Ethan Cumbler, MD

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
2. Radiation exposure in integrated healthcare systems, 1996-2010
3. Postoperative troponin predicts 30-day mortality
4. Clinical prediction model of mortality in acute heart failure
5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
6. Early surgery for high-risk, native-valve endocarditis patients
7. Risk factors after ED visit for syncope
8. Acute hyperglycemia in CAP patients
9. Hospital delirium associated with cognitive decline, institutionalization, and death
10. Seven-day ciprofloxacin effective against acute pyelonephritis
11. Advance directives in community patients with heart failure
12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
13. Simulation training improves lumbar puncture skills
14. PCP referrals to hospitals and publicly reported data
15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
2. Radiation exposure in integrated healthcare systems, 1996-2010
3. Postoperative troponin predicts 30-day mortality
4. Clinical prediction model of mortality in acute heart failure
5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
6. Early surgery for high-risk, native-valve endocarditis patients
7. Risk factors after ED visit for syncope
8. Acute hyperglycemia in CAP patients
9. Hospital delirium associated with cognitive decline, institutionalization, and death
10. Seven-day ciprofloxacin effective against acute pyelonephritis
11. Advance directives in community patients with heart failure
12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
13. Simulation training improves lumbar puncture skills
14. PCP referrals to hospitals and publicly reported data
15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Prediction tool for neurological outcomes after in-hospital cardiac arrest
2. Radiation exposure in integrated healthcare systems, 1996-2010
3. Postoperative troponin predicts 30-day mortality
4. Clinical prediction model of mortality in acute heart failure
5. Indwelling pleural catheter vs. talc pleurodesis via chest tube
6. Early surgery for high-risk, native-valve endocarditis patients
7. Risk factors after ED visit for syncope
8. Acute hyperglycemia in CAP patients
9. Hospital delirium associated with cognitive decline, institutionalization, and death
10. Seven-day ciprofloxacin effective against acute pyelonephritis
11. Advance directives in community patients with heart failure
12. Chlorhexidine bathing effective against CVC-associated bloodstream infections
13. Simulation training improves lumbar puncture skills
14. PCP referrals to hospitals and publicly reported data
15. Medication reconciliation best practices

Prediction Tool Validated for Prognosticating Favorable Neurological Outcome after In-Hospital Cardiac Arrest

Clinical question: Does the Cardiac Arrest Survival Post Resuscitation In-Hospital (CASPRI) score accurately predict favorable neurological outcomes?

Background: Previous cardiac arrest prediction models have been focused on survival to discharge without consideration of neurological status and have not been translated into valid bedside prognostication tools. Neurologic prognosis can assist patients, families, and physicians in decisions about continued goals of care post-arrest.

Study design: Retrospective cohort study.

Setting: Acute-care hospitals.

Synopsis: Using the Get with the Guidelines Resuscitation Registry, 551 hospitals identified 42,957 patients who were successfully resuscitated from an in-hospital cardiac arrest from January 2000 to October 2009. Researchers developed a simple prediction tool for favorable neurological outcomes (defined as “no” or “moderate” neurological disability) at discharge. The 11 predictors used to calculate the CASPRI score are age; time to defibrillation; pre-arrest neurological status; hospital location; duration of resuscitation; and pre-arrest comorbidities: mechanical ventilation, renal insufficiency, hepatic insufficiency, sepsis, malignancy,

and hypotension.

Rates of favorable neurological outcome were similar between derivation cohort (24.6%) and validation cohort (24.5%). The model had excellent discrimination with a C score of 0.80. Probability of favorable neurological survival ranged from 70.7% in the top decile of patients (CASPRI <10) and 2.8% in bottom decile (CASPRI ≥ 28).

This tool is not generalizable to patients with out-of-hospital arrest or undergoing therapeutic hypothermia.

Bottom line: CASPRI is a simple bedside tool validated to estimate probability of favorable neurological outcome after in-hospital cardiac arrest.

Citation: Chan PS, Spertus JA, Krumholz HA, et al. A validated prediction tool for initial survivors in in-hospital cardiac arrest. Arch Intern Med. 2012;172(12):947-953.

Increased Use of Radiologic Imaging and Associated Radiation Exposure in Integrated Healthcare Systems, 1996-2010

Clinical question: How much has imaging utilization and associated radiation exposure increased over 15 years in integrated healthcare systems independent of financial incentives in a fee-for-service system?

Background: Use of diagnostic imaging has increased significantly within fee-for-service healthcare models. The associated radiation exposure has increased the risk of radiation-induced malignancies. Little is known about the pattern of imaging use in integrated healthcare systems without the financial incentives seen in other models of care.

Study design: Retrospective cohort study.

Setting: Six integrated healthcare systems in the U.S.

Synopsis: The number of diagnostic imaging studies performed and estimated radiation exposure were determined from analysis of electronic medical records from member patients enrolled in health systems in the HMO Research Network from 1996 to 2010. Annual increases in use of advanced diagnostics were noted in CT (7.8% annual growth), MRI (10%), ultrasound (3.9%), and PET (57%) studies.

Increased CT use over the 15-year study period resulted in increased radiation exposure, doubling mean per capita effective dose (1.2 mSv to 2.3 mSv), as well as those receiving high exposure (1.2% to 2.5%) and very high exposure (0.6% to 1.4%).

The increased imaging use and radiation exposure among HMO enrollees was similar to that of fee-for-service Medicare patients in previous studies.

Bottom line: There is a significant increase in use of diagnostic imaging studies and associated radiation exposure among integrated healthcare system enrollees from 1996 to 2010, similar to patients in fee-for-service health plans.

Citation: Smith-Bindman R, Miglioretti DL, Johnson E, et al. Use of diagnostic imaging studies and associated radiation exposure for patients enrolled in large integrated health care systems, 1996-2010. JAMA. 2012;307(22):2400-2409.

Postoperative Troponin Predicts 30-Day Mortality

Clinical question: Does postoperative peak troponin level predict 30-day mortality in patients undergoing noncardiac surgery?

Background: The use of postoperative peak troponin levels in predicting 30-day mortality for patients undergoing noncardiac surgery has not been studied extensively. Identifying patients at high risk for death following noncardiac surgery could facilitate appropriate postoperative care and improve survival.

Study design: Prospective cohort study.

Setting: International university and nonuniversity hospitals.

Synopsis: The Vascular Events In Noncardiac Surgery Patients Cohort Evaluation (VISION) Study is a large, international, multicenter, prospective cohort study designed to evaluate the major complications of noncardiac surgery. More than 15,100 patients ages 45 and older requiring at least an overnight hospitalization were enrolled following noncardiac surgery.

Peak troponin measurements during the first three postoperative days of 0.01 ng/ml or less, 0.02 ng/ml, 0.03 ng/ml to 0.29 ng/ml, and 0.3 ng/ml or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively.

This study demonstrates the sensitivity of troponin measurement for predicting postoperative 30-day mortality in patients undergoing noncardiac surgery. The study does not address interventions based on an increased postoperative troponin level. Future studies might investigate postoperative modifiable risk factors.

Bottom line: Postoperative peak troponin level predicts 30-day mortality in patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Chan MT, Alonso-Coello P, et al. Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery. JAMA. 2012;307(21):2295-2304.

Clinical Prediction Model of Mortality in Acute Heart Failure

Clinical question: Can a clinical prediction model accurately risk-stratify patients presenting to the ED with acute heart failure?

Background: Accurately prognosticating mortality is essential when determining whether to hospitalize or discharge patients presenting to the ED with acute heart failure. Evidence-based clinical prediction models enable physicians to risk-stratify patients and optimize care.

Study design: Retrospective cohort study.

Setting: Multicenter study of 86 hospitals in Ontario, Canada.

Synopsis: Data collected from 12,591 patients who presented to EDs with acute heart failure in Ontario were analyzed. A clinical prediction model of seven-day mortality of discharged and hospitalized patients was derived and validated. The Emergency Heart Failure Mortality Risk Grade (EHMRG) found an increased mortality based on higher triage heart rate, lower triage systolic blood pressure, initial oxygen saturation, and elevated troponin levels. This model uses readily available data collected in ED visits. The high-risk EHMRG score predicted about 8% seven-day mortality versus 0.3% in the low-risk score.

This model was not applied to chronic heart failure, did not utilize left ventricular function, and does not differentiate between systolic and diastolic heart failure.

Bottom line: The Emergency Heart Failure Mortality Risk Grade predicts seven-day mortality in acute heart failure in the emergent setting.

Citation: Lee DS, Stitt A, Austin PC, et al. Prediction of heart failure mortality in emergent care: a cohort study. Ann Intern Med. 2012;156(11):767-775.

Indwelling Pleural Catheter Is as Effective as Talc Pleurodesis Via Chest Tube in Relieving Dyspnea in Patients with Malignant Pleural Effusion

Clinical question: Is indwelling pleural catheter (IPC) as effective as chest tube and talc pleurodesis (talc) in improving dyspnea from malignant pleural effusion in patients who had no previous pleurodesis?

