Frank Wharton, MD

Clinical question: Is there any difference between oral and intravenous methylprednisolone for multiple sclerosis relapses?

Background: When relapses of multiple sclerosis occur, studies have shown that intravenous steroids are the treatment of choice. Prior Cochrane meta-analyses have not found any significant difference between intravenous and oral treatments; however, the studies all have had limitations. This study was designed to provide a statistically significant answer.

Study design: Randomized, double-blinded, noninferiority trial.

Setting: Thirteen multiple sclerosis centers in France.

Synopsis: Patients were selected if they had had a relapse within the previous 15 days; the mean time was seven days. One hundred patients were in the oral steroid group, and 99 were in the intravenous steroid group. Each group received 1 g of methylprednisolone daily for three days. In addition, each group received saline infusions or placebo capsules to keep the study blind.

After 28 days, 81% of the oral group and 80% of the intravenous group had improvements of their symptoms. Side effects from the medications were similar as well.

The study was limited by the fixed dosing (1 g daily) that was not bioequivalent. Also, MRIs, although not always used in relapses, could have added more objective information, as everyone was followed clinically using the Kurtzke Functional System Scale.

Bottom line: Consider using oral instead of IV steroids in patients with relapsing multiple sclerosis.

Citation: Le Page E, Veillard D, Laplaud DA, et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2015;386(9997):974-981.

Clinical question: Is there any difference between oral and intravenous methylprednisolone for multiple sclerosis relapses?

Background: When relapses of multiple sclerosis occur, studies have shown that intravenous steroids are the treatment of choice. Prior Cochrane meta-analyses have not found any significant difference between intravenous and oral treatments; however, the studies all have had limitations. This study was designed to provide a statistically significant answer.

Study design: Randomized, double-blinded, noninferiority trial.

Setting: Thirteen multiple sclerosis centers in France.

Synopsis: Patients were selected if they had had a relapse within the previous 15 days; the mean time was seven days. One hundred patients were in the oral steroid group, and 99 were in the intravenous steroid group. Each group received 1 g of methylprednisolone daily for three days. In addition, each group received saline infusions or placebo capsules to keep the study blind.

After 28 days, 81% of the oral group and 80% of the intravenous group had improvements of their symptoms. Side effects from the medications were similar as well.

The study was limited by the fixed dosing (1 g daily) that was not bioequivalent. Also, MRIs, although not always used in relapses, could have added more objective information, as everyone was followed clinically using the Kurtzke Functional System Scale.

Bottom line: Consider using oral instead of IV steroids in patients with relapsing multiple sclerosis.

Citation: Le Page E, Veillard D, Laplaud DA, et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2015;386(9997):974-981.

Clinical question: Is there any difference between oral and intravenous methylprednisolone for multiple sclerosis relapses?

Background: When relapses of multiple sclerosis occur, studies have shown that intravenous steroids are the treatment of choice. Prior Cochrane meta-analyses have not found any significant difference between intravenous and oral treatments; however, the studies all have had limitations. This study was designed to provide a statistically significant answer.

Study design: Randomized, double-blinded, noninferiority trial.

Setting: Thirteen multiple sclerosis centers in France.

Synopsis: Patients were selected if they had had a relapse within the previous 15 days; the mean time was seven days. One hundred patients were in the oral steroid group, and 99 were in the intravenous steroid group. Each group received 1 g of methylprednisolone daily for three days. In addition, each group received saline infusions or placebo capsules to keep the study blind.

After 28 days, 81% of the oral group and 80% of the intravenous group had improvements of their symptoms. Side effects from the medications were similar as well.

The study was limited by the fixed dosing (1 g daily) that was not bioequivalent. Also, MRIs, although not always used in relapses, could have added more objective information, as everyone was followed clinically using the Kurtzke Functional System Scale.

Bottom line: Consider using oral instead of IV steroids in patients with relapsing multiple sclerosis.

Citation: Le Page E, Veillard D, Laplaud DA, et al. Oral versus intravenous high-dose methylprednisolone for treatment of relapses in patients with multiple sclerosis (COPOUSEP): a randomised, controlled, double-blind, non-inferiority trial. Lancet. 2015;386(9997):974-981.

Clinical question: Are there any differences in care and outcomes for in-hospital versus community-onset stroke?

Background: In-hospital stroke accounts for 4%-17% of all strokes. Hospitalists and other non-neurological services have to identify and treat subsequent stroke in their patients. There is not much literature detailing the differences between hospitalized stroke patients and those admitted for stroke.

Study design: Prospective cohort study.

Setting: All regional stroke centers in Ontario, Canada.

Synopsis: During a period of nine years, 973 in-hospital and 28,837 community-acquired stroke patients were followed. Compared to community-acquired stroke patients, in-hospital stroke patients had longer time to confirmatory neuroimaging, lower use of thrombolysis, lower use of investigational tests, and longer length of stay, and they were more likely to be disabled or dead at discharge. The two cohorts had similar mortality outcomes after discharge at 30 days and one year, after adjusting for multiple factors. Interestingly, in-hospital stroke patients were more likely to be given the proper medications for secondary prevention at discharge.

The study was limited in that the authors were unable to research why in-hospital patients did not get timely diagnosis and comparable treatment. The admission diagnoses were not enough for the authors to determine if that condition mattered in care. Secondary analysis found that in-hospital stroke patients were older and had more comorbidities (i.e., diabetes, hypertension, hyperlipidemia, and atrial fibrillation). The primary reason in-hospital stroke patients did not get thrombolysis was because of a contraindication.

Bottom line: In-hospital stroke patients have increased lengths of stay and more disability compared to community-onset stroke patients.

Citation: Saltman AP, Silver FL, Fang J, Stamplecoski M, Kapral MK. Care and outcomes of patients with in-hospital stroke. JAMA Neurol. 2015;72(7):749-755.

Clinical question: Are there any differences in care and outcomes for in-hospital versus community-onset stroke?

