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Statins may do double duty as antidepressants

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Changed

– The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.

Bruce Jancin/MDedge News
Dr. Christian Otte

Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.

SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.

For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).

His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).

At a symposium on repurposing statins as antidepressants held at ECNP 2019, Dr. Otte was joined by other researchers who have made key contributions in this area. All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.

Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.

 

 



Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).

Bruce Jancin/MDedge News
Dr. Ole Kohler

He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.

The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.

Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).

Bruce Jancin/MDedge News
Dr. Estela Salagre
However, those three randomized trials, while well conducted, have major limitations. They included only 165 participants in total, with just 6-12 weeks of follow-up. Moreover, all three RCTs were performed in one country – Iran – raising questions about their generalizability, Dr. Salagre said.
 

 



Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).

Bruce Jancin/MDedge News
Dr. Femke Lamers

“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.

All speakers reported having no financial conflicts of interest.

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– The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.

Bruce Jancin/MDedge News
Dr. Christian Otte

Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.

SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.

For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).

His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).

At a symposium on repurposing statins as antidepressants held at ECNP 2019, Dr. Otte was joined by other researchers who have made key contributions in this area. All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.

Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.

 

 



Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).

Bruce Jancin/MDedge News
Dr. Ole Kohler

He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.

The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.

Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).

Bruce Jancin/MDedge News
Dr. Estela Salagre
However, those three randomized trials, while well conducted, have major limitations. They included only 165 participants in total, with just 6-12 weeks of follow-up. Moreover, all three RCTs were performed in one country – Iran – raising questions about their generalizability, Dr. Salagre said.
 

 



Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).

Bruce Jancin/MDedge News
Dr. Femke Lamers

“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.

All speakers reported having no financial conflicts of interest.

– The tantalizing prospect that statins could be repurposed as adjunctive antidepressant drugs in a defined subgroup of patients with major depression is finally about to undergo rigorous testing.

Bruce Jancin/MDedge News
Dr. Christian Otte

Several lines of preliminary evidence, including large observational cohort studies as well as three small, short-duration randomized trials, suggest that this might indeed be the case. It’s an extremely attractive possibility, since patients and physicians wish that antidepressant therapy were more effective, statins are among the most widely prescribed drugs worldwide, and their safety profile is thoroughly established. The expectation is that a definitive answer as to whether repurposing of statins as antidepressants is worthwhile will be provided by the SIMCODE trial, recently approved for funding by the German Federal Ministry of Education and Research, Christian Otte, MD, announced at the annual congress of the European College of Neuropsychopharmacology.

SIMCODE is a multicenter, double-blind, placebo-controlled randomized trial to be conducted at eight German academic medical centers. Participants, all of whom must have major depressive disorder and comorbid obesity, will be randomized to simvastatin or placebo on top of standard antidepressant therapy with escitalopram, an SSRI which, like simvastatin, is available as a relatively inexpensive generic, explained Dr. Otte, professor and vice director of the department of psychiatry and psychotherapy at Charite University in Berlin.

For Dr. Otte, SIMCODE will close a circle he helped open with his 2012 report from the Heart and Soul Study, a prospective longitudinal study of nearly 1,000 San Francisco Bay Area patients with coronary heart disease who were assessed annually for depressive symptoms for 6 years. The 65% of patients who were on statin therapy, albeit in nonrandomized fashion, had an adjusted 38% lower risk of developing depression (J Clin Psychiatry. 2012 May;73[5]:610-5).

His was one of seven observational studies involving more than 9,000 patients included in a subsequent meta-analysis showing that statin users were 37% less likely to develop depression than were nonusers (J Affect Disord. 2014 May;160:62-7).

At a symposium on repurposing statins as antidepressants held at ECNP 2019, Dr. Otte was joined by other researchers who have made key contributions in this area. All agreed that the verdict isn’t in yet as to statins’ effectiveness as adjunctive antidepressants, and that the subgroup of patients with major depression who are most likely to gain added antidepressive effect from a statin are those with what the speakers variously described as comorbid cardiometabolic disease, immunometabolic disease, or simply, as in SIMCODE, obesity. These are patients with a high degree of systemic inflammation, which often makes their depression less responsive to standard antidepressant therapies. The working hypothesis is that the pleiotropic anti-inflammatory effects of statins will result in a greater response to conventional antidepressants.

Animal studies point to multiple potential mechanisms by which statins might have antidepressant efficacy in clinical practice, according to Dr. Otte. Beyond their anti-inflammatory effects, these include the drugs’ documented effects on glutamatergic N-methyl-D-aspartate (NMDA) receptors, dopamine receptors, brain-derived neurotrophic factor, glucocorticoid receptors, and hippocampal serotonin 2A receptors.

 

 



Ole Kohler, MD, a psychiatrist at Aarhus (Denmark) University, presented highlights of his eye-popping population-based study of more than 872,000 Danes on an SSRI in 1997-2012, more than 113,000 of whom were on a concomitant statin. The key finding: During roughly 3 years of follow-up, the risk of contact with a psychiatric hospital for depression was 36% lower in the group on concomitant SSRI/statin therapy than in those not on a statin (Am J Psychiatry. 2016 Aug 1;173[8]:807-15).

Bruce Jancin/MDedge News
Dr. Ole Kohler

He was quick to observe that a study such as this is vulnerable to various forms of confounding. This risk can be mitigated to a considerable extent by careful propensity score matching. Of note, however, none of the three studies that have been conducted with propensity score matching, including his own recent study of nearly 194,000 statin users and an equal number of matched nonusers, showed a difference in risk of depression between statin users and nonusers. All three studies were performed in general populations without known depression, leading Dr. Kohler to conclude that it’s unlikely that statins have a role in preventing depression in nondepressed individuals.

The focus should instead be on the possible role of statins in reducing the risk of depression in patients with cardiometabolic disease – that is, heart disease, metabolic syndrome, or type 2 diabetes – where more than a half-dozen cohort studies, including the Heart and Soul Study, have found that statins have a favorable impact, he added.

Estela Salagre, MD, a psychiatrist at the University of Barcelona, has carried out a meta-analysis of the three randomized, double-blind, placebo-controlled trials of add-on statin therapy in patients on standard therapies for moderate to severe depression published to date. She found that statin therapy was associated with a 27% greater reduction in scores on the Hamilton Depression Rating Scale, compared with placebo (J Affect Disord. 2016 Aug;200:235-42). Those findings recently were confirmed in a separate meta-analysis by other investigators using different methodologies (J Affect Disord. 2019 Oct 1;257:55-63).

Bruce Jancin/MDedge News
Dr. Estela Salagre
However, those three randomized trials, while well conducted, have major limitations. They included only 165 participants in total, with just 6-12 weeks of follow-up. Moreover, all three RCTs were performed in one country – Iran – raising questions about their generalizability, Dr. Salagre said.
 

 



Femke Lamers, PhD, presented evidence based on the nearly 3,000-subject longitudinal Netherlands Study of Depression and Anxiety that roughly one-quarter of individuals with major depressive disorder have a distinct subtype of nonmelancholic depression characterized by a clustering of obesity, inflammation, increased appetite, fatigue, hypersomnia, and increased levels of insulin and leptin. She calls it immunometabolic depression. She and her coinvestigators in the international Psychiatric Genomics Consortium have demonstrated that this phenotypic clustering is associated with a shared genetic vulnerability between major depression and obesity (JAMA Psychiatry. 2017 Dec 1;74[12]:1214-25).

Bruce Jancin/MDedge News
Dr. Femke Lamers

“Major depressive disorder is not a one-size-fits-all disorder. There is an immunometabolic form of depression,” declared Dr. Lamers, an epidemiologist at the University of Amsterdam.

All speakers reported having no financial conflicts of interest.

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Exercise intervention reverses functional decline in elderly patients during acute hospitalization

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Background: Acute hospitalization has been associated with functional and cognitive decline, particularly in elderly adults. This decline is associated with increased morbidity and mortality.

Dr. Constance Chace


Study design: Single-center, single-blind, randomized clinical trial.

Setting: Acute care unit in a tertiary public hospital in Navarra, Spain.

Synopsis: 370 patients aged 75 years or older who were hospitalized in an acute care unit received either individualized moderate intensity exercise regimens (focusing on resistance, balance, and walking) or standard hospital care (with physical rehabilitation as appropriate). Patients who received standard care had a decrease in functional capacity at discharge when compared with their baseline function (mean change of –5.0 points on the Barthel Index of Independence; 95% confidence interval, –6.8 to –3.2 points), while those who received the exercise intervention had no functional decline from baseline on discharge (mean change of 1.9 points; 95% CI, 0.2-3.7 points).

Patients who received the exercise intervention had significantly higher scores on functional and cognitive assessments at discharge, compared with patients who received standard hospital care alone. Specifically, the study demonstrated a mean increase of 2.2 points (95% CI, 1.7-2.6 points) on the Short Physical Performance Battery, 6.9 points (95% CI, 4.4-9.5 points) on the Barthel Index, and 1.8 points (95% CI, 1.3-2.3 points) on a cognitive assessment, compared with those who received standard hospital care.

