Hae-Won Kim, MD

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

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

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

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

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

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

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

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

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

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

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What medication reconciliation practices are the most effective and beneficial to patients?

Background: Medication reconciliation identifies the most accurate medications a patient is taking which can limit adverse drug events. A wide variety of practices have been reported.

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

Synopsis: Using both MEDLINE and manual search, 26 studies of medication reconciliation practices were identified that met inclusion criteria. Studies were divided into pharmacist-related interventions, information technology interventions, and other. Reported interventions were found to successfully reduce medication discrepancies but the effects on adverse drug event reduction were inconsistent. The scarcity of rigorously designed studies does limit the ability to compare medication reconciliation strategies. Only 6 of the reviewed studies were considered good quality. Future studies will require more standardized methods and rigorous outcome measurements.

Bottom line: Current data regarding medication reconciliation is limited, but supports use of pharmacy staff and focusing efforts on patients at high risk for adverse drug events.

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

Read more of our physician reviews of recent, HM-relevant literature.

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.

Clinical question: What is the optimal duration of oral ciprofloxacin in women with acute community-acquired pyelonephritis?

Background: Despite being a commonly encountered infection, there are little data on the appropriate duration of therapy for acute pyelonephritis in women.

Study design: Prospective, randomized, open-labeled, double-blinded, noninferiority trial.

Setting: Twenty-one infectious diseases centers in Sweden.

Synopsis: Two hundred forty-eight women aged 18 or older with a presumed diagnosis of pyelonephritis were randomized to treatment with seven or 14 days of oral ciprofloxacin 500 mg twice daily. One hundred fifty-six per protocol patients were analyzed, and short-term clinical cure was shown to be noninferior, with cure of 97% in the seven-day group and 96% in the 14-day group (90% confidence interval -6.5-4.8, P=0.004). Results were also shown to be valid for older women and those with more severe infections. With growing concerns of antibiotic resistance and adverse drug events, using shorter courses of antibiotics has come into favor. The authors warn that these findings should not be extrapolated to other classes of antibiotics.

Bottom line: Treatment of community-acquired acute pyelonephritis in women with ciprofloxacin 500 mg twice daily for seven days is not inferior to 14 days.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012; Jun 20: [Epub ahead of print].

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What is the optimal duration of oral ciprofloxacin in women with acute community-acquired pyelonephritis?

Background: Despite being a commonly encountered infection, there are little data on the appropriate duration of therapy for acute pyelonephritis in women.

Study design: Prospective, randomized, open-labeled, double-blinded, noninferiority trial.

Setting: Twenty-one infectious diseases centers in Sweden.

Synopsis: Two hundred forty-eight women aged 18 or older with a presumed diagnosis of pyelonephritis were randomized to treatment with seven or 14 days of oral ciprofloxacin 500 mg twice daily. One hundred fifty-six per protocol patients were analyzed, and short-term clinical cure was shown to be noninferior, with cure of 97% in the seven-day group and 96% in the 14-day group (90% confidence interval -6.5-4.8, P=0.004). Results were also shown to be valid for older women and those with more severe infections. With growing concerns of antibiotic resistance and adverse drug events, using shorter courses of antibiotics has come into favor. The authors warn that these findings should not be extrapolated to other classes of antibiotics.

Bottom line: Treatment of community-acquired acute pyelonephritis in women with ciprofloxacin 500 mg twice daily for seven days is not inferior to 14 days.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012; Jun 20: [Epub ahead of print].

Read more of our physician reviews of recent, HM-relevant literature.

Clinical question: What is the optimal duration of oral ciprofloxacin in women with acute community-acquired pyelonephritis?

Background: Despite being a commonly encountered infection, there are little data on the appropriate duration of therapy for acute pyelonephritis in women.

Study design: Prospective, randomized, open-labeled, double-blinded, noninferiority trial.

Setting: Twenty-one infectious diseases centers in Sweden.

Synopsis: Two hundred forty-eight women aged 18 or older with a presumed diagnosis of pyelonephritis were randomized to treatment with seven or 14 days of oral ciprofloxacin 500 mg twice daily. One hundred fifty-six per protocol patients were analyzed, and short-term clinical cure was shown to be noninferior, with cure of 97% in the seven-day group and 96% in the 14-day group (90% confidence interval -6.5-4.8, P=0.004). Results were also shown to be valid for older women and those with more severe infections. With growing concerns of antibiotic resistance and adverse drug events, using shorter courses of antibiotics has come into favor. The authors warn that these findings should not be extrapolated to other classes of antibiotics.

Bottom line: Treatment of community-acquired acute pyelonephritis in women with ciprofloxacin 500 mg twice daily for seven days is not inferior to 14 days.

Citation: Sandberg T, Skoog G, Hermansson AB, et al. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open-label and double-blind, placebo-controlled, non-inferiority trial. Lancet. 2012; Jun 20: [Epub ahead of print].

Read more of our physician reviews of recent, HM-relevant literature.

In This Edition

Literature at a Glance

A guide to this month’s studies

• CPOE and quality outcomes
• Outcomes of standardized management of endocarditis
• Effect of tPA three to 4.5 hours after stroke onset
• Failure to notify patients of significant test results
• PFO repair and stroke rate
• Predictors of delay in defibrillation for in-hospital arrest
• H. pylori eradication and risk of future gastric cancer
• Bleeding risk with fondaparinux vs. enoxaparin in ACS
• Perceptions of physician ability to predict medical futility

CPOE Is Associated with Improvement in Quality Measures

Clinical question: Is computerized physician order entry (CPOE) associated with improved outcomes across a large, nationally representative sample of hospitals?

Background: Several single-institution studies suggest CPOE leads to better outcomes in quality measures for heart failure, acute myocardial infarction, and pneumonia as defined by the Hospital Quality Alliance (HQA) initiative, led by the Centers for Medicare and Medicaid Services (CMS). Little systematic information is known about the effects of CPOE on quality of care.

Study design: Cross-sectional study.

Setting: The Health Information Management System Society (HIMSS) analytics database of 3,364 hospitals throughout the U.S.

Synopsis: Of the hospitals that reported CPOE utilization to HIMSS, 264 (7.8%) fully implement CPOE throughout their institutions. These CPOE hospitals outperformed their peers on five of 11 quality measures related to ordering medications, and in one of nine non-medication-related measures. No difference was noted in the other measures, except CPOE hospitals were less effective at providing antibiotics within four hours of pneumonia diagnosis. Hospitals that utilized CPOE were generally academic, larger, and nonprofit. After adjusting for these differences, benefits were still preserved.

The authors indicate that the lack of systematic outperformance by CPOE hospitals in all 20 of the quality categories inherently suggests that other factors (e.g., concomitant QI efforts) are not affecting these results. Given the observational nature of this study, no causal relationship can be established between CPOE and the observed benefits. CPOE might represent the commitment of certain hospitals to quality measures, but further study is needed.

Bottom line: Enhanced compliance in several CMS-established quality measures is seen in hospitals that utilize CPOE throughout their institutions.

Citation: Yu FB, Menachemi N, Berner ES, Allison JJ, Weissman NW, Houston TK. Full implementation of computerized physician order entry and medication-related quality outcomes: a study of 3,364 hospitals. Am J Med Qual. 2009;24(4):278-286.

Standardized Management of Endocarditis Leads to Significant Mortality Benefit

Clinical question: Does a standardized approach to the treatment of infective endocarditis reduce mortality and morbidity?

Background: Despite epidemiological changes to the inciting bacteria and improvements in available antibiotics, mortality and morbidity associated with endocarditis remain high. The contribution of inconsistent or inaccurate treatment of endocarditis is unclear.

Study design: Case series with historical controls from 1994 to 2001, compared with protocolized patients from 2002 to 2006.

Setting: Single teaching tertiary-care hospital in France.

Synopsis: The authors established a diagnostic protocol for infectious endocarditis from 1994 to 2001 (period 1) and established a treatment protocol from 2002 to 2006 (period 2). Despite a statistically significant sicker population (older, higher comorbidities, higher coagulase-negative staphylococcal infections, and fewer healthy valves), the period-2 patients had a dramatically lower mortality rate of 8.2% (P<0.001), compared with 18.5% in period-1 patients. Fewer episodes of renal failure, organ failure, and deaths associated with embolism were noted in period 2.

Whether these results are due to more frequent care, more aggressive care (patients were “summoned” if they did not show for appointments), standardized medication and surgical options, or the effects of long-term collaboration, these results appear durable, remarkable, and reproducible.

This study is limited by its lack of randomization and extensive time frame, with concomitant changes in medical treatment and observed infectious organisms.

Bottom line: Implementation of a standardized approach to endocarditis has significant benefit on mortality and morbidity.

Citation: Botelho-Nevers E, Thuny F, Casalta JP, et al. Dramatic reduction in infective endocarditis-related mortality with a management-based approach. Arch Intern Med. 2009;169(14):1290-1298.

Treatment with tPA in the Three- to 4.5-Hour Time Window after Stroke Is Beneficial

Clinical question: What is the effect of tissue plasminogen activator (tPA) on outcomes in patients treated in the three- to 4.5-hour window after stroke?

Background: The third European Cooperative Acute Stroke Study 3 (ECASS-3) demonstrated benefit of treatment of acute stroke with tPA in the three- to 4.5-hour time window. Prior studies, however, did not show superiority of tPA over placebo, and there is a lack of a confirmatory randomized, controlled trial of tPA in this time frame.

Study design: Meta-analysis of randomized, controlled trials.

Setting: Four studies involving 1,622 patients who were treated with intravenous tPA for acute ischemic stroke from three to 4.5 hours after stroke compared with placebo.

Synopsis: Of the randomized, controlled trials of intravenous tPA for treatment of acute ischemic stroke from three to 4.5 hours after stroke, four trials (ECASS-1, ECASS-2, ECASS-3, and ATLANTIS) were included in the analysis. Treatment with tPA in the three- to 4.5-hour time window is associated with increased favorable outcomes based on the global outcome measure (OR 1.31; 95% CI: 1.10-1.56, P=0.002) and the modified Rankin Scale (OR 1.31; 95% CI: 1.07-1.59, P=0.01), compared with placebo. The 90-day mortality rate was not significantly different between the treatment and placebo groups (OR 1.04; 95% CI 0.75-1.43, P=0.83).

Due to the relatively high dose of tPA (1.1 mg/kg) administered in the ECASS-1 trial, a separate meta-analysis looking at the other three trials (tPA dose of 0.9 mg/kg) was conducted, and the favorable outcome with tPA remained.

Bottom line: Treatment of acute ischemic stroke with tPA in the three- to 4.5-hour time window results in an increased rate of favorable functional outcomes without a significant difference in mortality.

Citation: Lansberg MG, Bluhmki E, Thijs VN. Efficacy and safety of tissue plasminogen activator 3 to 4.5 hours after acute ischemic stroke: a metaanalysis. Stroke. 2009;40(7):2438-2441.

Outpatients Often Are Not Notified of Clinically Significant Test Results

Clinical question: How frequently do primary-care physicians (PCPs) fail to inform patients of clinically significant outpatient test results?

Background: Diagnostic errors are the most common cause of malpractice claims in the U.S. It is unclear how often providers fail to either inform patients of abnormal test results or document that patients have been notified.

Study design: Retrospective chart review.

Setting: Twenty-three primary-care practices: 19 private, four academic.

Synopsis: More than 5,400 charts were reviewed, and 1,889 abnormal test results were identified in this study. Failure to inform or document notification was identified in 135 cases (7.1%). The failure rates in the practices ranged from 0.0% to 26.2%. Practices with the best processes for managing test results had the lowest failure rates; these processes included: all results being routed to the responsible physician; the physician signing off on all results; the practice informing patients of all results, both normal and abnormal; documenting when the patient is informed; and instructing patients to call if not notified of test results within a certain time interval.

Limitations of this study include the potential of over- or underreporting of failures to inform as a chart review was used, and only practices that agreed to participate were included.

Bottom line: Failure to notify outpatients of test results is common but can be minimized by creating a systematic management of test results that include best practices.

Citation: Casalino LP, Dunham D, Chin MH, et al. Frequency of failure to inform patients of clinically significant outpatient test results. Arch Intern Med. 2009;169(12):1123-1129.

Repair of Incidental PFO Discovered During Cardiothoracic Surgery Repair Increases Postoperative Stroke Risk

Clinical question: What is the impact of closing incidentally discovered patent foramen ovale (PFO) defects during cardiothoracic surgery?

