Literature Review

ITL: Physician Reviews of HM-Relevant Research


In This Edition

Literature At A Glance

A guide to this month’s studies

  1. Burnout among physicians and the general workforce
  2. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke
  3. Performance of the HEMORR2AGES, ATRIA, and HAS-BLED bleeding risk prediction scores in patients with atrial fibrillation undergoing anticoagulation
  4. Probiotics for secondary prevention of hepatic encephalopathy
  5. Capsule endoscopy for acute obscure GI bleeding
  6. Perceptions of readmitted patients transitioning from hospital to home
  7. Thirty-day readmissions after acute myocardial infarction
  8. One-hour rule-out or rule-in for AMI patients in chest pain
  9. Aspirin increases bleed risk without reducing risk of stroke in CKD and NVAF patients

Burnout among Physicians and the General Workforce

Clinical question: What is the degree and distribution of burnout within the physician workforce, and how does that compare to the general U.S. workforce?

Background: Professional burnout, work satisfaction, and work-life balance are critical elements to understand in the physician workforce. It is well documented that physicians are at high risk for burnout; however, few extensive studies have looked at rates and the identification of high-risk subpopulations.

Study design: Cross-sectional survey.

Setting: U.S. workforce.

Synopsis: This study included 7,288 physicians (26.7% response rate) and 5,930 controls from the general U.S. population. Validated survey instruments were employed to assess the degree and presence of burnout, depression, and satisfaction with work-life balance.

In aggregate, using a validated, two-item burnout measure, 35.2% of physicians were characterized as having burnout, compared with 27.6% of the general population (P<0.001). Within the physician community, the specialties with the highest risk of burnout included emergency medicine, general internal medicine, family medicine, and neurology.

Important limitations of this study include that the physician and general population surveys were performed at different times (six months apart), that the groups were not ideally matched (age and sex, for example), and the overall response rate of the physician survey was low.

This study sheds light on an important topic for hospitalists. Future studies should continue to probe the problem of burnout and look for creative solutions to mitigate risks that might threaten professional longevity.

Bottom line: Burnout is prevalent among physicians, especially when compared to the general workforce. Physician specialties in front-line patient care are at highest risk.

Citation: Shanafelt TD, Boone S, Tan L, et al. Burnout and satisfaction with work-life balance among US physicians relative to the general US population. Arch Intern Med. 2012;20 [Epub ahead of print].

Effects of Clopidogrel Added to Aspirin in Patients with Recent Lacunar Stroke

Clinical question: Does the addition of clopidogrel to aspirin reduce the risk of any type of recurrent stroke, or affect the risk of bleeding or death, in patients who recently suffered a lacunar stroke?

Background: There are no prior randomized, multicenter trials on secondary prevention of lacunar stroke; aspirin is the standard antiplatelet therapy in this setting.

Study design: Double-blind, randomized, multicenter trial.

Setting: Eighty-two clinical centers in North America, Latin America, and Spain.

Synopsis: Researchers enrolled 3,020 patients from 2003 to 2011; criteria included age >30 years old and symptomatic lacunar stroke (proven by MRI) in the preceding 180 days.

Results showed no significant difference between recurrent strokes (any type) in the aspirin-only group (2.7% per year) versus the aspirin-plus-clopidogrel group (2.5% per year). Major hemorrhage risk was much higher in the aspirin-plus-clopidogrel group (2.1% per year) versus aspirin-only group (1.1% per year). All-cause mortality also was much higher in the aspirin-plus-clopidogrel group (N=113) versus the aspirin-only group (N=77).

Bottom line: The addition of clopidogrel to aspirin for secondary prevention does not significantly reduce the risk of recurrent stroke, but it does significantly increase the risk of bleeding and death.

Citation: Benavente OR, Hart RG, McClure LA, et al. Effects of clopidogrel added to aspirin in patients with recent lacunar stroke. N Engl J Med. 2012;367:817-825.

Bleeding Risk Prediction Scores in Patients with Atrial Fibrillation Undergoing Anticoagulation

Clinical question: What are the relative predictive values of the HEMORR2AGES, ATRIA, and HAS-BLED risk-prediction schemes?

Background: The tools predict bleeding risk in patients anticoagulated for atrial fibrillation (afib), but it is unknown which is the best to predict clinically relevant bleeding.

Study design: Post-hoc analysis.