Bottom line: An individualized, multicomponent exercise intervention can help reverse functional and cognitive decline associated with acute hospitalization in elderly patients.

Citation: Martinez-Velilla N et al. Effect of exercise intervention on functional decline in very elderly adults during acute hospitalization. JAMA Intern Med. 2019;179(1):28-36.

Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.

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Background: Acute hospitalization has been associated with functional and cognitive decline, particularly in elderly adults. This decline is associated with increased morbidity and mortality.

Dr. Constance Chace


Study design: Single-center, single-blind, randomized clinical trial.

Setting: Acute care unit in a tertiary public hospital in Navarra, Spain.

Synopsis: 370 patients aged 75 years or older who were hospitalized in an acute care unit received either individualized moderate intensity exercise regimens (focusing on resistance, balance, and walking) or standard hospital care (with physical rehabilitation as appropriate). Patients who received standard care had a decrease in functional capacity at discharge when compared with their baseline function (mean change of –5.0 points on the Barthel Index of Independence; 95% confidence interval, –6.8 to –3.2 points), while those who received the exercise intervention had no functional decline from baseline on discharge (mean change of 1.9 points; 95% CI, 0.2-3.7 points).

Patients who received the exercise intervention had significantly higher scores on functional and cognitive assessments at discharge, compared with patients who received standard hospital care alone. Specifically, the study demonstrated a mean increase of 2.2 points (95% CI, 1.7-2.6 points) on the Short Physical Performance Battery, 6.9 points (95% CI, 4.4-9.5 points) on the Barthel Index, and 1.8 points (95% CI, 1.3-2.3 points) on a cognitive assessment, compared with those who received standard hospital care.

Bottom line: An individualized, multicomponent exercise intervention can help reverse functional and cognitive decline associated with acute hospitalization in elderly patients.

Citation: Martinez-Velilla N et al. Effect of exercise intervention on functional decline in very elderly adults during acute hospitalization. JAMA Intern Med. 2019;179(1):28-36.

Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: Acute hospitalization has been associated with functional and cognitive decline, particularly in elderly adults. This decline is associated with increased morbidity and mortality.

Dr. Constance Chace


Study design: Single-center, single-blind, randomized clinical trial.

Setting: Acute care unit in a tertiary public hospital in Navarra, Spain.

Synopsis: 370 patients aged 75 years or older who were hospitalized in an acute care unit received either individualized moderate intensity exercise regimens (focusing on resistance, balance, and walking) or standard hospital care (with physical rehabilitation as appropriate). Patients who received standard care had a decrease in functional capacity at discharge when compared with their baseline function (mean change of –5.0 points on the Barthel Index of Independence; 95% confidence interval, –6.8 to –3.2 points), while those who received the exercise intervention had no functional decline from baseline on discharge (mean change of 1.9 points; 95% CI, 0.2-3.7 points).

Patients who received the exercise intervention had significantly higher scores on functional and cognitive assessments at discharge, compared with patients who received standard hospital care alone. Specifically, the study demonstrated a mean increase of 2.2 points (95% CI, 1.7-2.6 points) on the Short Physical Performance Battery, 6.9 points (95% CI, 4.4-9.5 points) on the Barthel Index, and 1.8 points (95% CI, 1.3-2.3 points) on a cognitive assessment, compared with those who received standard hospital care.

Bottom line: An individualized, multicomponent exercise intervention can help reverse functional and cognitive decline associated with acute hospitalization in elderly patients.

Citation: Martinez-Velilla N et al. Effect of exercise intervention on functional decline in very elderly adults during acute hospitalization. JAMA Intern Med. 2019;179(1):28-36.

Dr. Chace is an associate physician in the division of hospital medicine at the University of California, San Diego.

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ARNIs effective for acute decompensated heart failure

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Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.



Study design: Multicenter, randomized, double-blind, active-controlled trial.

Setting: A total of 129 centers in the United States.

Synopsis: Of 881 patients with acute HFrEF, 440 were randomized to receive sacubitril/valsartan and 441 were randomized to receive enalapril. The majority of patients were men; mean age was 61 years. The primary outcome was the mean reduction in NT-proBNP concentration at weeks 4 and 8 as compared with baseline. In the sacubitril/valsartan group, there was a 46.7% reduction from baseline, and in the enalapril group, there was a 25.3% reduction from baseline. With regard to drug safety, there was no difference between groups in worsening renal function, symptomatic hypotension, or hyperkalemia.

A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.

Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.

Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

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Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.



Study design: Multicenter, randomized, double-blind, active-controlled trial.

Setting: A total of 129 centers in the United States.

Synopsis: Of 881 patients with acute HFrEF, 440 were randomized to receive sacubitril/valsartan and 441 were randomized to receive enalapril. The majority of patients were men; mean age was 61 years. The primary outcome was the mean reduction in NT-proBNP concentration at weeks 4 and 8 as compared with baseline. In the sacubitril/valsartan group, there was a 46.7% reduction from baseline, and in the enalapril group, there was a 25.3% reduction from baseline. With regard to drug safety, there was no difference between groups in worsening renal function, symptomatic hypotension, or hyperkalemia.

A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.

Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.

Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: The PARADIGM-HF trial demonstrated that patients with chronic HFrEF treated with an ARNI (sacubitril/valsartan) had significantly reduced cardiovascular mortality and hospitalizations when compared with enalapril. Patients with acute decompensated heart failure were excluded from this trial. The PIONEER-HF trial was designed to determine whether initiation of an ARNI in patients with acute decompensated heart failure is effective.



Study design: Multicenter, randomized, double-blind, active-controlled trial.

Setting: A total of 129 centers in the United States.

Synopsis: Of 881 patients with acute HFrEF, 440 were randomized to receive sacubitril/valsartan and 441 were randomized to receive enalapril. The majority of patients were men; mean age was 61 years. The primary outcome was the mean reduction in NT-proBNP concentration at weeks 4 and 8 as compared with baseline. In the sacubitril/valsartan group, there was a 46.7% reduction from baseline, and in the enalapril group, there was a 25.3% reduction from baseline. With regard to drug safety, there was no difference between groups in worsening renal function, symptomatic hypotension, or hyperkalemia.

A limitation of this study is that 20% of patients in each group discontinued treatment by 8 weeks secondary to an adverse event. Additionally, a clinical measure such as cardiovascular mortality, all-cause mortality, or rehospitalization for heart failure was not included in the primary outcome.

Bottom line: In patients with acute decompensated HFrEF, ARNIs are more effective at reducing NT-proBNP levels than enalapril, while maintaining a similar safety profile. Further investigation to evaluate clinical outcomes needs to be completed.

Citation: Velazquez EJ et al. Angiotensin–neprilysin inhibition in acute decompensated heart failure. N Engl J Med. 2018 Nov 11. doi: 10.1056/NEJMoa1812851.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

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Wrong cuff size throws off pediatric BP by 5 mm Hg

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An arm cuff that’s one size too small in children will artificially elevate blood pressure 5 mm Hg, while one size too large will drop it 5 mm Hg, according to investigators from Columbia University in New York.

M. Alexander Otto/MDedge News
Dr. Ruchi Gupta Mahajan

There are five cuff sizes in pediatrics, depending on a child’s arm circumference. Ideally, it’s measured beforehand so the right cuff size is used, but that doesn’t always happen in everyday practice.

Sometimes, clinicians just estimate arm size before choosing a cuff or opt for the medium-sized cuff in most kids; other times, the correct size has gone missing, said lead investigator Ruchi Gupta Mahajan, MD, a pediatric nephrology fellow at Columbia.

For those situations, she and her colleagues wanted to quantify how much the wrong cuff size throws off blood pressure readings in children, something that’s been done before in adult medicine, but not in pediatrics.

The idea was to give clinicians a decent estimate of true blood pressure even when the cuff isn’t quite right, something that’s particularly important with an increasing emphasis on catching hypertension as early as possible in children, she said.

After her subjects sat quietly for 10 minutes, Dr. Mahajan took automated blood pressure readings on 137 children; once with the right cuff size, once with a cuff one size too small, and once with a cuff one size too big, with a minute apart between readings.

The children were aged 4-12 years old and were in the office for wellness visits. None of them had heart or kidney disease, and none were on steroids or any other medications that affect blood pressure. There were a few more boys than girls, and almost all the children were Hispanic.

Overall, systolic blood pressure was an average of 5 mm Hg less with the larger cuff and 5 mm Hg more with the smaller cuff. The finding was the same in both girls and boys, and it held across age groups and in under, over, and normal weight children.

“I was really surprised there was no difference between ages, 4-12 years of age, its just a single number: 5. [Even] if [you] don’t have the appropriate cuff size,” the finding means that it’s still possible to have a good estimate of blood pressure, Dr. Mahajan said at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

Meanwhile, cuff size didn’t have any statistically significant effect on diastolic pressure.

There was no outside funding for the study and Dr. Mahajan reported having no disclosures.

SOURCE: Mahajan RG et al. Joint Hypertension 2019, Abstract P182.

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An arm cuff that’s one size too small in children will artificially elevate blood pressure 5 mm Hg, while one size too large will drop it 5 mm Hg, according to investigators from Columbia University in New York.

