Literature Review

Transplanted nerve cells may survive for nearly a quarter of a century in a patient’s brain despite ongoing Parkinson’s disease, according to data published online ahead of print May 2 in the Proceedings of the National Academy of Sciences of the United States of America. A transplant of cells into the putamen yields dense reinnervation similar to that of healthy brains. The case study also suggests that the initial clinical benefits of the transplant gradually deteriorate when pathology spreads from the patient’s brain to the transplanted cells.

“This is the first time a patient has shown such a well-functioning transplant so many years after transplantation of nerve cells to the brain,” said Olle Lindvall, MD, PhD, Professor of Clinical Neurology and Chairman of Neurology at the University Hospital in Lund, Sweden. “At the same time, we have observed that the transplant’s positive effects on this patient gradually disappeared as the disease spread to more structures in the brain.”

Olle Lindvall, MD, PhD

Dr. Lindvall and colleagues followed a patient with Parkinson’s disease for 24 years after he received a transplant of embryonic dopaminergic neurons. The patient had developed Parkinson’s disease in 1980 and had started L-dopa treatment in 1982. The therapy appeared to be efficacious, but in 1986, the patient developed “on–off” symptoms. During “off” periods, he experienced resting tremor, hypokinetic movements, and rigidity, especially on the left side of his body. During “on” periods, he displayed mild parkinsonian symptoms.

In 1989, the patient, who was then age 59, underwent transplantation with ventral mesencephalic tissue from four human embryos into the right putamen. He was monitored for 10 years post transplantation. In the first three years, researchers noted significant improvement, and L-dopa was withdrawn at 32 months. At 64 months post transplantation, immunosuppressive treatment was stopped. When symptoms progressed at 74 months, a low dose of L-dopa was reintroduced. The patient had a marked clinical benefit, including a near-absence of rigidity, at 10 years. At 12 years, however, he had worsening hypokinesia; as a result, a low-dose dopamine agonist was added for two years, and the L-dopa dose was increased.

The patient responded well to his treatment change at first, but at 14 years, his condition worsened. He began to experience increasing rigidity, hypokinesia, and a gradual loss of beneficial L-dopa response. During this time, cognitive impairment and onset of progressive dementia were first noted. At 18 years, no graft-related motor improvement remained, and the patient was unable to walk, swallow, or speak. At 24 years, the patient died of cardiac insufficiency. Autopsy revealed no evidence of an ongoing immune or inflammatory response. The patient had a dense, near-normal dopaminergic reinnervation derived from the grafts at 24 years post transplantation.

This case study provides the first evidence that rich dopaminergic innervation that develops in the first three years after transplantation and causes dramatic motor improvement can be preserved for 24 years in Parkinson’s disease, according to the authors. The clinical results, however, showed that even a viable graft could eventually lose its efficacy if widespread alpha-synucleinopathy progresses and degeneration occurs in the host brain.

“This study is completely unique,” said Anders Bjorklund, Professor at the Wallenberg Neuroscience Center at Lund University. “No transplanted Parkinson’s patient has ever been followed so closely and over such a long period...What we have learnt from the study of this patient will be of great value for future attempts to transplant dopamine-producing nerve cells obtained from stem cells, a new development led by researchers in Lund.”

—Erica Robinson

Transplanted nerve cells may survive for nearly a quarter of a century in a patient’s brain despite ongoing Parkinson’s disease, according to data published online ahead of print May 2 in the Proceedings of the National Academy of Sciences of the United States of America. A transplant of cells into the putamen yields dense reinnervation similar to that of healthy brains. The case study also suggests that the initial clinical benefits of the transplant gradually deteriorate when pathology spreads from the patient’s brain to the transplanted cells.

“This is the first time a patient has shown such a well-functioning transplant so many years after transplantation of nerve cells to the brain,” said Olle Lindvall, MD, PhD, Professor of Clinical Neurology and Chairman of Neurology at the University Hospital in Lund, Sweden. “At the same time, we have observed that the transplant’s positive effects on this patient gradually disappeared as the disease spread to more structures in the brain.”

Olle Lindvall, MD, PhD

Dr. Lindvall and colleagues followed a patient with Parkinson’s disease for 24 years after he received a transplant of embryonic dopaminergic neurons. The patient had developed Parkinson’s disease in 1980 and had started L-dopa treatment in 1982. The therapy appeared to be efficacious, but in 1986, the patient developed “on–off” symptoms. During “off” periods, he experienced resting tremor, hypokinetic movements, and rigidity, especially on the left side of his body. During “on” periods, he displayed mild parkinsonian symptoms.

In 1989, the patient, who was then age 59, underwent transplantation with ventral mesencephalic tissue from four human embryos into the right putamen. He was monitored for 10 years post transplantation. In the first three years, researchers noted significant improvement, and L-dopa was withdrawn at 32 months. At 64 months post transplantation, immunosuppressive treatment was stopped. When symptoms progressed at 74 months, a low dose of L-dopa was reintroduced. The patient had a marked clinical benefit, including a near-absence of rigidity, at 10 years. At 12 years, however, he had worsening hypokinesia; as a result, a low-dose dopamine agonist was added for two years, and the L-dopa dose was increased.

