D’anna Saul, MD

Clinical question: Does the risk of pneumonia vary for different inhaled agents?

Background: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in COPD patients; duration, dosage, and various agents, especially fluticasone and budesonide, were investigated.

Study design: Nested, case-control analysis.

Setting: Quebec health insurance database for new users with COPD, 1990–2005, with follow-up through 2007.

Synopsis: Investigators analyzed 163,514 patients, including 20,344 patients with serious pneumonia; current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63-1.75). The increased risk was sustained with long-term use but declined gradually to zero at six months after stopping ICS. The risk of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93-2.10) than budesonide (RR 1.17; 95% CI 1.09-1.26).

Bottom line: Fluticasone was associated with an increased risk of pneumonia in COPD patients, consistent with earlier clinical trials, but the risk with budesonide was much lower.

Citation: Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68(11):1029-1036.

Clinical question: Does the risk of pneumonia vary for different inhaled agents?

Background: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in COPD patients; duration, dosage, and various agents, especially fluticasone and budesonide, were investigated.

Study design: Nested, case-control analysis.

Setting: Quebec health insurance database for new users with COPD, 1990–2005, with follow-up through 2007.

Synopsis: Investigators analyzed 163,514 patients, including 20,344 patients with serious pneumonia; current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63-1.75). The increased risk was sustained with long-term use but declined gradually to zero at six months after stopping ICS. The risk of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93-2.10) than budesonide (RR 1.17; 95% CI 1.09-1.26).

Bottom line: Fluticasone was associated with an increased risk of pneumonia in COPD patients, consistent with earlier clinical trials, but the risk with budesonide was much lower.

Citation: Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68(11):1029-1036.

Clinical question: Does the risk of pneumonia vary for different inhaled agents?

Background: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in COPD patients; duration, dosage, and various agents, especially fluticasone and budesonide, were investigated.

Study design: Nested, case-control analysis.

Setting: Quebec health insurance database for new users with COPD, 1990–2005, with follow-up through 2007.

Synopsis: Investigators analyzed 163,514 patients, including 20,344 patients with serious pneumonia; current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63-1.75). The increased risk was sustained with long-term use but declined gradually to zero at six months after stopping ICS. The risk of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93-2.10) than budesonide (RR 1.17; 95% CI 1.09-1.26).

Bottom line: Fluticasone was associated with an increased risk of pneumonia in COPD patients, consistent with earlier clinical trials, but the risk with budesonide was much lower.

Citation: Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68(11):1029-1036.

Clinical question: Does the risk of pneumonia vary for different inhaled agents?

Background: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in COPD patients; duration, dosage, and various agents were investigated, especially fluticasone and budesonide.

Study design: Nested, case-control analysis.

Setting: Quebec health insurance database for new users with COPD, 1990-2005, with follow-up through 2007.

Synopsis: Investigators analyzed 163,514 patients, including 20,344 patients with serious pneumonia; current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63-1.75). The increased risk was sustained with long-term use but declined gradually to zero at six months after stopping ICS. The risk of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93-2.10) than budesonide (RR 1.17; 95% CI 1.09-1.26).

Bottom line: Fluticasone was associated with an increased risk of pneumonia in COPD patients, consistent with earlier clinical trials, but the risk with budesonide was much lower.

Citation: Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68(11):1029-1036.

Clinical question: Does the risk of pneumonia vary for different inhaled agents?

Background: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in COPD patients; duration, dosage, and various agents were investigated, especially fluticasone and budesonide.

Study design: Nested, case-control analysis.

Setting: Quebec health insurance database for new users with COPD, 1990-2005, with follow-up through 2007.

Synopsis: Investigators analyzed 163,514 patients, including 20,344 patients with serious pneumonia; current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63-1.75). The increased risk was sustained with long-term use but declined gradually to zero at six months after stopping ICS. The risk of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93-2.10) than budesonide (RR 1.17; 95% CI 1.09-1.26).

Bottom line: Fluticasone was associated with an increased risk of pneumonia in COPD patients, consistent with earlier clinical trials, but the risk with budesonide was much lower.

Citation: Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68(11):1029-1036.

Clinical question: Does the risk of pneumonia vary for different inhaled agents?

Background: Inhaled corticosteroids (ICS) are known to increase the risk of pneumonia in COPD patients; duration, dosage, and various agents were investigated, especially fluticasone and budesonide.

Study design: Nested, case-control analysis.

Setting: Quebec health insurance database for new users with COPD, 1990-2005, with follow-up through 2007.

Synopsis: Investigators analyzed 163,514 patients, including 20,344 patients with serious pneumonia; current use of ICS was associated with a 69% increase in the rate of serious pneumonia (RR 1.69; 95% CI 1.63-1.75). The increased risk was sustained with long-term use but declined gradually to zero at six months after stopping ICS. The risk of serious pneumonia was higher with fluticasone (RR 2.01; 95% CI 1.93-2.10) than budesonide (RR 1.17; 95% CI 1.09-1.26).

Bottom line: Fluticasone was associated with an increased risk of pneumonia in COPD patients, consistent with earlier clinical trials, but the risk with budesonide was much lower.

Citation: Suissa S, Patenaude V, Lapi F, Ernst P. Inhaled corticosteroids in COPD and the risk of serious pneumonia. Thorax. 2013;68(11):1029-1036.

Clinical question: Which criteria identify ambulatory patients with exacerbations of mild to moderate COPD who do not need antibiotics?

