Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Clinical question: What are the complications and outcomes of respiratory syncytial virus (RSV) infection in adults requiring hospitalization?

Background: RSV is a common cause of lower respiratory tract infection in infants and young children, leading to hospitalization and even death. RSV has been estimated to affect 3%-10% of adults annually, generally causing mild disease. However, the outcomes of adults with more severe disease are not fully known.

Study design: Retrospective cohort study.

Setting: Three acute care, public hospitals in Hong Kong.

Synopsis: All adult patients hospitalized with laboratory-confirmed RSV infection were included during the defined time period. The main outcome measure was all-cause death, with secondary outcome measures of development of acute respiratory failure requiring ventilator support and total duration of hospitalization among survivors. Additionally, the cohort of RSV patients was compared to patients admitted with seasonal influenza during this same time frame. Patients with pandemic 2009 H1N1 infection were not included.

Of patients with RSV, pneumonia was found in 42.3%, bacterial superinfection in 12.5%, and cardiovascular complications in 14.3%. Additionally, 11.1% developed respiratory failure requiring ventilator support. All-cause mortality at 30 days and 60 days was 9.1% and 11.9%, respectively, with pneumonia the most common cause of death. Use of systemic corticosteroids did not improve survival. When the RSV cohort was compared to the influenza cohort, the patients were similar in age, but the RSV patients were more likely to have underlying chronic lung disease and major systemic co-morbidities. The rate of survival and duration of hospitalization were not significantly different.

Bottom line: RSV infection is an underappreciated cause of lower tract respiratory infection in adults; severe infections that require hospitalization have rates of mortality similar to seasonal influenza. Further research on treatment or immunization is needed.

Citation: Lee N, Lui GC, Wong KT, et al. High morbidity and mortality in adults hospitalized for respiratory syncytial virus infections. Clin Infect Dis. 2013;57(8):1069-1077.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Clinical question: Does ICU strain negatively affect the outcomes of patients transferred to the floor?

Background: With healthcare costs increasing and critical care staff shortages projected, ICUs will have to operate under increasing strain. This may influence decisions on discharging patients from ICUs and could affect patient outcomes.

Study design: Retrospective cohort study.

Setting: One hundred fifty-five ICUs in the United States.

Synopsis: Using the Project IMPACT database, 200,730 adult patients from 107 different hospitals were evaluated in times of ICU strain, determined by the current census, new admissions, and acuity level. Outcomes measured were initial ICU length of stay (LOS), readmission within 72 hours, in-hospital mortality rates, and post-ICU discharge LOS.

Increases of the strain variables from the fifth to the 95th percentiles resulted in a 6.3-hour reduction in ICU LOS, a 2.0-hour decrease in post-ICU discharge LOS, and a 1.0% increase in probability of ICU readmission within 72 hours. Mortality rates during the hospital stay and odds of being discharged home showed no significant change. This study was limited because the ICUs participating were not randomly chosen, outcomes of patients transferred to other hospitals were not measured, and no post-hospital data was collected, so no long-term outcomes could be measured.

Bottom line: ICU bed pressures prompt physicians to allocate ICU resources more efficiently without changing short-term patient outcomes.

Citation: Wagner J, Gabler NB, Ratcliffe SJ, Brown SE, Strom BL, Halpern SD. Outcomes among patients discharged from busy intensive care units. Ann Intern Med. 2013;159(7):447-455.

Clinical question: Does low-dose dopamine or low-dose nesiritide added to diuretic therapy enhance pulmonary volume reduction and preserve renal function in patients with acute heart failure and renal dysfunction, compared to placebo?

Background: Small studies have suggested that low-dose dopamine or low-dose nesiritide may be beneficial in enhancing decongestion and improving renal dysfunction; however, there is ambiguity in overall benefit. Some observational studies suggest that dopamine and nesiritide are associated with higher length of stay, higher costs, and greater mortality.

Study Design: RCT.

Setting: Twenty-six hospital sites in the U.S. and Canada.

Synopsis: Three hundred sixty patients with acute heart failure and renal dysfunction were randomized to receive either nesiritide or dopamine within 24 hours of admission. Within each of these arms, patients were then randomized, in a double-blinded 2:1 fashion, into active treatment versus placebo groups. Treatment groups were compared to the pooled placebo groups.

Two main endpoints were urine output and change in serum cystatin C, from enrollment to 72 hours. Compared with placebo, low-dose dopamine had no significant effect on urine output or serum cystatin C level. Similarly, low-dose nesiritide had no significant effect on 72-hour urine output or serum cystatin C level.

Other studies have shown these drugs to be potentially harmful. Hospitalists should use caution and carefully interpret the relevant evidence when considering their use.

Bottom line: Neither low-dose nesiritide nor low-dose dopamine improved urine output or serum cystatin C levels at 72 hours in patients with acute heart failure and renal dysfunction.

Citation: Chen HH, Anstrom KJ, Givertz MM, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: The ROSE acute heart failure randomized trial. JAMA. 2013;310(23):2533-2543.

Clinical question: Does low-dose dopamine or low-dose nesiritide added to diuretic therapy enhance pulmonary volume reduction and preserve renal function in patients with acute heart failure and renal dysfunction, compared to placebo?