Background: In-hospital stroke accounts for 4%-17% of all strokes. Hospitalists and other non-neurological services have to identify and treat subsequent stroke in their patients. There is not much literature detailing the differences between hospitalized stroke patients and those admitted for stroke.

Study design: Prospective cohort study.

Setting: All regional stroke centers in Ontario, Canada.

Synopsis: During a period of nine years, 973 in-hospital and 28,837 community-acquired stroke patients were followed. Compared to community-acquired stroke patients, in-hospital stroke patients had longer time to confirmatory neuroimaging, lower use of thrombolysis, lower use of investigational tests, and longer length of stay, and they were more likely to be disabled or dead at discharge. The two cohorts had similar mortality outcomes after discharge at 30 days and one year, after adjusting for multiple factors. Interestingly, in-hospital stroke patients were more likely to be given the proper medications for secondary prevention at discharge.

The study was limited in that the authors were unable to research why in-hospital patients did not get timely diagnosis and comparable treatment. The admission diagnoses were not enough for the authors to determine if that condition mattered in care. Secondary analysis found that in-hospital stroke patients were older and had more comorbidities (i.e., diabetes, hypertension, hyperlipidemia, and atrial fibrillation). The primary reason in-hospital stroke patients did not get thrombolysis was because of a contraindication.

Bottom line: In-hospital stroke patients have increased lengths of stay and more disability compared to community-onset stroke patients.

Citation: Saltman AP, Silver FL, Fang J, Stamplecoski M, Kapral MK. Care and outcomes of patients with in-hospital stroke. JAMA Neurol. 2015;72(7):749-755.

Clinical question: Are there any differences in care and outcomes for in-hospital versus community-onset stroke?

Background: In-hospital stroke accounts for 4%-17% of all strokes. Hospitalists and other non-neurological services have to identify and treat subsequent stroke in their patients. There is not much literature detailing the differences between hospitalized stroke patients and those admitted for stroke.

Study design: Prospective cohort study.

Setting: All regional stroke centers in Ontario, Canada.

Synopsis: During a period of nine years, 973 in-hospital and 28,837 community-acquired stroke patients were followed. Compared to community-acquired stroke patients, in-hospital stroke patients had longer time to confirmatory neuroimaging, lower use of thrombolysis, lower use of investigational tests, and longer length of stay, and they were more likely to be disabled or dead at discharge. The two cohorts had similar mortality outcomes after discharge at 30 days and one year, after adjusting for multiple factors. Interestingly, in-hospital stroke patients were more likely to be given the proper medications for secondary prevention at discharge.

The study was limited in that the authors were unable to research why in-hospital patients did not get timely diagnosis and comparable treatment. The admission diagnoses were not enough for the authors to determine if that condition mattered in care. Secondary analysis found that in-hospital stroke patients were older and had more comorbidities (i.e., diabetes, hypertension, hyperlipidemia, and atrial fibrillation). The primary reason in-hospital stroke patients did not get thrombolysis was because of a contraindication.

Bottom line: In-hospital stroke patients have increased lengths of stay and more disability compared to community-onset stroke patients.

Citation: Saltman AP, Silver FL, Fang J, Stamplecoski M, Kapral MK. Care and outcomes of patients with in-hospital stroke. JAMA Neurol. 2015;72(7):749-755.

Clinical question: Is lung ultrasound a useful tool for helping to diagnose acute decompensated heart failure (ADHF)?

Background: Lung ultrasound is an emerging bedside tool that has been promoted to help evaluate lung water content to help clinicians differentiate ADHF from other causes of dyspnea.

Study design: Prospective, multicenter, observational cohort study.

Setting: Seven EDs in Italy.

Synopsis: A total of 1,005 patients were enrolled in the study. Upon presentation to the ED, patients received a standard workup, including history, physical examination, EKG, and arterial blood gas sampling. Physicians were asked to render a diagnosis of ADHF or noncardiogenic dyspnea. The same physician then performed a lung ultrasound and rendered a revised diagnosis based on the ultrasound findings. A second ED physician and cardiologist, blinded to the ultrasound results, reviewed the medical record and rendered a final diagnosis as to the cause of the patient’s dyspnea.

The ultrasound approach had a higher accuracy than clinical evaluation alone in differentiating ADHF from noncardiac causes of dyspnea (97% vs. 85.3%). The authors also report a higher sensitivity compared to chest X-ray alone (69.5%) and natriuretic peptide testing (85%).

Bottom line: Lung ultrasound combined with clinical evaluation may improve the accuracy of ADHF diagnosis, but its usefulness may be limited by the need for ED physicians to have some degree of expertise in the use of ultrasound.

Citation: Pivetta E, Goffi A, Lupia E, et al. Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: a SIMEU multicenter study. Chest. 2015;148(1):202-210.

Clinical question: Is lung ultrasound a useful tool for helping to diagnose acute decompensated heart failure (ADHF)?

Background: Lung ultrasound is an emerging bedside tool that has been promoted to help evaluate lung water content to help clinicians differentiate ADHF from other causes of dyspnea.

Study design: Prospective, multicenter, observational cohort study.

Setting: Seven EDs in Italy.

Synopsis: A total of 1,005 patients were enrolled in the study. Upon presentation to the ED, patients received a standard workup, including history, physical examination, EKG, and arterial blood gas sampling. Physicians were asked to render a diagnosis of ADHF or noncardiogenic dyspnea. The same physician then performed a lung ultrasound and rendered a revised diagnosis based on the ultrasound findings. A second ED physician and cardiologist, blinded to the ultrasound results, reviewed the medical record and rendered a final diagnosis as to the cause of the patient’s dyspnea.

The ultrasound approach had a higher accuracy than clinical evaluation alone in differentiating ADHF from noncardiac causes of dyspnea (97% vs. 85.3%). The authors also report a higher sensitivity compared to chest X-ray alone (69.5%) and natriuretic peptide testing (85%).

