Nita Shrikant Kulkarni, MD

Clinical question: Do interdisciplinary team care interventions affect outcomes for hospitalized patients in general medical wards?

Bottom line: Interdisciplinary team care interventions do not significantly affect oft-used quality measures such as length of stay, readmissions, or mortality. However, some experts question whether these measures are appropriate for assessing the effectiveness of such interventions. A small body of evidence suggests that interdisciplinary interventions may affect complications of care or preventable adverse events. In the future, these and other more appropriate measures should be used when assessing interdisciplinary team care interventions. (LOE = 2a)

Reference: Pannick S, Davis R, Ashrafian H, et al. Effects of interdisciplinary team care interventions on general medical wards. JAMA Intern Med 2015;175(8):1288-1298.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis

These investigators searched multiple databases including EMBASE and MEDLINE, as well as reference lists of included studies, to find trials that evaluated the effects of interdisciplinary team care on objective patient outcomes in the general medical wards. Study selection, data extraction, and assessment of bias were performed by independent reviewers.

Thirty studies (randomized controlled trials, cluster studies, and before-after studies) were included in the review. The studies had heterogeneous designs and outcome measures and all of them had a medium or high risk of bias. The majority of the studies, however, reported on complications of care, length of stay, readmission, or mortality.

Out of 10 studies that examined complications of care, five showed a reduction in this outcome by formalizing interdisciplinary rounds or adding specialized clinicians or pharmacists to the interdisciplinary team. Overall, 20% of the studies that looked at length of stay showed a reduction in this measure, but these results may have been confounded by secular trends toward length of stay reduction. No study showed a consistent or persistent effect on readmissions or mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Do interdisciplinary team care interventions affect outcomes for hospitalized patients in general medical wards?

Bottom line: Interdisciplinary team care interventions do not significantly affect oft-used quality measures such as length of stay, readmissions, or mortality. However, some experts question whether these measures are appropriate for assessing the effectiveness of such interventions. A small body of evidence suggests that interdisciplinary interventions may affect complications of care or preventable adverse events. In the future, these and other more appropriate measures should be used when assessing interdisciplinary team care interventions. (LOE = 2a)

Reference: Pannick S, Davis R, Ashrafian H, et al. Effects of interdisciplinary team care interventions on general medical wards. JAMA Intern Med 2015;175(8):1288-1298.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis

These investigators searched multiple databases including EMBASE and MEDLINE, as well as reference lists of included studies, to find trials that evaluated the effects of interdisciplinary team care on objective patient outcomes in the general medical wards. Study selection, data extraction, and assessment of bias were performed by independent reviewers.

Thirty studies (randomized controlled trials, cluster studies, and before-after studies) were included in the review. The studies had heterogeneous designs and outcome measures and all of them had a medium or high risk of bias. The majority of the studies, however, reported on complications of care, length of stay, readmission, or mortality.

Out of 10 studies that examined complications of care, five showed a reduction in this outcome by formalizing interdisciplinary rounds or adding specialized clinicians or pharmacists to the interdisciplinary team. Overall, 20% of the studies that looked at length of stay showed a reduction in this measure, but these results may have been confounded by secular trends toward length of stay reduction. No study showed a consistent or persistent effect on readmissions or mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Do interdisciplinary team care interventions affect outcomes for hospitalized patients in general medical wards?

Bottom line: Interdisciplinary team care interventions do not significantly affect oft-used quality measures such as length of stay, readmissions, or mortality. However, some experts question whether these measures are appropriate for assessing the effectiveness of such interventions. A small body of evidence suggests that interdisciplinary interventions may affect complications of care or preventable adverse events. In the future, these and other more appropriate measures should be used when assessing interdisciplinary team care interventions. (LOE = 2a)

Reference: Pannick S, Davis R, Ashrafian H, et al. Effects of interdisciplinary team care interventions on general medical wards. JAMA Intern Med 2015;175(8):1288-1298.

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis

These investigators searched multiple databases including EMBASE and MEDLINE, as well as reference lists of included studies, to find trials that evaluated the effects of interdisciplinary team care on objective patient outcomes in the general medical wards. Study selection, data extraction, and assessment of bias were performed by independent reviewers.

Thirty studies (randomized controlled trials, cluster studies, and before-after studies) were included in the review. The studies had heterogeneous designs and outcome measures and all of them had a medium or high risk of bias. The majority of the studies, however, reported on complications of care, length of stay, readmission, or mortality.

Out of 10 studies that examined complications of care, five showed a reduction in this outcome by formalizing interdisciplinary rounds or adding specialized clinicians or pharmacists to the interdisciplinary team. Overall, 20% of the studies that looked at length of stay showed a reduction in this measure, but these results may have been confounded by secular trends toward length of stay reduction. No study showed a consistent or persistent effect on readmissions or mortality.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of perioperative beta-blockers affect the outcomes in patients undergoing noncardiac surgery?

Bottom line: Determining the presence or absence of cardiac risk factors is important when deciding whether to use beta-blockers during the perioperative period for patients undergoing noncardiac surgery. This study shows that although perioperative beta-blockade may benefit patients with high cardiac risk, it increases short-term mortality in those with no cardiac risk factors. (LOE = 2b)

Reference: Friedell ML, Van Way CW, Freyberg RW, Almenoff PL. Beta-blockade and operative mortality in noncardiac surgery: harmful or helpful. JAMA Surg. 2015;150(7):658-663.

Study design: Cohort (retrospective)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using data collected from the Veterans Health Administration, these investigators identified more than 325,000 patients hospitalized for surgery. The use of perioperative beta-blockers in this cohort was determined by using pharmacy data. It was unclear whether the beta-blocker was a new medication or a continuation of a home medication and the study did not measure if the beta-blocker was given preoperatively or postoperatively.

Each patient was assigned a cardiac risk score (1 point each for the presence of renal failure, coronary artery disease, diabetes, and abdominal/thoracic surgery) and grouped into 1 of 3 categories: 0 risk factors, 1 to 2 risk factors, and 3 to 4 risk factors. The results showed that the effect of the beta-blockers on mortality varied according to the presence of cardiac risk factors in patients undergoing noncardiac surgery (n = 314,114). In an adjusted analysis, patients with no cardiac risk factors who received beta-blockers had increased 30-day mortality compared with those who did not receive beta-blockers (odds ratio [OR] 1.19, 95% CI 1.06-1.35).

The opposite was true for patients with 3 to 4 cardiac risk factors: Those who received beta-blockers were less likely to die than those who did not receive them (OR 0.63, 95% CI 0.43-0.93). For patients with 1 to 2 risk factors, there was a nonsignificant reduction in mortality with the use of beta-blockers. For the minority of the cohort who actually underwent cardiac surgery (n = 12,375), there was no significant interaction seen between the number of cardiac risk factors and the use of beta-blockers on mortality. Of note, more than 90% of patients in this study population were men, thus these findings may not be generalizable to women.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of perioperative beta-blockers affect the outcomes in patients undergoing noncardiac surgery?

