David Lee, MD, MBA

Clinical question: Is routine preoperative urine screening beneficial?

Background: The value of preoperative urine screening is unproven, except before urologic procedures. Furthermore, treatment of asymptomatic bacteriuria may lead to adverse events, including diarrhea, allergic reactions, and Clostridium difficile infection (CDI).

Study design: Retrospective chart review.

Setting: Patients who underwent cardiothoracic, orthopedic, and vascular surgeries at the Minneapolis Veterans Affairs Medical Center in 2010.

Synopsis: A total of 1,934 procedures were performed on 1,699 patients, most of which were orthopedics procedures (1,291 in 1,115 patients). A urine culture was obtained before 25% of procedures with significant variation by service (cardiothoracic, 85%; vascular, 48%; orthopedic, 4%). Bacteriuria was detected in 11% of urine cultures (54 of 489), but antimicrobial drugs were dispensed to just 16 patients.

To identify correlates of preoperative urine culture use, patients with and without urine cultures were compared. The rate of surgical-site infection was similar for both groups. Postoperative UTI was more frequent among patients with bacteriuria. Rates of diarrhea, allergy, and CDI did not differ. Paradoxically, patients treated for preoperative UTI were more likely to develop surgical-site infections (45% vs. 14%; P=0.03). Postoperative UTI was also more frequent among treated patients versus untreated patients (18% vs. 7%).

Bottom line: This is the largest study to assess outcomes for routine preoperative urine cultures. These findings demonstrate that preoperative screening for, and treatment of, asymptomatic bacteriuria should be avoided in patients undergoing nonurologic surgical procedures.

Citation: Drekonja DM, Zarmbinski B, Johnson JR. Preoperative urine culture at a veterans affairs medical center. JAMA Intern Med. 2013;173(1):71-72.

Visit our website for more physician reviews of recent HM-relevant literature.

Clinical question: Is routine preoperative urine screening beneficial?

Background: The value of preoperative urine screening is unproven, except before urologic procedures. Furthermore, treatment of asymptomatic bacteriuria may lead to adverse events, including diarrhea, allergic reactions, and Clostridium difficile infection (CDI).

Study design: Retrospective chart review.

Setting: Patients who underwent cardiothoracic, orthopedic, and vascular surgeries at the Minneapolis Veterans Affairs Medical Center in 2010.

Synopsis: A total of 1,934 procedures were performed on 1,699 patients, most of which were orthopedics procedures (1,291 in 1,115 patients). A urine culture was obtained before 25% of procedures with significant variation by service (cardiothoracic, 85%; vascular, 48%; orthopedic, 4%). Bacteriuria was detected in 11% of urine cultures (54 of 489), but antimicrobial drugs were dispensed to just 16 patients.

To identify correlates of preoperative urine culture use, patients with and without urine cultures were compared. The rate of surgical-site infection was similar for both groups. Postoperative UTI was more frequent among patients with bacteriuria. Rates of diarrhea, allergy, and CDI did not differ. Paradoxically, patients treated for preoperative UTI were more likely to develop surgical-site infections (45% vs. 14%; P=0.03). Postoperative UTI was also more frequent among treated patients versus untreated patients (18% vs. 7%).

Bottom line: This is the largest study to assess outcomes for routine preoperative urine cultures. These findings demonstrate that preoperative screening for, and treatment of, asymptomatic bacteriuria should be avoided in patients undergoing nonurologic surgical procedures.

Citation: Drekonja DM, Zarmbinski B, Johnson JR. Preoperative urine culture at a veterans affairs medical center. JAMA Intern Med. 2013;173(1):71-72.

Visit our website for more physician reviews of recent HM-relevant literature.

Clinical question: Is routine preoperative urine screening beneficial?

Background: The value of preoperative urine screening is unproven, except before urologic procedures. Furthermore, treatment of asymptomatic bacteriuria may lead to adverse events, including diarrhea, allergic reactions, and Clostridium difficile infection (CDI).

Study design: Retrospective chart review.

Setting: Patients who underwent cardiothoracic, orthopedic, and vascular surgeries at the Minneapolis Veterans Affairs Medical Center in 2010.

Synopsis: A total of 1,934 procedures were performed on 1,699 patients, most of which were orthopedics procedures (1,291 in 1,115 patients). A urine culture was obtained before 25% of procedures with significant variation by service (cardiothoracic, 85%; vascular, 48%; orthopedic, 4%). Bacteriuria was detected in 11% of urine cultures (54 of 489), but antimicrobial drugs were dispensed to just 16 patients.

To identify correlates of preoperative urine culture use, patients with and without urine cultures were compared. The rate of surgical-site infection was similar for both groups. Postoperative UTI was more frequent among patients with bacteriuria. Rates of diarrhea, allergy, and CDI did not differ. Paradoxically, patients treated for preoperative UTI were more likely to develop surgical-site infections (45% vs. 14%; P=0.03). Postoperative UTI was also more frequent among treated patients versus untreated patients (18% vs. 7%).

Bottom line: This is the largest study to assess outcomes for routine preoperative urine cultures. These findings demonstrate that preoperative screening for, and treatment of, asymptomatic bacteriuria should be avoided in patients undergoing nonurologic surgical procedures.

Citation: Drekonja DM, Zarmbinski B, Johnson JR. Preoperative urine culture at a veterans affairs medical center. JAMA Intern Med. 2013;173(1):71-72.

Visit our website for more physician reviews of recent HM-relevant literature.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Value of routine preoperative urine screening assessed
2. Impact of hospitalist-led intermediate care on patient survival
3. Risks of blood transfusion to treat upper GI bleeding
4. Low-dose steroids and increased mortality in sepsis
5. Reduced length of stay and hospital readmission rates
6. Restrictive blood transfusion strategies better for acute myocardial infarction
7. Trends in GI illnesses and their associated costs
8. Apixaban as a stand-alone anticoagulant in patients with VTE
9. Guidelines for upper endoscopy use in gastroesophageal reflux disease

Avoid Preoperative Urine Culture in Nonurologic Surgical Procedures

Clinical question: Is routine preoperative urine screening beneficial?

Background: The value of preoperative urine screening is unproven, except before urologic procedures. Furthermore, treatment of asymptomatic bacteriuria may lead to adverse events, including diarrhea, allergic reactions, and Clostridium difficile infection (CDI).

Study design: Retrospective chart review.

Setting: Patients who underwent cardiothoracic, orthopedic, and vascular surgeries at the Minneapolis Veterans Affairs Medical Center in 2010.

Synopsis: A total of 1,934 procedures were performed on 1,699 patients, most of which were orthopedics procedures (1,291 in 1,115 patients). A urine culture was obtained before 25% of procedures with significant variation by service (cardiothoracic, 85%; vascular, 48%; orthopedic, 4%). Bacteriuria was detected in 11% of urine cultures (54 of 489), but antimicrobial drugs were dispensed to just 16 patients.

To identify correlates of preoperative urine culture use, patients with and without urine cultures were compared. The rate of surgical-site infection was similar for both groups. Postoperative UTI was more frequent among patients with bacteriuria. Rates of diarrhea, allergy, and CDI did not differ. Paradoxically, patients treated for preoperative UTI were more likely to develop surgical-site infections (45% vs. 14%; P=0.03). Postoperative UTI was also more frequent among treated patients versus untreated patients (18% vs. 7%).

Bottom line: This is the largest study to assess outcomes for routine preoperative urine cultures. These findings demonstrate that preoperative screening for, and treatment of, asymptomatic bacteriuria should be avoided in patients undergoing nonurologic surgical procedures.

Citation: Drekonja DM, Zarmbinski B, Johnson JR. Preoperative urine culture at a veterans affairs medical center. JAMA Intern Med. 2013;173(1):71-72.

Intermediate Care Staffed by Hospitalists: Impact on Mortality, Comanagement, and Teaching

Clinical question: Does a hospitalist-led intermediate-care unit improve patient survival?

Background: Hospitalized patients are complex, and institutions often have to balance matching patient acuity to either an ICU or a regular ward. However, an intermediate-care setting might be an attractive strategy to provide rational care according to patient needs while expanding comanagement and teaching services.

Study design: Retrospective observational study.

Setting: Intermediate-care unit of a single academic hospital.

Synopsis: In-hospital mortality in this intermediate-care unit was 20.6%, whereas the expected mortality was 23.2% based on Simplified Acute Physiology Score II (SAPS II) score. The correlation between SAPS II predicted and observed death rates was accurate and statistically significant (P<0.001). Comanagement was performed with several medical and surgical teams, with an increase in perioperative comanagement of 22.7% (P=0.014). The number of training residents in the intermediate-care unit increased to 30.4% from 4.3% (P=0.002).

Bottom line: An intermediate-care unit led by hospitalists showed encouraging results in patient mortality, as well as comanagement and teaching opportunities.

Citation: Lucena JF, Alegre F, Rodil R, et al. Results of a retrospective observational study of intermediate care staffed by hospitalists: impact on mortality, co-management, and teaching. J Hosp Med. 2012;7(5):411-415.

Blood Transfusion Associated with Increased Risk of Rebleeding in Patients with Nonvariceal Upper GI Bleeding

Clinical question: Does more liberal use of blood transfusions in the setting of nonvariceal upper GI bleeding result in patient harm?

Background: Randomized controlled trials have demonstrated that a more liberal approach to blood transfusions for patients in the medical intensive-care unit results in higher mortality. However, the potential harmful effect of blood transfusions in the setting of GI bleeding has not been demonstrated.

Study design: Retrospective cohort study.

Setting: Canadian hospitals.

Synopsis: Based on a retrospective analysis of the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), the authors determined there was a statistically significant association between patients who received a blood transfusion for the management of nonvariceal upper GI bleeding and the risk of rebleeding. The rate of rebleeding in patients who received a blood transfusion was 23.6% compared with 11.3% in patients who were not transfused (P<0.01). There was no statistically significant difference in mortality.

Although this was a reasonably large observational study that included 1,677 patients with nonvariceal upper GI bleeding, it is vulnerable to confounding. It suggests the need to further study potential harm of blood transfusion in the setting of GI bleeding, but it should not result in a change in clinical practice at this time.

Bottom line: Prospective randomized studies are needed to determine if there are harmful effects of blood transfusions in the setting of GI bleeding and to better define a threshold for transfusion.

Citation: Restellini S, Kherad O, Jairath V, Martel M, Barkun AN. Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding. Aliment Pharmacol Ther. 2013;37:316-322.

Low-Dose Steroids in Sepsis Associated with Increase in Mortality

Clinical question: What is the role of steroids in the treatment of adult patients with sepsis?

Background: The Surviving Sepsis Campaign guidelines have previously recommended administering steroids to patients with septic shock not responsive to fluid resuscitation and who require vasopressors. However, prior randomized clinical trials studying the use of steroids in these settings have produced conflicting results.

Study design: Retrospective cohort study.

Setting: Two hundred fifty-two hospitals in North America, South America, and Europe.

Synopsis: The Surviving Sepsis Campaign management bundle has been shown to reduce mortality in patients with sepsis. However, it is not known which particular elements of the management bundle result in improved mortality. The Surviving Sepsis Campaign database included 17,847 patients who required vasopressor therapy after adequate fluid resuscitation. This subgroup was analyzed to see if there was a difference in mortality between patients who received low-dose steroids versus those who did not receive steroids. The mortality rate among those who received steroids was statistically higher (with odds ratio of 1.18 and P<0.001) compared with those who did not receive steroids. This finding adds to the body of evidence that calls into question the commonplace practice of administrating steroids to septic patients on vasopressor therapy.

The most recent campaign guidelines recommend the use of steroids in septic patients only if both adequate fluid resuscitation and vasopressor therapy are not able to restore hemodynamic stability.

Bottom line: Further studies are needed to better define the role of steroids in the treatment of sepsis.

Citation: Casserly B, Gerlach H, Phillips GS, et al. Low-dose steroids in adult septic shock: results of the Surviving Sepsis Campaign. Intensive Care Med. 2012;38:1946-1954.

Link Between Length of Stay and Readmission Rates

Clinical question: How has reducing length of stay affected hospital readmission rates?

Background: There are ongoing concerns that improving a hospital’s efficiency by reducing length of stay (LOS) could be associated with higher hospital readmission rates. However, no studies evaluating the relationship between LOS and readmission rates have been done using recent data.

Study design: Retrospective observational study.

Setting: All acute-care Veterans Affairs (VA) hospitals in the U.S.

Synopsis: A total of 4,124,907 index admissions were included in the final sample from all acute medical admissions in 129 acute-care VA hospitals from October 1996 to September 2010. The primary outcomes were the hospital LOS and the 30-day readmission rate. Index admissions for heart failure, chronic obstructive pulmonary disease (COPD), acute myocardial infarction (AMI), community-acquired pneumonia, and gastrointestinal hemorrhage were also analyzed separately.

The risk-adjusted analysis of LOS demonstrated significant reductions for all admissions over the 14-year period, to 3.98 days from 5.44 days, and for all of the individual conditions with reductions ranging from 1.40 days for gastrointestinal hemorrhage to 2.85 days for AMI. There were similar significant reductions in 30-day readmission rates for all admissions to 13.8% from 16.5% and within the individual conditions ranging from 0.9% in community-acquired pneumonia to 3.3% in COPD. These results show that the reductions in LOS did not increase the risk of readmissions. The major limitation of the study was that these data are only from a single healthcare system.

