Jonathan T. Crocker, MD

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Neutral head position safe for internal jugular vein cannulation
2. Thrombolysis decreases mortality in unstable patients with acute PE
3. Rectal indomethacin decreases incidence of post-ERCP pancreatitis
4. CHADS2-VASc and HAS-BLED as predictors in afib patients
5. No readmission, mortality decreases with self-supported COPD management
6. Medicare Premier P4P initiatives do not decrease mortality
7. In-hospital rate of DVT/PE after hip and knee arthroplasty
8. Sodium chloride prevents contrast-induced nephropathy

Neutral Head Position Is Safe for Internal Jugular Vein Cannulation

Clinical question: Is there a difference in the complication rate between neutral head position and 45-degree neck rotation during ultrasound-guided internal jugular vein cannulation?

Background: Cannulation of the internal jugular vein using ultrasound decreases the rate of major complications (carotid artery puncture, pneumothorax, and hemothorax). The relative positions of the internal jugular vein and the carotid artery change based on degree of neck rotation. The optimal position for ultrasound-guided vein puncture has not been shown.

Study design: Prospective, randomized, controlled, non-blinded study.

Setting: Tertiary neurosurgical center in Milan, Italy.

Synopsis: One thousand, three hundred thirty-two patients undergoing major neurosurgical procedures who needed central venous catheter placement were randomized to a neutral head position (NH) or a 45-degree neck rotation (HT) during ultrasound-guided internal jugular vein cannulation. Exclusion criteria were consent refusal, age <12 years, and coagulopathy. Six experienced anesthesiologists performed the procedures; blinding was not possible.

There was no difference in the rate of major complications (carotid artery puncture, pneumothorax, or hemothorax) based on head position (0.9% in NH vs. 0.6% in HT). Minor complications (multiple skin punctures, multiple vein punctures, difficulty inserting the guidewire) were similar in the two groups (13.2% in NG vs. 12.6% in HT). Neck rotation was not associated with operator-reported difficulty or vascular access time.

Limitations of the study include the inability to blind the operator. Additionally, the study involved six experienced anesthesiologists at one center who performed the procedure on patients needing an elective central line. The ability to generalize the findings to other settings, less experienced providers, and patients who need an emergency line is not certain.

Bottom line: Neutral head position is as safe as 45-degree neck rotation for elective ultrasound-guided internal jugular vein cannulation.

Citation: Lamperti M, Subert M, Cortellazzi P, et al. Is a neutral head position safer than 45-degree neck rotation during ultrasound-guided internal jugular vein cannulation? Results of a randomized controlled clinical trial. Anesth Analg. 2012;114:777-784.

Thrombolysis Decreases Mortality in Unstable Patients with Acute Pulmonary Embolism

Clinical question: Does thrombolytic therapy decrease mortality in unstable patients with acute pulmonary embolism (PE)?

Background: PE is a common problem; associated mortality is high. Despite this fact, the data supporting thrombolytic therapy in hemodynamically unstable patients are not robust, and randomized, controlled trials are unlikely to be performed.

Study design: Retrospective cohort study.

Setting: One thousand nonfederal, short-term U.S. hospitals.

Synopsis: Using data from the Nationwide Inpatient Sample database from 1999-2008, investigators found that thrombolysis decreased both all-cause and PE-specific mortality for unstable patients, defined as those either in shock or on a ventilator. Specifically for all-cause mortality, 15% of patients who received thrombolysis died vs. 47% of those who did not (RR 0.31, 95% CI 0.30-0.32). Placement of an inferior vena cava (IVC) filter further reduced mortality, to only 7.6% in patients who received both IVC filter and thrombolysis.

For PE-specific mortality, patients who received thrombolysis also had decreased rates, from 42% to 8.4% (RR 0.20; 95% CI 0.19-0.22). Across all age groups, patients who received thrombolysis had decreased all-cause and PE-specific mortality. Patients who did not receive thrombolysis had additional comorbidities.

As this study is retrospective, it might be affected by unknown confounding. In addition, it relies on coding data to identify patient stability and treatment. Despite this limitation, a randomized, controlled trial is unlikely to be performed at this stage. This study provides evidence to support use of thrombolysis in unstable patients.

Bottom line: Thrombolysis might reduce mortality in unstable patients with acute PE. In combination with IVC filters, the mortality reduction might be even greater.

Citation: Stein PD, Matta F. Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused. Am J Med. 2012;125(5):465-470.

Rectal Indomethacin Decreases Incidence of Post-ERCP Pancreatitis

Clinical question: Does rectal indomethacin reduce the incidence of pancreatitis after ERCP?

Background: Acute pancreatitis is the most common complication from endoscopic retrograde cholangiopancreatography (ERCP). No pharmacologic treatment has proven to reduce the incidence of pancreatitis. Preliminary studies, including a meta-analysis, suggest that the use of NSAIDs might reduce the incidence of post-ERCP pancreatitis.

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

Setting: Multicenter trial at four university-affiliated medical centers in the U.S.

Synopsis: More than 600 patients at high risk for post-ERCP pancreatitis were randomized to receive either two 50-mg indomethacin suppositories or two identical-appearing placebo suppositories. Patients were considered at high risk for pancreatitis based on previously identified patient- and procedure-related risk factors. Most of the participants had sphincter of Oddi dysfunction (84.4% of the indomethacin group and 80.5% of the placebo group). Exclusion criteria included elevated creatinine and active peptic ulcer disease. The indomethacin or placebo suppositories were given immediately following the ERCP.

Post-ERCP pancreatitis, defined by upper abdominal pain, elevation of pancreatic enzymes, and hospitalization for at least two nights, was significantly higher in the placebo group compared with the indomethacin group (16.9% vs. 9.2%, P=0.005). Moderate or severe post-ERCP pancreatitis was significantly higher in the placebo group compared with the indomethacin group (8.8% vs. 4.4%, P=0.03).

There were no significant differences in the rates of clinically significant bleeding or acute renal failure between the two groups. The ability to generalize these findings to patients without risk factors for post-ERCP pancreatitis is not clear.

Bottom line: Rectal indomethacin decreases the rate of post-ERCP pancreatitis in patients who are at high risk for this complication.

Citation: Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012;366(15):1414-1422.

CHADS2-VASc and HAS-BLED Can Predict Thromboembolism and Bleeding Risk in Afib Patients

Clinical question: What are the risk factors for stroke/thromboembolism and bleeding from atrial fibrillation (afib), and how well do the CHADS2-VASc and HAS-BLED stroke and bleeding risk-assessment tools perform against other published stroke and bleeding risk-assessment tools (CHADS2 and HEMORR2HAGES) for patients with afib?

Background: In afib patients, the CHADS2-VASc tool might offer more comprehensive stroke assessment over the CHADS2 by identifying truly-low-risk patients with afib who might not even need antiplatelet therapy. HAS-BLED, a newer bleeding-risk-assessment tool, has been validated in previous trials and is more user-friendly than others. Use of CHADS2-VASc and HAS-BLED are recommended by the European Society of Cardiology to assess stroke and bleeding risks for patients with afib.

Study design: Prospective cohort study.

Setting: All hospitals in Sweden.

Synopsis: Investigators identified 182,678 afib patients via ICD-10 data from Sweden’s National Hospital Discharge Registry ICD-10 from 2005 to 2008. Approximately half the patients were not taking anticoagulants. Analysis assessed risk factors for stroke and bleeding and the performance of CHADS2-VASc and HAS-BLED against CHADS2 and HEMORR2HAGES stroke and bleeding risk-assessment tools.

Risk of composite thromboembolism (unspecified stroke, TIA, systemic embolism) was significantly higher in patients with increased age, peripheral arterial disease, prior myocardial infarction (MI), prior coronary artery bypass grafting (CABG), female gender, renal failure, and aspirin use, as well as hypertension, diabetes, prior thromboembolic event, or prior intracranial hemorrhage (ICH). Interestingly, a statistically increased risk was seen with aspirin use.

Conversely, history of heart failure, thyroid disease, and obesity were not associated with increased composite thromboembolic risk. The use of CHADS2-VASc was marginally better than CHADS2 in predicting stroke risk.

ICH risk was increased in patients with older age, prior ischemic stroke, prior ICH, and hypertension. Risk of composite bleeding (from ICH or other major bleeding) was significantly higher in patients with these risk factors, as well as renal failure, liver disease, anemia, dysfunctional platelets, alcohol use, and cancer. Ischemic heart disease was associated with a statistically significant lower risk of ICH, but not of composite bleeding risk.

HAS-BLED usage was as good as, and easier to use than, HEMORR2HAGES in predicting bleeding risk.

Bottom line: CHADS2-VASc might be better than CHADS2 in predicting truly-low-risk patients with nonvalvular afib; HAS-BLED is just as good as, and easier to use than, HEMORR2HAGES in predicting bleeding risk for patients with nonvalvular afib who are to receive antithrombotic therapy.

Citation: Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500-10 [Epub 2012 Jan 13].

Supported Self-Management of COPD Does Not Decrease Readmission or Mortality Rates

Clinical question: Does supported self-management of patients with chronic obstructive pulmonary disease (COPD) decrease COPD-related hospital readmission or death?

Clinical background: Supported self-management has benefited patients with such chronic diseases as heart failure and asthma. Evidence to support such a strategy for patients with COPD is relatively lacking.

Study design: Randomized, controlled trial.

Setting: Community-based care following urban hospitalization in western Scotland.

Synopsis: From June 2007 to May 2009, and following hospitalization for COPD exacerbation, 464 patients were randomized to receive routine community-based care with or without 12 months of support and training to detect, and promptly treat, recurrent exacerbations. Independent of disease severity or demographics, investigators found no difference in combined readmission (48% vs. 47%, 95% confidence interval [CI] 0.80-1.38) or death (10% vs. 7%, 95% CI 0.71-2.61).

Based on review of appropriateness of self-management strategies used by the intervention group, unplanned exploratory subgroup analysis classified a minority of the intervention group as “successful” (42%) supported self-managers, and demonstrated decreased COPD readmissions and death (27% vs. 49%, 95% CI 0.25-0.76, P=0.003) vs. “unsuccessful” self-managers. This successful group was younger and tended to live with others. Further research to define characteristics of patients who benefit from self-management is needed.

Bottom line: Supported self-management of COPD does not reduce COPD-related readmission or death in a large population.

Citation: Bucknall CE, Miller G, Lloyd SM, et al. Glasgow supported self-management trial (GSuST) for patients with moderate to severe COPD: randomised controlled trial. BMJ. 2012;344:e1060 [Epub ahead of print].

Medicare Premier P4P Initiatives Do Not Decrease Mortality

Clinical question: Has the Medicare Premier Hospital Quality Incentive Demonstration (HQID) resulted in lower mortality?

Background: The Centers for Medicare & Medicaid Services’ (CMS) value-based purchasing program will expand to include 30-day mortality in 2013, but do pay-for-performance (P4P) initiatives result in improved mortality? Studies have demonstrated improvement in process of care but have not demonstrated mortality benefit thus far.

Study design: Cohort study.

Setting: Two hundred fifty-two hospitals participating in the Premier HQID compared with 3,363 control hospitals participating in the Hospital Compare program.

Synopsis: Researchers examined 30-day mortality for patients admitted with acute myocardial infarction, congestive heart failure, pneumonia, and for coronary artery bypass grafting (CABG) from 2003 to 2009. Results showed no difference in 30-day mortality rates over the six-year span of the program for any of the conditions studied in the Premier hospitals (participating in the voluntary pay-for-performance program) vs. non-Premier hospitals (11.82% vs. 11.74%). This held true for each condition measured individually, with a higher mortality rate for patients undergoing CABG at the Premier hospitals.

In addition, in the hospitals that underperformed initially, there was no difference with respect to rate of improvement when comparing Premier vs. non-Premier hospitals. Furthermore, mortality rate trends did not differ between those conditions that were incentivized (acute MI and CABG) compared with those that were not (congestive heart failure and pneumonia).

The authors concluded that there was “little evidence” that the Premier HQID pay-for-performance program resulted in reduced 30-day mortality.

Bottom line: Programs participating in the Medicare Premier HQID pay-for-performance program had similar 30-day mortality compared with nonparticipating programs.

Citation: Jha AK, Joynt KE, Orav EJ, Epstein AM. The long-term effect of premier pay for performance on patient outcomes. N Engl J Med. 2012;366:1606-1615.

In-Hospital Rate of DVT/PE After Hip and Knee Arthroplasty with Guideline-Recommended Prophylaxis

Clinical question: What is the rate of symptomatic DVT/PE after total or partial hip (TPHA) or knee (TPKA) arthroplasty using currently recommended prophylaxis?

Background: The rate of postoperative DVT/PE after TPHA/TPKA has dropped dramatically with use of pharmacologic prophylaxis. However, the current rate of symptomatic DVT/PE using current pharmacologic prophylaxis is not known. Such rates are needed for informed patient consent and development of patient safety benchmarks.

Study design: Systematic review.

Setting: Randomized clinical trials (RCTs) and observational studies worldwide of adult inpatients undergoing TPHA and/or TPKA from 1996 to 2011.

Synopsis: Forty-seven studies were included, of which 41 were RCTs and six were observational studies. Twenty-one studies evaluated rates after TPHA, 20 after TPKA, and six after both. More than 44,000 patients were included, with ages ranging from 58 to 74 years. The mean duration of prophylaxis was eight days, with a mean follow-up of 13 days.

In-hospital rates of symptomatic venous thromboembolism (VTE) were higher in patients undergoing TPKA than TPHA (1.09% vs. 0.53% for VTE, 0.63% vs. 0.26% for DVT, and 0.27% vs. 0.14% for PE). This is in contrast to the higher rates of VTE observed after TPHA when the post-discharge period is included. The pooled incidence of VTE was lower with use of direct inhibitors of Factors Xa or IIa when compared to low-molecular-weight heparin, although a direct efficacy comparison could not be made.

Because the majority of studies were RCTs with restrictive inclusion criteria, rates of DVT/PE in actual practice might be higher.

Bottom line: When informing patients of postoperative VTE risk, or establishing benchmarks to evaluate patient safety, one can anticipate an in-hospital VTE rate of 0.5% following TPHA and 1% following TPKA.