Bottom line: Determining the presence or absence of cardiac risk factors is important when deciding whether to use beta-blockers during the perioperative period for patients undergoing noncardiac surgery. This study shows that although perioperative beta-blockade may benefit patients with high cardiac risk, it increases short-term mortality in those with no cardiac risk factors. (LOE = 2b)

Reference: Friedell ML, Van Way CW, Freyberg RW, Almenoff PL. Beta-blockade and operative mortality in noncardiac surgery: harmful or helpful. JAMA Surg. 2015;150(7):658-663.

Study design: Cohort (retrospective)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using data collected from the Veterans Health Administration, these investigators identified more than 325,000 patients hospitalized for surgery. The use of perioperative beta-blockers in this cohort was determined by using pharmacy data. It was unclear whether the beta-blocker was a new medication or a continuation of a home medication and the study did not measure if the beta-blocker was given preoperatively or postoperatively.

Each patient was assigned a cardiac risk score (1 point each for the presence of renal failure, coronary artery disease, diabetes, and abdominal/thoracic surgery) and grouped into 1 of 3 categories: 0 risk factors, 1 to 2 risk factors, and 3 to 4 risk factors. The results showed that the effect of the beta-blockers on mortality varied according to the presence of cardiac risk factors in patients undergoing noncardiac surgery (n = 314,114). In an adjusted analysis, patients with no cardiac risk factors who received beta-blockers had increased 30-day mortality compared with those who did not receive beta-blockers (odds ratio [OR] 1.19, 95% CI 1.06-1.35).

The opposite was true for patients with 3 to 4 cardiac risk factors: Those who received beta-blockers were less likely to die than those who did not receive them (OR 0.63, 95% CI 0.43-0.93). For patients with 1 to 2 risk factors, there was a nonsignificant reduction in mortality with the use of beta-blockers. For the minority of the cohort who actually underwent cardiac surgery (n = 12,375), there was no significant interaction seen between the number of cardiac risk factors and the use of beta-blockers on mortality. Of note, more than 90% of patients in this study population were men, thus these findings may not be generalizable to women.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of perioperative beta-blockers affect the outcomes in patients undergoing noncardiac surgery?

Bottom line: Determining the presence or absence of cardiac risk factors is important when deciding whether to use beta-blockers during the perioperative period for patients undergoing noncardiac surgery. This study shows that although perioperative beta-blockade may benefit patients with high cardiac risk, it increases short-term mortality in those with no cardiac risk factors. (LOE = 2b)

Reference: Friedell ML, Van Way CW, Freyberg RW, Almenoff PL. Beta-blockade and operative mortality in noncardiac surgery: harmful or helpful. JAMA Surg. 2015;150(7):658-663.

Study design: Cohort (retrospective)

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: Using data collected from the Veterans Health Administration, these investigators identified more than 325,000 patients hospitalized for surgery. The use of perioperative beta-blockers in this cohort was determined by using pharmacy data. It was unclear whether the beta-blocker was a new medication or a continuation of a home medication and the study did not measure if the beta-blocker was given preoperatively or postoperatively.

Each patient was assigned a cardiac risk score (1 point each for the presence of renal failure, coronary artery disease, diabetes, and abdominal/thoracic surgery) and grouped into 1 of 3 categories: 0 risk factors, 1 to 2 risk factors, and 3 to 4 risk factors. The results showed that the effect of the beta-blockers on mortality varied according to the presence of cardiac risk factors in patients undergoing noncardiac surgery (n = 314,114). In an adjusted analysis, patients with no cardiac risk factors who received beta-blockers had increased 30-day mortality compared with those who did not receive beta-blockers (odds ratio [OR] 1.19, 95% CI 1.06-1.35).

The opposite was true for patients with 3 to 4 cardiac risk factors: Those who received beta-blockers were less likely to die than those who did not receive them (OR 0.63, 95% CI 0.43-0.93). For patients with 1 to 2 risk factors, there was a nonsignificant reduction in mortality with the use of beta-blockers. For the minority of the cohort who actually underwent cardiac surgery (n = 12,375), there was no significant interaction seen between the number of cardiac risk factors and the use of beta-blockers on mortality. Of note, more than 90% of patients in this study population were men, thus these findings may not be generalizable to women.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: How useful is the Wells score for risk-stratifying hospitalized patients with suspected deep vein thrombosis?

Bottom line: The Wells score is not helpful in the inpatient setting to predict the presence or absence of deep vein thrombosis (DVT). Based on this study, if a hospitalized patient has a low Wells score, the risk of having DVT is still relatively high (6%). If a patient has a moderate or high score, however, the risk of having DVT is fairly low (10% to 16%). In all 3 categories, a patient would need further testing with ultrasound to evaluate for DVT. (LOE = 2b)

Reference: Silveira PC, Ip IK, Goldhaber SZ, Piazza G, Benson CB, Khorasani R. Performance of Wells score for deep vein thrombosis in the inpatient setting. JAMA Intern Med. 2015;175(7):1112-1117.

Study design: Diagnostic test evaluation

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: The Wells score has been previously validated to risk-stratify outpatients with suspected DVT but its utility in the inpatient setting is unknown. These investigators evaluated 1135 hospitalized patients with suspected DVT who underwent a lower extremity ultrasound study in the hospital. When ordering these studies, clinicians were required to enter information regarding clinical predictors in order to calculate an individual patient's Wells score. The patients were divided into 3 Wells score categories that determined their pre-test probability for DVT (low risk = 0 or lower, moderate risk = 1 or 2, high risk = 3 or higher). Baseline characteristics for the patients in the study showed that 71% were recently bedridden or had recent major surgery and almost 40% had active cancer.

Overall, 12% of patients in the study had proximal DVT confirmed by a lower extremity ultrasound study. When classified by Wells score categories, the incidence of proximal DVT was 5.9%, 9.5%, and 16.4% in low, moderate, and high pre-test probability groups, respectively. The area under the receiving operating characteristics curve for the Wells score as a diagnostic test was 0.60.

This indicates that the ability of the Wells score to discriminate between the presence and absence of DVT in hospitalized patients was only slightly better than chance. The authors postulate that the reason for this is that hospitalized patients are inherently different from outpatients: they have a higher prevalence of immobilization and/or have active cancer; they receive routine DVT prophylaxis; and they are more likely to have other comorbidities that increase DVT risk, such as heart failure and chronic obstructive pulmonary disease — risk factors that are not accounted for in the Wells score calculation. As such, the Wells score is less meaningful in this population.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: How useful is the Wells score for risk-stratifying hospitalized patients with suspected deep vein thrombosis?

Bottom line: The Wells score is not helpful in the inpatient setting to predict the presence or absence of deep vein thrombosis (DVT). Based on this study, if a hospitalized patient has a low Wells score, the risk of having DVT is still relatively high (6%). If a patient has a moderate or high score, however, the risk of having DVT is fairly low (10% to 16%). In all 3 categories, a patient would need further testing with ultrasound to evaluate for DVT. (LOE = 2b)

Reference: Silveira PC, Ip IK, Goldhaber SZ, Piazza G, Benson CB, Khorasani R. Performance of Wells score for deep vein thrombosis in the inpatient setting. JAMA Intern Med. 2015;175(7):1112-1117.