Bottom line: Data from VA hospitals show that reductions in LOS do not have adverse effects on 30-day readmission rates; instead, both LOS and readmission rates improved over the same time period.

Citation: Kaboli PJ, Go JT, Hockenberry J, et al. Associations between reduced hospital length of stay and 30-day readmission rate and mortality: 14-year experience in 129 Veterans Affairs hospitals. Ann Intern Med. 2012;157:837-845.

Better to Restrict Blood Transfusions in Acute Myocardial Infarction

Clinical question: Is a liberal or restrictive blood transfusion strategy better in patients with anemia and acute myocardial infarction?

Background: Patients with acute myocardial infarction (AMI) are often given therapies that can increase their risk for bleeding and anemia, and it is known that AMI patients have a worse prognosis if they have concomitant anemia. No clear consensus exists on the benefit or harm of blood transfusions in AMI patients.

Study design: Systematic review and meta-analysis.

Setting: Ten articles included in the qualitative and quantitative analyses out of 729 screened articles from Jan. 1, 1966, to March 31, 2012, using the search terms “transfusion,” “myocardial infarction,” and “mortality” in English language.

Synopsis: A total of 203,665 study participants were identified from the 10 studies (one randomized and nine observational) that met the inclusion and exclusion criteria. All-cause mortality was significantly higher in AMI patients who received a blood transfusion compared with those who did not (18.2% vs. 10.2%). However, this difference was not statistically significant in patients that had a STEMI or in patients with a baseline hematocrit less than 30%. A multivariate meta-regression with several covariates, excluding demographics, also showed that blood transfusion was associated with higher mortality and higher risk for subsequent myocardial infarction. There was significant heterogeneity in all results, but no single study was found as the source of the heterogeneity, and no significant publication bias was identified. The major limitations to this study are that there is a paucity of randomized trials available that pertain to this specific topic and the authors did not have patient-level covariates to include in their analyses.

Bottom line: There appears to be an increased risk of mortality and subsequent myocardial infarction in AMI patients who receive blood transfusions versus those who do not.

Citation: Chatterjee S, Wetterslev J, Sharma A, Lichstein E, Mukherjee D. Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diversity-adjusted study sequential analysis. JAMA Intern Med. 2013;173(2):132-139.

Trends in GI Illnesses and Their Associated Costs

Clinical question: What are the new trends in GI illnesses and their associated costs?

Background: The frequency of illnesses and their treatment costs have changed over the last decade. In order to help healthcare providers focus their attention on these new trends, a new compilation of data is needed.

Study design: Epidemiological analysis.

Setting: Various governmental and private databases representing outpatient clinics, hospitals, and death certificates from multiple regions of the U.S.

Synopsis: The analysis was blinded to patient identifiers but represented multiple regions of the U.S. Symptoms were abstracted from patient surveys, and the rest of the data were collected from record review. The most common reported symptoms were abdominal pain, followed by nausea, vomiting, diarrhea, constipation, and heartburn. The most common clinic diagnoses were reflux, abdominal pain, enteritis/dyspepsia, and constipation. The most common inpatient discharge primary diagnoses included acute pancreatitis, cholecystitis, and diverticulitis. Impressive increases were seen in the number of morbidly obese, C. diff, and fatty liver diagnoses.

Colon cancer was the most common GI malignancy and had the highest mortality. C. diff was the ninth-leading cause of GI-related deaths. All types of scopes (except endoscopic retrograde cholangiopancreatography) were performed more commonly now than in the past, with colonoscopy being the most common. The most common indication for an upper endoscopy was reflux, which was also the most common outpatient GI diagnosis.

Bottom line: Healthcare providers need to be aware of new GI illness trends and their associated costs.

Citation: Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterol. 2012;143:1179-1187.

Is Apixaban a Good Stand-Alone Anticoagulant for Extended Treatment in VTE Patients?

Clinical question: Is apixaban an option for the extended treatment of VTE in a simple, fixed-dose regimen?

Background: Apixaban is an oral factor Xa inhibitor that is administered in fixed doses without the need for laboratory monitoring. In the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy—Extended Treatment (AMPLIFY-EXT) study, investigators compared the efficacy and safety of two doses of apixaban (2.5 mg and 5 mg) with those of placebo in patients with VTE who had completed six to 12 months of anticoagulation therapy and for whom treating physicians were uncertain about continuing therapy. Additional aims of the study were to determine whether the lower dose of apixaban was effective and whether it was associated with less bleeding than the higher dose, and to examine the effect of treatment on arterial thrombotic outcomes.

Study design: Randomized, double-blind study.

Synopsis: A total of 2,486 patients underwent randomization, 2,482 of whom were included in the intention-to-treat analyses. Symptomatic recurrent VTE or death from VTE occurred in 73 of the 829 patients (8.8%) who were receiving placebo, compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group.

Bottom line: Apixaban is a safe and effective anticoagulant for extended anticoagulation in patients with VTE initially treated with six to 12 months of warfarin.

Citation: Agnelli GM, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699-708.

ACP Guideline Review: Upper Endoscopy for Gastroesophageal Reflux Disease

Clinical question: What are the indications of upper endoscopy in the setting of gastroesophageal reflux disease (GERD)?

Background: GERD is a common condition. Upper endoscopy is widely available and routinely used for diagnosis and management of GERD and its complications. The indications for this procedure are not clearly defined. Overuse of upper endoscopy contributes to higher healthcare costs without improving patient outcomes.

Study design: Literature review and comparison of clinical guidelines from professional organizations by a team of general internists, gastroenterologists, and clinical epidemiologists. The document was not based on a formal systemic review but was intended to provide practical advice based on the best available evidence.

Synopsis: Best practice advice No. 1: Upper endoscopy is indicated in men and women with heartburn and alarm symptoms (dysphagia, bleeding, anemia, weight loss, and recurrent vomiting).

Best practice advice No. 2: Upper endoscopy is indicated in men and women with typical GERD symptoms that persist despite a therapeutic trial of four to eight weeks of twice-daily proton-pump inhibitor therapy, severe erosive esophagitis after a two-month course of proton-pump inhibitor therapy to assess healing and rule out Barrett esophagus, and history of esophageal stricture who have recurrent symptoms of dysphagia.

Best practice advice No. 3: Upper endoscopy might be indicated in men older than 50 with chronic GERD symptoms (symptoms for more than five years) and additional risk factors (nocturnal reflux symptoms, hiatal hernia, elevated body mass index, tobacco use, and intra-abdominal distribution of fat) to detect esophageal adenocarcinoma and Barrett esophagus. It might also be indicated for surveillance evaluation in men and women with a history of Barrett esophagus. In men and women with Barrett esophagus and no dysplasia, surveillance examinations should occur at intervals no more frequently than three to five years. More frequent intervals are indicated in patients with Barrett esophagus and dysplasia.

Bottom line: Use upper endoscopy selectively for patients with GERD.

Citation: Shaheen NJ, Weinberg DS, Denberg TD, et al. Upper endoscopy for gastroesophageal reflux disease: best practice advice from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2012;157(11):808-816.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Value of routine preoperative urine screening assessed
2. Impact of hospitalist-led intermediate care on patient survival
3. Risks of blood transfusion to treat upper GI bleeding
4. Low-dose steroids and increased mortality in sepsis
5. Reduced length of stay and hospital readmission rates
6. Restrictive blood transfusion strategies better for acute myocardial infarction
7. Trends in GI illnesses and their associated costs
8. Apixaban as a stand-alone anticoagulant in patients with VTE
9. Guidelines for upper endoscopy use in gastroesophageal reflux disease

Avoid Preoperative Urine Culture in Nonurologic Surgical Procedures

Clinical question: Is routine preoperative urine screening beneficial?

Background: The value of preoperative urine screening is unproven, except before urologic procedures. Furthermore, treatment of asymptomatic bacteriuria may lead to adverse events, including diarrhea, allergic reactions, and Clostridium difficile infection (CDI).

Study design: Retrospective chart review.

Setting: Patients who underwent cardiothoracic, orthopedic, and vascular surgeries at the Minneapolis Veterans Affairs Medical Center in 2010.

Synopsis: A total of 1,934 procedures were performed on 1,699 patients, most of which were orthopedics procedures (1,291 in 1,115 patients). A urine culture was obtained before 25% of procedures with significant variation by service (cardiothoracic, 85%; vascular, 48%; orthopedic, 4%). Bacteriuria was detected in 11% of urine cultures (54 of 489), but antimicrobial drugs were dispensed to just 16 patients.

To identify correlates of preoperative urine culture use, patients with and without urine cultures were compared. The rate of surgical-site infection was similar for both groups. Postoperative UTI was more frequent among patients with bacteriuria. Rates of diarrhea, allergy, and CDI did not differ. Paradoxically, patients treated for preoperative UTI were more likely to develop surgical-site infections (45% vs. 14%; P=0.03). Postoperative UTI was also more frequent among treated patients versus untreated patients (18% vs. 7%).

Bottom line: This is the largest study to assess outcomes for routine preoperative urine cultures. These findings demonstrate that preoperative screening for, and treatment of, asymptomatic bacteriuria should be avoided in patients undergoing nonurologic surgical procedures.

Citation: Drekonja DM, Zarmbinski B, Johnson JR. Preoperative urine culture at a veterans affairs medical center. JAMA Intern Med. 2013;173(1):71-72.

Intermediate Care Staffed by Hospitalists: Impact on Mortality, Comanagement, and Teaching

Clinical question: Does a hospitalist-led intermediate-care unit improve patient survival?

Background: Hospitalized patients are complex, and institutions often have to balance matching patient acuity to either an ICU or a regular ward. However, an intermediate-care setting might be an attractive strategy to provide rational care according to patient needs while expanding comanagement and teaching services.

Study design: Retrospective observational study.

Setting: Intermediate-care unit of a single academic hospital.

Synopsis: In-hospital mortality in this intermediate-care unit was 20.6%, whereas the expected mortality was 23.2% based on Simplified Acute Physiology Score II (SAPS II) score. The correlation between SAPS II predicted and observed death rates was accurate and statistically significant (P<0.001). Comanagement was performed with several medical and surgical teams, with an increase in perioperative comanagement of 22.7% (P=0.014). The number of training residents in the intermediate-care unit increased to 30.4% from 4.3% (P=0.002).

Bottom line: An intermediate-care unit led by hospitalists showed encouraging results in patient mortality, as well as comanagement and teaching opportunities.

Citation: Lucena JF, Alegre F, Rodil R, et al. Results of a retrospective observational study of intermediate care staffed by hospitalists: impact on mortality, co-management, and teaching. J Hosp Med. 2012;7(5):411-415.

Blood Transfusion Associated with Increased Risk of Rebleeding in Patients with Nonvariceal Upper GI Bleeding

Clinical question: Does more liberal use of blood transfusions in the setting of nonvariceal upper GI bleeding result in patient harm?

Background: Randomized controlled trials have demonstrated that a more liberal approach to blood transfusions for patients in the medical intensive-care unit results in higher mortality. However, the potential harmful effect of blood transfusions in the setting of GI bleeding has not been demonstrated.

Study design: Retrospective cohort study.

Setting: Canadian hospitals.

Synopsis: Based on a retrospective analysis of the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), the authors determined there was a statistically significant association between patients who received a blood transfusion for the management of nonvariceal upper GI bleeding and the risk of rebleeding. The rate of rebleeding in patients who received a blood transfusion was 23.6% compared with 11.3% in patients who were not transfused (P<0.01). There was no statistically significant difference in mortality.

Although this was a reasonably large observational study that included 1,677 patients with nonvariceal upper GI bleeding, it is vulnerable to confounding. It suggests the need to further study potential harm of blood transfusion in the setting of GI bleeding, but it should not result in a change in clinical practice at this time.

Bottom line: Prospective randomized studies are needed to determine if there are harmful effects of blood transfusions in the setting of GI bleeding and to better define a threshold for transfusion.

Citation: Restellini S, Kherad O, Jairath V, Martel M, Barkun AN. Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding. Aliment Pharmacol Ther. 2013;37:316-322.

Low-Dose Steroids in Sepsis Associated with Increase in Mortality

Clinical question: What is the role of steroids in the treatment of adult patients with sepsis?

Background: The Surviving Sepsis Campaign guidelines have previously recommended administering steroids to patients with septic shock not responsive to fluid resuscitation and who require vasopressors. However, prior randomized clinical trials studying the use of steroids in these settings have produced conflicting results.

Study design: Retrospective cohort study.

Setting: Two hundred fifty-two hospitals in North America, South America, and Europe.

Synopsis: The Surviving Sepsis Campaign management bundle has been shown to reduce mortality in patients with sepsis. However, it is not known which particular elements of the management bundle result in improved mortality. The Surviving Sepsis Campaign database included 17,847 patients who required vasopressor therapy after adequate fluid resuscitation. This subgroup was analyzed to see if there was a difference in mortality between patients who received low-dose steroids versus those who did not receive steroids. The mortality rate among those who received steroids was statistically higher (with odds ratio of 1.18 and P<0.001) compared with those who did not receive steroids. This finding adds to the body of evidence that calls into question the commonplace practice of administrating steroids to septic patients on vasopressor therapy.