Background: Small studies have suggested that low-dose dopamine or low-dose nesiritide may be beneficial in enhancing decongestion and improving renal dysfunction; however, there is ambiguity in overall benefit. Some observational studies suggest that dopamine and nesiritide are associated with higher length of stay, higher costs, and greater mortality.

Study Design: RCT.

Setting: Twenty-six hospital sites in the U.S. and Canada.

Synopsis: Three hundred sixty patients with acute heart failure and renal dysfunction were randomized to receive either nesiritide or dopamine within 24 hours of admission. Within each of these arms, patients were then randomized, in a double-blinded 2:1 fashion, into active treatment versus placebo groups. Treatment groups were compared to the pooled placebo groups.

Two main endpoints were urine output and change in serum cystatin C, from enrollment to 72 hours. Compared with placebo, low-dose dopamine had no significant effect on urine output or serum cystatin C level. Similarly, low-dose nesiritide had no significant effect on 72-hour urine output or serum cystatin C level.

Other studies have shown these drugs to be potentially harmful. Hospitalists should use caution and carefully interpret the relevant evidence when considering their use.

Bottom line: Neither low-dose nesiritide nor low-dose dopamine improved urine output or serum cystatin C levels at 72 hours in patients with acute heart failure and renal dysfunction.

Citation: Chen HH, Anstrom KJ, Givertz MM, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: The ROSE acute heart failure randomized trial. JAMA. 2013;310(23):2533-2543.

Clinical question: Does low-dose dopamine or low-dose nesiritide added to diuretic therapy enhance pulmonary volume reduction and preserve renal function in patients with acute heart failure and renal dysfunction, compared to placebo?

Background: Small studies have suggested that low-dose dopamine or low-dose nesiritide may be beneficial in enhancing decongestion and improving renal dysfunction; however, there is ambiguity in overall benefit. Some observational studies suggest that dopamine and nesiritide are associated with higher length of stay, higher costs, and greater mortality.

Study Design: RCT.

Setting: Twenty-six hospital sites in the U.S. and Canada.

Synopsis: Three hundred sixty patients with acute heart failure and renal dysfunction were randomized to receive either nesiritide or dopamine within 24 hours of admission. Within each of these arms, patients were then randomized, in a double-blinded 2:1 fashion, into active treatment versus placebo groups. Treatment groups were compared to the pooled placebo groups.

Two main endpoints were urine output and change in serum cystatin C, from enrollment to 72 hours. Compared with placebo, low-dose dopamine had no significant effect on urine output or serum cystatin C level. Similarly, low-dose nesiritide had no significant effect on 72-hour urine output or serum cystatin C level.

Other studies have shown these drugs to be potentially harmful. Hospitalists should use caution and carefully interpret the relevant evidence when considering their use.

Bottom line: Neither low-dose nesiritide nor low-dose dopamine improved urine output or serum cystatin C levels at 72 hours in patients with acute heart failure and renal dysfunction.

Citation: Chen HH, Anstrom KJ, Givertz MM, et al. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: The ROSE acute heart failure randomized trial. JAMA. 2013;310(23):2533-2543.

Clinical question: Does the use and timing of beta blockers in COPD patients experiencing a first myocardial infarction (MI) affect survival after the event?

Background: Beta blockers are effective in reducing mortality and reinfarction after an MI; however, concerns regarding the side effects of beta blockers, such as bronchospasm, continue to limit their use in patients with COPD.

Study design: Population-based cohort study.

Setting: The Myocardial Ischemia National Audit Project, linked to the General Practice Research Database, in the United Kingdom.

Synopsis: Researchers identified 1,063 patients over the age of 18 with COPD admitted to the hospital with a first acute MI. Use of beta blockers during hospitalization was associated with increased overall and one-year survival. Initiation of beta blockers during an MI had a mortality-adjusted hazard ratio of 0.50 (95% CI 0.36 to 0.69; P<0.001; median follow-up time=2.9 years).

Patients already on beta blockers prior to the MI had overall survival-adjusted hazard ratio of 0.59 (95% CI 0.44 to 0.79; P<0.001). Both scenarios showed survival benefits compared to COPD patients who were not prescribed beta blockers. Patients given beta blockers with COPD either during the MI hospitalization or before the event were younger and had fewer comorbidities. This may have accounted for some of the survival bias.

Bottom line: The use of beta blockers in patients with COPD started prior to, or at the time of, hospital admission for a first MI is associated with improved survival.

Citation: Quint JK, Herret E, Bhaskaran K, et al. Effect of ß blockers on mortality after myocardial infarction in adults with COPD: population-based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.

Clinical question: Does the use and timing of beta blockers in COPD patients experiencing a first myocardial infarction (MI) affect survival after the event?

Background: Beta blockers are effective in reducing mortality and reinfarction after an MI; however, concerns regarding the side effects of beta blockers, such as bronchospasm, continue to limit their use in patients with COPD.

Study design: Population-based cohort study.

Setting: The Myocardial Ischemia National Audit Project, linked to the General Practice Research Database, in the United Kingdom.

Synopsis: Researchers identified 1,063 patients over the age of 18 with COPD admitted to the hospital with a first acute MI. Use of beta blockers during hospitalization was associated with increased overall and one-year survival. Initiation of beta blockers during an MI had a mortality-adjusted hazard ratio of 0.50 (95% CI 0.36 to 0.69; P<0.001; median follow-up time=2.9 years).