Background: PFO’s role in cryptogenic stroke remains controversial. Incidental PFO is commonly detected by transesophageal echocardiography (TEE) during cardiothoracic surgery. Routine PFO closure has been recommended when almost no alteration of the surgical plan is required.

Study design: Retrospective chart review.

Setting: The Cleveland Clinic.

Synopsis: Between 1995 and 2006, 13,092 patients undergoing cardiothoracic surgery had TEE data with no previous diagnosis of PFO, but the review found that 2,277 (17%) had PFO discovered intraoperatively. Of these, 639 (28%) had the PFO repaired.

Patients with an intraoperative diagnosis of PFO had similar rates of in-hospital stroke and hospital death compared with those without PFO. Patients who had their PFO repaired had a greater in-hospital stroke risk (2.8% vs. 1.2%; P=0.04) compared with those with a non-repaired PFO, representing nearly 2.5 times greater odds of having an in-hospital stroke. No other difference was noted in perioperative outcomes for patients who underwent intraoperative repair compared with those who did not, including risk of in-hospital death, hospital length of stay, ICU length of stay, and time on cardiopulmonary bypass. Long-term analysis demonstrated that PFO repair was associated with no survival difference.

The study is limited by its retrospective nature.

Bottom line: Routine surgical closure of incidental PFO detected during intraoperative imaging should be discouraged.

Citation: Krasuski RA, Hart SA, Allen D, et al. Prevalence and repair of interoperatively diagnosed patent foramen ovale and association with perioperative outcomes and long-term survival. JAMA. 2009;302(3):290-297.

Hospital-Level Differences Are Strong Predictors of Time to Defibrillation Delay In Cardiac Arrest

Clinical question: What are the predictors of delay in the time to defibrillation after in-hospital cardiac arrest?

Background: Thirty percent of in-hospital cardiac arrests from ventricular arrhythmias are not treated within the American Heart Association’s recommendation of two minutes. This delay is associated with a 50% lower rate of in-hospital survival. Exploring the hospital-level variation in delays to defibrillation is a critical step toward sharing the best practices.

Study design: Retrospective review of registry data.

Setting: The National Registry of Cardiopulmonary Resuscitation (NRCPR) survey of 200 acute-care, nonpediatric hospitals.

Synopsis: The registry identified 7,479 patients who experienced cardiac arrest from ventricular tachycardia or pulseless ventricular fibrillation. The primary outcome was the hospital rate of delayed defibrillation (time to defibrillation > two minutes), which ranged from 2% to 51%.

Time to defibrillation was found to be a major predictor of survival after a cardiac arrest. Only bed volume and arrest location were associated with differences in rates of delayed defibrillation (lower rates in larger hospitals and in ICUs). The variability was not due to differences in patient characteristics, but was due to hospital-level effects. Academic status, geographical location, arrest volume, and daily admission volume did not affect the time to defibrillation.

The study was able to identify only a few facility characteristics that account for the variability between hospitals in the rate of delayed defibrillation. The study emphasizes the need for new approaches to identifying hospital innovations in process-of-care measures that are associated with improved performance in defibrillation times.

Bottom Line: Future research is needed to better understand the reason for the wide variation between hospitals in the rate of delayed defibrillation after in-hospital cardiac arrest.

Citation: Chan PS, Nichol G, Krumholz HM, Spertus JA, Nallamothu BK; American Heart Association National Registry of Cardiopulmonary Resuscitation (NRCPR) Investigators. Hospital variation in time to defibrillation after in-hospital cardiac arrest. Arch Intern Med. 2009;169(14):1265-1273.

Treating for H. Pylori Reduces the Risk for Developing Gastric Cancer in High-Risk Patients

Clinical question: In patients with high-baseline incidence of gastric cancer, does H. pylori eradication reduce the risk for developing gastric cancer?

Background: Gastric cancer remains a major health problem in Asia. The link of H. pylori and gastric cancer has been established, but it remains unclear whether treatment for H. pylori is effective primary prevention for the development of gastric cancer.

Study design: Meta-analysis of six studies.

Setting: All but one trial was performed in Asia.

Synopsis: Seven studies met inclusion criteria, one of which was excluded due to heterogeneity. The six remaining studies were pooled, with 37 of 3,388 (1.1%) treated patients developing a new gastric cancer, compared with 56 of 3,307 (1.7%) patients who received placebo or were in the control group (RR 0.65; 0.43-0.98). Most patients received gastric biopsy prior to enrollment, and most of those demonstrated gastric atrophy or intestinal metaplasia.

These patients, despite more advanced precancerous pathology findings, still benefited from eradication. The seventh study, which was excluded, enrolled patients with early gastric cancer; these patients still benefited from H. pylori eradication and, when included in the meta-analysis, the RR was even lower, 0.57 (0.49-0.81).

Only two trials were double-blinded, but all of the studies employed the same definition of gastric cancer and held to excellent data reporting standards. This study encourages screening and treatment in high-risk patients given the widespread incidence of H. pylori.

Bottom Line: Treatment of H. pylori reduces the risk of gastric cancer in high-risk patients.

Citation: Fuccio L, Zagari RM, Eusebi LH, et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151(2):121-128.

Patients on Anti-Platelet Agents with Acute Coronary Syndrome Have a Lower Bleeding Risk When Treated with Fondaparinux

Clinical question: Is there a difference in bleeding risk with fondaparinux and enoxaparin when used with GPIIb/IIIa inhibitors or thienopyridines in NSTEMI-ACS?

Background: The OASIS 5 study reported a 50% reduction in severe bleeding when comparing fondaparinux to enoxaparin in ACS while maintaining a similar efficacy. This subgroup analysis was performed to evaluate whether reduced bleeding risk with fondaparinux remains in patients treated with additional anti-platelet agents.

Study design: Subgroup analysis of a large, multicenter, randomized, double-blind trial.

Setting: Acute-care hospitals in North America, Eastern and Western Europe, Latin America, Australia, and Asia.

Synopsis: Patients with NSTE-ACS received either fondaparinux or enoxaparin and were treated with GPIIb/IIIa inhibitors or thienopyridines at the discretion of their physician. At 30 days, the fondaparinux group had similar efficacy and decreased bleeding risk in both the GPIIb/IIIa and the thienopyridine groups. Of the 3,630 patients in the GPIIb/IIIa group, the risk for major bleeding with fondaparinux was 5.2%, whereas the risk with enoxaparin was 8.3% (HR 0.61; P<0.001) compared with enoxaparin. Of the 1,352 patients treated with thienopyridines, the risk for major bleeding with fondaparinux was 3.4%, whereas the risk with enoxaparin was 5.4% (HR 0.62; P<0.001).

Bottom Line: This subgroup analysis suggests there are less-severe bleeding complications in patients treated with fondaparinux when compared with enoxaparin in the setting of cotreatment with GPIIb/IIIa inhibitors, thienopyridines, or both.

Citation: Jolly SS, Faxon DP, Fox KA, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors of thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. J Am Coll Cardiol. 2009;54(5):468-476.

Surrogate Decision-Makers Frequently Doubt Clinicians’ Ability to Predict Medical Futility

Clinical question: What attitudes do surrogate decision-makers hold toward clinicians’ predictions of medical futility in critically-ill patients?

Background: The clinical judgment of medical futility leading to the withdrawal of life-sustaining treatment—despite the objections of surrogate decision-makers—is controversial. Very little is known about how surrogate decision-makers view the futility rationale when physicians suggest limiting the use of life-sustaining treatment.

Study design: Multicenter, mixed, qualitative and quantitative study.

Setting: Three ICUs in three different California hospitals from 2006 to 2007.

Synopsis: Semi-structured interviews of surrogate decision-makers for 50 incapacitated, critically-ill patients were performed to ascertain their beliefs about medical futility in response to hypothetical situations. Of the surrogates surveyed, 64% expressed doubt about physicians’ futility predictions.

The interviewees gave four main reasons for their doubts. Two reasons not previously described were doubts about the accuracy of physicians’ predictions and the need for surrogates to see futility themselves. Previously described sources of conflict included a misunderstanding about prognosis and religious-based objections. Surrogates with religious objections were more likely to request continuation of life-sustaining treatments than those with secular or experiential objections (OR 4; 95% CI 1.2-14.0; P=0.03). Nearly a third (32%) of surrogates elected to continue life support with a <1% survival estimate; 18% elected to continue life support when physicians thought there was no chance of survival.

This study has several limitations: a small sample size, the use of hypothetical situations, and the inability to assess attitudes as they change over time.

Bottom line: The nature of surrogate decision-makers’ doubts about medical futility can help predict whether they accept predictions of medical futility from physicians.

Citation: Zier LS, Burack JH, Micco G, Chipman AK, Frank JA, White DB. Surrogate decision makers’ responses to physicians’ predictions of medical futility. Chest. 2009;136:110-117. TH

PEDIATRIC HM LITerature

House-Staff Signout Complexities Remain

By Mark Shen, MD

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

Clinical question: What are the characteristics of signout among house staff?

Background: Inadequate signout is a recognized contributor to medical errors. As care has become increasingly fragmented among house staff who must comply with work-hour restrictions, both the absolute number of signouts and the potential for incomplete transfer of information increase. Despite recent Joint Commission requirements to standardize handoffs, comprehensive analyses of the process remain scarce.

Study design: Quantitative and qualitative analysis of audiotaped oral internal-medicine signout.

Setting: Academic teaching hospital.

Synopsis: Audiotaped signout for eight internal-medicine house-staff teams during two time periods in 2006 were analyzed for content, clarity of language, and surrounding environment. Most signout (59.2%) did not include questions, and questioning of patient management was often indirect when it occurred. A spectrum of clarity existed from unclear anticipatory guidance to clear, concise instructions. Interruptions occurred less than 20% of the time. Familiarity with patients, sense of responsibility for patients, sequential signouts, experience, and comprehensiveness of the written form affected the content of the signout.

This study provides insight into the broad array of factors that affect signout. Despite the potential for interactive facilitation of understanding, the process is often one-sided and operator-dependent. Such systems-based factors as familiarity with patients and sequential signouts might affect quality, while cultural norms (such as sense of responsibility) also play a role.

Limitations of this study include the nonblinded observation method and the potential for institution-specific culture to limit applicability. Nonetheless, this study adds to literature painting a broader and complex picture of a routine hospital process often taken for granted.

Bottom line: Improving and standardizing handoffs requires attention to multifaceted domains that commonly affect complex human organizations.

Citation: Horwitz LI, Moin T, Krumholz HM, Wang L, Bradley EH. What are covering doctors told about their patients? Analysis of sign-out among internal medicine house staff. Qual Saf Health Care. 2009;18(4):248-255.

In This Edition

Literature at a Glance

A guide to this month’s studies

• CPOE and quality outcomes
• Outcomes of standardized management of endocarditis
• Effect of tPA three to 4.5 hours after stroke onset
• Failure to notify patients of significant test results
• PFO repair and stroke rate
• Predictors of delay in defibrillation for in-hospital arrest
• H. pylori eradication and risk of future gastric cancer
• Bleeding risk with fondaparinux vs. enoxaparin in ACS
• Perceptions of physician ability to predict medical futility

CPOE Is Associated with Improvement in Quality Measures

Clinical question: Is computerized physician order entry (CPOE) associated with improved outcomes across a large, nationally representative sample of hospitals?

Background: Several single-institution studies suggest CPOE leads to better outcomes in quality measures for heart failure, acute myocardial infarction, and pneumonia as defined by the Hospital Quality Alliance (HQA) initiative, led by the Centers for Medicare and Medicaid Services (CMS). Little systematic information is known about the effects of CPOE on quality of care.

Study design: Cross-sectional study.

Setting: The Health Information Management System Society (HIMSS) analytics database of 3,364 hospitals throughout the U.S.

Synopsis: Of the hospitals that reported CPOE utilization to HIMSS, 264 (7.8%) fully implement CPOE throughout their institutions. These CPOE hospitals outperformed their peers on five of 11 quality measures related to ordering medications, and in one of nine non-medication-related measures. No difference was noted in the other measures, except CPOE hospitals were less effective at providing antibiotics within four hours of pneumonia diagnosis. Hospitals that utilized CPOE were generally academic, larger, and nonprofit. After adjusting for these differences, benefits were still preserved.

The authors indicate that the lack of systematic outperformance by CPOE hospitals in all 20 of the quality categories inherently suggests that other factors (e.g., concomitant QI efforts) are not affecting these results. Given the observational nature of this study, no causal relationship can be established between CPOE and the observed benefits. CPOE might represent the commitment of certain hospitals to quality measures, but further study is needed.