The most recent campaign guidelines recommend the use of steroids in septic patients only if both adequate fluid resuscitation and vasopressor therapy are not able to restore hemodynamic stability.

Bottom line: Further studies are needed to better define the role of steroids in the treatment of sepsis.

Citation: Casserly B, Gerlach H, Phillips GS, et al. Low-dose steroids in adult septic shock: results of the Surviving Sepsis Campaign. Intensive Care Med. 2012;38:1946-1954.

Link Between Length of Stay and Readmission Rates

Clinical question: How has reducing length of stay affected hospital readmission rates?

Background: There are ongoing concerns that improving a hospital’s efficiency by reducing length of stay (LOS) could be associated with higher hospital readmission rates. However, no studies evaluating the relationship between LOS and readmission rates have been done using recent data.

Study design: Retrospective observational study.

Setting: All acute-care Veterans Affairs (VA) hospitals in the U.S.

Synopsis: A total of 4,124,907 index admissions were included in the final sample from all acute medical admissions in 129 acute-care VA hospitals from October 1996 to September 2010. The primary outcomes were the hospital LOS and the 30-day readmission rate. Index admissions for heart failure, chronic obstructive pulmonary disease (COPD), acute myocardial infarction (AMI), community-acquired pneumonia, and gastrointestinal hemorrhage were also analyzed separately.

The risk-adjusted analysis of LOS demonstrated significant reductions for all admissions over the 14-year period, to 3.98 days from 5.44 days, and for all of the individual conditions with reductions ranging from 1.40 days for gastrointestinal hemorrhage to 2.85 days for AMI. There were similar significant reductions in 30-day readmission rates for all admissions to 13.8% from 16.5% and within the individual conditions ranging from 0.9% in community-acquired pneumonia to 3.3% in COPD. These results show that the reductions in LOS did not increase the risk of readmissions. The major limitation of the study was that these data are only from a single healthcare system.

Bottom line: Data from VA hospitals show that reductions in LOS do not have adverse effects on 30-day readmission rates; instead, both LOS and readmission rates improved over the same time period.

Citation: Kaboli PJ, Go JT, Hockenberry J, et al. Associations between reduced hospital length of stay and 30-day readmission rate and mortality: 14-year experience in 129 Veterans Affairs hospitals. Ann Intern Med. 2012;157:837-845.

Better to Restrict Blood Transfusions in Acute Myocardial Infarction

Clinical question: Is a liberal or restrictive blood transfusion strategy better in patients with anemia and acute myocardial infarction?

Background: Patients with acute myocardial infarction (AMI) are often given therapies that can increase their risk for bleeding and anemia, and it is known that AMI patients have a worse prognosis if they have concomitant anemia. No clear consensus exists on the benefit or harm of blood transfusions in AMI patients.

Study design: Systematic review and meta-analysis.

Setting: Ten articles included in the qualitative and quantitative analyses out of 729 screened articles from Jan. 1, 1966, to March 31, 2012, using the search terms “transfusion,” “myocardial infarction,” and “mortality” in English language.

Synopsis: A total of 203,665 study participants were identified from the 10 studies (one randomized and nine observational) that met the inclusion and exclusion criteria. All-cause mortality was significantly higher in AMI patients who received a blood transfusion compared with those who did not (18.2% vs. 10.2%). However, this difference was not statistically significant in patients that had a STEMI or in patients with a baseline hematocrit less than 30%. A multivariate meta-regression with several covariates, excluding demographics, also showed that blood transfusion was associated with higher mortality and higher risk for subsequent myocardial infarction. There was significant heterogeneity in all results, but no single study was found as the source of the heterogeneity, and no significant publication bias was identified. The major limitations to this study are that there is a paucity of randomized trials available that pertain to this specific topic and the authors did not have patient-level covariates to include in their analyses.

Bottom line: There appears to be an increased risk of mortality and subsequent myocardial infarction in AMI patients who receive blood transfusions versus those who do not.

Citation: Chatterjee S, Wetterslev J, Sharma A, Lichstein E, Mukherjee D. Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diversity-adjusted study sequential analysis. JAMA Intern Med. 2013;173(2):132-139.

Trends in GI Illnesses and Their Associated Costs

Clinical question: What are the new trends in GI illnesses and their associated costs?

Background: The frequency of illnesses and their treatment costs have changed over the last decade. In order to help healthcare providers focus their attention on these new trends, a new compilation of data is needed.

Study design: Epidemiological analysis.

Setting: Various governmental and private databases representing outpatient clinics, hospitals, and death certificates from multiple regions of the U.S.

Synopsis: The analysis was blinded to patient identifiers but represented multiple regions of the U.S. Symptoms were abstracted from patient surveys, and the rest of the data were collected from record review. The most common reported symptoms were abdominal pain, followed by nausea, vomiting, diarrhea, constipation, and heartburn. The most common clinic diagnoses were reflux, abdominal pain, enteritis/dyspepsia, and constipation. The most common inpatient discharge primary diagnoses included acute pancreatitis, cholecystitis, and diverticulitis. Impressive increases were seen in the number of morbidly obese, C. diff, and fatty liver diagnoses.

Colon cancer was the most common GI malignancy and had the highest mortality. C. diff was the ninth-leading cause of GI-related deaths. All types of scopes (except endoscopic retrograde cholangiopancreatography) were performed more commonly now than in the past, with colonoscopy being the most common. The most common indication for an upper endoscopy was reflux, which was also the most common outpatient GI diagnosis.

Bottom line: Healthcare providers need to be aware of new GI illness trends and their associated costs.

Citation: Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterol. 2012;143:1179-1187.

Is Apixaban a Good Stand-Alone Anticoagulant for Extended Treatment in VTE Patients?

Clinical question: Is apixaban an option for the extended treatment of VTE in a simple, fixed-dose regimen?

Background: Apixaban is an oral factor Xa inhibitor that is administered in fixed doses without the need for laboratory monitoring. In the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy—Extended Treatment (AMPLIFY-EXT) study, investigators compared the efficacy and safety of two doses of apixaban (2.5 mg and 5 mg) with those of placebo in patients with VTE who had completed six to 12 months of anticoagulation therapy and for whom treating physicians were uncertain about continuing therapy. Additional aims of the study were to determine whether the lower dose of apixaban was effective and whether it was associated with less bleeding than the higher dose, and to examine the effect of treatment on arterial thrombotic outcomes.

Study design: Randomized, double-blind study.

Synopsis: A total of 2,486 patients underwent randomization, 2,482 of whom were included in the intention-to-treat analyses. Symptomatic recurrent VTE or death from VTE occurred in 73 of the 829 patients (8.8%) who were receiving placebo, compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group.

Bottom line: Apixaban is a safe and effective anticoagulant for extended anticoagulation in patients with VTE initially treated with six to 12 months of warfarin.

Citation: Agnelli GM, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699-708.

ACP Guideline Review: Upper Endoscopy for Gastroesophageal Reflux Disease

Clinical question: What are the indications of upper endoscopy in the setting of gastroesophageal reflux disease (GERD)?

Background: GERD is a common condition. Upper endoscopy is widely available and routinely used for diagnosis and management of GERD and its complications. The indications for this procedure are not clearly defined. Overuse of upper endoscopy contributes to higher healthcare costs without improving patient outcomes.

Study design: Literature review and comparison of clinical guidelines from professional organizations by a team of general internists, gastroenterologists, and clinical epidemiologists. The document was not based on a formal systemic review but was intended to provide practical advice based on the best available evidence.

Synopsis: Best practice advice No. 1: Upper endoscopy is indicated in men and women with heartburn and alarm symptoms (dysphagia, bleeding, anemia, weight loss, and recurrent vomiting).

Best practice advice No. 2: Upper endoscopy is indicated in men and women with typical GERD symptoms that persist despite a therapeutic trial of four to eight weeks of twice-daily proton-pump inhibitor therapy, severe erosive esophagitis after a two-month course of proton-pump inhibitor therapy to assess healing and rule out Barrett esophagus, and history of esophageal stricture who have recurrent symptoms of dysphagia.

Best practice advice No. 3: Upper endoscopy might be indicated in men older than 50 with chronic GERD symptoms (symptoms for more than five years) and additional risk factors (nocturnal reflux symptoms, hiatal hernia, elevated body mass index, tobacco use, and intra-abdominal distribution of fat) to detect esophageal adenocarcinoma and Barrett esophagus. It might also be indicated for surveillance evaluation in men and women with a history of Barrett esophagus. In men and women with Barrett esophagus and no dysplasia, surveillance examinations should occur at intervals no more frequently than three to five years. More frequent intervals are indicated in patients with Barrett esophagus and dysplasia.

Bottom line: Use upper endoscopy selectively for patients with GERD.

Citation: Shaheen NJ, Weinberg DS, Denberg TD, et al. Upper endoscopy for gastroesophageal reflux disease: best practice advice from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2012;157(11):808-816.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Value of routine preoperative urine screening assessed
2. Impact of hospitalist-led intermediate care on patient survival
3. Risks of blood transfusion to treat upper GI bleeding
4. Low-dose steroids and increased mortality in sepsis
5. Reduced length of stay and hospital readmission rates
6. Restrictive blood transfusion strategies better for acute myocardial infarction
7. Trends in GI illnesses and their associated costs
8. Apixaban as a stand-alone anticoagulant in patients with VTE
9. Guidelines for upper endoscopy use in gastroesophageal reflux disease

Avoid Preoperative Urine Culture in Nonurologic Surgical Procedures

Clinical question: Is routine preoperative urine screening beneficial?

Background: The value of preoperative urine screening is unproven, except before urologic procedures. Furthermore, treatment of asymptomatic bacteriuria may lead to adverse events, including diarrhea, allergic reactions, and Clostridium difficile infection (CDI).

Study design: Retrospective chart review.

Setting: Patients who underwent cardiothoracic, orthopedic, and vascular surgeries at the Minneapolis Veterans Affairs Medical Center in 2010.

Synopsis: A total of 1,934 procedures were performed on 1,699 patients, most of which were orthopedics procedures (1,291 in 1,115 patients). A urine culture was obtained before 25% of procedures with significant variation by service (cardiothoracic, 85%; vascular, 48%; orthopedic, 4%). Bacteriuria was detected in 11% of urine cultures (54 of 489), but antimicrobial drugs were dispensed to just 16 patients.

To identify correlates of preoperative urine culture use, patients with and without urine cultures were compared. The rate of surgical-site infection was similar for both groups. Postoperative UTI was more frequent among patients with bacteriuria. Rates of diarrhea, allergy, and CDI did not differ. Paradoxically, patients treated for preoperative UTI were more likely to develop surgical-site infections (45% vs. 14%; P=0.03). Postoperative UTI was also more frequent among treated patients versus untreated patients (18% vs. 7%).

Bottom line: This is the largest study to assess outcomes for routine preoperative urine cultures. These findings demonstrate that preoperative screening for, and treatment of, asymptomatic bacteriuria should be avoided in patients undergoing nonurologic surgical procedures.

Citation: Drekonja DM, Zarmbinski B, Johnson JR. Preoperative urine culture at a veterans affairs medical center. JAMA Intern Med. 2013;173(1):71-72.

Intermediate Care Staffed by Hospitalists: Impact on Mortality, Comanagement, and Teaching

Clinical question: Does a hospitalist-led intermediate-care unit improve patient survival?

Background: Hospitalized patients are complex, and institutions often have to balance matching patient acuity to either an ICU or a regular ward. However, an intermediate-care setting might be an attractive strategy to provide rational care according to patient needs while expanding comanagement and teaching services.

Study design: Retrospective observational study.

Setting: Intermediate-care unit of a single academic hospital.

Synopsis: In-hospital mortality in this intermediate-care unit was 20.6%, whereas the expected mortality was 23.2% based on Simplified Acute Physiology Score II (SAPS II) score. The correlation between SAPS II predicted and observed death rates was accurate and statistically significant (P<0.001). Comanagement was performed with several medical and surgical teams, with an increase in perioperative comanagement of 22.7% (P=0.014). The number of training residents in the intermediate-care unit increased to 30.4% from 4.3% (P=0.002).

Bottom line: An intermediate-care unit led by hospitalists showed encouraging results in patient mortality, as well as comanagement and teaching opportunities.

Citation: Lucena JF, Alegre F, Rodil R, et al. Results of a retrospective observational study of intermediate care staffed by hospitalists: impact on mortality, co-management, and teaching. J Hosp Med. 2012;7(5):411-415.

Blood Transfusion Associated with Increased Risk of Rebleeding in Patients with Nonvariceal Upper GI Bleeding

Clinical question: Does more liberal use of blood transfusions in the setting of nonvariceal upper GI bleeding result in patient harm?

Background: Randomized controlled trials have demonstrated that a more liberal approach to blood transfusions for patients in the medical intensive-care unit results in higher mortality. However, the potential harmful effect of blood transfusions in the setting of GI bleeding has not been demonstrated.

