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Genetic Testing Can Improve Pediatric Epilepsy Care
If a genetic disorder is suspected as the cause of treatment-resistant epilepsy, appropriate genetic tests may lead to timely diagnosis and targeted therapy, as well as reduce overall costs and limit anxiety to families, said Anup Patel, MD, in a review paper published online ahead of print September 8 in Epilepsia. In a literature review, Dr. Patel and Margie A. Ream, MD, PhD, discussed the genetic methods available, along with their advantages and disadvantages.
“Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors unless the ordering neurologist has a strong background in and understanding of genetics,” the authors advised. Drs. Ream and Patel are Assistant Professors in the Department of Pediatrics at Nationwide Children’s Hospital and Ohio State University in Columbus.
Generally, genetic testing is not recommended for patients with drug-responsive epilepsy or at epilepsy onset, although comparative genomic hybridization can be useful at first evaluation of a patient with global developmental delay. Metabolic testing should be undertaken at the onset of epilepsy in infants without a structural or syndromic cause of their seizures.
For children with drug-resistant epilepsy, Drs. Ream and Patel proposed a diagnosis algorithm. Biochemical testing should be the first line of action to uncover treatable metabolic disorders such as inborn errors of metabolism, which often cause seizures. Metabolic testing gives quicker results than targeted genetic studies or gene panels, thus allowing for more rapid treatment initiation. In most cases, there are several phenotypic variations of genetic epilepsy, and many genes would need to be tested for a given phenotype. This situation often makes targeted gene sequencing costlier than a gene panel.
Drug-resistant epilepsy, especially when associated with developmental delay or congenital anomalies, should prompt comparative genomic hybridization analysis, which detects copy number variations (ie, DNA deletions or duplications). The analysis’s sensitivity of 23.5% increases when multiple abnormalities are present. Aneuploidy and balanced translocations not detectable by comparative genomic hybridization can be found with karyotype.
The next test in the algorithm is a gene panel. This broad genetic test is useful in identifying specific genes and may be the most cost-effective way to approach diagnosing a broad phenotype.
Beyond gene panel testing, an even broader genetic evaluation is whole exome sequencing. This method tests all exons in the genome, is not limited to known epilepsy genes, and has 39% sensitivity. Whole exome sequencing is indicated in genetically heterogeneous disorders, when there is a suspected genetic disease lacking a specific test, when other genetic tests are negative for suspected disorders, and, in some cases, for prenatal testing. The disadvantage of whole exome sequencing is that it results in complex data, but it holds the potential for gene discovery in patients with similar phenotypes or if gene mutations occur in a common biochemical pathway. Whole exome sequencing costs in the range of $5,000 to $14,000 but sometimes can be less costly than traditional molecular diagnostic approaches.
Drs. Ream and Patel recommended “reserving whole exome sequencing for the most elusive cases” until it becomes more cost-effective. Ideally, they said, in the future, “whole exome sequencing could be tailored for epilepsy patients by optimizing coverage of known epilepsy genes.”
—Evelyn Tran
Suggested Reading
Ream MA, Patel AD. Obtaining genetic testing in pediatric epilepsy. Epilepsia. 2015 Sep 8 [Epub ahead of print].
If a genetic disorder is suspected as the cause of treatment-resistant epilepsy, appropriate genetic tests may lead to timely diagnosis and targeted therapy, as well as reduce overall costs and limit anxiety to families, said Anup Patel, MD, in a review paper published online ahead of print September 8 in Epilepsia. In a literature review, Dr. Patel and Margie A. Ream, MD, PhD, discussed the genetic methods available, along with their advantages and disadvantages.
“Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors unless the ordering neurologist has a strong background in and understanding of genetics,” the authors advised. Drs. Ream and Patel are Assistant Professors in the Department of Pediatrics at Nationwide Children’s Hospital and Ohio State University in Columbus.
Generally, genetic testing is not recommended for patients with drug-responsive epilepsy or at epilepsy onset, although comparative genomic hybridization can be useful at first evaluation of a patient with global developmental delay. Metabolic testing should be undertaken at the onset of epilepsy in infants without a structural or syndromic cause of their seizures.
For children with drug-resistant epilepsy, Drs. Ream and Patel proposed a diagnosis algorithm. Biochemical testing should be the first line of action to uncover treatable metabolic disorders such as inborn errors of metabolism, which often cause seizures. Metabolic testing gives quicker results than targeted genetic studies or gene panels, thus allowing for more rapid treatment initiation. In most cases, there are several phenotypic variations of genetic epilepsy, and many genes would need to be tested for a given phenotype. This situation often makes targeted gene sequencing costlier than a gene panel.
Drug-resistant epilepsy, especially when associated with developmental delay or congenital anomalies, should prompt comparative genomic hybridization analysis, which detects copy number variations (ie, DNA deletions or duplications). The analysis’s sensitivity of 23.5% increases when multiple abnormalities are present. Aneuploidy and balanced translocations not detectable by comparative genomic hybridization can be found with karyotype.
The next test in the algorithm is a gene panel. This broad genetic test is useful in identifying specific genes and may be the most cost-effective way to approach diagnosing a broad phenotype.
Beyond gene panel testing, an even broader genetic evaluation is whole exome sequencing. This method tests all exons in the genome, is not limited to known epilepsy genes, and has 39% sensitivity. Whole exome sequencing is indicated in genetically heterogeneous disorders, when there is a suspected genetic disease lacking a specific test, when other genetic tests are negative for suspected disorders, and, in some cases, for prenatal testing. The disadvantage of whole exome sequencing is that it results in complex data, but it holds the potential for gene discovery in patients with similar phenotypes or if gene mutations occur in a common biochemical pathway. Whole exome sequencing costs in the range of $5,000 to $14,000 but sometimes can be less costly than traditional molecular diagnostic approaches.
Drs. Ream and Patel recommended “reserving whole exome sequencing for the most elusive cases” until it becomes more cost-effective. Ideally, they said, in the future, “whole exome sequencing could be tailored for epilepsy patients by optimizing coverage of known epilepsy genes.”
—Evelyn Tran
If a genetic disorder is suspected as the cause of treatment-resistant epilepsy, appropriate genetic tests may lead to timely diagnosis and targeted therapy, as well as reduce overall costs and limit anxiety to families, said Anup Patel, MD, in a review paper published online ahead of print September 8 in Epilepsia. In a literature review, Dr. Patel and Margie A. Ream, MD, PhD, discussed the genetic methods available, along with their advantages and disadvantages.
“Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors unless the ordering neurologist has a strong background in and understanding of genetics,” the authors advised. Drs. Ream and Patel are Assistant Professors in the Department of Pediatrics at Nationwide Children’s Hospital and Ohio State University in Columbus.
Generally, genetic testing is not recommended for patients with drug-responsive epilepsy or at epilepsy onset, although comparative genomic hybridization can be useful at first evaluation of a patient with global developmental delay. Metabolic testing should be undertaken at the onset of epilepsy in infants without a structural or syndromic cause of their seizures.
For children with drug-resistant epilepsy, Drs. Ream and Patel proposed a diagnosis algorithm. Biochemical testing should be the first line of action to uncover treatable metabolic disorders such as inborn errors of metabolism, which often cause seizures. Metabolic testing gives quicker results than targeted genetic studies or gene panels, thus allowing for more rapid treatment initiation. In most cases, there are several phenotypic variations of genetic epilepsy, and many genes would need to be tested for a given phenotype. This situation often makes targeted gene sequencing costlier than a gene panel.
Drug-resistant epilepsy, especially when associated with developmental delay or congenital anomalies, should prompt comparative genomic hybridization analysis, which detects copy number variations (ie, DNA deletions or duplications). The analysis’s sensitivity of 23.5% increases when multiple abnormalities are present. Aneuploidy and balanced translocations not detectable by comparative genomic hybridization can be found with karyotype.
The next test in the algorithm is a gene panel. This broad genetic test is useful in identifying specific genes and may be the most cost-effective way to approach diagnosing a broad phenotype.
Beyond gene panel testing, an even broader genetic evaluation is whole exome sequencing. This method tests all exons in the genome, is not limited to known epilepsy genes, and has 39% sensitivity. Whole exome sequencing is indicated in genetically heterogeneous disorders, when there is a suspected genetic disease lacking a specific test, when other genetic tests are negative for suspected disorders, and, in some cases, for prenatal testing. The disadvantage of whole exome sequencing is that it results in complex data, but it holds the potential for gene discovery in patients with similar phenotypes or if gene mutations occur in a common biochemical pathway. Whole exome sequencing costs in the range of $5,000 to $14,000 but sometimes can be less costly than traditional molecular diagnostic approaches.