M. Alexander Otto/MDedge News
Dr. Ruchi Gupta Mahajan

There are five cuff sizes in pediatrics, depending on a child’s arm circumference. Ideally, it’s measured beforehand so the right cuff size is used, but that doesn’t always happen in everyday practice.

Sometimes, clinicians just estimate arm size before choosing a cuff or opt for the medium-sized cuff in most kids; other times, the correct size has gone missing, said lead investigator Ruchi Gupta Mahajan, MD, a pediatric nephrology fellow at Columbia.

For those situations, she and her colleagues wanted to quantify how much the wrong cuff size throws off blood pressure readings in children, something that’s been done before in adult medicine, but not in pediatrics.

The idea was to give clinicians a decent estimate of true blood pressure even when the cuff isn’t quite right, something that’s particularly important with an increasing emphasis on catching hypertension as early as possible in children, she said.

After her subjects sat quietly for 10 minutes, Dr. Mahajan took automated blood pressure readings on 137 children; once with the right cuff size, once with a cuff one size too small, and once with a cuff one size too big, with a minute apart between readings.

The children were aged 4-12 years old and were in the office for wellness visits. None of them had heart or kidney disease, and none were on steroids or any other medications that affect blood pressure. There were a few more boys than girls, and almost all the children were Hispanic.

Overall, systolic blood pressure was an average of 5 mm Hg less with the larger cuff and 5 mm Hg more with the smaller cuff. The finding was the same in both girls and boys, and it held across age groups and in under, over, and normal weight children.

“I was really surprised there was no difference between ages, 4-12 years of age, its just a single number: 5. [Even] if [you] don’t have the appropriate cuff size,” the finding means that it’s still possible to have a good estimate of blood pressure, Dr. Mahajan said at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

Meanwhile, cuff size didn’t have any statistically significant effect on diastolic pressure.

There was no outside funding for the study and Dr. Mahajan reported having no disclosures.

SOURCE: Mahajan RG et al. Joint Hypertension 2019, Abstract P182.

 

An arm cuff that’s one size too small in children will artificially elevate blood pressure 5 mm Hg, while one size too large will drop it 5 mm Hg, according to investigators from Columbia University in New York.

M. Alexander Otto/MDedge News
Dr. Ruchi Gupta Mahajan

There are five cuff sizes in pediatrics, depending on a child’s arm circumference. Ideally, it’s measured beforehand so the right cuff size is used, but that doesn’t always happen in everyday practice.

Sometimes, clinicians just estimate arm size before choosing a cuff or opt for the medium-sized cuff in most kids; other times, the correct size has gone missing, said lead investigator Ruchi Gupta Mahajan, MD, a pediatric nephrology fellow at Columbia.

For those situations, she and her colleagues wanted to quantify how much the wrong cuff size throws off blood pressure readings in children, something that’s been done before in adult medicine, but not in pediatrics.

The idea was to give clinicians a decent estimate of true blood pressure even when the cuff isn’t quite right, something that’s particularly important with an increasing emphasis on catching hypertension as early as possible in children, she said.

After her subjects sat quietly for 10 minutes, Dr. Mahajan took automated blood pressure readings on 137 children; once with the right cuff size, once with a cuff one size too small, and once with a cuff one size too big, with a minute apart between readings.

The children were aged 4-12 years old and were in the office for wellness visits. None of them had heart or kidney disease, and none were on steroids or any other medications that affect blood pressure. There were a few more boys than girls, and almost all the children were Hispanic.

Overall, systolic blood pressure was an average of 5 mm Hg less with the larger cuff and 5 mm Hg more with the smaller cuff. The finding was the same in both girls and boys, and it held across age groups and in under, over, and normal weight children.

“I was really surprised there was no difference between ages, 4-12 years of age, its just a single number: 5. [Even] if [you] don’t have the appropriate cuff size,” the finding means that it’s still possible to have a good estimate of blood pressure, Dr. Mahajan said at the joint scientific sessions of the American Heart Association (AHA) Council on Hypertension, AHA Council on Kidney in Cardiovascular Disease, and American Society of Hypertension.

Meanwhile, cuff size didn’t have any statistically significant effect on diastolic pressure.

There was no outside funding for the study and Dr. Mahajan reported having no disclosures.

SOURCE: Mahajan RG et al. Joint Hypertension 2019, Abstract P182.

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REPORTING FROM JOINT HYPERTENSION 2019

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Battling hospitalist burnout

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Higher salaries are not sufficient

Hospitalist Rahul C. Borsadia, MD, had been working with Orlando Health Inpatient Medicine Group since the year of its founding in 2011.

The salaries of the practice’s physicians back then were based on relative value units (RVU) – the more patients that physicians saw, the higher their salaries. But a problem arose, Dr. Borsadia said. Physicians were trying to squeeze in two dozen or more patients a day “in a practice that is modeled for quality.”

“By the time the end of the day comes, it’s 9 or 10 p.m. and you are leaving but coming back at 6:30 the next morning. So, lack of sleep, more patients, striving to earn that higher salary,” he said. “The desire to perform quality work with that kind of patient load was not fulfilled and that lead to dissatisfaction and stress, which lead to irritation and exodus from the group.”

Three years ago, the practice transitioned to a throughput process with a census limit of 18 patients or less, without an RVU system, but with salary incentives based on patient satisfaction, billing, and documentation.

“We’ve not had anybody leave the hospital because of burnout or dissatisfaction” since the new system was put into place, Dr. Borsadia said. “Less burnout means more people are happy.”

Although symptoms of burnout still seem to be rampant across hospital medicine, hospitalists are putting potential solutions into place. And – sometimes – they are making progress, through tweaks in schedules and responsibilities, incentives suited to different goals, and better communication.
 

Scheduling problems

The need for continuing efforts to improve the work experience for hospitalists is apparent, said Henry Michtalik, MD, MPH, MHS, assistant professor of general internal medicine at Johns Hopkins, Baltimore, who led a workshop on the topic at the 2019 Annual Conference of the Society of Hospital Medicine (HM19).

Dr. Henry Michtalik

A 2016 survey of academic general internal medicine clinicians – including about 600 hospitalists and outpatient physicians – found that 67% reported high stress, 38% said they were “burned out,” 50% said they felt they had “low control” over their work, and 60% said they felt high documentation pressures. Still, 68% said they were satisfied with the values of their departments.

Hospitalists surveyed were actually less likely to say they were burned out, compared with outpatient internists – 52%, compared with 55% – but they were more likely to score low on a scale measuring personal accomplishments, compared with the outpatient clinicians – 20% to 10%. The survey found no significant difference between the two groups in depression or suicidality. But with 40% reporting depression and 10% reporting thoughts of suicide, the numbers virtually cry out for solutions.

Hospitalists in the HM19 workshop, as in other sessions at the Annual Conference, questioned whether the standard 7-days-on, 7-days-off work schedule – seven 12-hour shifts followed by 7 days off – allows hospitalists to pair their works lives with their personal lives in a sustainable way. They described the way that the stress and fatigue of such an intense work period bleeds into the days off that follow after it.

“By the end of seven 12’s, they’re bleary eyed, they’re upset, they go home (for) 2 days of washout before they even start to enjoy whatever life they have left,” said Jonathan Martin, MD, director of medicine at Cumberland Medical Center in Crossville, Tenn. “It’s hard to get hospitalists to buy in, which increases their dissatisfaction.”

Dr. Michtalik had a similar perspective.

“You just shut the rest of your life down completely for those 7 days and then, on your 7 days off, you’ve scheduled your life,” he said. “But that last off day – day number 7 – you feel that pit in your stomach, that the streak is coming.” He joked that the feeling was similar to the dread inspired by the phrase “winter is coming” in the popular HBO series “Game of Thrones.”

Systematic reviews of the literature have found that it’s mostly changes at the organization level – rather than changes that an individual physician makes on his or her own – that tend to make significant differences. Changes to structure, communication, and scheduling tend to work better than working on mindfulness, education, or trying to improve resilience, Dr. Michtalik said.

In one study discussed at the HM19 workshop, researchers compared a schedule in which an intensivist works in-house for 7 days, with home call at night, to a schedule in which the intensivist is completely off at night, with an in-house intensivist covering the night shift. The schedule in which the intensivist was truly off for the night significantly reduced reports of burnout, while not affecting length of stay or patient-experience outcomes.

Dr. Michtalik said that another study compared 4-week rotations to 2-week rotations for attending physicians. Researchers found that the 2-week version resulted in lower reports of burnout, with readmissions and patient experience unaffected, although they noted that residents tended to prefer 4-week schedules because they felt it resulted in better relationships with the attending physician.

Perhaps the dominant factor in job satisfaction that’s been identified in surveys is how physicians, patients, and administrators relate to one another, Dr. Michtalik said.

“The important concept here is that relationships were really important in driving job satisfaction, whether that be with our colleagues, our patients, or with the staff that you’re working with,” he said. “It’s always easier to decline a consultation or have a bad interaction with someone over the phone than it is if you actually know them or you are communicating face to face. That’s why it’s important to develop these kinds of relationships, which also put a face to what’s going on.”
 