Bottom line: Lung ultrasound combined with clinical evaluation may improve the accuracy of ADHF diagnosis, but its usefulness may be limited by the need for ED physicians to have some degree of expertise in the use of ultrasound.

Citation: Pivetta E, Goffi A, Lupia E, et al. Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: a SIMEU multicenter study. Chest. 2015;148(1):202-210.

Clinical question: Is lung ultrasound a useful tool for helping to diagnose acute decompensated heart failure (ADHF)?

Background: Lung ultrasound is an emerging bedside tool that has been promoted to help evaluate lung water content to help clinicians differentiate ADHF from other causes of dyspnea.

Study design: Prospective, multicenter, observational cohort study.

Setting: Seven EDs in Italy.

Synopsis: A total of 1,005 patients were enrolled in the study. Upon presentation to the ED, patients received a standard workup, including history, physical examination, EKG, and arterial blood gas sampling. Physicians were asked to render a diagnosis of ADHF or noncardiogenic dyspnea. The same physician then performed a lung ultrasound and rendered a revised diagnosis based on the ultrasound findings. A second ED physician and cardiologist, blinded to the ultrasound results, reviewed the medical record and rendered a final diagnosis as to the cause of the patient’s dyspnea.

The ultrasound approach had a higher accuracy than clinical evaluation alone in differentiating ADHF from noncardiac causes of dyspnea (97% vs. 85.3%). The authors also report a higher sensitivity compared to chest X-ray alone (69.5%) and natriuretic peptide testing (85%).

Bottom line: Lung ultrasound combined with clinical evaluation may improve the accuracy of ADHF diagnosis, but its usefulness may be limited by the need for ED physicians to have some degree of expertise in the use of ultrasound.

Citation: Pivetta E, Goffi A, Lupia E, et al. Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: a SIMEU multicenter study. Chest. 2015;148(1):202-210.

Clinical question: When evaluating the intermediate-risk patient with chest pain, should coronary computed tomography angiography (CCTA) be used instead of myocardial perfusion imaging (MPI)?

Background: CCTA has been shown in prior randomized controlled trials to save time and money compared to other protocols, including stress ECG, echocardiogram, and MPI. Less information is available as to whether CCTA provides a better selection of patients for cardiac catheterization compared to MPI.

Study design: Randomized, controlled, comparative effectiveness trial.

Setting: Telemetry ward of an urban medical center.

Synopsis: Four hundred patients admitted with chest pain and an intermediate, pre-test probability of coronary artery disease were randomized to either CCTA or MPI. Patients were predominantly female, were ethnically varied, and had a mean age of 57 years.

Study results showed no significant difference in rates of cardiac catheterization that did not lead to revascularization at one-year follow-up. Specifically, 7.5% of patients in the CCTA group underwent catheterization not leading to revascularization, compared to 10% in the MPI group.

One limitation of the study is that it was conducted at a single site. Furthermore, the decision to proceed to catheterization was made clinically and not based on a predefined algorithm.

Bottom line: CCTA and MPI are both acceptable choices to determine the need for invasive testing in patients admitted with chest pain.

Citation: Levsky JM, Spevack DM, Travin MI, et al. Coronary computed tomography angiography versus radionuclide myocardial perfusion imaging in patients with chest pain admitted to telemetry: a randomized trial. Ann Intern Med. 2015;163(3):174-183.

Clinical question: When evaluating the intermediate-risk patient with chest pain, should coronary computed tomography angiography (CCTA) be used instead of myocardial perfusion imaging (MPI)?

Background: CCTA has been shown in prior randomized controlled trials to save time and money compared to other protocols, including stress ECG, echocardiogram, and MPI. Less information is available as to whether CCTA provides a better selection of patients for cardiac catheterization compared to MPI.

Study design: Randomized, controlled, comparative effectiveness trial.

Setting: Telemetry ward of an urban medical center.

Synopsis: Four hundred patients admitted with chest pain and an intermediate, pre-test probability of coronary artery disease were randomized to either CCTA or MPI. Patients were predominantly female, were ethnically varied, and had a mean age of 57 years.

Study results showed no significant difference in rates of cardiac catheterization that did not lead to revascularization at one-year follow-up. Specifically, 7.5% of patients in the CCTA group underwent catheterization not leading to revascularization, compared to 10% in the MPI group.

One limitation of the study is that it was conducted at a single site. Furthermore, the decision to proceed to catheterization was made clinically and not based on a predefined algorithm.

Bottom line: CCTA and MPI are both acceptable choices to determine the need for invasive testing in patients admitted with chest pain.

Citation: Levsky JM, Spevack DM, Travin MI, et al. Coronary computed tomography angiography versus radionuclide myocardial perfusion imaging in patients with chest pain admitted to telemetry: a randomized trial. Ann Intern Med. 2015;163(3):174-183.

Clinical question: When evaluating the intermediate-risk patient with chest pain, should coronary computed tomography angiography (CCTA) be used instead of myocardial perfusion imaging (MPI)?

Background: CCTA has been shown in prior randomized controlled trials to save time and money compared to other protocols, including stress ECG, echocardiogram, and MPI. Less information is available as to whether CCTA provides a better selection of patients for cardiac catheterization compared to MPI.

Study design: Randomized, controlled, comparative effectiveness trial.

Setting: Telemetry ward of an urban medical center.

Synopsis: Four hundred patients admitted with chest pain and an intermediate, pre-test probability of coronary artery disease were randomized to either CCTA or MPI. Patients were predominantly female, were ethnically varied, and had a mean age of 57 years.

Study results showed no significant difference in rates of cardiac catheterization that did not lead to revascularization at one-year follow-up. Specifically, 7.5% of patients in the CCTA group underwent catheterization not leading to revascularization, compared to 10% in the MPI group.