Patients already on beta blockers prior to the MI had overall survival-adjusted hazard ratio of 0.59 (95% CI 0.44 to 0.79; P<0.001). Both scenarios showed survival benefits compared to COPD patients who were not prescribed beta blockers. Patients given beta blockers with COPD either during the MI hospitalization or before the event were younger and had fewer comorbidities. This may have accounted for some of the survival bias.

Bottom line: The use of beta blockers in patients with COPD started prior to, or at the time of, hospital admission for a first MI is associated with improved survival.

Citation: Quint JK, Herret E, Bhaskaran K, et al. Effect of ß blockers on mortality after myocardial infarction in adults with COPD: population-based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.

Clinical question: Does the use and timing of beta blockers in COPD patients experiencing a first myocardial infarction (MI) affect survival after the event?

Background: Beta blockers are effective in reducing mortality and reinfarction after an MI; however, concerns regarding the side effects of beta blockers, such as bronchospasm, continue to limit their use in patients with COPD.

Study design: Population-based cohort study.

Setting: The Myocardial Ischemia National Audit Project, linked to the General Practice Research Database, in the United Kingdom.

Synopsis: Researchers identified 1,063 patients over the age of 18 with COPD admitted to the hospital with a first acute MI. Use of beta blockers during hospitalization was associated with increased overall and one-year survival. Initiation of beta blockers during an MI had a mortality-adjusted hazard ratio of 0.50 (95% CI 0.36 to 0.69; P<0.001; median follow-up time=2.9 years).

Patients already on beta blockers prior to the MI had overall survival-adjusted hazard ratio of 0.59 (95% CI 0.44 to 0.79; P<0.001). Both scenarios showed survival benefits compared to COPD patients who were not prescribed beta blockers. Patients given beta blockers with COPD either during the MI hospitalization or before the event were younger and had fewer comorbidities. This may have accounted for some of the survival bias.

Bottom line: The use of beta blockers in patients with COPD started prior to, or at the time of, hospital admission for a first MI is associated with improved survival.

Citation: Quint JK, Herret E, Bhaskaran K, et al. Effect of ß blockers on mortality after myocardial infarction in adults with COPD: population-based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.

News that healthcare spending's growth rate slowed in 2013 but is expected to pick up in the next decade isn't all rosy for hospitalists, says a member of SHM's Public Policy Committee.

Committee member Bradley Flansbaum, DO, MPH, SFHM, says he expects the amount of funding going to hospitalists to decrease in the coming years as healthcare reform focuses on keeping patients out of the hospital.

"The slice that's going to be dedicated to inpatient medicine in hospitals is going to shrink," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York City. "From a hospitalist standpoint, I don't think it's kick back, flip open the beer lid, and turn the game on. Things are really going to change."

A report in this month's Health Affairs shows that spending growth in 2013 fell to 3.6%, down from 7.2% annually on average between 1990 and 2008. The decreased rate is attributed to a "sluggish economic recovery, the effects of sequestration, and continued increases in private health insurance cost-sharing requirements," according to the report.

However, the combination of money being pumped into healthcare reform and a growing economy is projected to push up spending by 5.6% this year and 6% annually each year from 2015 to 2023, according to the report. How much of that money will flow into HM depends, in part, on how well the specialty improves patient care and hospital bottom lines, Dr. Flansbaum says. "And teasing out that effect is tough," he says. "Mainly, is it that we're ordering less tests or are the prices going down or neither, and [are] other forces contributing to efficiency gains? Those are very different variables."

News that healthcare spending's growth rate slowed in 2013 but is expected to pick up in the next decade isn't all rosy for hospitalists, says a member of SHM's Public Policy Committee.

Committee member Bradley Flansbaum, DO, MPH, SFHM, says he expects the amount of funding going to hospitalists to decrease in the coming years as healthcare reform focuses on keeping patients out of the hospital.

"The slice that's going to be dedicated to inpatient medicine in hospitals is going to shrink," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York City. "From a hospitalist standpoint, I don't think it's kick back, flip open the beer lid, and turn the game on. Things are really going to change."

A report in this month's Health Affairs shows that spending growth in 2013 fell to 3.6%, down from 7.2% annually on average between 1990 and 2008. The decreased rate is attributed to a "sluggish economic recovery, the effects of sequestration, and continued increases in private health insurance cost-sharing requirements," according to the report.

However, the combination of money being pumped into healthcare reform and a growing economy is projected to push up spending by 5.6% this year and 6% annually each year from 2015 to 2023, according to the report. How much of that money will flow into HM depends, in part, on how well the specialty improves patient care and hospital bottom lines, Dr. Flansbaum says. "And teasing out that effect is tough," he says. "Mainly, is it that we're ordering less tests or are the prices going down or neither, and [are] other forces contributing to efficiency gains? Those are very different variables."

News that healthcare spending's growth rate slowed in 2013 but is expected to pick up in the next decade isn't all rosy for hospitalists, says a member of SHM's Public Policy Committee.

Committee member Bradley Flansbaum, DO, MPH, SFHM, says he expects the amount of funding going to hospitalists to decrease in the coming years as healthcare reform focuses on keeping patients out of the hospital.