Citation: Januel JM, Chen G, Ruffieux C, et al. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review. JAMA. 2012;307(3):294-303.

Sodium Chloride Prevents Contrast-Induced Nephropathy

Clinical question: Is sodium chloride more effective than sodium bicarbonate for preventing contrast-induced nephropathy?

Background: Contrast-induced nephropathy can be prevented with precontrast hydration. Study authors sought to compare sodium chloride administered over 24 hours with sodium bicarbonate administered over seven hours, and with sodium bicarbonate administered orally.

Study design: Randomized, open-label, controlled trial.

Setting: Three European medical centers.

Synopsis: The study examined 258 patients with an estimated glomerular filtration rate <60mL/min/1.73m2 undergoing intravenous or intra-arterial contrast procedure. Patients with Class III or IV heart failure were excluded. The remaining patients were randomized to receive one of three regimens: sodium chloride at 1 ml/kg/hr for 12 hours prior to and 12 hours following the procedure; intravenous sodium bicarbonate for one hour prior to and six hours following the procedure; or intravenous and oral sodium bicarbonate 20 minutes prior to the procedure.

The group that received saline had a lower incidence of contrast-induced nephropathy than the bicarbonate groups (1% vs. 9% vs. 10%). The oral bicarbonate strategy was noninferior to the seven-hour intravenous bicarbonate strategy.

The authors postulated that saline should be used for high-risk patients, but that given the overall low incidence of contrast-induced nephropathy, the short-term bicarbonate strategy (intravenous followed by oral) is a viable alternative for low-risk patients.

Bottom line: Sodium chloride is more effective than sodium bicarbonate for preventing contrast-induced nephropathy, but in light of the low incidence, a short course of sodium bicarbonate is a possible convenient alternative for low-risk patients.

Citation: Klima T, Christ A, Marana I, et al. Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial. Eur Heart J. 2012 Jan 19 [Epub ahead of print].

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Neutral head position safe for internal jugular vein cannulation
2. Thrombolysis decreases mortality in unstable patients with acute PE
3. Rectal indomethacin decreases incidence of post-ERCP pancreatitis
4. CHADS2-VASc and HAS-BLED as predictors in afib patients
5. No readmission, mortality decreases with self-supported COPD management
6. Medicare Premier P4P initiatives do not decrease mortality
7. In-hospital rate of DVT/PE after hip and knee arthroplasty
8. Sodium chloride prevents contrast-induced nephropathy

Neutral Head Position Is Safe for Internal Jugular Vein Cannulation

Clinical question: Is there a difference in the complication rate between neutral head position and 45-degree neck rotation during ultrasound-guided internal jugular vein cannulation?

Background: Cannulation of the internal jugular vein using ultrasound decreases the rate of major complications (carotid artery puncture, pneumothorax, and hemothorax). The relative positions of the internal jugular vein and the carotid artery change based on degree of neck rotation. The optimal position for ultrasound-guided vein puncture has not been shown.

Study design: Prospective, randomized, controlled, non-blinded study.

Setting: Tertiary neurosurgical center in Milan, Italy.

Synopsis: One thousand, three hundred thirty-two patients undergoing major neurosurgical procedures who needed central venous catheter placement were randomized to a neutral head position (NH) or a 45-degree neck rotation (HT) during ultrasound-guided internal jugular vein cannulation. Exclusion criteria were consent refusal, age <12 years, and coagulopathy. Six experienced anesthesiologists performed the procedures; blinding was not possible.

There was no difference in the rate of major complications (carotid artery puncture, pneumothorax, or hemothorax) based on head position (0.9% in NH vs. 0.6% in HT). Minor complications (multiple skin punctures, multiple vein punctures, difficulty inserting the guidewire) were similar in the two groups (13.2% in NG vs. 12.6% in HT). Neck rotation was not associated with operator-reported difficulty or vascular access time.

Limitations of the study include the inability to blind the operator. Additionally, the study involved six experienced anesthesiologists at one center who performed the procedure on patients needing an elective central line. The ability to generalize the findings to other settings, less experienced providers, and patients who need an emergency line is not certain.

Bottom line: Neutral head position is as safe as 45-degree neck rotation for elective ultrasound-guided internal jugular vein cannulation.

Citation: Lamperti M, Subert M, Cortellazzi P, et al. Is a neutral head position safer than 45-degree neck rotation during ultrasound-guided internal jugular vein cannulation? Results of a randomized controlled clinical trial. Anesth Analg. 2012;114:777-784.

Thrombolysis Decreases Mortality in Unstable Patients with Acute Pulmonary Embolism

Clinical question: Does thrombolytic therapy decrease mortality in unstable patients with acute pulmonary embolism (PE)?

Background: PE is a common problem; associated mortality is high. Despite this fact, the data supporting thrombolytic therapy in hemodynamically unstable patients are not robust, and randomized, controlled trials are unlikely to be performed.

Study design: Retrospective cohort study.

Setting: One thousand nonfederal, short-term U.S. hospitals.

Synopsis: Using data from the Nationwide Inpatient Sample database from 1999-2008, investigators found that thrombolysis decreased both all-cause and PE-specific mortality for unstable patients, defined as those either in shock or on a ventilator. Specifically for all-cause mortality, 15% of patients who received thrombolysis died vs. 47% of those who did not (RR 0.31, 95% CI 0.30-0.32). Placement of an inferior vena cava (IVC) filter further reduced mortality, to only 7.6% in patients who received both IVC filter and thrombolysis.

For PE-specific mortality, patients who received thrombolysis also had decreased rates, from 42% to 8.4% (RR 0.20; 95% CI 0.19-0.22). Across all age groups, patients who received thrombolysis had decreased all-cause and PE-specific mortality. Patients who did not receive thrombolysis had additional comorbidities.

As this study is retrospective, it might be affected by unknown confounding. In addition, it relies on coding data to identify patient stability and treatment. Despite this limitation, a randomized, controlled trial is unlikely to be performed at this stage. This study provides evidence to support use of thrombolysis in unstable patients.

Bottom line: Thrombolysis might reduce mortality in unstable patients with acute PE. In combination with IVC filters, the mortality reduction might be even greater.

Citation: Stein PD, Matta F. Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused. Am J Med. 2012;125(5):465-470.

Rectal Indomethacin Decreases Incidence of Post-ERCP Pancreatitis

Clinical question: Does rectal indomethacin reduce the incidence of pancreatitis after ERCP?

Background: Acute pancreatitis is the most common complication from endoscopic retrograde cholangiopancreatography (ERCP). No pharmacologic treatment has proven to reduce the incidence of pancreatitis. Preliminary studies, including a meta-analysis, suggest that the use of NSAIDs might reduce the incidence of post-ERCP pancreatitis.

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

Setting: Multicenter trial at four university-affiliated medical centers in the U.S.

Synopsis: More than 600 patients at high risk for post-ERCP pancreatitis were randomized to receive either two 50-mg indomethacin suppositories or two identical-appearing placebo suppositories. Patients were considered at high risk for pancreatitis based on previously identified patient- and procedure-related risk factors. Most of the participants had sphincter of Oddi dysfunction (84.4% of the indomethacin group and 80.5% of the placebo group). Exclusion criteria included elevated creatinine and active peptic ulcer disease. The indomethacin or placebo suppositories were given immediately following the ERCP.

Post-ERCP pancreatitis, defined by upper abdominal pain, elevation of pancreatic enzymes, and hospitalization for at least two nights, was significantly higher in the placebo group compared with the indomethacin group (16.9% vs. 9.2%, P=0.005). Moderate or severe post-ERCP pancreatitis was significantly higher in the placebo group compared with the indomethacin group (8.8% vs. 4.4%, P=0.03).

There were no significant differences in the rates of clinically significant bleeding or acute renal failure between the two groups. The ability to generalize these findings to patients without risk factors for post-ERCP pancreatitis is not clear.

Bottom line: Rectal indomethacin decreases the rate of post-ERCP pancreatitis in patients who are at high risk for this complication.

Citation: Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012;366(15):1414-1422.

CHADS2-VASc and HAS-BLED Can Predict Thromboembolism and Bleeding Risk in Afib Patients

Clinical question: What are the risk factors for stroke/thromboembolism and bleeding from atrial fibrillation (afib), and how well do the CHADS2-VASc and HAS-BLED stroke and bleeding risk-assessment tools perform against other published stroke and bleeding risk-assessment tools (CHADS2 and HEMORR2HAGES) for patients with afib?

Background: In afib patients, the CHADS2-VASc tool might offer more comprehensive stroke assessment over the CHADS2 by identifying truly-low-risk patients with afib who might not even need antiplatelet therapy. HAS-BLED, a newer bleeding-risk-assessment tool, has been validated in previous trials and is more user-friendly than others. Use of CHADS2-VASc and HAS-BLED are recommended by the European Society of Cardiology to assess stroke and bleeding risks for patients with afib.

Study design: Prospective cohort study.

Setting: All hospitals in Sweden.

Synopsis: Investigators identified 182,678 afib patients via ICD-10 data from Sweden’s National Hospital Discharge Registry ICD-10 from 2005 to 2008. Approximately half the patients were not taking anticoagulants. Analysis assessed risk factors for stroke and bleeding and the performance of CHADS2-VASc and HAS-BLED against CHADS2 and HEMORR2HAGES stroke and bleeding risk-assessment tools.

Risk of composite thromboembolism (unspecified stroke, TIA, systemic embolism) was significantly higher in patients with increased age, peripheral arterial disease, prior myocardial infarction (MI), prior coronary artery bypass grafting (CABG), female gender, renal failure, and aspirin use, as well as hypertension, diabetes, prior thromboembolic event, or prior intracranial hemorrhage (ICH). Interestingly, a statistically increased risk was seen with aspirin use.

Conversely, history of heart failure, thyroid disease, and obesity were not associated with increased composite thromboembolic risk. The use of CHADS2-VASc was marginally better than CHADS2 in predicting stroke risk.

ICH risk was increased in patients with older age, prior ischemic stroke, prior ICH, and hypertension. Risk of composite bleeding (from ICH or other major bleeding) was significantly higher in patients with these risk factors, as well as renal failure, liver disease, anemia, dysfunctional platelets, alcohol use, and cancer. Ischemic heart disease was associated with a statistically significant lower risk of ICH, but not of composite bleeding risk.

HAS-BLED usage was as good as, and easier to use than, HEMORR2HAGES in predicting bleeding risk.

Bottom line: CHADS2-VASc might be better than CHADS2 in predicting truly-low-risk patients with nonvalvular afib; HAS-BLED is just as good as, and easier to use than, HEMORR2HAGES in predicting bleeding risk for patients with nonvalvular afib who are to receive antithrombotic therapy.

Citation: Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500-10 [Epub 2012 Jan 13].

Supported Self-Management of COPD Does Not Decrease Readmission or Mortality Rates

Clinical question: Does supported self-management of patients with chronic obstructive pulmonary disease (COPD) decrease COPD-related hospital readmission or death?

Clinical background: Supported self-management has benefited patients with such chronic diseases as heart failure and asthma. Evidence to support such a strategy for patients with COPD is relatively lacking.

Study design: Randomized, controlled trial.

Setting: Community-based care following urban hospitalization in western Scotland.

Synopsis: From June 2007 to May 2009, and following hospitalization for COPD exacerbation, 464 patients were randomized to receive routine community-based care with or without 12 months of support and training to detect, and promptly treat, recurrent exacerbations. Independent of disease severity or demographics, investigators found no difference in combined readmission (48% vs. 47%, 95% confidence interval [CI] 0.80-1.38) or death (10% vs. 7%, 95% CI 0.71-2.61).

Based on review of appropriateness of self-management strategies used by the intervention group, unplanned exploratory subgroup analysis classified a minority of the intervention group as “successful” (42%) supported self-managers, and demonstrated decreased COPD readmissions and death (27% vs. 49%, 95% CI 0.25-0.76, P=0.003) vs. “unsuccessful” self-managers. This successful group was younger and tended to live with others. Further research to define characteristics of patients who benefit from self-management is needed.

Bottom line: Supported self-management of COPD does not reduce COPD-related readmission or death in a large population.

Citation: Bucknall CE, Miller G, Lloyd SM, et al. Glasgow supported self-management trial (GSuST) for patients with moderate to severe COPD: randomised controlled trial. BMJ. 2012;344:e1060 [Epub ahead of print].

Medicare Premier P4P Initiatives Do Not Decrease Mortality

Clinical question: Has the Medicare Premier Hospital Quality Incentive Demonstration (HQID) resulted in lower mortality?

Background: The Centers for Medicare & Medicaid Services’ (CMS) value-based purchasing program will expand to include 30-day mortality in 2013, but do pay-for-performance (P4P) initiatives result in improved mortality? Studies have demonstrated improvement in process of care but have not demonstrated mortality benefit thus far.

Study design: Cohort study.

Setting: Two hundred fifty-two hospitals participating in the Premier HQID compared with 3,363 control hospitals participating in the Hospital Compare program.

Synopsis: Researchers examined 30-day mortality for patients admitted with acute myocardial infarction, congestive heart failure, pneumonia, and for coronary artery bypass grafting (CABG) from 2003 to 2009. Results showed no difference in 30-day mortality rates over the six-year span of the program for any of the conditions studied in the Premier hospitals (participating in the voluntary pay-for-performance program) vs. non-Premier hospitals (11.82% vs. 11.74%). This held true for each condition measured individually, with a higher mortality rate for patients undergoing CABG at the Premier hospitals.

In addition, in the hospitals that underperformed initially, there was no difference with respect to rate of improvement when comparing Premier vs. non-Premier hospitals. Furthermore, mortality rate trends did not differ between those conditions that were incentivized (acute MI and CABG) compared with those that were not (congestive heart failure and pneumonia).

The authors concluded that there was “little evidence” that the Premier HQID pay-for-performance program resulted in reduced 30-day mortality.

Bottom line: Programs participating in the Medicare Premier HQID pay-for-performance program had similar 30-day mortality compared with nonparticipating programs.