One limitation of the study is that it was conducted at a single site. Furthermore, the decision to proceed to catheterization was made clinically and not based on a predefined algorithm.

Bottom line: CCTA and MPI are both acceptable choices to determine the need for invasive testing in patients admitted with chest pain.

Citation: Levsky JM, Spevack DM, Travin MI, et al. Coronary computed tomography angiography versus radionuclide myocardial perfusion imaging in patients with chest pain admitted to telemetry: a randomized trial. Ann Intern Med. 2015;163(3):174-183.

Clinical question: Can a low-risk patient newly diagnosed with VTE in the ED be immediately discharged home on a direct factor Xa inhibitor?

Background: Studies have shown that rivaroxaban incurs a risk of 2.1% in VTE recurrence and of 9.4% in clinically relevant major and non-major bleeding (in an average 208 days follow-up). More information is required to determine if similar success can be achieved by discharging low-risk patients from the ED.

Study design: Prospective, observational study.

Setting: EDs at two urban, teaching hospitals.

Synopsis: After fulfilling the criteria for low risk, 106 patients were discharged from the ED with DVT, pulmonary embolism (PE), or both. Most patients were 50 years or younger and had unprovoked VTE. Three of the 106 patients had recurrence of VTE (2.8%, 95% CI=0.6% to 8%) at a mean duration of 389 days. No patient had a major bleeding event.

In this small study, fewer than 80% of patients discharged had at least one clinic follow-up; the majority of these patients (75%) followed up in a clinic staffed by ED physicians. Therefore, ability for close follow-up must be taken into consideration prior to discharge from the ED.

Moreover, one to two days post-discharge, a member of the care team called the patient to confirm their ability to fill the rivaroxaban prescription and to answer other questions related to the new diagnosis.

Bottom line: With close follow-up and confirmation of the ability to fill a rivaroxaban prescription, patients with low-risk VTE may be discharged home from the ED.

Citation: Beam DM, Kahler ZP, Kline JA. Immediate discharge and home treatment with rivaroxaban of low-risk venous thromboembolism diagnosed in two U.S. emergency departments: a one-year preplanned analysis. Acad Emerg Med. 2015;22(7):788-795.

Clinical question: Can a low-risk patient newly diagnosed with VTE in the ED be immediately discharged home on a direct factor Xa inhibitor?

Background: Studies have shown that rivaroxaban incurs a risk of 2.1% in VTE recurrence and of 9.4% in clinically relevant major and non-major bleeding (in an average 208 days follow-up). More information is required to determine if similar success can be achieved by discharging low-risk patients from the ED.

Study design: Prospective, observational study.

Setting: EDs at two urban, teaching hospitals.

Synopsis: After fulfilling the criteria for low risk, 106 patients were discharged from the ED with DVT, pulmonary embolism (PE), or both. Most patients were 50 years or younger and had unprovoked VTE. Three of the 106 patients had recurrence of VTE (2.8%, 95% CI=0.6% to 8%) at a mean duration of 389 days. No patient had a major bleeding event.

In this small study, fewer than 80% of patients discharged had at least one clinic follow-up; the majority of these patients (75%) followed up in a clinic staffed by ED physicians. Therefore, ability for close follow-up must be taken into consideration prior to discharge from the ED.

Moreover, one to two days post-discharge, a member of the care team called the patient to confirm their ability to fill the rivaroxaban prescription and to answer other questions related to the new diagnosis.

Bottom line: With close follow-up and confirmation of the ability to fill a rivaroxaban prescription, patients with low-risk VTE may be discharged home from the ED.

Citation: Beam DM, Kahler ZP, Kline JA. Immediate discharge and home treatment with rivaroxaban of low-risk venous thromboembolism diagnosed in two U.S. emergency departments: a one-year preplanned analysis. Acad Emerg Med. 2015;22(7):788-795.

Clinical question: Can a low-risk patient newly diagnosed with VTE in the ED be immediately discharged home on a direct factor Xa inhibitor?

Background: Studies have shown that rivaroxaban incurs a risk of 2.1% in VTE recurrence and of 9.4% in clinically relevant major and non-major bleeding (in an average 208 days follow-up). More information is required to determine if similar success can be achieved by discharging low-risk patients from the ED.

Study design: Prospective, observational study.

Setting: EDs at two urban, teaching hospitals.

Synopsis: After fulfilling the criteria for low risk, 106 patients were discharged from the ED with DVT, pulmonary embolism (PE), or both. Most patients were 50 years or younger and had unprovoked VTE. Three of the 106 patients had recurrence of VTE (2.8%, 95% CI=0.6% to 8%) at a mean duration of 389 days. No patient had a major bleeding event.

In this small study, fewer than 80% of patients discharged had at least one clinic follow-up; the majority of these patients (75%) followed up in a clinic staffed by ED physicians. Therefore, ability for close follow-up must be taken into consideration prior to discharge from the ED.

Moreover, one to two days post-discharge, a member of the care team called the patient to confirm their ability to fill the rivaroxaban prescription and to answer other questions related to the new diagnosis.

Bottom line: With close follow-up and confirmation of the ability to fill a rivaroxaban prescription, patients with low-risk VTE may be discharged home from the ED.

Citation: Beam DM, Kahler ZP, Kline JA. Immediate discharge and home treatment with rivaroxaban of low-risk venous thromboembolism diagnosed in two U.S. emergency departments: a one-year preplanned analysis. Acad Emerg Med. 2015;22(7):788-795.

Clinical question: How would an evidence-based clinical pathway for cellulitis affect process metrics, patient outcomes, and clinical cost?

Background: Cellulitis is a common hospital problem, but its evaluation and treatment vary widely. Specifically, broad-spectrum antibiotics and imaging studies are overutilized when compared to recommended guidelines. A standardized clinical pathway is proposed as a possible solution.

Study design: Retrospective, observational, pre-/post-intervention study.

Setting: University of Utah Health Sciences Center, Salt Lake City.