Study design: Retrospective cohort study.

Setting: Canadian hospitals.

Synopsis: Based on a retrospective analysis of the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), the authors determined there was a statistically significant association between patients who received a blood transfusion for the management of nonvariceal upper GI bleeding and the risk of rebleeding. The rate of rebleeding in patients who received a blood transfusion was 23.6% compared with 11.3% in patients who were not transfused (P<0.01). There was no statistically significant difference in mortality.

Although this was a reasonably large observational study that included 1,677 patients with nonvariceal upper GI bleeding, it is vulnerable to confounding. It suggests the need to further study potential harm of blood transfusion in the setting of GI bleeding, but it should not result in a change in clinical practice at this time.

Bottom line: Prospective randomized studies are needed to determine if there are harmful effects of blood transfusions in the setting of GI bleeding and to better define a threshold for transfusion.

Citation: Restellini S, Kherad O, Jairath V, Martel M, Barkun AN. Red blood cell transfusion is associated with increased rebleeding in patients with nonvariceal upper gastrointestinal bleeding. Aliment Pharmacol Ther. 2013;37:316-322.

Low-Dose Steroids in Sepsis Associated with Increase in Mortality

Clinical question: What is the role of steroids in the treatment of adult patients with sepsis?

Background: The Surviving Sepsis Campaign guidelines have previously recommended administering steroids to patients with septic shock not responsive to fluid resuscitation and who require vasopressors. However, prior randomized clinical trials studying the use of steroids in these settings have produced conflicting results.

Study design: Retrospective cohort study.

Setting: Two hundred fifty-two hospitals in North America, South America, and Europe.

Synopsis: The Surviving Sepsis Campaign management bundle has been shown to reduce mortality in patients with sepsis. However, it is not known which particular elements of the management bundle result in improved mortality. The Surviving Sepsis Campaign database included 17,847 patients who required vasopressor therapy after adequate fluid resuscitation. This subgroup was analyzed to see if there was a difference in mortality between patients who received low-dose steroids versus those who did not receive steroids. The mortality rate among those who received steroids was statistically higher (with odds ratio of 1.18 and P<0.001) compared with those who did not receive steroids. This finding adds to the body of evidence that calls into question the commonplace practice of administrating steroids to septic patients on vasopressor therapy.

The most recent campaign guidelines recommend the use of steroids in septic patients only if both adequate fluid resuscitation and vasopressor therapy are not able to restore hemodynamic stability.

Bottom line: Further studies are needed to better define the role of steroids in the treatment of sepsis.

Citation: Casserly B, Gerlach H, Phillips GS, et al. Low-dose steroids in adult septic shock: results of the Surviving Sepsis Campaign. Intensive Care Med. 2012;38:1946-1954.

Link Between Length of Stay and Readmission Rates

Clinical question: How has reducing length of stay affected hospital readmission rates?

Background: There are ongoing concerns that improving a hospital’s efficiency by reducing length of stay (LOS) could be associated with higher hospital readmission rates. However, no studies evaluating the relationship between LOS and readmission rates have been done using recent data.

Study design: Retrospective observational study.

Setting: All acute-care Veterans Affairs (VA) hospitals in the U.S.

Synopsis: A total of 4,124,907 index admissions were included in the final sample from all acute medical admissions in 129 acute-care VA hospitals from October 1996 to September 2010. The primary outcomes were the hospital LOS and the 30-day readmission rate. Index admissions for heart failure, chronic obstructive pulmonary disease (COPD), acute myocardial infarction (AMI), community-acquired pneumonia, and gastrointestinal hemorrhage were also analyzed separately.

The risk-adjusted analysis of LOS demonstrated significant reductions for all admissions over the 14-year period, to 3.98 days from 5.44 days, and for all of the individual conditions with reductions ranging from 1.40 days for gastrointestinal hemorrhage to 2.85 days for AMI. There were similar significant reductions in 30-day readmission rates for all admissions to 13.8% from 16.5% and within the individual conditions ranging from 0.9% in community-acquired pneumonia to 3.3% in COPD. These results show that the reductions in LOS did not increase the risk of readmissions. The major limitation of the study was that these data are only from a single healthcare system.

Bottom line: Data from VA hospitals show that reductions in LOS do not have adverse effects on 30-day readmission rates; instead, both LOS and readmission rates improved over the same time period.

Citation: Kaboli PJ, Go JT, Hockenberry J, et al. Associations between reduced hospital length of stay and 30-day readmission rate and mortality: 14-year experience in 129 Veterans Affairs hospitals. Ann Intern Med. 2012;157:837-845.

Better to Restrict Blood Transfusions in Acute Myocardial Infarction

Clinical question: Is a liberal or restrictive blood transfusion strategy better in patients with anemia and acute myocardial infarction?

Background: Patients with acute myocardial infarction (AMI) are often given therapies that can increase their risk for bleeding and anemia, and it is known that AMI patients have a worse prognosis if they have concomitant anemia. No clear consensus exists on the benefit or harm of blood transfusions in AMI patients.

Study design: Systematic review and meta-analysis.

Setting: Ten articles included in the qualitative and quantitative analyses out of 729 screened articles from Jan. 1, 1966, to March 31, 2012, using the search terms “transfusion,” “myocardial infarction,” and “mortality” in English language.

Synopsis: A total of 203,665 study participants were identified from the 10 studies (one randomized and nine observational) that met the inclusion and exclusion criteria. All-cause mortality was significantly higher in AMI patients who received a blood transfusion compared with those who did not (18.2% vs. 10.2%). However, this difference was not statistically significant in patients that had a STEMI or in patients with a baseline hematocrit less than 30%. A multivariate meta-regression with several covariates, excluding demographics, also showed that blood transfusion was associated with higher mortality and higher risk for subsequent myocardial infarction. There was significant heterogeneity in all results, but no single study was found as the source of the heterogeneity, and no significant publication bias was identified. The major limitations to this study are that there is a paucity of randomized trials available that pertain to this specific topic and the authors did not have patient-level covariates to include in their analyses.

Bottom line: There appears to be an increased risk of mortality and subsequent myocardial infarction in AMI patients who receive blood transfusions versus those who do not.

Citation: Chatterjee S, Wetterslev J, Sharma A, Lichstein E, Mukherjee D. Association of blood transfusion with increased mortality in myocardial infarction: a meta-analysis and diversity-adjusted study sequential analysis. JAMA Intern Med. 2013;173(2):132-139.

Trends in GI Illnesses and Their Associated Costs

Clinical question: What are the new trends in GI illnesses and their associated costs?

Background: The frequency of illnesses and their treatment costs have changed over the last decade. In order to help healthcare providers focus their attention on these new trends, a new compilation of data is needed.

Study design: Epidemiological analysis.

Setting: Various governmental and private databases representing outpatient clinics, hospitals, and death certificates from multiple regions of the U.S.

Synopsis: The analysis was blinded to patient identifiers but represented multiple regions of the U.S. Symptoms were abstracted from patient surveys, and the rest of the data were collected from record review. The most common reported symptoms were abdominal pain, followed by nausea, vomiting, diarrhea, constipation, and heartburn. The most common clinic diagnoses were reflux, abdominal pain, enteritis/dyspepsia, and constipation. The most common inpatient discharge primary diagnoses included acute pancreatitis, cholecystitis, and diverticulitis. Impressive increases were seen in the number of morbidly obese, C. diff, and fatty liver diagnoses.

Colon cancer was the most common GI malignancy and had the highest mortality. C. diff was the ninth-leading cause of GI-related deaths. All types of scopes (except endoscopic retrograde cholangiopancreatography) were performed more commonly now than in the past, with colonoscopy being the most common. The most common indication for an upper endoscopy was reflux, which was also the most common outpatient GI diagnosis.

Bottom line: Healthcare providers need to be aware of new GI illness trends and their associated costs.

Citation: Peery AF, Dellon ES, Lund J, et al. Burden of gastrointestinal disease in the United States: 2012 update. Gastroenterol. 2012;143:1179-1187.

Is Apixaban a Good Stand-Alone Anticoagulant for Extended Treatment in VTE Patients?

Clinical question: Is apixaban an option for the extended treatment of VTE in a simple, fixed-dose regimen?

Background: Apixaban is an oral factor Xa inhibitor that is administered in fixed doses without the need for laboratory monitoring. In the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy—Extended Treatment (AMPLIFY-EXT) study, investigators compared the efficacy and safety of two doses of apixaban (2.5 mg and 5 mg) with those of placebo in patients with VTE who had completed six to 12 months of anticoagulation therapy and for whom treating physicians were uncertain about continuing therapy. Additional aims of the study were to determine whether the lower dose of apixaban was effective and whether it was associated with less bleeding than the higher dose, and to examine the effect of treatment on arterial thrombotic outcomes.

Study design: Randomized, double-blind study.

Synopsis: A total of 2,486 patients underwent randomization, 2,482 of whom were included in the intention-to-treat analyses. Symptomatic recurrent VTE or death from VTE occurred in 73 of the 829 patients (8.8%) who were receiving placebo, compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group.

Bottom line: Apixaban is a safe and effective anticoagulant for extended anticoagulation in patients with VTE initially treated with six to 12 months of warfarin.

Citation: Agnelli GM, Buller HR, Cohen A, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699-708.

ACP Guideline Review: Upper Endoscopy for Gastroesophageal Reflux Disease

Clinical question: What are the indications of upper endoscopy in the setting of gastroesophageal reflux disease (GERD)?

Background: GERD is a common condition. Upper endoscopy is widely available and routinely used for diagnosis and management of GERD and its complications. The indications for this procedure are not clearly defined. Overuse of upper endoscopy contributes to higher healthcare costs without improving patient outcomes.

Study design: Literature review and comparison of clinical guidelines from professional organizations by a team of general internists, gastroenterologists, and clinical epidemiologists. The document was not based on a formal systemic review but was intended to provide practical advice based on the best available evidence.

Synopsis: Best practice advice No. 1: Upper endoscopy is indicated in men and women with heartburn and alarm symptoms (dysphagia, bleeding, anemia, weight loss, and recurrent vomiting).

Best practice advice No. 2: Upper endoscopy is indicated in men and women with typical GERD symptoms that persist despite a therapeutic trial of four to eight weeks of twice-daily proton-pump inhibitor therapy, severe erosive esophagitis after a two-month course of proton-pump inhibitor therapy to assess healing and rule out Barrett esophagus, and history of esophageal stricture who have recurrent symptoms of dysphagia.

Best practice advice No. 3: Upper endoscopy might be indicated in men older than 50 with chronic GERD symptoms (symptoms for more than five years) and additional risk factors (nocturnal reflux symptoms, hiatal hernia, elevated body mass index, tobacco use, and intra-abdominal distribution of fat) to detect esophageal adenocarcinoma and Barrett esophagus. It might also be indicated for surveillance evaluation in men and women with a history of Barrett esophagus. In men and women with Barrett esophagus and no dysplasia, surveillance examinations should occur at intervals no more frequently than three to five years. More frequent intervals are indicated in patients with Barrett esophagus and dysplasia.

Bottom line: Use upper endoscopy selectively for patients with GERD.

Citation: Shaheen NJ, Weinberg DS, Denberg TD, et al. Upper endoscopy for gastroesophageal reflux disease: best practice advice from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2012;157(11):808-816.

Clinical question: How does a brief period of CPR with early analysis of rhythm compare with the strategy of a longer period of CPR with delayed analysis of rhythm in patients with out-of-hospital cardiac arrest?

Background: Based on current guidelines, emergency medical service (EMS) personnel could provide two minutes of CPR before the first analysis of cardiac rhythm. However, there is a paucity of data on the outcomes of this strategy versus the short CPR and early rhythm analysis.

Study design: The EMS groups participating in the study were cluster-randomized to one strategy or the other.

Settings: The Resuscitation Outcome Consortium (ROC) is a clinical trial consortium comprising 10 U.S. and Canadian universities and their regional EMS systems. The trial was conducted at 150 of the 260 EMS agencies participating in the ROC.

Synopsis: This is a cluster-randomized trial involving adults with out-of-hospital cardiac arrest. Patients in the early-analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR, and those in the later-analysis group were assigned to receive 180 seconds of CPR, before the initial electrocardiographic analysis. The primary outcome was survival to hospital discharge with satisfactory functional status (a modified Rankin scale score of =3, on a scale of 0 to 6, with higher scores indicating greater disability).

The study included 9,933 patients, of whom 5,290 were assigned to early analysis of cardiac rhythm and 4,643 to later analysis. A total of 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the criteria for the primary outcome, with a cluster-adjusted difference of -0.2 percentage points (95% confidence interval, -1.1 to 0.7; P=0.59).

Analyses of the data with adjustment for confounding factors, as well as subgroup analyses, showed no survival benefit for either study group.

Bottom line: Among patients who had an out-of-hospital cardiac arrest, there is no difference in the outcomes with a brief period, as compared with a longer period, of EMS-administered CPR before the first analysis of cardiac rhythm.

Citation: Stiell IG, Nichol G, Leroux BG, et al. Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest. N Engl J Med. 2011;365;787-797.