Background: Despite guidelines recommending chest tube insertion with pleurodesis as a first-line treatment for symptom palliation from malignant pleural effusion, there has been no randomized trial comparing indwelling pleural catheter with chest tube and talc pleurodesis.

Study design: Open-label, randomized controlled trial.

Setting: Seven hospitals in the United Kingdom.

Synopsis: One hundred six patients with malignant pleural effusion were randomized to undergo either IPC or talc treatment, and their daily mean dyspnea was measured. There was a clinically significant improvement of dyspnea in both IPC and talc groups over the first 42 days of the trial, without any significant difference in dyspnea between the two groups. After six months, researchers found a clinically significant decrease in dyspnea in the IPC group compared with the talc group. Chest pain and global quality of life were improved and were similar in both groups throughout the trial period. Length of hospital stay was significantly shorter in the IPC group compared with the talc group, but more patients in the IPC group experienced adverse events.

Bottom line: Indwelling pleural catheter is as effective as talc pleurodesis in reliving dyspnea from malignant pleural effusion; however, IPC is associated with increased adverse events despite shorter length of hospital stay.

Citation: Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs. chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: the TIME2 randomized controlled trial. JAMA. 2012;307(22):2383-2389.

Early Surgery Better than Conventional Treatment in High-Risk Native-Valve Endocarditis

Clinical question: Is early cardiac surgery better than conventional treatment for patients with left-sided, native-valve, infective endocarditis?

Background: Although guidelines strongly recommend early surgery for patients with infective endocarditis and congestive heart failure, the timing of surgery for patients with large vegetations and high risk of embolism without heart failure symptoms remains controversial.

Study design: Prospective, randomized trial.

Setting: Two medical centers in South Korea.

Synopsis: Seventy-six patients with left-sided, native-valve, infective endocarditis with a high risk of embolism (defined as vegetation with a diameter greater than 10 mm or severe mitral or aortic valve disease) were randomized to undergo early surgery (within 48 hours of enrollment) or conventional treatment (antibiotic therapy and surgery only if complications required urgent surgery). The primary outcome of composite in-hospital death or

clinical embolic events within six weeks of the trial occurred in only one patient in the early surgery group, compared with nine patients in the conventional group (hazard ratio 0.10, 95% CI, 0.01-0.82, P=0.03).

There was no difference in all-cause mortality at six months between the two groups, but the rate of composite endpoint of death from any cause, embolic events, or recurrence of infective endocarditis at six months was significantly lower in the early surgery group compared with the conventional group.

Bottom line: Early cardiac surgery for patients with left-sided, native-valve infective endocarditis with a high risk of embolism significantly improved the composite outcome of all-cause mortality, embolic events, or recurrence of endocarditis compared with the conventional therapy.

Citation: Kang DH, Kim YJ, Kim SH, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med. 2012;366(26):2466-2473.

Risk Factors for Short-Term Mortality after Emergency Department Visit for Syncope

Clinical question: What are the risk factors for short-term mortality after an ED evaluation for syncope or near-syncope?

Background: Syncope accounts for 1% to 2% of all ED visits and an equal number of hospital admissions. The risk of death after an ED visit for syncope is poorly understood, resulting in frequent hospital admissions.

Study design: Retrospective cohort study.

Setting: EDs in Southern California.

Synopsis: Authors evaluated 23,951 ED visits resulting in syncope as sole primary diagnosis. Age was identified as the most significant risk factor for short-term mortality. Cumulative survival data revealed that more than 1% of patients 60 or older died by 30 days. There were 215 deaths (2.84%) in patients hospitalized from the ED and 66 deaths (0.45%) among patients not hospitalized.

Pre-existing comorbidities significantly associated with increased mortality included heart failure (HR=14.3 in ages 18-53; HR=3.09 in ages 60-79; HR=2.34 in ages 80-plus), diabetes (HR=1.49), seizure (HR=1.65), dementia (HR=1.41), and a recent prior visit for syncope (HR=1.86). The risk of death by 30 days was less than 0.2% in patients under 60 without heart failure and more than 2.5% in patients of all ages with heart failure.

Bottom line: After an ED visit for syncope, patients with a history of heart failure and patients 60 and older have a significantly increased risk of short-term mortality.

Citation: Derose SF, Gabayan GZ, Chiu VY, Sun BC. Patterns and preexisting risk factors of 30-day mortality after a primary discharge diagnosis of syncope or near syncope. Acad Emerg Med. 2012;19(5):488-496.

Acute Hyperglycemia Associated with Increased Mortality in Community-Acquired Pneumonia

Clinical question: In patients admitted to the hospital for community-acquired pneumonia, is serum glucose level on admission associated with mortality?

Background: Some retrospective studies have shown an association between alterations in serum glucose levels or pre-existing diabetes and higher mortality due to infections, while other studies have shown no clear association.

Study design: Multicenter, prospective cohort study.

Setting: Hospitals and private practices in Germany, Switzerland, and Austria.

Synopsis: Prospective data from 6,891 patients were included in the analysis. Patients without diabetes and normal serum glucose levels had the lowest mortality after 90 days. Patients without diabetes but with mild acute hyperglycemia (108 mg/dL to 198 mg/dL) had a significantly increased risk of death at 90 days (HR 1.56), and patients without diabetes but with more severe acute hyperglycemia (over 252 mg/dL) had an even higher risk of death at 90 days (HR 2.37).

The 90-day mortality rate was significantly higher in patients with pre-existing diabetes (HR 2.47), although this was not affected by serum glucose levels on admission.

Bottom line: Acute hyperglycemia, as well as pre-existing diabetes, was associated with an increased risk of 90-day mortality in patients with community acquired pneumonia.

Citation: Lepper PM, Ott S, Nüesch E, et al. Serum glucose levels for predicting death in patients admitted to hospital for community acquired pneumonia: prospective cohort study. BMJ. 2012;344:e3397.

Hospital Delirium Associated with Cognitive Decline, Institutionalization, and Death

Clinical question: What is the risk of subsequent cognitive decline, institutionalization, or death due to delirium in patients with dementia?

Background: Patients suffering delirium during hospitalization can suffer additional cognitive decline. Whether this is due to additional damage from the delirium state or reflects pre-existing cognitive vulnerability remains uncertain.

Study design: Prospective analysis of a cohort of Alzheimer’s patients.

Setting: Massachusetts community-based disease registry.

Synopsis: The analysis compared nonhospitalized individuals to patients hospitalized with, and without, delirium. In 771 individuals with dementia, at least one adverse outcome (including cognitive decline, institutionalization, or death) occurred in 32% of those not hospitalized, 55% of those hospitalized without delirium, and 79% of those hospitalized with delirium. Even after adjusting for confounders, hospitalization increased the risk for each of the adverse outcomes; the highest risk was in those with delirium.

Among hospitalized patients, the authors estimated 1 in 5 cases of cognitive decline, 1 in 7 institutionalizations, and 1 in 16 deaths were attributable to delirium. Some of the attributed risk could be the result of residual confounding from unmeasured variables, limiting conclusions of causality. Despite these limitations, this study supports the hypothesis that delirium prevention measures could improve important patient outcomes.

Bottom line: Hospitalization is associated with high rates of adverse outcomes in elderly patients with dementia, the worst of which occurs in those who experience delirium.

Citation: Fong TG, Jones RN, Marcantonio ER, et al. Adverse outcomes after hospitalization and delirium in persons with Alzheimer disease. Ann Int Med. 2012;156:848-856.

In Acute Pyelonephritis, a Seven-Day Course of Ciprofloxacin is Effective in Obtaining Clinical Cure

Clinical question: What is the efficacy of ciprofloxacin for seven days compared with 14 days in women with community-acquired acute pyelonephritis?

Background: Community-acquired acute pyelonephritis is a common and sometimes serious infection in women. In an era of increasing antibiotic resistance worldwide, it is prudent to reduce antibiotic utilization. There are limited controlled trials to assess the optimum duration of antibiotic treatment for this common infection.

Study design: Prospective, randomized, double-blind, noninferiority trial.

Setting: Twenty-one infectious-disease centers in Sweden.

Synopsis: Researchers randomly assigned 284 women 18 or older with a presumptive diagnosis of acute pyelonephritis to ciprofloxacin treatment for seven or 14 days. The primary endpoint was clinical and bacteriological cure 10 to 14 days after the completion of the treatment regimen. Short-term clinical cure occurred in 97% of the patients treated for seven days and 96% treated for 14 days. Long-term follow-up showed cumulative efficacy of 93% in each group. Both regimens were well tolerated.