"The slice that's going to be dedicated to inpatient medicine in hospitals is going to shrink," says Dr. Flansbaum, a hospitalist at Lenox Hill Hospital in New York City. "From a hospitalist standpoint, I don't think it's kick back, flip open the beer lid, and turn the game on. Things are really going to change."

A report in this month's Health Affairs shows that spending growth in 2013 fell to 3.6%, down from 7.2% annually on average between 1990 and 2008. The decreased rate is attributed to a "sluggish economic recovery, the effects of sequestration, and continued increases in private health insurance cost-sharing requirements," according to the report.

However, the combination of money being pumped into healthcare reform and a growing economy is projected to push up spending by 5.6% this year and 6% annually each year from 2015 to 2023, according to the report. How much of that money will flow into HM depends, in part, on how well the specialty improves patient care and hospital bottom lines, Dr. Flansbaum says. "And teasing out that effect is tough," he says. "Mainly, is it that we're ordering less tests or are the prices going down or neither, and [are] other forces contributing to efficiency gains? Those are very different variables."

Clinical question: What is the long-term efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation (Afib)?

Background: Edoxaban is an oral factor Xa inhibitor approved for use in Japan for the prevention of venous thromboembolism after orthopedic surgery. No specific antidote for edoxaban exists, but hemostatic agents can reverse its anticoagulation effect.

Study design: RCT.

Setting: More than 1,300 centers in 46 countries.

Synopsis: Researchers randomized 21,105 patients in a 1:1:1 ratio to receive warfarin (goal INR of 2-3), low-dose edoxaban, or high-dose edoxoban. All patients received two sets of drugs, either active warfarin with placebo edoxaban or active edoxaban (high- or low-dose) and placebo warfarin (with sham INRs drawn), and were followed for a median of 2.8 years.

The annualized rate of stroke or systemic embolic event was 1.5% in the warfarin group, compared with 1.18% in the high-dose edoxaban group (hazard ratio 0.79; P<0.001) and 1.61% in the low-dose edoxaban group (hazard ratio 1.07; P=0.005). Annualized rate of major bleeding was 3.43% with warfarin, 2.75% with high-dose edoxoban (hazard ratio 0.80; P<0.001), and 1.61% with low-dose edoxaban (hazard ratio 0.47; P<0.001).

Both edoxaban regimens were noninferior to warfarin for the prevention of stroke or systemic emboli. The rates of cardiovascular events, bleeding, or death from any cause was lower with both doses of edoxaban as compared with warfarin.

Bottom line: Once-daily edoxaban is noninferior to warfarin for the prevention of stroke or systemic emboli and is associated with lower rates of bleeding and death.

Citation: Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2013;369(22):2093-2104.

Clinical question: What is the long-term efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation (Afib)?

Background: Edoxaban is an oral factor Xa inhibitor approved for use in Japan for the prevention of venous thromboembolism after orthopedic surgery. No specific antidote for edoxaban exists, but hemostatic agents can reverse its anticoagulation effect.

Study design: RCT.

Setting: More than 1,300 centers in 46 countries.

Synopsis: Researchers randomized 21,105 patients in a 1:1:1 ratio to receive warfarin (goal INR of 2-3), low-dose edoxaban, or high-dose edoxoban. All patients received two sets of drugs, either active warfarin with placebo edoxaban or active edoxaban (high- or low-dose) and placebo warfarin (with sham INRs drawn), and were followed for a median of 2.8 years.

The annualized rate of stroke or systemic embolic event was 1.5% in the warfarin group, compared with 1.18% in the high-dose edoxaban group (hazard ratio 0.79; P<0.001) and 1.61% in the low-dose edoxaban group (hazard ratio 1.07; P=0.005). Annualized rate of major bleeding was 3.43% with warfarin, 2.75% with high-dose edoxoban (hazard ratio 0.80; P<0.001), and 1.61% with low-dose edoxaban (hazard ratio 0.47; P<0.001).

Both edoxaban regimens were noninferior to warfarin for the prevention of stroke or systemic emboli. The rates of cardiovascular events, bleeding, or death from any cause was lower with both doses of edoxaban as compared with warfarin.

Bottom line: Once-daily edoxaban is noninferior to warfarin for the prevention of stroke or systemic emboli and is associated with lower rates of bleeding and death.

Citation: Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2013;369(22):2093-2104.

Clinical question: What is the long-term efficacy and safety of edoxaban compared with warfarin in patients with atrial fibrillation (Afib)?

Background: Edoxaban is an oral factor Xa inhibitor approved for use in Japan for the prevention of venous thromboembolism after orthopedic surgery. No specific antidote for edoxaban exists, but hemostatic agents can reverse its anticoagulation effect.

Study design: RCT.

Setting: More than 1,300 centers in 46 countries.

Synopsis: Researchers randomized 21,105 patients in a 1:1:1 ratio to receive warfarin (goal INR of 2-3), low-dose edoxaban, or high-dose edoxoban. All patients received two sets of drugs, either active warfarin with placebo edoxaban or active edoxaban (high- or low-dose) and placebo warfarin (with sham INRs drawn), and were followed for a median of 2.8 years.

The annualized rate of stroke or systemic embolic event was 1.5% in the warfarin group, compared with 1.18% in the high-dose edoxaban group (hazard ratio 0.79; P<0.001) and 1.61% in the low-dose edoxaban group (hazard ratio 1.07; P=0.005). Annualized rate of major bleeding was 3.43% with warfarin, 2.75% with high-dose edoxoban (hazard ratio 0.80; P<0.001), and 1.61% with low-dose edoxaban (hazard ratio 0.47; P<0.001).