The patient responded well to his treatment change at first, but at 14 years, his condition worsened. He began to experience increasing rigidity, hypokinesia, and a gradual loss of beneficial L-dopa response. During this time, cognitive impairment and onset of progressive dementia were first noted. At 18 years, no graft-related motor improvement remained, and the patient was unable to walk, swallow, or speak. At 24 years, the patient died of cardiac insufficiency. Autopsy revealed no evidence of an ongoing immune or inflammatory response. The patient had a dense, near-normal dopaminergic reinnervation derived from the grafts at 24 years post transplantation.

This case study provides the first evidence that rich dopaminergic innervation that develops in the first three years after transplantation and causes dramatic motor improvement can be preserved for 24 years in Parkinson’s disease, according to the authors. The clinical results, however, showed that even a viable graft could eventually lose its efficacy if widespread alpha-synucleinopathy progresses and degeneration occurs in the host brain.

“This study is completely unique,” said Anders Bjorklund, Professor at the Wallenberg Neuroscience Center at Lund University. “No transplanted Parkinson’s patient has ever been followed so closely and over such a long period...What we have learnt from the study of this patient will be of great value for future attempts to transplant dopamine-producing nerve cells obtained from stem cells, a new development led by researchers in Lund.”

—Erica Robinson

Transplanted nerve cells may survive for nearly a quarter of a century in a patient’s brain despite ongoing Parkinson’s disease, according to data published online ahead of print May 2 in the Proceedings of the National Academy of Sciences of the United States of America. A transplant of cells into the putamen yields dense reinnervation similar to that of healthy brains. The case study also suggests that the initial clinical benefits of the transplant gradually deteriorate when pathology spreads from the patient’s brain to the transplanted cells.

“This is the first time a patient has shown such a well-functioning transplant so many years after transplantation of nerve cells to the brain,” said Olle Lindvall, MD, PhD, Professor of Clinical Neurology and Chairman of Neurology at the University Hospital in Lund, Sweden. “At the same time, we have observed that the transplant’s positive effects on this patient gradually disappeared as the disease spread to more structures in the brain.”

Olle Lindvall, MD, PhD

Dr. Lindvall and colleagues followed a patient with Parkinson’s disease for 24 years after he received a transplant of embryonic dopaminergic neurons. The patient had developed Parkinson’s disease in 1980 and had started L-dopa treatment in 1982. The therapy appeared to be efficacious, but in 1986, the patient developed “on–off” symptoms. During “off” periods, he experienced resting tremor, hypokinetic movements, and rigidity, especially on the left side of his body. During “on” periods, he displayed mild parkinsonian symptoms.

In 1989, the patient, who was then age 59, underwent transplantation with ventral mesencephalic tissue from four human embryos into the right putamen. He was monitored for 10 years post transplantation. In the first three years, researchers noted significant improvement, and L-dopa was withdrawn at 32 months. At 64 months post transplantation, immunosuppressive treatment was stopped. When symptoms progressed at 74 months, a low dose of L-dopa was reintroduced. The patient had a marked clinical benefit, including a near-absence of rigidity, at 10 years. At 12 years, however, he had worsening hypokinesia; as a result, a low-dose dopamine agonist was added for two years, and the L-dopa dose was increased.

The patient responded well to his treatment change at first, but at 14 years, his condition worsened. He began to experience increasing rigidity, hypokinesia, and a gradual loss of beneficial L-dopa response. During this time, cognitive impairment and onset of progressive dementia were first noted. At 18 years, no graft-related motor improvement remained, and the patient was unable to walk, swallow, or speak. At 24 years, the patient died of cardiac insufficiency. Autopsy revealed no evidence of an ongoing immune or inflammatory response. The patient had a dense, near-normal dopaminergic reinnervation derived from the grafts at 24 years post transplantation.

This case study provides the first evidence that rich dopaminergic innervation that develops in the first three years after transplantation and causes dramatic motor improvement can be preserved for 24 years in Parkinson’s disease, according to the authors. The clinical results, however, showed that even a viable graft could eventually lose its efficacy if widespread alpha-synucleinopathy progresses and degeneration occurs in the host brain.

“This study is completely unique,” said Anders Bjorklund, Professor at the Wallenberg Neuroscience Center at Lund University. “No transplanted Parkinson’s patient has ever been followed so closely and over such a long period...What we have learnt from the study of this patient will be of great value for future attempts to transplant dopamine-producing nerve cells obtained from stem cells, a new development led by researchers in Lund.”

—Erica Robinson

First-trimester exposure to pregabalin may increase the risk of major birth defects, according to a study published online ahead of print May 18 in Neurology.

Pregabalin is an FDA-approved treatment for seizures and neuropathic pain. It is also a common off-label treatment for restless legs syndrome, cyclic mood disorders, and generalized anxiety disorder.

Ursula Winterfeld, PhD, of the Swiss Teratogen Information Service and Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and colleagues conducted a multicenter, observational cohort study in which they compared pregnancy outcomes of 164 women exposed to pregabalin with 656 controls who were not exposed to any known teratogenic medications or antiepileptic drugs. Data for this study were collected from 2004 to 2013 and included data from France, the United Kingdom, Italy, Finland, Switzerland, the Netherlands, and Turkey.

Of the women on the medication, 77% started taking pregabalin before they became pregnant and stopped taking the drug at a median of six weeks into their pregnancies. Of the women taking pregabalin, 13% were also taking another antiepileptic drug.