Check out more physician reviews of HM-relevant literature on our website.

Clinical question: How does a brief period of CPR with early analysis of rhythm compare with the strategy of a longer period of CPR with delayed analysis of rhythm in patients with out-of-hospital cardiac arrest?

Background: Based on current guidelines, emergency medical service (EMS) personnel could provide two minutes of CPR before the first analysis of cardiac rhythm. However, there is a paucity of data on the outcomes of this strategy versus the short CPR and early rhythm analysis.

Study design: The EMS groups participating in the study were cluster-randomized to one strategy or the other.

Settings: The Resuscitation Outcome Consortium (ROC) is a clinical trial consortium comprising 10 U.S. and Canadian universities and their regional EMS systems. The trial was conducted at 150 of the 260 EMS agencies participating in the ROC.

Synopsis: This is a cluster-randomized trial involving adults with out-of-hospital cardiac arrest. Patients in the early-analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR, and those in the later-analysis group were assigned to receive 180 seconds of CPR, before the initial electrocardiographic analysis. The primary outcome was survival to hospital discharge with satisfactory functional status (a modified Rankin scale score of =3, on a scale of 0 to 6, with higher scores indicating greater disability).

The study included 9,933 patients, of whom 5,290 were assigned to early analysis of cardiac rhythm and 4,643 to later analysis. A total of 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the criteria for the primary outcome, with a cluster-adjusted difference of -0.2 percentage points (95% confidence interval, -1.1 to 0.7; P=0.59).

Analyses of the data with adjustment for confounding factors, as well as subgroup analyses, showed no survival benefit for either study group.

Bottom line: Among patients who had an out-of-hospital cardiac arrest, there is no difference in the outcomes with a brief period, as compared with a longer period, of EMS-administered CPR before the first analysis of cardiac rhythm.

Citation: Stiell IG, Nichol G, Leroux BG, et al. Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest. N Engl J Med. 2011;365;787-797.

Check out more physician reviews of HM-relevant literature on our website.

Clinical question: How does a brief period of CPR with early analysis of rhythm compare with the strategy of a longer period of CPR with delayed analysis of rhythm in patients with out-of-hospital cardiac arrest?

Background: Based on current guidelines, emergency medical service (EMS) personnel could provide two minutes of CPR before the first analysis of cardiac rhythm. However, there is a paucity of data on the outcomes of this strategy versus the short CPR and early rhythm analysis.

Study design: The EMS groups participating in the study were cluster-randomized to one strategy or the other.

Settings: The Resuscitation Outcome Consortium (ROC) is a clinical trial consortium comprising 10 U.S. and Canadian universities and their regional EMS systems. The trial was conducted at 150 of the 260 EMS agencies participating in the ROC.

Synopsis: This is a cluster-randomized trial involving adults with out-of-hospital cardiac arrest. Patients in the early-analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR, and those in the later-analysis group were assigned to receive 180 seconds of CPR, before the initial electrocardiographic analysis. The primary outcome was survival to hospital discharge with satisfactory functional status (a modified Rankin scale score of =3, on a scale of 0 to 6, with higher scores indicating greater disability).

The study included 9,933 patients, of whom 5,290 were assigned to early analysis of cardiac rhythm and 4,643 to later analysis. A total of 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the criteria for the primary outcome, with a cluster-adjusted difference of -0.2 percentage points (95% confidence interval, -1.1 to 0.7; P=0.59).

Analyses of the data with adjustment for confounding factors, as well as subgroup analyses, showed no survival benefit for either study group.

Bottom line: Among patients who had an out-of-hospital cardiac arrest, there is no difference in the outcomes with a brief period, as compared with a longer period, of EMS-administered CPR before the first analysis of cardiac rhythm.

Citation: Stiell IG, Nichol G, Leroux BG, et al. Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest. N Engl J Med. 2011;365;787-797.

Check out more physician reviews of HM-relevant literature on our website.

Clinical question: In patients undergoing coronary and peripheral angiography, does acetylcysteine before and after the procedure protect the kidneys?

Background: Contrast-induced acute kidney injury is a serious complication of procedures that use iodinated contrast material and can lead to the need for dialysis, prolonged hospital stay, and increased cost and mortality. Acetylcysteine is thought to prevent this, but previous results from more than 40 trials conflict regarding its effectiveness.

Study design: Double-blinded randomized trial.

Setting: Forty-six centers in Brazil.

Synopsis: The study enrolled 2,308 patients with at least one risk factor for contrast-induced kidney injury and undergoing coronary or peripheral arterial diagnostic intravascular angiography or percutaneous intervention. Participants received two doses of acetylcysteine or placebo before and after contrast administration. End points included contrast-induced acute kidney injury, mortality, and the need for dialysis at 30 days.

Disappointingly, acetylcysteine did not significantly reduce the incidence of the end points in any patients, including the high-risk subgroups of those with diabetes mellitus and chronic renal failure, and those receiving the largest amounts of contrast. Limitations of the study include only a small number of events, as a larger number of events may help more accurately assess mortality and the need for dialysis. Additionally, creatinine may not be as good a marker for contrast-induced acute kidney injury as newer markers like cystatin C. The median volume of contrast used was low compared with previous studies, and cointerventions, such as hydration, were at the discretion of the attending physician.

Bottom line: Acetylcysteine use did not result in a lower incidence of contrast-induced acute kidney injury or other renal outcomes, and routine use prior to angiography is not recommended.

Citation: Berwange O, Cavalcanti AB, Sousa AG, et al. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized acetylcysteine for contrast-induced nephropathy trial (ACT). Circulation. 2011;124:1250-1259.

Clinical question: In patients undergoing coronary and peripheral angiography, does acetylcysteine before and after the procedure protect the kidneys?

Background: Contrast-induced acute kidney injury is a serious complication of procedures that use iodinated contrast material and can lead to the need for dialysis, prolonged hospital stay, and increased cost and mortality. Acetylcysteine is thought to prevent this, but previous results from more than 40 trials conflict regarding its effectiveness.

Study design: Double-blinded randomized trial.

Setting: Forty-six centers in Brazil.

Synopsis: The study enrolled 2,308 patients with at least one risk factor for contrast-induced kidney injury and undergoing coronary or peripheral arterial diagnostic intravascular angiography or percutaneous intervention. Participants received two doses of acetylcysteine or placebo before and after contrast administration. End points included contrast-induced acute kidney injury, mortality, and the need for dialysis at 30 days.

Disappointingly, acetylcysteine did not significantly reduce the incidence of the end points in any patients, including the high-risk subgroups of those with diabetes mellitus and chronic renal failure, and those receiving the largest amounts of contrast. Limitations of the study include only a small number of events, as a larger number of events may help more accurately assess mortality and the need for dialysis. Additionally, creatinine may not be as good a marker for contrast-induced acute kidney injury as newer markers like cystatin C. The median volume of contrast used was low compared with previous studies, and cointerventions, such as hydration, were at the discretion of the attending physician.

Bottom line: Acetylcysteine use did not result in a lower incidence of contrast-induced acute kidney injury or other renal outcomes, and routine use prior to angiography is not recommended.

Citation: Berwange O, Cavalcanti AB, Sousa AG, et al. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized acetylcysteine for contrast-induced nephropathy trial (ACT). Circulation. 2011;124:1250-1259.

Clinical question: In patients undergoing coronary and peripheral angiography, does acetylcysteine before and after the procedure protect the kidneys?

Background: Contrast-induced acute kidney injury is a serious complication of procedures that use iodinated contrast material and can lead to the need for dialysis, prolonged hospital stay, and increased cost and mortality. Acetylcysteine is thought to prevent this, but previous results from more than 40 trials conflict regarding its effectiveness.

Study design: Double-blinded randomized trial.

Setting: Forty-six centers in Brazil.

Synopsis: The study enrolled 2,308 patients with at least one risk factor for contrast-induced kidney injury and undergoing coronary or peripheral arterial diagnostic intravascular angiography or percutaneous intervention. Participants received two doses of acetylcysteine or placebo before and after contrast administration. End points included contrast-induced acute kidney injury, mortality, and the need for dialysis at 30 days.

Disappointingly, acetylcysteine did not significantly reduce the incidence of the end points in any patients, including the high-risk subgroups of those with diabetes mellitus and chronic renal failure, and those receiving the largest amounts of contrast. Limitations of the study include only a small number of events, as a larger number of events may help more accurately assess mortality and the need for dialysis. Additionally, creatinine may not be as good a marker for contrast-induced acute kidney injury as newer markers like cystatin C. The median volume of contrast used was low compared with previous studies, and cointerventions, such as hydration, were at the discretion of the attending physician.

Bottom line: Acetylcysteine use did not result in a lower incidence of contrast-induced acute kidney injury or other renal outcomes, and routine use prior to angiography is not recommended.

Citation: Berwange O, Cavalcanti AB, Sousa AG, et al. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized acetylcysteine for contrast-induced nephropathy trial (ACT). Circulation. 2011;124:1250-1259.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Hospitalist views on readmission prevention
2. Characteristics of hospital ICU readmission
3. Effect of clopidogrel on bleeding outcomes in vascular surgery
4. Time-versus tissue-based diagnosis of TIA
5. ETT versus ETT with imaging for the diagnosis of CAD in women
6. Effect of high urine output with adequate hydration on contrast-induced nephropathy
7. Stroke rate in CABG patients with severe carotid artery stenosis
8. Effect of cardiac arrest on long-term cognition

Hospitalists View Readmissions as Potentially Preventable by Team-Based Care

Clinical question: How do front-line hospitalists perceive the preventability of early hospital readmissions?

Background: Hospital readmission has received national attention as an indicator of poor healthcare quality and unnecessary costs. While some studies suggest that some readmissions are preventable, the exact number is unknown. Understanding preventability and the views of front-line clinicians might help hospitalists balance multifactorial compromise between throughput and length of stay.

Study design: Retrospective cohort study.

Setting: Two community tertiary-care hospitals and two suburban hospitals staffed by a single hospitalist group in Portland, Ore.

Synopsis: A group of 17 hospitalists analyzed the inpatient and outpatient charts of 300 consecutive patients readmitted within 21 days of discharge using a structured data collection tool to record patient characteristics, process measures, and perceived preventability of the readmission. Patients were either discharged by internal-medicine hospitalists or had an internal-medicine consultation during their initial stay.

Characteristics of readmitted patients and initial hospital stays were similar to those previously reported in other studies. More than 60% of readmissions were deemed preventable (15%) or possibly preventable (46%). As prevention strategies for these readmissions, hospitalists most frequently suggested interventions under their control, such as longer initial hospital stay (23%). Other potential interventions focused on system approaches, including outpatient appointments, case management, palliative care, and home health.

In most cases (96%), the reviewer was not the discharging hospitalist. Only six hospitalists performed 83% of the reviews, and inter-reviewer reliability was not assessed. Other limitations included confounding biases, such as timing of review, source hospital reviewed, reviewer optimism, and previous primary-care experience of reviewer.

Bottom line: Prevention of hospital readmissions will require a balance between increased length of stay and system-based team approaches beyond the direct control of hospitalists.

Citation: Koekkoek D, Bayley KB, Brown A, Rustvold DL. Hospitalists assess the causes of early hospital readmissions. J Hosp Med. 2011;6:383-388.

Patients with Complex, Severe Illnesses and Persistent Physiologic Abnormalities Have Higher Risk of Intensive-Care-Unit Readmission

Clinical question: Which patient characteristics increase the risk for intensive-care-unit (ICU) readmission?

Background: Patients are often discharged from the ICU based on subjective criteria, workload, and bed demand, making ICU readmission a tempting quality indicator. Studies have examined institutional characteristics leading to ICU readmission, but few have shown how patient case mix affects longer lengths of ICU and hospital stays and higher in-hospital mortality.

Study design: Retrospective observational cohort study using a large, multi-institutional U.S. database.

Setting: Computerized data collection and analysis system from 97 intensive- and cardiac-care units at 35 hospitals in the United States.

Synopsis: Patient-level characteristics and outcomes of 229,375 initial ICU admissions from 2001 to 2009 were compared for patients with and without ICU readmission using the Acute Physiology and Chronic Health Evaluation (APACHE) IV database (Cerner Corporation, Kansas City, Mo.). Multivariable logistic regression analysis identified potential characteristics increasing the risk for ICU readmission. Case-mix adjusted outcomes for mortality and length of stay were calculated.

A total of 13,980 (6.1%) patients were readmitted to the ICUs. Characteristics associated with ICU readmission were similar to those previously reported. In addition to illness severity at initial admission, readmission was associated with complications, poor response to therapy, or persistent physiologic abnormalities at ICU discharge. Patients who were readmitted to the ICU had a risk-adjusted, fourfold greater probability of in-hospital mortality and a 2.5-fold increase in length of hospital stay.

Data were obtained solely from hospitals with an APACHE system, and included only one hospital from the Northeast. Not all ICUs from a single-study hospital were included. DNR orders were not available in the database for analysis.

Bottom line: Persistent physiologic derangements at ICU discharge are as influential on ICU readmission and poor outcomes as other known risk factors, potentially warranting slightly longer ICU stays for these specific patients.