Both edoxaban regimens were noninferior to warfarin for the prevention of stroke or systemic emboli. The rates of cardiovascular events, bleeding, or death from any cause was lower with both doses of edoxaban as compared with warfarin.

Bottom line: Once-daily edoxaban is noninferior to warfarin for the prevention of stroke or systemic emboli and is associated with lower rates of bleeding and death.

Citation: Giugliano RP, Ruff CT, Braunwald E, et al. Edoxaban versus warfarin in patients with atrial fibrillation. New Engl J Med. 2013;369(22):2093-2104.

Clinical question: Can intervention by pharmacists and physicians improve compliance to cardio-protective medications?

Background: Adherence to cardio-protective medications in the year after hospitalization for acute coronary syndrome is poor.

Study design: RCT.

Setting: Four Department of Veterans Affairs medical centers.

Synopsis: The intervention consisted of pharmacist-led medication reconciliation, patient education, pharmacist and PCP +/- cardiologist collaboration, and voice messaging. The outcome measured was the proportion of patients adherent to medication regimens based on a mean proportion of days covered (PDC) >0.80 in the year after discharge, using pharmacy refill data for clopidogrel, beta blockers, statins, and ACEI/ARBs.

Two hundred forty-one patients (95.3%) completed the study. In the intervention group, 89.3% of patients were adherent vs. 73.9% in the usual care group (P=0.003). Mean PDC was higher in the intervention group (0.94 vs. 0.87; P<0.001). A greater proportion of intervention patients were adherent to clopidogrel (86.8% vs. 70.7%; P=0.03), statins (93.2% vs. 71.3%; P<0.001), and ACEI/ARBs (93.1% vs. 81.7%; P=0.03), but not beta blockers (88.1% vs. 84.8%; P=0.59). There were no statistically significant differences in the proportion of patients who achieved blood pressure and LDL-C level goals.

Bottom line: An interdisciplinary, multi-faceted intervention increased medication compliance in the year after discharge for ACS but did not improve blood pressure or LDL-C levels.

Citation: Ho PM, Lambert-Kerzner A, Carey EP, et al. Multifaceted intervention to improve medication adherence and secondary prevention measures after acute coronary syndrome hospital discharge. JAMA Intern Med. 2014;174(2):186-193.

Clinical question: Can intervention by pharmacists and physicians improve compliance to cardio-protective medications?

Background: Adherence to cardio-protective medications in the year after hospitalization for acute coronary syndrome is poor.

Study design: RCT.

Setting: Four Department of Veterans Affairs medical centers.

Synopsis: The intervention consisted of pharmacist-led medication reconciliation, patient education, pharmacist and PCP +/- cardiologist collaboration, and voice messaging. The outcome measured was the proportion of patients adherent to medication regimens based on a mean proportion of days covered (PDC) >0.80 in the year after discharge, using pharmacy refill data for clopidogrel, beta blockers, statins, and ACEI/ARBs.

Two hundred forty-one patients (95.3%) completed the study. In the intervention group, 89.3% of patients were adherent vs. 73.9% in the usual care group (P=0.003). Mean PDC was higher in the intervention group (0.94 vs. 0.87; P<0.001). A greater proportion of intervention patients were adherent to clopidogrel (86.8% vs. 70.7%; P=0.03), statins (93.2% vs. 71.3%; P<0.001), and ACEI/ARBs (93.1% vs. 81.7%; P=0.03), but not beta blockers (88.1% vs. 84.8%; P=0.59). There were no statistically significant differences in the proportion of patients who achieved blood pressure and LDL-C level goals.

Bottom line: An interdisciplinary, multi-faceted intervention increased medication compliance in the year after discharge for ACS but did not improve blood pressure or LDL-C levels.

Citation: Ho PM, Lambert-Kerzner A, Carey EP, et al. Multifaceted intervention to improve medication adherence and secondary prevention measures after acute coronary syndrome hospital discharge. JAMA Intern Med. 2014;174(2):186-193.

Clinical question: Can intervention by pharmacists and physicians improve compliance to cardio-protective medications?

Background: Adherence to cardio-protective medications in the year after hospitalization for acute coronary syndrome is poor.

Study design: RCT.

Setting: Four Department of Veterans Affairs medical centers.

Synopsis: The intervention consisted of pharmacist-led medication reconciliation, patient education, pharmacist and PCP +/- cardiologist collaboration, and voice messaging. The outcome measured was the proportion of patients adherent to medication regimens based on a mean proportion of days covered (PDC) >0.80 in the year after discharge, using pharmacy refill data for clopidogrel, beta blockers, statins, and ACEI/ARBs.

Two hundred forty-one patients (95.3%) completed the study. In the intervention group, 89.3% of patients were adherent vs. 73.9% in the usual care group (P=0.003). Mean PDC was higher in the intervention group (0.94 vs. 0.87; P<0.001). A greater proportion of intervention patients were adherent to clopidogrel (86.8% vs. 70.7%; P=0.03), statins (93.2% vs. 71.3%; P<0.001), and ACEI/ARBs (93.1% vs. 81.7%; P=0.03), but not beta blockers (88.1% vs. 84.8%; P=0.59). There were no statistically significant differences in the proportion of patients who achieved blood pressure and LDL-C level goals.