Pregnancies of the women who took pregabalin during the first trimester of pregnancy were three times more likely to result in major birth defects than those of women who did not take the drug—6.0% versus 2.1%, respectively. The major birth defects included heart defects and structural problems with the CNS or other organ systems. The study also revealed a lower rate of live births in the pregabalin group due to elective and medically indicated pregnancy terminations.

“We can’t draw any definitive conclusions from this study, since many of the women were taking other drugs that could have played a role in the birth defects and because the study was small and the results need to be confirmed with larger studies, but these results do signal that there may be an increased risk for major birth defects after taking pregabalin during the first trimester of pregnancy,” said Dr. Winterfeld.

She suggested that before a woman is prescribed pregabalin, it is important to make sure the benefits outweigh the risks and that she is carefully informed about the use of effective birth control.

—Adaeze Stephanie Onyechi

First-trimester exposure to pregabalin may increase the risk of major birth defects, according to a study published online ahead of print May 18 in Neurology.

Pregabalin is an FDA-approved treatment for seizures and neuropathic pain. It is also a common off-label treatment for restless legs syndrome, cyclic mood disorders, and generalized anxiety disorder.

Ursula Winterfeld, PhD, of the Swiss Teratogen Information Service and Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and colleagues conducted a multicenter, observational cohort study in which they compared pregnancy outcomes of 164 women exposed to pregabalin with 656 controls who were not exposed to any known teratogenic medications or antiepileptic drugs. Data for this study were collected from 2004 to 2013 and included data from France, the United Kingdom, Italy, Finland, Switzerland, the Netherlands, and Turkey.

Of the women on the medication, 77% started taking pregabalin before they became pregnant and stopped taking the drug at a median of six weeks into their pregnancies. Of the women taking pregabalin, 13% were also taking another antiepileptic drug.

Pregnancies of the women who took pregabalin during the first trimester of pregnancy were three times more likely to result in major birth defects than those of women who did not take the drug—6.0% versus 2.1%, respectively. The major birth defects included heart defects and structural problems with the CNS or other organ systems. The study also revealed a lower rate of live births in the pregabalin group due to elective and medically indicated pregnancy terminations.

“We can’t draw any definitive conclusions from this study, since many of the women were taking other drugs that could have played a role in the birth defects and because the study was small and the results need to be confirmed with larger studies, but these results do signal that there may be an increased risk for major birth defects after taking pregabalin during the first trimester of pregnancy,” said Dr. Winterfeld.

She suggested that before a woman is prescribed pregabalin, it is important to make sure the benefits outweigh the risks and that she is carefully informed about the use of effective birth control.

—Adaeze Stephanie Onyechi

First-trimester exposure to pregabalin may increase the risk of major birth defects, according to a study published online ahead of print May 18 in Neurology.

Pregabalin is an FDA-approved treatment for seizures and neuropathic pain. It is also a common off-label treatment for restless legs syndrome, cyclic mood disorders, and generalized anxiety disorder.

Ursula Winterfeld, PhD, of the Swiss Teratogen Information Service and Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and colleagues conducted a multicenter, observational cohort study in which they compared pregnancy outcomes of 164 women exposed to pregabalin with 656 controls who were not exposed to any known teratogenic medications or antiepileptic drugs. Data for this study were collected from 2004 to 2013 and included data from France, the United Kingdom, Italy, Finland, Switzerland, the Netherlands, and Turkey.

Of the women on the medication, 77% started taking pregabalin before they became pregnant and stopped taking the drug at a median of six weeks into their pregnancies. Of the women taking pregabalin, 13% were also taking another antiepileptic drug.

Pregnancies of the women who took pregabalin during the first trimester of pregnancy were three times more likely to result in major birth defects than those of women who did not take the drug—6.0% versus 2.1%, respectively. The major birth defects included heart defects and structural problems with the CNS or other organ systems. The study also revealed a lower rate of live births in the pregabalin group due to elective and medically indicated pregnancy terminations.

“We can’t draw any definitive conclusions from this study, since many of the women were taking other drugs that could have played a role in the birth defects and because the study was small and the results need to be confirmed with larger studies, but these results do signal that there may be an increased risk for major birth defects after taking pregabalin during the first trimester of pregnancy,” said Dr. Winterfeld.

She suggested that before a woman is prescribed pregabalin, it is important to make sure the benefits outweigh the risks and that she is carefully informed about the use of effective birth control.

—Adaeze Stephanie Onyechi

Clinical question: Is one dose of dexamethasone comparable to five days of prednisone for treating mild-to-moderate asthma exacerbations?

Background: Corticosteroids are the mainstay of initial treatment for asthma exacerbations. The National Heart, Lung, and Blood Institute recommends a minimum of five days of prednisone, though studies have shown incomplete adherence to prolonged therapies. Dexamethasone has a longer duration of action than prednisone.

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

Setting: Urban, safety-net, teaching hospital.

Synopsis: The study included 376 adults ages 18–55 presenting to the emergency department for a mild-to-moderate asthma exacerbation who were randomized to two treatment courses of corticosteroids: one 12 mg dose of oral dexamethasone followed by four days of placebo versus five days of 60 mg of oral prednisone. Two weeks later, a telephone survey asked if they had relapsed and had to seek medical attention. This study did not show noninferiority of the dexamethasone option compared to the standard of care. Specifically, it showed a 12.1% relapse rate in the dexamethasone group versus a 9.8% relapse rate for prednisone (95% CI, -4.1% to 8.6%).