Study design: Diagnostic test evaluation

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: The Wells score has been previously validated to risk-stratify outpatients with suspected DVT but its utility in the inpatient setting is unknown. These investigators evaluated 1135 hospitalized patients with suspected DVT who underwent a lower extremity ultrasound study in the hospital. When ordering these studies, clinicians were required to enter information regarding clinical predictors in order to calculate an individual patient's Wells score. The patients were divided into 3 Wells score categories that determined their pre-test probability for DVT (low risk = 0 or lower, moderate risk = 1 or 2, high risk = 3 or higher). Baseline characteristics for the patients in the study showed that 71% were recently bedridden or had recent major surgery and almost 40% had active cancer.

Overall, 12% of patients in the study had proximal DVT confirmed by a lower extremity ultrasound study. When classified by Wells score categories, the incidence of proximal DVT was 5.9%, 9.5%, and 16.4% in low, moderate, and high pre-test probability groups, respectively. The area under the receiving operating characteristics curve for the Wells score as a diagnostic test was 0.60.

This indicates that the ability of the Wells score to discriminate between the presence and absence of DVT in hospitalized patients was only slightly better than chance. The authors postulate that the reason for this is that hospitalized patients are inherently different from outpatients: they have a higher prevalence of immobilization and/or have active cancer; they receive routine DVT prophylaxis; and they are more likely to have other comorbidities that increase DVT risk, such as heart failure and chronic obstructive pulmonary disease — risk factors that are not accounted for in the Wells score calculation. As such, the Wells score is less meaningful in this population.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: How useful is the Wells score for risk-stratifying hospitalized patients with suspected deep vein thrombosis?

Bottom line: The Wells score is not helpful in the inpatient setting to predict the presence or absence of deep vein thrombosis (DVT). Based on this study, if a hospitalized patient has a low Wells score, the risk of having DVT is still relatively high (6%). If a patient has a moderate or high score, however, the risk of having DVT is fairly low (10% to 16%). In all 3 categories, a patient would need further testing with ultrasound to evaluate for DVT. (LOE = 2b)

Reference: Silveira PC, Ip IK, Goldhaber SZ, Piazza G, Benson CB, Khorasani R. Performance of Wells score for deep vein thrombosis in the inpatient setting. JAMA Intern Med. 2015;175(7):1112-1117.

Study design: Diagnostic test evaluation

Funding source: Unknown/not stated

Allocation: Uncertain

Setting: Inpatient (any location)

Synopsis: The Wells score has been previously validated to risk-stratify outpatients with suspected DVT but its utility in the inpatient setting is unknown. These investigators evaluated 1135 hospitalized patients with suspected DVT who underwent a lower extremity ultrasound study in the hospital. When ordering these studies, clinicians were required to enter information regarding clinical predictors in order to calculate an individual patient's Wells score. The patients were divided into 3 Wells score categories that determined their pre-test probability for DVT (low risk = 0 or lower, moderate risk = 1 or 2, high risk = 3 or higher). Baseline characteristics for the patients in the study showed that 71% were recently bedridden or had recent major surgery and almost 40% had active cancer.

Overall, 12% of patients in the study had proximal DVT confirmed by a lower extremity ultrasound study. When classified by Wells score categories, the incidence of proximal DVT was 5.9%, 9.5%, and 16.4% in low, moderate, and high pre-test probability groups, respectively. The area under the receiving operating characteristics curve for the Wells score as a diagnostic test was 0.60.

This indicates that the ability of the Wells score to discriminate between the presence and absence of DVT in hospitalized patients was only slightly better than chance. The authors postulate that the reason for this is that hospitalized patients are inherently different from outpatients: they have a higher prevalence of immobilization and/or have active cancer; they receive routine DVT prophylaxis; and they are more likely to have other comorbidities that increase DVT risk, such as heart failure and chronic obstructive pulmonary disease — risk factors that are not accounted for in the Wells score calculation. As such, the Wells score is less meaningful in this population.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does high-flow oxygen therapy result in a decreased rate of intubation for patients with nonhypercapnic acute hypoxemic respiratory failure?

Bottom line: In this underpowered study, the use of high-flow oxygen therapy did not significantly reduce the rate of intubation as compared with standard oxygen therapy or noninvasive positive pressure ventilation in patients with nonhypercapnic acute hypoxemic respiratory failure. However, patients in the high-flow oxygen group had decreased 90-day mortality, as well as an increased number of ventilator-free days. Patients in the high-flow oxygen group also reported less respiratory discomfort and dyspnea than patients in the other 2 groups. (LOE = 1b-)

Reference: Frat J, Thille AW, Mercat A, et al, for the FLORALI Study Group and the REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372(23):2185-2196.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis: High-flow oxygen therapy uses oxygen delivered via nasal cannula at high flow rates to provide low-level positive pressure and reduce effective deadspace in the airways. Its effectiveness in the treatment of acute hypoxemic respiratory failure has not been established. In this study, investigators compared high-flow oxygen therapy with noninvasive positive pressure ventilation as well as with standard oxygen therapy in patients with nonhypercapnic acute hypoxemic respiratory failure.

Using concealed allocation, patients were randomized into 1 of 3 groups: (1) standard oxygen therapy using a nonrebreather face mask at a flow rate of 10 liters per minute or more; (2) high-flow oxygen therapy provided through a heated humidifier at a rate of 50 liters per minute for at least 2 days; or (3) noninvasive positive pressure ventilation for 8 hours per day for at least 2 days. With all 3 strategies, the goal was to maintain an oxygen saturation level of 92% or more. The 3 groups were similar at baseline with the majority of patients having community-acquired pneumonia as a cause of their acute respiratory failure. Analysis was by intention to treat.

For the primary outcome, the high-flow oxygen therapy group had a lower rate of intubation at 28 days than the other 2 groups, but this difference was not statistically significant (38% in high-flow group, 47% in standard group, 50% in noninvasive ventilation group; P = .18). Of note, the intubation rate in the standard oxygen therapy group was lower than the expected 60%, thus the study was underpowered to detect a difference if it truly exists. The high-flow therapy resulted in reduced 90-day mortality as compared with both standard therapy (hazard ratio [HR] = 2.01, 95% CI 1.01-3.99; P = .046) and noninvasive ventilation (HR = 2.50, 1.31-4.78; P = .006).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does high-flow oxygen therapy result in a decreased rate of intubation for patients with nonhypercapnic acute hypoxemic respiratory failure?

Bottom line: In this underpowered study, the use of high-flow oxygen therapy did not significantly reduce the rate of intubation as compared with standard oxygen therapy or noninvasive positive pressure ventilation in patients with nonhypercapnic acute hypoxemic respiratory failure. However, patients in the high-flow oxygen group had decreased 90-day mortality, as well as an increased number of ventilator-free days. Patients in the high-flow oxygen group also reported less respiratory discomfort and dyspnea than patients in the other 2 groups. (LOE = 1b-)

Reference: Frat J, Thille AW, Mercat A, et al, for the FLORALI Study Group and the REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372(23):2185-2196.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis: High-flow oxygen therapy uses oxygen delivered via nasal cannula at high flow rates to provide low-level positive pressure and reduce effective deadspace in the airways. Its effectiveness in the treatment of acute hypoxemic respiratory failure has not been established. In this study, investigators compared high-flow oxygen therapy with noninvasive positive pressure ventilation as well as with standard oxygen therapy in patients with nonhypercapnic acute hypoxemic respiratory failure.