 

 

Beyond salary adjustments

Hospitalists attending the HM19 workshop said they thought that participating in administration committees at their own institutions helps keep hospitalists involved in hospital matters, limiting the effects of burnout and improving workplace satisfaction.

Kevin McAninch, DO, a hospitalist with Central Ohio Primary Care in Westerville, said a shift in work responsibilities has made an improvement at his hospital. There is now an “inpatient support center” – which has a physician and a nurse in an office taking calls from 6 p.m. to 7 a.m., so that rounders can stop taking floor calls during that time.

The system “takes the pressure off our admitters at night and our nurses because they’re not getting floor calls anymore, so they’re just taking care of the admissions from the ER,” he said.

A recurring theme of the discussion was that salary alone seems universally incapable of eradicating feelings of burnout. One hospitalist said that in surveys, higher-paid physicians insist that monetary compensation is their main driver, but still often complain of burnout because they must work extra shifts to earn that higher level of pay.

Instead, burnout and satisfaction indicators tend to have more do to with time, control, and support, Dr. Michtalik noted.

Mangla Gulati, MD, SFHM, chief quality officer at the University of Maryland Medical Center in Baltimore, said that there’s no big secret about what hospitalists want from their places of employment. They want things like getting patients to service faster so they can make diagnoses, making sure patients get the care they need, fixing the problems associated with electronic medical records, and having a work-life “integration.”

“The questions is – how do we get there?” Dr. Gulati wondered. She suggested that hospitalists have to be more assertive and explanatory in their interactions with members of the hospital C-suite.

“I think it’s really important for you to understand or ask your C-suite, ‘Where are you in this whole journey? What is your perception of wellness? Tell me some of the measures of staff wellness,’ ” she said.

If the C-suite says “we have no money” to make improvements, hospitalists must be willing to say, ‘Well, you’re going to have to invest a little bit.’ ” Dr. Gulati said. “What is the ROI (return on investment) on the turnover of a physician? Because when you turn a physician over, you have to recruit and hire new staff.”

Dr. Gulati said that hospitalists should provide C-suite leaders with a detailed walk-through of their actual workflows – what their workdays look like – because “it’s not something they’re familiar with.”

Aside from improving relations with hospital administration, Dr. Gulati suggested creating CME programs for wellness, offering time and funding for physician support meetings, supporting flexibility in work hours, and creating programs specifically to help clinicians with burnout symptoms.

She also touted the benefits of “Schwartz Rounds,” in which several medical disciplines gather to talk about a case that was particularly challenging, clinically complex, and emotionally draining for everyone involved.

At Cumberland Medical Center, Dr. Martin said he has two meetings a month with executives in the hospital’s C-suite. One is with his hospitalist group, TeamHealth, and one is more direct, between himself and hospital administrators. It’s just 2 hours a month, but these conversations have undoubtedly helped, he said, although he cautioned that “the meetings themselves don’t have as much meaning if you aren’t communicating effectively,” meaning hospitalists must understand how the C-suite thinks and learn to speak in terms they understand.

“When I go to the administration now and I say ‘Hey, this is a problem that we’re having. I need your help in solving it,’ the executives are much more likely to respond to me than if they’d never seen me, or only see me rarely,” Dr. Martin said.

As a result, a collaborative approach to such conversations tends to be more effective.

“If you go to the C-suite and say, ‘Here’s our issue, how can you help us?’ – as opposed to telling the administration, ‘This is what I need’ – they are more likely to work with you to generate a solution.”

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Higher salaries are not sufficient

Higher salaries are not sufficient

Hospitalist Rahul C. Borsadia, MD, had been working with Orlando Health Inpatient Medicine Group since the year of its founding in 2011.

The salaries of the practice’s physicians back then were based on relative value units (RVU) – the more patients that physicians saw, the higher their salaries. But a problem arose, Dr. Borsadia said. Physicians were trying to squeeze in two dozen or more patients a day “in a practice that is modeled for quality.”

“By the time the end of the day comes, it’s 9 or 10 p.m. and you are leaving but coming back at 6:30 the next morning. So, lack of sleep, more patients, striving to earn that higher salary,” he said. “The desire to perform quality work with that kind of patient load was not fulfilled and that lead to dissatisfaction and stress, which lead to irritation and exodus from the group.”

Three years ago, the practice transitioned to a throughput process with a census limit of 18 patients or less, without an RVU system, but with salary incentives based on patient satisfaction, billing, and documentation.

“We’ve not had anybody leave the hospital because of burnout or dissatisfaction” since the new system was put into place, Dr. Borsadia said. “Less burnout means more people are happy.”

Although symptoms of burnout still seem to be rampant across hospital medicine, hospitalists are putting potential solutions into place. And – sometimes – they are making progress, through tweaks in schedules and responsibilities, incentives suited to different goals, and better communication.
 

Scheduling problems

The need for continuing efforts to improve the work experience for hospitalists is apparent, said Henry Michtalik, MD, MPH, MHS, assistant professor of general internal medicine at Johns Hopkins, Baltimore, who led a workshop on the topic at the 2019 Annual Conference of the Society of Hospital Medicine (HM19).

Dr. Henry Michtalik

A 2016 survey of academic general internal medicine clinicians – including about 600 hospitalists and outpatient physicians – found that 67% reported high stress, 38% said they were “burned out,” 50% said they felt they had “low control” over their work, and 60% said they felt high documentation pressures. Still, 68% said they were satisfied with the values of their departments.

Hospitalists surveyed were actually less likely to say they were burned out, compared with outpatient internists – 52%, compared with 55% – but they were more likely to score low on a scale measuring personal accomplishments, compared with the outpatient clinicians – 20% to 10%. The survey found no significant difference between the two groups in depression or suicidality. But with 40% reporting depression and 10% reporting thoughts of suicide, the numbers virtually cry out for solutions.

Hospitalists in the HM19 workshop, as in other sessions at the Annual Conference, questioned whether the standard 7-days-on, 7-days-off work schedule – seven 12-hour shifts followed by 7 days off – allows hospitalists to pair their works lives with their personal lives in a sustainable way. They described the way that the stress and fatigue of such an intense work period bleeds into the days off that follow after it.

“By the end of seven 12’s, they’re bleary eyed, they’re upset, they go home (for) 2 days of washout before they even start to enjoy whatever life they have left,” said Jonathan Martin, MD, director of medicine at Cumberland Medical Center in Crossville, Tenn. “It’s hard to get hospitalists to buy in, which increases their dissatisfaction.”

Dr. Michtalik had a similar perspective.

“You just shut the rest of your life down completely for those 7 days and then, on your 7 days off, you’ve scheduled your life,” he said. “But that last off day – day number 7 – you feel that pit in your stomach, that the streak is coming.” He joked that the feeling was similar to the dread inspired by the phrase “winter is coming” in the popular HBO series “Game of Thrones.”

Systematic reviews of the literature have found that it’s mostly changes at the organization level – rather than changes that an individual physician makes on his or her own – that tend to make significant differences. Changes to structure, communication, and scheduling tend to work better than working on mindfulness, education, or trying to improve resilience, Dr. Michtalik said.

In one study discussed at the HM19 workshop, researchers compared a schedule in which an intensivist works in-house for 7 days, with home call at night, to a schedule in which the intensivist is completely off at night, with an in-house intensivist covering the night shift. The schedule in which the intensivist was truly off for the night significantly reduced reports of burnout, while not affecting length of stay or patient-experience outcomes.

Dr. Michtalik said that another study compared 4-week rotations to 2-week rotations for attending physicians. Researchers found that the 2-week version resulted in lower reports of burnout, with readmissions and patient experience unaffected, although they noted that residents tended to prefer 4-week schedules because they felt it resulted in better relationships with the attending physician.

Perhaps the dominant factor in job satisfaction that’s been identified in surveys is how physicians, patients, and administrators relate to one another, Dr. Michtalik said.

“The important concept here is that relationships were really important in driving job satisfaction, whether that be with our colleagues, our patients, or with the staff that you’re working with,” he said. “It’s always easier to decline a consultation or have a bad interaction with someone over the phone than it is if you actually know them or you are communicating face to face. That’s why it’s important to develop these kinds of relationships, which also put a face to what’s going on.”
 

 

 

Beyond salary adjustments

Hospitalists attending the HM19 workshop said they thought that participating in administration committees at their own institutions helps keep hospitalists involved in hospital matters, limiting the effects of burnout and improving workplace satisfaction.

Kevin McAninch, DO, a hospitalist with Central Ohio Primary Care in Westerville, said a shift in work responsibilities has made an improvement at his hospital. There is now an “inpatient support center” – which has a physician and a nurse in an office taking calls from 6 p.m. to 7 a.m., so that rounders can stop taking floor calls during that time.

The system “takes the pressure off our admitters at night and our nurses because they’re not getting floor calls anymore, so they’re just taking care of the admissions from the ER,” he said.

A recurring theme of the discussion was that salary alone seems universally incapable of eradicating feelings of burnout. One hospitalist said that in surveys, higher-paid physicians insist that monetary compensation is their main driver, but still often complain of burnout because they must work extra shifts to earn that higher level of pay.