This was a small study looking at adults without other chronic lung diseases or diabetes. The authors did not include those patients who were either lost to follow-up (20% of those initially randomized) or ultimately admitted after their emergency department course.

Hospitalists who care for patients with asthma should look to the current standards of corticosteroid selection and duration to minimize clinical relapses and possibly readmissions.

Bottom line: One large dose of dexamethasone is inferior to the standard five days of prednisone for treating acute asthma exacerbations in adults.

Citation: Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma [published online ahead of print April 14, 2016]. Ann Emerg Med. doi:10.1016/j.annemergmed.2016.03.017.

Short Take

Guideline Recommends ED Asthma Management Associated with Shorter Inpatient Stay

Observational study found ED treatment concordance with four guideline-based processes for acute asthma treatment (inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, and avoidance of methylxanthines) is associated with a 17% shorter hospital length of stay.

Citation: Hasegawa K, Brenner BE, Nowak RM, et al. Association of guideline-concordant acute asthma care in the emergency department with shorter hospital length of stay: a multicenter observational study. Acad Emerg Med. 2016;23(5):616-622.

Clinical question: Is one dose of dexamethasone comparable to five days of prednisone for treating mild-to-moderate asthma exacerbations?

Background: Corticosteroids are the mainstay of initial treatment for asthma exacerbations. The National Heart, Lung, and Blood Institute recommends a minimum of five days of prednisone, though studies have shown incomplete adherence to prolonged therapies. Dexamethasone has a longer duration of action than prednisone.

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

Setting: Urban, safety-net, teaching hospital.

Synopsis: The study included 376 adults ages 18–55 presenting to the emergency department for a mild-to-moderate asthma exacerbation who were randomized to two treatment courses of corticosteroids: one 12 mg dose of oral dexamethasone followed by four days of placebo versus five days of 60 mg of oral prednisone. Two weeks later, a telephone survey asked if they had relapsed and had to seek medical attention. This study did not show noninferiority of the dexamethasone option compared to the standard of care. Specifically, it showed a 12.1% relapse rate in the dexamethasone group versus a 9.8% relapse rate for prednisone (95% CI, -4.1% to 8.6%).

This was a small study looking at adults without other chronic lung diseases or diabetes. The authors did not include those patients who were either lost to follow-up (20% of those initially randomized) or ultimately admitted after their emergency department course.

Hospitalists who care for patients with asthma should look to the current standards of corticosteroid selection and duration to minimize clinical relapses and possibly readmissions.

Bottom line: One large dose of dexamethasone is inferior to the standard five days of prednisone for treating acute asthma exacerbations in adults.

Citation: Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma [published online ahead of print April 14, 2016]. Ann Emerg Med. doi:10.1016/j.annemergmed.2016.03.017.

Short Take

Guideline Recommends ED Asthma Management Associated with Shorter Inpatient Stay

Observational study found ED treatment concordance with four guideline-based processes for acute asthma treatment (inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, and avoidance of methylxanthines) is associated with a 17% shorter hospital length of stay.

Citation: Hasegawa K, Brenner BE, Nowak RM, et al. Association of guideline-concordant acute asthma care in the emergency department with shorter hospital length of stay: a multicenter observational study. Acad Emerg Med. 2016;23(5):616-622.

Clinical question: Is one dose of dexamethasone comparable to five days of prednisone for treating mild-to-moderate asthma exacerbations?

Background: Corticosteroids are the mainstay of initial treatment for asthma exacerbations. The National Heart, Lung, and Blood Institute recommends a minimum of five days of prednisone, though studies have shown incomplete adherence to prolonged therapies. Dexamethasone has a longer duration of action than prednisone.

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

Setting: Urban, safety-net, teaching hospital.

Synopsis: The study included 376 adults ages 18–55 presenting to the emergency department for a mild-to-moderate asthma exacerbation who were randomized to two treatment courses of corticosteroids: one 12 mg dose of oral dexamethasone followed by four days of placebo versus five days of 60 mg of oral prednisone. Two weeks later, a telephone survey asked if they had relapsed and had to seek medical attention. This study did not show noninferiority of the dexamethasone option compared to the standard of care. Specifically, it showed a 12.1% relapse rate in the dexamethasone group versus a 9.8% relapse rate for prednisone (95% CI, -4.1% to 8.6%).

This was a small study looking at adults without other chronic lung diseases or diabetes. The authors did not include those patients who were either lost to follow-up (20% of those initially randomized) or ultimately admitted after their emergency department course.

Hospitalists who care for patients with asthma should look to the current standards of corticosteroid selection and duration to minimize clinical relapses and possibly readmissions.

Bottom line: One large dose of dexamethasone is inferior to the standard five days of prednisone for treating acute asthma exacerbations in adults.

Citation: Rehrer MW, Liu B, Rodriguez M, Lam J, Alter HJ. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma [published online ahead of print April 14, 2016]. Ann Emerg Med. doi:10.1016/j.annemergmed.2016.03.017.