Drs. Ream and Patel recommended “reserving whole exome sequencing for the most elusive cases” until it becomes more cost-effective. Ideally, they said, in the future, “whole exome sequencing could be tailored for epilepsy patients by optimizing coverage of known epilepsy genes.”
—Evelyn Tran
Suggested Reading
Ream MA, Patel AD. Obtaining genetic testing in pediatric epilepsy. Epilepsia. 2015 Sep 8 [Epub ahead of print].
Suggested Reading
Ream MA, Patel AD. Obtaining genetic testing in pediatric epilepsy. Epilepsia. 2015 Sep 8 [Epub ahead of print].
Perampanel Shows Efficacy in Pivotal Trial
Perampanel, when used as adjunctive therapy in the treatment of drug-resistant primary generalized tonic-clonic seizures in patients 12 and older, reduced median seizure frequency, compared with placebo, according to the results of a phase III trial published online ahead of print August 21 in Neurology. Results of the multicenter, randomized, double-blind, placebo-controlled clinical trial of 162 patients who were taking one to three antiepileptic drugs showed that patients taking perampanel achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency per 28 days. This result was statistically significant when compared with a 38% reduction with placebo. Additionally, 64% of patients taking perampanel experienced a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo.
“These data showed a significant median reduction in the frequency of primary generalized tonic-clonic seizures in patients that had [perampanel] added to their treatment regimen,” said lead author Jacqueline A. French, MD, Professor at New York University Comprehensive Epilepsy Center and Chief Science Officer of the Epilepsy Foundation. “As the number of treatment options are limited for patients with primary generalized tonic-clonic seizures, [perampanel] may provide a new option for this group.”
Dr. French and colleagues enrolled patients age 12 or older with primary generalized tonic-clonic seizures and idiopathic generalized epilepsy. Study participants were randomized to placebo or perampanel during a four-week titration period. During this period, perampanel was titrated from 2 to 8 mg/day or to the highest tolerated dose. The titration period was followed by a 13-week maintenance period.
The primary end point was percent change in seizure frequency per 28 days. The secondary end point was 50% primary generalized tonic-clonic seizure responder rate, which was defined as patients achieving a 50% or greater reduction in seizure frequency.
The full analysis set included 162 patients. The control and treatment groups each had 81 patients. Compared with placebo, perampanel conferred a greater median percent change in primary generalized tonic-clonic seizure frequency per 28 days (-38.4% for placebo vs -76.5% for perampanel). The 50% seizure responder rate was 39.5% for placebo and 64.2% for perampanel. During the maintenance period, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved seizure freedom. The most frequently reported treatment-emergent adverse events were dizziness (32.1%) and fatigue (14.8%).
The authors concluded that “this study provides Class I evidence that adjunctive perampanel reduces primary generalized tonic-clonic seizure frequency, compared with placebo, in patients with drug-resistant primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.”
—Glenn S. Williams
Suggested Reading
French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy. Neurology. 2015 August 21 [Epub ahead of print].
Perampanel, when used as adjunctive therapy in the treatment of drug-resistant primary generalized tonic-clonic seizures in patients 12 and older, reduced median seizure frequency, compared with placebo, according to the results of a phase III trial published online ahead of print August 21 in Neurology. Results of the multicenter, randomized, double-blind, placebo-controlled clinical trial of 162 patients who were taking one to three antiepileptic drugs showed that patients taking perampanel achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency per 28 days. This result was statistically significant when compared with a 38% reduction with placebo. Additionally, 64% of patients taking perampanel experienced a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo.
“These data showed a significant median reduction in the frequency of primary generalized tonic-clonic seizures in patients that had [perampanel] added to their treatment regimen,” said lead author Jacqueline A. French, MD, Professor at New York University Comprehensive Epilepsy Center and Chief Science Officer of the Epilepsy Foundation. “As the number of treatment options are limited for patients with primary generalized tonic-clonic seizures, [perampanel] may provide a new option for this group.”
Dr. French and colleagues enrolled patients age 12 or older with primary generalized tonic-clonic seizures and idiopathic generalized epilepsy. Study participants were randomized to placebo or perampanel during a four-week titration period. During this period, perampanel was titrated from 2 to 8 mg/day or to the highest tolerated dose. The titration period was followed by a 13-week maintenance period.
The primary end point was percent change in seizure frequency per 28 days. The secondary end point was 50% primary generalized tonic-clonic seizure responder rate, which was defined as patients achieving a 50% or greater reduction in seizure frequency.
The full analysis set included 162 patients. The control and treatment groups each had 81 patients. Compared with placebo, perampanel conferred a greater median percent change in primary generalized tonic-clonic seizure frequency per 28 days (-38.4% for placebo vs -76.5% for perampanel). The 50% seizure responder rate was 39.5% for placebo and 64.2% for perampanel. During the maintenance period, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved seizure freedom. The most frequently reported treatment-emergent adverse events were dizziness (32.1%) and fatigue (14.8%).
The authors concluded that “this study provides Class I evidence that adjunctive perampanel reduces primary generalized tonic-clonic seizure frequency, compared with placebo, in patients with drug-resistant primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.”
—Glenn S. Williams
Perampanel, when used as adjunctive therapy in the treatment of drug-resistant primary generalized tonic-clonic seizures in patients 12 and older, reduced median seizure frequency, compared with placebo, according to the results of a phase III trial published online ahead of print August 21 in Neurology. Results of the multicenter, randomized, double-blind, placebo-controlled clinical trial of 162 patients who were taking one to three antiepileptic drugs showed that patients taking perampanel achieved a 76% median reduction in primary generalized tonic-clonic seizure frequency per 28 days. This result was statistically significant when compared with a 38% reduction with placebo. Additionally, 64% of patients taking perampanel experienced a 50% or greater reduction in primary generalized tonic-clonic seizure frequency versus 40% with placebo.
“These data showed a significant median reduction in the frequency of primary generalized tonic-clonic seizures in patients that had [perampanel] added to their treatment regimen,” said lead author Jacqueline A. French, MD, Professor at New York University Comprehensive Epilepsy Center and Chief Science Officer of the Epilepsy Foundation. “As the number of treatment options are limited for patients with primary generalized tonic-clonic seizures, [perampanel] may provide a new option for this group.”
Dr. French and colleagues enrolled patients age 12 or older with primary generalized tonic-clonic seizures and idiopathic generalized epilepsy. Study participants were randomized to placebo or perampanel during a four-week titration period. During this period, perampanel was titrated from 2 to 8 mg/day or to the highest tolerated dose. The titration period was followed by a 13-week maintenance period.
The primary end point was percent change in seizure frequency per 28 days. The secondary end point was 50% primary generalized tonic-clonic seizure responder rate, which was defined as patients achieving a 50% or greater reduction in seizure frequency.
The full analysis set included 162 patients. The control and treatment groups each had 81 patients. Compared with placebo, perampanel conferred a greater median percent change in primary generalized tonic-clonic seizure frequency per 28 days (-38.4% for placebo vs -76.5% for perampanel). The 50% seizure responder rate was 39.5% for placebo and 64.2% for perampanel. During the maintenance period, 12.3% of placebo-treated patients and 30.9% of perampanel-treated patients achieved seizure freedom. The most frequently reported treatment-emergent adverse events were dizziness (32.1%) and fatigue (14.8%).
The authors concluded that “this study provides Class I evidence that adjunctive perampanel reduces primary generalized tonic-clonic seizure frequency, compared with placebo, in patients with drug-resistant primary generalized tonic-clonic seizures in idiopathic generalized epilepsy.”
—Glenn S. Williams
Suggested Reading
French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy. Neurology. 2015 August 21 [Epub ahead of print].
Suggested Reading
French JA, Krauss GL, Wechsler RT, et al. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy. Neurology. 2015 August 21 [Epub ahead of print].
Chemotherapy Does Not Improve Quality of Life with End-Stage Cancer
Clinical question: Does palliative chemotherapy improve quality of life (QOL) in patients with end-stage cancer, regardless of performance status?