Setting: Data previously collected for the AMADEUS trial (2,293 patients taking warfarin; 251 had at least one clinically relevant bleeding event) were used to test each of the three bleeding risk-prediction schemes on the same data set.

Synopsis: Using three analysis methods (net reclassification improvement, receiver-operating characteristic [ROC], and decision-curve analysis), the researchers compared the three schemes’ performance. HAS-BLED performed best in all three of the analysis methods.

The HAS-BLED score calculation requires the following patient information: history of hypertension, renal disease, liver disease, stroke, prior major bleeding event, and labile INR; age >65; and use of antiplatelet agents, aspirin, and alcohol.

Bottom line: HAS-BLED was the best of the three schemes, although all three had only modest ability to predict clinically relevant bleeding.

Citation: Apostolakis S, Lane DA, Guo Y, et al. Performance of the HEMORRAGES, ATRIA and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation. J Am Coll Cardiol. 2012;60(9):861-867

Probiotics for Secondary Prevention of Hepatic Encephalopathy

Clinical question: Are probiotics as effective as lactulose for secondary prevention of hepatic encephalopathy (HE)?

Background: Probiotics alter the gut flora, resulting in decreased ammonia production and absorption. Probiotics have been shown to reduce the incidence of low-grade HE. However, studies on probiotics usage for secondary prevention of HE are lacking.

Study design: Prospective, randomized, controlled, nonblinded, single-center study.

Setting: Tertiary-care center, New Delhi.

Synopsis: Three hundred sixty patients who had recovered from HE from October 2008 to December 2009 were screened; 235 met the inclusion criteria. They were randomized to receive either lactulose (Gp-L), probiotics (Gp-P), or no therapy (Gp-N). The Gp-L group received 30 to 60 ml of lactulose in two to three divided doses; the Gp-P group received three capsules per day containing lactobacillus, bifidobacterium, and Streptococcus salivarius strains.

The primary endpoints were the development of overt HE (assessed by the West Haven Criteria) or a follow-up of 12 months. Lactulose therapy was significantly more effective in secondary prophylaxis than no therapy (26.2% vs. 56.9%, P=0.001), as was probiotics therapy compared with no therapy (34.4% vs. 56.9%, P=0.02), but no significant difference was found between lactulose and probiotics therapy (26.2% vs. 34.4%, P=0.349).

The major limitation of the study was its open-label design. The study also used a high concentration of probiotics, and the results could be strain-specific and hence require validation with other probiotics combinations. The Gp-N group continued the previous therapy (excluding lactulose), with an unknown number on rifaximin.

Bottom line: Lactulose and probiotics are equally effective in secondary prophylaxis of hepatic encephalopathy.

Citation: Agrawal A, Sharma BC, Sharma P, Sarin SK. Secondary prophylaxis of hepatic encephalopathy in cirrhosis: an open-label, randomized controlled trial of lactulose, probiotics and no therapy. Am J Gastroenterol. 2012;107:1043-1050.

Capsule Endoscopy for Acute Obscure GI Bleeding

Clinical question: What testing modality is most appropriate for acute obscure GI bleeding: capsule endoscopy (CE) or angiography?

Background: Acute obscure GI bleeding (OGIB): remains a diagnostic challenge, accounting for 7% to 8% of patients presenting with GI bleeding. CE enables direct visualization of small bowel mucosa but lacks the ability for therapeutic intervention. Angiography is frequently chosen for massive bleeding; however, it is invasive and does not enable visualization of the bowel.

Study design: Prospective, randomized, controlled, blinded, single-center study.

Setting: Prince of Wales Hospital, Hong Kong.

Synopsis: Ninety-one patients with active OGIB from June 2005 to November 2007 were assessed for eligibility; 60 met the criteria and were randomized to either CE or angiography. Overt OGIB was defined as patients who had nondiagnostic upper endoscopy and colonoscopy.

The primary outcome was diagnostic yield of CE or mesenteric angiography in identifying the bleeding source. Secondary outcomes were long-term rebleeding rates, readmissions for bleeding or anemia, blood transfusions, and death.

CE was positive in 16 patients (53.3%) and angiography was positive in six patients (20%). The diagnostic yield of CE was significantly higher than angiography (difference=33.3%, 95% CI 8.9-52.8%, P=0.016). The mean follow-up period was 48.5 months. The cumulative risk of rebleeding was higher in the angiography group, but this was not statistically significant. There was no significant difference in rates of subsequent hospitalization, death, or transfusions between the two groups.