Synopsis: A multidisciplinary team created a guideline-based care pathway for cellulitis and enrolled 677 adult patients for retrospective analysis during a two-year period. The study showed an overall 59% decrease in the odds of ordering broad-spectrum antibiotics, 23% decrease in pharmacy cost, 44% decrease in laboratory cost, and 13% decrease in overall facility cost, pre-/post-intervention. It also demonstrated no adverse effect on length of stay or 30-day readmission rates.

Given the retrospective, single-center nature of this study, as well as some baseline characteristic differences between enrolled patients, careful conclusions regarding external validity on diverse patient populations must be considered; however, the history of clinical care pathways supports many of the study’s findings. The results make a compelling case for hospitalist groups to implement similar cellulitis pathways and research their effectiveness.

Bottom line: Clinical care pathways for cellulitis provide an opportunity to improve antibiotic stewardship and lower hospital costs without compromising quality of care.

Citation: Yarbrough PM, Kukhareva PV, Spivak ES, Hopkins C, Kawamoto K. Evidence-based care pathway for cellulitis improves process, clinical, and cost outcomes [published online ahead of print July 28, 2015]. J Hosp Med. doi: 10.1002/jhm.2433.

Clinical question: How would an evidence-based clinical pathway for cellulitis affect process metrics, patient outcomes, and clinical cost?

Background: Cellulitis is a common hospital problem, but its evaluation and treatment vary widely. Specifically, broad-spectrum antibiotics and imaging studies are overutilized when compared to recommended guidelines. A standardized clinical pathway is proposed as a possible solution.

Study design: Retrospective, observational, pre-/post-intervention study.

Setting: University of Utah Health Sciences Center, Salt Lake City.

Synopsis: A multidisciplinary team created a guideline-based care pathway for cellulitis and enrolled 677 adult patients for retrospective analysis during a two-year period. The study showed an overall 59% decrease in the odds of ordering broad-spectrum antibiotics, 23% decrease in pharmacy cost, 44% decrease in laboratory cost, and 13% decrease in overall facility cost, pre-/post-intervention. It also demonstrated no adverse effect on length of stay or 30-day readmission rates.

Given the retrospective, single-center nature of this study, as well as some baseline characteristic differences between enrolled patients, careful conclusions regarding external validity on diverse patient populations must be considered; however, the history of clinical care pathways supports many of the study’s findings. The results make a compelling case for hospitalist groups to implement similar cellulitis pathways and research their effectiveness.

Bottom line: Clinical care pathways for cellulitis provide an opportunity to improve antibiotic stewardship and lower hospital costs without compromising quality of care.

Citation: Yarbrough PM, Kukhareva PV, Spivak ES, Hopkins C, Kawamoto K. Evidence-based care pathway for cellulitis improves process, clinical, and cost outcomes [published online ahead of print July 28, 2015]. J Hosp Med. doi: 10.1002/jhm.2433.

Clinical question: How would an evidence-based clinical pathway for cellulitis affect process metrics, patient outcomes, and clinical cost?

Background: Cellulitis is a common hospital problem, but its evaluation and treatment vary widely. Specifically, broad-spectrum antibiotics and imaging studies are overutilized when compared to recommended guidelines. A standardized clinical pathway is proposed as a possible solution.

Study design: Retrospective, observational, pre-/post-intervention study.

Setting: University of Utah Health Sciences Center, Salt Lake City.

Synopsis: A multidisciplinary team created a guideline-based care pathway for cellulitis and enrolled 677 adult patients for retrospective analysis during a two-year period. The study showed an overall 59% decrease in the odds of ordering broad-spectrum antibiotics, 23% decrease in pharmacy cost, 44% decrease in laboratory cost, and 13% decrease in overall facility cost, pre-/post-intervention. It also demonstrated no adverse effect on length of stay or 30-day readmission rates.

Given the retrospective, single-center nature of this study, as well as some baseline characteristic differences between enrolled patients, careful conclusions regarding external validity on diverse patient populations must be considered; however, the history of clinical care pathways supports many of the study’s findings. The results make a compelling case for hospitalist groups to implement similar cellulitis pathways and research their effectiveness.

Bottom line: Clinical care pathways for cellulitis provide an opportunity to improve antibiotic stewardship and lower hospital costs without compromising quality of care.

Citation: Yarbrough PM, Kukhareva PV, Spivak ES, Hopkins C, Kawamoto K. Evidence-based care pathway for cellulitis improves process, clinical, and cost outcomes [published online ahead of print July 28, 2015]. J Hosp Med. doi: 10.1002/jhm.2433.

Clinical question: Does palliative chemotherapy improve quality of life (QOL) in patients with end-stage cancer, regardless of performance status?

Background: There is continued debate about the benefit of palliative chemotherapy at the end of life. Guidelines recommend a good performance score as an indicator of appropriate use of therapy; however, little is known about the benefits and harms of chemotherapy in metastatic cancer patients stratified by performance status.

Study design: Longitudinal, prospective cohort study.

Setting: Multi-institutional in the United States.

Synopsis: Five U.S. institutions enrolled 661 patients with metastatic cancer and estimated life expectancy less than six months; 312 patients who died during the study period were included in the final analysis of postmortem questionnaires of caretakers regarding QOL in the patients’ last week of life. Contrary to current thought, the study demonstrated that patients undergoing end-of-life palliative chemotherapy with good ECOG performance status (0-1) had significantly worse QOL than those avoiding palliative chemotherapy. There was no difference in QOL in patients with worse performance status (ECOG 2-3).

This study is one of the first prospective investigations of this topic and makes a compelling case for withholding palliative chemotherapy at the end of life regardless of performance status. The study is somewhat limited in that the QOL measurement is only for the last week of life and the patients were not randomized into the chemotherapy arm, which could bias results.

Bottom line: Palliative chemotherapy does not improve QOL near death, and may actually worsen QOL in patients with good performance status.