Background: There is continued debate about the benefit of palliative chemotherapy at the end of life. Guidelines recommend a good performance score as an indicator of appropriate use of therapy; however, little is known about the benefits and harms of chemotherapy in metastatic cancer patients stratified by performance status.
Study design: Longitudinal, prospective cohort study.
Setting: Multi-institutional in the United States.
Synopsis: Five U.S. institutions enrolled 661 patients with metastatic cancer and estimated life expectancy less than six months; 312 patients who died during the study period were included in the final analysis of postmortem questionnaires of caretakers regarding QOL in the patients’ last week of life. Contrary to current thought, the study demonstrated that patients undergoing end-of-life palliative chemotherapy with good ECOG performance status (0-1) had significantly worse QOL than those avoiding palliative chemotherapy. There was no difference in QOL in patients with worse performance status (ECOG 2-3).
This study is one of the first prospective investigations of this topic and makes a compelling case for withholding palliative chemotherapy at the end of life regardless of performance status. The study is somewhat limited in that the QOL measurement is only for the last week of life and the patients were not randomized into the chemotherapy arm, which could bias results.
Bottom line: Palliative chemotherapy does not improve QOL near death, and may actually worsen QOL in patients with good performance status.
Citation: Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015;1(6):778-784.
Clinical question: Does palliative chemotherapy improve quality of life (QOL) in patients with end-stage cancer, regardless of performance status?
Background: There is continued debate about the benefit of palliative chemotherapy at the end of life. Guidelines recommend a good performance score as an indicator of appropriate use of therapy; however, little is known about the benefits and harms of chemotherapy in metastatic cancer patients stratified by performance status.
Study design: Longitudinal, prospective cohort study.
Setting: Multi-institutional in the United States.
Synopsis: Five U.S. institutions enrolled 661 patients with metastatic cancer and estimated life expectancy less than six months; 312 patients who died during the study period were included in the final analysis of postmortem questionnaires of caretakers regarding QOL in the patients’ last week of life. Contrary to current thought, the study demonstrated that patients undergoing end-of-life palliative chemotherapy with good ECOG performance status (0-1) had significantly worse QOL than those avoiding palliative chemotherapy. There was no difference in QOL in patients with worse performance status (ECOG 2-3).
This study is one of the first prospective investigations of this topic and makes a compelling case for withholding palliative chemotherapy at the end of life regardless of performance status. The study is somewhat limited in that the QOL measurement is only for the last week of life and the patients were not randomized into the chemotherapy arm, which could bias results.
Bottom line: Palliative chemotherapy does not improve QOL near death, and may actually worsen QOL in patients with good performance status.
Citation: Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015;1(6):778-784.
Clinical question: Does palliative chemotherapy improve quality of life (QOL) in patients with end-stage cancer, regardless of performance status?
Background: There is continued debate about the benefit of palliative chemotherapy at the end of life. Guidelines recommend a good performance score as an indicator of appropriate use of therapy; however, little is known about the benefits and harms of chemotherapy in metastatic cancer patients stratified by performance status.
Study design: Longitudinal, prospective cohort study.
Setting: Multi-institutional in the United States.
Synopsis: Five U.S. institutions enrolled 661 patients with metastatic cancer and estimated life expectancy less than six months; 312 patients who died during the study period were included in the final analysis of postmortem questionnaires of caretakers regarding QOL in the patients’ last week of life. Contrary to current thought, the study demonstrated that patients undergoing end-of-life palliative chemotherapy with good ECOG performance status (0-1) had significantly worse QOL than those avoiding palliative chemotherapy. There was no difference in QOL in patients with worse performance status (ECOG 2-3).
This study is one of the first prospective investigations of this topic and makes a compelling case for withholding palliative chemotherapy at the end of life regardless of performance status. The study is somewhat limited in that the QOL measurement is only for the last week of life and the patients were not randomized into the chemotherapy arm, which could bias results.
Bottom line: Palliative chemotherapy does not improve QOL near death, and may actually worsen QOL in patients with good performance status.
Citation: Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy use, performance status, and quality of life at the end of life. JAMA Oncol. 2015;1(6):778-784.
Job Stress Elevates Stroke Risk
Having a high-stress job may be linked to an increased risk of stroke, according to a meta-analysis published online ahead of print October 14 in Neurology. “Having a lot of job stress has been linked to heart disease, but studies on job stress and stroke have shown inconsistent results,” said Dingli Xu, MD, of the Department of Cardiology at Nanfang Hospital, Southern Medical University in Guangzhou, China. “It’s possible that high-stress jobs lead to more unhealthy behaviors, such as poor eating habits, smoking, and a lack of exercise.”
Dr. Xu and colleagues conducted a meta-analysis to evaluate the association between job strain and the risk of stroke. The analysis looked at all of the available research on job strain and stroke risk. The six prospective cohort studies analyzed comprised 138,782 participants who were followed for three to 17 years.
Jobs were classified into four groups based on psychological job demand and job control. Psychological job demand, the researchers explained, referred to time pressure, mental load, and coordination responsibilities. Job control was defined as an individual’s potential control over work-related decision-making. The four groups of jobs were low-strain jobs (ie, those with low demand and high control), passive jobs (ie, those with low demand and low control), active jobs (ie, those with high demand and high control), and high-strain jobs (ie, those with high demand and low control).
Examples of passive jobs include janitors, miners, and other manual laborers. Low-stress jobs included natural scientists and architects. High-stress jobs are found in the service industry and include waitresses and nursing aides. Active jobs include doctors, teachers, and engineers. In the six studies, the percentage of those with high-stress jobs ranged from 11% to 27% of participants.
The analysis found that people with high-stress jobs had a 22% higher risk of stroke than those with low-stress jobs. Women with high-stress jobs had a 33% higher risk of stroke than women with low-stress jobs. People with high-stress jobs were 58% more likely to have an ischemic stroke than those with low-stress jobs. People in passive and active jobs did not have any increased risk of stroke.
The researchers calculated that 4.4% of the stroke risk resulted from the high-stress jobs. For women, that number increased to 6.5%.
“Based on this study, it is reasonable to consider testing interventions aimed at increasing job control, such as decentralization of decision-making, and flexibility in job structure, such as telecommuting. If effective, such workplace changes could have a major public health impact,” said Jennifer J. Majersik, MD, Associate Professor of Neurology at the University of Utah in Salt Lake City, in an accompanying editorial.
One limitation of the research, Dr. Xu noted, was that job stress was measured at only one point in time. In addition, other factors such as high blood pressure or high cholesterol were not adequately adjusted for in the original studies.
Suggested Reading
Huang Y, Xu S, Hua J, et al. Association between job strain and risk of incident stroke: a meta-analysis. Neurology. 2015 Oct 14 [Epub ahead of print].
Majersik JJ. Doctor, did stress cause my stroke? Neurology. 2015 Oct 14 [Epub ahead of print].
Having a high-stress job may be linked to an increased risk of stroke, according to a meta-analysis published online ahead of print October 14 in Neurology. “Having a lot of job stress has been linked to heart disease, but studies on job stress and stroke have shown inconsistent results,” said Dingli Xu, MD, of the Department of Cardiology at Nanfang Hospital, Southern Medical University in Guangzhou, China. “It’s possible that high-stress jobs lead to more unhealthy behaviors, such as poor eating habits, smoking, and a lack of exercise.”
Dr. Xu and colleagues conducted a meta-analysis to evaluate the association between job strain and the risk of stroke. The analysis looked at all of the available research on job strain and stroke risk. The six prospective cohort studies analyzed comprised 138,782 participants who were followed for three to 17 years.
Jobs were classified into four groups based on psychological job demand and job control. Psychological job demand, the researchers explained, referred to time pressure, mental load, and coordination responsibilities. Job control was defined as an individual’s potential control over work-related decision-making. The four groups of jobs were low-strain jobs (ie, those with low demand and high control), passive jobs (ie, those with low demand and low control), active jobs (ie, those with high demand and high control), and high-strain jobs (ie, those with high demand and low control).
Examples of passive jobs include janitors, miners, and other manual laborers. Low-stress jobs included natural scientists and architects. High-stress jobs are found in the service industry and include waitresses and nursing aides. Active jobs include doctors, teachers, and engineers. In the six studies, the percentage of those with high-stress jobs ranged from 11% to 27% of participants.