Instead, burnout and satisfaction indicators tend to have more do to with time, control, and support, Dr. Michtalik noted.

Mangla Gulati, MD, SFHM, chief quality officer at the University of Maryland Medical Center in Baltimore, said that there’s no big secret about what hospitalists want from their places of employment. They want things like getting patients to service faster so they can make diagnoses, making sure patients get the care they need, fixing the problems associated with electronic medical records, and having a work-life “integration.”

“The questions is – how do we get there?” Dr. Gulati wondered. She suggested that hospitalists have to be more assertive and explanatory in their interactions with members of the hospital C-suite.

“I think it’s really important for you to understand or ask your C-suite, ‘Where are you in this whole journey? What is your perception of wellness? Tell me some of the measures of staff wellness,’ ” she said.

If the C-suite says “we have no money” to make improvements, hospitalists must be willing to say, ‘Well, you’re going to have to invest a little bit.’ ” Dr. Gulati said. “What is the ROI (return on investment) on the turnover of a physician? Because when you turn a physician over, you have to recruit and hire new staff.”

Dr. Gulati said that hospitalists should provide C-suite leaders with a detailed walk-through of their actual workflows – what their workdays look like – because “it’s not something they’re familiar with.”

Aside from improving relations with hospital administration, Dr. Gulati suggested creating CME programs for wellness, offering time and funding for physician support meetings, supporting flexibility in work hours, and creating programs specifically to help clinicians with burnout symptoms.

She also touted the benefits of “Schwartz Rounds,” in which several medical disciplines gather to talk about a case that was particularly challenging, clinically complex, and emotionally draining for everyone involved.

At Cumberland Medical Center, Dr. Martin said he has two meetings a month with executives in the hospital’s C-suite. One is with his hospitalist group, TeamHealth, and one is more direct, between himself and hospital administrators. It’s just 2 hours a month, but these conversations have undoubtedly helped, he said, although he cautioned that “the meetings themselves don’t have as much meaning if you aren’t communicating effectively,” meaning hospitalists must understand how the C-suite thinks and learn to speak in terms they understand.

“When I go to the administration now and I say ‘Hey, this is a problem that we’re having. I need your help in solving it,’ the executives are much more likely to respond to me than if they’d never seen me, or only see me rarely,” Dr. Martin said.

As a result, a collaborative approach to such conversations tends to be more effective.

“If you go to the C-suite and say, ‘Here’s our issue, how can you help us?’ – as opposed to telling the administration, ‘This is what I need’ – they are more likely to work with you to generate a solution.”

Hospitalist Rahul C. Borsadia, MD, had been working with Orlando Health Inpatient Medicine Group since the year of its founding in 2011.

The salaries of the practice’s physicians back then were based on relative value units (RVU) – the more patients that physicians saw, the higher their salaries. But a problem arose, Dr. Borsadia said. Physicians were trying to squeeze in two dozen or more patients a day “in a practice that is modeled for quality.”

“By the time the end of the day comes, it’s 9 or 10 p.m. and you are leaving but coming back at 6:30 the next morning. So, lack of sleep, more patients, striving to earn that higher salary,” he said. “The desire to perform quality work with that kind of patient load was not fulfilled and that lead to dissatisfaction and stress, which lead to irritation and exodus from the group.”

Three years ago, the practice transitioned to a throughput process with a census limit of 18 patients or less, without an RVU system, but with salary incentives based on patient satisfaction, billing, and documentation.

“We’ve not had anybody leave the hospital because of burnout or dissatisfaction” since the new system was put into place, Dr. Borsadia said. “Less burnout means more people are happy.”

Although symptoms of burnout still seem to be rampant across hospital medicine, hospitalists are putting potential solutions into place. And – sometimes – they are making progress, through tweaks in schedules and responsibilities, incentives suited to different goals, and better communication.
 

Scheduling problems

The need for continuing efforts to improve the work experience for hospitalists is apparent, said Henry Michtalik, MD, MPH, MHS, assistant professor of general internal medicine at Johns Hopkins, Baltimore, who led a workshop on the topic at the 2019 Annual Conference of the Society of Hospital Medicine (HM19).

Dr. Henry Michtalik

A 2016 survey of academic general internal medicine clinicians – including about 600 hospitalists and outpatient physicians – found that 67% reported high stress, 38% said they were “burned out,” 50% said they felt they had “low control” over their work, and 60% said they felt high documentation pressures. Still, 68% said they were satisfied with the values of their departments.

Hospitalists surveyed were actually less likely to say they were burned out, compared with outpatient internists – 52%, compared with 55% – but they were more likely to score low on a scale measuring personal accomplishments, compared with the outpatient clinicians – 20% to 10%. The survey found no significant difference between the two groups in depression or suicidality. But with 40% reporting depression and 10% reporting thoughts of suicide, the numbers virtually cry out for solutions.

Hospitalists in the HM19 workshop, as in other sessions at the Annual Conference, questioned whether the standard 7-days-on, 7-days-off work schedule – seven 12-hour shifts followed by 7 days off – allows hospitalists to pair their works lives with their personal lives in a sustainable way. They described the way that the stress and fatigue of such an intense work period bleeds into the days off that follow after it.

“By the end of seven 12’s, they’re bleary eyed, they’re upset, they go home (for) 2 days of washout before they even start to enjoy whatever life they have left,” said Jonathan Martin, MD, director of medicine at Cumberland Medical Center in Crossville, Tenn. “It’s hard to get hospitalists to buy in, which increases their dissatisfaction.”

Dr. Michtalik had a similar perspective.

“You just shut the rest of your life down completely for those 7 days and then, on your 7 days off, you’ve scheduled your life,” he said. “But that last off day – day number 7 – you feel that pit in your stomach, that the streak is coming.” He joked that the feeling was similar to the dread inspired by the phrase “winter is coming” in the popular HBO series “Game of Thrones.”

Systematic reviews of the literature have found that it’s mostly changes at the organization level – rather than changes that an individual physician makes on his or her own – that tend to make significant differences. Changes to structure, communication, and scheduling tend to work better than working on mindfulness, education, or trying to improve resilience, Dr. Michtalik said.

In one study discussed at the HM19 workshop, researchers compared a schedule in which an intensivist works in-house for 7 days, with home call at night, to a schedule in which the intensivist is completely off at night, with an in-house intensivist covering the night shift. The schedule in which the intensivist was truly off for the night significantly reduced reports of burnout, while not affecting length of stay or patient-experience outcomes.

Dr. Michtalik said that another study compared 4-week rotations to 2-week rotations for attending physicians. Researchers found that the 2-week version resulted in lower reports of burnout, with readmissions and patient experience unaffected, although they noted that residents tended to prefer 4-week schedules because they felt it resulted in better relationships with the attending physician.

Perhaps the dominant factor in job satisfaction that’s been identified in surveys is how physicians, patients, and administrators relate to one another, Dr. Michtalik said.

“The important concept here is that relationships were really important in driving job satisfaction, whether that be with our colleagues, our patients, or with the staff that you’re working with,” he said. “It’s always easier to decline a consultation or have a bad interaction with someone over the phone than it is if you actually know them or you are communicating face to face. That’s why it’s important to develop these kinds of relationships, which also put a face to what’s going on.”
 

 

 

Beyond salary adjustments

Hospitalists attending the HM19 workshop said they thought that participating in administration committees at their own institutions helps keep hospitalists involved in hospital matters, limiting the effects of burnout and improving workplace satisfaction.

Kevin McAninch, DO, a hospitalist with Central Ohio Primary Care in Westerville, said a shift in work responsibilities has made an improvement at his hospital. There is now an “inpatient support center” – which has a physician and a nurse in an office taking calls from 6 p.m. to 7 a.m., so that rounders can stop taking floor calls during that time.

The system “takes the pressure off our admitters at night and our nurses because they’re not getting floor calls anymore, so they’re just taking care of the admissions from the ER,” he said.

A recurring theme of the discussion was that salary alone seems universally incapable of eradicating feelings of burnout. One hospitalist said that in surveys, higher-paid physicians insist that monetary compensation is their main driver, but still often complain of burnout because they must work extra shifts to earn that higher level of pay.

Instead, burnout and satisfaction indicators tend to have more do to with time, control, and support, Dr. Michtalik noted.

Mangla Gulati, MD, SFHM, chief quality officer at the University of Maryland Medical Center in Baltimore, said that there’s no big secret about what hospitalists want from their places of employment. They want things like getting patients to service faster so they can make diagnoses, making sure patients get the care they need, fixing the problems associated with electronic medical records, and having a work-life “integration.”

“The questions is – how do we get there?” Dr. Gulati wondered. She suggested that hospitalists have to be more assertive and explanatory in their interactions with members of the hospital C-suite.

“I think it’s really important for you to understand or ask your C-suite, ‘Where are you in this whole journey? What is your perception of wellness? Tell me some of the measures of staff wellness,’ ” she said.

