Rebecca Calabrese, MD

Clinical question: Among patients discharged from the hospital, how do patient-reported outcome (PRO) measures change after discharge, and can they predict readmission or ED visit?

Background: Variables to predict 30-day rehospitalizations of discharged general medical patients have been looked into, but not many strategies have incorporated PRO measures in predictive models.

Study design: Longitudinal cohort study.

Setting: Patients discharged from an urban safety-net hospital that serves 128 municipalities in northeastern Illinois, including the city of Chicago.

Synopsis: One hundred ninety-six patients completed the initial survey; completion rates were 98%, 90%, and 88% for the 30-, 90-, and 180-day follow-up surveys, respectively. The Memorial Symptom Assessment Scale (MSAS) and the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health short form assessing general self-rated health (GSRH), global physical health (GPH), and global mental health (GMH) were administered. In-hospital assessments of GMH and GSRH predicted 14-day reutilization, whereas post-hospitalization assessments of MSAS and GPH predicted subsequent utilizations. Notable limitations of the study include small sample size with high proportion of uninsured and racial/ethnic minorities and inability to count utilization at hospital(s) other than the hospital studied.

Bottom line: PRO measures are likely to be useful predictors in clinical medicine. More research is needed to improve the generalizability of PRO measures. Perhaps determination of specific measures of high predictive value may be more useful.

Citation: Hinami K, Smith J, Deamant CD, DuBeshter K, Trick WE. When do patient-reported outcome measures inform readmission risk? J Hosp Med. 2015;10(5):294-300.

Clinical question: Among patients discharged from the hospital, how do patient-reported outcome (PRO) measures change after discharge, and can they predict readmission or ED visit?

Background: Variables to predict 30-day rehospitalizations of discharged general medical patients have been looked into, but not many strategies have incorporated PRO measures in predictive models.

Study design: Longitudinal cohort study.

Setting: Patients discharged from an urban safety-net hospital that serves 128 municipalities in northeastern Illinois, including the city of Chicago.

Synopsis: One hundred ninety-six patients completed the initial survey; completion rates were 98%, 90%, and 88% for the 30-, 90-, and 180-day follow-up surveys, respectively. The Memorial Symptom Assessment Scale (MSAS) and the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health short form assessing general self-rated health (GSRH), global physical health (GPH), and global mental health (GMH) were administered. In-hospital assessments of GMH and GSRH predicted 14-day reutilization, whereas post-hospitalization assessments of MSAS and GPH predicted subsequent utilizations. Notable limitations of the study include small sample size with high proportion of uninsured and racial/ethnic minorities and inability to count utilization at hospital(s) other than the hospital studied.

Bottom line: PRO measures are likely to be useful predictors in clinical medicine. More research is needed to improve the generalizability of PRO measures. Perhaps determination of specific measures of high predictive value may be more useful.

Citation: Hinami K, Smith J, Deamant CD, DuBeshter K, Trick WE. When do patient-reported outcome measures inform readmission risk? J Hosp Med. 2015;10(5):294-300.

Clinical question: Among patients discharged from the hospital, how do patient-reported outcome (PRO) measures change after discharge, and can they predict readmission or ED visit?

Background: Variables to predict 30-day rehospitalizations of discharged general medical patients have been looked into, but not many strategies have incorporated PRO measures in predictive models.

Study design: Longitudinal cohort study.

Setting: Patients discharged from an urban safety-net hospital that serves 128 municipalities in northeastern Illinois, including the city of Chicago.

Synopsis: One hundred ninety-six patients completed the initial survey; completion rates were 98%, 90%, and 88% for the 30-, 90-, and 180-day follow-up surveys, respectively. The Memorial Symptom Assessment Scale (MSAS) and the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health short form assessing general self-rated health (GSRH), global physical health (GPH), and global mental health (GMH) were administered. In-hospital assessments of GMH and GSRH predicted 14-day reutilization, whereas post-hospitalization assessments of MSAS and GPH predicted subsequent utilizations. Notable limitations of the study include small sample size with high proportion of uninsured and racial/ethnic minorities and inability to count utilization at hospital(s) other than the hospital studied.

Bottom line: PRO measures are likely to be useful predictors in clinical medicine. More research is needed to improve the generalizability of PRO measures. Perhaps determination of specific measures of high predictive value may be more useful.

Citation: Hinami K, Smith J, Deamant CD, DuBeshter K, Trick WE. When do patient-reported outcome measures inform readmission risk? J Hosp Med. 2015;10(5):294-300.

Clinical question: Is there a standardized way to identify doctors at high risk of incurring repeated medicolegal events?

Background: Medicolegal agencies react to episodes of substandard care rather than intervening to prevent them due to lack of robust prediction tools at the individual practitioner level. Various studies have tried to predict complaints at the individual practitioner level accurately but had limited success.