Background: The Anthonisen criteria (increased dyspnea, sputum volume, sputum purulence) are commonly used to identify which patients with COPD exacerbations would benefit from antibiotics. These criteria, however, were derived in patients with severe COPD. It is unknown whether these criteria are predictive in patients with mild to moderate COPD.

Study design: Multivariate logistic regression analysis of placebo group of a double-blinded RCT.

Setting: Multicenter, ambulatory, primary care clinics in Spain.

Synopsis: The original RCT enrolled 310 ambulatory patients with exacerbations of mild to moderate COPD and tested the efficacy of amoxicillin/clavulanate. Clinical failure without antibiotics was 19.9% compared to 9.5% with antibiotics (P=0.022). Here they analyzed the 152 patients from the placebo group to identify factors associated with increased risk of clinical failure. Only increased sputum purulence (OR 6.1, CI 1.5-25; P=0.005) or C-reactive protein (CRP) >40 mg/L (OR 13.4, CI 4.5-38.8, P<0.001) were independently associated with increased risk of failure. Presence of both predicted a 63.7% failure without antibiotics.

The study did not define “increased sputum purulence,” but this is similar to real-life clinical practice. Placebo effect cannot be ruled out, but correlation of the objective measures with the clinical assessments suggests that the clinical assessments were accurate. The study did not have a protocol for administering co-medications such as steroids and inhalers. Despite these limitations, the criteria of increased sputum purulence and CRP >40 mg/L identified COPD patients likely to have a clinical failure without antibiotics.

Bottom line: Patients with exacerbations of mild to moderate COPD who do not have increased sputum purulence or CRP >40 mg/L can be safely managed without antibiotics.

Citation: Maravitlles M, Moravas A, Hernandez S, Bayona C, Llor C. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest. 2013;144(5):1571-1577.

Clinical question: Which criteria identify ambulatory patients with exacerbations of mild to moderate COPD who do not need antibiotics?

Background: The Anthonisen criteria (increased dyspnea, sputum volume, sputum purulence) are commonly used to identify which patients with COPD exacerbations would benefit from antibiotics. These criteria, however, were derived in patients with severe COPD. It is unknown whether these criteria are predictive in patients with mild to moderate COPD.

Study design: Multivariate logistic regression analysis of placebo group of a double-blinded RCT.

Setting: Multicenter, ambulatory, primary care clinics in Spain.

Synopsis: The original RCT enrolled 310 ambulatory patients with exacerbations of mild to moderate COPD and tested the efficacy of amoxicillin/clavulanate. Clinical failure without antibiotics was 19.9% compared to 9.5% with antibiotics (P=0.022). Here they analyzed the 152 patients from the placebo group to identify factors associated with increased risk of clinical failure. Only increased sputum purulence (OR 6.1, CI 1.5-25; P=0.005) or C-reactive protein (CRP) >40 mg/L (OR 13.4, CI 4.5-38.8, P<0.001) were independently associated with increased risk of failure. Presence of both predicted a 63.7% failure without antibiotics.

The study did not define “increased sputum purulence,” but this is similar to real-life clinical practice. Placebo effect cannot be ruled out, but correlation of the objective measures with the clinical assessments suggests that the clinical assessments were accurate. The study did not have a protocol for administering co-medications such as steroids and inhalers. Despite these limitations, the criteria of increased sputum purulence and CRP >40 mg/L identified COPD patients likely to have a clinical failure without antibiotics.

Bottom line: Patients with exacerbations of mild to moderate COPD who do not have increased sputum purulence or CRP >40 mg/L can be safely managed without antibiotics.

Citation: Maravitlles M, Moravas A, Hernandez S, Bayona C, Llor C. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest. 2013;144(5):1571-1577.

Clinical question: Which criteria identify ambulatory patients with exacerbations of mild to moderate COPD who do not need antibiotics?

Background: The Anthonisen criteria (increased dyspnea, sputum volume, sputum purulence) are commonly used to identify which patients with COPD exacerbations would benefit from antibiotics. These criteria, however, were derived in patients with severe COPD. It is unknown whether these criteria are predictive in patients with mild to moderate COPD.

Study design: Multivariate logistic regression analysis of placebo group of a double-blinded RCT.

Setting: Multicenter, ambulatory, primary care clinics in Spain.

Synopsis: The original RCT enrolled 310 ambulatory patients with exacerbations of mild to moderate COPD and tested the efficacy of amoxicillin/clavulanate. Clinical failure without antibiotics was 19.9% compared to 9.5% with antibiotics (P=0.022). Here they analyzed the 152 patients from the placebo group to identify factors associated with increased risk of clinical failure. Only increased sputum purulence (OR 6.1, CI 1.5-25; P=0.005) or C-reactive protein (CRP) >40 mg/L (OR 13.4, CI 4.5-38.8, P<0.001) were independently associated with increased risk of failure. Presence of both predicted a 63.7% failure without antibiotics.

The study did not define “increased sputum purulence,” but this is similar to real-life clinical practice. Placebo effect cannot be ruled out, but correlation of the objective measures with the clinical assessments suggests that the clinical assessments were accurate. The study did not have a protocol for administering co-medications such as steroids and inhalers. Despite these limitations, the criteria of increased sputum purulence and CRP >40 mg/L identified COPD patients likely to have a clinical failure without antibiotics.

Bottom line: Patients with exacerbations of mild to moderate COPD who do not have increased sputum purulence or CRP >40 mg/L can be safely managed without antibiotics.