Patients in this study had a low occurrence of complicated (9%) and recurrent (13%) infections. Whether short courses of antibiotics are effective in more complicated infections cannot be ascertained from this study. Also, the high cure rate obtained with a seven-day course of ciprofloxacin should not be extrapolated to other classes of antibiotics. Fluoroquinolones, such as ciprofloxacin, are recommended as first-line agents for empiric oral treatment of acute pyelonephritis if the resistance rate of the uropathogens remains lower than 10%; however, there is growing evidence that E. coli strains are becoming increasingly resistant to ciprofloxacin, limiting its usefulness.

Bottom line: Acute pyelonephritis in women can be treated successfully and safely with a seven-day course of ciprofloxacin, in areas with low ciprofloxacin resistance.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomized, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012;380:484-490.

Advance Directives in Community Patients with Heart Failure

Clinical question: How prevalent are advance directives in heart-failure patients, and does a completed advance directive decrease end-of-life resource use (hospitalizations, ICU admissions, mechanical ventilation)?

Background: Heart failure is a common chronic and fatal disease. End-of-life care in heart-failure patients is associated with extremely high healthcare utilization. Heart failure guidelines recommend completing advance directives in all patients.

Study design: Population-based longitudinal cohort study.

Setting: Rochester Epidemiology Project in Olmstead County, Minn.

Synopsis: Investigators enrolled 608 patients presenting with heart failure between October 2007 and October 2011. At the time of enrollment, only 41% of the patients had existing advance directives. Independent predictors of advance directive completion included older age, history of malignancy, and renal dysfunction.

After a mean follow-up of 1.8 years, 164 patients (27%) had died. Among those patients, 106 had an advance directive (64.6%) at time of death—75 had an advance directive at the time of enrollment and another 31 completed an advance directive after enrollment.

Twenty-five patients (23.6%) specified DNR/DNI and another 39 (36.8%) denoted limitations on aggressiveness of care if death was imminent. Among the patients who died, 88 (53.7%) were hospitalized in the last month of their life and 50 (30.5%) died in the hospital. There was no difference in hospitalizations between those with an advance directive specifying limits and those who did not specify limits (OR 1.26, 95% CI 0.64-2.48). However, those with an advance directive specifying limits were less frequently mechanically ventilated (OR 0.26, 95% CI 0.06-0.88), and there was a trend toward them being less frequently admitted into the ICU (OR 0.45, 95% CI 0.16-1.29).

Bottom line: Less than half of community patients with heart failure had an advance directive, and many of these failed to address end-of-life decisions. Patients with an advance directive that specified limits in care were less likely to receive mechanical ventilation.

Citation: Dunlay SM, Swetz KM, Mueller PS, Roger VL. Advance directives in community patients with heart failure. Circ Cardiovasc Qual Outcomes. 2012;5:283-289.

Chlorhexidine Bathing Associated with Significant, Sustainable Reductions in Central-Venous-Catheter-Associated Bloodstream Infection

Clinical question: What is the impact, and sustainability, of chlorhexidine bathing on central-venous-catheter-associated bloodstream infections?

Background: Chlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. No prospective studies have evaluated the impact and sustainability of chlorhexidine bathing.

Study design: Prospective, three-phase study.

Setting: Medical-surgical ICUs and respiratory-care units at five New York hospitals.

Synopsis: In the pre-intervention phase (six to nine months, 1,808 admissions), patients were bathed with soap and water or nonmedicated bathing cloths. In the intervention phase (eight months, 1,832 admissions), patients were bathed with 2% chlorhexidine cloths. In the post-intervention phase (12 months, 2,834 admissions), chlorhexidine bathing was continued without oversight by researchers.

During the intervention phase, there were significantly fewer central-venous-catheter-associated bloodstream infections (2.6/1,000 catheter days vs. 6.4/1,000 pre-intervention). The reductions in bloodstream infections were sustained during the post-intervention period (2.9/1,000 catheter days). Compliance with chlorhexidine bathing was 82% and 88% during the intervention and post-intervention phases, and was well tolerated by the patients.

Limitations of this study include lack of patient-specific data and severity of illness data, as well as lack of randomization and blinding. Although not evaluated in this study, the savings associated with decreased bloodstream infections likely outweigh the cost of chlorhexidine bathing.

Bottom line: Chlorhexidine bathing is a well-tolerated, sustainable intervention that significantly reduces central-venous-catheter-associated bloodstream infections.

Citation: Montecalvo MA, McKenna D, Yarrish R, et al. Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability. Am J Med. 2012;125(5):505-511.

Simulation Training Improves Lumbar Puncture Skills

Clinical question: What effect does simulation have on lumbar puncture (LP) skills of PGY1 internal-medicine (IM) residents compared with PGY2-4 neurology residents who have not received simulation training?

Background: LPs are common procedures. The American College of General Medical Education does not define competency; neither do the internal-medicine (IM) or neurology board certifications. Simulation can improve skills in many areas but has not been well studied in LPs.

Study design: Pre-test-post-test.

Setting: Northwestern University’s Feinberg School of Medicine in Chicago.

Synopsis: The intervention group included 58 PGY1 IM residents, while the control group was 49 PGY2-to-PGY4 neurology residents. The pre-test consisted of a 21-point checklist. IM residents watched a three-hour video, performed LPs on simulators, and received feedback. The post-test was a clinical skills examination using the checklist. If this exam was failed, the participant practiced and was retested. Neurology residents completed the pre-test and demonstrated an LP using the simulator.

Pre-test passing was achieved by only 2% of IM residents and 6% of neurology residents. Post-test passing was achieved by 95% of the IM residents on the first trial and 100% of IM residents after an hour of additional training. IM mean scores increased to 95.7% from 46.3%, while the mean score of neurology residents was 65.4%.

This study is limited by its single-center nature, as education is variable from center to center. The study evaluated the proficiency on simulators only, and it did not evaluate the proficiency of the participants on patients.

Bottom line: Simulation training improves lumbar puncture skills.

Citation: Barsuk JH, Cohen ER, Caprio T, McGaghie WC, Simuni T, Wayne DB. Simulation-based education with mastery learning improves residents’ lumbar puncture skills. Neurology. 2012;79(2):132-137.

Primary-Care Physicians Do Not Use Publicly Reported Data When Referring Patients to Hospitals

Clinical question: When referring patients with pneumonia to the hospital, what factors do primary-care physicians (PCPs) consider?

Background: Publicly reported data are widely available. Pneumonia has publicly reported quality measures and is a common reason for hospitalization. Fewer PCPs are attending in the hospital due to the hospitalist movement; therefore, PCPs refer patients to a hospital when the need arises.

Study design: Online survey.

Setting: PCPs within 10 miles of Springfield, Mass.

Synopsis: A total of 92 PCPs responded to the survey, which included presentation of a case regarding a patient with pneumonia. PCPs were asked the importance of multiple factors leading to their decision to refer to a hospital. Familiarity with the hospital (70%), patient preference (62%), and admitting arrangements with a hospitalist group (62%) were considered to be very important to the PCPs that responded to the survey. Publicly reported data were very important to only 18% of respondents, and zero reported using publicly reported data when referring patients.

Importance of specific quality measures also was queried; antibiotics given within six hours of arrival (66%), appropriate choice of antibiotics (63%), and blood cultures prior to antibiotic administration (51%) were very important to respondents. Prestige, such as magnet status and U.S. News and World Report “Best Hospital” status, were deemed important by about 40% of PCPs.

Bottom line: Despite the availability of publicly reported data, PCPs do not use this information to refer patients to the hospital.

Citation: Morsi E, Lindenauer PK, Rothberg MB. Primary care physicians’ use of publicly reported quality data in hospital referral decisions. J Hosp Med. 2012;7(5):370-375.

What Works for Medication Reconciliation?

Clinical question: What are the most effective practices for medication reconciliation in the hospital setting?

Background: Medication discrepancies are common, occurring in as many as 70% of patients at hospital admission or discharge. Up to a third of these discrepancies have potential to cause patient harm, including prolonged hospital stays, ED visits, hospital recidivism, and use of other healthcare resources. Medication reconciliation (“med rec”) is a strategy for reducing these errors, though previous literature has not systematically reviewed best practices for hospital-based med rec.

Study design: Systematic review of literature.

Setting: Controlled studies from the U.S., Canada, Australia, New Zealand, Northern Ireland, United Kingdom, Belgium, Denmark, the Netherlands, and Sweden.

Synopsis: Investigators identified 26 controlled studies using a systematic search of English-language articles on med rec during inpatient hospitalizations published between Jan. 1, 1966, and Oct. 31, 2010. Fifteen studies reported on pharmacist-related interventions; six reported on technology-specific interventions; and five reported on other types of interventions, including staff education and use of standardized med-rec tools.

Analysis of these studies revealed that all of these interventions successfully decreased medication discrepancies and potential adverse drug events, but there was inconsistent benefit with regard to adverse drug events and healthcare utilization compared with usual care. The literature was most supportive of pharmacist-related interventions, including but not limited to comprehensive medication history at admission, med rec at discharge, patient counseling, discharge communication with outpatient providers, and post-discharge communication with the patient and post-hospital providers.