Bottom line: An interdisciplinary, multi-faceted intervention increased medication compliance in the year after discharge for ACS but did not improve blood pressure or LDL-C levels.

Citation: Ho PM, Lambert-Kerzner A, Carey EP, et al. Multifaceted intervention to improve medication adherence and secondary prevention measures after acute coronary syndrome hospital discharge. JAMA Intern Med. 2014;174(2):186-193.

Clinical question: What risk factors identified at the onset of illness are associated with recurrent C. diff infection (CDI)?

Background: After initial infection, 10%–25% of patients experience recurrent CDI. The identification of patients at high risk of recurrence would be beneficial for therapeutic decision-making.

Study design: Retrospective cohort study.

Setting: Large, urban, academic medical center.

Synopsis: Authors included 4,196 patients with an initial infection defined by a positive C. diff toxin assay and unformed stools. A repeat positive toxin within 42 days of completing treatment for the initial infection represented recurrent CDI. Multiple characteristics were examined to identify risks of recurrent infection, including demographics and those related to acute and chronic disease. A logistic regression model was used to identify risk factors for recurrence. Recurrent CDI occurred in 425 patients (10.1%). Age, fluoroquinolone and high-risk antibiotic use, community-acquired healthcare-associated infection, multiple hospitalizations, and gastric acid suppression were found to predict recurrent infection through multivariate analysis. Limitations of the study included potential confounding, use of observational data, and generalizability given the urban academic medical center setting. This prediction model differs from previously developed models in that it identifies factors present at the onset of infection.

Bottom line: Multiple factors identified at the onset of illness can predict CDI recurrence.

Citation: Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER. Development and validation of a recurrent Clostridium difficile risk-prediction model. J Hosp Med. 2014;9(7):418-423. TH

Clinical question: What risk factors identified at the onset of illness are associated with recurrent C. diff infection (CDI)?

Background: After initial infection, 10%–25% of patients experience recurrent CDI. The identification of patients at high risk of recurrence would be beneficial for therapeutic decision-making.

Study design: Retrospective cohort study.

Setting: Large, urban, academic medical center.

Synopsis: Authors included 4,196 patients with an initial infection defined by a positive C. diff toxin assay and unformed stools. A repeat positive toxin within 42 days of completing treatment for the initial infection represented recurrent CDI. Multiple characteristics were examined to identify risks of recurrent infection, including demographics and those related to acute and chronic disease. A logistic regression model was used to identify risk factors for recurrence. Recurrent CDI occurred in 425 patients (10.1%). Age, fluoroquinolone and high-risk antibiotic use, community-acquired healthcare-associated infection, multiple hospitalizations, and gastric acid suppression were found to predict recurrent infection through multivariate analysis. Limitations of the study included potential confounding, use of observational data, and generalizability given the urban academic medical center setting. This prediction model differs from previously developed models in that it identifies factors present at the onset of infection.

Bottom line: Multiple factors identified at the onset of illness can predict CDI recurrence.

Citation: Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER. Development and validation of a recurrent Clostridium difficile risk-prediction model. J Hosp Med. 2014;9(7):418-423. TH

Clinical question: What risk factors identified at the onset of illness are associated with recurrent C. diff infection (CDI)?

Background: After initial infection, 10%–25% of patients experience recurrent CDI. The identification of patients at high risk of recurrence would be beneficial for therapeutic decision-making.

Study design: Retrospective cohort study.

Setting: Large, urban, academic medical center.

Synopsis: Authors included 4,196 patients with an initial infection defined by a positive C. diff toxin assay and unformed stools. A repeat positive toxin within 42 days of completing treatment for the initial infection represented recurrent CDI. Multiple characteristics were examined to identify risks of recurrent infection, including demographics and those related to acute and chronic disease. A logistic regression model was used to identify risk factors for recurrence. Recurrent CDI occurred in 425 patients (10.1%). Age, fluoroquinolone and high-risk antibiotic use, community-acquired healthcare-associated infection, multiple hospitalizations, and gastric acid suppression were found to predict recurrent infection through multivariate analysis. Limitations of the study included potential confounding, use of observational data, and generalizability given the urban academic medical center setting. This prediction model differs from previously developed models in that it identifies factors present at the onset of infection.

Bottom line: Multiple factors identified at the onset of illness can predict CDI recurrence.

Citation: Zilberberg MD, Reske K, Olsen M, Yan Y, Dubberke ER. Development and validation of a recurrent Clostridium difficile risk-prediction model. J Hosp Med. 2014;9(7):418-423. TH

Clinical question: In critically ill patients admitted to the ICU with hypovolemic shock, does the use of colloid for fluid resuscitation, compared with crystalloid, improve mortality?

Background: The current Surviving Sepsis Campaign guidelines recommend crystalloids as the preferred fluid for resuscitation of patients with hypovolemic shock; however, evidence supporting the choice of intravenous colloid vs. crystalloid solutions for management of hypovolemic shock is weak.

Study design: RCT.

Setting: International, multi-center study.

Synopsis: Researchers randomized 2,857 adult patients who were admitted to an ICU and required fluid resuscitation for acute hypovolemia to receive either crystalloids or colloids.