The analysis found that people with high-stress jobs had a 22% higher risk of stroke than those with low-stress jobs. Women with high-stress jobs had a 33% higher risk of stroke than women with low-stress jobs. People with high-stress jobs were 58% more likely to have an ischemic stroke than those with low-stress jobs. People in passive and active jobs did not have any increased risk of stroke.
The researchers calculated that 4.4% of the stroke risk resulted from the high-stress jobs. For women, that number increased to 6.5%.
“Based on this study, it is reasonable to consider testing interventions aimed at increasing job control, such as decentralization of decision-making, and flexibility in job structure, such as telecommuting. If effective, such workplace changes could have a major public health impact,” said Jennifer J. Majersik, MD, Associate Professor of Neurology at the University of Utah in Salt Lake City, in an accompanying editorial.
One limitation of the research, Dr. Xu noted, was that job stress was measured at only one point in time. In addition, other factors such as high blood pressure or high cholesterol were not adequately adjusted for in the original studies.
Having a high-stress job may be linked to an increased risk of stroke, according to a meta-analysis published online ahead of print October 14 in Neurology. “Having a lot of job stress has been linked to heart disease, but studies on job stress and stroke have shown inconsistent results,” said Dingli Xu, MD, of the Department of Cardiology at Nanfang Hospital, Southern Medical University in Guangzhou, China. “It’s possible that high-stress jobs lead to more unhealthy behaviors, such as poor eating habits, smoking, and a lack of exercise.”
Dr. Xu and colleagues conducted a meta-analysis to evaluate the association between job strain and the risk of stroke. The analysis looked at all of the available research on job strain and stroke risk. The six prospective cohort studies analyzed comprised 138,782 participants who were followed for three to 17 years.
Jobs were classified into four groups based on psychological job demand and job control. Psychological job demand, the researchers explained, referred to time pressure, mental load, and coordination responsibilities. Job control was defined as an individual’s potential control over work-related decision-making. The four groups of jobs were low-strain jobs (ie, those with low demand and high control), passive jobs (ie, those with low demand and low control), active jobs (ie, those with high demand and high control), and high-strain jobs (ie, those with high demand and low control).
Examples of passive jobs include janitors, miners, and other manual laborers. Low-stress jobs included natural scientists and architects. High-stress jobs are found in the service industry and include waitresses and nursing aides. Active jobs include doctors, teachers, and engineers. In the six studies, the percentage of those with high-stress jobs ranged from 11% to 27% of participants.
The analysis found that people with high-stress jobs had a 22% higher risk of stroke than those with low-stress jobs. Women with high-stress jobs had a 33% higher risk of stroke than women with low-stress jobs. People with high-stress jobs were 58% more likely to have an ischemic stroke than those with low-stress jobs. People in passive and active jobs did not have any increased risk of stroke.
The researchers calculated that 4.4% of the stroke risk resulted from the high-stress jobs. For women, that number increased to 6.5%.
“Based on this study, it is reasonable to consider testing interventions aimed at increasing job control, such as decentralization of decision-making, and flexibility in job structure, such as telecommuting. If effective, such workplace changes could have a major public health impact,” said Jennifer J. Majersik, MD, Associate Professor of Neurology at the University of Utah in Salt Lake City, in an accompanying editorial.
One limitation of the research, Dr. Xu noted, was that job stress was measured at only one point in time. In addition, other factors such as high blood pressure or high cholesterol were not adequately adjusted for in the original studies.
Suggested Reading
Huang Y, Xu S, Hua J, et al. Association between job strain and risk of incident stroke: a meta-analysis. Neurology. 2015 Oct 14 [Epub ahead of print].
Majersik JJ. Doctor, did stress cause my stroke? Neurology. 2015 Oct 14 [Epub ahead of print].
Suggested Reading
Huang Y, Xu S, Hua J, et al. Association between job strain and risk of incident stroke: a meta-analysis. Neurology. 2015 Oct 14 [Epub ahead of print].
Majersik JJ. Doctor, did stress cause my stroke? Neurology. 2015 Oct 14 [Epub ahead of print].
Post-Operative Transfusions after Noncardiac Surgery Associated with Increased Adverse Outcomes
Clinical question: Do transfusions affect post-operative outcomes after noncardiac surgery?
Background: Studies have demonstrated that a restrictive transfusion strategy is probably superior to a liberal transfusion strategy in many clinical settings. Despite this data, there continues to be wide variation in the use of blood transfusions in the peri-operative setting.
Study design: Retrospective cohort study.
Setting: Fifty-two community and academic hospitals in Michigan.
Synopsis: Demographic, operative, and outcomes data were extracted from the Michigan Surgical Quality Collaborative and reviewed for 48,720 patients who underwent noncardiac surgery between 2012-2014. A total of 4.6% of patients received a blood transfusion within 72 hours after surgery. The patients who received blood products were at increased risk for death at 30 days (3.6% excess absolute risk), for infectious complications (1% excess absolute risk), and for having at least one post-operative noninfectious complication (4.4% increased absolute risk).
Bottom line: Although observational in nature, this study adds to the increasing body of evidence supporting an increase in surgical morbidity and mortality associated with blood transfusions.
Citation: Abdelsattar ZM, Hendren S, Wong SL, Campbell DA Jr, Henke P. Variation in transfusion practices and the effect on outcomes after noncardiac surgery. Ann Surg. 2015;262(1):1-6.
Clinical question: Do transfusions affect post-operative outcomes after noncardiac surgery?
Background: Studies have demonstrated that a restrictive transfusion strategy is probably superior to a liberal transfusion strategy in many clinical settings. Despite this data, there continues to be wide variation in the use of blood transfusions in the peri-operative setting.
Study design: Retrospective cohort study.
Setting: Fifty-two community and academic hospitals in Michigan.
Synopsis: Demographic, operative, and outcomes data were extracted from the Michigan Surgical Quality Collaborative and reviewed for 48,720 patients who underwent noncardiac surgery between 2012-2014. A total of 4.6% of patients received a blood transfusion within 72 hours after surgery. The patients who received blood products were at increased risk for death at 30 days (3.6% excess absolute risk), for infectious complications (1% excess absolute risk), and for having at least one post-operative noninfectious complication (4.4% increased absolute risk).
Bottom line: Although observational in nature, this study adds to the increasing body of evidence supporting an increase in surgical morbidity and mortality associated with blood transfusions.
Citation: Abdelsattar ZM, Hendren S, Wong SL, Campbell DA Jr, Henke P. Variation in transfusion practices and the effect on outcomes after noncardiac surgery. Ann Surg. 2015;262(1):1-6.
Clinical question: Do transfusions affect post-operative outcomes after noncardiac surgery?
Background: Studies have demonstrated that a restrictive transfusion strategy is probably superior to a liberal transfusion strategy in many clinical settings. Despite this data, there continues to be wide variation in the use of blood transfusions in the peri-operative setting.
Study design: Retrospective cohort study.
Setting: Fifty-two community and academic hospitals in Michigan.
Synopsis: Demographic, operative, and outcomes data were extracted from the Michigan Surgical Quality Collaborative and reviewed for 48,720 patients who underwent noncardiac surgery between 2012-2014. A total of 4.6% of patients received a blood transfusion within 72 hours after surgery. The patients who received blood products were at increased risk for death at 30 days (3.6% excess absolute risk), for infectious complications (1% excess absolute risk), and for having at least one post-operative noninfectious complication (4.4% increased absolute risk).
Bottom line: Although observational in nature, this study adds to the increasing body of evidence supporting an increase in surgical morbidity and mortality associated with blood transfusions.
Citation: Abdelsattar ZM, Hendren S, Wong SL, Campbell DA Jr, Henke P. Variation in transfusion practices and the effect on outcomes after noncardiac surgery. Ann Surg. 2015;262(1):1-6.
Left Atrial Appendage Closure Favorable Over Warfarin for Atrial Fibrillation
Clinical question: Is there a favorable risk-benefit ratio for left atrial appendage closure (LAAC) compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation?
Background: LAAC with the WATCHMAN device was shown to be noninferior to warfarin for the prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation in two trials: PROTECT AF and PREVAIL. Further efficacy concerns were raised following routine regulatory filings, leading to the need for continued evaluation.
Study design: Meta-analysis.
Setting: Patient-level data were combined and analyzed from the PROTECT AF and PREVAIL trails and two nonrandomized registries of LAAC with the WATCHMAN device: the Continued Access PROTECT AF registry (CAP) and the Continued Access to PREVAIL registry (CAP2).