Bottom line: Successful med rec requires multiple interventions at various transitions of care and involves a variety of medical professionals. Patient-targeted interventions, including pharmacists, have the potential to decrease errors and adverse events.

Citation: Mueller S, Sponsler K, Kripalani S, Schnipper J. Hospital-based medication reconciliation practices: a systematic review. Arch Intern Med. 2012;172(14):1057-1069.

In This Edition

Literature at a Glance

A guide to this month’s studies

• PE and COPD exacerbations.
• Care bundles and readmission rates.
• Family history and VTE risk.
• Vasopressor choice and mortality in sepsis.
• Vitamin K use in overanticoagulation.
• Appropriate treatment of asymptomatic bacteriuria.
• Guideline adherence in thrombocytopenia.

Pulmonary Embolism Frequently Complicates COPD Exacerbations

Clinical question: What percentage of patients with acute chronic obstructive pulmonary disease (COPD) exacerbations has pulmonary emboli?

Background: As many as 30% of COPD exacerbations have no apparent precipitating event. Even in patients with evidence of a precipitating event, such as an upper-respiratory illness or increased environmental irritants, pulmonary emboli (PE) may coexist and warrant evaluation.

Study design: Literature review.

Setting: Multiple studies in Europe and the U.S.

Synopsis: This literature review included five studies to estimate the rate of PE in patients with a COPD exacerbation. Overall incidence of PE in COPD exacerbations was 19.9%, but of those patients requiring hospitalization, the incidence was as high as 25.5%. Incidence estimates varied based on interpretation of data that were missing or inconsistent between studies. Patients most commonly present with dyspnea, chest pain, hemoptysis, cough, and palpitations. Six percent of PE patients presented with syncope; no patients with an exacerbation without a PE presented with syncope.

Risk of mortality from PE is almost twice as high in patients with a COPD exacerbation compared with PE in other settings. A significant number of patients have PE without history or evidence of DVT, so in situ thrombosis is a significant factor. The interpretation of these results is limited by the heterogeneity of the study designs, and by the relatively low number of cases. Larger trials are necessary.

Bottom line: Pulmonary emboli are present in as many as 25% of all COPD exacerbations. Delay in diagnosis of PE in COPD patients affects morbidity and mortality. PE should be a consideration in many COPD exacerbations.

Citation: Rizkallah J, Man SF, Din DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793.

Targeted-Care Bundle Can Reduce ED Visits and Readmission Rates in High-Risk Elderly Patients

Clinical question: Can a care coordination bundle reduce length of stay (LOS), ED visits, or readmissions within 30 days of a hospital admission?

Background: Hospital-based care coordination interventions have shown mixed results in affecting LOS, post-discharge ED visits, and readmission rates. Although there has been some success with particular interventions, no consistent benefit has been demonstrated. Most notably, a recent meta-analysis of several different interventions showed no improvement in mortality, LOS, or readmission rates.

Study design: A randomized, controlled trial of select high-risk elderly patients.

Setting: A large teaching hospital at Baylor University Medical Center.

Synopsis: A “targeted-care bundle” was implemented with high-risk elderly patients to try to reduce LOS, readmissions, and ED visits. High-risk patients were identified by age, diagnosis-related group (DRG), number of medications at admission, comorbid conditions, and need for assistance in activities of daily living. Subjects were randomized to usual care or to receive a targeted-care bundle. The targeted-care bundle included multiple interventions. A study care coordinator provided daily patient education, including condition-specific teaching, discharge teaching and planning, and a follow-up phone call at five to seven days after discharge. A clinical pharmacist intervened for medication reconciliation at admission and discharge, medication teaching, and a follow-up phone call at five to seven days after discharge. Structured documents, including a personal health record and supplemental discharge form, were implemented.

The study had low enrollment, largely due to the requirement to obtain informed consent from all participants. Therefore, the study was underpowered to detect such target endpoints as LOS. A significant decrease in 30-day readmission rates/ED visits was noticed, but there was no persistent effect at 60 days.

The intervention was designed to use existing hospital staff in order to be practical for broad utilization. Future studies need to focus on increased enrollment to demonstrate beneficial effect.

Bottom line: Targeted health interventions focusing on education and coordination of care might effect some significant outcomes, most notably readmissions or ED visits within 30 days, but the nature of the clinical problem makes rigorous testing of interventions a challenge.

Citation: Kohler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.

Family History Is a Risk Factor for Venous Thrombosis

Clinical question: Is family history of additional value in predicting an individual’s risk of venous thrombosis once a genetic risk factor is identified?

Background: A positive family history of venous thrombosis might suggest the presence of genetic risk factors in a given family. However, it is not known whether family history is of additional significance—once a risk factor is identified—in predicting an individual’s risk for venous thrombosis.

Study design: Population-based, case-control study.

Setting: Participants in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study.

Synopsis: Recruitment, data collection, and blood samples were obtained from individuals in the MEGA study. Participants completed a questionnaire about risk factors for venous thrombosis and family history. A positive family history more than doubled the risk of venous thrombosis, and when more than one family member was affected, the risk increased fourfold. The risk for venous thrombosis increased 64 times for individuals who had a family history, genetic risk factor, and environmental risk factor when compared with those with a negative family history and no known risk factors.

The underreporting or overestimation of the prevalence of a positive family history might limit this study.

Bottom line: Family history is a risk indictor for a first venous thrombosis, despite the presence of other risk factors.

Citation: Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med. 2009;169(6):610-615.

Vasopressor Choice Predicts Mortality in Septic Shock

Clinical question: Does vasopressor choice affect mortality in patients with community-acquired septic shock?

Background: Community-acquired septic shock is a common illness and, despite aggressive care, a leading cause of death. Randomized clinical control trials evaluating the efficacy and safety of different adrenergic supportive agents are lacking. Thus, both norepinephrine and dopamine are recommended as first-line agents in the treatment of septic shock by the Surviving Sepsis Campaign guidelines.

Study design: Multicenter, cohort observational study.

Setting: Seventeen intensive-care units in Portugal.

Synopsis: In adjusted analysis controlling for Simplified Acute Physiology Score (SAPS) II, use of norepinephrine in community-acquired septic shock was associated with higher hospital mortality and lower 28-day survival when compared with dopamine. Specifically, patients treated with norepinephrine had a statistically significant higher hospital mortality rate than those treated with dopamine (52% and 38.5%, respectively, P=0.002) and a lower 28-day survival (log rank=22.6; P<0.001). While this data is valuable, the nonrandomized, observational study design limits firm conclusions regarding vasopressor choice. Further results from three large trials comparing vasopressor use in septic shock should continue to shed light on this debate.

Bottom line: Norepinephrine administration is associated with higher hospital mortality and lower 28-day survival when compared with dopamine in patients with community-acquired septic shock.

Citation: Póvoa PR, Carneiro AH, Ribeiro OS, Pereira AC, Portuguese Community-Acquired Sepsis Study Group. Influence of vasopressor agent in septic shock mortality. Results from the Portuguese Community-Acquired Sepsis Study (SACiUCI study). Crit Care Med. 2009;37(2):410-416.

Oral Vitamin K Versus Placebo to Correct Excess Anticoagulation in Warfarin Patients

Clinical question: In nonbleeding patients with warfarin-associated coagulopathy, does oral vitamin K reduce bleeding events when compared to placebo?

Background: Warfarin is a common drug for primary and secondary prevention of thromboembolism, but it requires continued monitoring of the international normalized ratio (INR) value. INR values >4.0 are associated with an increase in bleeding complications, with specific concern for intracranial bleeding when INR values exceed 4.5. Small, randomized trials have shown that single, low-dose administration of oral vitamin K effectively reduces the INR in nonbleeding, overanticoagulated patients.

However, these studies have not shown if vitamin K reduces risk for bleeding without increasing the risk for thromboembolism.

Study design: Randomized, placebo-controlled trial.

Setting: Fourteen anticoagulation clinics in Canada, Italy, and the U.S.

Synopsis: Nonbleeding patients with supratherapeutic INR values between 4.5 and 10.0 were randomly assigned to receive 1.25 mg of oral vitamin K or placebo, then evaluated for all forms of bleeding for 90 days. Bleeding events were defined as “major bleeding,” “minor bleeding,” and “trivial bleeding.”

Though patients who received oral vitamin K had a significantly more rapid INR decrease, there were no differences between the two groups with regard to all bleeding events, thromboembolism, or death. The study was underpowered to detect differences in major bleeding.

Bottom line: Low-dose oral vitamin K leads to more rapid correction of the INR in overanticoagulated patients on warfarin therapy, but has little effect on clinical outcomes at 90 days.

Citation: Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150(5):293-300.

Inappropriate Treatment of Catheter-Associated Asymptomatic Bacteriuria

Clinical question: Are hospitalized patients with urinary catheters inappropriately treated with antibiotics for asymptomatic bacteriuria?