Using concealed allocation, patients were randomized into 1 of 3 groups: (1) standard oxygen therapy using a nonrebreather face mask at a flow rate of 10 liters per minute or more; (2) high-flow oxygen therapy provided through a heated humidifier at a rate of 50 liters per minute for at least 2 days; or (3) noninvasive positive pressure ventilation for 8 hours per day for at least 2 days. With all 3 strategies, the goal was to maintain an oxygen saturation level of 92% or more. The 3 groups were similar at baseline with the majority of patients having community-acquired pneumonia as a cause of their acute respiratory failure. Analysis was by intention to treat.

For the primary outcome, the high-flow oxygen therapy group had a lower rate of intubation at 28 days than the other 2 groups, but this difference was not statistically significant (38% in high-flow group, 47% in standard group, 50% in noninvasive ventilation group; P = .18). Of note, the intubation rate in the standard oxygen therapy group was lower than the expected 60%, thus the study was underpowered to detect a difference if it truly exists. The high-flow therapy resulted in reduced 90-day mortality as compared with both standard therapy (hazard ratio [HR] = 2.01, 95% CI 1.01-3.99; P = .046) and noninvasive ventilation (HR = 2.50, 1.31-4.78; P = .006).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does high-flow oxygen therapy result in a decreased rate of intubation for patients with nonhypercapnic acute hypoxemic respiratory failure?

Bottom line: In this underpowered study, the use of high-flow oxygen therapy did not significantly reduce the rate of intubation as compared with standard oxygen therapy or noninvasive positive pressure ventilation in patients with nonhypercapnic acute hypoxemic respiratory failure. However, patients in the high-flow oxygen group had decreased 90-day mortality, as well as an increased number of ventilator-free days. Patients in the high-flow oxygen group also reported less respiratory discomfort and dyspnea than patients in the other 2 groups. (LOE = 1b-)

Reference: Frat J, Thille AW, Mercat A, et al, for the FLORALI Study Group and the REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372(23):2185-2196.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis: High-flow oxygen therapy uses oxygen delivered via nasal cannula at high flow rates to provide low-level positive pressure and reduce effective deadspace in the airways. Its effectiveness in the treatment of acute hypoxemic respiratory failure has not been established. In this study, investigators compared high-flow oxygen therapy with noninvasive positive pressure ventilation as well as with standard oxygen therapy in patients with nonhypercapnic acute hypoxemic respiratory failure.

Using concealed allocation, patients were randomized into 1 of 3 groups: (1) standard oxygen therapy using a nonrebreather face mask at a flow rate of 10 liters per minute or more; (2) high-flow oxygen therapy provided through a heated humidifier at a rate of 50 liters per minute for at least 2 days; or (3) noninvasive positive pressure ventilation for 8 hours per day for at least 2 days. With all 3 strategies, the goal was to maintain an oxygen saturation level of 92% or more. The 3 groups were similar at baseline with the majority of patients having community-acquired pneumonia as a cause of their acute respiratory failure. Analysis was by intention to treat.

For the primary outcome, the high-flow oxygen therapy group had a lower rate of intubation at 28 days than the other 2 groups, but this difference was not statistically significant (38% in high-flow group, 47% in standard group, 50% in noninvasive ventilation group; P = .18). Of note, the intubation rate in the standard oxygen therapy group was lower than the expected 60%, thus the study was underpowered to detect a difference if it truly exists. The high-flow therapy resulted in reduced 90-day mortality as compared with both standard therapy (hazard ratio [HR] = 2.01, 95% CI 1.01-3.99; P = .046) and noninvasive ventilation (HR = 2.50, 1.31-4.78; P = .006).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of a patient navigator to guide hospitalized patients through the health care system reduce 30-day readmission rates?

Bottom line: The use of a community health worker acting as a patient navigator (PN), both during hospitalization and after discharge, to assist patients with coordination of care, follow-up appointments, provider communication, and medication compliance decreases the 30-day readmission rate in older high-risk patients, but increased admissions in younger patients, suggesting that the younger population may require different strategies to decrease their use of hospital-based care. (LOE = 1b-)

Reference: Balaban RB, Galbraith AA, Burns ME, Vialle-Valentin CE, Larochelle MR, Ross-Degnan D. A patient navigator intervention to reduce hospital readmissions among high-risk safety-net patients: a randomized controlled trial. J Gen Intern Med 2015;30(7):907-915.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: This US study took place within a safety-net hospital system in Massachusetts that has a large underserved patient population. The authors enrolled more than 1500 hospitalized patients with at least 1 of 5 risk factors for readmission (older than 60 years, previous hospitalization within the last 6 months, length of stay of 3 days or more, or admission diagnoses of heart failure or chronic obstructive pulmonary disease). Patients in the intervention group were assigned to a hospital-based community health worker, or PN, while patients in the control group received usual care. The PN's primary responsibility was helping the patient navigate through the health care system, including assessing postdischarge needs, assisting with communication with inpatient providers and primary care physicians, confirming and rescheduling follow-up appointments, addressing barriers to taking medications, and assisting with transportation and insurance issues. These services were provided through a hospital visit and at least 3 weekly postdischarge phone calls. Patients in both groups were racially diverse and the majority carried public insurance. The patients older than 60 years were more medically complex, but younger patients had more psychiatric disorders and substance use disorders, as well as higher rates of previous hospitalizations and longer lengths of stay.

Overall, the 30-day readmission rate did not differ significantly between the control and intervention groups, but the study was underpowered given the limits to enrollment during the prespecified period. In an adjusted analysis of the 2 age subgroups, however, readmissions decreased by 4% in older intervention patients and they increased by 12% in younger intervention patients (both differences statistically significant).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of a patient navigator to guide hospitalized patients through the health care system reduce 30-day readmission rates?

Bottom line: The use of a community health worker acting as a patient navigator (PN), both during hospitalization and after discharge, to assist patients with coordination of care, follow-up appointments, provider communication, and medication compliance decreases the 30-day readmission rate in older high-risk patients, but increased admissions in younger patients, suggesting that the younger population may require different strategies to decrease their use of hospital-based care. (LOE = 1b-)

Reference: Balaban RB, Galbraith AA, Burns ME, Vialle-Valentin CE, Larochelle MR, Ross-Degnan D. A patient navigator intervention to reduce hospital readmissions among high-risk safety-net patients: a randomized controlled trial. J Gen Intern Med 2015;30(7):907-915.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: This US study took place within a safety-net hospital system in Massachusetts that has a large underserved patient population. The authors enrolled more than 1500 hospitalized patients with at least 1 of 5 risk factors for readmission (older than 60 years, previous hospitalization within the last 6 months, length of stay of 3 days or more, or admission diagnoses of heart failure or chronic obstructive pulmonary disease). Patients in the intervention group were assigned to a hospital-based community health worker, or PN, while patients in the control group received usual care. The PN's primary responsibility was helping the patient navigate through the health care system, including assessing postdischarge needs, assisting with communication with inpatient providers and primary care physicians, confirming and rescheduling follow-up appointments, addressing barriers to taking medications, and assisting with transportation and insurance issues. These services were provided through a hospital visit and at least 3 weekly postdischarge phone calls. Patients in both groups were racially diverse and the majority carried public insurance. The patients older than 60 years were more medically complex, but younger patients had more psychiatric disorders and substance use disorders, as well as higher rates of previous hospitalizations and longer lengths of stay.