Synopsis: A total of 2,406 patients were enrolled from all four data sets from 2005-2014. Of those, 1,877 were treated with the WATCHMAN device and 382 were treated with warfarin. Annualized risk of stroke if untreated with anticoagulation for all patients was 5.7% to 7.6%, indicating that all were eligible to be treated with warfarin. Ninety percent of patients had moderate to high risk of bleeding. Analysis showed that LAAC was noninferior to warfarin for stroke, systemic embolism, and cardiovascular death.
A slight increase in ischemic stroke in the LAAC group was counterbalanced by the significant reduction in hemorrhagic stroke in the LAAC group versus the warfarin group. Cardiovascular deaths were significantly fewer in the LAAC cohort; all-cause mortality favored LAAC but did not reach statistical significance. There was also a significant reduction in nonprocedure-related major bleeding in the LAAC group. Limitations of this study include the limited number of patients treated with warfarin and lack of comparison to new oral anticoagulants (NOACs).
Bottom line: Patients with increased stroke risk from nonvalvular atrial fibrillation treated with the WATCHMAN device for LAAC have significant reductions in hemorrhagic stroke, cardiovascular death, and nonprocedure-related major bleeding, but slightly increased risk of ischemic stroke compared to those treated with warfarin.
Citaiton: Holmes DR Jr, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol. 2015;65(24):2614-2623.
Clinical question: Is there a favorable risk-benefit ratio for left atrial appendage closure (LAAC) compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation?
Background: LAAC with the WATCHMAN device was shown to be noninferior to warfarin for the prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation in two trials: PROTECT AF and PREVAIL. Further efficacy concerns were raised following routine regulatory filings, leading to the need for continued evaluation.
Study design: Meta-analysis.
Setting: Patient-level data were combined and analyzed from the PROTECT AF and PREVAIL trails and two nonrandomized registries of LAAC with the WATCHMAN device: the Continued Access PROTECT AF registry (CAP) and the Continued Access to PREVAIL registry (CAP2).
Synopsis: A total of 2,406 patients were enrolled from all four data sets from 2005-2014. Of those, 1,877 were treated with the WATCHMAN device and 382 were treated with warfarin. Annualized risk of stroke if untreated with anticoagulation for all patients was 5.7% to 7.6%, indicating that all were eligible to be treated with warfarin. Ninety percent of patients had moderate to high risk of bleeding. Analysis showed that LAAC was noninferior to warfarin for stroke, systemic embolism, and cardiovascular death.
A slight increase in ischemic stroke in the LAAC group was counterbalanced by the significant reduction in hemorrhagic stroke in the LAAC group versus the warfarin group. Cardiovascular deaths were significantly fewer in the LAAC cohort; all-cause mortality favored LAAC but did not reach statistical significance. There was also a significant reduction in nonprocedure-related major bleeding in the LAAC group. Limitations of this study include the limited number of patients treated with warfarin and lack of comparison to new oral anticoagulants (NOACs).
Bottom line: Patients with increased stroke risk from nonvalvular atrial fibrillation treated with the WATCHMAN device for LAAC have significant reductions in hemorrhagic stroke, cardiovascular death, and nonprocedure-related major bleeding, but slightly increased risk of ischemic stroke compared to those treated with warfarin.
Citaiton: Holmes DR Jr, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol. 2015;65(24):2614-2623.
Clinical question: Is there a favorable risk-benefit ratio for left atrial appendage closure (LAAC) compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation?
Background: LAAC with the WATCHMAN device was shown to be noninferior to warfarin for the prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation in two trials: PROTECT AF and PREVAIL. Further efficacy concerns were raised following routine regulatory filings, leading to the need for continued evaluation.
Study design: Meta-analysis.
Setting: Patient-level data were combined and analyzed from the PROTECT AF and PREVAIL trails and two nonrandomized registries of LAAC with the WATCHMAN device: the Continued Access PROTECT AF registry (CAP) and the Continued Access to PREVAIL registry (CAP2).
Synopsis: A total of 2,406 patients were enrolled from all four data sets from 2005-2014. Of those, 1,877 were treated with the WATCHMAN device and 382 were treated with warfarin. Annualized risk of stroke if untreated with anticoagulation for all patients was 5.7% to 7.6%, indicating that all were eligible to be treated with warfarin. Ninety percent of patients had moderate to high risk of bleeding. Analysis showed that LAAC was noninferior to warfarin for stroke, systemic embolism, and cardiovascular death.
A slight increase in ischemic stroke in the LAAC group was counterbalanced by the significant reduction in hemorrhagic stroke in the LAAC group versus the warfarin group. Cardiovascular deaths were significantly fewer in the LAAC cohort; all-cause mortality favored LAAC but did not reach statistical significance. There was also a significant reduction in nonprocedure-related major bleeding in the LAAC group. Limitations of this study include the limited number of patients treated with warfarin and lack of comparison to new oral anticoagulants (NOACs).
Bottom line: Patients with increased stroke risk from nonvalvular atrial fibrillation treated with the WATCHMAN device for LAAC have significant reductions in hemorrhagic stroke, cardiovascular death, and nonprocedure-related major bleeding, but slightly increased risk of ischemic stroke compared to those treated with warfarin.
Citaiton: Holmes DR Jr, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol. 2015;65(24):2614-2623.
Pediatric Trigger Tool Helps Identify Inpatient Pediatric Harm
Clinical question: Can a trigger tool identify harms for hospitalized children?
Background: An estimated 400,000 people die annually in the United States as a result of hospital-associated harm. The Centers for Medicare and Medicaid Services define harm as “unintended physical injury … by medical care that required additional monitoring, treatment, or hospitalization or that resulted in death.” Although harm is common, voluntary reporting of events has been shown to capture only 2%-8% of harm. Global Trigger Tools (GTT) are an alternative to voluntary reports. These tools use “triggers,” or clues, to help reviewers identify potential harms when reviewing the electronic heath record. The Institute for Healthcare Improvement (IHI) has created an adult-focused GTT; however, no pediatric-focused GTT exists.
Study design: Cross-sectional, retrospective chart review.
Setting: Children <22 years old discharged from six freestanding U.S. children’s hospitals in February 2012.
Synopsis: In a prior paper, the authors described how they used a modified Delphi technique to develop a pediatric GTT based upon the IHI GTT. Here they piloted this new pediatric-focused GTT through a retrospective chart review. One clinical nonphysician reviewer and one physician reviewer were selected from each site and received training on use of the pediatric GTT and the identification of harms. One hundred charts from each site were randomly selected for application of the GTT. The reviewers examined the charts for harms and then applied the GTT. When reviewers found a harm, they determined the likelihood that the harm was preventable.
Of the 600 records reviewed, 240 harms were found. The GTT identified 1,093 potential harms, leading to identification of 204 harms. The remaining 36 harms did not cause a trigger and were found by chart review. The positive predictive value of the aggregate GTT was 22%. There were 40 harms per 100 patients, and 24.3% of patients had one or more harm. Sixty-eight percent of harms were of the least severe type, and only one led to a patient death. The most common harms were intravenous catheter infiltration, respiratory distress, constipation, pain, and surgical complications.
Bottom line: The pediatric GTT appears to be a moderately sensitive indicator for inpatient pediatric harm. Inpatient pediatric harm occurs frequently, with about one in four pediatric inpatients suffering from harm. Serious harm appears uncommon.
Citation: Stockwell DC, Bisarya H, Classen DC, et al. A trigger tool to detect harm in pediatric inpatient settings. Pediatrics. 2015;135(6):1036-1042.
Clinical question: Can a trigger tool identify harms for hospitalized children?
Background: An estimated 400,000 people die annually in the United States as a result of hospital-associated harm. The Centers for Medicare and Medicaid Services define harm as “unintended physical injury … by medical care that required additional monitoring, treatment, or hospitalization or that resulted in death.” Although harm is common, voluntary reporting of events has been shown to capture only 2%-8% of harm. Global Trigger Tools (GTT) are an alternative to voluntary reports. These tools use “triggers,” or clues, to help reviewers identify potential harms when reviewing the electronic heath record. The Institute for Healthcare Improvement (IHI) has created an adult-focused GTT; however, no pediatric-focused GTT exists.
Study design: Cross-sectional, retrospective chart review.