Background: Persons with catheters acquire bacteriuria at the rate of 3% to 10% per day, but in the majority of cases, no symptoms or secondary complications occur. Evidenced-based guidelines state that asymptomatic bacteriuria is not a clinically significant infection, and numerous studies have shown that treatment is unlikely to confer clinical benefit.

Study design: Retrospective cohort study.

Setting: A single-site Veterans Affairs hospital.

Synopsis: Using urine culture results over a three-month period from a single VA medical center, 280 cases were analyzed: 164 catheter-associated asymptomatic bacteriuria and 116 catheter-associated urinary tract infections (UTIs). A UTI was defined as having one or more of these symptoms: fever, urgency, frequency, dysuria, suprapubic tenderness, altered mental status, or hypotension in a patient without another recognized infection and a positive urine culture. Of the asymptomatic bacteriuria cases, 68% were managed appropriately with no antibiotic treatment; 32% were inappropriately treated with antibiotics.

In multivariate analysis, older patient age, predominance of gram-negative bacteria, and higher urine white blood cell count were significantly associated with inappropriate treatment.

This study highlights the fact that antibiotics continue to be used inappropriately in patients with catheters. Current guidelines do not distinguish well between asymptomatic bacteriuria and UTI, so there might be a knowledge gap. This study was based on urine culture data, not urinalysis of all patients with a catheter, so the symptomatic patients were likely over-represented.

An associated editorial observes that the study extrapolates data from studies that involved patients with uncomplicated UTIs and, therefore, might reach erroneous conclusions. Further, viewing catheter-associated symptomatic UTIs and catheter-associated asymptomatic bactiuria as dichotomous and warranting inherently different management fails to encompass a number of clinical factors, including co-infection, and further fails to acknowledge that removal of the catheter is the first step in treatment. However, the finding that antibiotics continue to be used inappropriately is useful.

Bottom line: A clinical determination of whether a patient with a catheter really has a symptomatic UTI/urosepsis or only has asymptomatic bacteriuria should precede starting antibiotics in hospitalized patients.

Citations: Cope M, Cevallos ME, Cadle RM, Darouiche RO, Musher DM, Trautner BW. Inappropriate treatment of catheter-associated asymptomatic bateriuria in a tertiary care hospital. Clin Infect Dis. 2009;48(9):1182-1188.

Kunin CM. Catheter-associated urinary tract infections: a syllogism compounded by a questionable dichotomy. Clin Infect Dis. 2009;48:1189-1190.

Current Practices in the Evaluation and Management of Thrombocytopenia in Heparin Patients

Clinical question: Are the current American College of Chest Physicians (ACCP) guidelines for the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) being followed?

Background: Heparin-based anticoagulation is frequently given to hospitalized patients, and approximately 1% to 5% of these patients develop HIT. In 2004, the ACCP published a consensus statement on the evaluation, management, and prevention of HIT.

Study design: Prospective, observational study.

Setting: Forty-eight U.S. hospitals in the Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

Synopsis: The CATCH trial enrolled patients receiving any form of heparin for >96 hours (n=2,420), cardiac-care-unit patients treated with heparin (n=1,090), and patients who had an HIT antibody assay performed (n=449), for a total of 3,536 total patients. The study included patients on unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Thrombocytopenia was defined at a platelet count <150,000, or a decrease of 50% when compared with admission.

In the prolonged heparin group, 36.4% of patients developed thrombocytopenia; however, HIT was suspected in only 19.8% of these high-risk patients. While physicians were more likely to consider HIT in the cardiac-care patients (37.6%), the diagnosis was considered>24 hours after the thrombocytopenia developed. Physicians often waited until after a thromboembolic complication occurred before evaluating for HIT. More often than not, preventive measures were missed (e.g., failing to check for HIT antibodies, continuing heparin after HIT was suspected).

Bottom line: Thrombocytopenia is a common occurrence in patients receiving heparin and, despite the risk of devastating complications from HIT, treatment infrequently conforms to the established guidelines.

Citation: Crespo EM, Oliveira GBF, Honeycutt EF, et al. Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry. Am Heart J. 2009;157(4):651-657. TH

PEDIATRIC HM LITerature

Epinephrine and Dexamethasone Alone Do Not Reduce Hospital Admissions in Infants with Bronchiolitis

By Mark Shen, MD

Clinical question: Does nebulized epinephrine, oral dexamethasone, or a combination of the two result in a decrease in hospital admissions when given in the ED to infants with bronchiolitis?

Background: Bronchiolitis is the most common lower-respiratory-tract infection of infancy. Rates of admission have climbed in the past two decades. Bronchodilators and corticosteroids are not routinely recommended, and the evidence surrounding epinephrine and dexamethasone has shown varying results.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Eight Canadian pediatric EDs.

Synopsis: Eight hundred infants ages six weeks to 12 months with a first episode of bronchiolitis were randomized to nebulized epinephrine and oral dexamethasone, epinephrine and oral placebo, dexamethasone and nebulized placebo, or oral and nebulized placebo. Epinephrine was delivered as two nebulizations 30 minutes apart, and dexamethasone was given as a 1 mg/kg oral dose, followed by five once-daily doses of 0.6 mg/kg. In unadjusted analysis, only the infants who received epinephrine and dexamethasone were less likely to be admitted to the hospital by day seven.

Limitations of this study include a small effect size and a non-statistically-significant difference between the epinephrine/dexamethasone group and placebo after statistical adjustment for multiple comparisons. Given that admission rates did not decrease in the epinephrine/placebo group and the dexamethasone/placebo group, this study supports national guidelines that do not recommend the routine use of these agents in bronchiolitis. The authors suggest that synergy between epinephrine and dexamethasone in bronchiolitis be further studied.

Bottom line: When given alone, epinephrine and dexamethasone do not reduce hospital admissions in infants with bronchiolitis.

Citation: Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360(20):2079-2089.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

In This Edition

Literature at a Glance

A guide to this month’s studies

• PE and COPD exacerbations.
• Care bundles and readmission rates.
• Family history and VTE risk.
• Vasopressor choice and mortality in sepsis.
• Vitamin K use in overanticoagulation.
• Appropriate treatment of asymptomatic bacteriuria.
• Guideline adherence in thrombocytopenia.

Pulmonary Embolism Frequently Complicates COPD Exacerbations

Clinical question: What percentage of patients with acute chronic obstructive pulmonary disease (COPD) exacerbations has pulmonary emboli?

Background: As many as 30% of COPD exacerbations have no apparent precipitating event. Even in patients with evidence of a precipitating event, such as an upper-respiratory illness or increased environmental irritants, pulmonary emboli (PE) may coexist and warrant evaluation.

Study design: Literature review.

Setting: Multiple studies in Europe and the U.S.

Synopsis: This literature review included five studies to estimate the rate of PE in patients with a COPD exacerbation. Overall incidence of PE in COPD exacerbations was 19.9%, but of those patients requiring hospitalization, the incidence was as high as 25.5%. Incidence estimates varied based on interpretation of data that were missing or inconsistent between studies. Patients most commonly present with dyspnea, chest pain, hemoptysis, cough, and palpitations. Six percent of PE patients presented with syncope; no patients with an exacerbation without a PE presented with syncope.

Risk of mortality from PE is almost twice as high in patients with a COPD exacerbation compared with PE in other settings. A significant number of patients have PE without history or evidence of DVT, so in situ thrombosis is a significant factor. The interpretation of these results is limited by the heterogeneity of the study designs, and by the relatively low number of cases. Larger trials are necessary.

Bottom line: Pulmonary emboli are present in as many as 25% of all COPD exacerbations. Delay in diagnosis of PE in COPD patients affects morbidity and mortality. PE should be a consideration in many COPD exacerbations.

Citation: Rizkallah J, Man SF, Din DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793.

Targeted-Care Bundle Can Reduce ED Visits and Readmission Rates in High-Risk Elderly Patients

Clinical question: Can a care coordination bundle reduce length of stay (LOS), ED visits, or readmissions within 30 days of a hospital admission?

Background: Hospital-based care coordination interventions have shown mixed results in affecting LOS, post-discharge ED visits, and readmission rates. Although there has been some success with particular interventions, no consistent benefit has been demonstrated. Most notably, a recent meta-analysis of several different interventions showed no improvement in mortality, LOS, or readmission rates.

Study design: A randomized, controlled trial of select high-risk elderly patients.

Setting: A large teaching hospital at Baylor University Medical Center.

Synopsis: A “targeted-care bundle” was implemented with high-risk elderly patients to try to reduce LOS, readmissions, and ED visits. High-risk patients were identified by age, diagnosis-related group (DRG), number of medications at admission, comorbid conditions, and need for assistance in activities of daily living. Subjects were randomized to usual care or to receive a targeted-care bundle. The targeted-care bundle included multiple interventions. A study care coordinator provided daily patient education, including condition-specific teaching, discharge teaching and planning, and a follow-up phone call at five to seven days after discharge. A clinical pharmacist intervened for medication reconciliation at admission and discharge, medication teaching, and a follow-up phone call at five to seven days after discharge. Structured documents, including a personal health record and supplemental discharge form, were implemented.