Short Take

Guideline Recommends ED Asthma Management Associated with Shorter Inpatient Stay

Observational study found ED treatment concordance with four guideline-based processes for acute asthma treatment (inhaled beta-agonists, inhaled anticholinergics, systemic corticosteroids, and avoidance of methylxanthines) is associated with a 17% shorter hospital length of stay.

Citation: Hasegawa K, Brenner BE, Nowak RM, et al. Association of guideline-concordant acute asthma care in the emergency department with shorter hospital length of stay: a multicenter observational study. Acad Emerg Med. 2016;23(5):616-622.

Clinical question: Does nasal high-flow (NHF) oxygen after extubation reduce reintubation rates in low-risk patients?

Background: NHF oxygen devices deliver warmed and humidified oxygen up to 60 liters per minutes. NHF provides positive end-expiratory pressure and dead-space washout. NHF in higher-risk post-extubation patients has been shown to have clinical benefits. Whether NHF post-extubation benefits patients at low risk of reintubation is unknown.

Study design: Randomized control trial (RCT).

Setting: Seven ICUs in Spain.

Synopsis: In this RCT, post-extubation NHF oxygen for 24 hours reduced the risk of reintubation among 527 ICU adults at low risk of reintubation when compared to conventional oxygen therapy (by nasal cannula or face mask). Patients with hypercapnia during weaning trials were excluded. The risk of reintubation was 4.9% versus 12.2% in NHF versus standard oxygen therapy, with an absolute difference of 7.2% (95% CI, 2.5–12.2%; P=0.004). ICU length of stay and mortality were not significantly different between the groups. The strengths of the study were adequate sample size, prespecified criteria for reintubation, and low number of crossover patients.

Limitations of the trial were the high percentage of surgical and neurologic cases, exclusion of patients with a variety of common comorbidities, and the inability to blind the physicians to the treatment arm of the subjects. Select patients may benefit from noninvasive ventilation to prevent reintubation, which was not studied. These results are highly relevant to post-extubation patients, with the optimum therapy for low-risk patients now appearing to be NHF.

Bottom line: NHF oxygen reduced reintubation compared to conventional oxygen therapy (nasal cannula or face mask) in extubated patients at low risk of reintubation.

Citation: Hernández G, Vaquero C, González P, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: a randomized clinical trial. JAMA. 2016;315(13):1354-1361. doi:10.1001/jama.2016.2711.

Clinical question: Does nasal high-flow (NHF) oxygen after extubation reduce reintubation rates in low-risk patients?

Background: NHF oxygen devices deliver warmed and humidified oxygen up to 60 liters per minutes. NHF provides positive end-expiratory pressure and dead-space washout. NHF in higher-risk post-extubation patients has been shown to have clinical benefits. Whether NHF post-extubation benefits patients at low risk of reintubation is unknown.

Study design: Randomized control trial (RCT).

Setting: Seven ICUs in Spain.

Synopsis: In this RCT, post-extubation NHF oxygen for 24 hours reduced the risk of reintubation among 527 ICU adults at low risk of reintubation when compared to conventional oxygen therapy (by nasal cannula or face mask). Patients with hypercapnia during weaning trials were excluded. The risk of reintubation was 4.9% versus 12.2% in NHF versus standard oxygen therapy, with an absolute difference of 7.2% (95% CI, 2.5–12.2%; P=0.004). ICU length of stay and mortality were not significantly different between the groups. The strengths of the study were adequate sample size, prespecified criteria for reintubation, and low number of crossover patients.

Limitations of the trial were the high percentage of surgical and neurologic cases, exclusion of patients with a variety of common comorbidities, and the inability to blind the physicians to the treatment arm of the subjects. Select patients may benefit from noninvasive ventilation to prevent reintubation, which was not studied. These results are highly relevant to post-extubation patients, with the optimum therapy for low-risk patients now appearing to be NHF.

Bottom line: NHF oxygen reduced reintubation compared to conventional oxygen therapy (nasal cannula or face mask) in extubated patients at low risk of reintubation.

Citation: Hernández G, Vaquero C, González P, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: a randomized clinical trial. JAMA. 2016;315(13):1354-1361. doi:10.1001/jama.2016.2711.

Clinical question: Does nasal high-flow (NHF) oxygen after extubation reduce reintubation rates in low-risk patients?

Background: NHF oxygen devices deliver warmed and humidified oxygen up to 60 liters per minutes. NHF provides positive end-expiratory pressure and dead-space washout. NHF in higher-risk post-extubation patients has been shown to have clinical benefits. Whether NHF post-extubation benefits patients at low risk of reintubation is unknown.

Study design: Randomized control trial (RCT).

Setting: Seven ICUs in Spain.

Synopsis: In this RCT, post-extubation NHF oxygen for 24 hours reduced the risk of reintubation among 527 ICU adults at low risk of reintubation when compared to conventional oxygen therapy (by nasal cannula or face mask). Patients with hypercapnia during weaning trials were excluded. The risk of reintubation was 4.9% versus 12.2% in NHF versus standard oxygen therapy, with an absolute difference of 7.2% (95% CI, 2.5–12.2%; P=0.004). ICU length of stay and mortality were not significantly different between the groups. The strengths of the study were adequate sample size, prespecified criteria for reintubation, and low number of crossover patients.