At 28 days, there were 359 deaths (25.4%) in the colloids group vs. 390 deaths (27.0%) in the crystalloids group (P=0.26). At 90 days, there were 434 deaths (30.7%) in the colloids group vs. 493 deaths (34.2%) in the crystalloids group (P=0.03).

Renal replacement therapy was used in 11.0% of the colloids group vs. 12.5% of the crystalloids group (P=0.19). There were more days alive without mechanical ventilation in the colloids group vs. the crystalloids group at seven days (P=0.01) and at 28 days (P=0.01), and there were more days alive without vasopressor therapy in the colloids group vs. the crystalloids group at seven days (P=0.04) and at 28 days (P=0.03).

Major limitations of the study included the use of open-labeled fluids during allocation, so the initial investigators were not blinded to the type of fluid. Moreover, the study compared two therapeutic strategies (colloid vs. crystalloids) rather than two types of molecules.

Bottom line: In ICU patients with hypovolemia requiring resuscitation, the use of colloids vs. crystalloids did not result in a significant difference in 28-day mortality; however, 90-day mortality was lower among patients receiving colloids.

Citation: Annane D, Siami S, Jaber S, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality of critically ill patients presenting with hypovolemic shock: the CRISTAL randomization trial. JAMA. 2013;310(17):1809-1817

Clinical question: In critically ill patients admitted to the ICU with hypovolemic shock, does the use of colloid for fluid resuscitation, compared with crystalloid, improve mortality?

Background: The current Surviving Sepsis Campaign guidelines recommend crystalloids as the preferred fluid for resuscitation of patients with hypovolemic shock; however, evidence supporting the choice of intravenous colloid vs. crystalloid solutions for management of hypovolemic shock is weak.

Study design: RCT.

Setting: International, multi-center study.

Synopsis: Researchers randomized 2,857 adult patients who were admitted to an ICU and required fluid resuscitation for acute hypovolemia to receive either crystalloids or colloids.

At 28 days, there were 359 deaths (25.4%) in the colloids group vs. 390 deaths (27.0%) in the crystalloids group (P=0.26). At 90 days, there were 434 deaths (30.7%) in the colloids group vs. 493 deaths (34.2%) in the crystalloids group (P=0.03).

Renal replacement therapy was used in 11.0% of the colloids group vs. 12.5% of the crystalloids group (P=0.19). There were more days alive without mechanical ventilation in the colloids group vs. the crystalloids group at seven days (P=0.01) and at 28 days (P=0.01), and there were more days alive without vasopressor therapy in the colloids group vs. the crystalloids group at seven days (P=0.04) and at 28 days (P=0.03).

Major limitations of the study included the use of open-labeled fluids during allocation, so the initial investigators were not blinded to the type of fluid. Moreover, the study compared two therapeutic strategies (colloid vs. crystalloids) rather than two types of molecules.

Bottom line: In ICU patients with hypovolemia requiring resuscitation, the use of colloids vs. crystalloids did not result in a significant difference in 28-day mortality; however, 90-day mortality was lower among patients receiving colloids.

Citation: Annane D, Siami S, Jaber S, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality of critically ill patients presenting with hypovolemic shock: the CRISTAL randomization trial. JAMA. 2013;310(17):1809-1817

Clinical question: In critically ill patients admitted to the ICU with hypovolemic shock, does the use of colloid for fluid resuscitation, compared with crystalloid, improve mortality?

Background: The current Surviving Sepsis Campaign guidelines recommend crystalloids as the preferred fluid for resuscitation of patients with hypovolemic shock; however, evidence supporting the choice of intravenous colloid vs. crystalloid solutions for management of hypovolemic shock is weak.

Study design: RCT.

Setting: International, multi-center study.

Synopsis: Researchers randomized 2,857 adult patients who were admitted to an ICU and required fluid resuscitation for acute hypovolemia to receive either crystalloids or colloids.

At 28 days, there were 359 deaths (25.4%) in the colloids group vs. 390 deaths (27.0%) in the crystalloids group (P=0.26). At 90 days, there were 434 deaths (30.7%) in the colloids group vs. 493 deaths (34.2%) in the crystalloids group (P=0.03).

Renal replacement therapy was used in 11.0% of the colloids group vs. 12.5% of the crystalloids group (P=0.19). There were more days alive without mechanical ventilation in the colloids group vs. the crystalloids group at seven days (P=0.01) and at 28 days (P=0.01), and there were more days alive without vasopressor therapy in the colloids group vs. the crystalloids group at seven days (P=0.04) and at 28 days (P=0.03).

Major limitations of the study included the use of open-labeled fluids during allocation, so the initial investigators were not blinded to the type of fluid. Moreover, the study compared two therapeutic strategies (colloid vs. crystalloids) rather than two types of molecules.

Bottom line: In ICU patients with hypovolemia requiring resuscitation, the use of colloids vs. crystalloids did not result in a significant difference in 28-day mortality; however, 90-day mortality was lower among patients receiving colloids.

Citation: Annane D, Siami S, Jaber S, et al. Effects of fluid resuscitation with colloids vs crystalloids on mortality of critically ill patients presenting with hypovolemic shock: the CRISTAL randomization trial. JAMA. 2013;310(17):1809-1817

Clinical question: How does “triple rule out” (TRO) computed tomographic (CT) angiography compare to other imaging modalities in evaluating coronary and other life-threatening etiologies of chest pain, such as pulmonary embolism (PE) and aortic dissection?