The study based the sample-size estimation on the diagnostic yield rather than clinical outcomes and, hence, was underpowered to detect any significant differences in clinical outcomes.

Bottom line: CE has a higher diagnostic yield than angiography in patients with active overt OGIB.

Citation: Leung WK, Ho S, Suen B, et al. Capsule endoscopy of angiography in patients with acute overt gastrointestinal bleeding: a prospective randomized study with long term follow up. Am J Gastroenterol. 2012;107:1370-1376.

Perceptions of Readmitted Patients Transitioning from Hospital to Home

Clinical question: What are patient-reported reasons for readmission to the hospital after discharge?

Background: Reducing readmissions is a critical component to improving the value of healthcare. While readmission reduction is a goal of all hospitals, there is much to be gleaned from evaluating patients’ view of the problem. This study used a survey to assess the patient’s viewpoint.

Study design: Cross-sectional survey.

Setting: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center, Philadelphia.

Synopsis: A survey of 36 questions was posed to 1,084 patients who were readmitted within 30 days of discharge from November 2010 to July 2011 (32% of eligible patients). The data were subdivided based on socioeconomic status and medical versus surgical patients.

Some issues patients raised regarding discharge planning included difficulty with paying for medications, challenges with travel to pharmacies, and concern over medication side effects.

Patients with low socioeconomic status had more difficulty taking medications and following instructions, had more depression, and had less social support.

Bottom line: Readmission rates are affected by a patient’s social situation. A team approach to discharge planning might mitigate some of these factors.

Citation: Kangovi S, Grande D, Meehan P, Mitra N, Shannon R, Long JA. Perceptions of readmitted patients on the transition from hospital to home. J Hosp Med. 2012 [Epub ahead of print].

30-Day Readmissions after Acute Myocardial Infarction

Clinical question: What are potential predictors of 30-day readmissions after acute myocardial infarction (MI)?

Background: Much attention has been given to evaluate the causes of readmissions of heart failure, acute MI, and pneumonia. This study looked at 30-day readmissions after an acute myocardial infarction (AMI).

Study design: Retrospective cohort study.

Setting: Olmstead County Hospital, Rochester, Minn.

Synopsis: A chart review of AMI based on ICD-9 codes from 1987 to 2010 identified 3,010 patients. Patients were verified using symptoms, cardiac enzymes, and EKG changes at the time of event. Interventions evaluated included fibrinolytic therapy, CABG, or primary PCI.

Survival increased to 96% from 89% during the period from 1987 to 2010. Researchers also noted more comorbid conditions, such as diabetes mellitus, COPD, and hypertension, noted over time. Of the patients evaluated, 643 readmissions occurred for 561 patients (18.6%). Of these, the most frequent causes were ischemic heart disease, respiratory symptoms, and heart failure. Comorbid conditions, such as diabetes, COPD, anemia, higher killip class on initial admission, duration of prior hospitalization, and procedural complications, independently increased the risk of readmission.

Bottom line: In addition to factors unrelated to an AMI, a patient’s comorbid conditions, post-procedure complications, and duration of hospitalization influence the risk of readmission.

Citation: Dunlay SM, Weston SA, Killian JM, et al. Thirty-day rehospitalizations after acute myocardial infarction: a cohort study. Ann Intern Med. 2012;157(1):11-18.

One-Hour Rule-Out or Rule-In for AMI in Chest Pain

Clinical question: How can we use the newly developed high-sensitivity cardiac troponin (hs-cTnT) to shorten the time to rule in and rule out AMI?

Background: The hs-cTnT assays available appear to improve the early diagnosis of AMI when compared to the regular cardiac troponins, but no clear guidelines are available as how to best use them in clinical practice.

Study design: Prospective, multicenter study.

Setting: Switzerland hospitals.

Synopsis: The study enrolled 872 unselected patients presenting to the ED with acute chest pain. Hs-cTnT level was measured in a blinded fashion at presentation and after one hour. Two independent cardiologists using all available medical records adjudicated the final AMI diagnosis. Optimal thresholds for rule-out were selected to allow for 100% sensitivity and negative predictive value. Rule-out criteria were defined as baseline hs-cTnT level <12 ng/L and an absolute change within the first hour of <3 ng/L. Rule-in criteria was defined as baseline hs-cTnT >52 ng/L or an absolute increase within the first hour of >5 ng/L.