Citation: Kramer AA, Higgins TL, Zimmerman JE. Intensive care unit readmissions in U.S. hospitals: patient characteristics, risk factors, and outcomes. Crit Care Med. 2012;40:3-10.

Clopidogrel Might Not Worsen Bleeding Complications During Surgery

Clinical question: Does clopidogrel cause bleeding complications during vascular surgery?

Background: There is no consensus and few large trials to decide if preoperative clopidogrel use causes bleeding complications in vascular surgeries.

Study design: Prospective.

Setting: New England academic and community centers.

Synopsis: The authors enrolled 10,406 patients from 15 academic and community centers in New England. These patients underwent carotid endarterectomy, lower-extremity bypass, and abdominal aortic aneurysm repair. Ruptured aortic aneurysms were excluded. The use of aspirin, clopidogrel, both, or no anti-platelet therapy within 48 hours before surgery was recorded. The outcomes measured were postoperative bleeding requiring reoperation and the need for packed red blood cell transfusions.

Clopidogrel therapy (n=229) compared with no anti-platelet therapy (n=2,010) did well when measured by reoperation (clopidogrel 0.9%, none 1.5%, P=0.74), incidence of transfusion (clopidogrel 0%, none 18%, P=0.1), and volume of transfusion (clopidogrel 0 units, none 0.7 units, P=0.1). However, the significance, especially for reoperation, is not impressive.

The power of the study could be improved with more clopidogrel users. Another limitation is that the aspirin and clopidogrel platelet effect lasts longer than the 48-hour cutoff. As there were more bleeding complications in the no-anti-platelet group, there is a concern for bias in how the patients were selected and treated.

Bottom line: Clopidogrel might be safe to continue in vascular surgeries, but larger and more valid studies are needed.

Citation: Stone DH, Goodney PP, Schanzer A, et al. Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery. J Vasc Surg. 2011;54:779-784.

Tissue-Defined TIAs Have Better Prognostic Benefits Than Time-Defined TIAs

Citation: Is risk stratification for recurrent stroke better when brain imaging is performed after a transient ischemic attack (TIA)?

Background: The presence of a TIA is a known risk factor for recurrent stroke. There is debate in changing the definition of TIA from time-based to tissue-based. However, it is not known if this will improve management.

Study design: Multicenter observation cohort.

Setting: Twelve independent international research centers.

Synopsis: The current definition of a TIA is a neurological deficit that resolves within 24 hours. To determine the urgency of an admission and work-up, the ABCD2 score (age, blood pressure, clinical symptoms, duration, and diabetes) is often used as a prognostic tool for recurrent stroke. The authors enrolled 4,574 patients with the traditional diagnosis of TIA. In addition to calculating their ABCD2 score, they were then classified as tissue-positive (infarction) or tissue-negative per MRI or CT. At both seven and 90 days after TIA, both imaging modalities when combined with ABCD2 were able to identify risk for recurrent stroke better than if they were used alone.

Limitations included the images being interpreted by their individual healthcare centers and that the stroke centers had lower recurrent rates of stroke compared with community centers. If only a CT can be used, it should be noted that the sensitivity is lower when compared with an MRI in this study.

Bottom line: This categorization of tissue- or non-tissue-positive TIAs improved the prognostic information provided by the ABCD2 score and might improve management decisions.

Citation: Giles MF, Albers GW, Amarenco P, et al. Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA: a multicenter study. Neurology. 2011;77:1222-1228.

ETT Comparable to MPI as Initial Diagnostic Test for Women Suspected of CAD

Clinical question: Is the exercise treadmill test (ETT) equivalent to myocardial perfusion imaging (MPI) as an initial diagnostic test for low-risk women capable of exercising with suspected coronary artery disease (CAD)?

Background: To date, the evidence base for diagnostic testing in women with suspected CAD has been limited, with no randomized trials to guide appropriate clinical decision-making in the choice of noninvasive testing strategies. The aim of this trial was to provide comparative-effectiveness data for women capable of performing exercise testing with regard to whether the addition of imaging to standard ETT provided incremental clinical benefit over index ETT alone.

Study design: Prospective randomized.

Settings: Forty-three cardiology practices across the U.S.

Synopsis: A total of 824 women 40 years of age or older with intermediate pretest CAD likelihood were randomized to ETT or MPI. All the women included in the study were symptomatic with suspected CAD, had an interpretable ECG, and were >5 on DASI (Duke Activity Status Index). A total of 17 primary end points were confirmed, including three nonfatal myocardial infarctions, one heart failure hospitalization, 12 acute coronary syndrome hospitalizations, and only one sudden cardiac death reported in 772 women.

At two years, major adverse cardiovascular events (MACE)-free survival was identical (98%) for women randomized to the ETT or exercise MPI arm (P=0.59). The observed two-year MACE rate was 1.7% for ETT and 2.3% for exercise MPI. For secondary end points, the overall rate of hospitalization for chest pain was 3%. By randomization, the two-year rate of hospitalization for chest pain symptoms was 3% for women in the ETT arm and 4% for those in the exercise MPI arm (P=0.39). An additional six women died from non-cardiac causes (ETT arm, 0.5%; exercise MPI arm, 1%; P=0.39).

Bottom line: ETT is of comparable diagnostic efficacy to MPI as an initial diagnostic test for women suspected of CAD, capable of exercising, based on two-year outcome of cardiac death, nonfatal myocardial infarction, or hospital admission for acute coronary syndrome or heart failure.

Citation: Shaw LJ, Mieres JH, Hendel RH, et al. Comparative effectiveness of exercise electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with suspected coronary artery disease: results from the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial. Circulation. 2011;124:1239-1249.

Controlled Forced Diuresis Is More Effective in High-Risk Patients for CI-AKI Prevention

Clinical question: Is a system of hydration that creates high urine output while maintaining fluid balance better than routine hydration in high-risk patients for preventing contrast-induced acute kidney injury (CI-AKI)?

Background: Hydration with sodium bicarbonate solution and administration of N-acetylcysteine (NAC) help prevent CI-AKI in low- to medium-risk patients. A recent study (PRINCE) suggests that increasing the urine flow rate (≥150 mL/hr) reduces the toxic effect of contrast, but this regimen requires forced diuresis with high doses of furosemide that may result in further renal damage due to negative fluid balance. The RenalGuard system (PLC Medical Systems Inc., Franklin, Mass.) can simultaneously achieve high urine output and maintain fluid balance.

Study design: Randomized, investigator-driven, open-label study comparing two different hydration strategies.

Setting: Multicenter trial in Italy involving patients with chronic kidney disease scheduled for angiography who met the inclusion and exclusion criteria for high risk of developing CI-AKI.

Synopsis: The study included 292 patients randomized to receive sodium bicarbonate solution (control group) versus hydration with saline controlled by the RenalGuard system with furosemide. Both groups received NAC, though at different doses and routes of administration. CI-AKI occurred in 20.5% (30 of 146) in the control group versus 11% (16 of 146) in the RenalGuard group.

Bottom line: Controlled forced diuresis to achieve high urine flow rate is more effective than conventional hydration with sodium bicarbonate solution in high-risk patients for preventing CI-AKI. Larger studies are needed to confirm and define the role of the RenalGuard system.

Citation: Briguori C, Visconti G, Focaccio A, et al. Renal insufficiency after contrast media administration trial II (REMEDIAL II). Circulation. 2011;124:1260-1269.

Severe Asymptomatic Carotid Artery Stenosis Does Not Increase Stroke or Mortality Risks after CAB Surgery

Clinical question: What is the risk for stroke in patients with asymptomatic carotid artery stenosis (CAS) who are undergoing coronary artery bypass grafting (CABG)?

Background: Stroke occurs as a complication of CABG in approximately 2% of patients. The vast majority occur within the first 24 hours of surgery and are associated with a high mortality rate.

Study design: Retrospective cohort.

Setting: A single institution in Washington, D.C.

Synopsis: Data were collected on 878 consecutive patients who had undergone carotid ultrasound before CABG over a six-year period. Patients with severe CAS of >75% (n=117) were compared with those with <75% stenosis (n=761) to assess the rates of in-hospital stroke and mortality.

Patients with severe CAS had similar rates of stroke compared with those without severe CAS (3.4% vs. 3.6%). Additionally, there was no difference in the incidence of in-hospital complications or mortality between the two groups.

Bottom line: The cause of stroke after CABG is complex and multifactorial, but severe CAS alone appears to not be the biggest risk factor for stroke in patients undergoing CABG.

Citation: Mahmoudi M, Hill PC, Xue Z, et al. Patients with severe asymptomatic carotid artery stenosis do not have a higher risk of stroke and mortality after coronary artery bypass surgery. Stroke. 2011;42:2801-2805.

Cardiac Arrest Survivors Have Long-Term Memory Deficits

Clinical question: Are there any lasting cognitive deficits in patients surviving out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation (VF)?

Background: Although advances have been made in the rapid intervention of OHCAs, there are no population-based, age-adjusted studies of the cognitive and neurologic outcomes of long-term survivors when the “chain of survival” is used (rapid emergency services, bystander CPR, early defibrillation, and advanced care).

Study design: Prospective population-based, age-adjusted study.

Setting: Single hospital in Olmsted County, Minn.

Synopsis: Of 332 OHCA patients, 47 survivors were enrolled for neurologic and neuropsychological testing at least six months after a near-death experience (median time since arrest, 7.8 years). Neurologic examination did not reveal any focal deficits related to the event, but long-term survivors had lower scores on measures of long-term memory and learning efficiency (P=0.001). Nearly all survivors were functionally independent at the time of testing. Interestingly, there was no correlation between prolonged call-to-shock time and cognitive ability, suggesting that there is a possibility of positive neurologic outcomes with a call-to-shock time as late as 10 minutes in OHCA. Older age was also not identified as a negative prognostic factor.

A limitation of the study was the small sample size, though larger populations of survivors are difficult to find. The precise meaning of “cognitive impairment” was also controversial and should be better defined for any future studies.

Bottom line: Long-term survivors of OHCA from VF have long-term memory impairment compared with the normal population at the same age and education level.

Citation: Mateen FJ, Josephs KA, Trenerry MR, et al. Long-term cognitive outcomes following out-of-hospital cardiac arrest. Neurology. 2011;77:1438-1445.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Hospitalist views on readmission prevention
2. Characteristics of hospital ICU readmission
3. Effect of clopidogrel on bleeding outcomes in vascular surgery
4. Time-versus tissue-based diagnosis of TIA
5. ETT versus ETT with imaging for the diagnosis of CAD in women
6. Effect of high urine output with adequate hydration on contrast-induced nephropathy
7. Stroke rate in CABG patients with severe carotid artery stenosis
8. Effect of cardiac arrest on long-term cognition

Hospitalists View Readmissions as Potentially Preventable by Team-Based Care

Clinical question: How do front-line hospitalists perceive the preventability of early hospital readmissions?

Background: Hospital readmission has received national attention as an indicator of poor healthcare quality and unnecessary costs. While some studies suggest that some readmissions are preventable, the exact number is unknown. Understanding preventability and the views of front-line clinicians might help hospitalists balance multifactorial compromise between throughput and length of stay.

Study design: Retrospective cohort study.

Setting: Two community tertiary-care hospitals and two suburban hospitals staffed by a single hospitalist group in Portland, Ore.

Synopsis: A group of 17 hospitalists analyzed the inpatient and outpatient charts of 300 consecutive patients readmitted within 21 days of discharge using a structured data collection tool to record patient characteristics, process measures, and perceived preventability of the readmission. Patients were either discharged by internal-medicine hospitalists or had an internal-medicine consultation during their initial stay.

Characteristics of readmitted patients and initial hospital stays were similar to those previously reported in other studies. More than 60% of readmissions were deemed preventable (15%) or possibly preventable (46%). As prevention strategies for these readmissions, hospitalists most frequently suggested interventions under their control, such as longer initial hospital stay (23%). Other potential interventions focused on system approaches, including outpatient appointments, case management, palliative care, and home health.

In most cases (96%), the reviewer was not the discharging hospitalist. Only six hospitalists performed 83% of the reviews, and inter-reviewer reliability was not assessed. Other limitations included confounding biases, such as timing of review, source hospital reviewed, reviewer optimism, and previous primary-care experience of reviewer.

Bottom line: Prevention of hospital readmissions will require a balance between increased length of stay and system-based team approaches beyond the direct control of hospitalists.

Citation: Koekkoek D, Bayley KB, Brown A, Rustvold DL. Hospitalists assess the causes of early hospital readmissions. J Hosp Med. 2011;6:383-388.

Patients with Complex, Severe Illnesses and Persistent Physiologic Abnormalities Have Higher Risk of Intensive-Care-Unit Readmission

Clinical question: Which patient characteristics increase the risk for intensive-care-unit (ICU) readmission?

Background: Patients are often discharged from the ICU based on subjective criteria, workload, and bed demand, making ICU readmission a tempting quality indicator. Studies have examined institutional characteristics leading to ICU readmission, but few have shown how patient case mix affects longer lengths of ICU and hospital stays and higher in-hospital mortality.

Study design: Retrospective observational cohort study using a large, multi-institutional U.S. database.