Citation: Maravitlles M, Moravas A, Hernandez S, Bayona C, Llor C. Is it possible to identify exacerbations of mild to moderate COPD that do not require antibiotic treatment? Chest. 2013;144(5):1571-1577.

Clinical question: Do patients receiving pre-operative angiotensin axis blockade (AAB) prior to elective major orthopedic surgery have an increased risk of peri-operative hypotension and acute kidney injury (AKI)?

Background: Patients with pre-operative AAB from angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have an increased incidence of peri-operative hypotension. Patients undergoing cardiothoracic and vascular surgery with pre-operative AAB have increased incidence of post-operative AKI; however, there is scant literature evaluating the hypotensive and renal effects of pre-operative AAB prior to elective major orthopedic surgery.

Study design: Retrospective, cohort study.

Setting: Academic medical center.

Synopsis: Retrospective review of 922 patients undergoing spinal fusion, total knee arthroplasty, or total hip arthroplasty in one academic medical center in 2010 found that 37% received pre-operative AAB. Post-induction hypotension (systolic blood pressure ≤80 mm Hg for five minutes) was significantly higher in patients receiving AAB (12.2% vs. 6.7%; odds ratio [OR] 1.93, P=0.005). Post-operative AKI was significantly higher in patients receiving AAB (8.3% vs. 1.7%; OR 5.40, P<0.001), remaining significant after adjusting for intra-operative hypotension (OR 2.60, P=0.042). Developing AKI resulted in a significantly higher mean length of stay (5.76 vs. 3.28 days, P<0.001) but no difference in two-year mortality.

The findings suggest an association exists between pre-operative angiotensin-converting enzyme inhibitors/ARB, hypotension, and AKI following major orthopedic surgeries but does not demonstrate causality. A prospective, multi-center, randomized trial is needed to confirm that holding pre-operative AAB would decrease the incidence of AKI in patients undergoing major orthopedic procedures under general anesthesia.

Bottom line: Patients who underwent elective major orthopedic surgery who received pre-operative AAB therapy had an associated increased risk of post-induction hypotension and post-operative AKI, resulting in a greater hospital length of stay.

Citation: Nielson E, Hennrikus E, Lehman E, Mets B. Angiotensin axis blockade, hypotension, and acute kidney injury in elective major orthopedic surgery. J Hosp Med. 2014;9(5):283-288.

Clinical question: Do patients receiving pre-operative angiotensin axis blockade (AAB) prior to elective major orthopedic surgery have an increased risk of peri-operative hypotension and acute kidney injury (AKI)?

Background: Patients with pre-operative AAB from angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have an increased incidence of peri-operative hypotension. Patients undergoing cardiothoracic and vascular surgery with pre-operative AAB have increased incidence of post-operative AKI; however, there is scant literature evaluating the hypotensive and renal effects of pre-operative AAB prior to elective major orthopedic surgery.

Study design: Retrospective, cohort study.

Setting: Academic medical center.

Synopsis: Retrospective review of 922 patients undergoing spinal fusion, total knee arthroplasty, or total hip arthroplasty in one academic medical center in 2010 found that 37% received pre-operative AAB. Post-induction hypotension (systolic blood pressure ≤80 mm Hg for five minutes) was significantly higher in patients receiving AAB (12.2% vs. 6.7%; odds ratio [OR] 1.93, P=0.005). Post-operative AKI was significantly higher in patients receiving AAB (8.3% vs. 1.7%; OR 5.40, P<0.001), remaining significant after adjusting for intra-operative hypotension (OR 2.60, P=0.042). Developing AKI resulted in a significantly higher mean length of stay (5.76 vs. 3.28 days, P<0.001) but no difference in two-year mortality.

The findings suggest an association exists between pre-operative angiotensin-converting enzyme inhibitors/ARB, hypotension, and AKI following major orthopedic surgeries but does not demonstrate causality. A prospective, multi-center, randomized trial is needed to confirm that holding pre-operative AAB would decrease the incidence of AKI in patients undergoing major orthopedic procedures under general anesthesia.

Bottom line: Patients who underwent elective major orthopedic surgery who received pre-operative AAB therapy had an associated increased risk of post-induction hypotension and post-operative AKI, resulting in a greater hospital length of stay.

Citation: Nielson E, Hennrikus E, Lehman E, Mets B. Angiotensin axis blockade, hypotension, and acute kidney injury in elective major orthopedic surgery. J Hosp Med. 2014;9(5):283-288.

Clinical question: Do patients receiving pre-operative angiotensin axis blockade (AAB) prior to elective major orthopedic surgery have an increased risk of peri-operative hypotension and acute kidney injury (AKI)?

Background: Patients with pre-operative AAB from angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have an increased incidence of peri-operative hypotension. Patients undergoing cardiothoracic and vascular surgery with pre-operative AAB have increased incidence of post-operative AKI; however, there is scant literature evaluating the hypotensive and renal effects of pre-operative AAB prior to elective major orthopedic surgery.

Study design: Retrospective, cohort study.

Setting: Academic medical center.

Synopsis: Retrospective review of 922 patients undergoing spinal fusion, total knee arthroplasty, or total hip arthroplasty in one academic medical center in 2010 found that 37% received pre-operative AAB. Post-induction hypotension (systolic blood pressure ≤80 mm Hg for five minutes) was significantly higher in patients receiving AAB (12.2% vs. 6.7%; odds ratio [OR] 1.93, P=0.005). Post-operative AKI was significantly higher in patients receiving AAB (8.3% vs. 1.7%; OR 5.40, P<0.001), remaining significant after adjusting for intra-operative hypotension (OR 2.60, P=0.042). Developing AKI resulted in a significantly higher mean length of stay (5.76 vs. 3.28 days, P<0.001) but no difference in two-year mortality.