Citation: Jha AK, Joynt KE, Orav EJ, Epstein AM. The long-term effect of premier pay for performance on patient outcomes. N Engl J Med. 2012;366:1606-1615.

In-Hospital Rate of DVT/PE After Hip and Knee Arthroplasty with Guideline-Recommended Prophylaxis

Clinical question: What is the rate of symptomatic DVT/PE after total or partial hip (TPHA) or knee (TPKA) arthroplasty using currently recommended prophylaxis?

Background: The rate of postoperative DVT/PE after TPHA/TPKA has dropped dramatically with use of pharmacologic prophylaxis. However, the current rate of symptomatic DVT/PE using current pharmacologic prophylaxis is not known. Such rates are needed for informed patient consent and development of patient safety benchmarks.

Study design: Systematic review.

Setting: Randomized clinical trials (RCTs) and observational studies worldwide of adult inpatients undergoing TPHA and/or TPKA from 1996 to 2011.

Synopsis: Forty-seven studies were included, of which 41 were RCTs and six were observational studies. Twenty-one studies evaluated rates after TPHA, 20 after TPKA, and six after both. More than 44,000 patients were included, with ages ranging from 58 to 74 years. The mean duration of prophylaxis was eight days, with a mean follow-up of 13 days.

In-hospital rates of symptomatic venous thromboembolism (VTE) were higher in patients undergoing TPKA than TPHA (1.09% vs. 0.53% for VTE, 0.63% vs. 0.26% for DVT, and 0.27% vs. 0.14% for PE). This is in contrast to the higher rates of VTE observed after TPHA when the post-discharge period is included. The pooled incidence of VTE was lower with use of direct inhibitors of Factors Xa or IIa when compared to low-molecular-weight heparin, although a direct efficacy comparison could not be made.

Because the majority of studies were RCTs with restrictive inclusion criteria, rates of DVT/PE in actual practice might be higher.

Bottom line: When informing patients of postoperative VTE risk, or establishing benchmarks to evaluate patient safety, one can anticipate an in-hospital VTE rate of 0.5% following TPHA and 1% following TPKA.

Citation: Januel JM, Chen G, Ruffieux C, et al. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review. JAMA. 2012;307(3):294-303.

Sodium Chloride Prevents Contrast-Induced Nephropathy

Clinical question: Is sodium chloride more effective than sodium bicarbonate for preventing contrast-induced nephropathy?

Background: Contrast-induced nephropathy can be prevented with precontrast hydration. Study authors sought to compare sodium chloride administered over 24 hours with sodium bicarbonate administered over seven hours, and with sodium bicarbonate administered orally.

Study design: Randomized, open-label, controlled trial.

Setting: Three European medical centers.

Synopsis: The study examined 258 patients with an estimated glomerular filtration rate <60mL/min/1.73m2 undergoing intravenous or intra-arterial contrast procedure. Patients with Class III or IV heart failure were excluded. The remaining patients were randomized to receive one of three regimens: sodium chloride at 1 ml/kg/hr for 12 hours prior to and 12 hours following the procedure; intravenous sodium bicarbonate for one hour prior to and six hours following the procedure; or intravenous and oral sodium bicarbonate 20 minutes prior to the procedure.

The group that received saline had a lower incidence of contrast-induced nephropathy than the bicarbonate groups (1% vs. 9% vs. 10%). The oral bicarbonate strategy was noninferior to the seven-hour intravenous bicarbonate strategy.

The authors postulated that saline should be used for high-risk patients, but that given the overall low incidence of contrast-induced nephropathy, the short-term bicarbonate strategy (intravenous followed by oral) is a viable alternative for low-risk patients.

Bottom line: Sodium chloride is more effective than sodium bicarbonate for preventing contrast-induced nephropathy, but in light of the low incidence, a short course of sodium bicarbonate is a possible convenient alternative for low-risk patients.

Citation: Klima T, Christ A, Marana I, et al. Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial. Eur Heart J. 2012 Jan 19 [Epub ahead of print].

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Neutral head position safe for internal jugular vein cannulation
2. Thrombolysis decreases mortality in unstable patients with acute PE
3. Rectal indomethacin decreases incidence of post-ERCP pancreatitis
4. CHADS2-VASc and HAS-BLED as predictors in afib patients
5. No readmission, mortality decreases with self-supported COPD management
6. Medicare Premier P4P initiatives do not decrease mortality
7. In-hospital rate of DVT/PE after hip and knee arthroplasty
8. Sodium chloride prevents contrast-induced nephropathy

Neutral Head Position Is Safe for Internal Jugular Vein Cannulation

Clinical question: Is there a difference in the complication rate between neutral head position and 45-degree neck rotation during ultrasound-guided internal jugular vein cannulation?

Background: Cannulation of the internal jugular vein using ultrasound decreases the rate of major complications (carotid artery puncture, pneumothorax, and hemothorax). The relative positions of the internal jugular vein and the carotid artery change based on degree of neck rotation. The optimal position for ultrasound-guided vein puncture has not been shown.

Study design: Prospective, randomized, controlled, non-blinded study.

Setting: Tertiary neurosurgical center in Milan, Italy.

Synopsis: One thousand, three hundred thirty-two patients undergoing major neurosurgical procedures who needed central venous catheter placement were randomized to a neutral head position (NH) or a 45-degree neck rotation (HT) during ultrasound-guided internal jugular vein cannulation. Exclusion criteria were consent refusal, age <12 years, and coagulopathy. Six experienced anesthesiologists performed the procedures; blinding was not possible.

There was no difference in the rate of major complications (carotid artery puncture, pneumothorax, or hemothorax) based on head position (0.9% in NH vs. 0.6% in HT). Minor complications (multiple skin punctures, multiple vein punctures, difficulty inserting the guidewire) were similar in the two groups (13.2% in NG vs. 12.6% in HT). Neck rotation was not associated with operator-reported difficulty or vascular access time.

Limitations of the study include the inability to blind the operator. Additionally, the study involved six experienced anesthesiologists at one center who performed the procedure on patients needing an elective central line. The ability to generalize the findings to other settings, less experienced providers, and patients who need an emergency line is not certain.

Bottom line: Neutral head position is as safe as 45-degree neck rotation for elective ultrasound-guided internal jugular vein cannulation.

Citation: Lamperti M, Subert M, Cortellazzi P, et al. Is a neutral head position safer than 45-degree neck rotation during ultrasound-guided internal jugular vein cannulation? Results of a randomized controlled clinical trial. Anesth Analg. 2012;114:777-784.

Thrombolysis Decreases Mortality in Unstable Patients with Acute Pulmonary Embolism

Clinical question: Does thrombolytic therapy decrease mortality in unstable patients with acute pulmonary embolism (PE)?

Background: PE is a common problem; associated mortality is high. Despite this fact, the data supporting thrombolytic therapy in hemodynamically unstable patients are not robust, and randomized, controlled trials are unlikely to be performed.

Study design: Retrospective cohort study.

Setting: One thousand nonfederal, short-term U.S. hospitals.

Synopsis: Using data from the Nationwide Inpatient Sample database from 1999-2008, investigators found that thrombolysis decreased both all-cause and PE-specific mortality for unstable patients, defined as those either in shock or on a ventilator. Specifically for all-cause mortality, 15% of patients who received thrombolysis died vs. 47% of those who did not (RR 0.31, 95% CI 0.30-0.32). Placement of an inferior vena cava (IVC) filter further reduced mortality, to only 7.6% in patients who received both IVC filter and thrombolysis.

For PE-specific mortality, patients who received thrombolysis also had decreased rates, from 42% to 8.4% (RR 0.20; 95% CI 0.19-0.22). Across all age groups, patients who received thrombolysis had decreased all-cause and PE-specific mortality. Patients who did not receive thrombolysis had additional comorbidities.

As this study is retrospective, it might be affected by unknown confounding. In addition, it relies on coding data to identify patient stability and treatment. Despite this limitation, a randomized, controlled trial is unlikely to be performed at this stage. This study provides evidence to support use of thrombolysis in unstable patients.

Bottom line: Thrombolysis might reduce mortality in unstable patients with acute PE. In combination with IVC filters, the mortality reduction might be even greater.

Citation: Stein PD, Matta F. Thrombolytic therapy in unstable patients with acute pulmonary embolism: saves lives but underused. Am J Med. 2012;125(5):465-470.

Rectal Indomethacin Decreases Incidence of Post-ERCP Pancreatitis

Clinical question: Does rectal indomethacin reduce the incidence of pancreatitis after ERCP?

Background: Acute pancreatitis is the most common complication from endoscopic retrograde cholangiopancreatography (ERCP). No pharmacologic treatment has proven to reduce the incidence of pancreatitis. Preliminary studies, including a meta-analysis, suggest that the use of NSAIDs might reduce the incidence of post-ERCP pancreatitis.

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

Setting: Multicenter trial at four university-affiliated medical centers in the U.S.

Synopsis: More than 600 patients at high risk for post-ERCP pancreatitis were randomized to receive either two 50-mg indomethacin suppositories or two identical-appearing placebo suppositories. Patients were considered at high risk for pancreatitis based on previously identified patient- and procedure-related risk factors. Most of the participants had sphincter of Oddi dysfunction (84.4% of the indomethacin group and 80.5% of the placebo group). Exclusion criteria included elevated creatinine and active peptic ulcer disease. The indomethacin or placebo suppositories were given immediately following the ERCP.

Post-ERCP pancreatitis, defined by upper abdominal pain, elevation of pancreatic enzymes, and hospitalization for at least two nights, was significantly higher in the placebo group compared with the indomethacin group (16.9% vs. 9.2%, P=0.005). Moderate or severe post-ERCP pancreatitis was significantly higher in the placebo group compared with the indomethacin group (8.8% vs. 4.4%, P=0.03).

There were no significant differences in the rates of clinically significant bleeding or acute renal failure between the two groups. The ability to generalize these findings to patients without risk factors for post-ERCP pancreatitis is not clear.

Bottom line: Rectal indomethacin decreases the rate of post-ERCP pancreatitis in patients who are at high risk for this complication.

Citation: Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis. N Engl J Med. 2012;366(15):1414-1422.

CHADS2-VASc and HAS-BLED Can Predict Thromboembolism and Bleeding Risk in Afib Patients

Clinical question: What are the risk factors for stroke/thromboembolism and bleeding from atrial fibrillation (afib), and how well do the CHADS2-VASc and HAS-BLED stroke and bleeding risk-assessment tools perform against other published stroke and bleeding risk-assessment tools (CHADS2 and HEMORR2HAGES) for patients with afib?

Background: In afib patients, the CHADS2-VASc tool might offer more comprehensive stroke assessment over the CHADS2 by identifying truly-low-risk patients with afib who might not even need antiplatelet therapy. HAS-BLED, a newer bleeding-risk-assessment tool, has been validated in previous trials and is more user-friendly than others. Use of CHADS2-VASc and HAS-BLED are recommended by the European Society of Cardiology to assess stroke and bleeding risks for patients with afib.

Study design: Prospective cohort study.

Setting: All hospitals in Sweden.

Synopsis: Investigators identified 182,678 afib patients via ICD-10 data from Sweden’s National Hospital Discharge Registry ICD-10 from 2005 to 2008. Approximately half the patients were not taking anticoagulants. Analysis assessed risk factors for stroke and bleeding and the performance of CHADS2-VASc and HAS-BLED against CHADS2 and HEMORR2HAGES stroke and bleeding risk-assessment tools.

Risk of composite thromboembolism (unspecified stroke, TIA, systemic embolism) was significantly higher in patients with increased age, peripheral arterial disease, prior myocardial infarction (MI), prior coronary artery bypass grafting (CABG), female gender, renal failure, and aspirin use, as well as hypertension, diabetes, prior thromboembolic event, or prior intracranial hemorrhage (ICH). Interestingly, a statistically increased risk was seen with aspirin use.

Conversely, history of heart failure, thyroid disease, and obesity were not associated with increased composite thromboembolic risk. The use of CHADS2-VASc was marginally better than CHADS2 in predicting stroke risk.

ICH risk was increased in patients with older age, prior ischemic stroke, prior ICH, and hypertension. Risk of composite bleeding (from ICH or other major bleeding) was significantly higher in patients with these risk factors, as well as renal failure, liver disease, anemia, dysfunctional platelets, alcohol use, and cancer. Ischemic heart disease was associated with a statistically significant lower risk of ICH, but not of composite bleeding risk.

HAS-BLED usage was as good as, and easier to use than, HEMORR2HAGES in predicting bleeding risk.

Bottom line: CHADS2-VASc might be better than CHADS2 in predicting truly-low-risk patients with nonvalvular afib; HAS-BLED is just as good as, and easier to use than, HEMORR2HAGES in predicting bleeding risk for patients with nonvalvular afib who are to receive antithrombotic therapy.

Citation: Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500-10 [Epub 2012 Jan 13].

Supported Self-Management of COPD Does Not Decrease Readmission or Mortality Rates

Clinical question: Does supported self-management of patients with chronic obstructive pulmonary disease (COPD) decrease COPD-related hospital readmission or death?

Clinical background: Supported self-management has benefited patients with such chronic diseases as heart failure and asthma. Evidence to support such a strategy for patients with COPD is relatively lacking.

Study design: Randomized, controlled trial.

Setting: Community-based care following urban hospitalization in western Scotland.

Synopsis: From June 2007 to May 2009, and following hospitalization for COPD exacerbation, 464 patients were randomized to receive routine community-based care with or without 12 months of support and training to detect, and promptly treat, recurrent exacerbations. Independent of disease severity or demographics, investigators found no difference in combined readmission (48% vs. 47%, 95% confidence interval [CI] 0.80-1.38) or death (10% vs. 7%, 95% CI 0.71-2.61).

Based on review of appropriateness of self-management strategies used by the intervention group, unplanned exploratory subgroup analysis classified a minority of the intervention group as “successful” (42%) supported self-managers, and demonstrated decreased COPD readmissions and death (27% vs. 49%, 95% CI 0.25-0.76, P=0.003) vs. “unsuccessful” self-managers. This successful group was younger and tended to live with others. Further research to define characteristics of patients who benefit from self-management is needed.