Study design: Retrospective cohort study.

Setting: Commissions in all Australian states, except South Australia, with 70,200 practicing doctors.

Synopsis: Researchers used administrative data to analyze a national sample of 13,849 formal complaints, which were lodged by patients in Australia over a 12-year period against 8,424 doctors. Using multivariate logistic regression analysis, predictors for subsequent complaints within two years of an index complaint were estimated. These predictors were used in a simple predictive algorithm, the PRONE (Predicted Risk Of New Event), a score designed for application at the doctor level. PRONE is a 22-point scoring system that estimates a doctor’s future complaint risk based on specialty, sex, the number of previous complaints, and the time since the last complaint.

Because the scoring system has strong validity and reliability, regulators could harness such information to target quality improvement interventions and prevent substandard care and patient dissatisfaction.

Bottom line: The PRONE score appears to be a valid method for assessing individual doctors’ risks of attracting recurrent complaints.

Citation: Spittal MJ, Bismark MM, Studdert DM. The PRONE score: an algorithm for predicting doctors risks of formal patient complaints using routinely collected administrative data. BMJ Qual Saf. 2015;24(6):360-368.

Clinical question: Is there a standardized way to identify doctors at high risk of incurring repeated medicolegal events?

Background: Medicolegal agencies react to episodes of substandard care rather than intervening to prevent them due to lack of robust prediction tools at the individual practitioner level. Various studies have tried to predict complaints at the individual practitioner level accurately but had limited success.

Study design: Retrospective cohort study.

Setting: Commissions in all Australian states, except South Australia, with 70,200 practicing doctors.

Synopsis: Researchers used administrative data to analyze a national sample of 13,849 formal complaints, which were lodged by patients in Australia over a 12-year period against 8,424 doctors. Using multivariate logistic regression analysis, predictors for subsequent complaints within two years of an index complaint were estimated. These predictors were used in a simple predictive algorithm, the PRONE (Predicted Risk Of New Event), a score designed for application at the doctor level. PRONE is a 22-point scoring system that estimates a doctor’s future complaint risk based on specialty, sex, the number of previous complaints, and the time since the last complaint.

Because the scoring system has strong validity and reliability, regulators could harness such information to target quality improvement interventions and prevent substandard care and patient dissatisfaction.

Bottom line: The PRONE score appears to be a valid method for assessing individual doctors’ risks of attracting recurrent complaints.

Citation: Spittal MJ, Bismark MM, Studdert DM. The PRONE score: an algorithm for predicting doctors risks of formal patient complaints using routinely collected administrative data. BMJ Qual Saf. 2015;24(6):360-368.

Clinical question: Is there a standardized way to identify doctors at high risk of incurring repeated medicolegal events?

Background: Medicolegal agencies react to episodes of substandard care rather than intervening to prevent them due to lack of robust prediction tools at the individual practitioner level. Various studies have tried to predict complaints at the individual practitioner level accurately but had limited success.

Study design: Retrospective cohort study.

Setting: Commissions in all Australian states, except South Australia, with 70,200 practicing doctors.

Synopsis: Researchers used administrative data to analyze a national sample of 13,849 formal complaints, which were lodged by patients in Australia over a 12-year period against 8,424 doctors. Using multivariate logistic regression analysis, predictors for subsequent complaints within two years of an index complaint were estimated. These predictors were used in a simple predictive algorithm, the PRONE (Predicted Risk Of New Event), a score designed for application at the doctor level. PRONE is a 22-point scoring system that estimates a doctor’s future complaint risk based on specialty, sex, the number of previous complaints, and the time since the last complaint.

Because the scoring system has strong validity and reliability, regulators could harness such information to target quality improvement interventions and prevent substandard care and patient dissatisfaction.

Bottom line: The PRONE score appears to be a valid method for assessing individual doctors’ risks of attracting recurrent complaints.

Citation: Spittal MJ, Bismark MM, Studdert DM. The PRONE score: an algorithm for predicting doctors risks of formal patient complaints using routinely collected administrative data. BMJ Qual Saf. 2015;24(6):360-368.

Clinical question: Can novel configured rapid response teams (RRTs) improve non-ICU cardiopulmonary arrest (CPA) and overall hospital mortality rate?

Background: RRTs are primarily executed in hospital settings to avert non-ICU CPA through early detection and intervention. Prevailing evidence has not shown consistent clear benefit of RRTs in this regard.

Study design: A parallel-controlled, before-after design.

Setting: Two urban university hospitals with approximately 500 medical/surgical beds.