The findings suggest an association exists between pre-operative angiotensin-converting enzyme inhibitors/ARB, hypotension, and AKI following major orthopedic surgeries but does not demonstrate causality. A prospective, multi-center, randomized trial is needed to confirm that holding pre-operative AAB would decrease the incidence of AKI in patients undergoing major orthopedic procedures under general anesthesia.

Bottom line: Patients who underwent elective major orthopedic surgery who received pre-operative AAB therapy had an associated increased risk of post-induction hypotension and post-operative AKI, resulting in a greater hospital length of stay.

Citation: Nielson E, Hennrikus E, Lehman E, Mets B. Angiotensin axis blockade, hypotension, and acute kidney injury in elective major orthopedic surgery. J Hosp Med. 2014;9(5):283-288.

Clinical question: What is the recommended threshold for red blood cell (RBC) transfusion and erythropoiesis-stimulating agents (ESA) in anemic hospitalized patients with coronary heart disease?

Background: Anemia can worsen cardiac function and is associated with increased risk of hospitalization and death in patients with coronary heart disease (CHD) or congestive heart failure (CHF). It is unclear if treatments such as RBC transfusion, ESA, or iron replacement improve outcomes in patients with heart disease.

Study design: Systematic review.

Setting: Studies of hospitalized medical and surgical patients.

Synopsis: The guideline was developed by reviewing studies evaluating anemia treatment outcomes, including mortality, hospitalization, exercise tolerance, quality of life, and cardiovascular events. Six studies evaluated the benefits and harms resulting from RBC transfusion, each determined to be low-quality evidence. The current evidence showed no benefit when comparing liberal (hemoglobin (Hgb) >10 g/dL) versus restrictive (Hgb <10 g/dL) transfusion thresholds. Potential harms of transfusion included fever, transfusion-related acute lung injury, and CHF.

Given the low-quality evidence, the American College of Physicians (ACP) makes a weak recommendation for a restrictive transfusion strategy of Hgb 7-8 g/dL in patients with CHD.

A review of 16 RCTs (moderate-quality evidence) evaluated the effects of ESAs in mild to moderate anemia and showed no difference in outcomes for patients with CHD and CHF. Harms associated with ESA therapy included hypertension and venous thrombosis. The ACP makes a strong recommendation not to use ESAs in patients with heart disease.

Bottom line: The ACP recommends restrictive transfusion with hemoglobin threshold of 7-8 g/dL in hospitalized patients with CHD (weak recommendation, low-quality evidence) and recommends against using erythropoiesis-stimulating agents for mild to moderate anemia in patients with CHF or CHD (strong recommendation, moderate-quality evidence).

Citation: Qaseem A, Humphrey LL, Fitterman N, Starkey M, Shekelle P. Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013;159(11):770-779.

Clinical question: What is the recommended threshold for red blood cell (RBC) transfusion and erythropoiesis-stimulating agents (ESA) in anemic hospitalized patients with coronary heart disease?

Background: Anemia can worsen cardiac function and is associated with increased risk of hospitalization and death in patients with coronary heart disease (CHD) or congestive heart failure (CHF). It is unclear if treatments such as RBC transfusion, ESA, or iron replacement improve outcomes in patients with heart disease.

Study design: Systematic review.

Setting: Studies of hospitalized medical and surgical patients.

Synopsis: The guideline was developed by reviewing studies evaluating anemia treatment outcomes, including mortality, hospitalization, exercise tolerance, quality of life, and cardiovascular events. Six studies evaluated the benefits and harms resulting from RBC transfusion, each determined to be low-quality evidence. The current evidence showed no benefit when comparing liberal (hemoglobin (Hgb) >10 g/dL) versus restrictive (Hgb <10 g/dL) transfusion thresholds. Potential harms of transfusion included fever, transfusion-related acute lung injury, and CHF.

Given the low-quality evidence, the American College of Physicians (ACP) makes a weak recommendation for a restrictive transfusion strategy of Hgb 7-8 g/dL in patients with CHD.

A review of 16 RCTs (moderate-quality evidence) evaluated the effects of ESAs in mild to moderate anemia and showed no difference in outcomes for patients with CHD and CHF. Harms associated with ESA therapy included hypertension and venous thrombosis. The ACP makes a strong recommendation not to use ESAs in patients with heart disease.

Bottom line: The ACP recommends restrictive transfusion with hemoglobin threshold of 7-8 g/dL in hospitalized patients with CHD (weak recommendation, low-quality evidence) and recommends against using erythropoiesis-stimulating agents for mild to moderate anemia in patients with CHF or CHD (strong recommendation, moderate-quality evidence).

Citation: Qaseem A, Humphrey LL, Fitterman N, Starkey M, Shekelle P. Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013;159(11):770-779.

Clinical question: What is the recommended threshold for red blood cell (RBC) transfusion and erythropoiesis-stimulating agents (ESA) in anemic hospitalized patients with coronary heart disease?

Background: Anemia can worsen cardiac function and is associated with increased risk of hospitalization and death in patients with coronary heart disease (CHD) or congestive heart failure (CHF). It is unclear if treatments such as RBC transfusion, ESA, or iron replacement improve outcomes in patients with heart disease.