Setting: Computerized data collection and analysis system from 97 intensive- and cardiac-care units at 35 hospitals in the United States.

Synopsis: Patient-level characteristics and outcomes of 229,375 initial ICU admissions from 2001 to 2009 were compared for patients with and without ICU readmission using the Acute Physiology and Chronic Health Evaluation (APACHE) IV database (Cerner Corporation, Kansas City, Mo.). Multivariable logistic regression analysis identified potential characteristics increasing the risk for ICU readmission. Case-mix adjusted outcomes for mortality and length of stay were calculated.

A total of 13,980 (6.1%) patients were readmitted to the ICUs. Characteristics associated with ICU readmission were similar to those previously reported. In addition to illness severity at initial admission, readmission was associated with complications, poor response to therapy, or persistent physiologic abnormalities at ICU discharge. Patients who were readmitted to the ICU had a risk-adjusted, fourfold greater probability of in-hospital mortality and a 2.5-fold increase in length of hospital stay.

Data were obtained solely from hospitals with an APACHE system, and included only one hospital from the Northeast. Not all ICUs from a single-study hospital were included. DNR orders were not available in the database for analysis.

Bottom line: Persistent physiologic derangements at ICU discharge are as influential on ICU readmission and poor outcomes as other known risk factors, potentially warranting slightly longer ICU stays for these specific patients.

Citation: Kramer AA, Higgins TL, Zimmerman JE. Intensive care unit readmissions in U.S. hospitals: patient characteristics, risk factors, and outcomes. Crit Care Med. 2012;40:3-10.

Clopidogrel Might Not Worsen Bleeding Complications During Surgery

Clinical question: Does clopidogrel cause bleeding complications during vascular surgery?

Background: There is no consensus and few large trials to decide if preoperative clopidogrel use causes bleeding complications in vascular surgeries.

Study design: Prospective.

Setting: New England academic and community centers.

Synopsis: The authors enrolled 10,406 patients from 15 academic and community centers in New England. These patients underwent carotid endarterectomy, lower-extremity bypass, and abdominal aortic aneurysm repair. Ruptured aortic aneurysms were excluded. The use of aspirin, clopidogrel, both, or no anti-platelet therapy within 48 hours before surgery was recorded. The outcomes measured were postoperative bleeding requiring reoperation and the need for packed red blood cell transfusions.

Clopidogrel therapy (n=229) compared with no anti-platelet therapy (n=2,010) did well when measured by reoperation (clopidogrel 0.9%, none 1.5%, P=0.74), incidence of transfusion (clopidogrel 0%, none 18%, P=0.1), and volume of transfusion (clopidogrel 0 units, none 0.7 units, P=0.1). However, the significance, especially for reoperation, is not impressive.

The power of the study could be improved with more clopidogrel users. Another limitation is that the aspirin and clopidogrel platelet effect lasts longer than the 48-hour cutoff. As there were more bleeding complications in the no-anti-platelet group, there is a concern for bias in how the patients were selected and treated.

Bottom line: Clopidogrel might be safe to continue in vascular surgeries, but larger and more valid studies are needed.

Citation: Stone DH, Goodney PP, Schanzer A, et al. Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery. J Vasc Surg. 2011;54:779-784.

Tissue-Defined TIAs Have Better Prognostic Benefits Than Time-Defined TIAs

Citation: Is risk stratification for recurrent stroke better when brain imaging is performed after a transient ischemic attack (TIA)?

Background: The presence of a TIA is a known risk factor for recurrent stroke. There is debate in changing the definition of TIA from time-based to tissue-based. However, it is not known if this will improve management.

Study design: Multicenter observation cohort.

Setting: Twelve independent international research centers.

Synopsis: The current definition of a TIA is a neurological deficit that resolves within 24 hours. To determine the urgency of an admission and work-up, the ABCD2 score (age, blood pressure, clinical symptoms, duration, and diabetes) is often used as a prognostic tool for recurrent stroke. The authors enrolled 4,574 patients with the traditional diagnosis of TIA. In addition to calculating their ABCD2 score, they were then classified as tissue-positive (infarction) or tissue-negative per MRI or CT. At both seven and 90 days after TIA, both imaging modalities when combined with ABCD2 were able to identify risk for recurrent stroke better than if they were used alone.

Limitations included the images being interpreted by their individual healthcare centers and that the stroke centers had lower recurrent rates of stroke compared with community centers. If only a CT can be used, it should be noted that the sensitivity is lower when compared with an MRI in this study.

Bottom line: This categorization of tissue- or non-tissue-positive TIAs improved the prognostic information provided by the ABCD2 score and might improve management decisions.

Citation: Giles MF, Albers GW, Amarenco P, et al. Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA: a multicenter study. Neurology. 2011;77:1222-1228.

ETT Comparable to MPI as Initial Diagnostic Test for Women Suspected of CAD

Clinical question: Is the exercise treadmill test (ETT) equivalent to myocardial perfusion imaging (MPI) as an initial diagnostic test for low-risk women capable of exercising with suspected coronary artery disease (CAD)?

Background: To date, the evidence base for diagnostic testing in women with suspected CAD has been limited, with no randomized trials to guide appropriate clinical decision-making in the choice of noninvasive testing strategies. The aim of this trial was to provide comparative-effectiveness data for women capable of performing exercise testing with regard to whether the addition of imaging to standard ETT provided incremental clinical benefit over index ETT alone.

Study design: Prospective randomized.

Settings: Forty-three cardiology practices across the U.S.

Synopsis: A total of 824 women 40 years of age or older with intermediate pretest CAD likelihood were randomized to ETT or MPI. All the women included in the study were symptomatic with suspected CAD, had an interpretable ECG, and were >5 on DASI (Duke Activity Status Index). A total of 17 primary end points were confirmed, including three nonfatal myocardial infarctions, one heart failure hospitalization, 12 acute coronary syndrome hospitalizations, and only one sudden cardiac death reported in 772 women.

At two years, major adverse cardiovascular events (MACE)-free survival was identical (98%) for women randomized to the ETT or exercise MPI arm (P=0.59). The observed two-year MACE rate was 1.7% for ETT and 2.3% for exercise MPI. For secondary end points, the overall rate of hospitalization for chest pain was 3%. By randomization, the two-year rate of hospitalization for chest pain symptoms was 3% for women in the ETT arm and 4% for those in the exercise MPI arm (P=0.39). An additional six women died from non-cardiac causes (ETT arm, 0.5%; exercise MPI arm, 1%; P=0.39).

Bottom line: ETT is of comparable diagnostic efficacy to MPI as an initial diagnostic test for women suspected of CAD, capable of exercising, based on two-year outcome of cardiac death, nonfatal myocardial infarction, or hospital admission for acute coronary syndrome or heart failure.

Citation: Shaw LJ, Mieres JH, Hendel RH, et al. Comparative effectiveness of exercise electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with suspected coronary artery disease: results from the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial. Circulation. 2011;124:1239-1249.

Controlled Forced Diuresis Is More Effective in High-Risk Patients for CI-AKI Prevention

Clinical question: Is a system of hydration that creates high urine output while maintaining fluid balance better than routine hydration in high-risk patients for preventing contrast-induced acute kidney injury (CI-AKI)?

Background: Hydration with sodium bicarbonate solution and administration of N-acetylcysteine (NAC) help prevent CI-AKI in low- to medium-risk patients. A recent study (PRINCE) suggests that increasing the urine flow rate (≥150 mL/hr) reduces the toxic effect of contrast, but this regimen requires forced diuresis with high doses of furosemide that may result in further renal damage due to negative fluid balance. The RenalGuard system (PLC Medical Systems Inc., Franklin, Mass.) can simultaneously achieve high urine output and maintain fluid balance.

Study design: Randomized, investigator-driven, open-label study comparing two different hydration strategies.

Setting: Multicenter trial in Italy involving patients with chronic kidney disease scheduled for angiography who met the inclusion and exclusion criteria for high risk of developing CI-AKI.

Synopsis: The study included 292 patients randomized to receive sodium bicarbonate solution (control group) versus hydration with saline controlled by the RenalGuard system with furosemide. Both groups received NAC, though at different doses and routes of administration. CI-AKI occurred in 20.5% (30 of 146) in the control group versus 11% (16 of 146) in the RenalGuard group.

Bottom line: Controlled forced diuresis to achieve high urine flow rate is more effective than conventional hydration with sodium bicarbonate solution in high-risk patients for preventing CI-AKI. Larger studies are needed to confirm and define the role of the RenalGuard system.

Citation: Briguori C, Visconti G, Focaccio A, et al. Renal insufficiency after contrast media administration trial II (REMEDIAL II). Circulation. 2011;124:1260-1269.

Severe Asymptomatic Carotid Artery Stenosis Does Not Increase Stroke or Mortality Risks after CAB Surgery

Clinical question: What is the risk for stroke in patients with asymptomatic carotid artery stenosis (CAS) who are undergoing coronary artery bypass grafting (CABG)?

Background: Stroke occurs as a complication of CABG in approximately 2% of patients. The vast majority occur within the first 24 hours of surgery and are associated with a high mortality rate.

Study design: Retrospective cohort.

Setting: A single institution in Washington, D.C.

Synopsis: Data were collected on 878 consecutive patients who had undergone carotid ultrasound before CABG over a six-year period. Patients with severe CAS of >75% (n=117) were compared with those with <75% stenosis (n=761) to assess the rates of in-hospital stroke and mortality.

Patients with severe CAS had similar rates of stroke compared with those without severe CAS (3.4% vs. 3.6%). Additionally, there was no difference in the incidence of in-hospital complications or mortality between the two groups.

Bottom line: The cause of stroke after CABG is complex and multifactorial, but severe CAS alone appears to not be the biggest risk factor for stroke in patients undergoing CABG.

Citation: Mahmoudi M, Hill PC, Xue Z, et al. Patients with severe asymptomatic carotid artery stenosis do not have a higher risk of stroke and mortality after coronary artery bypass surgery. Stroke. 2011;42:2801-2805.

Cardiac Arrest Survivors Have Long-Term Memory Deficits

Clinical question: Are there any lasting cognitive deficits in patients surviving out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation (VF)?

Background: Although advances have been made in the rapid intervention of OHCAs, there are no population-based, age-adjusted studies of the cognitive and neurologic outcomes of long-term survivors when the “chain of survival” is used (rapid emergency services, bystander CPR, early defibrillation, and advanced care).

Study design: Prospective population-based, age-adjusted study.

Setting: Single hospital in Olmsted County, Minn.

Synopsis: Of 332 OHCA patients, 47 survivors were enrolled for neurologic and neuropsychological testing at least six months after a near-death experience (median time since arrest, 7.8 years). Neurologic examination did not reveal any focal deficits related to the event, but long-term survivors had lower scores on measures of long-term memory and learning efficiency (P=0.001). Nearly all survivors were functionally independent at the time of testing. Interestingly, there was no correlation between prolonged call-to-shock time and cognitive ability, suggesting that there is a possibility of positive neurologic outcomes with a call-to-shock time as late as 10 minutes in OHCA. Older age was also not identified as a negative prognostic factor.

A limitation of the study was the small sample size, though larger populations of survivors are difficult to find. The precise meaning of “cognitive impairment” was also controversial and should be better defined for any future studies.

Bottom line: Long-term survivors of OHCA from VF have long-term memory impairment compared with the normal population at the same age and education level.

Citation: Mateen FJ, Josephs KA, Trenerry MR, et al. Long-term cognitive outcomes following out-of-hospital cardiac arrest. Neurology. 2011;77:1438-1445.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Hospitalist views on readmission prevention
2. Characteristics of hospital ICU readmission
3. Effect of clopidogrel on bleeding outcomes in vascular surgery
4. Time-versus tissue-based diagnosis of TIA
5. ETT versus ETT with imaging for the diagnosis of CAD in women
6. Effect of high urine output with adequate hydration on contrast-induced nephropathy
7. Stroke rate in CABG patients with severe carotid artery stenosis
8. Effect of cardiac arrest on long-term cognition

Hospitalists View Readmissions as Potentially Preventable by Team-Based Care

Clinical question: How do front-line hospitalists perceive the preventability of early hospital readmissions?

Background: Hospital readmission has received national attention as an indicator of poor healthcare quality and unnecessary costs. While some studies suggest that some readmissions are preventable, the exact number is unknown. Understanding preventability and the views of front-line clinicians might help hospitalists balance multifactorial compromise between throughput and length of stay.

Study design: Retrospective cohort study.

Setting: Two community tertiary-care hospitals and two suburban hospitals staffed by a single hospitalist group in Portland, Ore.

Synopsis: A group of 17 hospitalists analyzed the inpatient and outpatient charts of 300 consecutive patients readmitted within 21 days of discharge using a structured data collection tool to record patient characteristics, process measures, and perceived preventability of the readmission. Patients were either discharged by internal-medicine hospitalists or had an internal-medicine consultation during their initial stay.

Characteristics of readmitted patients and initial hospital stays were similar to those previously reported in other studies. More than 60% of readmissions were deemed preventable (15%) or possibly preventable (46%). As prevention strategies for these readmissions, hospitalists most frequently suggested interventions under their control, such as longer initial hospital stay (23%). Other potential interventions focused on system approaches, including outpatient appointments, case management, palliative care, and home health.