Limitations of the trial were the high percentage of surgical and neurologic cases, exclusion of patients with a variety of common comorbidities, and the inability to blind the physicians to the treatment arm of the subjects. Select patients may benefit from noninvasive ventilation to prevent reintubation, which was not studied. These results are highly relevant to post-extubation patients, with the optimum therapy for low-risk patients now appearing to be NHF.

Bottom line: NHF oxygen reduced reintubation compared to conventional oxygen therapy (nasal cannula or face mask) in extubated patients at low risk of reintubation.

Citation: Hernández G, Vaquero C, González P, et al. Effect of postextubation high-flow nasal cannula vs conventional oxygen therapy on reintubation in low-risk patients: a randomized clinical trial. JAMA. 2016;315(13):1354-1361. doi:10.1001/jama.2016.2711.

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: How do interhospital handoff practices differ among U.S. tertiary care centers, and what challenges and innovations have providers encountered?

Background: Little has been studied regarding interhospital transfers. Many centers differ in the processes they follow, and well-delineated national guidelines are lacking. Adverse events occur in up to 30% of transfers. Standardization of these handoffs has been shown to reduce preventable errors and near misses.

Study design: Survey of convenience sample of institutions.

Setting: Transfer center directors from 32 tertiary care centers in the U.S.

Synopsis: The authors surveyed directors of 32 transfer centers between 2013 and 2015. Hospitals were selected from a nationally ranked list as well as those comparable to the authors’ own institutions. The median number of patients transferred per month was 700.

Only 23% of hospitals surveyed identified significant EHR interoperability. Almost all required three-way recorded discussion between transfer center staff and referring and accepting physicians. Only 29% had available objective clinical information to share. Only 23% recorded a three-way nursing handoff, and only 32% used their EHR to document the transfer process and share clinical information among providers.

Innovations included electronic transfer notes, a standardized system of feedback to referring hospitals, automatic internal review for adverse events and delayed transfers, and use of a scorecard with key measures shared with stakeholders.

Barriers noted included complexity, acuity, and lack of continuity. Increased use of EHRs, checklists, and common processes were identified as best practices.

Limitations of the study included reliance on verbal qualitative data, a single investigator doing most of the discussions, and possible sampling bias.

Bottom line: Interhospital transfer practices at academic tertiary care centers vary widely, and optimizing and aligning practices between sending and receiving hospitals may improve efficiency and patient outcomes.

References: Herrigel DJ, Carroll M, Fanning C, Steinberg MB, Parikh A, Usher M. Interhospital transfer handoff practices among US tertiary care centers: a descriptive survey. J Hosp Med. 2016;11(6):413-417.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.

Clinical question: Are oral steroids as effective as NSAIDs in treating acute gout?

Background: Two small trials have suggested that oral steroids are as effective as NSAIDs in treating acute gout. Wider acceptance of steroids as first-line agents for acute gout may require more robust evidence supporting their safety and efficacy.

Study design: Multicenter, double-blind, randomized equivalence trial.

Setting: Four EDs in Hong Kong.

Synopsis: The study included 416 patients presenting to the ED with clinically suspected acute gout who were randomized to treatment with either oral indomethacin or oral prednisolone for five days. A research investigator assessed response to therapy in the ED at 30, 60, 90, and 120 minutes after administration of the initial dose of medication. Patients then kept pain-assessment diaries for 14 days after discharge from the ED.

Pain scores were assessed using a visual analog scale of 0 mm (no pain) to 100 mm (worst pain the patient had experienced). Clinically significant changes in pain scores were defined as decreases of >13 mm on the visual analog scale.

The number of patients with clinically significant decreases in pain scores did not differ statistically between groups. Both groups had similar reductions in mean pain scores over the course of the study. Patients in the indomethacin group had a statistically significant increase in minor adverse events. No patients in either group had major adverse events.

Bottom line: Oral prednisolone appears to be a safe and effective first-line agent for the treatment of acute gout.

Citation: Rainer TH, Chen CH, Janssens HJEM, et al. Oral prednisolone in the treatment of acute gout. Ann Intern Med. 2016;164(7):464-471.

Short Take

Rate Control as Effective as Rhythm Control in Postoperative Atrial Fibrillation

This study randomized patients with postoperative atrial fibrillation to rhythm control (using amiodarone and/or direct current cardioversion) or rate control and found neither treatment strategy has a clinical benefit over the other.

Citation: Gillinov AM, Bagiella E, Moskowitz AJ, et al. Rate control versus rhythm control for atrial fibrillation after cardiac surgery. N Engl J Med. 2016;374(20):1911-1921.

Clinical question: What is the contribution of hospital-based medical errors to national mortality in the U.S. compared to other causes listed by the Centers for Disease Control and Prevention (CDC)?

Background: Medical error can contribute to patient mortality. Currently, the annual list of the most common causes of death in the U.S. is compiled by the CDC using the International Classification of Diseases (ICD) codes on death certificates. Deaths caused by errors are unmeasured because medical errors are not included in the death certificate.

Study design: Analysis of existing literature on medical errors.

Setting: U.S. hospitals.

Synopsis: Findings of four studies on U.S. death rates from medical errors published between 2000 and 2008 were synthesized and extrapolated to the total number of U.S. hospital admissions in 2013. This resulted in a mean rate of death from medical errors of 251,454 per year, which is much higher than the annual incidence of 44,000–98,000 deaths published in the 1999 Institute of Medicine report. Comparing these data to the CDC ranking makes medical errors the third-leading cause of death in the U.S.