Study design: Systematic review.

Setting: Studies of hospitalized medical and surgical patients.

Synopsis: The guideline was developed by reviewing studies evaluating anemia treatment outcomes, including mortality, hospitalization, exercise tolerance, quality of life, and cardiovascular events. Six studies evaluated the benefits and harms resulting from RBC transfusion, each determined to be low-quality evidence. The current evidence showed no benefit when comparing liberal (hemoglobin (Hgb) >10 g/dL) versus restrictive (Hgb <10 g/dL) transfusion thresholds. Potential harms of transfusion included fever, transfusion-related acute lung injury, and CHF.

Given the low-quality evidence, the American College of Physicians (ACP) makes a weak recommendation for a restrictive transfusion strategy of Hgb 7-8 g/dL in patients with CHD.

A review of 16 RCTs (moderate-quality evidence) evaluated the effects of ESAs in mild to moderate anemia and showed no difference in outcomes for patients with CHD and CHF. Harms associated with ESA therapy included hypertension and venous thrombosis. The ACP makes a strong recommendation not to use ESAs in patients with heart disease.

Bottom line: The ACP recommends restrictive transfusion with hemoglobin threshold of 7-8 g/dL in hospitalized patients with CHD (weak recommendation, low-quality evidence) and recommends against using erythropoiesis-stimulating agents for mild to moderate anemia in patients with CHF or CHD (strong recommendation, moderate-quality evidence).

Citation: Qaseem A, Humphrey LL, Fitterman N, Starkey M, Shekelle P. Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013;159(11):770-779.

Clinical question: Can right ventricular (RV) dysfunction and troponin levels be used to risk stratify hemodynamically stable patients with acute pulmonary embolism (PE)?

Background: PE can present with varying degrees of clinical severity, necessitating appropriate risk stratification for decision making and management. Observational studies have demonstrated that RV dysfunction and injury provide important prognostic information in patients with acute PE, but this has not been confirmed in large prospective studies.

Study design: Prospective, cohort study.

Setting: Multicenter registry of academic and community hospitals in Italy.

Synopsis: Using the Italian Pulmonary Embolism Registry database of 860 hemodynamically stable patients with PE who underwent troponin measurement and echocardiogram, this study demonstrated that a model including RV dysfunction and injury has an incremental prognostic value for risk stratification of in-hospital death or clinical deterioration. The negative predictive value of negative echocardiography with negative troponin was 100% for in-hospital death and 99% for in-hospital clinical deterioration.

This study was limited by its observational approach; in addition, it did not provide its metrics for defining hemodynamic stability and did not standardize or report treatment strategies for these patients.

The predictive value of this study is impressive and could lead to the identification of patients in whom early discharge or brief hospitalization is appropriate; however, its application could be challenging in clinical environments where timely echocardiography resources are not readily available to a hemodynamically stable patient population.

Bottom line: Negative troponin and absence of RV dysfunction predict clinically stable pulmonary embolism.

Citation: Becattini C, Casazza F, Forgione C, et al. Acute pulmonary embolism: external validation of an integrated risk stratification model. Chest. 2013;144(5):1539-1545.

Clinical question: Can right ventricular (RV) dysfunction and troponin levels be used to risk stratify hemodynamically stable patients with acute pulmonary embolism (PE)?

Background: PE can present with varying degrees of clinical severity, necessitating appropriate risk stratification for decision making and management. Observational studies have demonstrated that RV dysfunction and injury provide important prognostic information in patients with acute PE, but this has not been confirmed in large prospective studies.

Study design: Prospective, cohort study.

Setting: Multicenter registry of academic and community hospitals in Italy.

Synopsis: Using the Italian Pulmonary Embolism Registry database of 860 hemodynamically stable patients with PE who underwent troponin measurement and echocardiogram, this study demonstrated that a model including RV dysfunction and injury has an incremental prognostic value for risk stratification of in-hospital death or clinical deterioration. The negative predictive value of negative echocardiography with negative troponin was 100% for in-hospital death and 99% for in-hospital clinical deterioration.

This study was limited by its observational approach; in addition, it did not provide its metrics for defining hemodynamic stability and did not standardize or report treatment strategies for these patients.

The predictive value of this study is impressive and could lead to the identification of patients in whom early discharge or brief hospitalization is appropriate; however, its application could be challenging in clinical environments where timely echocardiography resources are not readily available to a hemodynamically stable patient population.

Bottom line: Negative troponin and absence of RV dysfunction predict clinically stable pulmonary embolism.

Citation: Becattini C, Casazza F, Forgione C, et al. Acute pulmonary embolism: external validation of an integrated risk stratification model. Chest. 2013;144(5):1539-1545.

Clinical question: Can right ventricular (RV) dysfunction and troponin levels be used to risk stratify hemodynamically stable patients with acute pulmonary embolism (PE)?

Background: PE can present with varying degrees of clinical severity, necessitating appropriate risk stratification for decision making and management. Observational studies have demonstrated that RV dysfunction and injury provide important prognostic information in patients with acute PE, but this has not been confirmed in large prospective studies.

Study design: Prospective, cohort study.

Setting: Multicenter registry of academic and community hospitals in Italy.

Synopsis: Using the Italian Pulmonary Embolism Registry database of 860 hemodynamically stable patients with PE who underwent troponin measurement and echocardiogram, this study demonstrated that a model including RV dysfunction and injury has an incremental prognostic value for risk stratification of in-hospital death or clinical deterioration. The negative predictive value of negative echocardiography with negative troponin was 100% for in-hospital death and 99% for in-hospital clinical deterioration.