Bottom line: Enhanced compliance in several CMS-established quality measures is seen in hospitals that utilize CPOE throughout their institutions.

Citation: Yu FB, Menachemi N, Berner ES, Allison JJ, Weissman NW, Houston TK. Full implementation of computerized physician order entry and medication-related quality outcomes: a study of 3,364 hospitals. Am J Med Qual. 2009;24(4):278-286.

Standardized Management of Endocarditis Leads to Significant Mortality Benefit

Clinical question: Does a standardized approach to the treatment of infective endocarditis reduce mortality and morbidity?

Background: Despite epidemiological changes to the inciting bacteria and improvements in available antibiotics, mortality and morbidity associated with endocarditis remain high. The contribution of inconsistent or inaccurate treatment of endocarditis is unclear.

Study design: Case series with historical controls from 1994 to 2001, compared with protocolized patients from 2002 to 2006.

Setting: Single teaching tertiary-care hospital in France.

Synopsis: The authors established a diagnostic protocol for infectious endocarditis from 1994 to 2001 (period 1) and established a treatment protocol from 2002 to 2006 (period 2). Despite a statistically significant sicker population (older, higher comorbidities, higher coagulase-negative staphylococcal infections, and fewer healthy valves), the period-2 patients had a dramatically lower mortality rate of 8.2% (P<0.001), compared with 18.5% in period-1 patients. Fewer episodes of renal failure, organ failure, and deaths associated with embolism were noted in period 2.

Whether these results are due to more frequent care, more aggressive care (patients were “summoned” if they did not show for appointments), standardized medication and surgical options, or the effects of long-term collaboration, these results appear durable, remarkable, and reproducible.

This study is limited by its lack of randomization and extensive time frame, with concomitant changes in medical treatment and observed infectious organisms.

Bottom line: Implementation of a standardized approach to endocarditis has significant benefit on mortality and morbidity.

Citation: Botelho-Nevers E, Thuny F, Casalta JP, et al. Dramatic reduction in infective endocarditis-related mortality with a management-based approach. Arch Intern Med. 2009;169(14):1290-1298.

Treatment with tPA in the Three- to 4.5-Hour Time Window after Stroke Is Beneficial

Clinical question: What is the effect of tissue plasminogen activator (tPA) on outcomes in patients treated in the three- to 4.5-hour window after stroke?

Background: The third European Cooperative Acute Stroke Study 3 (ECASS-3) demonstrated benefit of treatment of acute stroke with tPA in the three- to 4.5-hour time window. Prior studies, however, did not show superiority of tPA over placebo, and there is a lack of a confirmatory randomized, controlled trial of tPA in this time frame.

Study design: Meta-analysis of randomized, controlled trials.

Setting: Four studies involving 1,622 patients who were treated with intravenous tPA for acute ischemic stroke from three to 4.5 hours after stroke compared with placebo.

Synopsis: Of the randomized, controlled trials of intravenous tPA for treatment of acute ischemic stroke from three to 4.5 hours after stroke, four trials (ECASS-1, ECASS-2, ECASS-3, and ATLANTIS) were included in the analysis. Treatment with tPA in the three- to 4.5-hour time window is associated with increased favorable outcomes based on the global outcome measure (OR 1.31; 95% CI: 1.10-1.56, P=0.002) and the modified Rankin Scale (OR 1.31; 95% CI: 1.07-1.59, P=0.01), compared with placebo. The 90-day mortality rate was not significantly different between the treatment and placebo groups (OR 1.04; 95% CI 0.75-1.43, P=0.83).

Due to the relatively high dose of tPA (1.1 mg/kg) administered in the ECASS-1 trial, a separate meta-analysis looking at the other three trials (tPA dose of 0.9 mg/kg) was conducted, and the favorable outcome with tPA remained.

Bottom line: Treatment of acute ischemic stroke with tPA in the three- to 4.5-hour time window results in an increased rate of favorable functional outcomes without a significant difference in mortality.

Citation: Lansberg MG, Bluhmki E, Thijs VN. Efficacy and safety of tissue plasminogen activator 3 to 4.5 hours after acute ischemic stroke: a metaanalysis. Stroke. 2009;40(7):2438-2441.

Outpatients Often Are Not Notified of Clinically Significant Test Results

Clinical question: How frequently do primary-care physicians (PCPs) fail to inform patients of clinically significant outpatient test results?

Background: Diagnostic errors are the most common cause of malpractice claims in the U.S. It is unclear how often providers fail to either inform patients of abnormal test results or document that patients have been notified.

Study design: Retrospective chart review.

Setting: Twenty-three primary-care practices: 19 private, four academic.

Synopsis: More than 5,400 charts were reviewed, and 1,889 abnormal test results were identified in this study. Failure to inform or document notification was identified in 135 cases (7.1%). The failure rates in the practices ranged from 0.0% to 26.2%. Practices with the best processes for managing test results had the lowest failure rates; these processes included: all results being routed to the responsible physician; the physician signing off on all results; the practice informing patients of all results, both normal and abnormal; documenting when the patient is informed; and instructing patients to call if not notified of test results within a certain time interval.

Limitations of this study include the potential of over- or underreporting of failures to inform as a chart review was used, and only practices that agreed to participate were included.

Bottom line: Failure to notify outpatients of test results is common but can be minimized by creating a systematic management of test results that include best practices.

Citation: Casalino LP, Dunham D, Chin MH, et al. Frequency of failure to inform patients of clinically significant outpatient test results. Arch Intern Med. 2009;169(12):1123-1129.

Repair of Incidental PFO Discovered During Cardiothoracic Surgery Repair Increases Postoperative Stroke Risk

Clinical question: What is the impact of closing incidentally discovered patent foramen ovale (PFO) defects during cardiothoracic surgery?

Background: PFO’s role in cryptogenic stroke remains controversial. Incidental PFO is commonly detected by transesophageal echocardiography (TEE) during cardiothoracic surgery. Routine PFO closure has been recommended when almost no alteration of the surgical plan is required.

Study design: Retrospective chart review.

Setting: The Cleveland Clinic.

Synopsis: Between 1995 and 2006, 13,092 patients undergoing cardiothoracic surgery had TEE data with no previous diagnosis of PFO, but the review found that 2,277 (17%) had PFO discovered intraoperatively. Of these, 639 (28%) had the PFO repaired.

Patients with an intraoperative diagnosis of PFO had similar rates of in-hospital stroke and hospital death compared with those without PFO. Patients who had their PFO repaired had a greater in-hospital stroke risk (2.8% vs. 1.2%; P=0.04) compared with those with a non-repaired PFO, representing nearly 2.5 times greater odds of having an in-hospital stroke. No other difference was noted in perioperative outcomes for patients who underwent intraoperative repair compared with those who did not, including risk of in-hospital death, hospital length of stay, ICU length of stay, and time on cardiopulmonary bypass. Long-term analysis demonstrated that PFO repair was associated with no survival difference.

The study is limited by its retrospective nature.

Bottom line: Routine surgical closure of incidental PFO detected during intraoperative imaging should be discouraged.

Citation: Krasuski RA, Hart SA, Allen D, et al. Prevalence and repair of interoperatively diagnosed patent foramen ovale and association with perioperative outcomes and long-term survival. JAMA. 2009;302(3):290-297.

Hospital-Level Differences Are Strong Predictors of Time to Defibrillation Delay In Cardiac Arrest

Clinical question: What are the predictors of delay in the time to defibrillation after in-hospital cardiac arrest?

Background: Thirty percent of in-hospital cardiac arrests from ventricular arrhythmias are not treated within the American Heart Association’s recommendation of two minutes. This delay is associated with a 50% lower rate of in-hospital survival. Exploring the hospital-level variation in delays to defibrillation is a critical step toward sharing the best practices.

Study design: Retrospective review of registry data.

Setting: The National Registry of Cardiopulmonary Resuscitation (NRCPR) survey of 200 acute-care, nonpediatric hospitals.

Synopsis: The registry identified 7,479 patients who experienced cardiac arrest from ventricular tachycardia or pulseless ventricular fibrillation. The primary outcome was the hospital rate of delayed defibrillation (time to defibrillation > two minutes), which ranged from 2% to 51%.

Time to defibrillation was found to be a major predictor of survival after a cardiac arrest. Only bed volume and arrest location were associated with differences in rates of delayed defibrillation (lower rates in larger hospitals and in ICUs). The variability was not due to differences in patient characteristics, but was due to hospital-level effects. Academic status, geographical location, arrest volume, and daily admission volume did not affect the time to defibrillation.

The study was able to identify only a few facility characteristics that account for the variability between hospitals in the rate of delayed defibrillation. The study emphasizes the need for new approaches to identifying hospital innovations in process-of-care measures that are associated with improved performance in defibrillation times.

Bottom Line: Future research is needed to better understand the reason for the wide variation between hospitals in the rate of delayed defibrillation after in-hospital cardiac arrest.

Citation: Chan PS, Nichol G, Krumholz HM, Spertus JA, Nallamothu BK; American Heart Association National Registry of Cardiopulmonary Resuscitation (NRCPR) Investigators. Hospital variation in time to defibrillation after in-hospital cardiac arrest. Arch Intern Med. 2009;169(14):1265-1273.

Treating for H. Pylori Reduces the Risk for Developing Gastric Cancer in High-Risk Patients

Clinical question: In patients with high-baseline incidence of gastric cancer, does H. pylori eradication reduce the risk for developing gastric cancer?

Background: Gastric cancer remains a major health problem in Asia. The link of H. pylori and gastric cancer has been established, but it remains unclear whether treatment for H. pylori is effective primary prevention for the development of gastric cancer.

Study design: Meta-analysis of six studies.

Setting: All but one trial was performed in Asia.

Synopsis: Seven studies met inclusion criteria, one of which was excluded due to heterogeneity. The six remaining studies were pooled, with 37 of 3,388 (1.1%) treated patients developing a new gastric cancer, compared with 56 of 3,307 (1.7%) patients who received placebo or were in the control group (RR 0.65; 0.43-0.98). Most patients received gastric biopsy prior to enrollment, and most of those demonstrated gastric atrophy or intestinal metaplasia.

These patients, despite more advanced precancerous pathology findings, still benefited from eradication. The seventh study, which was excluded, enrolled patients with early gastric cancer; these patients still benefited from H. pylori eradication and, when included in the meta-analysis, the RR was even lower, 0.57 (0.49-0.81).

Only two trials were double-blinded, but all of the studies employed the same definition of gastric cancer and held to excellent data reporting standards. This study encourages screening and treatment in high-risk patients given the widespread incidence of H. pylori.

Bottom Line: Treatment of H. pylori reduces the risk of gastric cancer in high-risk patients.

Citation: Fuccio L, Zagari RM, Eusebi LH, et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151(2):121-128.

Patients on Anti-Platelet Agents with Acute Coronary Syndrome Have a Lower Bleeding Risk When Treated with Fondaparinux

Clinical question: Is there a difference in bleeding risk with fondaparinux and enoxaparin when used with GPIIb/IIIa inhibitors or thienopyridines in NSTEMI-ACS?

Background: The OASIS 5 study reported a 50% reduction in severe bleeding when comparing fondaparinux to enoxaparin in ACS while maintaining a similar efficacy. This subgroup analysis was performed to evaluate whether reduced bleeding risk with fondaparinux remains in patients treated with additional anti-platelet agents.

Study design: Subgroup analysis of a large, multicenter, randomized, double-blind trial.

Setting: Acute-care hospitals in North America, Eastern and Western Europe, Latin America, Australia, and Asia.

Synopsis: Patients with NSTE-ACS received either fondaparinux or enoxaparin and were treated with GPIIb/IIIa inhibitors or thienopyridines at the discretion of their physician. At 30 days, the fondaparinux group had similar efficacy and decreased bleeding risk in both the GPIIb/IIIa and the thienopyridine groups. Of the 3,630 patients in the GPIIb/IIIa group, the risk for major bleeding with fondaparinux was 5.2%, whereas the risk with enoxaparin was 8.3% (HR 0.61; P<0.001) compared with enoxaparin. Of the 1,352 patients treated with thienopyridines, the risk for major bleeding with fondaparinux was 3.4%, whereas the risk with enoxaparin was 5.4% (HR 0.62; P<0.001).