Background: TRO CT angiography is a noninvasive technology that evaluates the coronary arteries, thoracic aorta, and pulmonary vasculature simultaneously. Comparison with other tests in the diagnosis of common clinical conditions is useful information for clinical practice.

Study design: Systematic review and meta-analysis.

Setting: Systematic review of 11 studies (one randomized, 10 observational).

Synopsis: Using an enrolled population of 3,539 patients, TRO CT was compared to other imaging modalities on the basis of image quality, diagnostic accuracy, radiation, and contrast volume. When TRO CT was compared to dedicated CT scans, no significant imaging difference was discovered. TRO CT detected CAD with a sensitivity of 94.3% (95% CI, 89.1% to 97.5%, I2=58.2%) and specificity of 97.4% (95% CI, 96.1% to 98.5%, I2=91.2%).

An insufficient number of patients with PE or aortic dissection were studied to generate diagnostic accuracy for these conditions. TRO CT involved greater radiation exposure and contrast exposure than non-TRO CT.

This study reports high accuracy of TRO CT in the diagnosis of coronary artery disease. Due to the low prevalence of patients with PE or aortic dissection (<1%), the data cannot be extrapolated to these conditions.

Bottom line: Although TRO CT is highly accurate for detecting coronary artery disease, there is insufficient data to recommend its use for the diagnosis of PE or aortic dissection.

Citation: Ayaram D, Bellolio MF, Murad MH, et al. Triple rule-out computed tomographic angiography for chest pain: a diagnostic systematic review and meta-analysis. Acad Emerg Med. 2013;20(9):861-871.

Clinical question: How does “triple rule out” (TRO) computed tomographic (CT) angiography compare to other imaging modalities in evaluating coronary and other life-threatening etiologies of chest pain, such as pulmonary embolism (PE) and aortic dissection?

Background: TRO CT angiography is a noninvasive technology that evaluates the coronary arteries, thoracic aorta, and pulmonary vasculature simultaneously. Comparison with other tests in the diagnosis of common clinical conditions is useful information for clinical practice.

Study design: Systematic review and meta-analysis.

Setting: Systematic review of 11 studies (one randomized, 10 observational).

Synopsis: Using an enrolled population of 3,539 patients, TRO CT was compared to other imaging modalities on the basis of image quality, diagnostic accuracy, radiation, and contrast volume. When TRO CT was compared to dedicated CT scans, no significant imaging difference was discovered. TRO CT detected CAD with a sensitivity of 94.3% (95% CI, 89.1% to 97.5%, I2=58.2%) and specificity of 97.4% (95% CI, 96.1% to 98.5%, I2=91.2%).

An insufficient number of patients with PE or aortic dissection were studied to generate diagnostic accuracy for these conditions. TRO CT involved greater radiation exposure and contrast exposure than non-TRO CT.

This study reports high accuracy of TRO CT in the diagnosis of coronary artery disease. Due to the low prevalence of patients with PE or aortic dissection (<1%), the data cannot be extrapolated to these conditions.

Bottom line: Although TRO CT is highly accurate for detecting coronary artery disease, there is insufficient data to recommend its use for the diagnosis of PE or aortic dissection.

Citation: Ayaram D, Bellolio MF, Murad MH, et al. Triple rule-out computed tomographic angiography for chest pain: a diagnostic systematic review and meta-analysis. Acad Emerg Med. 2013;20(9):861-871.

Clinical question: How does “triple rule out” (TRO) computed tomographic (CT) angiography compare to other imaging modalities in evaluating coronary and other life-threatening etiologies of chest pain, such as pulmonary embolism (PE) and aortic dissection?

Background: TRO CT angiography is a noninvasive technology that evaluates the coronary arteries, thoracic aorta, and pulmonary vasculature simultaneously. Comparison with other tests in the diagnosis of common clinical conditions is useful information for clinical practice.

Study design: Systematic review and meta-analysis.

Setting: Systematic review of 11 studies (one randomized, 10 observational).

Synopsis: Using an enrolled population of 3,539 patients, TRO CT was compared to other imaging modalities on the basis of image quality, diagnostic accuracy, radiation, and contrast volume. When TRO CT was compared to dedicated CT scans, no significant imaging difference was discovered. TRO CT detected CAD with a sensitivity of 94.3% (95% CI, 89.1% to 97.5%, I2=58.2%) and specificity of 97.4% (95% CI, 96.1% to 98.5%, I2=91.2%).

An insufficient number of patients with PE or aortic dissection were studied to generate diagnostic accuracy for these conditions. TRO CT involved greater radiation exposure and contrast exposure than non-TRO CT.

This study reports high accuracy of TRO CT in the diagnosis of coronary artery disease. Due to the low prevalence of patients with PE or aortic dissection (<1%), the data cannot be extrapolated to these conditions.

Bottom line: Although TRO CT is highly accurate for detecting coronary artery disease, there is insufficient data to recommend its use for the diagnosis of PE or aortic dissection.

Citation: Ayaram D, Bellolio MF, Murad MH, et al. Triple rule-out computed tomographic angiography for chest pain: a diagnostic systematic review and meta-analysis. Acad Emerg Med. 2013;20(9):861-871.