This study was limited by its observational approach; in addition, it did not provide its metrics for defining hemodynamic stability and did not standardize or report treatment strategies for these patients.

The predictive value of this study is impressive and could lead to the identification of patients in whom early discharge or brief hospitalization is appropriate; however, its application could be challenging in clinical environments where timely echocardiography resources are not readily available to a hemodynamically stable patient population.

Bottom line: Negative troponin and absence of RV dysfunction predict clinically stable pulmonary embolism.

Citation: Becattini C, Casazza F, Forgione C, et al. Acute pulmonary embolism: external validation of an integrated risk stratification model. Chest. 2013;144(5):1539-1545.

Clinical question: In patients with possible cardiac chest pain, does an accelerated diagnostic protocol result in higher rates of successful early discharge when compared with the standard care pathway?

Background: An accelerated diagnostic pathway (ADP), which combines TIMI [thrombolysis in myocardial infarction] score, EKG, and zero- and two-hour troponin levels, can identify low-risk patients presenting with chest pain; however, little is known about its effect on the rates of early, successful discharge in a real-world population.

Study design: RCT.

Setting: An academic general and tertiary care hospital in Christchurch, New Zealand.

Synopsis: This study of 542 patients ages 18 years and older who presented with chest pain demonstrated that when compared with a conventional pathway, an ADP results in nearly twice the proportion of patients (19.3% vs. 11.0%; P=0.008) achieving safe, early discharge from the ED, defined as discharge within six hours and no major adverse cardiac events within 30 days. This was a single-center trial in New Zealand, which limits its sample size and its generalizability; however, if larger studies led to the implementation of ADP by ED physicians, there would likely be fewer low-risk patients admitted to hospitalist services for evaluation of chest pain.

Bottom line: An accelerated diagnostic chest pain protocol results in earlier discharge of low-risk patients.

Citation: Than M, Aldous S, Lord SJ, et al. A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Intern Med. 2014;174(1):51-58.

Clinical question: In patients with possible cardiac chest pain, does an accelerated diagnostic protocol result in higher rates of successful early discharge when compared with the standard care pathway?

Background: An accelerated diagnostic pathway (ADP), which combines TIMI [thrombolysis in myocardial infarction] score, EKG, and zero- and two-hour troponin levels, can identify low-risk patients presenting with chest pain; however, little is known about its effect on the rates of early, successful discharge in a real-world population.

Study design: RCT.

Setting: An academic general and tertiary care hospital in Christchurch, New Zealand.

Synopsis: This study of 542 patients ages 18 years and older who presented with chest pain demonstrated that when compared with a conventional pathway, an ADP results in nearly twice the proportion of patients (19.3% vs. 11.0%; P=0.008) achieving safe, early discharge from the ED, defined as discharge within six hours and no major adverse cardiac events within 30 days. This was a single-center trial in New Zealand, which limits its sample size and its generalizability; however, if larger studies led to the implementation of ADP by ED physicians, there would likely be fewer low-risk patients admitted to hospitalist services for evaluation of chest pain.

Bottom line: An accelerated diagnostic chest pain protocol results in earlier discharge of low-risk patients.

Citation: Than M, Aldous S, Lord SJ, et al. A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Intern Med. 2014;174(1):51-58.

Clinical question: In patients with possible cardiac chest pain, does an accelerated diagnostic protocol result in higher rates of successful early discharge when compared with the standard care pathway?

Background: An accelerated diagnostic pathway (ADP), which combines TIMI [thrombolysis in myocardial infarction] score, EKG, and zero- and two-hour troponin levels, can identify low-risk patients presenting with chest pain; however, little is known about its effect on the rates of early, successful discharge in a real-world population.

Study design: RCT.

Setting: An academic general and tertiary care hospital in Christchurch, New Zealand.

Synopsis: This study of 542 patients ages 18 years and older who presented with chest pain demonstrated that when compared with a conventional pathway, an ADP results in nearly twice the proportion of patients (19.3% vs. 11.0%; P=0.008) achieving safe, early discharge from the ED, defined as discharge within six hours and no major adverse cardiac events within 30 days. This was a single-center trial in New Zealand, which limits its sample size and its generalizability; however, if larger studies led to the implementation of ADP by ED physicians, there would likely be fewer low-risk patients admitted to hospitalist services for evaluation of chest pain.

Bottom line: An accelerated diagnostic chest pain protocol results in earlier discharge of low-risk patients.

Citation: Than M, Aldous S, Lord SJ, et al. A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: a randomized clinical trial. JAMA Intern Med. 2014;174(1):51-58.

Clinical question: What effect does a restrictive hemoglobin transfusion trigger of <7 g/dL have on clinical outcomes compared to more liberal transfusion triggers?

Background: Blood transfusions are standard of care in managing anemia despite sparse evidence that they improve clinical outcomes. As more evidence mounts that blood transfusions are associated with worse outcomes, the threshold hemoglobin level for transfusion has decreased. The safest hemoglobin trigger for blood transfusion remains unknown.

Study design: Meta-analysis of randomized control trials (RCTs) and systematic review of observational studies.

Setting: Data from MEDLINE.