Overall, the 30-day readmission rate did not differ significantly between the control and intervention groups, but the study was underpowered given the limits to enrollment during the prespecified period. In an adjusted analysis of the 2 age subgroups, however, readmissions decreased by 4% in older intervention patients and they increased by 12% in younger intervention patients (both differences statistically significant).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of a patient navigator to guide hospitalized patients through the health care system reduce 30-day readmission rates?

Bottom line: The use of a community health worker acting as a patient navigator (PN), both during hospitalization and after discharge, to assist patients with coordination of care, follow-up appointments, provider communication, and medication compliance decreases the 30-day readmission rate in older high-risk patients, but increased admissions in younger patients, suggesting that the younger population may require different strategies to decrease their use of hospital-based care. (LOE = 1b-)

Reference: Balaban RB, Galbraith AA, Burns ME, Vialle-Valentin CE, Larochelle MR, Ross-Degnan D. A patient navigator intervention to reduce hospital readmissions among high-risk safety-net patients: a randomized controlled trial. J Gen Intern Med 2015;30(7):907-915.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: This US study took place within a safety-net hospital system in Massachusetts that has a large underserved patient population. The authors enrolled more than 1500 hospitalized patients with at least 1 of 5 risk factors for readmission (older than 60 years, previous hospitalization within the last 6 months, length of stay of 3 days or more, or admission diagnoses of heart failure or chronic obstructive pulmonary disease). Patients in the intervention group were assigned to a hospital-based community health worker, or PN, while patients in the control group received usual care. The PN's primary responsibility was helping the patient navigate through the health care system, including assessing postdischarge needs, assisting with communication with inpatient providers and primary care physicians, confirming and rescheduling follow-up appointments, addressing barriers to taking medications, and assisting with transportation and insurance issues. These services were provided through a hospital visit and at least 3 weekly postdischarge phone calls. Patients in both groups were racially diverse and the majority carried public insurance. The patients older than 60 years were more medically complex, but younger patients had more psychiatric disorders and substance use disorders, as well as higher rates of previous hospitalizations and longer lengths of stay.

Overall, the 30-day readmission rate did not differ significantly between the control and intervention groups, but the study was underpowered given the limits to enrollment during the prespecified period. In an adjusted analysis of the 2 age subgroups, however, readmissions decreased by 4% in older intervention patients and they increased by 12% in younger intervention patients (both differences statistically significant).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?

Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)

Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.

Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).

However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?

Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)

Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.

Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).

However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Is trimethoprim-sulfamethoxazole equivalent to vancomycin for the treatment of severe infections caused by methicillin-resistant Staphyloccus aureus?

Bottom line: Trimethoprim-sulfamethoxazole (TMP-SMX) did not achieve noninferiority as compared with vancomycin for the treatment of severe methicillin-resistant Staphyloccus aureus (MRSA) infections in hospitalized patients, and it may lead to increased mortality in the subset of patients with bacteremia. (LOE = 1b)

Reference: Paul M, Bishara J, Yahav D, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin-resistant Staphylococcus aureus. BMJ 2015;350:h2219.

Study design: Randomized controlled trial (nonblinded)

Funding source: Foundation

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

Although TMP-SMX can be used to treat uncomplicated skin and soft-tissue infections caused by MRSA, it is not currently recommended for more serious MRSA infections such as bacteremia or pneumonia. In this study, investigators tested whether TMP-SMX is noninferior to vancomycin for the treatment of hospitalized patients with severe MRSA infections. Patients included in the study (N = 252) had microbiologically documented MRSA infections, including complicated skin and soft-tissue infections, bone or joint infections, pneumonia, or primary bacteremia. Patients with MRSA isolates resistant to TMP-SMX or vancomycin were excluded.

Using concealed allocation, the investigators randomized the patients to receive either high-dose TMP-SMX (320 mg trimethoprim/1600 mg sulfamethoxazole intravenously twice daily) or vancomycin (1 mg intravenously twice daily) for at least 7 days. In the TMP-SMX group, treatment could be transitioned to an oral regimen of an equivalent dose at the clinician's discretion. The 2 groups had similar baseline characteristics with a mean age of 66 years and similar comorbidities, though the vancomycin group had a higher percentage of patients with bacteremia than the TMP-SMX group (30% vs 43%; P = .042). The primary outcome was treatment failure at 7 days, defined as a composite of death, persistent fever or hypotension, stable or worsening Sequential Organ Failure Assessment score, or persistent bacteremia. There was no statistically significant difference detected between the 2 groups for this outcome (38% treatment failure with TMP-SMX vs 27% with vancomycin; absolute difference 10.4%, 95% CI -1.2% to 21.5%).

However, since the 95% confidence interval for the absolute difference fell outside the predefined lower limit of noninferiority of 15%, the authors concluded that TMP-SMX failed to achieve noninferiority as compared with vancomycin. Additionally, in the subgroup of patients with bacteremia, patients were more likely to die in the TMP-SMX group as compared with the vancomycin group, although this difference again was not statistically significant (34% with TMP-SMX vs 18% with vancomycin; relative risk 1.90, 0.92-3.93).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of routine thrombectomy for patients presenting with ST-segment elevation myocardial infarction improve outcomes?

Bottom line: For patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), the routine use of manual thrombectomy improves some electrocardiographic and angiographic outcomes, but ultimately does not result in improved cardiovascular morbidity or mortality. Moreover, thrombectomy may increase the risk of stroke. (LOE = 1b)

Reference: Jolly SS, Cairns JA, Yusuf S, et al, for the TOTAL Investigators. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med. 2015;372(15):1389–1398.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Manual thrombectomy with aspiration of thrombus prior to PCI is thought to prevent distal embolization and improve microvascular perfusion. Whether this results in clinical benefit is unclear. In this study, the investigators randomized patients presenting with STEMI to undergo either routine thrombus aspiration followed by PCI or PCI alone. Those who had a previous history of coronary-artery bypass grafting or those who had received fibrinolytics were excluded. The 2 groups were balanced at baseline, with almost 80% of patients in each group noted to have a high thrombus burden. A modified intention-to-treat analysis was used that included only those patients who actually underwent PCI for the index STEMI.

Although electrocardiographic and angiographic outcomes improved with thrombectomy (eg, increased ST-segment resolution, decreased distal embolization), no clinical benefit was found. Specifically, for the primary outcome of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association class IV heart failure within 180 days of randomization, there were no significant differences detected between the 2 groups. The components of the composite outcome taken individually were also similar in each group. These results persisted across prespecified analyses of the as-treated population, per-protocol population, and the subgroup with high thrombus burden. Additionally, patients in the thrombectomy group were more likely to have a stroke within 30 days and 180 days, although the number of events was relatively small (for 30 days: 0.7% vs 0.3%, P = .02; for 180 days: 1% vs 0.5%, P = .002).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of routine thrombectomy for patients presenting with ST-segment elevation myocardial infarction improve outcomes?

