:1 ratio either to nasoenteric tube feeding started within 24 hours of randomization (early) or to an oral diet starting at 72 hours, with a switch to nasoenteric tube feeding only if unable to tolerate adequate oral intake at that time (on-demand).

The primary end point was a composite of major infection (defined as infected pancreatic necrosis, bacteremia, or pneumonia) or death within 6 months after randomization. The primary end point occurred in 30 of 101 (30%) patients in the early group vs. 28 of 104 (27%) patients in the on-demand group (risk ratio, 1.07; 95% CI 0.79-1.44; P=0.76). There were no significant differences between the early group and the on-demand group in the rate of major infection (25% vs. 26% respectively, P=0.87) or death (11% vs. 7% respectively, P=0.33).

The results of this study differ from those of previous studies, which showed an improved outcome with early nasoenteric tube feeding as compared to total parenteral nutrition. The authors of this study postulate that one of the reasons for this difference may have to do with the high rate of complications associated with total parenteral feeding.

In other news…

A large cohort study published in Annals of Internal Medicine examined the effect of renin-angiotensin systemic blockade therapy use on survival rates after undergoing surgical aortic valve replacement for severe aortic stenosis [8]. The authors of this study found an association of increased survival rates in patients after SAVR for severe AS who had received renin–angiotensin system blockade therapy.

Results of the HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study were published in JAMA Internal Medicine, comparing the effectiveness of PEG to standard lactulose therapy in patients with cirrhosis hospitalized at an academic tertiary hospital for acute hepatic encephalopathy [9]. Interestingly, PEG led to more rapid HE resolution than standard therapy.

As a part of the MESA (Multi-Ethnic Study of Atherosclerosis) study, investigators sought to examine the association between baseline QT interval and incident cardiovascular events in healthy individuals [10], concluding that the QT interval was associated with incident events in middle-aged and older adults without prior CVD.

A Swedish registry-based observational study designed to determine the excess risk of death in type 1 diabetics based on level of glycemic control was published in the New England Journal of Medicine this week [11]. This study found that their patients had an increased risk of death from any cause or from cardiovascular causes twice as high as the risk for matched controls.

Dr. Chio Yokose is a 1st year resident at NYU Langone Medical Center.

Peer Reviewed by Cilian J. White, M.D., Internal Medicine Resident, NYU Langone Medical Center

Image courtesy of Wikimedia Commons


1. Thompson C. Buffalo Snow Storm Traps Residents in Homes. Huffington Post Online. 19 Nov 2014.

2. Rice D. Epic snowstorm on track to set a record in Buffalo. USA Today Online. 20 Nov 2014.

3. Sanchez R, Fantz A, and Payne E. Eight dead in storm as Buffalo braces for more snow. CNN Online. 20 Nov 2014.

4. Darvishian M, Maarten JB, Eelko H, et al. Effectiveness of seasonal influenza vaccine in community-

dwelling elderly poeple: a meta-analysis of test-negative design case-control studies. Lancet Infectious Diseases. 2014; 14: 1228-1239.

5. Lamberts M, Lip G, Hansen ML, et al. Relation of Nonsteroidal Anti-inflammatory Drugs to Serious Bleeding and Thromboembolism Risk in Patients With Atrial Fibrillation Receiving Antithrombotic Therapy: A Nationwide Cohort Study. Ann Intern Med. 2014; 161(10): 690-698.

6. Lund LH, Benson L, Dahlstrom U, et al. Association Between Use of beta-Blockers and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction. JAMA. 2014; 312(19): 2008-2018.

7. Bakker OJ, van Brunschot S, van Santvoort HC, et al. Early versus On-Demand Nasoenteric Tube Feeding in Acute Pancreatitis. N Engl J Med. 2014; 371(21): 1983-1993.

8. Goel SS, Aksoy O, Gupta S, et al. Renin-Angiotensin system blockade therapy after surgical aortic valve replacement for severe aortic stenosis: a cohort study. Ann Intern Med. 2014; 161(10): 699-710.

9. Rahimi RS, Singal AG, Cuthbert JA, et al. Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution for Treatment of Overt Hepatic Encephalopathy: The HELP Randomized Clinical Trial. JAMA Intern Med. 2014; 174(11): 1727-1733.

10. Beinart R, Zhang Y, Lima J, et al. The QT Interval is Associated with Incident Cardiovascular Events. Journal of the American College of Cardiology. 2014; 64: 2111-2119.

11. Lind M, Svensson AM, Kosiborod M, et al. Glycemic Control and Excess Mortality in Type 1 Diabetes. N Engl J Med. 2014; 371(21): 1972-1982.