In most cases (96%), the reviewer was not the discharging hospitalist. Only six hospitalists performed 83% of the reviews, and inter-reviewer reliability was not assessed. Other limitations included confounding biases, such as timing of review, source hospital reviewed, reviewer optimism, and previous primary-care experience of reviewer.

Bottom line: Prevention of hospital readmissions will require a balance between increased length of stay and system-based team approaches beyond the direct control of hospitalists.

Citation: Koekkoek D, Bayley KB, Brown A, Rustvold DL. Hospitalists assess the causes of early hospital readmissions. J Hosp Med. 2011;6:383-388.

Patients with Complex, Severe Illnesses and Persistent Physiologic Abnormalities Have Higher Risk of Intensive-Care-Unit Readmission

Clinical question: Which patient characteristics increase the risk for intensive-care-unit (ICU) readmission?

Background: Patients are often discharged from the ICU based on subjective criteria, workload, and bed demand, making ICU readmission a tempting quality indicator. Studies have examined institutional characteristics leading to ICU readmission, but few have shown how patient case mix affects longer lengths of ICU and hospital stays and higher in-hospital mortality.

Study design: Retrospective observational cohort study using a large, multi-institutional U.S. database.

Setting: Computerized data collection and analysis system from 97 intensive- and cardiac-care units at 35 hospitals in the United States.

Synopsis: Patient-level characteristics and outcomes of 229,375 initial ICU admissions from 2001 to 2009 were compared for patients with and without ICU readmission using the Acute Physiology and Chronic Health Evaluation (APACHE) IV database (Cerner Corporation, Kansas City, Mo.). Multivariable logistic regression analysis identified potential characteristics increasing the risk for ICU readmission. Case-mix adjusted outcomes for mortality and length of stay were calculated.

A total of 13,980 (6.1%) patients were readmitted to the ICUs. Characteristics associated with ICU readmission were similar to those previously reported. In addition to illness severity at initial admission, readmission was associated with complications, poor response to therapy, or persistent physiologic abnormalities at ICU discharge. Patients who were readmitted to the ICU had a risk-adjusted, fourfold greater probability of in-hospital mortality and a 2.5-fold increase in length of hospital stay.

Data were obtained solely from hospitals with an APACHE system, and included only one hospital from the Northeast. Not all ICUs from a single-study hospital were included. DNR orders were not available in the database for analysis.

Bottom line: Persistent physiologic derangements at ICU discharge are as influential on ICU readmission and poor outcomes as other known risk factors, potentially warranting slightly longer ICU stays for these specific patients.

Citation: Kramer AA, Higgins TL, Zimmerman JE. Intensive care unit readmissions in U.S. hospitals: patient characteristics, risk factors, and outcomes. Crit Care Med. 2012;40:3-10.

Clopidogrel Might Not Worsen Bleeding Complications During Surgery

Clinical question: Does clopidogrel cause bleeding complications during vascular surgery?

Background: There is no consensus and few large trials to decide if preoperative clopidogrel use causes bleeding complications in vascular surgeries.

Study design: Prospective.

Setting: New England academic and community centers.

Synopsis: The authors enrolled 10,406 patients from 15 academic and community centers in New England. These patients underwent carotid endarterectomy, lower-extremity bypass, and abdominal aortic aneurysm repair. Ruptured aortic aneurysms were excluded. The use of aspirin, clopidogrel, both, or no anti-platelet therapy within 48 hours before surgery was recorded. The outcomes measured were postoperative bleeding requiring reoperation and the need for packed red blood cell transfusions.

Clopidogrel therapy (n=229) compared with no anti-platelet therapy (n=2,010) did well when measured by reoperation (clopidogrel 0.9%, none 1.5%, P=0.74), incidence of transfusion (clopidogrel 0%, none 18%, P=0.1), and volume of transfusion (clopidogrel 0 units, none 0.7 units, P=0.1). However, the significance, especially for reoperation, is not impressive.

The power of the study could be improved with more clopidogrel users. Another limitation is that the aspirin and clopidogrel platelet effect lasts longer than the 48-hour cutoff. As there were more bleeding complications in the no-anti-platelet group, there is a concern for bias in how the patients were selected and treated.

Bottom line: Clopidogrel might be safe to continue in vascular surgeries, but larger and more valid studies are needed.

Citation: Stone DH, Goodney PP, Schanzer A, et al. Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery. J Vasc Surg. 2011;54:779-784.

Tissue-Defined TIAs Have Better Prognostic Benefits Than Time-Defined TIAs

Citation: Is risk stratification for recurrent stroke better when brain imaging is performed after a transient ischemic attack (TIA)?

Background: The presence of a TIA is a known risk factor for recurrent stroke. There is debate in changing the definition of TIA from time-based to tissue-based. However, it is not known if this will improve management.

Study design: Multicenter observation cohort.

Setting: Twelve independent international research centers.

Synopsis: The current definition of a TIA is a neurological deficit that resolves within 24 hours. To determine the urgency of an admission and work-up, the ABCD2 score (age, blood pressure, clinical symptoms, duration, and diabetes) is often used as a prognostic tool for recurrent stroke. The authors enrolled 4,574 patients with the traditional diagnosis of TIA. In addition to calculating their ABCD2 score, they were then classified as tissue-positive (infarction) or tissue-negative per MRI or CT. At both seven and 90 days after TIA, both imaging modalities when combined with ABCD2 were able to identify risk for recurrent stroke better than if they were used alone.

Limitations included the images being interpreted by their individual healthcare centers and that the stroke centers had lower recurrent rates of stroke compared with community centers. If only a CT can be used, it should be noted that the sensitivity is lower when compared with an MRI in this study.

Bottom line: This categorization of tissue- or non-tissue-positive TIAs improved the prognostic information provided by the ABCD2 score and might improve management decisions.

Citation: Giles MF, Albers GW, Amarenco P, et al. Early stroke risk and ABCD2 score performance in tissue- vs time-defined TIA: a multicenter study. Neurology. 2011;77:1222-1228.

ETT Comparable to MPI as Initial Diagnostic Test for Women Suspected of CAD

Clinical question: Is the exercise treadmill test (ETT) equivalent to myocardial perfusion imaging (MPI) as an initial diagnostic test for low-risk women capable of exercising with suspected coronary artery disease (CAD)?

Background: To date, the evidence base for diagnostic testing in women with suspected CAD has been limited, with no randomized trials to guide appropriate clinical decision-making in the choice of noninvasive testing strategies. The aim of this trial was to provide comparative-effectiveness data for women capable of performing exercise testing with regard to whether the addition of imaging to standard ETT provided incremental clinical benefit over index ETT alone.

Study design: Prospective randomized.

Settings: Forty-three cardiology practices across the U.S.

Synopsis: A total of 824 women 40 years of age or older with intermediate pretest CAD likelihood were randomized to ETT or MPI. All the women included in the study were symptomatic with suspected CAD, had an interpretable ECG, and were >5 on DASI (Duke Activity Status Index). A total of 17 primary end points were confirmed, including three nonfatal myocardial infarctions, one heart failure hospitalization, 12 acute coronary syndrome hospitalizations, and only one sudden cardiac death reported in 772 women.

At two years, major adverse cardiovascular events (MACE)-free survival was identical (98%) for women randomized to the ETT or exercise MPI arm (P=0.59). The observed two-year MACE rate was 1.7% for ETT and 2.3% for exercise MPI. For secondary end points, the overall rate of hospitalization for chest pain was 3%. By randomization, the two-year rate of hospitalization for chest pain symptoms was 3% for women in the ETT arm and 4% for those in the exercise MPI arm (P=0.39). An additional six women died from non-cardiac causes (ETT arm, 0.5%; exercise MPI arm, 1%; P=0.39).

Bottom line: ETT is of comparable diagnostic efficacy to MPI as an initial diagnostic test for women suspected of CAD, capable of exercising, based on two-year outcome of cardiac death, nonfatal myocardial infarction, or hospital admission for acute coronary syndrome or heart failure.

Citation: Shaw LJ, Mieres JH, Hendel RH, et al. Comparative effectiveness of exercise electrocardiography with or without myocardial perfusion single photon emission computed tomography in women with suspected coronary artery disease: results from the What Is the Optimal Method for Ischemia Evaluation in Women (WOMEN) trial. Circulation. 2011;124:1239-1249.

Controlled Forced Diuresis Is More Effective in High-Risk Patients for CI-AKI Prevention

Clinical question: Is a system of hydration that creates high urine output while maintaining fluid balance better than routine hydration in high-risk patients for preventing contrast-induced acute kidney injury (CI-AKI)?

Background: Hydration with sodium bicarbonate solution and administration of N-acetylcysteine (NAC) help prevent CI-AKI in low- to medium-risk patients. A recent study (PRINCE) suggests that increasing the urine flow rate (≥150 mL/hr) reduces the toxic effect of contrast, but this regimen requires forced diuresis with high doses of furosemide that may result in further renal damage due to negative fluid balance. The RenalGuard system (PLC Medical Systems Inc., Franklin, Mass.) can simultaneously achieve high urine output and maintain fluid balance.

Study design: Randomized, investigator-driven, open-label study comparing two different hydration strategies.

Setting: Multicenter trial in Italy involving patients with chronic kidney disease scheduled for angiography who met the inclusion and exclusion criteria for high risk of developing CI-AKI.

Synopsis: The study included 292 patients randomized to receive sodium bicarbonate solution (control group) versus hydration with saline controlled by the RenalGuard system with furosemide. Both groups received NAC, though at different doses and routes of administration. CI-AKI occurred in 20.5% (30 of 146) in the control group versus 11% (16 of 146) in the RenalGuard group.

Bottom line: Controlled forced diuresis to achieve high urine flow rate is more effective than conventional hydration with sodium bicarbonate solution in high-risk patients for preventing CI-AKI. Larger studies are needed to confirm and define the role of the RenalGuard system.

Citation: Briguori C, Visconti G, Focaccio A, et al. Renal insufficiency after contrast media administration trial II (REMEDIAL II). Circulation. 2011;124:1260-1269.

Severe Asymptomatic Carotid Artery Stenosis Does Not Increase Stroke or Mortality Risks after CAB Surgery

Clinical question: What is the risk for stroke in patients with asymptomatic carotid artery stenosis (CAS) who are undergoing coronary artery bypass grafting (CABG)?

Background: Stroke occurs as a complication of CABG in approximately 2% of patients. The vast majority occur within the first 24 hours of surgery and are associated with a high mortality rate.

Study design: Retrospective cohort.

Setting: A single institution in Washington, D.C.

Synopsis: Data were collected on 878 consecutive patients who had undergone carotid ultrasound before CABG over a six-year period. Patients with severe CAS of >75% (n=117) were compared with those with <75% stenosis (n=761) to assess the rates of in-hospital stroke and mortality.

Patients with severe CAS had similar rates of stroke compared with those without severe CAS (3.4% vs. 3.6%). Additionally, there was no difference in the incidence of in-hospital complications or mortality between the two groups.

Bottom line: The cause of stroke after CABG is complex and multifactorial, but severe CAS alone appears to not be the biggest risk factor for stroke in patients undergoing CABG.

Citation: Mahmoudi M, Hill PC, Xue Z, et al. Patients with severe asymptomatic carotid artery stenosis do not have a higher risk of stroke and mortality after coronary artery bypass surgery. Stroke. 2011;42:2801-2805.

Cardiac Arrest Survivors Have Long-Term Memory Deficits

Clinical question: Are there any lasting cognitive deficits in patients surviving out-of-hospital cardiac arrest (OHCA) from ventricular fibrillation (VF)?

Background: Although advances have been made in the rapid intervention of OHCAs, there are no population-based, age-adjusted studies of the cognitive and neurologic outcomes of long-term survivors when the “chain of survival” is used (rapid emergency services, bystander CPR, early defibrillation, and advanced care).

Study design: Prospective population-based, age-adjusted study.

Setting: Single hospital in Olmsted County, Minn.

Synopsis: Of 332 OHCA patients, 47 survivors were enrolled for neurologic and neuropsychological testing at least six months after a near-death experience (median time since arrest, 7.8 years). Neurologic examination did not reveal any focal deficits related to the event, but long-term survivors had lower scores on measures of long-term memory and learning efficiency (P=0.001). Nearly all survivors were functionally independent at the time of testing. Interestingly, there was no correlation between prolonged call-to-shock time and cognitive ability, suggesting that there is a possibility of positive neurologic outcomes with a call-to-shock time as late as 10 minutes in OHCA. Older age was also not identified as a negative prognostic factor.

A limitation of the study was the small sample size, though larger populations of survivors are difficult to find. The precise meaning of “cognitive impairment” was also controversial and should be better defined for any future studies.

Bottom line: Long-term survivors of OHCA from VF have long-term memory impairment compared with the normal population at the same age and education level.

Citation: Mateen FJ, Josephs KA, Trenerry MR, et al. Long-term cognitive outcomes following out-of-hospital cardiac arrest. Neurology. 2011;77:1438-1445.