The study had low enrollment, largely due to the requirement to obtain informed consent from all participants. Therefore, the study was underpowered to detect such target endpoints as LOS. A significant decrease in 30-day readmission rates/ED visits was noticed, but there was no persistent effect at 60 days.

The intervention was designed to use existing hospital staff in order to be practical for broad utilization. Future studies need to focus on increased enrollment to demonstrate beneficial effect.

Bottom line: Targeted health interventions focusing on education and coordination of care might effect some significant outcomes, most notably readmissions or ED visits within 30 days, but the nature of the clinical problem makes rigorous testing of interventions a challenge.

Citation: Kohler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.

Family History Is a Risk Factor for Venous Thrombosis

Clinical question: Is family history of additional value in predicting an individual’s risk of venous thrombosis once a genetic risk factor is identified?

Background: A positive family history of venous thrombosis might suggest the presence of genetic risk factors in a given family. However, it is not known whether family history is of additional significance—once a risk factor is identified—in predicting an individual’s risk for venous thrombosis.

Study design: Population-based, case-control study.

Setting: Participants in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study.

Synopsis: Recruitment, data collection, and blood samples were obtained from individuals in the MEGA study. Participants completed a questionnaire about risk factors for venous thrombosis and family history. A positive family history more than doubled the risk of venous thrombosis, and when more than one family member was affected, the risk increased fourfold. The risk for venous thrombosis increased 64 times for individuals who had a family history, genetic risk factor, and environmental risk factor when compared with those with a negative family history and no known risk factors.

The underreporting or overestimation of the prevalence of a positive family history might limit this study.

Bottom line: Family history is a risk indictor for a first venous thrombosis, despite the presence of other risk factors.

Citation: Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med. 2009;169(6):610-615.

Vasopressor Choice Predicts Mortality in Septic Shock

Clinical question: Does vasopressor choice affect mortality in patients with community-acquired septic shock?

Background: Community-acquired septic shock is a common illness and, despite aggressive care, a leading cause of death. Randomized clinical control trials evaluating the efficacy and safety of different adrenergic supportive agents are lacking. Thus, both norepinephrine and dopamine are recommended as first-line agents in the treatment of septic shock by the Surviving Sepsis Campaign guidelines.

Study design: Multicenter, cohort observational study.

Setting: Seventeen intensive-care units in Portugal.

Synopsis: In adjusted analysis controlling for Simplified Acute Physiology Score (SAPS) II, use of norepinephrine in community-acquired septic shock was associated with higher hospital mortality and lower 28-day survival when compared with dopamine. Specifically, patients treated with norepinephrine had a statistically significant higher hospital mortality rate than those treated with dopamine (52% and 38.5%, respectively, P=0.002) and a lower 28-day survival (log rank=22.6; P<0.001). While this data is valuable, the nonrandomized, observational study design limits firm conclusions regarding vasopressor choice. Further results from three large trials comparing vasopressor use in septic shock should continue to shed light on this debate.

Bottom line: Norepinephrine administration is associated with higher hospital mortality and lower 28-day survival when compared with dopamine in patients with community-acquired septic shock.

Citation: Póvoa PR, Carneiro AH, Ribeiro OS, Pereira AC, Portuguese Community-Acquired Sepsis Study Group. Influence of vasopressor agent in septic shock mortality. Results from the Portuguese Community-Acquired Sepsis Study (SACiUCI study). Crit Care Med. 2009;37(2):410-416.

Oral Vitamin K Versus Placebo to Correct Excess Anticoagulation in Warfarin Patients

Clinical question: In nonbleeding patients with warfarin-associated coagulopathy, does oral vitamin K reduce bleeding events when compared to placebo?

Background: Warfarin is a common drug for primary and secondary prevention of thromboembolism, but it requires continued monitoring of the international normalized ratio (INR) value. INR values >4.0 are associated with an increase in bleeding complications, with specific concern for intracranial bleeding when INR values exceed 4.5. Small, randomized trials have shown that single, low-dose administration of oral vitamin K effectively reduces the INR in nonbleeding, overanticoagulated patients.

However, these studies have not shown if vitamin K reduces risk for bleeding without increasing the risk for thromboembolism.

Study design: Randomized, placebo-controlled trial.

Setting: Fourteen anticoagulation clinics in Canada, Italy, and the U.S.

Synopsis: Nonbleeding patients with supratherapeutic INR values between 4.5 and 10.0 were randomly assigned to receive 1.25 mg of oral vitamin K or placebo, then evaluated for all forms of bleeding for 90 days. Bleeding events were defined as “major bleeding,” “minor bleeding,” and “trivial bleeding.”

Though patients who received oral vitamin K had a significantly more rapid INR decrease, there were no differences between the two groups with regard to all bleeding events, thromboembolism, or death. The study was underpowered to detect differences in major bleeding.

Bottom line: Low-dose oral vitamin K leads to more rapid correction of the INR in overanticoagulated patients on warfarin therapy, but has little effect on clinical outcomes at 90 days.

Citation: Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150(5):293-300.

Inappropriate Treatment of Catheter-Associated Asymptomatic Bacteriuria

Clinical question: Are hospitalized patients with urinary catheters inappropriately treated with antibiotics for asymptomatic bacteriuria?

Background: Persons with catheters acquire bacteriuria at the rate of 3% to 10% per day, but in the majority of cases, no symptoms or secondary complications occur. Evidenced-based guidelines state that asymptomatic bacteriuria is not a clinically significant infection, and numerous studies have shown that treatment is unlikely to confer clinical benefit.

Study design: Retrospective cohort study.

Setting: A single-site Veterans Affairs hospital.

Synopsis: Using urine culture results over a three-month period from a single VA medical center, 280 cases were analyzed: 164 catheter-associated asymptomatic bacteriuria and 116 catheter-associated urinary tract infections (UTIs). A UTI was defined as having one or more of these symptoms: fever, urgency, frequency, dysuria, suprapubic tenderness, altered mental status, or hypotension in a patient without another recognized infection and a positive urine culture. Of the asymptomatic bacteriuria cases, 68% were managed appropriately with no antibiotic treatment; 32% were inappropriately treated with antibiotics.

In multivariate analysis, older patient age, predominance of gram-negative bacteria, and higher urine white blood cell count were significantly associated with inappropriate treatment.

This study highlights the fact that antibiotics continue to be used inappropriately in patients with catheters. Current guidelines do not distinguish well between asymptomatic bacteriuria and UTI, so there might be a knowledge gap. This study was based on urine culture data, not urinalysis of all patients with a catheter, so the symptomatic patients were likely over-represented.

An associated editorial observes that the study extrapolates data from studies that involved patients with uncomplicated UTIs and, therefore, might reach erroneous conclusions. Further, viewing catheter-associated symptomatic UTIs and catheter-associated asymptomatic bactiuria as dichotomous and warranting inherently different management fails to encompass a number of clinical factors, including co-infection, and further fails to acknowledge that removal of the catheter is the first step in treatment. However, the finding that antibiotics continue to be used inappropriately is useful.

Bottom line: A clinical determination of whether a patient with a catheter really has a symptomatic UTI/urosepsis or only has asymptomatic bacteriuria should precede starting antibiotics in hospitalized patients.

Citations: Cope M, Cevallos ME, Cadle RM, Darouiche RO, Musher DM, Trautner BW. Inappropriate treatment of catheter-associated asymptomatic bateriuria in a tertiary care hospital. Clin Infect Dis. 2009;48(9):1182-1188.

Kunin CM. Catheter-associated urinary tract infections: a syllogism compounded by a questionable dichotomy. Clin Infect Dis. 2009;48:1189-1190.

Current Practices in the Evaluation and Management of Thrombocytopenia in Heparin Patients

Clinical question: Are the current American College of Chest Physicians (ACCP) guidelines for the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) being followed?

Background: Heparin-based anticoagulation is frequently given to hospitalized patients, and approximately 1% to 5% of these patients develop HIT. In 2004, the ACCP published a consensus statement on the evaluation, management, and prevention of HIT.

Study design: Prospective, observational study.

Setting: Forty-eight U.S. hospitals in the Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

Synopsis: The CATCH trial enrolled patients receiving any form of heparin for >96 hours (n=2,420), cardiac-care-unit patients treated with heparin (n=1,090), and patients who had an HIT antibody assay performed (n=449), for a total of 3,536 total patients. The study included patients on unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Thrombocytopenia was defined at a platelet count <150,000, or a decrease of 50% when compared with admission.