Citation: Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015;1(6):778-784.

Clinical question: Does palliative chemotherapy improve quality of life (QOL) in patients with end-stage cancer, regardless of performance status?

Background: There is continued debate about the benefit of palliative chemotherapy at the end of life. Guidelines recommend a good performance score as an indicator of appropriate use of therapy; however, little is known about the benefits and harms of chemotherapy in metastatic cancer patients stratified by performance status.

Study design: Longitudinal, prospective cohort study.

Setting: Multi-institutional in the United States.

Synopsis: Five U.S. institutions enrolled 661 patients with metastatic cancer and estimated life expectancy less than six months; 312 patients who died during the study period were included in the final analysis of postmortem questionnaires of caretakers regarding QOL in the patients’ last week of life. Contrary to current thought, the study demonstrated that patients undergoing end-of-life palliative chemotherapy with good ECOG performance status (0-1) had significantly worse QOL than those avoiding palliative chemotherapy. There was no difference in QOL in patients with worse performance status (ECOG 2-3).

This study is one of the first prospective investigations of this topic and makes a compelling case for withholding palliative chemotherapy at the end of life regardless of performance status. The study is somewhat limited in that the QOL measurement is only for the last week of life and the patients were not randomized into the chemotherapy arm, which could bias results.

Bottom line: Palliative chemotherapy does not improve QOL near death, and may actually worsen QOL in patients with good performance status.

Citation: Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015;1(6):778-784.

Clinical question: Does palliative chemotherapy improve quality of life (QOL) in patients with end-stage cancer, regardless of performance status?

Background: There is continued debate about the benefit of palliative chemotherapy at the end of life. Guidelines recommend a good performance score as an indicator of appropriate use of therapy; however, little is known about the benefits and harms of chemotherapy in metastatic cancer patients stratified by performance status.

Study design: Longitudinal, prospective cohort study.

Setting: Multi-institutional in the United States.

Synopsis: Five U.S. institutions enrolled 661 patients with metastatic cancer and estimated life expectancy less than six months; 312 patients who died during the study period were included in the final analysis of postmortem questionnaires of caretakers regarding QOL in the patients’ last week of life. Contrary to current thought, the study demonstrated that patients undergoing end-of-life palliative chemotherapy with good ECOG performance status (0-1) had significantly worse QOL than those avoiding palliative chemotherapy. There was no difference in QOL in patients with worse performance status (ECOG 2-3).

This study is one of the first prospective investigations of this topic and makes a compelling case for withholding palliative chemotherapy at the end of life regardless of performance status. The study is somewhat limited in that the QOL measurement is only for the last week of life and the patients were not randomized into the chemotherapy arm, which could bias results.

Bottom line: Palliative chemotherapy does not improve QOL near death, and may actually worsen QOL in patients with good performance status.

Citation: Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015;1(6):778-784.

Clinical question: Do transfusions affect post-operative outcomes after noncardiac surgery?

Background: Studies have demonstrated that a restrictive transfusion strategy is probably superior to a liberal transfusion strategy in many clinical settings. Despite this data, there continues to be wide variation in the use of blood transfusions in the peri-operative setting.

Study design: Retrospective cohort study.

Setting: Fifty-two community and academic hospitals in Michigan.

Synopsis: Demographic, operative, and outcomes data were extracted from the Michigan Surgical Quality Collaborative and reviewed for 48,720 patients who underwent noncardiac surgery between 2012-2014. A total of 4.6% of patients received a blood transfusion within 72 hours after surgery. The patients who received blood products were at increased risk for death at 30 days (3.6% excess absolute risk), for infectious complications (1% excess absolute risk), and for having at least one post-operative noninfectious complication (4.4% increased absolute risk).

Bottom line: Although observational in nature, this study adds to the increasing body of evidence supporting an increase in surgical morbidity and mortality associated with blood transfusions.

Citation: Abdelsattar ZM, Hendren S, Wong SL, Campbell DA Jr, Henke P. Variation in transfusion practices and the effect on outcomes after noncardiac surgery. Ann Surg. 2015;262(1):1-6.

Clinical question: Do transfusions affect post-operative outcomes after noncardiac surgery?

Background: Studies have demonstrated that a restrictive transfusion strategy is probably superior to a liberal transfusion strategy in many clinical settings. Despite this data, there continues to be wide variation in the use of blood transfusions in the peri-operative setting.

Study design: Retrospective cohort study.

Setting: Fifty-two community and academic hospitals in Michigan.

Synopsis: Demographic, operative, and outcomes data were extracted from the Michigan Surgical Quality Collaborative and reviewed for 48,720 patients who underwent noncardiac surgery between 2012-2014. A total of 4.6% of patients received a blood transfusion within 72 hours after surgery. The patients who received blood products were at increased risk for death at 30 days (3.6% excess absolute risk), for infectious complications (1% excess absolute risk), and for having at least one post-operative noninfectious complication (4.4% increased absolute risk).

Bottom line: Although observational in nature, this study adds to the increasing body of evidence supporting an increase in surgical morbidity and mortality associated with blood transfusions.

Citation: Abdelsattar ZM, Hendren S, Wong SL, Campbell DA Jr, Henke P. Variation in transfusion practices and the effect on outcomes after noncardiac surgery. Ann Surg. 2015;262(1):1-6.

Clinical question: Do transfusions affect post-operative outcomes after noncardiac surgery?

Background: Studies have demonstrated that a restrictive transfusion strategy is probably superior to a liberal transfusion strategy in many clinical settings. Despite this data, there continues to be wide variation in the use of blood transfusions in the peri-operative setting.

Study design: Retrospective cohort study.

Setting: Fifty-two community and academic hospitals in Michigan.