Setting: Children <22 years old discharged from six freestanding U.S. children’s hospitals in February 2012.
Synopsis: In a prior paper, the authors described how they used a modified Delphi technique to develop a pediatric GTT based upon the IHI GTT. Here they piloted this new pediatric-focused GTT through a retrospective chart review. One clinical nonphysician reviewer and one physician reviewer were selected from each site and received training on use of the pediatric GTT and the identification of harms. One hundred charts from each site were randomly selected for application of the GTT. The reviewers examined the charts for harms and then applied the GTT. When reviewers found a harm, they determined the likelihood that the harm was preventable.
Of the 600 records reviewed, 240 harms were found. The GTT identified 1,093 potential harms, leading to identification of 204 harms. The remaining 36 harms did not cause a trigger and were found by chart review. The positive predictive value of the aggregate GTT was 22%. There were 40 harms per 100 patients, and 24.3% of patients had one or more harm. Sixty-eight percent of harms were of the least severe type, and only one led to a patient death. The most common harms were intravenous catheter infiltration, respiratory distress, constipation, pain, and surgical complications.
Bottom line: The pediatric GTT appears to be a moderately sensitive indicator for inpatient pediatric harm. Inpatient pediatric harm occurs frequently, with about one in four pediatric inpatients suffering from harm. Serious harm appears uncommon.
Citation: Stockwell DC, Bisarya H, Classen DC, et al. A trigger tool to detect harm in pediatric inpatient settings. Pediatrics. 2015;135(6):1036-1042.
Clinical question: Can a trigger tool identify harms for hospitalized children?
Background: An estimated 400,000 people die annually in the United States as a result of hospital-associated harm. The Centers for Medicare and Medicaid Services define harm as “unintended physical injury … by medical care that required additional monitoring, treatment, or hospitalization or that resulted in death.” Although harm is common, voluntary reporting of events has been shown to capture only 2%-8% of harm. Global Trigger Tools (GTT) are an alternative to voluntary reports. These tools use “triggers,” or clues, to help reviewers identify potential harms when reviewing the electronic heath record. The Institute for Healthcare Improvement (IHI) has created an adult-focused GTT; however, no pediatric-focused GTT exists.
Study design: Cross-sectional, retrospective chart review.
Setting: Children <22 years old discharged from six freestanding U.S. children’s hospitals in February 2012.
Synopsis: In a prior paper, the authors described how they used a modified Delphi technique to develop a pediatric GTT based upon the IHI GTT. Here they piloted this new pediatric-focused GTT through a retrospective chart review. One clinical nonphysician reviewer and one physician reviewer were selected from each site and received training on use of the pediatric GTT and the identification of harms. One hundred charts from each site were randomly selected for application of the GTT. The reviewers examined the charts for harms and then applied the GTT. When reviewers found a harm, they determined the likelihood that the harm was preventable.
Of the 600 records reviewed, 240 harms were found. The GTT identified 1,093 potential harms, leading to identification of 204 harms. The remaining 36 harms did not cause a trigger and were found by chart review. The positive predictive value of the aggregate GTT was 22%. There were 40 harms per 100 patients, and 24.3% of patients had one or more harm. Sixty-eight percent of harms were of the least severe type, and only one led to a patient death. The most common harms were intravenous catheter infiltration, respiratory distress, constipation, pain, and surgical complications.
Bottom line: The pediatric GTT appears to be a moderately sensitive indicator for inpatient pediatric harm. Inpatient pediatric harm occurs frequently, with about one in four pediatric inpatients suffering from harm. Serious harm appears uncommon.
Citation: Stockwell DC, Bisarya H, Classen DC, et al. A trigger tool to detect harm in pediatric inpatient settings. Pediatrics. 2015;135(6):1036-1042.
Easing the Grieving Process for Families of Patients Dying in the ICU
Clinical question: Can we dignify death in the ICU and ease the grieving process by soliciting wishes from patients, families, and care team members?
Background: The death of the critically ill patient in the ICU can be dehumanizing and overwhelming for the patient’s family and friends, leading to prolonged physical and psychological stress. These deaths might have similar effects on the clinicians caring for the patients.
Study design: Mixed methods.
Setting: Medical-surgical ICU at a 21-bed, academic tertiary medical center in Ontario, Canada.
Synopsis: Semi-structured interviews were conducted with at least one family member and three clinicians per patient. A total of 40 patients were screened and deemed eligible for inclusion. Only seven patients were able to provide input on the wishes or interviews; the others had impaired consciousness. The team obtained 163 wishes from those individuals, and was able to implement 159 of them (97.5%). At least three wishes from each patient-family dyad were implemented.
The wishes were classified into five categories:
- Humanizing the environment;
- Personal tributes;
- Family reconnections;
- Rituals and observances; and
- Paying it forward.
These wishes were implemented before (51.6%) and after (48.4%) death and were generally inexpensive (less than $200 per patient).
From the 160 interviews of 170 individuals, the central theme that emerged was personalization of the dying process in the ICU through three related domains: dignifying the patient, giving the family a voice, and fostering clinician compassion.
The 3 Wishes Project provides a framework to foster discussion among care team members and families to ensure personalization and dignity in the dying process.
Bottom line: Solicitation of wishes from dying patients, their families, and their care team members can have a positive impact by allowing individualized end-of-life care.
Citation: Cook D, Swinton M, Toledo F, et al. Personalizing death in the intensive care unit: the 3 Wishes Project: a mixed-methods study. Ann Intern Med. 2015;163(4):271-279.
Clinical question: Can we dignify death in the ICU and ease the grieving process by soliciting wishes from patients, families, and care team members?
Background: The death of the critically ill patient in the ICU can be dehumanizing and overwhelming for the patient’s family and friends, leading to prolonged physical and psychological stress. These deaths might have similar effects on the clinicians caring for the patients.
Study design: Mixed methods.
Setting: Medical-surgical ICU at a 21-bed, academic tertiary medical center in Ontario, Canada.
Synopsis: Semi-structured interviews were conducted with at least one family member and three clinicians per patient. A total of 40 patients were screened and deemed eligible for inclusion. Only seven patients were able to provide input on the wishes or interviews; the others had impaired consciousness. The team obtained 163 wishes from those individuals, and was able to implement 159 of them (97.5%). At least three wishes from each patient-family dyad were implemented.
The wishes were classified into five categories:
- Humanizing the environment;
- Personal tributes;
- Family reconnections;
- Rituals and observances; and
- Paying it forward.
These wishes were implemented before (51.6%) and after (48.4%) death and were generally inexpensive (less than $200 per patient).
From the 160 interviews of 170 individuals, the central theme that emerged was personalization of the dying process in the ICU through three related domains: dignifying the patient, giving the family a voice, and fostering clinician compassion.
The 3 Wishes Project provides a framework to foster discussion among care team members and families to ensure personalization and dignity in the dying process.
Bottom line: Solicitation of wishes from dying patients, their families, and their care team members can have a positive impact by allowing individualized end-of-life care.
Citation: Cook D, Swinton M, Toledo F, et al. Personalizing death in the intensive care unit: the 3 Wishes Project: a mixed-methods study. Ann Intern Med. 2015;163(4):271-279.
Clinical question: Can we dignify death in the ICU and ease the grieving process by soliciting wishes from patients, families, and care team members?
Background: The death of the critically ill patient in the ICU can be dehumanizing and overwhelming for the patient’s family and friends, leading to prolonged physical and psychological stress. These deaths might have similar effects on the clinicians caring for the patients.
Study design: Mixed methods.
Setting: Medical-surgical ICU at a 21-bed, academic tertiary medical center in Ontario, Canada.
Synopsis: Semi-structured interviews were conducted with at least one family member and three clinicians per patient. A total of 40 patients were screened and deemed eligible for inclusion. Only seven patients were able to provide input on the wishes or interviews; the others had impaired consciousness. The team obtained 163 wishes from those individuals, and was able to implement 159 of them (97.5%). At least three wishes from each patient-family dyad were implemented.
The wishes were classified into five categories:
- Humanizing the environment;
- Personal tributes;
- Family reconnections;
- Rituals and observances; and
- Paying it forward.
These wishes were implemented before (51.6%) and after (48.4%) death and were generally inexpensive (less than $200 per patient).
From the 160 interviews of 170 individuals, the central theme that emerged was personalization of the dying process in the ICU through three related domains: dignifying the patient, giving the family a voice, and fostering clinician compassion.