If the C-suite says “we have no money” to make improvements, hospitalists must be willing to say, ‘Well, you’re going to have to invest a little bit.’ ” Dr. Gulati said. “What is the ROI (return on investment) on the turnover of a physician? Because when you turn a physician over, you have to recruit and hire new staff.”

Dr. Gulati said that hospitalists should provide C-suite leaders with a detailed walk-through of their actual workflows – what their workdays look like – because “it’s not something they’re familiar with.”

Aside from improving relations with hospital administration, Dr. Gulati suggested creating CME programs for wellness, offering time and funding for physician support meetings, supporting flexibility in work hours, and creating programs specifically to help clinicians with burnout symptoms.

She also touted the benefits of “Schwartz Rounds,” in which several medical disciplines gather to talk about a case that was particularly challenging, clinically complex, and emotionally draining for everyone involved.

At Cumberland Medical Center, Dr. Martin said he has two meetings a month with executives in the hospital’s C-suite. One is with his hospitalist group, TeamHealth, and one is more direct, between himself and hospital administrators. It’s just 2 hours a month, but these conversations have undoubtedly helped, he said, although he cautioned that “the meetings themselves don’t have as much meaning if you aren’t communicating effectively,” meaning hospitalists must understand how the C-suite thinks and learn to speak in terms they understand.

“When I go to the administration now and I say ‘Hey, this is a problem that we’re having. I need your help in solving it,’ the executives are much more likely to respond to me than if they’d never seen me, or only see me rarely,” Dr. Martin said.

As a result, a collaborative approach to such conversations tends to be more effective.

“If you go to the C-suite and say, ‘Here’s our issue, how can you help us?’ – as opposed to telling the administration, ‘This is what I need’ – they are more likely to work with you to generate a solution.”

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Health care–associated infection rates going down

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Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

Dr. Jonathan McIntyre

Study design: Point-prevalence survey.

Setting: A collection of 199 Emerging Infection Program hospitals in 10 states.

Synopsis: Of 12,299 patients surveyed, 3.2% (95% confidence interval, 2.9%-3.5%) were found to have at least one HAI. This was a statistically significant reduction compared to the prevalence of 4% (95% CI, 3.7%-4.4%) found in the 2011 study. Approximately 75% of patients were on a medical ward, and 15% of patients were in the ICU. The age and sex of patients were similar to those of patients in the 2011 study.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

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Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

Dr. Jonathan McIntyre

Study design: Point-prevalence survey.

Setting: A collection of 199 Emerging Infection Program hospitals in 10 states.

Synopsis: Of 12,299 patients surveyed, 3.2% (95% confidence interval, 2.9%-3.5%) were found to have at least one HAI. This was a statistically significant reduction compared to the prevalence of 4% (95% CI, 3.7%-4.4%) found in the 2011 study. Approximately 75% of patients were on a medical ward, and 15% of patients were in the ICU. The age and sex of patients were similar to those of patients in the 2011 study.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: HAIs are key drivers of morbidity and mortality for hospitalized patients. In 2011, the Centers for Disease Control and Prevention (CDC) conducted a point-prevalence survey that revealed an HAI in 4% of hospitalized patients. The most common infections included pneumonia, gastrointestinal infections, and surgical-site infections. Over time, efforts in patient safety and quality have expanded to reduce the rate of HAIs. This same survey was repeated in 2015 to assess for improvements.

Dr. Jonathan McIntyre

Study design: Point-prevalence survey.

Setting: A collection of 199 Emerging Infection Program hospitals in 10 states.

Synopsis: Of 12,299 patients surveyed, 3.2% (95% confidence interval, 2.9%-3.5%) were found to have at least one HAI. This was a statistically significant reduction compared to the prevalence of 4% (95% CI, 3.7%-4.4%) found in the 2011 study. Approximately 75% of patients were on a medical ward, and 15% of patients were in the ICU. The age and sex of patients were similar to those of patients in the 2011 study.

The reduction in HAIs was primarily driven by a reduction in surgical-site infections and urinary tract infections. There was no reduction in the prevalence of health care–associated pneumonia, Clostridium difficile infection, or mortality. Consequently, this emphasizes the necessity of further work in these domains.

Bottom line: The overall prevalence of HAIs has decreased, but further quality improvement work is needed in order to expand this reduction to health care–associated pneumonia, C. difficile infection, and mortality from HAIs.

Citation: Magill SS et al. Changes in prevalence of heath care–associated infections in U.S. hospitals. N Engl J Med. 2018;379(18):1732-44.

Dr. McIntyre is an associate physician in the division of hospital medicine at the University of California, San Diego.

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Use of a CDSS increases safe outpatient management of low-risk PE patients

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Background: Despite multiple guidelines that support outpatient management of acute PE in the appropriate patient population, the rate of hospital admission for patients eligible for outpatient management remains high. One explanation is that physicians may have difficulty identifying which patients meet discharge criteria.



Study design: Controlled pragmatic trial.

Setting: Kaiser Permanente Northern California (KPNC).

Synopsis: A total of 21 KPNC EDs participated in this 16-month study of 1,703 patients; 11 EDs served as control sites and 10 as intervention sites. At month 9, ED physician study champions at intervention sites provided in-person training on outpatient PE management, the validated PE severity index (PESI), and the electronic CDSS. The CDSS was designed to use evidence-based guidelines to assist physicians in identifying patients eligible for outpatient care or short-term (less than 24-hour) observation in the ED. The CDSS was incorporated into the electronic medical record navigator used by ED physicians and not only calculated the PESI score, but also provided the patient’s risk class and 30-day all-cause mortality estimate. Adverse outcomes were defined as 5-day return visits for PE-related symptoms, recurrent VTE, major hemorrhage, and all-cause 30-day mortality. Results demonstrated an increase in home discharge at intervention sites (17.4% pre to 28% post) without an increase in adverse outcomes.

Bottom line: Use of an electronic CDSS to identify patients appropriate for home management of acute PE decreased admission rates without increasing adverse outcomes.

Citation: Vinson DR et al. Increasing safe outpatient management of emergency department patients with pulmonary embolism: a controlled pragmatic trial. Ann Int Med. 2018;169(12):855-65.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

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Background: Despite multiple guidelines that support outpatient management of acute PE in the appropriate patient population, the rate of hospital admission for patients eligible for outpatient management remains high. One explanation is that physicians may have difficulty identifying which patients meet discharge criteria.



Study design: Controlled pragmatic trial.

Setting: Kaiser Permanente Northern California (KPNC).

Synopsis: A total of 21 KPNC EDs participated in this 16-month study of 1,703 patients; 11 EDs served as control sites and 10 as intervention sites. At month 9, ED physician study champions at intervention sites provided in-person training on outpatient PE management, the validated PE severity index (PESI), and the electronic CDSS. The CDSS was designed to use evidence-based guidelines to assist physicians in identifying patients eligible for outpatient care or short-term (less than 24-hour) observation in the ED. The CDSS was incorporated into the electronic medical record navigator used by ED physicians and not only calculated the PESI score, but also provided the patient’s risk class and 30-day all-cause mortality estimate. Adverse outcomes were defined as 5-day return visits for PE-related symptoms, recurrent VTE, major hemorrhage, and all-cause 30-day mortality. Results demonstrated an increase in home discharge at intervention sites (17.4% pre to 28% post) without an increase in adverse outcomes.

Bottom line: Use of an electronic CDSS to identify patients appropriate for home management of acute PE decreased admission rates without increasing adverse outcomes.

Citation: Vinson DR et al. Increasing safe outpatient management of emergency department patients with pulmonary embolism: a controlled pragmatic trial. Ann Int Med. 2018;169(12):855-65.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: Despite multiple guidelines that support outpatient management of acute PE in the appropriate patient population, the rate of hospital admission for patients eligible for outpatient management remains high. One explanation is that physicians may have difficulty identifying which patients meet discharge criteria.



Study design: Controlled pragmatic trial.

Setting: Kaiser Permanente Northern California (KPNC).

Synopsis: A total of 21 KPNC EDs participated in this 16-month study of 1,703 patients; 11 EDs served as control sites and 10 as intervention sites. At month 9, ED physician study champions at intervention sites provided in-person training on outpatient PE management, the validated PE severity index (PESI), and the electronic CDSS. The CDSS was designed to use evidence-based guidelines to assist physicians in identifying patients eligible for outpatient care or short-term (less than 24-hour) observation in the ED. The CDSS was incorporated into the electronic medical record navigator used by ED physicians and not only calculated the PESI score, but also provided the patient’s risk class and 30-day all-cause mortality estimate. Adverse outcomes were defined as 5-day return visits for PE-related symptoms, recurrent VTE, major hemorrhage, and all-cause 30-day mortality. Results demonstrated an increase in home discharge at intervention sites (17.4% pre to 28% post) without an increase in adverse outcomes.

Bottom line: Use of an electronic CDSS to identify patients appropriate for home management of acute PE decreased admission rates without increasing adverse outcomes.