Synopsis: Researchers compared annual non-ICU CPA rates from two university hospitals with newly configured RRTs (implemented in November 2007) from July 2005 through June 2011 and found a decline in the incidence of non-ICU CPA to 1.1 from 2.7 per 1000 discharges (P<0.0001) while comparing pre- (2005/2006 to 2006/2007) to post- RRT implementation (2007-2011), respectively. Post-implementation, the overall hospital mortality dropped to 1.74% from 2.12% (P<0.001). With year-over-year, the RRT activation was found to be inversely related to Code Blue activations (r=-0.68, P<0.001), while the case mix index coefficients were still high.

The study lacks internal validation and may carry bias by including just one pre-implementation year (2006) data. It demonstrates that the rounding of unit manager (charge nurse) on “at risk” patients might avert decompensation; however, there was no determination of their decision-making process, with regard to RRT activation. No comparison was done with other RRT configurations.

Bottom line: Novel configured RRTs may improve non-ICU CPA and overall hospital mortality rate.

Citation: Davis DP, Aguilar SA, Graham PG, et al. A novel configuration of a traditional rapid response team decreases non-intensive care unit arrests and overall hospital mortality. J Hosp Med. 2015;10(6):352-357.

Clinical question: Can novel configured rapid response teams (RRTs) improve non-ICU cardiopulmonary arrest (CPA) and overall hospital mortality rate?

Background: RRTs are primarily executed in hospital settings to avert non-ICU CPA through early detection and intervention. Prevailing evidence has not shown consistent clear benefit of RRTs in this regard.

Study design: A parallel-controlled, before-after design.

Setting: Two urban university hospitals with approximately 500 medical/surgical beds.

Synopsis: Researchers compared annual non-ICU CPA rates from two university hospitals with newly configured RRTs (implemented in November 2007) from July 2005 through June 2011 and found a decline in the incidence of non-ICU CPA to 1.1 from 2.7 per 1000 discharges (P<0.0001) while comparing pre- (2005/2006 to 2006/2007) to post- RRT implementation (2007-2011), respectively. Post-implementation, the overall hospital mortality dropped to 1.74% from 2.12% (P<0.001). With year-over-year, the RRT activation was found to be inversely related to Code Blue activations (r=-0.68, P<0.001), while the case mix index coefficients were still high.

The study lacks internal validation and may carry bias by including just one pre-implementation year (2006) data. It demonstrates that the rounding of unit manager (charge nurse) on “at risk” patients might avert decompensation; however, there was no determination of their decision-making process, with regard to RRT activation. No comparison was done with other RRT configurations.

Bottom line: Novel configured RRTs may improve non-ICU CPA and overall hospital mortality rate.

Citation: Davis DP, Aguilar SA, Graham PG, et al. A novel configuration of a traditional rapid response team decreases non-intensive care unit arrests and overall hospital mortality. J Hosp Med. 2015;10(6):352-357.

Clinical question: Can novel configured rapid response teams (RRTs) improve non-ICU cardiopulmonary arrest (CPA) and overall hospital mortality rate?

Background: RRTs are primarily executed in hospital settings to avert non-ICU CPA through early detection and intervention. Prevailing evidence has not shown consistent clear benefit of RRTs in this regard.

Study design: A parallel-controlled, before-after design.

Setting: Two urban university hospitals with approximately 500 medical/surgical beds.

Synopsis: Researchers compared annual non-ICU CPA rates from two university hospitals with newly configured RRTs (implemented in November 2007) from July 2005 through June 2011 and found a decline in the incidence of non-ICU CPA to 1.1 from 2.7 per 1000 discharges (P<0.0001) while comparing pre- (2005/2006 to 2006/2007) to post- RRT implementation (2007-2011), respectively. Post-implementation, the overall hospital mortality dropped to 1.74% from 2.12% (P<0.001). With year-over-year, the RRT activation was found to be inversely related to Code Blue activations (r=-0.68, P<0.001), while the case mix index coefficients were still high.

The study lacks internal validation and may carry bias by including just one pre-implementation year (2006) data. It demonstrates that the rounding of unit manager (charge nurse) on “at risk” patients might avert decompensation; however, there was no determination of their decision-making process, with regard to RRT activation. No comparison was done with other RRT configurations.

Bottom line: Novel configured RRTs may improve non-ICU CPA and overall hospital mortality rate.

Citation: Davis DP, Aguilar SA, Graham PG, et al. A novel configuration of a traditional rapid response team decreases non-intensive care unit arrests and overall hospital mortality. J Hosp Med. 2015;10(6):352-357.

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.

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: 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.

Clinical question: Do patients who experience overcrowding and long waits in the emergency department (ED) prefer boarding within ED hallways or within inpatient medical unit hallways?

Background: Boarding of admitted patients in EDs can be problematic, especially with regard to patient safety and patient satisfaction. Patient satisfaction data comparing boarding in the ED versus boarding in an inpatient unit hallway is limited.

Study design: Post-discharge, structured, telephone satisfaction survey.

Setting: Suburban, university-based teaching hospital.