Bottom line: Supported self-management of COPD does not reduce COPD-related readmission or death in a large population.

Citation: Bucknall CE, Miller G, Lloyd SM, et al. Glasgow supported self-management trial (GSuST) for patients with moderate to severe COPD: randomised controlled trial. BMJ. 2012;344:e1060 [Epub ahead of print].

Medicare Premier P4P Initiatives Do Not Decrease Mortality

Clinical question: Has the Medicare Premier Hospital Quality Incentive Demonstration (HQID) resulted in lower mortality?

Background: The Centers for Medicare & Medicaid Services’ (CMS) value-based purchasing program will expand to include 30-day mortality in 2013, but do pay-for-performance (P4P) initiatives result in improved mortality? Studies have demonstrated improvement in process of care but have not demonstrated mortality benefit thus far.

Study design: Cohort study.

Setting: Two hundred fifty-two hospitals participating in the Premier HQID compared with 3,363 control hospitals participating in the Hospital Compare program.

Synopsis: Researchers examined 30-day mortality for patients admitted with acute myocardial infarction, congestive heart failure, pneumonia, and for coronary artery bypass grafting (CABG) from 2003 to 2009. Results showed no difference in 30-day mortality rates over the six-year span of the program for any of the conditions studied in the Premier hospitals (participating in the voluntary pay-for-performance program) vs. non-Premier hospitals (11.82% vs. 11.74%). This held true for each condition measured individually, with a higher mortality rate for patients undergoing CABG at the Premier hospitals.

In addition, in the hospitals that underperformed initially, there was no difference with respect to rate of improvement when comparing Premier vs. non-Premier hospitals. Furthermore, mortality rate trends did not differ between those conditions that were incentivized (acute MI and CABG) compared with those that were not (congestive heart failure and pneumonia).

The authors concluded that there was “little evidence” that the Premier HQID pay-for-performance program resulted in reduced 30-day mortality.

Bottom line: Programs participating in the Medicare Premier HQID pay-for-performance program had similar 30-day mortality compared with nonparticipating programs.

Citation: Jha AK, Joynt KE, Orav EJ, Epstein AM. The long-term effect of premier pay for performance on patient outcomes. N Engl J Med. 2012;366:1606-1615.

In-Hospital Rate of DVT/PE After Hip and Knee Arthroplasty with Guideline-Recommended Prophylaxis

Clinical question: What is the rate of symptomatic DVT/PE after total or partial hip (TPHA) or knee (TPKA) arthroplasty using currently recommended prophylaxis?

Background: The rate of postoperative DVT/PE after TPHA/TPKA has dropped dramatically with use of pharmacologic prophylaxis. However, the current rate of symptomatic DVT/PE using current pharmacologic prophylaxis is not known. Such rates are needed for informed patient consent and development of patient safety benchmarks.

Study design: Systematic review.

Setting: Randomized clinical trials (RCTs) and observational studies worldwide of adult inpatients undergoing TPHA and/or TPKA from 1996 to 2011.

Synopsis: Forty-seven studies were included, of which 41 were RCTs and six were observational studies. Twenty-one studies evaluated rates after TPHA, 20 after TPKA, and six after both. More than 44,000 patients were included, with ages ranging from 58 to 74 years. The mean duration of prophylaxis was eight days, with a mean follow-up of 13 days.

In-hospital rates of symptomatic venous thromboembolism (VTE) were higher in patients undergoing TPKA than TPHA (1.09% vs. 0.53% for VTE, 0.63% vs. 0.26% for DVT, and 0.27% vs. 0.14% for PE). This is in contrast to the higher rates of VTE observed after TPHA when the post-discharge period is included. The pooled incidence of VTE was lower with use of direct inhibitors of Factors Xa or IIa when compared to low-molecular-weight heparin, although a direct efficacy comparison could not be made.

Because the majority of studies were RCTs with restrictive inclusion criteria, rates of DVT/PE in actual practice might be higher.

Bottom line: When informing patients of postoperative VTE risk, or establishing benchmarks to evaluate patient safety, one can anticipate an in-hospital VTE rate of 0.5% following TPHA and 1% following TPKA.

Citation: Januel JM, Chen G, Ruffieux C, et al. Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review. JAMA. 2012;307(3):294-303.

Sodium Chloride Prevents Contrast-Induced Nephropathy

Clinical question: Is sodium chloride more effective than sodium bicarbonate for preventing contrast-induced nephropathy?

Background: Contrast-induced nephropathy can be prevented with precontrast hydration. Study authors sought to compare sodium chloride administered over 24 hours with sodium bicarbonate administered over seven hours, and with sodium bicarbonate administered orally.

Study design: Randomized, open-label, controlled trial.

Setting: Three European medical centers.

Synopsis: The study examined 258 patients with an estimated glomerular filtration rate <60mL/min/1.73m2 undergoing intravenous or intra-arterial contrast procedure. Patients with Class III or IV heart failure were excluded. The remaining patients were randomized to receive one of three regimens: sodium chloride at 1 ml/kg/hr for 12 hours prior to and 12 hours following the procedure; intravenous sodium bicarbonate for one hour prior to and six hours following the procedure; or intravenous and oral sodium bicarbonate 20 minutes prior to the procedure.

The group that received saline had a lower incidence of contrast-induced nephropathy than the bicarbonate groups (1% vs. 9% vs. 10%). The oral bicarbonate strategy was noninferior to the seven-hour intravenous bicarbonate strategy.

The authors postulated that saline should be used for high-risk patients, but that given the overall low incidence of contrast-induced nephropathy, the short-term bicarbonate strategy (intravenous followed by oral) is a viable alternative for low-risk patients.

Bottom line: Sodium chloride is more effective than sodium bicarbonate for preventing contrast-induced nephropathy, but in light of the low incidence, a short course of sodium bicarbonate is a possible convenient alternative for low-risk patients.

Citation: Klima T, Christ A, Marana I, et al. Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial. Eur Heart J. 2012 Jan 19 [Epub ahead of print].

Clinical question: Does supported self-management of patients with chronic obstructive pulmonary disease (COPD) decrease COPD-related hospital readmission or death?

Clinical background: Supported self-management has benefited patients with such chronic diseases as heart failure and asthma. Evidence to support such a strategy for patients with COPD is relatively lacking.

Study design: Randomized, controlled trial.

Setting: Community-based care following urban hospitalization in western Scotland.

Synopsis: From June 2007 to May 2009, and following hospitalization for COPD exacerbation, 464 patients were randomized to receive routine community-based care with or without 12 months of support and training to detect, and promptly treat, recurrent exacerbations. Independent of disease severity or demographics, investigators found no difference in combined readmission rates (48% vs. 47%, 95% confidence interval [CI] 0.80-1.38) or death (10% vs. 7%, 95% CI 0.71-2.61).

Based on review of appropriateness of self-management strategies used by the intervention group, unplanned exploratory subgroup analysis classified a minority of the intervention group as “successful” (42%) supported self-managers, and demonstrated decreased COPD readmissions and deaths (27% vs. 49%, 95% CI 0.25-0.76, P=0.003) vs. “unsuccessful” self-managers. This successful group was younger and tended to live with others. Further research to define characteristics of patients who benefit from self-management is needed.

Bottom line: Supported self-management of COPD does not reduce COPD-related readmissions or deaths in a large population.

Citation: Bucknall CE, Miller G, Lloyd SM, et al. Glasgow supported self-management trial (GSuST) for patients with moderate to severe COPD: randomised controlled trial. BMJ. 2012;344:e1060.

Check out more physician reviews of HM-relevant research.

Clinical question: Does supported self-management of patients with chronic obstructive pulmonary disease (COPD) decrease COPD-related hospital readmission or death?

Clinical background: Supported self-management has benefited patients with such chronic diseases as heart failure and asthma. Evidence to support such a strategy for patients with COPD is relatively lacking.

Study design: Randomized, controlled trial.

Setting: Community-based care following urban hospitalization in western Scotland.

Synopsis: From June 2007 to May 2009, and following hospitalization for COPD exacerbation, 464 patients were randomized to receive routine community-based care with or without 12 months of support and training to detect, and promptly treat, recurrent exacerbations. Independent of disease severity or demographics, investigators found no difference in combined readmission rates (48% vs. 47%, 95% confidence interval [CI] 0.80-1.38) or death (10% vs. 7%, 95% CI 0.71-2.61).

Based on review of appropriateness of self-management strategies used by the intervention group, unplanned exploratory subgroup analysis classified a minority of the intervention group as “successful” (42%) supported self-managers, and demonstrated decreased COPD readmissions and deaths (27% vs. 49%, 95% CI 0.25-0.76, P=0.003) vs. “unsuccessful” self-managers. This successful group was younger and tended to live with others. Further research to define characteristics of patients who benefit from self-management is needed.

Bottom line: Supported self-management of COPD does not reduce COPD-related readmissions or deaths in a large population.

Citation: Bucknall CE, Miller G, Lloyd SM, et al. Glasgow supported self-management trial (GSuST) for patients with moderate to severe COPD: randomised controlled trial. BMJ. 2012;344:e1060.

Check out more physician reviews of HM-relevant research.

Clinical question: Does supported self-management of patients with chronic obstructive pulmonary disease (COPD) decrease COPD-related hospital readmission or death?

Clinical background: Supported self-management has benefited patients with such chronic diseases as heart failure and asthma. Evidence to support such a strategy for patients with COPD is relatively lacking.

Study design: Randomized, controlled trial.

Setting: Community-based care following urban hospitalization in western Scotland.

Synopsis: From June 2007 to May 2009, and following hospitalization for COPD exacerbation, 464 patients were randomized to receive routine community-based care with or without 12 months of support and training to detect, and promptly treat, recurrent exacerbations. Independent of disease severity or demographics, investigators found no difference in combined readmission rates (48% vs. 47%, 95% confidence interval [CI] 0.80-1.38) or death (10% vs. 7%, 95% CI 0.71-2.61).

Based on review of appropriateness of self-management strategies used by the intervention group, unplanned exploratory subgroup analysis classified a minority of the intervention group as “successful” (42%) supported self-managers, and demonstrated decreased COPD readmissions and deaths (27% vs. 49%, 95% CI 0.25-0.76, P=0.003) vs. “unsuccessful” self-managers. This successful group was younger and tended to live with others. Further research to define characteristics of patients who benefit from self-management is needed.

Bottom line: Supported self-management of COPD does not reduce COPD-related readmissions or deaths in a large population.

Citation: Bucknall CE, Miller G, Lloyd SM, et al. Glasgow supported self-management trial (GSuST) for patients with moderate to severe COPD: randomised controlled trial. BMJ. 2012;344:e1060.

Check out more physician reviews of HM-relevant research.

Clinical question: Do oral fluoroquinolones increase the risk of retinal detachment?

Background: Fluoroquinolones are increasingly used in both inpatient and outpatient settings, given their broad antimicrobial coverage. However, adverse effects, including those related to connective tissue and the eye, are increasingly reported. Whether that also includes retinal detachment is not yet known.

Study design: Nested case control study.

Setting: Canadian province.

Synopsis: Using data from administrative databases to identify patients who visited ophthalmologists in British Columbia between 2000 and 2007, the investigators identified 4,384 cases of retinal detachment, and matched those cases to controls at a rate of 10:1. Current, recent, and past fluoroquinolone usage was the exposure of interest.

Patients actively taking a fluoroquinolone had a higher risk of retinal detachment compared with those not taking the drug (adjusted RR of 4.5, 95% CI of 3.56-5.70). Prior or recent use of a fluoroquinolone did not increase the rate of retinal detachment. The patients were more likely to be male, myopic, diabetic, and have a prior history of cataract surgery. Ciprofloxacin was the drug most frequently involved, but this is not adjusted by frequency of prescription. Despite this association, the actual outcome is quite rare (approximately 1,440 cases per year in the U.S.).

This study has the benefit of a large amount of data and captures prescription data well. It relied on coding to identify the cases and might have missed or inappropriately categorized some cases. Despite these caveats, this study adds to the concerning adverse events due to the increasing use of fluoroquinolone therapy, and hospitalists should use appropriate clinical judgment when prescribing and educating patients about the risks and benefits.

Bottom line: Fluoroquinolone use might increase the rate of retinal detachment in patients, but the absolute risk of the event is low.

Citation: Etminan M, Forooghian F, Brophy JM, Bird ST, Maberley D. Oral fluoroquinolones and the risk of retinal detachment. JAMA. 2012;307:1414-1419.

Clinical question: Do oral fluoroquinolones increase the risk of retinal detachment?

Background: Fluoroquinolones are increasingly used in both inpatient and outpatient settings, given their broad antimicrobial coverage. However, adverse effects, including those related to connective tissue and the eye, are increasingly reported. Whether that also includes retinal detachment is not yet known.

Study design: Nested case control study.

Setting: Canadian province.

Synopsis: Using data from administrative databases to identify patients who visited ophthalmologists in British Columbia between 2000 and 2007, the investigators identified 4,384 cases of retinal detachment, and matched those cases to controls at a rate of 10:1. Current, recent, and past fluoroquinolone usage was the exposure of interest.

Patients actively taking a fluoroquinolone had a higher risk of retinal detachment compared with those not taking the drug (adjusted RR of 4.5, 95% CI of 3.56-5.70). Prior or recent use of a fluoroquinolone did not increase the rate of retinal detachment. The patients were more likely to be male, myopic, diabetic, and have a prior history of cataract surgery. Ciprofloxacin was the drug most frequently involved, but this is not adjusted by frequency of prescription. Despite this association, the actual outcome is quite rare (approximately 1,440 cases per year in the U.S.).

This study has the benefit of a large amount of data and captures prescription data well. It relied on coding to identify the cases and might have missed or inappropriately categorized some cases. Despite these caveats, this study adds to the concerning adverse events due to the increasing use of fluoroquinolone therapy, and hospitalists should use appropriate clinical judgment when prescribing and educating patients about the risks and benefits.

Bottom line: Fluoroquinolone use might increase the rate of retinal detachment in patients, but the absolute risk of the event is low.

Citation: Etminan M, Forooghian F, Brophy JM, Bird ST, Maberley D. Oral fluoroquinolones and the risk of retinal detachment. JAMA. 2012;307:1414-1419.