Bottom line: For patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), the routine use of manual thrombectomy improves some electrocardiographic and angiographic outcomes, but ultimately does not result in improved cardiovascular morbidity or mortality. Moreover, thrombectomy may increase the risk of stroke. (LOE = 1b)

Reference: Jolly SS, Cairns JA, Yusuf S, et al, for the TOTAL Investigators. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med. 2015;372(15):1389–1398.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Manual thrombectomy with aspiration of thrombus prior to PCI is thought to prevent distal embolization and improve microvascular perfusion. Whether this results in clinical benefit is unclear. In this study, the investigators randomized patients presenting with STEMI to undergo either routine thrombus aspiration followed by PCI or PCI alone. Those who had a previous history of coronary-artery bypass grafting or those who had received fibrinolytics were excluded. The 2 groups were balanced at baseline, with almost 80% of patients in each group noted to have a high thrombus burden. A modified intention-to-treat analysis was used that included only those patients who actually underwent PCI for the index STEMI.

Although electrocardiographic and angiographic outcomes improved with thrombectomy (eg, increased ST-segment resolution, decreased distal embolization), no clinical benefit was found. Specifically, for the primary outcome of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association class IV heart failure within 180 days of randomization, there were no significant differences detected between the 2 groups. The components of the composite outcome taken individually were also similar in each group. These results persisted across prespecified analyses of the as-treated population, per-protocol population, and the subgroup with high thrombus burden. Additionally, patients in the thrombectomy group were more likely to have a stroke within 30 days and 180 days, although the number of events was relatively small (for 30 days: 0.7% vs 0.3%, P = .02; for 180 days: 1% vs 0.5%, P = .002).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of routine thrombectomy for patients presenting with ST-segment elevation myocardial infarction improve outcomes?

Bottom line: For patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), the routine use of manual thrombectomy improves some electrocardiographic and angiographic outcomes, but ultimately does not result in improved cardiovascular morbidity or mortality. Moreover, thrombectomy may increase the risk of stroke. (LOE = 1b)

Reference: Jolly SS, Cairns JA, Yusuf S, et al, for the TOTAL Investigators. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med. 2015;372(15):1389–1398.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry + govt

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

Manual thrombectomy with aspiration of thrombus prior to PCI is thought to prevent distal embolization and improve microvascular perfusion. Whether this results in clinical benefit is unclear. In this study, the investigators randomized patients presenting with STEMI to undergo either routine thrombus aspiration followed by PCI or PCI alone. Those who had a previous history of coronary-artery bypass grafting or those who had received fibrinolytics were excluded. The 2 groups were balanced at baseline, with almost 80% of patients in each group noted to have a high thrombus burden. A modified intention-to-treat analysis was used that included only those patients who actually underwent PCI for the index STEMI.

Although electrocardiographic and angiographic outcomes improved with thrombectomy (eg, increased ST-segment resolution, decreased distal embolization), no clinical benefit was found. Specifically, for the primary outcome of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, or New York Heart Association class IV heart failure within 180 days of randomization, there were no significant differences detected between the 2 groups. The components of the composite outcome taken individually were also similar in each group. These results persisted across prespecified analyses of the as-treated population, per-protocol population, and the subgroup with high thrombus burden. Additionally, patients in the thrombectomy group were more likely to have a stroke within 30 days and 180 days, although the number of events was relatively small (for 30 days: 0.7% vs 0.3%, P = .02; for 180 days: 1% vs 0.5%, P = .002).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the insertion of a retrievable inferior vena cava filter in addition to anticoagulation prevent the recurrence of pulmonary embolism in high-risk patients?

Bottom line: For patients with pulmonary embolism (PE) who are at high risk of recurrence or who have poor cardiopulmonary reserve, the addition of a retrievable inferior vena cava (IVC) filter plus anticoagulation does not decrease the risk of recurrent PE as compared with anticoagulation alone. Although this study was underpowered to detect a difference if one truly exists, the authors postulate that such a difference would likely be small and thus clinically irrelevant. (LOE = 1b-)

Reference: Mismetti P, Laporte S, Pellerin O, et al, for the PREPIC2 Study Group. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism. JAMA. 2015;313(16):1627–1635.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The utility of retrievable IVC filters added to anticoagulation for the prevention of recurrent PE is unknown. This study included adults who were hospitalized for acute PE associated with lower extremity venous thrombosis and had one additional criterion for severity (older than 75 years, active cancer, chronic cardiopulmonary conditions, recent stroke with leg paralysis, iliocaval or bilateral venous thromboses, or evidence of right ventricular dysfunction or myocardial injury).

The patients were randomized, using concealed allocation, to receive a filter plus anticoagulation or anticoagulation alone. Both groups were anticoagulated for at least 6 months and filters were retrieved at 3 months. More patients in the filter group had chronic respiratory failure at baseline but the groups were otherwise well matched. Analysis was by intention to treat.

At 3 months, the rate of recurrent PE did not differ between the 2 groups (3% in filter group vs 1.5% in control group; P = .50; RR with filter 2.00; 95% CI 0.51-7.89). Additionally, there were no differences detected in venous thromboembolism recurrence, major bleeding, or death at either 3 or 6 months. Complications in the filter group included access site hematomas, filter thromboses, and filter retrieval failures. The authors based their analysis on an expected PE recurrence rate of 8% in the control group but the actual rate was much lower. Although this results in an underpowered study, the authors note that the point estimate of the relative risk still favors the control group and if filters did confer a small advantage it would likely not be clinically meaningful.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the insertion of a retrievable inferior vena cava filter in addition to anticoagulation prevent the recurrence of pulmonary embolism in high-risk patients?

Bottom line: For patients with pulmonary embolism (PE) who are at high risk of recurrence or who have poor cardiopulmonary reserve, the addition of a retrievable inferior vena cava (IVC) filter plus anticoagulation does not decrease the risk of recurrent PE as compared with anticoagulation alone. Although this study was underpowered to detect a difference if one truly exists, the authors postulate that such a difference would likely be small and thus clinically irrelevant. (LOE = 1b-)

Reference: Mismetti P, Laporte S, Pellerin O, et al, for the PREPIC2 Study Group. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism. JAMA. 2015;313(16):1627–1635.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The utility of retrievable IVC filters added to anticoagulation for the prevention of recurrent PE is unknown. This study included adults who were hospitalized for acute PE associated with lower extremity venous thrombosis and had one additional criterion for severity (older than 75 years, active cancer, chronic cardiopulmonary conditions, recent stroke with leg paralysis, iliocaval or bilateral venous thromboses, or evidence of right ventricular dysfunction or myocardial injury).

The patients were randomized, using concealed allocation, to receive a filter plus anticoagulation or anticoagulation alone. Both groups were anticoagulated for at least 6 months and filters were retrieved at 3 months. More patients in the filter group had chronic respiratory failure at baseline but the groups were otherwise well matched. Analysis was by intention to treat.