AMI was the final diagnosis in 17% of patients; AMI was ruled out in 60%; and the remaining 23% were placed in observation.

Primary prognostic endpoint was 30-day mortality rate, which was 0.2% in the rule-out group, validating the suitability of these patients for early discharge.

Study limitations were that it was an observational study not used for clinical decision-making, no dialysis patients were included, and only one specific hs-cTnT assay was tested.

Bottom line: Using hs-cTnT levels at presentation and absolute changes within the first hour, a safe rule-out or rule-in of AMI can be performed in 77% of patients presenting with chest pain.

Citation: Reichlin T, Schindler C, Drexler B, et al. One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Arch Intern Med. 2012;172(16):1-8.

Aspirin Increases Bleed Risk without Reducing Risk of Stroke in CKD and NVAF Patients

Clinical question: Is there a difference between aspirin and warfarin in preventing thromboembolic complications and risk of bleeding in patients with chronic kidney disease (CKD) and nonvalvular afib (NVAF)?

Background: Data are lacking on risks and benefits of aspirin and warfarin in CKD, as this group of patients largely has been excluded from anticoagulation therapy trials for NVAF. This study examined the risks and benefits of aspirin and warfarin in patients with CKD with NVAF.

Study design: Retrospective, observational cohort study.

Setting: Danish National Registries.

Synopsis: Of 132,372 patients with NVAF, 2.7% had CKD and 0.7% had end-stage renal disease (ESRD). Compared to patients with no CKD, there was increased risk of stroke or systemic thromboembolism in patients with ESRD (HR, 1.83; 95% CI, 1.57-2.14) and with non-end-stage CKD (HR 1.49; 95% CI 1.38-1.59).

In patients with CKD, warfarin significantly reduced stroke risk (HR, 0.76; 95% CI, 0.64-0.91) and significantly increased bleeding risk (HR, 1.33; 95% CI, 1.16-1.53); aspirin significantly increased bleeding risk (HR, 1.17; 95% CI, 1.02-1.34) with no reduction in stroke risk.

Bottom line: CKD was associated with an increased risk of stroke among NVAF patients. While both aspirin and warfarin were associated with increased risk of bleeding, there was a reduction in the risk of stroke with warfarin, but not with aspirin.

Citation: Olesen JB, Lip GY, Kamper AL, et al. Stroke and bleeding in atrial fibrillation with chronic kidney disease. N Engl J Med. 2012;367(7):625-635.

Clinical Shorts


This multicenter randomized trial comparing early coronary CTA with standard evaluation for suspected ACS showed CTA did not decrease overall cost of care, and increased downstream testing and radiation exposure.

Citation: Hoffman U, Truong QA, Schoenfeld DA, et al. Coronary CT angiography versus standard evaluation in acute chest pain. N Engl J Med. 2012;367(4):299-308.


CDC has reported outbreaks of the H3N2 variant since July 2012. Prolonged exposure to pigs is a risk factor for acquiring the virus, and children and those with chronic conditions, such as asthma and diabetes, are at increased risk for complications.

Citation: Centers for Disease Control and Prevention. Influenza A (H3N2) variant virus outbreaks. Centers for Disease Control and Prevention website. Available at: Accessed Sept. 10, 2012.


This Cochrane review provides moderate-quality evidence that in severe GBS, IVIg started within two weeks of disease onset is as effective as PE, with no significant difference in adverse events.

Citation: Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain-Barré syndrome. Cochrane Database Syst Rev. 2012;7:CD002063.


A comparative study looking at publicly reported performance metrics from 4,809 U.S. hospitals demonstrated that teaching institutions were associated with higher quality and safety and similar overall costs.

Citation: Shahian DM, Nordberg P, Meyer GS, et al. Contemporary performance of U.S. teaching and non-teaching hospitals. Acad Med. 2012;87(6):701-708.


A new ARDS definition was developed in 2011; it defines mild, moderate, and severe ARDS and predicts mortality better than the prior definition.

Citation: Ranieri VM, Rubenfeld GD, Thompson BT, et al. Acute respiratory distress syndrome. JAMA. 2012;307 (23):2526-2533.


Among patients 65 years and older with a cataract, those who had cataract surgery had a lower risk of hip fracture within one year compared to those who did not have cataract surgery.

Citation: Tseng VL, Yu F, Lum F, Coleman AL. Risk of fractures following cataract surgery in Medicare beneficiaries. JAMA. 2012;308(5):493-501.

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