Clinical question: Do oral fluoroquinolones increase the risk of retinal detachment?

Background: Fluoroquinolones are increasingly used in both inpatient and outpatient settings, given their broad antimicrobial coverage. However, adverse effects, including those related to connective tissue and the eye, are increasingly reported. Whether that also includes retinal detachment is not yet known.

Study design: Nested case control study.

Setting: Canadian province.

Synopsis: Using data from administrative databases to identify patients who visited ophthalmologists in British Columbia between 2000 and 2007, the investigators identified 4,384 cases of retinal detachment, and matched those cases to controls at a rate of 10:1. Current, recent, and past fluoroquinolone usage was the exposure of interest.

Patients actively taking a fluoroquinolone had a higher risk of retinal detachment compared with those not taking the drug (adjusted RR of 4.5, 95% CI of 3.56-5.70). Prior or recent use of a fluoroquinolone did not increase the rate of retinal detachment. The patients were more likely to be male, myopic, diabetic, and have a prior history of cataract surgery. Ciprofloxacin was the drug most frequently involved, but this is not adjusted by frequency of prescription. Despite this association, the actual outcome is quite rare (approximately 1,440 cases per year in the U.S.).

This study has the benefit of a large amount of data and captures prescription data well. It relied on coding to identify the cases and might have missed or inappropriately categorized some cases. Despite these caveats, this study adds to the concerning adverse events due to the increasing use of fluoroquinolone therapy, and hospitalists should use appropriate clinical judgment when prescribing and educating patients about the risks and benefits.

Bottom line: Fluoroquinolone use might increase the rate of retinal detachment in patients, but the absolute risk of the event is low.

Citation: Etminan M, Forooghian F, Brophy JM, Bird ST, Maberley D. Oral fluoroquinolones and the risk of retinal detachment. JAMA. 2012;307:1414-1419.

Clinical question: With the current use of warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation, what do the most recent data show with regard to time spent in the therapeutic window, stroke risk, and bleeding risk?

Background: Historically, warfarin has been shown to decrease stroke risk in nonvalvular atrial fibrillation by 62% compared with placebo, balanced by a significant risk of bleeding. Despite the availability of multiple new antithrombotic agents, warfarin will likely continue to be widely used given its lower cost. As a result, physicians need an accurate estimate of warfarin’s efficacy and safety as currently used in practice.

Study design: Meta-analysis of randomized controlled trials (RCTs).

Setting: RCTs comparing warfarin to an alternative antithrombotic agent from 2001 to 2011.

Synopsis: Eight RCTs of nonvalvular atrial fibrillation were included, yielding data on 32,053 patients with a mean age range of 70 to 82 years and widely variable CHADS2 scores. The time spent at a therapeutic INR was found to be improved when compared to historical rates, ranging from 55% to 68%. The rate of stroke or non-central-nervous-system embolism ranged from 1.2% to 2.3% per year, with a pooled event rate of 1.66% per year, compared with 2.09% per year in earlier trials.

Major bleeding was defined differently across studies, with a reported incidence of 1.4% to 3.4% per year, a pooled event rate of intracranial hemorrhage of 0.61%, and a cumulative adverse event rate of 3.0% to 7.64%. Stroke rates were highest in patients older than 75 years, women, those with a history of transient ischemic attack or stroke, those new to warfarin, and those with higher CHADS2 scores.

Bottom line: Warfarin as currently used is associated with an annual rate of stroke or systemic embolism of 1.66% and an annual rate of major bleeding ranging from 1.4% to 3.4%.

Citation: Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med. 2012;172:623-631.

Clinical question: With the current use of warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation, what do the most recent data show with regard to time spent in the therapeutic window, stroke risk, and bleeding risk?

Background: Historically, warfarin has been shown to decrease stroke risk in nonvalvular atrial fibrillation by 62% compared with placebo, balanced by a significant risk of bleeding. Despite the availability of multiple new antithrombotic agents, warfarin will likely continue to be widely used given its lower cost. As a result, physicians need an accurate estimate of warfarin’s efficacy and safety as currently used in practice.

Study design: Meta-analysis of randomized controlled trials (RCTs).

Setting: RCTs comparing warfarin to an alternative antithrombotic agent from 2001 to 2011.

Synopsis: Eight RCTs of nonvalvular atrial fibrillation were included, yielding data on 32,053 patients with a mean age range of 70 to 82 years and widely variable CHADS2 scores. The time spent at a therapeutic INR was found to be improved when compared to historical rates, ranging from 55% to 68%. The rate of stroke or non-central-nervous-system embolism ranged from 1.2% to 2.3% per year, with a pooled event rate of 1.66% per year, compared with 2.09% per year in earlier trials.

Major bleeding was defined differently across studies, with a reported incidence of 1.4% to 3.4% per year, a pooled event rate of intracranial hemorrhage of 0.61%, and a cumulative adverse event rate of 3.0% to 7.64%. Stroke rates were highest in patients older than 75 years, women, those with a history of transient ischemic attack or stroke, those new to warfarin, and those with higher CHADS2 scores.

Bottom line: Warfarin as currently used is associated with an annual rate of stroke or systemic embolism of 1.66% and an annual rate of major bleeding ranging from 1.4% to 3.4%.

Citation: Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med. 2012;172:623-631.

Clinical question: With the current use of warfarin for stroke prophylaxis in patients with nonvalvular atrial fibrillation, what do the most recent data show with regard to time spent in the therapeutic window, stroke risk, and bleeding risk?

Background: Historically, warfarin has been shown to decrease stroke risk in nonvalvular atrial fibrillation by 62% compared with placebo, balanced by a significant risk of bleeding. Despite the availability of multiple new antithrombotic agents, warfarin will likely continue to be widely used given its lower cost. As a result, physicians need an accurate estimate of warfarin’s efficacy and safety as currently used in practice.

Study design: Meta-analysis of randomized controlled trials (RCTs).

Setting: RCTs comparing warfarin to an alternative antithrombotic agent from 2001 to 2011.

Synopsis: Eight RCTs of nonvalvular atrial fibrillation were included, yielding data on 32,053 patients with a mean age range of 70 to 82 years and widely variable CHADS2 scores. The time spent at a therapeutic INR was found to be improved when compared to historical rates, ranging from 55% to 68%. The rate of stroke or non-central-nervous-system embolism ranged from 1.2% to 2.3% per year, with a pooled event rate of 1.66% per year, compared with 2.09% per year in earlier trials.

Major bleeding was defined differently across studies, with a reported incidence of 1.4% to 3.4% per year, a pooled event rate of intracranial hemorrhage of 0.61%, and a cumulative adverse event rate of 3.0% to 7.64%. Stroke rates were highest in patients older than 75 years, women, those with a history of transient ischemic attack or stroke, those new to warfarin, and those with higher CHADS2 scores.

Bottom line: Warfarin as currently used is associated with an annual rate of stroke or systemic embolism of 1.66% and an annual rate of major bleeding ranging from 1.4% to 3.4%.

Citation: Agarwal S, Hachamovitch R, Menon V. Current trial-associated outcomes with warfarin in prevention of stroke in patients with nonvalvular atrial fibrillation: a meta-analysis. Arch Intern Med. 2012;172:623-631.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. High-dose vs. low-dose clopidogrel after cardiac stenting
2. Rates of overdiagnosis of PE with CTPA
3. Outcomes of hospitalists with PAs or residents
4. White coats and MRSA
5. Correlation of vital signs and pain
6. Rate of asymptomatic perioperative MI
7. Relationship of opioid prescription patterns and overdose
8. Interdisciplinary rounds and rates of adverse events

High-Dose Clopidogrel Is Not Superior to Standard-Dose Clopidogrel in Patients with High On-Treatment Platelet Activity after Percutaneous Corona

Clinical question: In patients with high on-treatment platelet activity, does the use of high-dose clopidogrel after percutaneous coronary intervention (PCI) decrease the risk of cardiovascular events?

Background: In patients receiving clopidogrel, high platelet reactivity after PCI is associated with an increase in cardiovascular events. At present, treatments targeted at this population are not well-defined.

Study design: Randomized, double-blind, active-control trial.

Setting: Eighty-three centers in North America.

Synopsis: Researchers randomized 2,214 patients with drug-eluting stents to receive either high-dose clopidogrel (600 mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily). At six months, the primary endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis was no different in the two groups (2.3% in the high-dose group versus 2.3% in the standard-dose group; hazard ratio 1.01).

Bottom line: High-dose clopidogrel adds no benefit over standard-dose clopidogrel in patients with high platelet reactivity who have undergone PCI with drug-eluting stent placement.

Citation: Price MJ, Berger PB, Teirstein PS, et al. Standard- vs. high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305(11):1097-1105.

Computed Tomographic Pulmonary Angiography (CTPA) Is Associated with Overdiagnosis and Overtreatment of Pulmonary Embolism (PE)

Clinical question: Is the use of CTPA associated with increased incidence of PE and increased complications from anticoagulation treatment?

Background: CTPA is a sensitive, noninvasive test for diagnosing PE that could have a drawback: identifying potentially clinically unimportant (small) pulmonary emboli that subsequently are treated. Overtreatment might be associated with patient harm due to increased complications of anticoagulation therapy.

Study design: Time-trend analysis of PE between the pre-CTPA period (1993 to 1998) and the post-CTPA period (1998 to 2006).

Setting: Nongovernmental U.S. hospitals.

Synopsis: The Nationwide Inpatient Sample and Multiple Cause-of-Death databases were used to determine national estimates of hospitalization for PE, along with morbidity and mortality from PE.

The age-adjusted analysis revealed a statistically significant increase in the incidence of PE diagnosis after introduction of CTPA (to 112 per 100,000 from 62 per 100,000), with minimal change in overall PE mortality. This was accompanied by a substantial reduction in PE case-fatality rate, the rate of hospital deaths among patients with a diagnosis of pulmonary embolism.

Availability of CTPA was associated with a significant increase in anticoagulation complication rates (to 5.3 per 100,000 from 3.1 per 100,000), including statistically significant increases in gastrointestinal hemorrhage and secondary thrombocytopenia, and a trend toward higher rates of intracranial hemorrhage.

Bottom line: Introduction of CTPA was associated with changes suggestive of overdiagnosis (increased incidence, relatively unchanged mortality) and overtreatment (increased complication rates) of PE, but it remains unknown which small PEs are clinically significant.

Citation: Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837.

Hospitalist-Physician Assistant Teams Associated with Longer Length of Stay, No Change in Mortality, Readmission Rates

Clinical question: Do length of stay (LOS), hospital mortality, or readmission rate change if hospitalists and physician assistants, or the traditional resident-hospitalist teams, provide the patient care?

Background: Resident work-hour limitations require new models of care for hospitalized patients. Many academic medical centers have hired physician assistants to work with hospitalists to provide care. Little is known about how these models affect such outcomes as LOS, inpatient mortality rates, and readmission rates.

Study design: Retrospective cohort.

Setting: A 430-bed urban academic medical center in Milwaukee.

Synopsis: Administrative data were gathered on 9,681 patients admitted to the general medical service. Of those enrolled, 2,171 were cared for by a hospitalist-physician assistant (H-PA) team, while resident-hospitalist teams cared for 7,510 patients. Patient assignment was dependent on time of admission but not on patient complexity. Patients admitted overnight after the resident team capped were assigned to the H-PA team the next morning, resulting in increased transitions of care for the H-PA team.

Adjusted analyses revealed a 6.45% increase in LOS for the H-PA team compared with the resident team. Charges, inpatient mortality, and readmission rates at seven, 14, and 30 days were unchanged. Subgroup analyses revealed smaller differences in LOS for H-PA teams and resident-hospitalist teams with the same hospitalist (LOS 5.44% higher, P=0.081).

Conclusions from this study are limited due to lack of randomization of assignment, the retrospective design, and the use of administrative data at one institution.

Bottom line: Hospitalist-PA teams might result in a slightly increased LOS compared with the traditional resident teams; however, inpatient mortality and readmission rates are similar.

Citation: Singh S, Fletcher KE, Schapira MM, et al. A comparison of outcomes of general medical inpatient care provided by a hospitalist-physician assistant model vs a traditional resident-based model. J Hosp Med. 2011;6:122-130.

Washing White Coats Does Not Lower MRSA Bacterial Contamination

Clinical question: Are clean, short-sleeved uniforms less likely to carry MRSA than regularly laundered long-sleeved white coats?

Background: Studies have shown that bacteria frequently colonize in physician garments. However, evidence that short-sleeved garments or newly laundered garments are less likely to be contaminated has been lacking. Despite the paucity of evidence, the British Department of Health barred the use of traditional white coats and long-sleeved garments in 2007.

Study design: Prospective, randomized, controlled trial.

Setting: Urban U.S. hospital.

Synopsis: Study authors randomized 100 internal-medicine residents and hospitalists to their own long-sleeved white coats or freshly laundered short-sleeved uniforms from August 2008 to November 2009. Swabs were taken from the sleeves of the white coats or uniform, the breast pocket, and the volar wrist surface of the dominant hand. Swabs were cultured for MRSA and for general colony count.

Results showed no significant difference in colony counts or MRSA colonization in any of the sites tested between the newly laundered uniforms and the white coats. Additionally, there was no effect in relation to the frequency of laundering the white coats. Notably, within three hours of donning freshly laundered uniforms, bacterial counts approached 50% of the total bacterial counts seen at eight hours.

Bottom line: Laundering of uniforms does not affect MRSA colonization rate or general bacterial burden on physician uniforms or skin surfaces, though the effect on nosocomial infection has not been established.

Citation: Burden M, Cervantes L, Weed D, Keniston A, Price CS, Albert RK. Newly cleaned physician uniforms and infrequently washed white coats have similar rates of bacterial contamination after an 8-hour workday: a randomized controlled trial. J Hosp Med. 2011;6:177-182.

Self-Reported Pain Severity Does Not Correlate with Heart Rate or Blood Pressure Measurements in Pre-Hospital Setting

Clinical question: Do measured vital signs, including heart rate, blood pressure, and respiratory rate, correlate with the degree of self-reported pain?