Bottom Line: This subgroup analysis suggests there are less-severe bleeding complications in patients treated with fondaparinux when compared with enoxaparin in the setting of cotreatment with GPIIb/IIIa inhibitors, thienopyridines, or both.

Citation: Jolly SS, Faxon DP, Fox KA, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors of thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. J Am Coll Cardiol. 2009;54(5):468-476.

Surrogate Decision-Makers Frequently Doubt Clinicians’ Ability to Predict Medical Futility

Clinical question: What attitudes do surrogate decision-makers hold toward clinicians’ predictions of medical futility in critically-ill patients?

Background: The clinical judgment of medical futility leading to the withdrawal of life-sustaining treatment—despite the objections of surrogate decision-makers—is controversial. Very little is known about how surrogate decision-makers view the futility rationale when physicians suggest limiting the use of life-sustaining treatment.

Study design: Multicenter, mixed, qualitative and quantitative study.

Setting: Three ICUs in three different California hospitals from 2006 to 2007.

Synopsis: Semi-structured interviews of surrogate decision-makers for 50 incapacitated, critically-ill patients were performed to ascertain their beliefs about medical futility in response to hypothetical situations. Of the surrogates surveyed, 64% expressed doubt about physicians’ futility predictions.

The interviewees gave four main reasons for their doubts. Two reasons not previously described were doubts about the accuracy of physicians’ predictions and the need for surrogates to see futility themselves. Previously described sources of conflict included a misunderstanding about prognosis and religious-based objections. Surrogates with religious objections were more likely to request continuation of life-sustaining treatments than those with secular or experiential objections (OR 4; 95% CI 1.2-14.0; P=0.03). Nearly a third (32%) of surrogates elected to continue life support with a <1% survival estimate; 18% elected to continue life support when physicians thought there was no chance of survival.

This study has several limitations: a small sample size, the use of hypothetical situations, and the inability to assess attitudes as they change over time.

Bottom line: The nature of surrogate decision-makers’ doubts about medical futility can help predict whether they accept predictions of medical futility from physicians.

Citation: Zier LS, Burack JH, Micco G, Chipman AK, Frank JA, White DB. Surrogate decision makers’ responses to physicians’ predictions of medical futility. Chest. 2009;136:110-117. TH

PEDIATRIC HM LITerature

House-Staff Signout Complexities Remain

By Mark Shen, MD

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

Clinical question: What are the characteristics of signout among house staff?

Background: Inadequate signout is a recognized contributor to medical errors. As care has become increasingly fragmented among house staff who must comply with work-hour restrictions, both the absolute number of signouts and the potential for incomplete transfer of information increase. Despite recent Joint Commission requirements to standardize handoffs, comprehensive analyses of the process remain scarce.

Study design: Quantitative and qualitative analysis of audiotaped oral internal-medicine signout.

Setting: Academic teaching hospital.

Synopsis: Audiotaped signout for eight internal-medicine house-staff teams during two time periods in 2006 were analyzed for content, clarity of language, and surrounding environment. Most signout (59.2%) did not include questions, and questioning of patient management was often indirect when it occurred. A spectrum of clarity existed from unclear anticipatory guidance to clear, concise instructions. Interruptions occurred less than 20% of the time. Familiarity with patients, sense of responsibility for patients, sequential signouts, experience, and comprehensiveness of the written form affected the content of the signout.

This study provides insight into the broad array of factors that affect signout. Despite the potential for interactive facilitation of understanding, the process is often one-sided and operator-dependent. Such systems-based factors as familiarity with patients and sequential signouts might affect quality, while cultural norms (such as sense of responsibility) also play a role.

Limitations of this study include the nonblinded observation method and the potential for institution-specific culture to limit applicability. Nonetheless, this study adds to literature painting a broader and complex picture of a routine hospital process often taken for granted.

Bottom line: Improving and standardizing handoffs requires attention to multifaceted domains that commonly affect complex human organizations.

Citation: Horwitz LI, Moin T, Krumholz HM, Wang L, Bradley EH. What are covering doctors told about their patients? Analysis of sign-out among internal medicine house staff. Qual Saf Health Care. 2009;18(4):248-255.

In This Edition

Literature at a Glance

A guide to this month’s studies

• CPOE and quality outcomes
• Outcomes of standardized management of endocarditis
• Effect of tPA three to 4.5 hours after stroke onset
• Failure to notify patients of significant test results
• PFO repair and stroke rate
• Predictors of delay in defibrillation for in-hospital arrest
• H. pylori eradication and risk of future gastric cancer
• Bleeding risk with fondaparinux vs. enoxaparin in ACS
• Perceptions of physician ability to predict medical futility

CPOE Is Associated with Improvement in Quality Measures

Clinical question: Is computerized physician order entry (CPOE) associated with improved outcomes across a large, nationally representative sample of hospitals?

Background: Several single-institution studies suggest CPOE leads to better outcomes in quality measures for heart failure, acute myocardial infarction, and pneumonia as defined by the Hospital Quality Alliance (HQA) initiative, led by the Centers for Medicare and Medicaid Services (CMS). Little systematic information is known about the effects of CPOE on quality of care.

Study design: Cross-sectional study.

Setting: The Health Information Management System Society (HIMSS) analytics database of 3,364 hospitals throughout the U.S.

Synopsis: Of the hospitals that reported CPOE utilization to HIMSS, 264 (7.8%) fully implement CPOE throughout their institutions. These CPOE hospitals outperformed their peers on five of 11 quality measures related to ordering medications, and in one of nine non-medication-related measures. No difference was noted in the other measures, except CPOE hospitals were less effective at providing antibiotics within four hours of pneumonia diagnosis. Hospitals that utilized CPOE were generally academic, larger, and nonprofit. After adjusting for these differences, benefits were still preserved.

The authors indicate that the lack of systematic outperformance by CPOE hospitals in all 20 of the quality categories inherently suggests that other factors (e.g., concomitant QI efforts) are not affecting these results. Given the observational nature of this study, no causal relationship can be established between CPOE and the observed benefits. CPOE might represent the commitment of certain hospitals to quality measures, but further study is needed.

Bottom line: Enhanced compliance in several CMS-established quality measures is seen in hospitals that utilize CPOE throughout their institutions.

Citation: Yu FB, Menachemi N, Berner ES, Allison JJ, Weissman NW, Houston TK. Full implementation of computerized physician order entry and medication-related quality outcomes: a study of 3,364 hospitals. Am J Med Qual. 2009;24(4):278-286.

Standardized Management of Endocarditis Leads to Significant Mortality Benefit

Clinical question: Does a standardized approach to the treatment of infective endocarditis reduce mortality and morbidity?

Background: Despite epidemiological changes to the inciting bacteria and improvements in available antibiotics, mortality and morbidity associated with endocarditis remain high. The contribution of inconsistent or inaccurate treatment of endocarditis is unclear.

Study design: Case series with historical controls from 1994 to 2001, compared with protocolized patients from 2002 to 2006.

Setting: Single teaching tertiary-care hospital in France.

Synopsis: The authors established a diagnostic protocol for infectious endocarditis from 1994 to 2001 (period 1) and established a treatment protocol from 2002 to 2006 (period 2). Despite a statistically significant sicker population (older, higher comorbidities, higher coagulase-negative staphylococcal infections, and fewer healthy valves), the period-2 patients had a dramatically lower mortality rate of 8.2% (P<0.001), compared with 18.5% in period-1 patients. Fewer episodes of renal failure, organ failure, and deaths associated with embolism were noted in period 2.

Whether these results are due to more frequent care, more aggressive care (patients were “summoned” if they did not show for appointments), standardized medication and surgical options, or the effects of long-term collaboration, these results appear durable, remarkable, and reproducible.

This study is limited by its lack of randomization and extensive time frame, with concomitant changes in medical treatment and observed infectious organisms.

Bottom line: Implementation of a standardized approach to endocarditis has significant benefit on mortality and morbidity.

Citation: Botelho-Nevers E, Thuny F, Casalta JP, et al. Dramatic reduction in infective endocarditis-related mortality with a management-based approach. Arch Intern Med. 2009;169(14):1290-1298.

Treatment with tPA in the Three- to 4.5-Hour Time Window after Stroke Is Beneficial

Clinical question: What is the effect of tissue plasminogen activator (tPA) on outcomes in patients treated in the three- to 4.5-hour window after stroke?

Background: The third European Cooperative Acute Stroke Study 3 (ECASS-3) demonstrated benefit of treatment of acute stroke with tPA in the three- to 4.5-hour time window. Prior studies, however, did not show superiority of tPA over placebo, and there is a lack of a confirmatory randomized, controlled trial of tPA in this time frame.

Study design: Meta-analysis of randomized, controlled trials.

Setting: Four studies involving 1,622 patients who were treated with intravenous tPA for acute ischemic stroke from three to 4.5 hours after stroke compared with placebo.

Synopsis: Of the randomized, controlled trials of intravenous tPA for treatment of acute ischemic stroke from three to 4.5 hours after stroke, four trials (ECASS-1, ECASS-2, ECASS-3, and ATLANTIS) were included in the analysis. Treatment with tPA in the three- to 4.5-hour time window is associated with increased favorable outcomes based on the global outcome measure (OR 1.31; 95% CI: 1.10-1.56, P=0.002) and the modified Rankin Scale (OR 1.31; 95% CI: 1.07-1.59, P=0.01), compared with placebo. The 90-day mortality rate was not significantly different between the treatment and placebo groups (OR 1.04; 95% CI 0.75-1.43, P=0.83).

Due to the relatively high dose of tPA (1.1 mg/kg) administered in the ECASS-1 trial, a separate meta-analysis looking at the other three trials (tPA dose of 0.9 mg/kg) was conducted, and the favorable outcome with tPA remained.

Bottom line: Treatment of acute ischemic stroke with tPA in the three- to 4.5-hour time window results in an increased rate of favorable functional outcomes without a significant difference in mortality.

Citation: Lansberg MG, Bluhmki E, Thijs VN. Efficacy and safety of tissue plasminogen activator 3 to 4.5 hours after acute ischemic stroke: a metaanalysis. Stroke. 2009;40(7):2438-2441.

Outpatients Often Are Not Notified of Clinically Significant Test Results

Clinical question: How frequently do primary-care physicians (PCPs) fail to inform patients of clinically significant outpatient test results?

Background: Diagnostic errors are the most common cause of malpractice claims in the U.S. It is unclear how often providers fail to either inform patients of abnormal test results or document that patients have been notified.

Study design: Retrospective chart review.

Setting: Twenty-three primary-care practices: 19 private, four academic.

Synopsis: More than 5,400 charts were reviewed, and 1,889 abnormal test results were identified in this study. Failure to inform or document notification was identified in 135 cases (7.1%). The failure rates in the practices ranged from 0.0% to 26.2%. Practices with the best processes for managing test results had the lowest failure rates; these processes included: all results being routed to the responsible physician; the physician signing off on all results; the practice informing patients of all results, both normal and abnormal; documenting when the patient is informed; and instructing patients to call if not notified of test results within a certain time interval.

Limitations of this study include the potential of over- or underreporting of failures to inform as a chart review was used, and only practices that agreed to participate were included.

Bottom line: Failure to notify outpatients of test results is common but can be minimized by creating a systematic management of test results that include best practices.

Citation: Casalino LP, Dunham D, Chin MH, et al. Frequency of failure to inform patients of clinically significant outpatient test results. Arch Intern Med. 2009;169(12):1123-1129.

Repair of Incidental PFO Discovered During Cardiothoracic Surgery Repair Increases Postoperative Stroke Risk

Clinical question: What is the impact of closing incidentally discovered patent foramen ovale (PFO) defects during cardiothoracic surgery?

Background: PFO’s role in cryptogenic stroke remains controversial. Incidental PFO is commonly detected by transesophageal echocardiography (TEE) during cardiothoracic surgery. Routine PFO closure has been recommended when almost no alteration of the surgical plan is required.

Study design: Retrospective chart review.

Setting: The Cleveland Clinic.

Synopsis: Between 1995 and 2006, 13,092 patients undergoing cardiothoracic surgery had TEE data with no previous diagnosis of PFO, but the review found that 2,277 (17%) had PFO discovered intraoperatively. Of these, 639 (28%) had the PFO repaired.