Synopsis: Pooled data from three RCTs, including 2364 patients, compared outcomes between a restrictive hemoglobin transfusion trigger of <7 g/dL with a more liberal trigger. The restrictive strategy resulted in decreased in-hospital mortality (RR 0.74, CI 0.6-0.92), total mortality (RR 0.8, CI 0.65-0.98), rebleeding (RR 0.64, CI 0.45-0.9), acute coronary syndrome (RR 0.44, CI 0.22-0.89), and pulmonary edema (RR 0.48, CI 0.33-0.72). Using the restrictive strategy, the number needed to treat to prevent one death was 33.

A second meta-analysis of 16 RCTs found that less restrictive transfusion strategies (triggers of 7.5 to 10 g/dL) were not effective in improving outcomes. A systematic review of observational studies suggested that normovolemic patients can tolerate hemoglobins of 5-6 g/dL without affecting oxygen delivery.

The primary meta-analysis was limited by the inclusion of adult and pediatric patients and different indications for transfusion (critical illness, gastrointestinal bleed), which could have introduced some bias. Although the safest transfusion trigger remains unknown, this study demonstrates that <7 g/dL is safer than more liberal triggers.

Bottom line: A restrictive blood transfusion strategy with hemoglobin trigger of <7 g/dL in patients with critical illness or bleeding significantly decreases rebleeding, cardiac events, and total mortality.

Citation: Salpeter SR, Buckley JS, Chatterjee S. Impact of more restrictive blood transfusion strategies on clinical outcomes: a meta-analysis and systematic review. Am J Med. 2014;127(2): 124-131.

Clinical question: What effect does a restrictive hemoglobin transfusion trigger of <7 g/dL have on clinical outcomes compared to more liberal transfusion triggers?

Background: Blood transfusions are standard of care in managing anemia despite sparse evidence that they improve clinical outcomes. As more evidence mounts that blood transfusions are associated with worse outcomes, the threshold hemoglobin level for transfusion has decreased. The safest hemoglobin trigger for blood transfusion remains unknown.

Study design: Meta-analysis of randomized control trials (RCTs) and systematic review of observational studies.

Setting: Data from MEDLINE.

Synopsis: Pooled data from three RCTs, including 2364 patients, compared outcomes between a restrictive hemoglobin transfusion trigger of <7 g/dL with a more liberal trigger. The restrictive strategy resulted in decreased in-hospital mortality (RR 0.74, CI 0.6-0.92), total mortality (RR 0.8, CI 0.65-0.98), rebleeding (RR 0.64, CI 0.45-0.9), acute coronary syndrome (RR 0.44, CI 0.22-0.89), and pulmonary edema (RR 0.48, CI 0.33-0.72). Using the restrictive strategy, the number needed to treat to prevent one death was 33.

A second meta-analysis of 16 RCTs found that less restrictive transfusion strategies (triggers of 7.5 to 10 g/dL) were not effective in improving outcomes. A systematic review of observational studies suggested that normovolemic patients can tolerate hemoglobins of 5-6 g/dL without affecting oxygen delivery.

The primary meta-analysis was limited by the inclusion of adult and pediatric patients and different indications for transfusion (critical illness, gastrointestinal bleed), which could have introduced some bias. Although the safest transfusion trigger remains unknown, this study demonstrates that <7 g/dL is safer than more liberal triggers.

Bottom line: A restrictive blood transfusion strategy with hemoglobin trigger of <7 g/dL in patients with critical illness or bleeding significantly decreases rebleeding, cardiac events, and total mortality.

Citation: Salpeter SR, Buckley JS, Chatterjee S. Impact of more restrictive blood transfusion strategies on clinical outcomes: a meta-analysis and systematic review. Am J Med. 2014;127(2): 124-131.

Clinical question: What effect does a restrictive hemoglobin transfusion trigger of <7 g/dL have on clinical outcomes compared to more liberal transfusion triggers?

Background: Blood transfusions are standard of care in managing anemia despite sparse evidence that they improve clinical outcomes. As more evidence mounts that blood transfusions are associated with worse outcomes, the threshold hemoglobin level for transfusion has decreased. The safest hemoglobin trigger for blood transfusion remains unknown.

Study design: Meta-analysis of randomized control trials (RCTs) and systematic review of observational studies.

Setting: Data from MEDLINE.

Synopsis: Pooled data from three RCTs, including 2364 patients, compared outcomes between a restrictive hemoglobin transfusion trigger of <7 g/dL with a more liberal trigger. The restrictive strategy resulted in decreased in-hospital mortality (RR 0.74, CI 0.6-0.92), total mortality (RR 0.8, CI 0.65-0.98), rebleeding (RR 0.64, CI 0.45-0.9), acute coronary syndrome (RR 0.44, CI 0.22-0.89), and pulmonary edema (RR 0.48, CI 0.33-0.72). Using the restrictive strategy, the number needed to treat to prevent one death was 33.

A second meta-analysis of 16 RCTs found that less restrictive transfusion strategies (triggers of 7.5 to 10 g/dL) were not effective in improving outcomes. A systematic review of observational studies suggested that normovolemic patients can tolerate hemoglobins of 5-6 g/dL without affecting oxygen delivery.

The primary meta-analysis was limited by the inclusion of adult and pediatric patients and different indications for transfusion (critical illness, gastrointestinal bleed), which could have introduced some bias. Although the safest transfusion trigger remains unknown, this study demonstrates that <7 g/dL is safer than more liberal triggers.

Bottom line: A restrictive blood transfusion strategy with hemoglobin trigger of <7 g/dL in patients with critical illness or bleeding significantly decreases rebleeding, cardiac events, and total mortality.