At 3 months, the rate of recurrent PE did not differ between the 2 groups (3% in filter group vs 1.5% in control group; P = .50; RR with filter 2.00; 95% CI 0.51-7.89). Additionally, there were no differences detected in venous thromboembolism recurrence, major bleeding, or death at either 3 or 6 months. Complications in the filter group included access site hematomas, filter thromboses, and filter retrieval failures. The authors based their analysis on an expected PE recurrence rate of 8% in the control group but the actual rate was much lower. Although this results in an underpowered study, the authors note that the point estimate of the relative risk still favors the control group and if filters did confer a small advantage it would likely not be clinically meaningful.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the insertion of a retrievable inferior vena cava filter in addition to anticoagulation prevent the recurrence of pulmonary embolism in high-risk patients?

Bottom line: For patients with pulmonary embolism (PE) who are at high risk of recurrence or who have poor cardiopulmonary reserve, the addition of a retrievable inferior vena cava (IVC) filter plus anticoagulation does not decrease the risk of recurrent PE as compared with anticoagulation alone. Although this study was underpowered to detect a difference if one truly exists, the authors postulate that such a difference would likely be small and thus clinically irrelevant. (LOE = 1b-)

Reference: Mismetti P, Laporte S, Pellerin O, et al, for the PREPIC2 Study Group. Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism. JAMA. 2015;313(16):1627–1635.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The utility of retrievable IVC filters added to anticoagulation for the prevention of recurrent PE is unknown. This study included adults who were hospitalized for acute PE associated with lower extremity venous thrombosis and had one additional criterion for severity (older than 75 years, active cancer, chronic cardiopulmonary conditions, recent stroke with leg paralysis, iliocaval or bilateral venous thromboses, or evidence of right ventricular dysfunction or myocardial injury).

The patients were randomized, using concealed allocation, to receive a filter plus anticoagulation or anticoagulation alone. Both groups were anticoagulated for at least 6 months and filters were retrieved at 3 months. More patients in the filter group had chronic respiratory failure at baseline but the groups were otherwise well matched. Analysis was by intention to treat.

At 3 months, the rate of recurrent PE did not differ between the 2 groups (3% in filter group vs 1.5% in control group; P = .50; RR with filter 2.00; 95% CI 0.51-7.89). Additionally, there were no differences detected in venous thromboembolism recurrence, major bleeding, or death at either 3 or 6 months. Complications in the filter group included access site hematomas, filter thromboses, and filter retrieval failures. The authors based their analysis on an expected PE recurrence rate of 8% in the control group but the actual rate was much lower. Although this results in an underpowered study, the authors note that the point estimate of the relative risk still favors the control group and if filters did confer a small advantage it would likely not be clinically meaningful.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does a restrictive transfusion strategy improve outcomes following nonemergent cardiac surgery?

Bottom line: For patients undergoing cardiac surgery, using a restrictive transfusion strategy with a hemoglobin threshold of 7.5 g/dL does not decrease serious infections or ischemic events and may lead to increased all-cause mortality at 90 days. (LOE = 1b)

Reference: Murphy GJ, Pike K, Rogers CA, et al, for the TITRe2 Investigators. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015;372(11):997-1008.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

This is yet another study that compares restrictive and liberal transfusion strategies, this time in a cardiac surgery population. These investigators enrolled patients undergoing nonemergency cardiac surgery (mostly coronary artery bypass grafts or valvular procedures) who had a drop of hemoglobin level to below 9 g/dL following surgery.

Patients were randomized, using concealed allocation, to the restrictive transfusion threshold group (threshold hemoglobin 7.5 g/dL) or liberal transfusion threshold group (threshold hemoglobin 9 g/dL). Patients were masked but physicians and nurses were aware of the group assignments.

In the liberal group, patients received one unit of red cell transfusion immediately after randomization followed by an additional unit if the hemoglobin level remained below or dropped below 9 g/dL again during the hospitalization. In the restrictive group, patients received one unit of red cells only if the hemoglobin level dropped below 7.5 g/dL. An additional unit was then given if hemoglobin remained below or dropped below 7.5 g/dL again during the hospitalization. The 2 groups were similar at baseline and analysis was by intention to treat. Not surprisingly, more patients in the liberal strategy group received transfusions than did those in the restrictive strategy group (95% vs 64%).

For the primary outcome—a composite of sepsis, wound infection, stroke, myocardial infarction, gut infarction, or acute kidney injury within 3 months of randomization—there was no significant difference detected between the 2 groups. However, the restrictive group had a higher mortality rate than the liberal group (4.2% vs 2.6%; P = .045). Although this was a secondary outcome, it is possible that a restrictive strategy may be harmful in this cohort, given that they may have less cardiovascular reserve than the general patient population.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does a restrictive transfusion strategy improve outcomes following nonemergent cardiac surgery?

Bottom line: For patients undergoing cardiac surgery, using a restrictive transfusion strategy with a hemoglobin threshold of 7.5 g/dL does not decrease serious infections or ischemic events and may lead to increased all-cause mortality at 90 days. (LOE = 1b)

Reference: Murphy GJ, Pike K, Rogers CA, et al, for the TITRe2 Investigators. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015;372(11):997-1008.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

This is yet another study that compares restrictive and liberal transfusion strategies, this time in a cardiac surgery population. These investigators enrolled patients undergoing nonemergency cardiac surgery (mostly coronary artery bypass grafts or valvular procedures) who had a drop of hemoglobin level to below 9 g/dL following surgery.

Patients were randomized, using concealed allocation, to the restrictive transfusion threshold group (threshold hemoglobin 7.5 g/dL) or liberal transfusion threshold group (threshold hemoglobin 9 g/dL). Patients were masked but physicians and nurses were aware of the group assignments.

In the liberal group, patients received one unit of red cell transfusion immediately after randomization followed by an additional unit if the hemoglobin level remained below or dropped below 9 g/dL again during the hospitalization. In the restrictive group, patients received one unit of red cells only if the hemoglobin level dropped below 7.5 g/dL. An additional unit was then given if hemoglobin remained below or dropped below 7.5 g/dL again during the hospitalization. The 2 groups were similar at baseline and analysis was by intention to treat. Not surprisingly, more patients in the liberal strategy group received transfusions than did those in the restrictive strategy group (95% vs 64%).

For the primary outcome—a composite of sepsis, wound infection, stroke, myocardial infarction, gut infarction, or acute kidney injury within 3 months of randomization—there was no significant difference detected between the 2 groups. However, the restrictive group had a higher mortality rate than the liberal group (4.2% vs 2.6%; P = .045). Although this was a secondary outcome, it is possible that a restrictive strategy may be harmful in this cohort, given that they may have less cardiovascular reserve than the general patient population.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does a restrictive transfusion strategy improve outcomes following nonemergent cardiac surgery?