Patients with an intraoperative diagnosis of PFO had similar rates of in-hospital stroke and hospital death compared with those without PFO. Patients who had their PFO repaired had a greater in-hospital stroke risk (2.8% vs. 1.2%; P=0.04) compared with those with a non-repaired PFO, representing nearly 2.5 times greater odds of having an in-hospital stroke. No other difference was noted in perioperative outcomes for patients who underwent intraoperative repair compared with those who did not, including risk of in-hospital death, hospital length of stay, ICU length of stay, and time on cardiopulmonary bypass. Long-term analysis demonstrated that PFO repair was associated with no survival difference.

The study is limited by its retrospective nature.

Bottom line: Routine surgical closure of incidental PFO detected during intraoperative imaging should be discouraged.

Citation: Krasuski RA, Hart SA, Allen D, et al. Prevalence and repair of interoperatively diagnosed patent foramen ovale and association with perioperative outcomes and long-term survival. JAMA. 2009;302(3):290-297.

Hospital-Level Differences Are Strong Predictors of Time to Defibrillation Delay In Cardiac Arrest

Clinical question: What are the predictors of delay in the time to defibrillation after in-hospital cardiac arrest?

Background: Thirty percent of in-hospital cardiac arrests from ventricular arrhythmias are not treated within the American Heart Association’s recommendation of two minutes. This delay is associated with a 50% lower rate of in-hospital survival. Exploring the hospital-level variation in delays to defibrillation is a critical step toward sharing the best practices.

Study design: Retrospective review of registry data.

Setting: The National Registry of Cardiopulmonary Resuscitation (NRCPR) survey of 200 acute-care, nonpediatric hospitals.

Synopsis: The registry identified 7,479 patients who experienced cardiac arrest from ventricular tachycardia or pulseless ventricular fibrillation. The primary outcome was the hospital rate of delayed defibrillation (time to defibrillation > two minutes), which ranged from 2% to 51%.

Time to defibrillation was found to be a major predictor of survival after a cardiac arrest. Only bed volume and arrest location were associated with differences in rates of delayed defibrillation (lower rates in larger hospitals and in ICUs). The variability was not due to differences in patient characteristics, but was due to hospital-level effects. Academic status, geographical location, arrest volume, and daily admission volume did not affect the time to defibrillation.

The study was able to identify only a few facility characteristics that account for the variability between hospitals in the rate of delayed defibrillation. The study emphasizes the need for new approaches to identifying hospital innovations in process-of-care measures that are associated with improved performance in defibrillation times.

Bottom Line: Future research is needed to better understand the reason for the wide variation between hospitals in the rate of delayed defibrillation after in-hospital cardiac arrest.

Citation: Chan PS, Nichol G, Krumholz HM, Spertus JA, Nallamothu BK; American Heart Association National Registry of Cardiopulmonary Resuscitation (NRCPR) Investigators. Hospital variation in time to defibrillation after in-hospital cardiac arrest. Arch Intern Med. 2009;169(14):1265-1273.

Treating for H. Pylori Reduces the Risk for Developing Gastric Cancer in High-Risk Patients

Clinical question: In patients with high-baseline incidence of gastric cancer, does H. pylori eradication reduce the risk for developing gastric cancer?

Background: Gastric cancer remains a major health problem in Asia. The link of H. pylori and gastric cancer has been established, but it remains unclear whether treatment for H. pylori is effective primary prevention for the development of gastric cancer.

Study design: Meta-analysis of six studies.

Setting: All but one trial was performed in Asia.

Synopsis: Seven studies met inclusion criteria, one of which was excluded due to heterogeneity. The six remaining studies were pooled, with 37 of 3,388 (1.1%) treated patients developing a new gastric cancer, compared with 56 of 3,307 (1.7%) patients who received placebo or were in the control group (RR 0.65; 0.43-0.98). Most patients received gastric biopsy prior to enrollment, and most of those demonstrated gastric atrophy or intestinal metaplasia.

These patients, despite more advanced precancerous pathology findings, still benefited from eradication. The seventh study, which was excluded, enrolled patients with early gastric cancer; these patients still benefited from H. pylori eradication and, when included in the meta-analysis, the RR was even lower, 0.57 (0.49-0.81).

Only two trials were double-blinded, but all of the studies employed the same definition of gastric cancer and held to excellent data reporting standards. This study encourages screening and treatment in high-risk patients given the widespread incidence of H. pylori.

Bottom Line: Treatment of H. pylori reduces the risk of gastric cancer in high-risk patients.

Citation: Fuccio L, Zagari RM, Eusebi LH, et al. Meta-analysis: can Helicobacter pylori eradication treatment reduce the risk for gastric cancer? Ann Intern Med. 2009;151(2):121-128.

Patients on Anti-Platelet Agents with Acute Coronary Syndrome Have a Lower Bleeding Risk When Treated with Fondaparinux

Clinical question: Is there a difference in bleeding risk with fondaparinux and enoxaparin when used with GPIIb/IIIa inhibitors or thienopyridines in NSTEMI-ACS?

Background: The OASIS 5 study reported a 50% reduction in severe bleeding when comparing fondaparinux to enoxaparin in ACS while maintaining a similar efficacy. This subgroup analysis was performed to evaluate whether reduced bleeding risk with fondaparinux remains in patients treated with additional anti-platelet agents.

Study design: Subgroup analysis of a large, multicenter, randomized, double-blind trial.

Setting: Acute-care hospitals in North America, Eastern and Western Europe, Latin America, Australia, and Asia.

Synopsis: Patients with NSTE-ACS received either fondaparinux or enoxaparin and were treated with GPIIb/IIIa inhibitors or thienopyridines at the discretion of their physician. At 30 days, the fondaparinux group had similar efficacy and decreased bleeding risk in both the GPIIb/IIIa and the thienopyridine groups. Of the 3,630 patients in the GPIIb/IIIa group, the risk for major bleeding with fondaparinux was 5.2%, whereas the risk with enoxaparin was 8.3% (HR 0.61; P<0.001) compared with enoxaparin. Of the 1,352 patients treated with thienopyridines, the risk for major bleeding with fondaparinux was 3.4%, whereas the risk with enoxaparin was 5.4% (HR 0.62; P<0.001).

Bottom Line: This subgroup analysis suggests there are less-severe bleeding complications in patients treated with fondaparinux when compared with enoxaparin in the setting of cotreatment with GPIIb/IIIa inhibitors, thienopyridines, or both.

Citation: Jolly SS, Faxon DP, Fox KA, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors of thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. J Am Coll Cardiol. 2009;54(5):468-476.

Surrogate Decision-Makers Frequently Doubt Clinicians’ Ability to Predict Medical Futility

Clinical question: What attitudes do surrogate decision-makers hold toward clinicians’ predictions of medical futility in critically-ill patients?

Background: The clinical judgment of medical futility leading to the withdrawal of life-sustaining treatment—despite the objections of surrogate decision-makers—is controversial. Very little is known about how surrogate decision-makers view the futility rationale when physicians suggest limiting the use of life-sustaining treatment.

Study design: Multicenter, mixed, qualitative and quantitative study.

Setting: Three ICUs in three different California hospitals from 2006 to 2007.

Synopsis: Semi-structured interviews of surrogate decision-makers for 50 incapacitated, critically-ill patients were performed to ascertain their beliefs about medical futility in response to hypothetical situations. Of the surrogates surveyed, 64% expressed doubt about physicians’ futility predictions.

The interviewees gave four main reasons for their doubts. Two reasons not previously described were doubts about the accuracy of physicians’ predictions and the need for surrogates to see futility themselves. Previously described sources of conflict included a misunderstanding about prognosis and religious-based objections. Surrogates with religious objections were more likely to request continuation of life-sustaining treatments than those with secular or experiential objections (OR 4; 95% CI 1.2-14.0; P=0.03). Nearly a third (32%) of surrogates elected to continue life support with a <1% survival estimate; 18% elected to continue life support when physicians thought there was no chance of survival.

This study has several limitations: a small sample size, the use of hypothetical situations, and the inability to assess attitudes as they change over time.

Bottom line: The nature of surrogate decision-makers’ doubts about medical futility can help predict whether they accept predictions of medical futility from physicians.

Citation: Zier LS, Burack JH, Micco G, Chipman AK, Frank JA, White DB. Surrogate decision makers’ responses to physicians’ predictions of medical futility. Chest. 2009;136:110-117. TH

PEDIATRIC HM LITerature

House-Staff Signout Complexities Remain

By Mark Shen, MD

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

Clinical question: What are the characteristics of signout among house staff?

Background: Inadequate signout is a recognized contributor to medical errors. As care has become increasingly fragmented among house staff who must comply with work-hour restrictions, both the absolute number of signouts and the potential for incomplete transfer of information increase. Despite recent Joint Commission requirements to standardize handoffs, comprehensive analyses of the process remain scarce.

Study design: Quantitative and qualitative analysis of audiotaped oral internal-medicine signout.

Setting: Academic teaching hospital.

Synopsis: Audiotaped signout for eight internal-medicine house-staff teams during two time periods in 2006 were analyzed for content, clarity of language, and surrounding environment. Most signout (59.2%) did not include questions, and questioning of patient management was often indirect when it occurred. A spectrum of clarity existed from unclear anticipatory guidance to clear, concise instructions. Interruptions occurred less than 20% of the time. Familiarity with patients, sense of responsibility for patients, sequential signouts, experience, and comprehensiveness of the written form affected the content of the signout.

This study provides insight into the broad array of factors that affect signout. Despite the potential for interactive facilitation of understanding, the process is often one-sided and operator-dependent. Such systems-based factors as familiarity with patients and sequential signouts might affect quality, while cultural norms (such as sense of responsibility) also play a role.

Limitations of this study include the nonblinded observation method and the potential for institution-specific culture to limit applicability. Nonetheless, this study adds to literature painting a broader and complex picture of a routine hospital process often taken for granted.

Bottom line: Improving and standardizing handoffs requires attention to multifaceted domains that commonly affect complex human organizations.

Citation: Horwitz LI, Moin T, Krumholz HM, Wang L, Bradley EH. What are covering doctors told about their patients? Analysis of sign-out among internal medicine house staff. Qual Saf Health Care. 2009;18(4):248-255.

Literature at a Glance

A guide to this month’s abstracts

• Steroids reduce mortality only in patients with confirmed bacterial meningitis.
• Probiotics can be useful in the treatment of acute diarrhea in children.
• CT pulmonary angiography is not inferior to V/Q scanning for exclusion of PE.
• Hospitalist care results in shorter LOS compared with care by traditional general internists and family practice physicians.
• The early risk of stroke after TIA is approximately 15% to 20% at 90 days after the sentinel event.
• Different anti-thrombotic strategies produce no difference in outcomes of early acute coronary syndromes.
• The risk of fatal PE is highest in the first year after medication is stopped.
• Beers criteria medications are associated with fewer ED visits by elderly patients compared with warfarin, digoxin, and insulin.

Do Steroids Affect the Outcome in Patients with Meningitis?

Background: Pyogenic (bacterial) meningitis has high morbidity and mortality. Studies suggest some benefit of steroids in children but provide limited evidence for adult use.

Study design: Intention-to-treat, randomized control trial.

Setting: Single hospital in Vietnam.

Synopsis: Of 435 patients older than 14 with suspected meningitis all received lumbar puncture with randomization to IV dexamethasone or placebo for four days. Results showed 69% of patients had definite meningitis, 28.3% were probable, and 2.8% had an alternative diagnosis based on culture results.

The primary outcome was death after one month, which did not differ among groups (risk ratio [RR] 0.79, confidence interval [CI] 0.45-1.39).

Predefined subgroup analysis of patients with definitive meningitis showed a significant reduction in mortality at one month (RR 0.43, CI 0.2-0.94) and death/disability at six months (odds ratio [OR] 0.56, CI 0.32-0.98).

In patients with probable meningitis, those who received steroids demonstrated a trend toward harm (OR 2.65, CI 0.73-9.63).

Probable versus definite meningitis was determined retrospectively based on cultures. The most common isolate was Streptococcus suis.

Bottom line: This study provides some evidence for using steroids in adults with confirmed bacterial meningitis. Clinical application is limited by bacterial epidemiology and the difficulty of prospectively separating patients who would benefit from those who might be harmed.

Citation: Nguyen TH, Tran TH, Thwaites G, et. al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med. 2007;357:2431-2439.

Which Probiotic Preparations Best Reduce the Duration of Acute Diarrhea in Children?

Background: Probiotics have been suggested as an adjunctive therapy to reduce the severity and duration of acute diarrhea in children. However, there are no clear data to suggest if specific probiotic agents are superior to others.

Study design: Prospective single-blind, randomized, controlled trial.

Setting: Outpatient primary care in Naples, Italy.