Citation: Salpeter SR, Buckley JS, Chatterjee S. Impact of more restrictive blood transfusion strategies on clinical outcomes: a meta-analysis and systematic review. Am J Med. 2014;127(2): 124-131.

Clinical question: Can an ED observation syncope protocol decrease resource utilization without adversely affecting outcomes?

Background: Syncope is a common complaint in EDs. Uncertainty in the best way to manage older adults at intermediate risk for adverse outcomes results in frequent, costly hospitalizations without clear improvement in outcomes. An observation syncope protocol may standardize care and reduce admissions without worsening safety.

Study design: Randomized, non-blinded, clinical trial.

Setting: Five EDs in the United States.

Synopsis: One hundred twenty-four intermediate-risk adults (≥50 years) presenting with syncope or near syncope were randomized to an ED observation syncope protocol vs. routine admission. The observation protocol resulted in a lower admission rate (15% vs. 92%), shorter stay (29 vs. 47 hours), and decreased index hospital costs ($629); however, there were no significant differences in serious outcomes after discharge at 30 days (3% vs. 0%) or six months (8% vs. 10%), 30-day quality of life scores, or patient satisfaction. Limitations include the small study size, the fact that half of eligible patients were excluded as high risk, higher number of abnormal ECGs in the control group, and a cost savings that was attenuated at 30 days.

This ED observation syncope protocol demonstrated an impressive decrease in admission rates and length of stay without compromising safety, but only a small fraction of patients met the inclusion criteria, and the cost savings were small and transient.

Bottom line: An ED observation syncope protocol for intermediate-risk patients decreased admission rates, length of stay, and index hospitalization costs without a difference in safety events, patient satisfaction, or quality of life.

Citation: Sun BC, McCreath H, Liang L, et al. Randomized clinical trial of an emergency department observation syncope protocol versus routine inpatient admission [published online ahead of print November 13, 2013]. Ann Emerg Med.

Clinical question: Can an ED observation syncope protocol decrease resource utilization without adversely affecting outcomes?

Background: Syncope is a common complaint in EDs. Uncertainty in the best way to manage older adults at intermediate risk for adverse outcomes results in frequent, costly hospitalizations without clear improvement in outcomes. An observation syncope protocol may standardize care and reduce admissions without worsening safety.

Study design: Randomized, non-blinded, clinical trial.

Setting: Five EDs in the United States.

Synopsis: One hundred twenty-four intermediate-risk adults (≥50 years) presenting with syncope or near syncope were randomized to an ED observation syncope protocol vs. routine admission. The observation protocol resulted in a lower admission rate (15% vs. 92%), shorter stay (29 vs. 47 hours), and decreased index hospital costs ($629); however, there were no significant differences in serious outcomes after discharge at 30 days (3% vs. 0%) or six months (8% vs. 10%), 30-day quality of life scores, or patient satisfaction. Limitations include the small study size, the fact that half of eligible patients were excluded as high risk, higher number of abnormal ECGs in the control group, and a cost savings that was attenuated at 30 days.

This ED observation syncope protocol demonstrated an impressive decrease in admission rates and length of stay without compromising safety, but only a small fraction of patients met the inclusion criteria, and the cost savings were small and transient.

Bottom line: An ED observation syncope protocol for intermediate-risk patients decreased admission rates, length of stay, and index hospitalization costs without a difference in safety events, patient satisfaction, or quality of life.

Citation: Sun BC, McCreath H, Liang L, et al. Randomized clinical trial of an emergency department observation syncope protocol versus routine inpatient admission [published online ahead of print November 13, 2013]. Ann Emerg Med.

Clinical question: Can an ED observation syncope protocol decrease resource utilization without adversely affecting outcomes?

Background: Syncope is a common complaint in EDs. Uncertainty in the best way to manage older adults at intermediate risk for adverse outcomes results in frequent, costly hospitalizations without clear improvement in outcomes. An observation syncope protocol may standardize care and reduce admissions without worsening safety.

Study design: Randomized, non-blinded, clinical trial.

Setting: Five EDs in the United States.

Synopsis: One hundred twenty-four intermediate-risk adults (≥50 years) presenting with syncope or near syncope were randomized to an ED observation syncope protocol vs. routine admission. The observation protocol resulted in a lower admission rate (15% vs. 92%), shorter stay (29 vs. 47 hours), and decreased index hospital costs ($629); however, there were no significant differences in serious outcomes after discharge at 30 days (3% vs. 0%) or six months (8% vs. 10%), 30-day quality of life scores, or patient satisfaction. Limitations include the small study size, the fact that half of eligible patients were excluded as high risk, higher number of abnormal ECGs in the control group, and a cost savings that was attenuated at 30 days.

This ED observation syncope protocol demonstrated an impressive decrease in admission rates and length of stay without compromising safety, but only a small fraction of patients met the inclusion criteria, and the cost savings were small and transient.

Bottom line: An ED observation syncope protocol for intermediate-risk patients decreased admission rates, length of stay, and index hospitalization costs without a difference in safety events, patient satisfaction, or quality of life.

Citation: Sun BC, McCreath H, Liang L, et al. Randomized clinical trial of an emergency department observation syncope protocol versus routine inpatient admission [published online ahead of print November 13, 2013]. Ann Emerg Med.

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

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

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

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

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

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

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

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

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

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

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

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

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

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

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

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

Study design: Systematic review of the literature.

Setting: Twenty-six controlled studies.

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

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

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

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