The 3 Wishes Project provides a framework to foster discussion among care team members and families to ensure personalization and dignity in the dying process.
Bottom line: Solicitation of wishes from dying patients, their families, and their care team members can have a positive impact by allowing individualized end-of-life care.
Citation: Cook D, Swinton M, Toledo F, et al. Personalizing death in the intensive care unit: the 3 Wishes Project: a mixed-methods study. Ann Intern Med. 2015;163(4):271-279.
Urinalysis Is Reliable Infection Predictor in Infants
Clinical question: In infants younger than three months of age with bacteremic urinary tract infection (UTI), how sensitive and specific are urinalysis (UA) findings?
Background: Infants are commonly hospitalized with UTIs. The gold standard for diagnosis is considered to be urine culture. When compared to this gold standard, the sensitivity of UA findings for the diagnosis of UTI has been previously reported to be around 75% to 85%; however, a positive urine culture alone in the setting of negative UA may not be reflective of a UTI due to asymptomatic bacteriuria or contamination. The 2011 American Academy of Pediatrics clinical guideline for UTIs suggests that the diagnosis should require positive urine culture in addition to abnormal UA. These guidelines do not include infants younger than two months of age, and positive cultures in this age group are generally regarded as a UTI and treated as such. Positive culture results with the same organism in the urine and blood indicates very low likelihood of contamination or asymptomatic bacteriuria, and patients with bacteremic UTI are likely to have a true infection.
Study design: Multicenter, retrospective, cross-sectional study.
Setting: Twenty hospitals in eleven hospital systems.
Synopsis: Researchers used a multicenter microbiology database to identify infants younger than three months of age with bacteremic UTI (same pathogenic organism in blood and urine). Data was collected on UA, including microscopy [white blood cells per high-power field (WBC/HPF), bacteria], dipstick [nitrites, leukocyte esterase (LE)], and urine culture in colony-forming units per mL (CFU/mL).
Exclusions included:
- Major comorbidities (defined in this study as neuromuscular conditions such as spina bifida, previous urologic surgery other than circumcision, or immunodeficiency);
- Patients managed in an ICU setting; and
- Patients with indwelling urinary or central venous catheters at the time of culture.
A total of 276 infants with bacteremic UTI were identified, with 31 exclusions (12 with no UA performed, 19 with cultures with <50,000 CFU/mL). The remaining 245 infants were included for analysis. The control group was a random sampling of 115 similarly aged infants who underwent evaluation for serious bacterial infection and had negative urine cultures.
Comparison between the study group (bacteremic UTI) and the controls showed:
- LE (including any “positive” LE) had a sensitivity of 97.6%, specificity of 93.9%;
- Considering “trace” LE as negative changed the sensitivity and specificity to 95.7% and 97.4%, respectively; and
- Positive nitrites had a specificity of 100%.
A definition of positive UA that includes pyuria (greater than 3 WBC/HPF) and/or any LE was highly sensitive (99.5%) and specific (87.8%). All but one of 203 infants with bacteremic UTI who had complete UA results were positive for LE and/or WBC/HPF. The one exception was a 64-day-old girl with Group B Streptococcus infection. Bacteria on microscopy showed poor specificity.
The authors discussed two possible explanations for the study’s finding of high sensitivity of the UA, including:
- The UA is in fact highly sensitive, and previous studies have been flawed by a faulty gold standard (positive cultures due to asymptomatic bacteriuria or contamination); or
- Screening tests are more sensitive in the setting of severe disease (in this case, UTI with bacteremia).
The second explanation is controversial, and the authors of this article cite previous studies showing minimal differences between UTI with or without bacteremia.
Bottom line: In infants younger than three months of age with bacteremic UTI, the findings of pyuria and/or any LE on UA are reliable predictors of infection, with higher sensitivity than previously reported.
Citation: Schroeder AR, Chang PW, Shen MW, Biondi EA, Greenhow TL. Diagnostic accuracy of the urinalysis for urinary tract infection in infants <3 months of age. Pediatrics. 2015;135(6):965-71.
Clinical question: In infants younger than three months of age with bacteremic urinary tract infection (UTI), how sensitive and specific are urinalysis (UA) findings?
Background: Infants are commonly hospitalized with UTIs. The gold standard for diagnosis is considered to be urine culture. When compared to this gold standard, the sensitivity of UA findings for the diagnosis of UTI has been previously reported to be around 75% to 85%; however, a positive urine culture alone in the setting of negative UA may not be reflective of a UTI due to asymptomatic bacteriuria or contamination. The 2011 American Academy of Pediatrics clinical guideline for UTIs suggests that the diagnosis should require positive urine culture in addition to abnormal UA. These guidelines do not include infants younger than two months of age, and positive cultures in this age group are generally regarded as a UTI and treated as such. Positive culture results with the same organism in the urine and blood indicates very low likelihood of contamination or asymptomatic bacteriuria, and patients with bacteremic UTI are likely to have a true infection.
Study design: Multicenter, retrospective, cross-sectional study.
Setting: Twenty hospitals in eleven hospital systems.
Synopsis: Researchers used a multicenter microbiology database to identify infants younger than three months of age with bacteremic UTI (same pathogenic organism in blood and urine). Data was collected on UA, including microscopy [white blood cells per high-power field (WBC/HPF), bacteria], dipstick [nitrites, leukocyte esterase (LE)], and urine culture in colony-forming units per mL (CFU/mL).
Exclusions included:
- Major comorbidities (defined in this study as neuromuscular conditions such as spina bifida, previous urologic surgery other than circumcision, or immunodeficiency);
- Patients managed in an ICU setting; and
- Patients with indwelling urinary or central venous catheters at the time of culture.
A total of 276 infants with bacteremic UTI were identified, with 31 exclusions (12 with no UA performed, 19 with cultures with <50,000 CFU/mL). The remaining 245 infants were included for analysis. The control group was a random sampling of 115 similarly aged infants who underwent evaluation for serious bacterial infection and had negative urine cultures.
Comparison between the study group (bacteremic UTI) and the controls showed:
- LE (including any “positive” LE) had a sensitivity of 97.6%, specificity of 93.9%;
- Considering “trace” LE as negative changed the sensitivity and specificity to 95.7% and 97.4%, respectively; and
- Positive nitrites had a specificity of 100%.
A definition of positive UA that includes pyuria (greater than 3 WBC/HPF) and/or any LE was highly sensitive (99.5%) and specific (87.8%). All but one of 203 infants with bacteremic UTI who had complete UA results were positive for LE and/or WBC/HPF. The one exception was a 64-day-old girl with Group B Streptococcus infection. Bacteria on microscopy showed poor specificity.
The authors discussed two possible explanations for the study’s finding of high sensitivity of the UA, including:
- The UA is in fact highly sensitive, and previous studies have been flawed by a faulty gold standard (positive cultures due to asymptomatic bacteriuria or contamination); or
- Screening tests are more sensitive in the setting of severe disease (in this case, UTI with bacteremia).
The second explanation is controversial, and the authors of this article cite previous studies showing minimal differences between UTI with or without bacteremia.
Bottom line: In infants younger than three months of age with bacteremic UTI, the findings of pyuria and/or any LE on UA are reliable predictors of infection, with higher sensitivity than previously reported.
Citation: Schroeder AR, Chang PW, Shen MW, Biondi EA, Greenhow TL. Diagnostic accuracy of the urinalysis for urinary tract infection in infants <3 months of age. Pediatrics. 2015;135(6):965-71.
Clinical question: In infants younger than three months of age with bacteremic urinary tract infection (UTI), how sensitive and specific are urinalysis (UA) findings?
Background: Infants are commonly hospitalized with UTIs. The gold standard for diagnosis is considered to be urine culture. When compared to this gold standard, the sensitivity of UA findings for the diagnosis of UTI has been previously reported to be around 75% to 85%; however, a positive urine culture alone in the setting of negative UA may not be reflective of a UTI due to asymptomatic bacteriuria or contamination. The 2011 American Academy of Pediatrics clinical guideline for UTIs suggests that the diagnosis should require positive urine culture in addition to abnormal UA. These guidelines do not include infants younger than two months of age, and positive cultures in this age group are generally regarded as a UTI and treated as such. Positive culture results with the same organism in the urine and blood indicates very low likelihood of contamination or asymptomatic bacteriuria, and patients with bacteremic UTI are likely to have a true infection.