Background: Because pain often can be associated with alterations in autonomic tone, it has been hypothesized that alterations in vital signs will occur in patients who report pain.

Study design: Retrospective cohort study.

Setting: Pre-hospital in Melbourne, Australia.

Synopsis: The authors reviewed all ambulance patient care records for patients age >14 years with a Glasgow Coma Score (GCS) >12 transported to a hospital during a seven-day period in 2005. Patients were selected for analysis if their patient care record included an initial assessment of pain severity, as measured by a numeric rating scale (NRS), in which patients rate their pain from 0 to 10.

More than half of the 3,357 patients transported by paramedics during the period were included in this analysis (n=1286). There was no correlation between heart rate or systolic blood pressure with the degree of self-reported pain. Although an increased respiratory rate was statistically correlated with a higher rating of pain, this relationship was not clinically significant, as each one-point increase in the pain rating scale was associated with a 0.16-breaths-per-minute increase in the respiratory rate.

Limitations included the large number of records excluded from analysis because pain was not evaluated, as well as numerous unmeasured confounders, including active disease processes such as sepsis, that were not accounted for.

Bottom line: Severity of pain did not correlate with heart rate or systolic blood pressure in the pre-hospital setting.

Citation: Lord B, Woollard M. The reliability of vital signs in estimating pain severity among adult patients treated by paramedics. Emerg Med J. 2011;28:147-150.

Asymptomatic Perioperative Myocardial Infarction Is Common in Patients Undergoing Noncardiac Surgery

Clinical question: In patients undergoing noncardiac surgery, what is the incidence and clinical characteristics of perioperative myocardial infarction (MI)?

Background: Though millions of patients experience perioperative MI after noncardiac surgery, little is known about the characteristics and outcomes of these patients.

Study design: Cohort study.

Setting: One hundred ninety centers in 23 countries.

Synopsis: Using data from the 8,351 patients in the POISE (PeriOperative ISchemic Evaluation) trial, this study showed that perioperative MI occurred in 5% of patients; 65% were asymptomatic. Patients who experienced postoperative MI were older and had more cardiovascular risk factors when compared to those who did not. The 30-day mortality was higher in patients with a perioperative MI (11.6%) compared with those who did not (2.2%); the presence or absence of ischemic symptoms was not associated with mortality rate.

Of the 8.3% of patients who experienced an elevation in cardiac biomarkers but who did not meet the definition of MI, there was an increased risk of nonfatal cardiac arrest and nonacute coronary revascularization. Those in the highest quartile also had increased 30-day mortality.

Bottom line: Given the high proportion of asymptomatic MIs and isolated elevations in cardiac biomarkers and the association between these events and increased risk of death, hospitalists should consider routine monitoring of troponin in at-risk patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154(8):523-528.

Patients Prescribed Higher Opioid Doses Are at Increased Risk of Opioid Overdose Death

Clinical question: What is the association between opioid prescribing patterns and fatal opioid overdose?

Background: In the past 10 years, the rate of fatal overdose from opioid prescription for pain has more than doubled. Little is known about how the indications (substance abuse disorders, cancer-related pain, chronic pain, acute pain), maximal daily dose, and scheduling (standing, as-needed, or both) of opioid prescriptions relate to this increased risk.

Study design: Case-cohort study.

Setting: Veterans Health Administration (VHA) patients.

Synopsis: The VHA’s National Patient Care Database was used to randomly select a cohort of 154,684 nonhospice/nonpalliative-care patients who were prescribed opioids from 2004 to 2008. They were compared with 750 patients who were treated with prescription opioids who died from opioid overdose during this time.

Fatal opioid overdose was a rare event (0.04%), but risk increased with higher prescribed maximum daily morphine dose-equivalence, especially when greater than or equal to 50 mg/day in all subgroups (substance abuse, acute and chronic pain, and cancer). Fatal overdoses were higher in middle-aged white men with acute or chronic pain, substance abuse disorders, and other psychiatric illness. Patients with cancer were at increased risk of fatal overdose if they were prescribed as-needed opioids alone.

Treatment with both as-needed and standing opioids did not statistically affect risk of overdose death in any subgroup.

Bottom line: Although rare, risk of fatal opioid overdose in patients prescribed opiate medication increases with higher maximum prescribed daily dose.

Citation: Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305:1315-1321.

Structured Interdisciplinary Rounds on Medical Teaching Unit Significantly Decrease Adverse Events

Clinical question: Do structured interdisciplinary rounds have an impact on the rate of adverse events?

Background: Many preventable adverse events occurring during hospitalization can be attributed to communication failures. Structured interdisciplinary rounds provide a format as well as a forum for team members to discuss patient care. Prior studies demonstrated improvements in collaboration; whether this translates to better patient care is not known.

Study design: Retrospective cohort using historic and concurrent control.

Setting: Tertiary-care teaching hospital in Chicago.

Synopsis: Structured interdisciplinary rounds, led by a nurse manager and medical director, and including nurses, residents, pharmacists, social workers, and case managers, were implemented on a medical teaching unit. New patients were discussed using a structured communication tool; existing patients were discussed in an unstructured format. Medical records were abstracted for 370 patients hospitalized after implementation of the intervention, equally divided between intervention and control units. One hundred eighty-five patients hospitalized on the intervention unit prior to the implementation of rounds served as a historic control.

Patients in the intervention unit had significantly lower rates of total adverse events (3.9 per 100 patient days in the intervention, compared with 7.2 and 7.7 per 100 patient days for the concurrent and historic control units, respectively), and preventable adverse events (0.9 per 100 patient days, compared with 2.8 and 2.1 per 100 patient days for the concurrent and historic controls, respectively).

Limitations of the study include lack of blinding of the medical record, slightly different patient populations in intervention and control groups, and the one-hospital setting, which could limit generalizability.

Bottom line: Structured interdisciplinary rounds might serve to improve communication between nurses, pharmacists, and physicians, resulting in decreases in adverse events.

Citation: O’Leary KJ, Buck R, Fligiel HM, et al. Structured interdisciplinary rounds in a medical teaching unit: improving patient safety. Arch Intern Med. 2011;171(7):678-684.

Pediatric HM Literature

Short-Course Antibiotic Therapy Effective for Bacterial Meningitis

Clinical question: Is five days of parenteral ceftriaxone as effective as 10 days for the treatment of bacterial meningitis in children?

Background: Morbidity and mortality in bacterial meningitis remain high, particularly in developing countries. Antibiotics are effective treatment, yet the optimal duration of treatment remains uncertain. Some data support a shorter duration of treatment (three to five days).

Study design: Multicountry, double-blind, placebo-controlled, randomized equivalence study.

Setting: Ten pediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam.

Synopsis: Children aged two months to 12 years with bacterial meningitis (due to Haemophilus influenza, Streptococcus pneumonia, Neisseria meningitidis, or culture-negative with indicative cerebrospinal fluid findings) and without complicating medical conditions were enrolled at participating centers. All children received 80 mg/kg to 100 mg/kg of parenteral ceftriaxone daily and a repeat lumbar puncture 48 to 72 hours after initiation of therapy.

Ultimately, 1,004 children without resistant organisms, persistently positive cultures, or suppurative complications were randomized on day five of therapy to placebo or continuance of ceftriaxone for five more days.

No bacteriologic failures (primary endpoint) were evident with either five or 10 days of treatment.

In addition, no statistically significant differences were found between the groups with respect to clinical treatment failure, hearing loss, neurological sequelae, or death. Secondary analysis by organism revealed similar results.

The primary limitation of this study is that it occurred in developing countries with a fair incidence of H. influenzae meningitis and a low rate of third-generation cephalosporin resistance.

However, pneumococcal and meningococcal disease remained prominent, and this study suggests that clinically stable patients might be treated with a shorter course of parenteral ceftriaxone therapy than currently is recommended.

Bottom line: Five days of ceftriaxone is as effective as 10 days for uncomplicated bacterial meningitis in children.

Citation: Molyneux E, Nizami SQ, Saha S, et al. 5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Lancet. 2011;377:1837-1845.

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

In This Edition

Literature At A Glance

A guide to this month’s studies

1. High-dose vs. low-dose clopidogrel after cardiac stenting
2. Rates of overdiagnosis of PE with CTPA
3. Outcomes of hospitalists with PAs or residents
4. White coats and MRSA
5. Correlation of vital signs and pain
6. Rate of asymptomatic perioperative MI
7. Relationship of opioid prescription patterns and overdose
8. Interdisciplinary rounds and rates of adverse events

High-Dose Clopidogrel Is Not Superior to Standard-Dose Clopidogrel in Patients with High On-Treatment Platelet Activity after Percutaneous Corona

Clinical question: In patients with high on-treatment platelet activity, does the use of high-dose clopidogrel after percutaneous coronary intervention (PCI) decrease the risk of cardiovascular events?

Background: In patients receiving clopidogrel, high platelet reactivity after PCI is associated with an increase in cardiovascular events. At present, treatments targeted at this population are not well-defined.

Study design: Randomized, double-blind, active-control trial.

Setting: Eighty-three centers in North America.

Synopsis: Researchers randomized 2,214 patients with drug-eluting stents to receive either high-dose clopidogrel (600 mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily). At six months, the primary endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis was no different in the two groups (2.3% in the high-dose group versus 2.3% in the standard-dose group; hazard ratio 1.01).

Bottom line: High-dose clopidogrel adds no benefit over standard-dose clopidogrel in patients with high platelet reactivity who have undergone PCI with drug-eluting stent placement.

Citation: Price MJ, Berger PB, Teirstein PS, et al. Standard- vs. high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305(11):1097-1105.

Computed Tomographic Pulmonary Angiography (CTPA) Is Associated with Overdiagnosis and Overtreatment of Pulmonary Embolism (PE)

Clinical question: Is the use of CTPA associated with increased incidence of PE and increased complications from anticoagulation treatment?

Background: CTPA is a sensitive, noninvasive test for diagnosing PE that could have a drawback: identifying potentially clinically unimportant (small) pulmonary emboli that subsequently are treated. Overtreatment might be associated with patient harm due to increased complications of anticoagulation therapy.

Study design: Time-trend analysis of PE between the pre-CTPA period (1993 to 1998) and the post-CTPA period (1998 to 2006).

Setting: Nongovernmental U.S. hospitals.

Synopsis: The Nationwide Inpatient Sample and Multiple Cause-of-Death databases were used to determine national estimates of hospitalization for PE, along with morbidity and mortality from PE.

The age-adjusted analysis revealed a statistically significant increase in the incidence of PE diagnosis after introduction of CTPA (to 112 per 100,000 from 62 per 100,000), with minimal change in overall PE mortality. This was accompanied by a substantial reduction in PE case-fatality rate, the rate of hospital deaths among patients with a diagnosis of pulmonary embolism.

Availability of CTPA was associated with a significant increase in anticoagulation complication rates (to 5.3 per 100,000 from 3.1 per 100,000), including statistically significant increases in gastrointestinal hemorrhage and secondary thrombocytopenia, and a trend toward higher rates of intracranial hemorrhage.

Bottom line: Introduction of CTPA was associated with changes suggestive of overdiagnosis (increased incidence, relatively unchanged mortality) and overtreatment (increased complication rates) of PE, but it remains unknown which small PEs are clinically significant.

Citation: Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837.

Hospitalist-Physician Assistant Teams Associated with Longer Length of Stay, No Change in Mortality, Readmission Rates

Clinical question: Do length of stay (LOS), hospital mortality, or readmission rate change if hospitalists and physician assistants, or the traditional resident-hospitalist teams, provide the patient care?

Background: Resident work-hour limitations require new models of care for hospitalized patients. Many academic medical centers have hired physician assistants to work with hospitalists to provide care. Little is known about how these models affect such outcomes as LOS, inpatient mortality rates, and readmission rates.

Study design: Retrospective cohort.

Setting: A 430-bed urban academic medical center in Milwaukee.

Synopsis: Administrative data were gathered on 9,681 patients admitted to the general medical service. Of those enrolled, 2,171 were cared for by a hospitalist-physician assistant (H-PA) team, while resident-hospitalist teams cared for 7,510 patients. Patient assignment was dependent on time of admission but not on patient complexity. Patients admitted overnight after the resident team capped were assigned to the H-PA team the next morning, resulting in increased transitions of care for the H-PA team.

Adjusted analyses revealed a 6.45% increase in LOS for the H-PA team compared with the resident team. Charges, inpatient mortality, and readmission rates at seven, 14, and 30 days were unchanged. Subgroup analyses revealed smaller differences in LOS for H-PA teams and resident-hospitalist teams with the same hospitalist (LOS 5.44% higher, P=0.081).

Conclusions from this study are limited due to lack of randomization of assignment, the retrospective design, and the use of administrative data at one institution.

Bottom line: Hospitalist-PA teams might result in a slightly increased LOS compared with the traditional resident teams; however, inpatient mortality and readmission rates are similar.

Citation: Singh S, Fletcher KE, Schapira MM, et al. A comparison of outcomes of general medical inpatient care provided by a hospitalist-physician assistant model vs a traditional resident-based model. J Hosp Med. 2011;6:122-130.

Washing White Coats Does Not Lower MRSA Bacterial Contamination

Clinical question: Are clean, short-sleeved uniforms less likely to carry MRSA than regularly laundered long-sleeved white coats?

Background: Studies have shown that bacteria frequently colonize in physician garments. However, evidence that short-sleeved garments or newly laundered garments are less likely to be contaminated has been lacking. Despite the paucity of evidence, the British Department of Health barred the use of traditional white coats and long-sleeved garments in 2007.

Study design: Prospective, randomized, controlled trial.

Setting: Urban U.S. hospital.

Synopsis: Study authors randomized 100 internal-medicine residents and hospitalists to their own long-sleeved white coats or freshly laundered short-sleeved uniforms from August 2008 to November 2009. Swabs were taken from the sleeves of the white coats or uniform, the breast pocket, and the volar wrist surface of the dominant hand. Swabs were cultured for MRSA and for general colony count.