Synopsis: This study compared five commercially available probiotic preparations (mix of Lactobacillus delbrueckii var bulgaricus/Streptococcus thermophilus/L. acidophilus/ Bifido-bacterium bifidum; L. rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; or Enterococcus faecium SF68) and a control group in the treatment of outpatient acute diarrhea in 571 children age 3 months to 36 months.

The primary outcomes were the duration of diarrhea and the number and consistency of stools. The groups receiving Lactobacillus GG and the mixture had a shorter total duration of diarrhea (78.5 and 70 hours, respectively), decreased total number of stools, and improved stool consistency when compared with the control (115.5 hours). The other therapies showed no improvement over the control group. These data report on products commercially available in Italy, which may differ greatly from products available locally.

Bottom line: Probiotic preparations for the treatment of acute diarrhea in children should be chosen based on effectiveness data.

Citation: Canani RB, Cirillo P, Terrin G, et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ 2007;335:340-345.

Is CTPA a Reliable Alternative to V/Q Scan for Diagnosing PE?

Background: Computed tomography pulmonary angiogram (CTPA) has replaced ventilation/perfusion (V/Q) scanning at many hospitals as the test of choice for ruling out pulmonary embolism (PE). But limited clinical data compare CTPA with V/Q scanning in those suspected of having venous thromboembolism (VTE).

Study design: Randomized, investigator blinded, controlled trial.

Setting: The emergency departments (ED), inpatient wards, and outpatient clinics of five academic centers.

Synopsis: In the study, 1,411 patients were enrolled from five medical centers. Of 694 patients randomized to CTPA, 133 (19.2%) were diagnosed with VTE in the initial evaluation period, while 101 of 712 patients (14.2%) receiving a V/Q scan were diagnosed with VTE.

Patients not initially diagnosed with VTE were monitored. At three-month follow-up, 0.4% of the CTPA group and 1.0% of the V/Q group had a diagnosed VTE.

The overall rate of VTE found in the initial diagnostic period was significantly greater in patients randomized to CTPA (19.2% vs. 14.2%; difference, 5.0%; 95% CI; 1.1% to 8.9% p=.01). This suggests CTPA has a higher false positive rate or detects clinically insignificant thrombi.

Bottom line: CTPA was not inferior to V/Q scanning for excluding clinically meaningful PE, but CTPA diagnosed about 30% more patients with VTE than did V/Q scanning.

Citation: Anderson DR, Kahn SR, Rodger MA, et al. Computed tomographic pulmonary angiography vs. ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-2753.

Does the Hospitalist Model Improve Length of Stay, Quality, and Cost of Care?

Background: The hospitalist model, with increased physician availability and expertise but greater discontinuity of care, is becoming more prevalent in U.S. medicine. What little is known about how this model will affect patient care is derived from a number of small studies.

Study design: Retrospective cohort study.

Setting: 45 small to midsize, predominantly nonteaching hospitals throughout the U.S.

Synopsis: Using the Premier Healthcare Informatics database, this study examined information on 76,926 patients admitted for seven common diagnoses to one of three services: hospitalist, general internist, or family physician. Analysis showed that patients on a hospitalist service had a 0.4-day shorter length of stay (p<0.001) compared with those on a general internist or family physician service.

The cost to patients cared for by a hospitalist was lower than the cost of family physicians ($125 less, p=0.33) and internists ($268 less, p=0.02). There was no difference found in death rate or 14-day readmission rate among the three services.

Given the retrospective design of this study, no causal relationship can be deduced. This study is further limited by its lack of specific data on the physicians categorized into one of the three groups solely by administrative data. The authors had concerns that the biases inherent to the retrospective nature of their work accounted for the significant difference found between hospitalists and internists.

Bottom line: The hospitalist model is associated with modest improvements in length of stay as compared with traditional inpatient approaches.

Citation: Lindenauer PK, Rothberg MB, Pekow PS, et. al. Outcomes of care by hospitalists, general internists, and family physicians. N Engl J Med. 2007;357:2589-2600.

What Is the Stroke Risk Soon after TIA, and What Factors Drive the Variability of Previous Findings?

Background: Many studies have attempted to estimate the risk of stroke in the early period after a transient ischemic attack (TIA). These studies vary widely in their calculation of the estimated risk. Further, the clinical and methodological factors underlying this variability are unclear.

Study design: Systematic review and meta-analysis.

Setting: Community and hospital.

Synopsis: Searching the Coch­rane review database, MEDLINE, EMBASE, CINAHL, and BIOSIS, 11 studies from 1973 to 2006 were included for meta-analysis, selected from 694 potential candidate studies identified on initial screening. The studies ranged in size from 62 to 2,285 patients.

The pooled estimate of risk for stroke following TIA was found to be 3.5%, 8%, and 9.2% at two, 30, and 90 days following TIA, respectively. However, there was significant heterogeneity for all periods considered (p<0.001).

Outcome ascertainment was identified as a major source of methodological heterogeneity. When risk of stroke at follow-up was determined by passive ascertainment (e.g., administrative documentation) the early risk of stroke was 3.1% two days after TIA, 6.4% at 30 days, and 8.7% at 90 days. But active ascertainment (e.g., direct, personal contact with study participants) determined stroke risk to be 9.9%, 13.4%, and 17.4% at two, 30, and 90 days after TIA, respectively.

Bottom line: Based on analysis of completed studies that included directly observed follow-up of study participants, the early risk of stroke after TIA is approximately 15% to 20% at 90 days following the sentinel event.

Citation: Wu CM, McLaughlin K, Lorenzetti DL, Hill MD, Manns BJ, Ghali WA. Early risk of stroke after transient ischemic attack. Arch Intern Med. 2007;167:2417-2422.

What Is the 1-year Ischemia and Mortality Rate for Three Anti-thrombotic Therapies for Early Invasive Management of ACS?

Background: Early interventional or surgical revascularization has improved morbidity and mortality in patients with acute coronary syndrome (ACS). The optimal anti-thrombotic regimen to reduce late ischemic and death rates has not been determined.

Study design: Prospective, open-label randomized control trial.

Setting: 450 academic and community-based institutions in 17 countries.

Synopsis: A total of 13,819 patients were enrolled between August 2003 and December 2005. They were assigned to heparin plus glycoprotein (GP) IIb/IIIa inhibitors (n=4,603), bivalirudin (Angiomax) plus IIb/IIIa inhibitors (n=4,604), or bivalirudin monotherapy (n=4,612).

For patients receiving GP IIb/IIIa inhibitors, a 2x2 factorial design assigned half the heparin and bivalirudin groups to routine upstream GP inhibitor administration (4,605 patients). The other half received selective GP IIb/IIIa inhibitors administration if PCI was indicated (4,602 patients).

At one year, there was no statistically significant difference in ischemia or mortality rate among the three therapy groups. No difference in ischemia rate was detected between the two GP IIb/IIIa inhibitor utilization strategies.

Since the hypotheses and the power for the one-year analysis in this trial were not prospectively determined, the results are considered to be exploratory and hypothesis generating.

Bottom line: At one year, there is no statistically significant difference in ischemia or mortality rate for the three antithrombotic regiments and the two glycoprotein utilization strategies.

Citation: Stone GW, Ware JH, Bertrand ME, et. al. Antithrombotic strategies in patients with acute coronary syndromes undergoing early invasive management. One-year results from the ACUITY trial. JAMA 2007;298:2497-2505.

What Is the PE Risk after Discontinuing Anticoagulation in Patients with Symptomatic VTE?

Background: The natural history of patients with symptomatic VTE who have completed anticoagulation is not well understood.

Study design: Inception cohort using pooled data from a prospective cohort study and one arm of an open-label randomized trial.

Setting: Academic medical centers in Canada, Sweden, and Italy.

Synopsis: Using pooled data from two previous studies, 2,052 patients with a first diagnosis of symptomatic VTE (lower-extremity deep-vein thrombosis [DVT], PE, or both) were evaluated for fatal PE after a standard course of therapy (mean of six months) with a vitamin K antagonist.

Patients were followed for up to 120 months. The investigators found an annual event risk of 0.19-0.49 per 100 person-years for fatal PE. Patients with prolonged immobility, active cancer, and thrombophilia were excluded, as were those with recurrent acute DVT.

Secondary analysis revealed an incidence of any fatal, definite or probable PE within the first year of discontinuing therapy of 0.35%-0.81%.

After the first year, the annual event risk ranged from 0.15-0.40 events per 100 person-years. Patients with advanced age, idiopathic VTE as well as those presenting with PE had higher rates of fatal PE.

Bottom line: There is a real though small (less than 1%) risk of fatal PE in the first year following discontinuation of anticoagulation for the first VTE episode. The optimal course of treatment for patients with idiopathic VTE is yet to be determined.

Citation: Douketis JD, Gu CS, Schulman S, et al. The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Ann Intern Med. 2007;147(11):766-774.

Do the Beers Criteria Predict ED Visits Associated with Adverse Drug Events?

Background: Adverse drug events are common in the elderly. The Beers criteria are a consensus-based list of 41 medications that are considered inappropriate for use in older adults and often lead to poor outcomes.

Study design: Retrospective medical record review and data analysis.

Setting: Three nationally representative, U.S. public health surveillance systems: the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance System (NEISS-CADES), 2004-2005; the National Ambulatory Medical Care Survey (NAMCS), 2004; and National Hospital Ambulatory Medical Care Survey (NHAMCS), 2004.

Synopsis: Using data collected from ED visits at 58 hospitals in the NEISS-CADES system, this study estimated that 177,504 visits for adverse drug events occur annually in the United States. Only 8.8% of such visits were attributable to the 41 medications included in the Beers criteria. Three drug classes (anticoagulant and antiplatelet agents, antidiabetic agents, and narrow therapeutic index agents) accounted for nearly half of all such ED visits. Warfarin (17.3%), insulin (13%), and digoxin (3.2%) were the most commonly implicated medications, collectively accounting for 33% of visits (CI, 27.8% to 38.7%).

This study suggests that because of the common use and high risk of adverse events associated with these three drugs, interventions targeting their use may prevent ED visits for adverse drug events in the elderly, compared with interventions aimed at reducing the use of medications identified in the Beers criteria.

This study only included adverse drug events identified in the ED and relied on the diagnosis and documentation of such events by the ED physician.

Bottom line: Beers criteria medications, although considered inappropriate for use in the elderly, were associated with significantly fewer ED visits for adverse events compared with warfarin, digoxin, and insulin.

Citation: Budnitz DS, Shehab N, Kegler SR, et. al. Medication use leading to emergency department visits for adverse drug events in older adults. Ann Intern Med. 2007;147:755-765. TH

Literature at a Glance

A guide to this month’s abstracts

• Steroids reduce mortality only in patients with confirmed bacterial meningitis.
• Probiotics can be useful in the treatment of acute diarrhea in children.
• CT pulmonary angiography is not inferior to V/Q scanning for exclusion of PE.
• Hospitalist care results in shorter LOS compared with care by traditional general internists and family practice physicians.
• The early risk of stroke after TIA is approximately 15% to 20% at 90 days after the sentinel event.
• Different anti-thrombotic strategies produce no difference in outcomes of early acute coronary syndromes.
• The risk of fatal PE is highest in the first year after medication is stopped.
• Beers criteria medications are associated with fewer ED visits by elderly patients compared with warfarin, digoxin, and insulin.

Do Steroids Affect the Outcome in Patients with Meningitis?

Background: Pyogenic (bacterial) meningitis has high morbidity and mortality. Studies suggest some benefit of steroids in children but provide limited evidence for adult use.

Study design: Intention-to-treat, randomized control trial.

Setting: Single hospital in Vietnam.

Synopsis: Of 435 patients older than 14 with suspected meningitis all received lumbar puncture with randomization to IV dexamethasone or placebo for four days. Results showed 69% of patients had definite meningitis, 28.3% were probable, and 2.8% had an alternative diagnosis based on culture results.

The primary outcome was death after one month, which did not differ among groups (risk ratio [RR] 0.79, confidence interval [CI] 0.45-1.39).

Predefined subgroup analysis of patients with definitive meningitis showed a significant reduction in mortality at one month (RR 0.43, CI 0.2-0.94) and death/disability at six months (odds ratio [OR] 0.56, CI 0.32-0.98).

In patients with probable meningitis, those who received steroids demonstrated a trend toward harm (OR 2.65, CI 0.73-9.63).

Probable versus definite meningitis was determined retrospectively based on cultures. The most common isolate was Streptococcus suis.