Citation: Vinson DR et al. Increasing safe outpatient management of emergency department patients with pulmonary embolism: a controlled pragmatic trial. Ann Int Med. 2018;169(12):855-65.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

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Type of renal dysfunction affects liver cirrhosis mortality risk

Cirrhotic patients are also at risk of chronic kidney disease
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For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 for 90 days with a final rate of at least 30 mL/min/1.73 m2. Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

 

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

Body

Cirrhotic patients with renal failure have a sevenfold increase in mortality compared with those without renal failure. Acute kidney injury (AKI) is common in cirrhosis; increasingly, cirrhotic patients awaiting liver transplantation have or are also at risk for CKD. They are sicker, older, and have more comorbidities such as obesity and diabetes. In this study, the cumulative incidence of death on the wait list was much more pronounced for any form of AKI, with those with AKI on CKD having the highest cumulative incidence of wait list mortality compared with those with normal renal function. The study notably raises several important issues. First, AKI exerts a greater influence in risk of mortality on CKD than it does on those with normal renal function. This is relevant given the increasing prevalence of CKD in this population. Second, it emphasizes the need to effectively measure renal function. All serum creatinine-based equations overestimate glomerular filtration rate in the presence of renal dysfunction. Finally, the study highlights the importance of extrahepatic factors in determining mortality on the wait list. While in all comers, a mathematical model such as the MELDNa score may be able to predict mortality, for a specific patient the presence of comorbid conditions, malnutrition and sarcopenia, infections, critical illness, and now pattern of renal dysfunction, may all play a role.

Dr. Sumeet K. Asrani
The study raises questions ripe for further study: Should we incorporate pattern of renal injury into prognostic models and allocation? Investigation should focus on identifying and validating biomarkers that represent the many phenotypes/mechanisms of AKI/CKD as there may be differential effects on morbidity and mortality in cirrhotic patients.

Sumeet K. Asrani, MD, MSc, is a hepatologist affiliated with Baylor University Medical Center, Dallas. He has no conflicts of interest.

 

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Body

Cirrhotic patients with renal failure have a sevenfold increase in mortality compared with those without renal failure. Acute kidney injury (AKI) is common in cirrhosis; increasingly, cirrhotic patients awaiting liver transplantation have or are also at risk for CKD. They are sicker, older, and have more comorbidities such as obesity and diabetes. In this study, the cumulative incidence of death on the wait list was much more pronounced for any form of AKI, with those with AKI on CKD having the highest cumulative incidence of wait list mortality compared with those with normal renal function. The study notably raises several important issues. First, AKI exerts a greater influence in risk of mortality on CKD than it does on those with normal renal function. This is relevant given the increasing prevalence of CKD in this population. Second, it emphasizes the need to effectively measure renal function. All serum creatinine-based equations overestimate glomerular filtration rate in the presence of renal dysfunction. Finally, the study highlights the importance of extrahepatic factors in determining mortality on the wait list. While in all comers, a mathematical model such as the MELDNa score may be able to predict mortality, for a specific patient the presence of comorbid conditions, malnutrition and sarcopenia, infections, critical illness, and now pattern of renal dysfunction, may all play a role.

Dr. Sumeet K. Asrani
The study raises questions ripe for further study: Should we incorporate pattern of renal injury into prognostic models and allocation? Investigation should focus on identifying and validating biomarkers that represent the many phenotypes/mechanisms of AKI/CKD as there may be differential effects on morbidity and mortality in cirrhotic patients.

Sumeet K. Asrani, MD, MSc, is a hepatologist affiliated with Baylor University Medical Center, Dallas. He has no conflicts of interest.

 

Body

Cirrhotic patients with renal failure have a sevenfold increase in mortality compared with those without renal failure. Acute kidney injury (AKI) is common in cirrhosis; increasingly, cirrhotic patients awaiting liver transplantation have or are also at risk for CKD. They are sicker, older, and have more comorbidities such as obesity and diabetes. In this study, the cumulative incidence of death on the wait list was much more pronounced for any form of AKI, with those with AKI on CKD having the highest cumulative incidence of wait list mortality compared with those with normal renal function. The study notably raises several important issues. First, AKI exerts a greater influence in risk of mortality on CKD than it does on those with normal renal function. This is relevant given the increasing prevalence of CKD in this population. Second, it emphasizes the need to effectively measure renal function. All serum creatinine-based equations overestimate glomerular filtration rate in the presence of renal dysfunction. Finally, the study highlights the importance of extrahepatic factors in determining mortality on the wait list. While in all comers, a mathematical model such as the MELDNa score may be able to predict mortality, for a specific patient the presence of comorbid conditions, malnutrition and sarcopenia, infections, critical illness, and now pattern of renal dysfunction, may all play a role.

Dr. Sumeet K. Asrani
The study raises questions ripe for further study: Should we incorporate pattern of renal injury into prognostic models and allocation? Investigation should focus on identifying and validating biomarkers that represent the many phenotypes/mechanisms of AKI/CKD as there may be differential effects on morbidity and mortality in cirrhotic patients.

Sumeet K. Asrani, MD, MSc, is a hepatologist affiliated with Baylor University Medical Center, Dallas. He has no conflicts of interest.

 

Title
Cirrhotic patients are also at risk of chronic kidney disease
Cirrhotic patients are also at risk of chronic kidney disease

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 for 90 days with a final rate of at least 30 mL/min/1.73 m2. Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

 

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

For non–status 1 patients with cirrhosis who are awaiting liver transplantation, type of renal dysfunction may be a key determinant of mortality risk, based on a retrospective analysis of more than 22,000 patients.

Risk of death was greatest for patients with acute on chronic kidney disease (AKI on CKD), followed by AKI alone, then CKD alone, reported lead author Giuseppe Cullaro, MD, of the University of California, San Francisco, and colleagues.

Although it is well known that renal dysfunction worsens outcomes among patients with liver cirrhosis, the impact of different types of kidney pathology on mortality risk has been minimally researched, the investigators wrote in Clinical Gastroenterology and Hepatology. “To date, studies evaluating the impact of renal dysfunction on prognosis in patients with cirrhosis have mostly focused on AKI.”

To learn more, the investigators performed a retrospective study involving acute, chronic, and acute on chronic kidney disease among patients with cirrhosis. They included data from 22,680 non–status 1 adults who were awaiting liver transplantation between 2007 and 2014, with at least 90 days on the wait list. Information was gathered from the Organ Procurement and Transplantation Network registry.

AKI was defined by fewer than 72 days of hemodialysis, or an increase in creatinine of at least 0.3 mg/dL or at least 50% in the last 7 days. CKD was identified by more than 72 days of hemodialysis, or an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 for 90 days with a final rate of at least 30 mL/min/1.73 m2. Using these criteria, the researchers put patients into four possible categories: AKI on CKD, AKI, CKD, or normal renal function. The primary outcome was wait list mortality, which was defined as death, or removal from the wait list for illness. Follow-up started at the time of addition to the wait list and continued until transplant, removal from the wait list, or death.

Multivariate analysis, which accounted for final MELD-Na score and other confounders, showed that patients with AKI on CKD fared worst, with a 2.86-fold higher mortality risk (subhazard [SHR] ratio, 2.86) than that of patients with normal renal function. The mortality risk for acute on chronic kidney disease was followed closely by patients with AKI alone (SHR, 2.42), and more distantly by patients with CKD alone (SHR, 1.56). Further analysis showed that the disparity between mortality risks of each subgroup became more pronounced with increased MELD-Na score. In addition, evaluation of receiver operating characteristic curves for 6-month wait list mortality showed that the addition of renal function to MELD-Na score increased the accuracy of prognosis from an area under the curve of 0.71 to 0.80 (P less than .001).

“This suggests that incorporating the pattern of renal function could provide an opportunity to better prognosticate risk of mortality in the patients with cirrhosis who are the sickest,” the investigators concluded.

They also speculated about why outcomes may vary by type of kidney dysfunction.

“We suspect that those patients who experience AKI and AKI on CKD in our cohort likely had a triggering event – infection, bleeding, hypovolemia – that put these patients at greater risk for waitlist mortality,” the investigators wrote. “These events inherently carry more risk than stable nonliver-related elevations in serum creatinine that are seen in patients with CKD. Because of this heterogeneity of etiology in renal dysfunction in patients with cirrhosis, it is perhaps not surprising that unique renal function patterns variably impact mortality.”

The investigators noted that the findings from the study have “important implications for clinical practice,” and suggested that including type of renal dysfunction would have the most significant affect on accuracy of prognoses among patients at greatest risk of mortality.

The study was funded by a Paul B. Beeson Career Development Award and the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Verna disclosed relationships with Salix, Merck, and Gilead.

 

SOURCE: Cullaro et al. Clin Gastroenterol Hepatol. 2019 Feb 1. doi: 10.1016/j.cgh.2019.01.043.

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Predicted risk of cardiac complications varies among risk calculators

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Background: A critical juncture in the American Heart Association/American College of Cardiology 2014 perioperative guidelines relies on clinicians categorizing patients undergoing noncardiac surgery as either low risk (less than 1%) or elevated risk (greater than or equal to 1%) for a MACE. The purpose of this study is to determine whether there is variability between the three risk calculators endorsed by the ACC/AHA guidelines as prediction tools to make this risk stratification.