Synopsis: Demographic, operative, and outcomes data were extracted from the Michigan Surgical Quality Collaborative and reviewed for 48,720 patients who underwent noncardiac surgery between 2012-2014. A total of 4.6% of patients received a blood transfusion within 72 hours after surgery. The patients who received blood products were at increased risk for death at 30 days (3.6% excess absolute risk), for infectious complications (1% excess absolute risk), and for having at least one post-operative noninfectious complication (4.4% increased absolute risk).

Bottom line: Although observational in nature, this study adds to the increasing body of evidence supporting an increase in surgical morbidity and mortality associated with blood transfusions.

Citation: Abdelsattar ZM, Hendren S, Wong SL, Campbell DA Jr, Henke P. Variation in transfusion practices and the effect on outcomes after noncardiac surgery. Ann Surg. 2015;262(1):1-6.

Clinical question: Is there a favorable risk-benefit ratio for left atrial appendage closure (LAAC) compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation?

Background: LAAC with the WATCHMAN device was shown to be noninferior to warfarin for the prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation in two trials: PROTECT AF and PREVAIL. Further efficacy concerns were raised following routine regulatory filings, leading to the need for continued evaluation.

Study design: Meta-analysis.

Setting: Patient-level data were combined and analyzed from the PROTECT AF and PREVAIL trails and two nonrandomized registries of LAAC with the WATCHMAN device: the Continued Access PROTECT AF registry (CAP) and the Continued Access to PREVAIL registry (CAP2).

Synopsis: A total of 2,406 patients were enrolled from all four data sets from 2005-2014. Of those, 1,877 were treated with the WATCHMAN device and 382 were treated with warfarin. Annualized risk of stroke if untreated with anticoagulation for all patients was 5.7% to 7.6%, indicating that all were eligible to be treated with warfarin. Ninety percent of patients had moderate to high risk of bleeding. Analysis showed that LAAC was noninferior to warfarin for stroke, systemic embolism, and cardiovascular death.

A slight increase in ischemic stroke in the LAAC group was counterbalanced by the significant reduction in hemorrhagic stroke in the LAAC group versus the warfarin group. Cardiovascular deaths were significantly fewer in the LAAC cohort; all-cause mortality favored LAAC but did not reach statistical significance. There was also a significant reduction in nonprocedure-related major bleeding in the LAAC group. Limitations of this study include the limited number of patients treated with warfarin and lack of comparison to new oral anticoagulants (NOACs).

Bottom line: Patients with increased stroke risk from nonvalvular atrial fibrillation treated with the WATCHMAN device for LAAC have significant reductions in hemorrhagic stroke, cardiovascular death, and nonprocedure-related major bleeding, but slightly increased risk of ischemic stroke compared to those treated with warfarin.

Citaiton: Holmes DR Jr, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol. 2015;65(24):2614-2623.

Clinical question: Is there a favorable risk-benefit ratio for left atrial appendage closure (LAAC) compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation?

Background: LAAC with the WATCHMAN device was shown to be noninferior to warfarin for the prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation in two trials: PROTECT AF and PREVAIL. Further efficacy concerns were raised following routine regulatory filings, leading to the need for continued evaluation.

Study design: Meta-analysis.

Setting: Patient-level data were combined and analyzed from the PROTECT AF and PREVAIL trails and two nonrandomized registries of LAAC with the WATCHMAN device: the Continued Access PROTECT AF registry (CAP) and the Continued Access to PREVAIL registry (CAP2).

Synopsis: A total of 2,406 patients were enrolled from all four data sets from 2005-2014. Of those, 1,877 were treated with the WATCHMAN device and 382 were treated with warfarin. Annualized risk of stroke if untreated with anticoagulation for all patients was 5.7% to 7.6%, indicating that all were eligible to be treated with warfarin. Ninety percent of patients had moderate to high risk of bleeding. Analysis showed that LAAC was noninferior to warfarin for stroke, systemic embolism, and cardiovascular death.

A slight increase in ischemic stroke in the LAAC group was counterbalanced by the significant reduction in hemorrhagic stroke in the LAAC group versus the warfarin group. Cardiovascular deaths were significantly fewer in the LAAC cohort; all-cause mortality favored LAAC but did not reach statistical significance. There was also a significant reduction in nonprocedure-related major bleeding in the LAAC group. Limitations of this study include the limited number of patients treated with warfarin and lack of comparison to new oral anticoagulants (NOACs).

Bottom line: Patients with increased stroke risk from nonvalvular atrial fibrillation treated with the WATCHMAN device for LAAC have significant reductions in hemorrhagic stroke, cardiovascular death, and nonprocedure-related major bleeding, but slightly increased risk of ischemic stroke compared to those treated with warfarin.

Citaiton: Holmes DR Jr, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol. 2015;65(24):2614-2623.

Clinical question: Is there a favorable risk-benefit ratio for left atrial appendage closure (LAAC) compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation?

Background: LAAC with the WATCHMAN device was shown to be noninferior to warfarin for the prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation in two trials: PROTECT AF and PREVAIL. Further efficacy concerns were raised following routine regulatory filings, leading to the need for continued evaluation.

Study design: Meta-analysis.

Setting: Patient-level data were combined and analyzed from the PROTECT AF and PREVAIL trails and two nonrandomized registries of LAAC with the WATCHMAN device: the Continued Access PROTECT AF registry (CAP) and the Continued Access to PREVAIL registry (CAP2).

Synopsis: A total of 2,406 patients were enrolled from all four data sets from 2005-2014. Of those, 1,877 were treated with the WATCHMAN device and 382 were treated with warfarin. Annualized risk of stroke if untreated with anticoagulation for all patients was 5.7% to 7.6%, indicating that all were eligible to be treated with warfarin. Ninety percent of patients had moderate to high risk of bleeding. Analysis showed that LAAC was noninferior to warfarin for stroke, systemic embolism, and cardiovascular death.