In the prolonged heparin group, 36.4% of patients developed thrombocytopenia; however, HIT was suspected in only 19.8% of these high-risk patients. While physicians were more likely to consider HIT in the cardiac-care patients (37.6%), the diagnosis was considered>24 hours after the thrombocytopenia developed. Physicians often waited until after a thromboembolic complication occurred before evaluating for HIT. More often than not, preventive measures were missed (e.g., failing to check for HIT antibodies, continuing heparin after HIT was suspected).

Bottom line: Thrombocytopenia is a common occurrence in patients receiving heparin and, despite the risk of devastating complications from HIT, treatment infrequently conforms to the established guidelines.

Citation: Crespo EM, Oliveira GBF, Honeycutt EF, et al. Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry. Am Heart J. 2009;157(4):651-657. TH

PEDIATRIC HM LITerature

Epinephrine and Dexamethasone Alone Do Not Reduce Hospital Admissions in Infants with Bronchiolitis

By Mark Shen, MD

Clinical question: Does nebulized epinephrine, oral dexamethasone, or a combination of the two result in a decrease in hospital admissions when given in the ED to infants with bronchiolitis?

Background: Bronchiolitis is the most common lower-respiratory-tract infection of infancy. Rates of admission have climbed in the past two decades. Bronchodilators and corticosteroids are not routinely recommended, and the evidence surrounding epinephrine and dexamethasone has shown varying results.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Eight Canadian pediatric EDs.

Synopsis: Eight hundred infants ages six weeks to 12 months with a first episode of bronchiolitis were randomized to nebulized epinephrine and oral dexamethasone, epinephrine and oral placebo, dexamethasone and nebulized placebo, or oral and nebulized placebo. Epinephrine was delivered as two nebulizations 30 minutes apart, and dexamethasone was given as a 1 mg/kg oral dose, followed by five once-daily doses of 0.6 mg/kg. In unadjusted analysis, only the infants who received epinephrine and dexamethasone were less likely to be admitted to the hospital by day seven.

Limitations of this study include a small effect size and a non-statistically-significant difference between the epinephrine/dexamethasone group and placebo after statistical adjustment for multiple comparisons. Given that admission rates did not decrease in the epinephrine/placebo group and the dexamethasone/placebo group, this study supports national guidelines that do not recommend the routine use of these agents in bronchiolitis. The authors suggest that synergy between epinephrine and dexamethasone in bronchiolitis be further studied.

Bottom line: When given alone, epinephrine and dexamethasone do not reduce hospital admissions in infants with bronchiolitis.

Citation: Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360(20):2079-2089.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

In This Edition

Literature at a Glance

A guide to this month’s studies

• PE and COPD exacerbations.
• Care bundles and readmission rates.
• Family history and VTE risk.
• Vasopressor choice and mortality in sepsis.
• Vitamin K use in overanticoagulation.
• Appropriate treatment of asymptomatic bacteriuria.
• Guideline adherence in thrombocytopenia.

Pulmonary Embolism Frequently Complicates COPD Exacerbations

Clinical question: What percentage of patients with acute chronic obstructive pulmonary disease (COPD) exacerbations has pulmonary emboli?

Background: As many as 30% of COPD exacerbations have no apparent precipitating event. Even in patients with evidence of a precipitating event, such as an upper-respiratory illness or increased environmental irritants, pulmonary emboli (PE) may coexist and warrant evaluation.

Study design: Literature review.

Setting: Multiple studies in Europe and the U.S.

Synopsis: This literature review included five studies to estimate the rate of PE in patients with a COPD exacerbation. Overall incidence of PE in COPD exacerbations was 19.9%, but of those patients requiring hospitalization, the incidence was as high as 25.5%. Incidence estimates varied based on interpretation of data that were missing or inconsistent between studies. Patients most commonly present with dyspnea, chest pain, hemoptysis, cough, and palpitations. Six percent of PE patients presented with syncope; no patients with an exacerbation without a PE presented with syncope.

Risk of mortality from PE is almost twice as high in patients with a COPD exacerbation compared with PE in other settings. A significant number of patients have PE without history or evidence of DVT, so in situ thrombosis is a significant factor. The interpretation of these results is limited by the heterogeneity of the study designs, and by the relatively low number of cases. Larger trials are necessary.

Bottom line: Pulmonary emboli are present in as many as 25% of all COPD exacerbations. Delay in diagnosis of PE in COPD patients affects morbidity and mortality. PE should be a consideration in many COPD exacerbations.

Citation: Rizkallah J, Man SF, Din DD. Prevalence of pulmonary embolism in acute exacerbations of COPD: a systematic review and metaanalysis. Chest. 2009;135(3):786-793.

Targeted-Care Bundle Can Reduce ED Visits and Readmission Rates in High-Risk Elderly Patients

Clinical question: Can a care coordination bundle reduce length of stay (LOS), ED visits, or readmissions within 30 days of a hospital admission?

Background: Hospital-based care coordination interventions have shown mixed results in affecting LOS, post-discharge ED visits, and readmission rates. Although there has been some success with particular interventions, no consistent benefit has been demonstrated. Most notably, a recent meta-analysis of several different interventions showed no improvement in mortality, LOS, or readmission rates.

Study design: A randomized, controlled trial of select high-risk elderly patients.

Setting: A large teaching hospital at Baylor University Medical Center.

Synopsis: A “targeted-care bundle” was implemented with high-risk elderly patients to try to reduce LOS, readmissions, and ED visits. High-risk patients were identified by age, diagnosis-related group (DRG), number of medications at admission, comorbid conditions, and need for assistance in activities of daily living. Subjects were randomized to usual care or to receive a targeted-care bundle. The targeted-care bundle included multiple interventions. A study care coordinator provided daily patient education, including condition-specific teaching, discharge teaching and planning, and a follow-up phone call at five to seven days after discharge. A clinical pharmacist intervened for medication reconciliation at admission and discharge, medication teaching, and a follow-up phone call at five to seven days after discharge. Structured documents, including a personal health record and supplemental discharge form, were implemented.

The study had low enrollment, largely due to the requirement to obtain informed consent from all participants. Therefore, the study was underpowered to detect such target endpoints as LOS. A significant decrease in 30-day readmission rates/ED visits was noticed, but there was no persistent effect at 60 days.

The intervention was designed to use existing hospital staff in order to be practical for broad utilization. Future studies need to focus on increased enrollment to demonstrate beneficial effect.

Bottom line: Targeted health interventions focusing on education and coordination of care might effect some significant outcomes, most notably readmissions or ED visits within 30 days, but the nature of the clinical problem makes rigorous testing of interventions a challenge.

Citation: Kohler BE, Richter KM, Youngblood L, et al. Reduction of 30-day postdischarge hospital readmission or emergency department (ED) visit rates in high-risk elderly medical patients through delivery of a targeted care bundle. J Hosp Med. 2009;4(4):211-218.

Family History Is a Risk Factor for Venous Thrombosis

Clinical question: Is family history of additional value in predicting an individual’s risk of venous thrombosis once a genetic risk factor is identified?

Background: A positive family history of venous thrombosis might suggest the presence of genetic risk factors in a given family. However, it is not known whether family history is of additional significance—once a risk factor is identified—in predicting an individual’s risk for venous thrombosis.

Study design: Population-based, case-control study.

Setting: Participants in the Multiple Environmental and Genetic Assessment (MEGA) of risk factors for venous thrombosis study.

Synopsis: Recruitment, data collection, and blood samples were obtained from individuals in the MEGA study. Participants completed a questionnaire about risk factors for venous thrombosis and family history. A positive family history more than doubled the risk of venous thrombosis, and when more than one family member was affected, the risk increased fourfold. The risk for venous thrombosis increased 64 times for individuals who had a family history, genetic risk factor, and environmental risk factor when compared with those with a negative family history and no known risk factors.

The underreporting or overestimation of the prevalence of a positive family history might limit this study.

Bottom line: Family history is a risk indictor for a first venous thrombosis, despite the presence of other risk factors.

Citation: Bezemer ID, van der Meer FJ, Eikenboom JC, Rosendaal FR, Doggen CJ. The value of family history as a risk indicator for venous thrombosis. Arch Intern Med. 2009;169(6):610-615.

Vasopressor Choice Predicts Mortality in Septic Shock

Clinical question: Does vasopressor choice affect mortality in patients with community-acquired septic shock?

Background: Community-acquired septic shock is a common illness and, despite aggressive care, a leading cause of death. Randomized clinical control trials evaluating the efficacy and safety of different adrenergic supportive agents are lacking. Thus, both norepinephrine and dopamine are recommended as first-line agents in the treatment of septic shock by the Surviving Sepsis Campaign guidelines.

Study design: Multicenter, cohort observational study.

Setting: Seventeen intensive-care units in Portugal.