Study design: Multicenter, retrospective, cross-sectional study.
Setting: Twenty hospitals in eleven hospital systems.
Synopsis: Researchers used a multicenter microbiology database to identify infants younger than three months of age with bacteremic UTI (same pathogenic organism in blood and urine). Data was collected on UA, including microscopy [white blood cells per high-power field (WBC/HPF), bacteria], dipstick [nitrites, leukocyte esterase (LE)], and urine culture in colony-forming units per mL (CFU/mL).
Exclusions included:
- Major comorbidities (defined in this study as neuromuscular conditions such as spina bifida, previous urologic surgery other than circumcision, or immunodeficiency);
- Patients managed in an ICU setting; and
- Patients with indwelling urinary or central venous catheters at the time of culture.
A total of 276 infants with bacteremic UTI were identified, with 31 exclusions (12 with no UA performed, 19 with cultures with <50,000 CFU/mL). The remaining 245 infants were included for analysis. The control group was a random sampling of 115 similarly aged infants who underwent evaluation for serious bacterial infection and had negative urine cultures.
Comparison between the study group (bacteremic UTI) and the controls showed:
- LE (including any “positive” LE) had a sensitivity of 97.6%, specificity of 93.9%;
- Considering “trace” LE as negative changed the sensitivity and specificity to 95.7% and 97.4%, respectively; and
- Positive nitrites had a specificity of 100%.
A definition of positive UA that includes pyuria (greater than 3 WBC/HPF) and/or any LE was highly sensitive (99.5%) and specific (87.8%). All but one of 203 infants with bacteremic UTI who had complete UA results were positive for LE and/or WBC/HPF. The one exception was a 64-day-old girl with Group B Streptococcus infection. Bacteria on microscopy showed poor specificity.
The authors discussed two possible explanations for the study’s finding of high sensitivity of the UA, including:
- The UA is in fact highly sensitive, and previous studies have been flawed by a faulty gold standard (positive cultures due to asymptomatic bacteriuria or contamination); or
- Screening tests are more sensitive in the setting of severe disease (in this case, UTI with bacteremia).
The second explanation is controversial, and the authors of this article cite previous studies showing minimal differences between UTI with or without bacteremia.
Bottom line: In infants younger than three months of age with bacteremic UTI, the findings of pyuria and/or any LE on UA are reliable predictors of infection, with higher sensitivity than previously reported.
Citation: Schroeder AR, Chang PW, Shen MW, Biondi EA, Greenhow TL. Diagnostic accuracy of the urinalysis for urinary tract infection in infants <3 months of age. Pediatrics. 2015;135(6):965-71.
High-Flow Nasal Oxygen Therapy Noninferior to BiPAP in Post-Operative Respiratory Failure
Clinical question: In post-operative cardiothoracic surgery patients, is high-flow nasal oxygen therapy inferior to BiPAP for resolution of acute respiratory failure?
Background: Acute respiratory failure is common following cardiothoracic surgery, and noninvasive ventilation often is used to avoid intubation. Noninvasive ventilation is resource-intensive and might be uncomfortable to patients. High-flow nasal oxygen therapy is an alternative modality, which provides large amounts of oxygen with more ease and patient comfort.
Study design: Multi-center, randomized, noninferiority trial.
Setting: Six ICUs in France.
Synopsis: Investigators randomized 830 patients who met criteria (obesity, heart failure, or failure of spontaneous breathing trial) after cardiothoracic surgery. These patients were prophylactically treated with high-flow nasal oxygen or BiPAP. Patients with sleep apnea, nausea/vomiting, agitation/confusion, or hemodynamic instability were excluded. Data collected included arterial blood gas, respiratory rate, and patient-rated dyspnea. The primary outcome was treatment failure as defined by reintubation and mechanical ventilation, a switch to the other study treatment, or study treatment discontinuation.
Complications included pneumothorax, colonic pseudoobstruction, and nosocomial pneumonia. The expected rate of failure for BiPAP was 20%. High-flow nasal oxygen therapy was not inferior to BiPAP, with similar treatment failure rates occurring in both groups (21.9% in BiPAP patients vs. 21% of high-flow nasal oxygen patients); 20% of patients experienced persistent discomfort with either treatment method.
There were no significant differences in complications between the two study groups. Limitations included lack of blinding and potential for bias, leading to treatment failure and crossover.
Bottom line: High-flow nasal oxygen was noninferior to BiPAP in patients with respiratory failure after cardiothoracic surgery.
Citation: Stéphan F, Barrucand B, Petit P, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. JAMA. 2015;313(23):2331-2339.
Clinical question: In post-operative cardiothoracic surgery patients, is high-flow nasal oxygen therapy inferior to BiPAP for resolution of acute respiratory failure?
Background: Acute respiratory failure is common following cardiothoracic surgery, and noninvasive ventilation often is used to avoid intubation. Noninvasive ventilation is resource-intensive and might be uncomfortable to patients. High-flow nasal oxygen therapy is an alternative modality, which provides large amounts of oxygen with more ease and patient comfort.
Study design: Multi-center, randomized, noninferiority trial.
Setting: Six ICUs in France.
Synopsis: Investigators randomized 830 patients who met criteria (obesity, heart failure, or failure of spontaneous breathing trial) after cardiothoracic surgery. These patients were prophylactically treated with high-flow nasal oxygen or BiPAP. Patients with sleep apnea, nausea/vomiting, agitation/confusion, or hemodynamic instability were excluded. Data collected included arterial blood gas, respiratory rate, and patient-rated dyspnea. The primary outcome was treatment failure as defined by reintubation and mechanical ventilation, a switch to the other study treatment, or study treatment discontinuation.
Complications included pneumothorax, colonic pseudoobstruction, and nosocomial pneumonia. The expected rate of failure for BiPAP was 20%. High-flow nasal oxygen therapy was not inferior to BiPAP, with similar treatment failure rates occurring in both groups (21.9% in BiPAP patients vs. 21% of high-flow nasal oxygen patients); 20% of patients experienced persistent discomfort with either treatment method.
There were no significant differences in complications between the two study groups. Limitations included lack of blinding and potential for bias, leading to treatment failure and crossover.
Bottom line: High-flow nasal oxygen was noninferior to BiPAP in patients with respiratory failure after cardiothoracic surgery.
Citation: Stéphan F, Barrucand B, Petit P, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. JAMA. 2015;313(23):2331-2339.
Clinical question: In post-operative cardiothoracic surgery patients, is high-flow nasal oxygen therapy inferior to BiPAP for resolution of acute respiratory failure?
Background: Acute respiratory failure is common following cardiothoracic surgery, and noninvasive ventilation often is used to avoid intubation. Noninvasive ventilation is resource-intensive and might be uncomfortable to patients. High-flow nasal oxygen therapy is an alternative modality, which provides large amounts of oxygen with more ease and patient comfort.
Study design: Multi-center, randomized, noninferiority trial.
Setting: Six ICUs in France.
Synopsis: Investigators randomized 830 patients who met criteria (obesity, heart failure, or failure of spontaneous breathing trial) after cardiothoracic surgery. These patients were prophylactically treated with high-flow nasal oxygen or BiPAP. Patients with sleep apnea, nausea/vomiting, agitation/confusion, or hemodynamic instability were excluded. Data collected included arterial blood gas, respiratory rate, and patient-rated dyspnea. The primary outcome was treatment failure as defined by reintubation and mechanical ventilation, a switch to the other study treatment, or study treatment discontinuation.
Complications included pneumothorax, colonic pseudoobstruction, and nosocomial pneumonia. The expected rate of failure for BiPAP was 20%. High-flow nasal oxygen therapy was not inferior to BiPAP, with similar treatment failure rates occurring in both groups (21.9% in BiPAP patients vs. 21% of high-flow nasal oxygen patients); 20% of patients experienced persistent discomfort with either treatment method.
There were no significant differences in complications between the two study groups. Limitations included lack of blinding and potential for bias, leading to treatment failure and crossover.
Bottom line: High-flow nasal oxygen was noninferior to BiPAP in patients with respiratory failure after cardiothoracic surgery.
Citation: Stéphan F, Barrucand B, Petit P, et al. High-flow nasal oxygen vs noninvasive positive airway pressure in hypoxemic patients after cardiothoracic surgery: a randomized clinical trial. JAMA. 2015;313(23):2331-2339.