A slight increase in ischemic stroke in the LAAC group was counterbalanced by the significant reduction in hemorrhagic stroke in the LAAC group versus the warfarin group. Cardiovascular deaths were significantly fewer in the LAAC cohort; all-cause mortality favored LAAC but did not reach statistical significance. There was also a significant reduction in nonprocedure-related major bleeding in the LAAC group. Limitations of this study include the limited number of patients treated with warfarin and lack of comparison to new oral anticoagulants (NOACs).

Bottom line: Patients with increased stroke risk from nonvalvular atrial fibrillation treated with the WATCHMAN device for LAAC have significant reductions in hemorrhagic stroke, cardiovascular death, and nonprocedure-related major bleeding, but slightly increased risk of ischemic stroke compared to those treated with warfarin.

Citaiton: Holmes DR Jr, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol. 2015;65(24):2614-2623.

Clinical question: Can we dignify death in the ICU and ease the grieving process by soliciting wishes from patients, families, and care team members?

Background: The death of the critically ill patient in the ICU can be dehumanizing and overwhelming for the patient’s family and friends, leading to prolonged physical and psychological stress. These deaths might have similar effects on the clinicians caring for the patients.

Study design: Mixed methods.

Setting: Medical-surgical ICU at a 21-bed, academic tertiary medical center in Ontario, Canada.

Synopsis: Semi-structured interviews were conducted with at least one family member and three clinicians per patient. A total of 40 patients were screened and deemed eligible for inclusion. Only seven patients were able to provide input on the wishes or interviews; the others had impaired consciousness. The team obtained 163 wishes from those individuals, and was able to implement 159 of them (97.5%). At least three wishes from each patient-family dyad were implemented.

The wishes were classified into five categories:

• Humanizing the environment;
• Personal tributes;
• Family reconnections;
• Rituals and observances; and
• Paying it forward.

These wishes were implemented before (51.6%) and after (48.4%) death and were generally inexpensive (less than $200 per patient).

From the 160 interviews of 170 individuals, the central theme that emerged was personalization of the dying process in the ICU through three related domains: dignifying the patient, giving the family a voice, and fostering clinician compassion.

The 3 Wishes Project provides a framework to foster discussion among care team members and families to ensure personalization and dignity in the dying process.

Bottom line: Solicitation of wishes from dying patients, their families, and their care team members can have a positive impact by allowing individualized end-of-life care.

Citation: Cook D, Swinton M, Toledo F, et al. Personalizing death in the intensive care unit: the 3 Wishes Project: a mixed-methods study. Ann Intern Med. 2015;163(4):271-279.

Clinical question: Can we dignify death in the ICU and ease the grieving process by soliciting wishes from patients, families, and care team members?

Background: The death of the critically ill patient in the ICU can be dehumanizing and overwhelming for the patient’s family and friends, leading to prolonged physical and psychological stress. These deaths might have similar effects on the clinicians caring for the patients.

Study design: Mixed methods.

Setting: Medical-surgical ICU at a 21-bed, academic tertiary medical center in Ontario, Canada.

Synopsis: Semi-structured interviews were conducted with at least one family member and three clinicians per patient. A total of 40 patients were screened and deemed eligible for inclusion. Only seven patients were able to provide input on the wishes or interviews; the others had impaired consciousness. The team obtained 163 wishes from those individuals, and was able to implement 159 of them (97.5%). At least three wishes from each patient-family dyad were implemented.

The wishes were classified into five categories:

• Humanizing the environment;
• Personal tributes;
• Family reconnections;
• Rituals and observances; and
• Paying it forward.

These wishes were implemented before (51.6%) and after (48.4%) death and were generally inexpensive (less than $200 per patient).

From the 160 interviews of 170 individuals, the central theme that emerged was personalization of the dying process in the ICU through three related domains: dignifying the patient, giving the family a voice, and fostering clinician compassion.

The 3 Wishes Project provides a framework to foster discussion among care team members and families to ensure personalization and dignity in the dying process.

Bottom line: Solicitation of wishes from dying patients, their families, and their care team members can have a positive impact by allowing individualized end-of-life care.

Citation: Cook D, Swinton M, Toledo F, et al. Personalizing death in the intensive care unit: the 3 Wishes Project: a mixed-methods study. Ann Intern Med. 2015;163(4):271-279.

Clinical question: Can we dignify death in the ICU and ease the grieving process by soliciting wishes from patients, families, and care team members?

Background: The death of the critically ill patient in the ICU can be dehumanizing and overwhelming for the patient’s family and friends, leading to prolonged physical and psychological stress. These deaths might have similar effects on the clinicians caring for the patients.

Study design: Mixed methods.

Setting: Medical-surgical ICU at a 21-bed, academic tertiary medical center in Ontario, Canada.

Synopsis: Semi-structured interviews were conducted with at least one family member and three clinicians per patient. A total of 40 patients were screened and deemed eligible for inclusion. Only seven patients were able to provide input on the wishes or interviews; the others had impaired consciousness. The team obtained 163 wishes from those individuals, and was able to implement 159 of them (97.5%). At least three wishes from each patient-family dyad were implemented.

The wishes were classified into five categories:

• Humanizing the environment;
• Personal tributes;
• Family reconnections;
• Rituals and observances; and
• Paying it forward.

These wishes were implemented before (51.6%) and after (48.4%) death and were generally inexpensive (less than $200 per patient).

From the 160 interviews of 170 individuals, the central theme that emerged was personalization of the dying process in the ICU through three related domains: dignifying the patient, giving the family a voice, and fostering clinician compassion.

The 3 Wishes Project provides a framework to foster discussion among care team members and families to ensure personalization and dignity in the dying process.

Bottom line: Solicitation of wishes from dying patients, their families, and their care team members can have a positive impact by allowing individualized end-of-life care.

Citation: Cook D, Swinton M, Toledo F, et al. Personalizing death in the intensive care unit: the 3 Wishes Project: a mixed-methods study. Ann Intern Med. 2015;163(4):271-279.