Although the accuracy of this result is limited to inpatient deaths and as the authors extrapolated the data from other studies, the number is still staggering and highlights the need for systematic measurement of the problem. One simple solution for this could be to have an extra field on the death certificate asking whether a preventable complication stemming from the patient’s medical care contributed to the death.

Bottom line: Medical error as the estimated third-leading cause of the death in the U.S. remains under-recognized, underappreciated, and highly unmeasured.

Citation: Makary MA, Daniel M. Medical error-the third leading cause of death in the US. BMJ. 2016;353:i2139.

Short Take

Isolating C. Difficile Carriers Decreases Hospital-Acquired C. Difficile Infections

In a nonblinded time-series analysis, screening all patients for asymptomatic C. diff carrier status and isolating carriers reduced rates of hospital-acquired C. diff, preventing 62.4% of expected cases.

Citation: Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C difficile infections: a quasi-experimental controlled study. JAMA Inter Med. 2016;176(6):796¬-804.

Clinical question: What is the contribution of hospital-based medical errors to national mortality in the U.S. compared to other causes listed by the Centers for Disease Control and Prevention (CDC)?

Background: Medical error can contribute to patient mortality. Currently, the annual list of the most common causes of death in the U.S. is compiled by the CDC using the International Classification of Diseases (ICD) codes on death certificates. Deaths caused by errors are unmeasured because medical errors are not included in the death certificate.

Study design: Analysis of existing literature on medical errors.

Setting: U.S. hospitals.

Synopsis: Findings of four studies on U.S. death rates from medical errors published between 2000 and 2008 were synthesized and extrapolated to the total number of U.S. hospital admissions in 2013. This resulted in a mean rate of death from medical errors of 251,454 per year, which is much higher than the annual incidence of 44,000–98,000 deaths published in the 1999 Institute of Medicine report. Comparing these data to the CDC ranking makes medical errors the third-leading cause of death in the U.S.

Although the accuracy of this result is limited to inpatient deaths and as the authors extrapolated the data from other studies, the number is still staggering and highlights the need for systematic measurement of the problem. One simple solution for this could be to have an extra field on the death certificate asking whether a preventable complication stemming from the patient’s medical care contributed to the death.

Bottom line: Medical error as the estimated third-leading cause of the death in the U.S. remains under-recognized, underappreciated, and highly unmeasured.

Citation: Makary MA, Daniel M. Medical error-the third leading cause of death in the US. BMJ. 2016;353:i2139.

Short Take

Isolating C. Difficile Carriers Decreases Hospital-Acquired C. Difficile Infections

In a nonblinded time-series analysis, screening all patients for asymptomatic C. diff carrier status and isolating carriers reduced rates of hospital-acquired C. diff, preventing 62.4% of expected cases.

Citation: Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C difficile infections: a quasi-experimental controlled study. JAMA Inter Med. 2016;176(6):796¬-804.

Clinical question: What is the contribution of hospital-based medical errors to national mortality in the U.S. compared to other causes listed by the Centers for Disease Control and Prevention (CDC)?

Background: Medical error can contribute to patient mortality. Currently, the annual list of the most common causes of death in the U.S. is compiled by the CDC using the International Classification of Diseases (ICD) codes on death certificates. Deaths caused by errors are unmeasured because medical errors are not included in the death certificate.

Study design: Analysis of existing literature on medical errors.

Setting: U.S. hospitals.

Synopsis: Findings of four studies on U.S. death rates from medical errors published between 2000 and 2008 were synthesized and extrapolated to the total number of U.S. hospital admissions in 2013. This resulted in a mean rate of death from medical errors of 251,454 per year, which is much higher than the annual incidence of 44,000–98,000 deaths published in the 1999 Institute of Medicine report. Comparing these data to the CDC ranking makes medical errors the third-leading cause of death in the U.S.

Although the accuracy of this result is limited to inpatient deaths and as the authors extrapolated the data from other studies, the number is still staggering and highlights the need for systematic measurement of the problem. One simple solution for this could be to have an extra field on the death certificate asking whether a preventable complication stemming from the patient’s medical care contributed to the death.

Bottom line: Medical error as the estimated third-leading cause of the death in the U.S. remains under-recognized, underappreciated, and highly unmeasured.

Citation: Makary MA, Daniel M. Medical error-the third leading cause of death in the US. BMJ. 2016;353:i2139.

Short Take

Isolating C. Difficile Carriers Decreases Hospital-Acquired C. Difficile Infections

In a nonblinded time-series analysis, screening all patients for asymptomatic C. diff carrier status and isolating carriers reduced rates of hospital-acquired C. diff, preventing 62.4% of expected cases.

Citation: Longtin Y, Paquet-Bolduc B, Gilca R, et al. Effect of detecting and isolating Clostridium difficile carriers at hospital admission on the incidence of C difficile infections: a quasi-experimental controlled study. JAMA Inter Med. 2016;176(6):796¬-804.

Clinical question: How do guideline-based care and outcomes of patients with transient ischemic attack (TIA) and minor ischemic stroke differ among patients admitted to the hospital and discharged from the ED, as well as in those referred versus not referred to stroke prevention clinics following discharge?