Study design: Retrospective observational study.

Setting: National Surgical Quality Improvement Program database.

Synopsis: The NSQIP database was used to identify 10,000 patients who had undergone noncardiac surgery. The risk of MACE for each patient was then calculated using the Revised Cardiac Risk Index, the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator, and the National Surgical Quality Improvement Program Myocardial Infarction or Cardiac Arrest calculator. Data were analyzed using the intraclass correlation coefficient and kappa analysis. Results demonstrated that 29% of the time the three calculators disagreed on which patients were classified as low risk. This suggests that, when following the ACC/AHA perioperative guidelines, a recommendation for further preoperative cardiac testing may depend on which risk prediction tool is used to calculate the risk of MACE.

Bottom line: Nearly one-third of the time, the three risk calculators recommended in the ACC/AHA 2014 perioperative guidelines do not agree on which patients are classified as low risk; this may affect clinical decision making for some patients.

Citation: Glance LG et al. Impact of the choice of risk model for identifying low-risk patients using the 2014 American College of Cardiology/American Heart Association perioperative guidelines. Anesthesiology. 2018;129(5):889-900.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

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Background: A critical juncture in the American Heart Association/American College of Cardiology 2014 perioperative guidelines relies on clinicians categorizing patients undergoing noncardiac surgery as either low risk (less than 1%) or elevated risk (greater than or equal to 1%) for a MACE. The purpose of this study is to determine whether there is variability between the three risk calculators endorsed by the ACC/AHA guidelines as prediction tools to make this risk stratification.



Study design: Retrospective observational study.

Setting: National Surgical Quality Improvement Program database.

Synopsis: The NSQIP database was used to identify 10,000 patients who had undergone noncardiac surgery. The risk of MACE for each patient was then calculated using the Revised Cardiac Risk Index, the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator, and the National Surgical Quality Improvement Program Myocardial Infarction or Cardiac Arrest calculator. Data were analyzed using the intraclass correlation coefficient and kappa analysis. Results demonstrated that 29% of the time the three calculators disagreed on which patients were classified as low risk. This suggests that, when following the ACC/AHA perioperative guidelines, a recommendation for further preoperative cardiac testing may depend on which risk prediction tool is used to calculate the risk of MACE.

Bottom line: Nearly one-third of the time, the three risk calculators recommended in the ACC/AHA 2014 perioperative guidelines do not agree on which patients are classified as low risk; this may affect clinical decision making for some patients.

Citation: Glance LG et al. Impact of the choice of risk model for identifying low-risk patients using the 2014 American College of Cardiology/American Heart Association perioperative guidelines. Anesthesiology. 2018;129(5):889-900.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

Background: A critical juncture in the American Heart Association/American College of Cardiology 2014 perioperative guidelines relies on clinicians categorizing patients undergoing noncardiac surgery as either low risk (less than 1%) or elevated risk (greater than or equal to 1%) for a MACE. The purpose of this study is to determine whether there is variability between the three risk calculators endorsed by the ACC/AHA guidelines as prediction tools to make this risk stratification.



Study design: Retrospective observational study.

Setting: National Surgical Quality Improvement Program database.

Synopsis: The NSQIP database was used to identify 10,000 patients who had undergone noncardiac surgery. The risk of MACE for each patient was then calculated using the Revised Cardiac Risk Index, the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator, and the National Surgical Quality Improvement Program Myocardial Infarction or Cardiac Arrest calculator. Data were analyzed using the intraclass correlation coefficient and kappa analysis. Results demonstrated that 29% of the time the three calculators disagreed on which patients were classified as low risk. This suggests that, when following the ACC/AHA perioperative guidelines, a recommendation for further preoperative cardiac testing may depend on which risk prediction tool is used to calculate the risk of MACE.

Bottom line: Nearly one-third of the time, the three risk calculators recommended in the ACC/AHA 2014 perioperative guidelines do not agree on which patients are classified as low risk; this may affect clinical decision making for some patients.

Citation: Glance LG et al. Impact of the choice of risk model for identifying low-risk patients using the 2014 American College of Cardiology/American Heart Association perioperative guidelines. Anesthesiology. 2018;129(5):889-900.

Dr. Bordin-Wosk is an assistant clinical professor in the division of hospital medicine at the University of California, San Diego.

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Early extubation to noninvasive ventilation did not decrease time to liberation from ventilation

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Background: Inclusion of noninvasive ventilation in weaning among chronic obstructive pulmonary disease (COPD) patients has been shown to reduce total duration of ventilation and invasive ventilator days with an associated reduction in morbidity and mortality. It is not well studied whether these results apply to general ICU patients.

Dr. Nhan Vuong


Study design: Randomized, allocation-concealed, open-label, multicenter trial.

Setting: United Kingdom National Health Service ICUs.

Synopsis: Patients from 41 general adult ICUs met inclusion criteria after they had been intubated for less than 48 hours and failed a spontaneous breathing trial. Intention-to-treat analysis in 319 of 364 patients (mean age, 63.1 years; 50.5% male) showed median time to liberation of 4.3 days in the noninvasive group versus 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% confidence interval, 0.89-1.40). However, secondary outcomes showed reduction in median time of invasive ventilation (1 day vs. 4 days) and total ventilator days (3 days vs. 4 days) in the noninvasive group without a significant difference in adverse events.

Not all secondary outcomes were powered to detect treatment differences. Hospitalists should consider noninvasive ventilation as an adjunct in weaning, especially in COPD patients, to reduce ventilator-associated complications and ICU resources when appropriate.

Bottom line: Protocolized early extubation to noninvasive ventilation was not associated with earlier liberation from all types of ventilation in the general ICU population.

Citation: Perkins GD et al. Effect of protocolized weaning with early extubation to noninvasive ventilation vs invasive weaning on time to liberation from mechanical ventilation among patients with respiratory failure: The breathe randomized clinical trial. JAMA. 2018;320(18):1881-8.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

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Background: Inclusion of noninvasive ventilation in weaning among chronic obstructive pulmonary disease (COPD) patients has been shown to reduce total duration of ventilation and invasive ventilator days with an associated reduction in morbidity and mortality. It is not well studied whether these results apply to general ICU patients.

Dr. Nhan Vuong


Study design: Randomized, allocation-concealed, open-label, multicenter trial.

Setting: United Kingdom National Health Service ICUs.

Synopsis: Patients from 41 general adult ICUs met inclusion criteria after they had been intubated for less than 48 hours and failed a spontaneous breathing trial. Intention-to-treat analysis in 319 of 364 patients (mean age, 63.1 years; 50.5% male) showed median time to liberation of 4.3 days in the noninvasive group versus 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% confidence interval, 0.89-1.40). However, secondary outcomes showed reduction in median time of invasive ventilation (1 day vs. 4 days) and total ventilator days (3 days vs. 4 days) in the noninvasive group without a significant difference in adverse events.

Not all secondary outcomes were powered to detect treatment differences. Hospitalists should consider noninvasive ventilation as an adjunct in weaning, especially in COPD patients, to reduce ventilator-associated complications and ICU resources when appropriate.

Bottom line: Protocolized early extubation to noninvasive ventilation was not associated with earlier liberation from all types of ventilation in the general ICU population.

Citation: Perkins GD et al. Effect of protocolized weaning with early extubation to noninvasive ventilation vs invasive weaning on time to liberation from mechanical ventilation among patients with respiratory failure: The breathe randomized clinical trial. JAMA. 2018;320(18):1881-8.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

Background: Inclusion of noninvasive ventilation in weaning among chronic obstructive pulmonary disease (COPD) patients has been shown to reduce total duration of ventilation and invasive ventilator days with an associated reduction in morbidity and mortality. It is not well studied whether these results apply to general ICU patients.

Dr. Nhan Vuong


Study design: Randomized, allocation-concealed, open-label, multicenter trial.

Setting: United Kingdom National Health Service ICUs.

Synopsis: Patients from 41 general adult ICUs met inclusion criteria after they had been intubated for less than 48 hours and failed a spontaneous breathing trial. Intention-to-treat analysis in 319 of 364 patients (mean age, 63.1 years; 50.5% male) showed median time to liberation of 4.3 days in the noninvasive group versus 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% confidence interval, 0.89-1.40). However, secondary outcomes showed reduction in median time of invasive ventilation (1 day vs. 4 days) and total ventilator days (3 days vs. 4 days) in the noninvasive group without a significant difference in adverse events.

Not all secondary outcomes were powered to detect treatment differences. Hospitalists should consider noninvasive ventilation as an adjunct in weaning, especially in COPD patients, to reduce ventilator-associated complications and ICU resources when appropriate.

Bottom line: Protocolized early extubation to noninvasive ventilation was not associated with earlier liberation from all types of ventilation in the general ICU population.

Citation: Perkins GD et al. Effect of protocolized weaning with early extubation to noninvasive ventilation vs invasive weaning on time to liberation from mechanical ventilation among patients with respiratory failure: The breathe randomized clinical trial. JAMA. 2018;320(18):1881-8.

Dr. Vuong is an associate physician in the division of hospital medicine at the University of California, San Diego.

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