Synopsis: In adjusted analysis controlling for Simplified Acute Physiology Score (SAPS) II, use of norepinephrine in community-acquired septic shock was associated with higher hospital mortality and lower 28-day survival when compared with dopamine. Specifically, patients treated with norepinephrine had a statistically significant higher hospital mortality rate than those treated with dopamine (52% and 38.5%, respectively, P=0.002) and a lower 28-day survival (log rank=22.6; P<0.001). While this data is valuable, the nonrandomized, observational study design limits firm conclusions regarding vasopressor choice. Further results from three large trials comparing vasopressor use in septic shock should continue to shed light on this debate.

Bottom line: Norepinephrine administration is associated with higher hospital mortality and lower 28-day survival when compared with dopamine in patients with community-acquired septic shock.

Citation: Póvoa PR, Carneiro AH, Ribeiro OS, Pereira AC, Portuguese Community-Acquired Sepsis Study Group. Influence of vasopressor agent in septic shock mortality. Results from the Portuguese Community-Acquired Sepsis Study (SACiUCI study). Crit Care Med. 2009;37(2):410-416.

Oral Vitamin K Versus Placebo to Correct Excess Anticoagulation in Warfarin Patients

Clinical question: In nonbleeding patients with warfarin-associated coagulopathy, does oral vitamin K reduce bleeding events when compared to placebo?

Background: Warfarin is a common drug for primary and secondary prevention of thromboembolism, but it requires continued monitoring of the international normalized ratio (INR) value. INR values >4.0 are associated with an increase in bleeding complications, with specific concern for intracranial bleeding when INR values exceed 4.5. Small, randomized trials have shown that single, low-dose administration of oral vitamin K effectively reduces the INR in nonbleeding, overanticoagulated patients.

However, these studies have not shown if vitamin K reduces risk for bleeding without increasing the risk for thromboembolism.

Study design: Randomized, placebo-controlled trial.

Setting: Fourteen anticoagulation clinics in Canada, Italy, and the U.S.

Synopsis: Nonbleeding patients with supratherapeutic INR values between 4.5 and 10.0 were randomly assigned to receive 1.25 mg of oral vitamin K or placebo, then evaluated for all forms of bleeding for 90 days. Bleeding events were defined as “major bleeding,” “minor bleeding,” and “trivial bleeding.”

Though patients who received oral vitamin K had a significantly more rapid INR decrease, there were no differences between the two groups with regard to all bleeding events, thromboembolism, or death. The study was underpowered to detect differences in major bleeding.

Bottom line: Low-dose oral vitamin K leads to more rapid correction of the INR in overanticoagulated patients on warfarin therapy, but has little effect on clinical outcomes at 90 days.

Citation: Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med. 2009;150(5):293-300.

Inappropriate Treatment of Catheter-Associated Asymptomatic Bacteriuria

Clinical question: Are hospitalized patients with urinary catheters inappropriately treated with antibiotics for asymptomatic bacteriuria?

Background: Persons with catheters acquire bacteriuria at the rate of 3% to 10% per day, but in the majority of cases, no symptoms or secondary complications occur. Evidenced-based guidelines state that asymptomatic bacteriuria is not a clinically significant infection, and numerous studies have shown that treatment is unlikely to confer clinical benefit.

Study design: Retrospective cohort study.

Setting: A single-site Veterans Affairs hospital.

Synopsis: Using urine culture results over a three-month period from a single VA medical center, 280 cases were analyzed: 164 catheter-associated asymptomatic bacteriuria and 116 catheter-associated urinary tract infections (UTIs). A UTI was defined as having one or more of these symptoms: fever, urgency, frequency, dysuria, suprapubic tenderness, altered mental status, or hypotension in a patient without another recognized infection and a positive urine culture. Of the asymptomatic bacteriuria cases, 68% were managed appropriately with no antibiotic treatment; 32% were inappropriately treated with antibiotics.

In multivariate analysis, older patient age, predominance of gram-negative bacteria, and higher urine white blood cell count were significantly associated with inappropriate treatment.

This study highlights the fact that antibiotics continue to be used inappropriately in patients with catheters. Current guidelines do not distinguish well between asymptomatic bacteriuria and UTI, so there might be a knowledge gap. This study was based on urine culture data, not urinalysis of all patients with a catheter, so the symptomatic patients were likely over-represented.

An associated editorial observes that the study extrapolates data from studies that involved patients with uncomplicated UTIs and, therefore, might reach erroneous conclusions. Further, viewing catheter-associated symptomatic UTIs and catheter-associated asymptomatic bactiuria as dichotomous and warranting inherently different management fails to encompass a number of clinical factors, including co-infection, and further fails to acknowledge that removal of the catheter is the first step in treatment. However, the finding that antibiotics continue to be used inappropriately is useful.

Bottom line: A clinical determination of whether a patient with a catheter really has a symptomatic UTI/urosepsis or only has asymptomatic bacteriuria should precede starting antibiotics in hospitalized patients.

Citations: Cope M, Cevallos ME, Cadle RM, Darouiche RO, Musher DM, Trautner BW. Inappropriate treatment of catheter-associated asymptomatic bateriuria in a tertiary care hospital. Clin Infect Dis. 2009;48(9):1182-1188.

Kunin CM. Catheter-associated urinary tract infections: a syllogism compounded by a questionable dichotomy. Clin Infect Dis. 2009;48:1189-1190.

Current Practices in the Evaluation and Management of Thrombocytopenia in Heparin Patients

Clinical question: Are the current American College of Chest Physicians (ACCP) guidelines for the recognition, treatment, and prevention of heparin-induced thrombocytopenia (HIT) being followed?

Background: Heparin-based anticoagulation is frequently given to hospitalized patients, and approximately 1% to 5% of these patients develop HIT. In 2004, the ACCP published a consensus statement on the evaluation, management, and prevention of HIT.

Study design: Prospective, observational study.

Setting: Forty-eight U.S. hospitals in the Complications After Thrombocytopenia Caused by Heparin (CATCH) registry.

Synopsis: The CATCH trial enrolled patients receiving any form of heparin for >96 hours (n=2,420), cardiac-care-unit patients treated with heparin (n=1,090), and patients who had an HIT antibody assay performed (n=449), for a total of 3,536 total patients. The study included patients on unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Thrombocytopenia was defined at a platelet count <150,000, or a decrease of 50% when compared with admission.

In the prolonged heparin group, 36.4% of patients developed thrombocytopenia; however, HIT was suspected in only 19.8% of these high-risk patients. While physicians were more likely to consider HIT in the cardiac-care patients (37.6%), the diagnosis was considered>24 hours after the thrombocytopenia developed. Physicians often waited until after a thromboembolic complication occurred before evaluating for HIT. More often than not, preventive measures were missed (e.g., failing to check for HIT antibodies, continuing heparin after HIT was suspected).

Bottom line: Thrombocytopenia is a common occurrence in patients receiving heparin and, despite the risk of devastating complications from HIT, treatment infrequently conforms to the established guidelines.

Citation: Crespo EM, Oliveira GBF, Honeycutt EF, et al. Evaluation and management of thrombocytopenia and suspected heparin-induced thrombocytopenia in hospitalized patients: The Complications After Thrombocytopenia Caused by Heparin (CATCH) registry. Am Heart J. 2009;157(4):651-657. TH

PEDIATRIC HM LITerature

Epinephrine and Dexamethasone Alone Do Not Reduce Hospital Admissions in Infants with Bronchiolitis

By Mark Shen, MD

Clinical question: Does nebulized epinephrine, oral dexamethasone, or a combination of the two result in a decrease in hospital admissions when given in the ED to infants with bronchiolitis?

Background: Bronchiolitis is the most common lower-respiratory-tract infection of infancy. Rates of admission have climbed in the past two decades. Bronchodilators and corticosteroids are not routinely recommended, and the evidence surrounding epinephrine and dexamethasone has shown varying results.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Eight Canadian pediatric EDs.

Synopsis: Eight hundred infants ages six weeks to 12 months with a first episode of bronchiolitis were randomized to nebulized epinephrine and oral dexamethasone, epinephrine and oral placebo, dexamethasone and nebulized placebo, or oral and nebulized placebo. Epinephrine was delivered as two nebulizations 30 minutes apart, and dexamethasone was given as a 1 mg/kg oral dose, followed by five once-daily doses of 0.6 mg/kg. In unadjusted analysis, only the infants who received epinephrine and dexamethasone were less likely to be admitted to the hospital by day seven.

Limitations of this study include a small effect size and a non-statistically-significant difference between the epinephrine/dexamethasone group and placebo after statistical adjustment for multiple comparisons. Given that admission rates did not decrease in the epinephrine/placebo group and the dexamethasone/placebo group, this study supports national guidelines that do not recommend the routine use of these agents in bronchiolitis. The authors suggest that synergy between epinephrine and dexamethasone in bronchiolitis be further studied.

Bottom line: When given alone, epinephrine and dexamethasone do not reduce hospital admissions in infants with bronchiolitis.

Citation: Plint AC, Johnson DW, Patel H, et al. Epinephrine and dexamethasone in children with bronchiolitis. N Engl J Med. 2009;360(20):2079-2089.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.