Bottom line: For patients undergoing cardiac surgery, using a restrictive transfusion strategy with a hemoglobin threshold of 7.5 g/dL does not decrease serious infections or ischemic events and may lead to increased all-cause mortality at 90 days. (LOE = 1b)

Reference: Murphy GJ, Pike K, Rogers CA, et al, for the TITRe2 Investigators. Liberal or restrictive transfusion after cardiac surgery. N Engl J Med 2015;372(11):997-1008.

Study design: Randomized controlled trial (single-blinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location)

Synopsis

This is yet another study that compares restrictive and liberal transfusion strategies, this time in a cardiac surgery population. These investigators enrolled patients undergoing nonemergency cardiac surgery (mostly coronary artery bypass grafts or valvular procedures) who had a drop of hemoglobin level to below 9 g/dL following surgery.

Patients were randomized, using concealed allocation, to the restrictive transfusion threshold group (threshold hemoglobin 7.5 g/dL) or liberal transfusion threshold group (threshold hemoglobin 9 g/dL). Patients were masked but physicians and nurses were aware of the group assignments.

In the liberal group, patients received one unit of red cell transfusion immediately after randomization followed by an additional unit if the hemoglobin level remained below or dropped below 9 g/dL again during the hospitalization. In the restrictive group, patients received one unit of red cells only if the hemoglobin level dropped below 7.5 g/dL. An additional unit was then given if hemoglobin remained below or dropped below 7.5 g/dL again during the hospitalization. The 2 groups were similar at baseline and analysis was by intention to treat. Not surprisingly, more patients in the liberal strategy group received transfusions than did those in the restrictive strategy group (95% vs 64%).

For the primary outcome—a composite of sepsis, wound infection, stroke, myocardial infarction, gut infarction, or acute kidney injury within 3 months of randomization—there was no significant difference detected between the 2 groups. However, the restrictive group had a higher mortality rate than the liberal group (4.2% vs 2.6%; P = .045). Although this was a secondary outcome, it is possible that a restrictive strategy may be harmful in this cohort, given that they may have less cardiovascular reserve than the general patient population.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular treatment improve outcomes for patients with acute ischemic stroke?

Bottom line: For patients with acute ischemic stroke and imaging that suggests a proximal artery occlusion with evidence of good collateral circulation, the use of rapid endovascular treatment improves functional outcomes and reduces mortality. (LOE = 1b)

Reference: Goyal M, Demchuk AM, Menon BK, et al, for the ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372(11):1019-1030.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The recent MR CLEAN study showed improved functional outcomes with the use of endovascular therapy for the treatment of acute ischemic stroke (N Engl J Med 2015;372:11-20).

In this study, investigators enrolled patients with acute disabling ischemic strokes and computed tomographic evidence of a small infarct core, an occluded proximal artery in the anterior circulation, and moderate-to-good collateral circulation. Patients were randomized, using concealed allocation, to receive either usual care or usual care plus rapid endovascular treatment with the use of mechanical thrombectomy and retrievable stents.

The 2 groups had similar baseline characteristics with a mean age of 70 years and a median National Institutes of Health Stroke Scale score of 16 to 17. The median time from stroke onset to reperfusion was 4 hours in the intervention group. The trial was stopped early because of the efficacy of the endovascular therapy. The primary outcome was a common odds ratio, indicating the odds of improvement by 1 point on the modified Rankin scale of 0 to 6 (0 = no symptoms, 1–2 = slight disability, 6 = death). This ratio favored the intervention (common odds ratio 2.6, 95% CI 1.7-3.8; P < .001).

Overall, at 90-day follow-up, the intervention group had a greater proportion of patients with a modified Rankin score of 0–2 (53% vs. 29%; P < .001), as well as decreased mortality (10% vs 19% in control group, P = .04). There was no difference between the 2 groups in the rate of symptomatic intracerebral bleeds.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular treatment improve outcomes for patients with acute ischemic stroke?

Bottom line: For patients with acute ischemic stroke and imaging that suggests a proximal artery occlusion with evidence of good collateral circulation, the use of rapid endovascular treatment improves functional outcomes and reduces mortality. (LOE = 1b)

Reference: Goyal M, Demchuk AM, Menon BK, et al, for the ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372(11):1019-1030.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The recent MR CLEAN study showed improved functional outcomes with the use of endovascular therapy for the treatment of acute ischemic stroke (N Engl J Med 2015;372:11-20).

In this study, investigators enrolled patients with acute disabling ischemic strokes and computed tomographic evidence of a small infarct core, an occluded proximal artery in the anterior circulation, and moderate-to-good collateral circulation. Patients were randomized, using concealed allocation, to receive either usual care or usual care plus rapid endovascular treatment with the use of mechanical thrombectomy and retrievable stents.

The 2 groups had similar baseline characteristics with a mean age of 70 years and a median National Institutes of Health Stroke Scale score of 16 to 17. The median time from stroke onset to reperfusion was 4 hours in the intervention group. The trial was stopped early because of the efficacy of the endovascular therapy. The primary outcome was a common odds ratio, indicating the odds of improvement by 1 point on the modified Rankin scale of 0 to 6 (0 = no symptoms, 1–2 = slight disability, 6 = death). This ratio favored the intervention (common odds ratio 2.6, 95% CI 1.7-3.8; P < .001).

Overall, at 90-day follow-up, the intervention group had a greater proportion of patients with a modified Rankin score of 0–2 (53% vs. 29%; P < .001), as well as decreased mortality (10% vs 19% in control group, P = .04). There was no difference between the 2 groups in the rate of symptomatic intracerebral bleeds.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does endovascular treatment improve outcomes for patients with acute ischemic stroke?

Bottom line: For patients with acute ischemic stroke and imaging that suggests a proximal artery occlusion with evidence of good collateral circulation, the use of rapid endovascular treatment improves functional outcomes and reduces mortality. (LOE = 1b)

Reference: Goyal M, Demchuk AM, Menon BK, et al, for the ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med 2015;372(11):1019-1030.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis

The recent MR CLEAN study showed improved functional outcomes with the use of endovascular therapy for the treatment of acute ischemic stroke (N Engl J Med 2015;372:11-20).

In this study, investigators enrolled patients with acute disabling ischemic strokes and computed tomographic evidence of a small infarct core, an occluded proximal artery in the anterior circulation, and moderate-to-good collateral circulation. Patients were randomized, using concealed allocation, to receive either usual care or usual care plus rapid endovascular treatment with the use of mechanical thrombectomy and retrievable stents.

The 2 groups had similar baseline characteristics with a mean age of 70 years and a median National Institutes of Health Stroke Scale score of 16 to 17. The median time from stroke onset to reperfusion was 4 hours in the intervention group. The trial was stopped early because of the efficacy of the endovascular therapy. The primary outcome was a common odds ratio, indicating the odds of improvement by 1 point on the modified Rankin scale of 0 to 6 (0 = no symptoms, 1–2 = slight disability, 6 = death). This ratio favored the intervention (common odds ratio 2.6, 95% CI 1.7-3.8; P < .001).

Overall, at 90-day follow-up, the intervention group had a greater proportion of patients with a modified Rankin score of 0–2 (53% vs. 29%; P < .001), as well as decreased mortality (10% vs 19% in control group, P = .04). There was no difference between the 2 groups in the rate of symptomatic intracerebral bleeds.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.