Bottom line: This study provides some evidence for using steroids in adults with confirmed bacterial meningitis. Clinical application is limited by bacterial epidemiology and the difficulty of prospectively separating patients who would benefit from those who might be harmed.

Citation: Nguyen TH, Tran TH, Thwaites G, et. al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med. 2007;357:2431-2439.

Which Probiotic Preparations Best Reduce the Duration of Acute Diarrhea in Children?

Background: Probiotics have been suggested as an adjunctive therapy to reduce the severity and duration of acute diarrhea in children. However, there are no clear data to suggest if specific probiotic agents are superior to others.

Study design: Prospective single-blind, randomized, controlled trial.

Setting: Outpatient primary care in Naples, Italy.

Synopsis: This study compared five commercially available probiotic preparations (mix of Lactobacillus delbrueckii var bulgaricus/Streptococcus thermophilus/L. acidophilus/ Bifido-bacterium bifidum; L. rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; or Enterococcus faecium SF68) and a control group in the treatment of outpatient acute diarrhea in 571 children age 3 months to 36 months.

The primary outcomes were the duration of diarrhea and the number and consistency of stools. The groups receiving Lactobacillus GG and the mixture had a shorter total duration of diarrhea (78.5 and 70 hours, respectively), decreased total number of stools, and improved stool consistency when compared with the control (115.5 hours). The other therapies showed no improvement over the control group. These data report on products commercially available in Italy, which may differ greatly from products available locally.

Bottom line: Probiotic preparations for the treatment of acute diarrhea in children should be chosen based on effectiveness data.

Citation: Canani RB, Cirillo P, Terrin G, et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ 2007;335:340-345.

Is CTPA a Reliable Alternative to V/Q Scan for Diagnosing PE?

Background: Computed tomography pulmonary angiogram (CTPA) has replaced ventilation/perfusion (V/Q) scanning at many hospitals as the test of choice for ruling out pulmonary embolism (PE). But limited clinical data compare CTPA with V/Q scanning in those suspected of having venous thromboembolism (VTE).

Study design: Randomized, investigator blinded, controlled trial.

Setting: The emergency departments (ED), inpatient wards, and outpatient clinics of five academic centers.

Synopsis: In the study, 1,411 patients were enrolled from five medical centers. Of 694 patients randomized to CTPA, 133 (19.2%) were diagnosed with VTE in the initial evaluation period, while 101 of 712 patients (14.2%) receiving a V/Q scan were diagnosed with VTE.

Patients not initially diagnosed with VTE were monitored. At three-month follow-up, 0.4% of the CTPA group and 1.0% of the V/Q group had a diagnosed VTE.

The overall rate of VTE found in the initial diagnostic period was significantly greater in patients randomized to CTPA (19.2% vs. 14.2%; difference, 5.0%; 95% CI; 1.1% to 8.9% p=.01). This suggests CTPA has a higher false positive rate or detects clinically insignificant thrombi.

Bottom line: CTPA was not inferior to V/Q scanning for excluding clinically meaningful PE, but CTPA diagnosed about 30% more patients with VTE than did V/Q scanning.

Citation: Anderson DR, Kahn SR, Rodger MA, et al. Computed tomographic pulmonary angiography vs. ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-2753.

Does the Hospitalist Model Improve Length of Stay, Quality, and Cost of Care?

Background: The hospitalist model, with increased physician availability and expertise but greater discontinuity of care, is becoming more prevalent in U.S. medicine. What little is known about how this model will affect patient care is derived from a number of small studies.

Study design: Retrospective cohort study.

Setting: 45 small to midsize, predominantly nonteaching hospitals throughout the U.S.

Synopsis: Using the Premier Healthcare Informatics database, this study examined information on 76,926 patients admitted for seven common diagnoses to one of three services: hospitalist, general internist, or family physician. Analysis showed that patients on a hospitalist service had a 0.4-day shorter length of stay (p<0.001) compared with those on a general internist or family physician service.

The cost to patients cared for by a hospitalist was lower than the cost of family physicians ($125 less, p=0.33) and internists ($268 less, p=0.02). There was no difference found in death rate or 14-day readmission rate among the three services.

Given the retrospective design of this study, no causal relationship can be deduced. This study is further limited by its lack of specific data on the physicians categorized into one of the three groups solely by administrative data. The authors had concerns that the biases inherent to the retrospective nature of their work accounted for the significant difference found between hospitalists and internists.

Bottom line: The hospitalist model is associated with modest improvements in length of stay as compared with traditional inpatient approaches.

Citation: Lindenauer PK, Rothberg MB, Pekow PS, et. al. Outcomes of care by hospitalists, general internists, and family physicians. N Engl J Med. 2007;357:2589-2600.

What Is the Stroke Risk Soon after TIA, and What Factors Drive the Variability of Previous Findings?

Background: Many studies have attempted to estimate the risk of stroke in the early period after a transient ischemic attack (TIA). These studies vary widely in their calculation of the estimated risk. Further, the clinical and methodological factors underlying this variability are unclear.

Study design: Systematic review and meta-analysis.

Setting: Community and hospital.

Synopsis: Searching the Coch­rane review database, MEDLINE, EMBASE, CINAHL, and BIOSIS, 11 studies from 1973 to 2006 were included for meta-analysis, selected from 694 potential candidate studies identified on initial screening. The studies ranged in size from 62 to 2,285 patients.

The pooled estimate of risk for stroke following TIA was found to be 3.5%, 8%, and 9.2% at two, 30, and 90 days following TIA, respectively. However, there was significant heterogeneity for all periods considered (p<0.001).

Outcome ascertainment was identified as a major source of methodological heterogeneity. When risk of stroke at follow-up was determined by passive ascertainment (e.g., administrative documentation) the early risk of stroke was 3.1% two days after TIA, 6.4% at 30 days, and 8.7% at 90 days. But active ascertainment (e.g., direct, personal contact with study participants) determined stroke risk to be 9.9%, 13.4%, and 17.4% at two, 30, and 90 days after TIA, respectively.

Bottom line: Based on analysis of completed studies that included directly observed follow-up of study participants, the early risk of stroke after TIA is approximately 15% to 20% at 90 days following the sentinel event.

Citation: Wu CM, McLaughlin K, Lorenzetti DL, Hill MD, Manns BJ, Ghali WA. Early risk of stroke after transient ischemic attack. Arch Intern Med. 2007;167:2417-2422.

What Is the 1-year Ischemia and Mortality Rate for Three Anti-thrombotic Therapies for Early Invasive Management of ACS?

Background: Early interventional or surgical revascularization has improved morbidity and mortality in patients with acute coronary syndrome (ACS). The optimal anti-thrombotic regimen to reduce late ischemic and death rates has not been determined.

Study design: Prospective, open-label randomized control trial.

Setting: 450 academic and community-based institutions in 17 countries.

Synopsis: A total of 13,819 patients were enrolled between August 2003 and December 2005. They were assigned to heparin plus glycoprotein (GP) IIb/IIIa inhibitors (n=4,603), bivalirudin (Angiomax) plus IIb/IIIa inhibitors (n=4,604), or bivalirudin monotherapy (n=4,612).

For patients receiving GP IIb/IIIa inhibitors, a 2x2 factorial design assigned half the heparin and bivalirudin groups to routine upstream GP inhibitor administration (4,605 patients). The other half received selective GP IIb/IIIa inhibitors administration if PCI was indicated (4,602 patients).

At one year, there was no statistically significant difference in ischemia or mortality rate among the three therapy groups. No difference in ischemia rate was detected between the two GP IIb/IIIa inhibitor utilization strategies.

Since the hypotheses and the power for the one-year analysis in this trial were not prospectively determined, the results are considered to be exploratory and hypothesis generating.

Bottom line: At one year, there is no statistically significant difference in ischemia or mortality rate for the three antithrombotic regiments and the two glycoprotein utilization strategies.

Citation: Stone GW, Ware JH, Bertrand ME, et. al. Antithrombotic strategies in patients with acute coronary syndromes undergoing early invasive management. One-year results from the ACUITY trial. JAMA 2007;298:2497-2505.

What Is the PE Risk after Discontinuing Anticoagulation in Patients with Symptomatic VTE?

Background: The natural history of patients with symptomatic VTE who have completed anticoagulation is not well understood.

Study design: Inception cohort using pooled data from a prospective cohort study and one arm of an open-label randomized trial.

Setting: Academic medical centers in Canada, Sweden, and Italy.

Synopsis: Using pooled data from two previous studies, 2,052 patients with a first diagnosis of symptomatic VTE (lower-extremity deep-vein thrombosis [DVT], PE, or both) were evaluated for fatal PE after a standard course of therapy (mean of six months) with a vitamin K antagonist.

Patients were followed for up to 120 months. The investigators found an annual event risk of 0.19-0.49 per 100 person-years for fatal PE. Patients with prolonged immobility, active cancer, and thrombophilia were excluded, as were those with recurrent acute DVT.

Secondary analysis revealed an incidence of any fatal, definite or probable PE within the first year of discontinuing therapy of 0.35%-0.81%.

After the first year, the annual event risk ranged from 0.15-0.40 events per 100 person-years. Patients with advanced age, idiopathic VTE as well as those presenting with PE had higher rates of fatal PE.

Bottom line: There is a real though small (less than 1%) risk of fatal PE in the first year following discontinuation of anticoagulation for the first VTE episode. The optimal course of treatment for patients with idiopathic VTE is yet to be determined.

Citation: Douketis JD, Gu CS, Schulman S, et al. The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Ann Intern Med. 2007;147(11):766-774.

Do the Beers Criteria Predict ED Visits Associated with Adverse Drug Events?

Background: Adverse drug events are common in the elderly. The Beers criteria are a consensus-based list of 41 medications that are considered inappropriate for use in older adults and often lead to poor outcomes.

Study design: Retrospective medical record review and data analysis.

Setting: Three nationally representative, U.S. public health surveillance systems: the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance System (NEISS-CADES), 2004-2005; the National Ambulatory Medical Care Survey (NAMCS), 2004; and National Hospital Ambulatory Medical Care Survey (NHAMCS), 2004.

Synopsis: Using data collected from ED visits at 58 hospitals in the NEISS-CADES system, this study estimated that 177,504 visits for adverse drug events occur annually in the United States. Only 8.8% of such visits were attributable to the 41 medications included in the Beers criteria. Three drug classes (anticoagulant and antiplatelet agents, antidiabetic agents, and narrow therapeutic index agents) accounted for nearly half of all such ED visits. Warfarin (17.3%), insulin (13%), and digoxin (3.2%) were the most commonly implicated medications, collectively accounting for 33% of visits (CI, 27.8% to 38.7%).

This study suggests that because of the common use and high risk of adverse events associated with these three drugs, interventions targeting their use may prevent ED visits for adverse drug events in the elderly, compared with interventions aimed at reducing the use of medications identified in the Beers criteria.

This study only included adverse drug events identified in the ED and relied on the diagnosis and documentation of such events by the ED physician.

Bottom line: Beers criteria medications, although considered inappropriate for use in the elderly, were associated with significantly fewer ED visits for adverse events compared with warfarin, digoxin, and insulin.

Citation: Budnitz DS, Shehab N, Kegler SR, et. al. Medication use leading to emergency department visits for adverse drug events in older adults. Ann Intern Med. 2007;147:755-765. TH

Literature at a Glance

A guide to this month’s abstracts

• Steroids reduce mortality only in patients with confirmed bacterial meningitis.
• Probiotics can be useful in the treatment of acute diarrhea in children.
• CT pulmonary angiography is not inferior to V/Q scanning for exclusion of PE.
• Hospitalist care results in shorter LOS compared with care by traditional general internists and family practice physicians.
• The early risk of stroke after TIA is approximately 15% to 20% at 90 days after the sentinel event.
• Different anti-thrombotic strategies produce no difference in outcomes of early acute coronary syndromes.
• The risk of fatal PE is highest in the first year after medication is stopped.
• Beers criteria medications are associated with fewer ED visits by elderly patients compared with warfarin, digoxin, and insulin.

Do Steroids Affect the Outcome in Patients with Meningitis?

Background: Pyogenic (bacterial) meningitis has high morbidity and mortality. Studies suggest some benefit of steroids in children but provide limited evidence for adult use.

Study design: Intention-to-treat, randomized control trial.

Setting: Single hospital in Vietnam.