Results showed no significant difference in colony counts or MRSA colonization in any of the sites tested between the newly laundered uniforms and the white coats. Additionally, there was no effect in relation to the frequency of laundering the white coats. Notably, within three hours of donning freshly laundered uniforms, bacterial counts approached 50% of the total bacterial counts seen at eight hours.

Bottom line: Laundering of uniforms does not affect MRSA colonization rate or general bacterial burden on physician uniforms or skin surfaces, though the effect on nosocomial infection has not been established.

Citation: Burden M, Cervantes L, Weed D, Keniston A, Price CS, Albert RK. Newly cleaned physician uniforms and infrequently washed white coats have similar rates of bacterial contamination after an 8-hour workday: a randomized controlled trial. J Hosp Med. 2011;6:177-182.

Self-Reported Pain Severity Does Not Correlate with Heart Rate or Blood Pressure Measurements in Pre-Hospital Setting

Clinical question: Do measured vital signs, including heart rate, blood pressure, and respiratory rate, correlate with the degree of self-reported pain?

Background: Because pain often can be associated with alterations in autonomic tone, it has been hypothesized that alterations in vital signs will occur in patients who report pain.

Study design: Retrospective cohort study.

Setting: Pre-hospital in Melbourne, Australia.

Synopsis: The authors reviewed all ambulance patient care records for patients age >14 years with a Glasgow Coma Score (GCS) >12 transported to a hospital during a seven-day period in 2005. Patients were selected for analysis if their patient care record included an initial assessment of pain severity, as measured by a numeric rating scale (NRS), in which patients rate their pain from 0 to 10.

More than half of the 3,357 patients transported by paramedics during the period were included in this analysis (n=1286). There was no correlation between heart rate or systolic blood pressure with the degree of self-reported pain. Although an increased respiratory rate was statistically correlated with a higher rating of pain, this relationship was not clinically significant, as each one-point increase in the pain rating scale was associated with a 0.16-breaths-per-minute increase in the respiratory rate.

Limitations included the large number of records excluded from analysis because pain was not evaluated, as well as numerous unmeasured confounders, including active disease processes such as sepsis, that were not accounted for.

Bottom line: Severity of pain did not correlate with heart rate or systolic blood pressure in the pre-hospital setting.

Citation: Lord B, Woollard M. The reliability of vital signs in estimating pain severity among adult patients treated by paramedics. Emerg Med J. 2011;28:147-150.

Asymptomatic Perioperative Myocardial Infarction Is Common in Patients Undergoing Noncardiac Surgery

Clinical question: In patients undergoing noncardiac surgery, what is the incidence and clinical characteristics of perioperative myocardial infarction (MI)?

Background: Though millions of patients experience perioperative MI after noncardiac surgery, little is known about the characteristics and outcomes of these patients.

Study design: Cohort study.

Setting: One hundred ninety centers in 23 countries.

Synopsis: Using data from the 8,351 patients in the POISE (PeriOperative ISchemic Evaluation) trial, this study showed that perioperative MI occurred in 5% of patients; 65% were asymptomatic. Patients who experienced postoperative MI were older and had more cardiovascular risk factors when compared to those who did not. The 30-day mortality was higher in patients with a perioperative MI (11.6%) compared with those who did not (2.2%); the presence or absence of ischemic symptoms was not associated with mortality rate.

Of the 8.3% of patients who experienced an elevation in cardiac biomarkers but who did not meet the definition of MI, there was an increased risk of nonfatal cardiac arrest and nonacute coronary revascularization. Those in the highest quartile also had increased 30-day mortality.

Bottom line: Given the high proportion of asymptomatic MIs and isolated elevations in cardiac biomarkers and the association between these events and increased risk of death, hospitalists should consider routine monitoring of troponin in at-risk patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154(8):523-528.

Patients Prescribed Higher Opioid Doses Are at Increased Risk of Opioid Overdose Death

Clinical question: What is the association between opioid prescribing patterns and fatal opioid overdose?

Background: In the past 10 years, the rate of fatal overdose from opioid prescription for pain has more than doubled. Little is known about how the indications (substance abuse disorders, cancer-related pain, chronic pain, acute pain), maximal daily dose, and scheduling (standing, as-needed, or both) of opioid prescriptions relate to this increased risk.

Study design: Case-cohort study.

Setting: Veterans Health Administration (VHA) patients.

Synopsis: The VHA’s National Patient Care Database was used to randomly select a cohort of 154,684 nonhospice/nonpalliative-care patients who were prescribed opioids from 2004 to 2008. They were compared with 750 patients who were treated with prescription opioids who died from opioid overdose during this time.

Fatal opioid overdose was a rare event (0.04%), but risk increased with higher prescribed maximum daily morphine dose-equivalence, especially when greater than or equal to 50 mg/day in all subgroups (substance abuse, acute and chronic pain, and cancer). Fatal overdoses were higher in middle-aged white men with acute or chronic pain, substance abuse disorders, and other psychiatric illness. Patients with cancer were at increased risk of fatal overdose if they were prescribed as-needed opioids alone.

Treatment with both as-needed and standing opioids did not statistically affect risk of overdose death in any subgroup.

Bottom line: Although rare, risk of fatal opioid overdose in patients prescribed opiate medication increases with higher maximum prescribed daily dose.

Citation: Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305:1315-1321.

Structured Interdisciplinary Rounds on Medical Teaching Unit Significantly Decrease Adverse Events

Clinical question: Do structured interdisciplinary rounds have an impact on the rate of adverse events?

Background: Many preventable adverse events occurring during hospitalization can be attributed to communication failures. Structured interdisciplinary rounds provide a format as well as a forum for team members to discuss patient care. Prior studies demonstrated improvements in collaboration; whether this translates to better patient care is not known.

Study design: Retrospective cohort using historic and concurrent control.

Setting: Tertiary-care teaching hospital in Chicago.

Synopsis: Structured interdisciplinary rounds, led by a nurse manager and medical director, and including nurses, residents, pharmacists, social workers, and case managers, were implemented on a medical teaching unit. New patients were discussed using a structured communication tool; existing patients were discussed in an unstructured format. Medical records were abstracted for 370 patients hospitalized after implementation of the intervention, equally divided between intervention and control units. One hundred eighty-five patients hospitalized on the intervention unit prior to the implementation of rounds served as a historic control.

Patients in the intervention unit had significantly lower rates of total adverse events (3.9 per 100 patient days in the intervention, compared with 7.2 and 7.7 per 100 patient days for the concurrent and historic control units, respectively), and preventable adverse events (0.9 per 100 patient days, compared with 2.8 and 2.1 per 100 patient days for the concurrent and historic controls, respectively).

Limitations of the study include lack of blinding of the medical record, slightly different patient populations in intervention and control groups, and the one-hospital setting, which could limit generalizability.

Bottom line: Structured interdisciplinary rounds might serve to improve communication between nurses, pharmacists, and physicians, resulting in decreases in adverse events.

Citation: O’Leary KJ, Buck R, Fligiel HM, et al. Structured interdisciplinary rounds in a medical teaching unit: improving patient safety. Arch Intern Med. 2011;171(7):678-684.

Pediatric HM Literature

Short-Course Antibiotic Therapy Effective for Bacterial Meningitis

Clinical question: Is five days of parenteral ceftriaxone as effective as 10 days for the treatment of bacterial meningitis in children?

Background: Morbidity and mortality in bacterial meningitis remain high, particularly in developing countries. Antibiotics are effective treatment, yet the optimal duration of treatment remains uncertain. Some data support a shorter duration of treatment (three to five days).

Study design: Multicountry, double-blind, placebo-controlled, randomized equivalence study.

Setting: Ten pediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam.

Synopsis: Children aged two months to 12 years with bacterial meningitis (due to Haemophilus influenza, Streptococcus pneumonia, Neisseria meningitidis, or culture-negative with indicative cerebrospinal fluid findings) and without complicating medical conditions were enrolled at participating centers. All children received 80 mg/kg to 100 mg/kg of parenteral ceftriaxone daily and a repeat lumbar puncture 48 to 72 hours after initiation of therapy.

Ultimately, 1,004 children without resistant organisms, persistently positive cultures, or suppurative complications were randomized on day five of therapy to placebo or continuance of ceftriaxone for five more days.

No bacteriologic failures (primary endpoint) were evident with either five or 10 days of treatment.

In addition, no statistically significant differences were found between the groups with respect to clinical treatment failure, hearing loss, neurological sequelae, or death. Secondary analysis by organism revealed similar results.

The primary limitation of this study is that it occurred in developing countries with a fair incidence of H. influenzae meningitis and a low rate of third-generation cephalosporin resistance.

However, pneumococcal and meningococcal disease remained prominent, and this study suggests that clinically stable patients might be treated with a shorter course of parenteral ceftriaxone therapy than currently is recommended.

Bottom line: Five days of ceftriaxone is as effective as 10 days for uncomplicated bacterial meningitis in children.

Citation: Molyneux E, Nizami SQ, Saha S, et al. 5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Lancet. 2011;377:1837-1845.

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

In This Edition

Literature At A Glance

A guide to this month’s studies

1. High-dose vs. low-dose clopidogrel after cardiac stenting
2. Rates of overdiagnosis of PE with CTPA
3. Outcomes of hospitalists with PAs or residents
4. White coats and MRSA
5. Correlation of vital signs and pain
6. Rate of asymptomatic perioperative MI
7. Relationship of opioid prescription patterns and overdose
8. Interdisciplinary rounds and rates of adverse events

High-Dose Clopidogrel Is Not Superior to Standard-Dose Clopidogrel in Patients with High On-Treatment Platelet Activity after Percutaneous Corona

Clinical question: In patients with high on-treatment platelet activity, does the use of high-dose clopidogrel after percutaneous coronary intervention (PCI) decrease the risk of cardiovascular events?

Background: In patients receiving clopidogrel, high platelet reactivity after PCI is associated with an increase in cardiovascular events. At present, treatments targeted at this population are not well-defined.

Study design: Randomized, double-blind, active-control trial.

Setting: Eighty-three centers in North America.

Synopsis: Researchers randomized 2,214 patients with drug-eluting stents to receive either high-dose clopidogrel (600 mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily). At six months, the primary endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis was no different in the two groups (2.3% in the high-dose group versus 2.3% in the standard-dose group; hazard ratio 1.01).

Bottom line: High-dose clopidogrel adds no benefit over standard-dose clopidogrel in patients with high platelet reactivity who have undergone PCI with drug-eluting stent placement.

Citation: Price MJ, Berger PB, Teirstein PS, et al. Standard- vs. high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305(11):1097-1105.

Computed Tomographic Pulmonary Angiography (CTPA) Is Associated with Overdiagnosis and Overtreatment of Pulmonary Embolism (PE)

Clinical question: Is the use of CTPA associated with increased incidence of PE and increased complications from anticoagulation treatment?

Background: CTPA is a sensitive, noninvasive test for diagnosing PE that could have a drawback: identifying potentially clinically unimportant (small) pulmonary emboli that subsequently are treated. Overtreatment might be associated with patient harm due to increased complications of anticoagulation therapy.

Study design: Time-trend analysis of PE between the pre-CTPA period (1993 to 1998) and the post-CTPA period (1998 to 2006).

Setting: Nongovernmental U.S. hospitals.

Synopsis: The Nationwide Inpatient Sample and Multiple Cause-of-Death databases were used to determine national estimates of hospitalization for PE, along with morbidity and mortality from PE.

The age-adjusted analysis revealed a statistically significant increase in the incidence of PE diagnosis after introduction of CTPA (to 112 per 100,000 from 62 per 100,000), with minimal change in overall PE mortality. This was accompanied by a substantial reduction in PE case-fatality rate, the rate of hospital deaths among patients with a diagnosis of pulmonary embolism.

Availability of CTPA was associated with a significant increase in anticoagulation complication rates (to 5.3 per 100,000 from 3.1 per 100,000), including statistically significant increases in gastrointestinal hemorrhage and secondary thrombocytopenia, and a trend toward higher rates of intracranial hemorrhage.

Bottom line: Introduction of CTPA was associated with changes suggestive of overdiagnosis (increased incidence, relatively unchanged mortality) and overtreatment (increased complication rates) of PE, but it remains unknown which small PEs are clinically significant.

Citation: Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831-837.

Hospitalist-Physician Assistant Teams Associated with Longer Length of Stay, No Change in Mortality, Readmission Rates

Clinical question: Do length of stay (LOS), hospital mortality, or readmission rate change if hospitalists and physician assistants, or the traditional resident-hospitalist teams, provide the patient care?

Background: Resident work-hour limitations require new models of care for hospitalized patients. Many academic medical centers have hired physician assistants to work with hospitalists to provide care. Little is known about how these models affect such outcomes as LOS, inpatient mortality rates, and readmission rates.

Study design: Retrospective cohort.

Setting: A 430-bed urban academic medical center in Milwaukee.

Synopsis: Administrative data were gathered on 9,681 patients admitted to the general medical service. Of those enrolled, 2,171 were cared for by a hospitalist-physician assistant (H-PA) team, while resident-hospitalist teams cared for 7,510 patients. Patient assignment was dependent on time of admission but not on patient complexity. Patients admitted overnight after the resident team capped were assigned to the H-PA team the next morning, resulting in increased transitions of care for the H-PA team.

Adjusted analyses revealed a 6.45% increase in LOS for the H-PA team compared with the resident team. Charges, inpatient mortality, and readmission rates at seven, 14, and 30 days were unchanged. Subgroup analyses revealed smaller differences in LOS for H-PA teams and resident-hospitalist teams with the same hospitalist (LOS 5.44% higher, P=0.081).

Conclusions from this study are limited due to lack of randomization of assignment, the retrospective design, and the use of administrative data at one institution.

Bottom line: Hospitalist-PA teams might result in a slightly increased LOS compared with the traditional resident teams; however, inpatient mortality and readmission rates are similar.

Citation: Singh S, Fletcher KE, Schapira MM, et al. A comparison of outcomes of general medical inpatient care provided by a hospitalist-physician assistant model vs a traditional resident-based model. J Hosp Med. 2011;6:122-130.

Washing White Coats Does Not Lower MRSA Bacterial Contamination

Clinical question: Are clean, short-sleeved uniforms less likely to carry MRSA than regularly laundered long-sleeved white coats?