Synopsis: A group of patients who experienced hallway boarding in the ED and then hallway boarding on the inpatient medical unit were identified. They were contacted by phone and asked to take a survey on their experience; 105 of 110 patients identified agreed. Patients were asked to rate their location preference with regard to various aspects of care. A five-point Likert scale consisting of the following answers was used: ED hallway much better, ED hallway better, no preference, inpatient hallway better, and inpatient hallway much better.

The inpatient hallway was the overall preferred location in 85% of respondents. Respondents preferred inpatient boarding with regard to multiple other parameters: rest, 85%; safety, 83%; confidentiality, 82%; treatment, 78%; comfort, 79%; quiet, 84%; staff availability, 84%; and privacy, 84%. For no item was there a preference for boarding in the ED.

Patient demographics in this hospital may differ from other settings and should be considered when applying the results. With Hospital Consumer Assessment of Healthcare Providers and Systems scores and ED throughput being publicly reported, further studies in this area would be valuable.

Bottom line: In a post-discharge telephone survey, patients preferred boarding in inpatient unit hallways rather than boarding in the ED.

Citation: Viccellio P, Zito JA, Sayage V, et al. Patients overwhelmingly prefer inpatient boarding to emergency department boarding. J Emerg Med. 2013;45(6):942-946.

Clinical question: Do patients who experience overcrowding and long waits in the emergency department (ED) prefer boarding within ED hallways or within inpatient medical unit hallways?

Background: Boarding of admitted patients in EDs can be problematic, especially with regard to patient safety and patient satisfaction. Patient satisfaction data comparing boarding in the ED versus boarding in an inpatient unit hallway is limited.

Study design: Post-discharge, structured, telephone satisfaction survey.

Setting: Suburban, university-based teaching hospital.

Synopsis: A group of patients who experienced hallway boarding in the ED and then hallway boarding on the inpatient medical unit were identified. They were contacted by phone and asked to take a survey on their experience; 105 of 110 patients identified agreed. Patients were asked to rate their location preference with regard to various aspects of care. A five-point Likert scale consisting of the following answers was used: ED hallway much better, ED hallway better, no preference, inpatient hallway better, and inpatient hallway much better.

The inpatient hallway was the overall preferred location in 85% of respondents. Respondents preferred inpatient boarding with regard to multiple other parameters: rest, 85%; safety, 83%; confidentiality, 82%; treatment, 78%; comfort, 79%; quiet, 84%; staff availability, 84%; and privacy, 84%. For no item was there a preference for boarding in the ED.

Patient demographics in this hospital may differ from other settings and should be considered when applying the results. With Hospital Consumer Assessment of Healthcare Providers and Systems scores and ED throughput being publicly reported, further studies in this area would be valuable.

Bottom line: In a post-discharge telephone survey, patients preferred boarding in inpatient unit hallways rather than boarding in the ED.

Citation: Viccellio P, Zito JA, Sayage V, et al. Patients overwhelmingly prefer inpatient boarding to emergency department boarding. J Emerg Med. 2013;45(6):942-946.

Clinical question: Do patients who experience overcrowding and long waits in the emergency department (ED) prefer boarding within ED hallways or within inpatient medical unit hallways?

Background: Boarding of admitted patients in EDs can be problematic, especially with regard to patient safety and patient satisfaction. Patient satisfaction data comparing boarding in the ED versus boarding in an inpatient unit hallway is limited.

Study design: Post-discharge, structured, telephone satisfaction survey.

Setting: Suburban, university-based teaching hospital.

Synopsis: A group of patients who experienced hallway boarding in the ED and then hallway boarding on the inpatient medical unit were identified. They were contacted by phone and asked to take a survey on their experience; 105 of 110 patients identified agreed. Patients were asked to rate their location preference with regard to various aspects of care. A five-point Likert scale consisting of the following answers was used: ED hallway much better, ED hallway better, no preference, inpatient hallway better, and inpatient hallway much better.

The inpatient hallway was the overall preferred location in 85% of respondents. Respondents preferred inpatient boarding with regard to multiple other parameters: rest, 85%; safety, 83%; confidentiality, 82%; treatment, 78%; comfort, 79%; quiet, 84%; staff availability, 84%; and privacy, 84%. For no item was there a preference for boarding in the ED.

Patient demographics in this hospital may differ from other settings and should be considered when applying the results. With Hospital Consumer Assessment of Healthcare Providers and Systems scores and ED throughput being publicly reported, further studies in this area would be valuable.

Bottom line: In a post-discharge telephone survey, patients preferred boarding in inpatient unit hallways rather than boarding in the ED.

Citation: Viccellio P, Zito JA, Sayage V, et al. Patients overwhelmingly prefer inpatient boarding to emergency department boarding. J Emerg Med. 2013;45(6):942-946.