Synopsis: Of 435 patients older than 14 with suspected meningitis all received lumbar puncture with randomization to IV dexamethasone or placebo for four days. Results showed 69% of patients had definite meningitis, 28.3% were probable, and 2.8% had an alternative diagnosis based on culture results.

The primary outcome was death after one month, which did not differ among groups (risk ratio [RR] 0.79, confidence interval [CI] 0.45-1.39).

Predefined subgroup analysis of patients with definitive meningitis showed a significant reduction in mortality at one month (RR 0.43, CI 0.2-0.94) and death/disability at six months (odds ratio [OR] 0.56, CI 0.32-0.98).

In patients with probable meningitis, those who received steroids demonstrated a trend toward harm (OR 2.65, CI 0.73-9.63).

Probable versus definite meningitis was determined retrospectively based on cultures. The most common isolate was Streptococcus suis.

Bottom line: This study provides some evidence for using steroids in adults with confirmed bacterial meningitis. Clinical application is limited by bacterial epidemiology and the difficulty of prospectively separating patients who would benefit from those who might be harmed.

Citation: Nguyen TH, Tran TH, Thwaites G, et. al. Dexamethasone in Vietnamese adolescents and adults with bacterial meningitis. N Engl J Med. 2007;357:2431-2439.

Which Probiotic Preparations Best Reduce the Duration of Acute Diarrhea in Children?

Background: Probiotics have been suggested as an adjunctive therapy to reduce the severity and duration of acute diarrhea in children. However, there are no clear data to suggest if specific probiotic agents are superior to others.

Study design: Prospective single-blind, randomized, controlled trial.

Setting: Outpatient primary care in Naples, Italy.

Synopsis: This study compared five commercially available probiotic preparations (mix of Lactobacillus delbrueckii var bulgaricus/Streptococcus thermophilus/L. acidophilus/ Bifido-bacterium bifidum; L. rhamnosus strain GG; Saccharomyces boulardii; Bacillus clausii; or Enterococcus faecium SF68) and a control group in the treatment of outpatient acute diarrhea in 571 children age 3 months to 36 months.

The primary outcomes were the duration of diarrhea and the number and consistency of stools. The groups receiving Lactobacillus GG and the mixture had a shorter total duration of diarrhea (78.5 and 70 hours, respectively), decreased total number of stools, and improved stool consistency when compared with the control (115.5 hours). The other therapies showed no improvement over the control group. These data report on products commercially available in Italy, which may differ greatly from products available locally.

Bottom line: Probiotic preparations for the treatment of acute diarrhea in children should be chosen based on effectiveness data.

Citation: Canani RB, Cirillo P, Terrin G, et al. Probiotics for treatment of acute diarrhoea in children: randomised clinical trial of five different preparations. BMJ 2007;335:340-345.

Is CTPA a Reliable Alternative to V/Q Scan for Diagnosing PE?

Background: Computed tomography pulmonary angiogram (CTPA) has replaced ventilation/perfusion (V/Q) scanning at many hospitals as the test of choice for ruling out pulmonary embolism (PE). But limited clinical data compare CTPA with V/Q scanning in those suspected of having venous thromboembolism (VTE).

Study design: Randomized, investigator blinded, controlled trial.

Setting: The emergency departments (ED), inpatient wards, and outpatient clinics of five academic centers.

Synopsis: In the study, 1,411 patients were enrolled from five medical centers. Of 694 patients randomized to CTPA, 133 (19.2%) were diagnosed with VTE in the initial evaluation period, while 101 of 712 patients (14.2%) receiving a V/Q scan were diagnosed with VTE.

Patients not initially diagnosed with VTE were monitored. At three-month follow-up, 0.4% of the CTPA group and 1.0% of the V/Q group had a diagnosed VTE.

The overall rate of VTE found in the initial diagnostic period was significantly greater in patients randomized to CTPA (19.2% vs. 14.2%; difference, 5.0%; 95% CI; 1.1% to 8.9% p=.01). This suggests CTPA has a higher false positive rate or detects clinically insignificant thrombi.

Bottom line: CTPA was not inferior to V/Q scanning for excluding clinically meaningful PE, but CTPA diagnosed about 30% more patients with VTE than did V/Q scanning.

Citation: Anderson DR, Kahn SR, Rodger MA, et al. Computed tomographic pulmonary angiography vs. ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial. JAMA. 2007;298(23):2743-2753.

Does the Hospitalist Model Improve Length of Stay, Quality, and Cost of Care?

Background: The hospitalist model, with increased physician availability and expertise but greater discontinuity of care, is becoming more prevalent in U.S. medicine. What little is known about how this model will affect patient care is derived from a number of small studies.

Study design: Retrospective cohort study.

Setting: 45 small to midsize, predominantly nonteaching hospitals throughout the U.S.

Synopsis: Using the Premier Healthcare Informatics database, this study examined information on 76,926 patients admitted for seven common diagnoses to one of three services: hospitalist, general internist, or family physician. Analysis showed that patients on a hospitalist service had a 0.4-day shorter length of stay (p<0.001) compared with those on a general internist or family physician service.

The cost to patients cared for by a hospitalist was lower than the cost of family physicians ($125 less, p=0.33) and internists ($268 less, p=0.02). There was no difference found in death rate or 14-day readmission rate among the three services.

Given the retrospective design of this study, no causal relationship can be deduced. This study is further limited by its lack of specific data on the physicians categorized into one of the three groups solely by administrative data. The authors had concerns that the biases inherent to the retrospective nature of their work accounted for the significant difference found between hospitalists and internists.

Bottom line: The hospitalist model is associated with modest improvements in length of stay as compared with traditional inpatient approaches.

Citation: Lindenauer PK, Rothberg MB, Pekow PS, et. al. Outcomes of care by hospitalists, general internists, and family physicians. N Engl J Med. 2007;357:2589-2600.

What Is the Stroke Risk Soon after TIA, and What Factors Drive the Variability of Previous Findings?

Background: Many studies have attempted to estimate the risk of stroke in the early period after a transient ischemic attack (TIA). These studies vary widely in their calculation of the estimated risk. Further, the clinical and methodological factors underlying this variability are unclear.

Study design: Systematic review and meta-analysis.

Setting: Community and hospital.

Synopsis: Searching the Coch­rane review database, MEDLINE, EMBASE, CINAHL, and BIOSIS, 11 studies from 1973 to 2006 were included for meta-analysis, selected from 694 potential candidate studies identified on initial screening. The studies ranged in size from 62 to 2,285 patients.

The pooled estimate of risk for stroke following TIA was found to be 3.5%, 8%, and 9.2% at two, 30, and 90 days following TIA, respectively. However, there was significant heterogeneity for all periods considered (p<0.001).

Outcome ascertainment was identified as a major source of methodological heterogeneity. When risk of stroke at follow-up was determined by passive ascertainment (e.g., administrative documentation) the early risk of stroke was 3.1% two days after TIA, 6.4% at 30 days, and 8.7% at 90 days. But active ascertainment (e.g., direct, personal contact with study participants) determined stroke risk to be 9.9%, 13.4%, and 17.4% at two, 30, and 90 days after TIA, respectively.

Bottom line: Based on analysis of completed studies that included directly observed follow-up of study participants, the early risk of stroke after TIA is approximately 15% to 20% at 90 days following the sentinel event.

Citation: Wu CM, McLaughlin K, Lorenzetti DL, Hill MD, Manns BJ, Ghali WA. Early risk of stroke after transient ischemic attack. Arch Intern Med. 2007;167:2417-2422.

What Is the 1-year Ischemia and Mortality Rate for Three Anti-thrombotic Therapies for Early Invasive Management of ACS?

Background: Early interventional or surgical revascularization has improved morbidity and mortality in patients with acute coronary syndrome (ACS). The optimal anti-thrombotic regimen to reduce late ischemic and death rates has not been determined.

Study design: Prospective, open-label randomized control trial.

Setting: 450 academic and community-based institutions in 17 countries.

Synopsis: A total of 13,819 patients were enrolled between August 2003 and December 2005. They were assigned to heparin plus glycoprotein (GP) IIb/IIIa inhibitors (n=4,603), bivalirudin (Angiomax) plus IIb/IIIa inhibitors (n=4,604), or bivalirudin monotherapy (n=4,612).

For patients receiving GP IIb/IIIa inhibitors, a 2x2 factorial design assigned half the heparin and bivalirudin groups to routine upstream GP inhibitor administration (4,605 patients). The other half received selective GP IIb/IIIa inhibitors administration if PCI was indicated (4,602 patients).

At one year, there was no statistically significant difference in ischemia or mortality rate among the three therapy groups. No difference in ischemia rate was detected between the two GP IIb/IIIa inhibitor utilization strategies.

Since the hypotheses and the power for the one-year analysis in this trial were not prospectively determined, the results are considered to be exploratory and hypothesis generating.

Bottom line: At one year, there is no statistically significant difference in ischemia or mortality rate for the three antithrombotic regiments and the two glycoprotein utilization strategies.

Citation: Stone GW, Ware JH, Bertrand ME, et. al. Antithrombotic strategies in patients with acute coronary syndromes undergoing early invasive management. One-year results from the ACUITY trial. JAMA 2007;298:2497-2505.

What Is the PE Risk after Discontinuing Anticoagulation in Patients with Symptomatic VTE?

Background: The natural history of patients with symptomatic VTE who have completed anticoagulation is not well understood.

Study design: Inception cohort using pooled data from a prospective cohort study and one arm of an open-label randomized trial.

Setting: Academic medical centers in Canada, Sweden, and Italy.

Synopsis: Using pooled data from two previous studies, 2,052 patients with a first diagnosis of symptomatic VTE (lower-extremity deep-vein thrombosis [DVT], PE, or both) were evaluated for fatal PE after a standard course of therapy (mean of six months) with a vitamin K antagonist.

Patients were followed for up to 120 months. The investigators found an annual event risk of 0.19-0.49 per 100 person-years for fatal PE. Patients with prolonged immobility, active cancer, and thrombophilia were excluded, as were those with recurrent acute DVT.

Secondary analysis revealed an incidence of any fatal, definite or probable PE within the first year of discontinuing therapy of 0.35%-0.81%.

After the first year, the annual event risk ranged from 0.15-0.40 events per 100 person-years. Patients with advanced age, idiopathic VTE as well as those presenting with PE had higher rates of fatal PE.

Bottom line: There is a real though small (less than 1%) risk of fatal PE in the first year following discontinuation of anticoagulation for the first VTE episode. The optimal course of treatment for patients with idiopathic VTE is yet to be determined.

Citation: Douketis JD, Gu CS, Schulman S, et al. The risk for fatal pulmonary embolism after discontinuing anticoagulant therapy for venous thromboembolism. Ann Intern Med. 2007;147(11):766-774.

Do the Beers Criteria Predict ED Visits Associated with Adverse Drug Events?

Background: Adverse drug events are common in the elderly. The Beers criteria are a consensus-based list of 41 medications that are considered inappropriate for use in older adults and often lead to poor outcomes.

Study design: Retrospective medical record review and data analysis.

Setting: Three nationally representative, U.S. public health surveillance systems: the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance System (NEISS-CADES), 2004-2005; the National Ambulatory Medical Care Survey (NAMCS), 2004; and National Hospital Ambulatory Medical Care Survey (NHAMCS), 2004.

Synopsis: Using data collected from ED visits at 58 hospitals in the NEISS-CADES system, this study estimated that 177,504 visits for adverse drug events occur annually in the United States. Only 8.8% of such visits were attributable to the 41 medications included in the Beers criteria. Three drug classes (anticoagulant and antiplatelet agents, antidiabetic agents, and narrow therapeutic index agents) accounted for nearly half of all such ED visits. Warfarin (17.3%), insulin (13%), and digoxin (3.2%) were the most commonly implicated medications, collectively accounting for 33% of visits (CI, 27.8% to 38.7%).

This study suggests that because of the common use and high risk of adverse events associated with these three drugs, interventions targeting their use may prevent ED visits for adverse drug events in the elderly, compared with interventions aimed at reducing the use of medications identified in the Beers criteria.

This study only included adverse drug events identified in the ED and relied on the diagnosis and documentation of such events by the ED physician.

Bottom line: Beers criteria medications, although considered inappropriate for use in the elderly, were associated with significantly fewer ED visits for adverse events compared with warfarin, digoxin, and insulin.

Citation: Budnitz DS, Shehab N, Kegler SR, et. al. Medication use leading to emergency department visits for adverse drug events in older adults. Ann Intern Med. 2007;147:755-765. TH