Background: Studies have shown that bacteria frequently colonize in physician garments. However, evidence that short-sleeved garments or newly laundered garments are less likely to be contaminated has been lacking. Despite the paucity of evidence, the British Department of Health barred the use of traditional white coats and long-sleeved garments in 2007.

Study design: Prospective, randomized, controlled trial.

Setting: Urban U.S. hospital.

Synopsis: Study authors randomized 100 internal-medicine residents and hospitalists to their own long-sleeved white coats or freshly laundered short-sleeved uniforms from August 2008 to November 2009. Swabs were taken from the sleeves of the white coats or uniform, the breast pocket, and the volar wrist surface of the dominant hand. Swabs were cultured for MRSA and for general colony count.

Results showed no significant difference in colony counts or MRSA colonization in any of the sites tested between the newly laundered uniforms and the white coats. Additionally, there was no effect in relation to the frequency of laundering the white coats. Notably, within three hours of donning freshly laundered uniforms, bacterial counts approached 50% of the total bacterial counts seen at eight hours.

Bottom line: Laundering of uniforms does not affect MRSA colonization rate or general bacterial burden on physician uniforms or skin surfaces, though the effect on nosocomial infection has not been established.

Citation: Burden M, Cervantes L, Weed D, Keniston A, Price CS, Albert RK. Newly cleaned physician uniforms and infrequently washed white coats have similar rates of bacterial contamination after an 8-hour workday: a randomized controlled trial. J Hosp Med. 2011;6:177-182.

Self-Reported Pain Severity Does Not Correlate with Heart Rate or Blood Pressure Measurements in Pre-Hospital Setting

Clinical question: Do measured vital signs, including heart rate, blood pressure, and respiratory rate, correlate with the degree of self-reported pain?

Background: Because pain often can be associated with alterations in autonomic tone, it has been hypothesized that alterations in vital signs will occur in patients who report pain.

Study design: Retrospective cohort study.

Setting: Pre-hospital in Melbourne, Australia.

Synopsis: The authors reviewed all ambulance patient care records for patients age >14 years with a Glasgow Coma Score (GCS) >12 transported to a hospital during a seven-day period in 2005. Patients were selected for analysis if their patient care record included an initial assessment of pain severity, as measured by a numeric rating scale (NRS), in which patients rate their pain from 0 to 10.

More than half of the 3,357 patients transported by paramedics during the period were included in this analysis (n=1286). There was no correlation between heart rate or systolic blood pressure with the degree of self-reported pain. Although an increased respiratory rate was statistically correlated with a higher rating of pain, this relationship was not clinically significant, as each one-point increase in the pain rating scale was associated with a 0.16-breaths-per-minute increase in the respiratory rate.

Limitations included the large number of records excluded from analysis because pain was not evaluated, as well as numerous unmeasured confounders, including active disease processes such as sepsis, that were not accounted for.

Bottom line: Severity of pain did not correlate with heart rate or systolic blood pressure in the pre-hospital setting.

Citation: Lord B, Woollard M. The reliability of vital signs in estimating pain severity among adult patients treated by paramedics. Emerg Med J. 2011;28:147-150.

Asymptomatic Perioperative Myocardial Infarction Is Common in Patients Undergoing Noncardiac Surgery

Clinical question: In patients undergoing noncardiac surgery, what is the incidence and clinical characteristics of perioperative myocardial infarction (MI)?

Background: Though millions of patients experience perioperative MI after noncardiac surgery, little is known about the characteristics and outcomes of these patients.

Study design: Cohort study.

Setting: One hundred ninety centers in 23 countries.

Synopsis: Using data from the 8,351 patients in the POISE (PeriOperative ISchemic Evaluation) trial, this study showed that perioperative MI occurred in 5% of patients; 65% were asymptomatic. Patients who experienced postoperative MI were older and had more cardiovascular risk factors when compared to those who did not. The 30-day mortality was higher in patients with a perioperative MI (11.6%) compared with those who did not (2.2%); the presence or absence of ischemic symptoms was not associated with mortality rate.

Of the 8.3% of patients who experienced an elevation in cardiac biomarkers but who did not meet the definition of MI, there was an increased risk of nonfatal cardiac arrest and nonacute coronary revascularization. Those in the highest quartile also had increased 30-day mortality.

Bottom line: Given the high proportion of asymptomatic MIs and isolated elevations in cardiac biomarkers and the association between these events and increased risk of death, hospitalists should consider routine monitoring of troponin in at-risk patients undergoing noncardiac surgery.

Citation: Devereaux PJ, Xavier D, Pogue J, et al. Characteristics and short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med. 2011;154(8):523-528.

Patients Prescribed Higher Opioid Doses Are at Increased Risk of Opioid Overdose Death

Clinical question: What is the association between opioid prescribing patterns and fatal opioid overdose?

Background: In the past 10 years, the rate of fatal overdose from opioid prescription for pain has more than doubled. Little is known about how the indications (substance abuse disorders, cancer-related pain, chronic pain, acute pain), maximal daily dose, and scheduling (standing, as-needed, or both) of opioid prescriptions relate to this increased risk.

Study design: Case-cohort study.

Setting: Veterans Health Administration (VHA) patients.

Synopsis: The VHA’s National Patient Care Database was used to randomly select a cohort of 154,684 nonhospice/nonpalliative-care patients who were prescribed opioids from 2004 to 2008. They were compared with 750 patients who were treated with prescription opioids who died from opioid overdose during this time.

Fatal opioid overdose was a rare event (0.04%), but risk increased with higher prescribed maximum daily morphine dose-equivalence, especially when greater than or equal to 50 mg/day in all subgroups (substance abuse, acute and chronic pain, and cancer). Fatal overdoses were higher in middle-aged white men with acute or chronic pain, substance abuse disorders, and other psychiatric illness. Patients with cancer were at increased risk of fatal overdose if they were prescribed as-needed opioids alone.

Treatment with both as-needed and standing opioids did not statistically affect risk of overdose death in any subgroup.

Bottom line: Although rare, risk of fatal opioid overdose in patients prescribed opiate medication increases with higher maximum prescribed daily dose.

Citation: Bohnert AS, Valenstein M, Bair M, et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011; 305:1315-1321.

Structured Interdisciplinary Rounds on Medical Teaching Unit Significantly Decrease Adverse Events

Clinical question: Do structured interdisciplinary rounds have an impact on the rate of adverse events?

Background: Many preventable adverse events occurring during hospitalization can be attributed to communication failures. Structured interdisciplinary rounds provide a format as well as a forum for team members to discuss patient care. Prior studies demonstrated improvements in collaboration; whether this translates to better patient care is not known.

Study design: Retrospective cohort using historic and concurrent control.

Setting: Tertiary-care teaching hospital in Chicago.

Synopsis: Structured interdisciplinary rounds, led by a nurse manager and medical director, and including nurses, residents, pharmacists, social workers, and case managers, were implemented on a medical teaching unit. New patients were discussed using a structured communication tool; existing patients were discussed in an unstructured format. Medical records were abstracted for 370 patients hospitalized after implementation of the intervention, equally divided between intervention and control units. One hundred eighty-five patients hospitalized on the intervention unit prior to the implementation of rounds served as a historic control.

Patients in the intervention unit had significantly lower rates of total adverse events (3.9 per 100 patient days in the intervention, compared with 7.2 and 7.7 per 100 patient days for the concurrent and historic control units, respectively), and preventable adverse events (0.9 per 100 patient days, compared with 2.8 and 2.1 per 100 patient days for the concurrent and historic controls, respectively).

Limitations of the study include lack of blinding of the medical record, slightly different patient populations in intervention and control groups, and the one-hospital setting, which could limit generalizability.

Bottom line: Structured interdisciplinary rounds might serve to improve communication between nurses, pharmacists, and physicians, resulting in decreases in adverse events.

Citation: O’Leary KJ, Buck R, Fligiel HM, et al. Structured interdisciplinary rounds in a medical teaching unit: improving patient safety. Arch Intern Med. 2011;171(7):678-684.

Pediatric HM Literature

Short-Course Antibiotic Therapy Effective for Bacterial Meningitis

Clinical question: Is five days of parenteral ceftriaxone as effective as 10 days for the treatment of bacterial meningitis in children?

Background: Morbidity and mortality in bacterial meningitis remain high, particularly in developing countries. Antibiotics are effective treatment, yet the optimal duration of treatment remains uncertain. Some data support a shorter duration of treatment (three to five days).

Study design: Multicountry, double-blind, placebo-controlled, randomized equivalence study.

Setting: Ten pediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam.

Synopsis: Children aged two months to 12 years with bacterial meningitis (due to Haemophilus influenza, Streptococcus pneumonia, Neisseria meningitidis, or culture-negative with indicative cerebrospinal fluid findings) and without complicating medical conditions were enrolled at participating centers. All children received 80 mg/kg to 100 mg/kg of parenteral ceftriaxone daily and a repeat lumbar puncture 48 to 72 hours after initiation of therapy.

Ultimately, 1,004 children without resistant organisms, persistently positive cultures, or suppurative complications were randomized on day five of therapy to placebo or continuance of ceftriaxone for five more days.

No bacteriologic failures (primary endpoint) were evident with either five or 10 days of treatment.

In addition, no statistically significant differences were found between the groups with respect to clinical treatment failure, hearing loss, neurological sequelae, or death. Secondary analysis by organism revealed similar results.

The primary limitation of this study is that it occurred in developing countries with a fair incidence of H. influenzae meningitis and a low rate of third-generation cephalosporin resistance.

However, pneumococcal and meningococcal disease remained prominent, and this study suggests that clinically stable patients might be treated with a shorter course of parenteral ceftriaxone therapy than currently is recommended.

Bottom line: Five days of ceftriaxone is as effective as 10 days for uncomplicated bacterial meningitis in children.

Citation: Molyneux E, Nizami SQ, Saha S, et al. 5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study. Lancet. 2011;377:1837-1845.

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

Clinical question: Is dalteparin better than unfractionated heparin at preventing venous thromboembolism (VTE) in ICU patients?

Background: VTE is an important health problem for critically ill patients, but prevention is possible, with both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) superior to placebo in previous studies. Studies comparing UFH and LMWH in ICU patients have been inconclusive thus far.

Study design: Randomized controlled trial.

Setting: Sixty-seven ICUs in six countries from 2006 to 2010.

Synopsis: Researchers randomized 3,746 patients who met the enrollment criteria to either the LMWH dalteparin 5,000 units daily or UFH 5,000 IU twice daily. The drug was held if major bleeding occurred or the patient developed thrombocytopenia concerning heparin-induced thrombocytopenia (HIT). Patients were followed until discharge or death. VTE was evaluated by ultrasound two days after ICU admission and then twice weekly.

There was no difference in incidence of VTE in patients receiving dalteparin versus UFH [5.1% vs. 5.8%, HR 0.92 (CI 0.68-1.23), P=0.57]. Fewer pulmonary emboli occurred in the dalteparin group (1.3% vs. 2.3%, HR 0.51, P=0.01). There was no difference in major bleeding or HIT between groups.

Bottom line: Dalteparin and UFH were equally effective at preventing proximal VTE in ICU patients, but dalteparin prevented more pulmonary emboli.

Citation: The PROTECT investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2010;364(14):1305-1314.

For more physician reviews of HM-related research, visit our website.

Clinical question: Is dalteparin better than unfractionated heparin at preventing venous thromboembolism (VTE) in ICU patients?

Background: VTE is an important health problem for critically ill patients, but prevention is possible, with both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) superior to placebo in previous studies. Studies comparing UFH and LMWH in ICU patients have been inconclusive thus far.

Study design: Randomized controlled trial.

Setting: Sixty-seven ICUs in six countries from 2006 to 2010.

Synopsis: Researchers randomized 3,746 patients who met the enrollment criteria to either the LMWH dalteparin 5,000 units daily or UFH 5,000 IU twice daily. The drug was held if major bleeding occurred or the patient developed thrombocytopenia concerning heparin-induced thrombocytopenia (HIT). Patients were followed until discharge or death. VTE was evaluated by ultrasound two days after ICU admission and then twice weekly.

There was no difference in incidence of VTE in patients receiving dalteparin versus UFH [5.1% vs. 5.8%, HR 0.92 (CI 0.68-1.23), P=0.57]. Fewer pulmonary emboli occurred in the dalteparin group (1.3% vs. 2.3%, HR 0.51, P=0.01). There was no difference in major bleeding or HIT between groups.

Bottom line: Dalteparin and UFH were equally effective at preventing proximal VTE in ICU patients, but dalteparin prevented more pulmonary emboli.

Citation: The PROTECT investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2010;364(14):1305-1314.

For more physician reviews of HM-related research, visit our website.

Clinical question: Is dalteparin better than unfractionated heparin at preventing venous thromboembolism (VTE) in ICU patients?

Background: VTE is an important health problem for critically ill patients, but prevention is possible, with both unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) superior to placebo in previous studies. Studies comparing UFH and LMWH in ICU patients have been inconclusive thus far.

Study design: Randomized controlled trial.

Setting: Sixty-seven ICUs in six countries from 2006 to 2010.

Synopsis: Researchers randomized 3,746 patients who met the enrollment criteria to either the LMWH dalteparin 5,000 units daily or UFH 5,000 IU twice daily. The drug was held if major bleeding occurred or the patient developed thrombocytopenia concerning heparin-induced thrombocytopenia (HIT). Patients were followed until discharge or death. VTE was evaluated by ultrasound two days after ICU admission and then twice weekly.

There was no difference in incidence of VTE in patients receiving dalteparin versus UFH [5.1% vs. 5.8%, HR 0.92 (CI 0.68-1.23), P=0.57]. Fewer pulmonary emboli occurred in the dalteparin group (1.3% vs. 2.3%, HR 0.51, P=0.01). There was no difference in major bleeding or HIT between groups.

Bottom line: Dalteparin and UFH were equally effective at preventing proximal VTE in ICU patients, but dalteparin prevented more pulmonary emboli.

Citation: The PROTECT investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2010;364(14):1305-1314.

For more physician reviews of HM-related research, visit our website.