Background: Previous research demonstrated that urgent outpatient management strategies for patients with TIA and minor ischemic stroke are superior to standard outpatient care. However, there is less known about how outpatient stroke care compares to inpatient care in terms of outcomes, rapid risk factor identification/modification, and initiation of antithrombotic therapy.

Study design: Retrospective cohort study.

Setting: EDs of acute-care hospitals in Ontario, Canada.

Synopsis: Using the Ontario Stroke Registry, 8,540 patients seen in the ED with TIA or minor ischemic stroke were identified. The use of guideline-based interventions was highest in admitted patients, followed by patients discharged from the ED with stroke clinic follow-up, followed by patients discharged without follow-up. There was no significant difference in one-year mortality between admitted and discharged patients when adjusted for age, sex, and comorbid conditions (adjusted hazard ratio, 1.11; 95% CI, 0.92–1.34). However, stroke clinic referral was associated with a lower risk of one-year mortality compared with those discharged without follow-up (adjusted hazard ratio, 0.49; 95% CI, 0.38–0.64).

Limitations of this study include that it was carried out only in Ontario, where there is a universal healthcare system, which may limit the generalizability of the findings. Additionally, patient information was limited to what was available through the registry, which may mean there were other unmeasurable differences among groups.

Bottom line: Admitted patients with TIA or minor ischemic stroke are more likely to receive guideline-based therapy, and among patients discharged from the ED, referral to stroke clinic improves outcomes, including one-year mortality.

Citation: Kapral MK, Hall R, Fang J, et al. Association between hospitalization and care after transient ischemic attack or minor stroke. Neurology. 2016;86(17):1582-1589.

Clinical question: How do guideline-based care and outcomes of patients with transient ischemic attack (TIA) and minor ischemic stroke differ among patients admitted to the hospital and discharged from the ED, as well as in those referred versus not referred to stroke prevention clinics following discharge?

Background: Previous research demonstrated that urgent outpatient management strategies for patients with TIA and minor ischemic stroke are superior to standard outpatient care. However, there is less known about how outpatient stroke care compares to inpatient care in terms of outcomes, rapid risk factor identification/modification, and initiation of antithrombotic therapy.

Study design: Retrospective cohort study.

Setting: EDs of acute-care hospitals in Ontario, Canada.

Synopsis: Using the Ontario Stroke Registry, 8,540 patients seen in the ED with TIA or minor ischemic stroke were identified. The use of guideline-based interventions was highest in admitted patients, followed by patients discharged from the ED with stroke clinic follow-up, followed by patients discharged without follow-up. There was no significant difference in one-year mortality between admitted and discharged patients when adjusted for age, sex, and comorbid conditions (adjusted hazard ratio, 1.11; 95% CI, 0.92–1.34). However, stroke clinic referral was associated with a lower risk of one-year mortality compared with those discharged without follow-up (adjusted hazard ratio, 0.49; 95% CI, 0.38–0.64).

Limitations of this study include that it was carried out only in Ontario, where there is a universal healthcare system, which may limit the generalizability of the findings. Additionally, patient information was limited to what was available through the registry, which may mean there were other unmeasurable differences among groups.

Bottom line: Admitted patients with TIA or minor ischemic stroke are more likely to receive guideline-based therapy, and among patients discharged from the ED, referral to stroke clinic improves outcomes, including one-year mortality.

Citation: Kapral MK, Hall R, Fang J, et al. Association between hospitalization and care after transient ischemic attack or minor stroke. Neurology. 2016;86(17):1582-1589.

Clinical question: How do guideline-based care and outcomes of patients with transient ischemic attack (TIA) and minor ischemic stroke differ among patients admitted to the hospital and discharged from the ED, as well as in those referred versus not referred to stroke prevention clinics following discharge?

Background: Previous research demonstrated that urgent outpatient management strategies for patients with TIA and minor ischemic stroke are superior to standard outpatient care. However, there is less known about how outpatient stroke care compares to inpatient care in terms of outcomes, rapid risk factor identification/modification, and initiation of antithrombotic therapy.

Study design: Retrospective cohort study.

Setting: EDs of acute-care hospitals in Ontario, Canada.

Synopsis: Using the Ontario Stroke Registry, 8,540 patients seen in the ED with TIA or minor ischemic stroke were identified. The use of guideline-based interventions was highest in admitted patients, followed by patients discharged from the ED with stroke clinic follow-up, followed by patients discharged without follow-up. There was no significant difference in one-year mortality between admitted and discharged patients when adjusted for age, sex, and comorbid conditions (adjusted hazard ratio, 1.11; 95% CI, 0.92–1.34). However, stroke clinic referral was associated with a lower risk of one-year mortality compared with those discharged without follow-up (adjusted hazard ratio, 0.49; 95% CI, 0.38–0.64).

Limitations of this study include that it was carried out only in Ontario, where there is a universal healthcare system, which may limit the generalizability of the findings. Additionally, patient information was limited to what was available through the registry, which may mean there were other unmeasurable differences among groups.

Bottom line: Admitted patients with TIA or minor ischemic stroke are more likely to receive guideline-based therapy, and among patients discharged from the ED, referral to stroke clinic improves outcomes, including one-year mortality.

Citation: Kapral MK, Hall R, Fang J, et al. Association between hospitalization and care after transient ischemic attack or minor stroke. Neurology. 2016;86(17):1582-1589.