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Emerging Trends in Mental Health Care (FULL)
The articles in this special issue reflect a number of emerging trends in federal practice. The first is that the optimal delivery of mental health clinical care as well as the conduct of cutting-edge clinical research are most often inter- and multidisciplinary collaborations. A background in public and military service instills the experience and training to maximize teamwork in the health care professionals of the VA, DoD, and PHS. Pharmacists, neuropsychologists, psychiatrists, social workers, nurses, and others come together to advance the science and scholarship that are the backbone for building efficacious patient-centered health care. Just as important, most of these articles reflect a partnership between VA and academic medical centers. The knowledge and skill of each partner amplifies the other to produce novel insights, which can be readily translated into treatment progress that benefits patients.
A case in point: Neurology and psychiatry have historically been different disciplines. However, some thought leaders recently suggested that the explosion of neuroscience has narrowed the gap between the specialties to a single field, as demonstrated by Langevin and colleagues. The authors propose the use of deep brain stimulation to treat patients with posttraumatic stress disorder (PTSD). Deep brain stimulation is a process in which electrodes are inserted into targeted areas of the brain and alter the neural impulses and physiology to relieve neuropsychiatric symptoms and, thus, modulate neural structure and function.
Up to one-third of veterans with PTSD also may have a substance use disorder. Pary and colleagues review the research on another trend in mental health treatment that is fast becoming a best practice: the integrated, coordinated treatment of co-occurring substance use and mental health disorders. This approach provides a comprehensive look at the diagnosis and treatment of depression and bipolar disorder coexistent with alcohol use disorder with both psycho- and pharmacotherapy.
Through its unique primary care psychiatry clinics, the VA has pioneered integrated care for individuals with serious mental illness and chronic medical conditions that may result in frequent hospitalization and increased overall health care utilization. Gill and colleagues emphasize the urgency and importance of these efforts given the increasing number of active-duty service members and veterans who served in Iraq and Afghanistan and are diagnosed with mental and physical conditions. Their outcomes data suggest that directing outpatient resources to patients with specific demographic and clinical factors may be beneficial.
The challenges of providing team-based care to patients with mental health disorders is borne out in the research of Lee and colleagues. Their examination of the risk of hospitalization for patients with PTSD who have been treated with benzodiazepine and opioids is a reminder of the challenge of treating patients with multiple comorbidities. The authors caution that prescribers should “limit benzodiazepine and opioid use in this population and consider safer nonpharmacologic and pharmacologic treatment options when possible.”
Many of these trends coalesce in my discussion with Larry Davis, MD, Distinguished Professor of Neurology at the University of New Mexico School of Medicine and Chief of Neurology at the New Mexico VA Health Care System. Dr. Davis describes a successful teleneurology program that treats patients in underserved rural areas in New Mexico and Colorado. He also touts the benefits of teleneurology to address the shortage of neurologists. Many of the most common and serious neurologic conditions, such as epilepsy, Alzheimer, and Parkinson, are managed through a teleneurology program that includes education and support for patients and caregivers.
The articles in this special issue reflect a number of emerging trends in federal practice. The first is that the optimal delivery of mental health clinical care as well as the conduct of cutting-edge clinical research are most often inter- and multidisciplinary collaborations. A background in public and military service instills the experience and training to maximize teamwork in the health care professionals of the VA, DoD, and PHS. Pharmacists, neuropsychologists, psychiatrists, social workers, nurses, and others come together to advance the science and scholarship that are the backbone for building efficacious patient-centered health care. Just as important, most of these articles reflect a partnership between VA and academic medical centers. The knowledge and skill of each partner amplifies the other to produce novel insights, which can be readily translated into treatment progress that benefits patients.
A case in point: Neurology and psychiatry have historically been different disciplines. However, some thought leaders recently suggested that the explosion of neuroscience has narrowed the gap between the specialties to a single field, as demonstrated by Langevin and colleagues. The authors propose the use of deep brain stimulation to treat patients with posttraumatic stress disorder (PTSD). Deep brain stimulation is a process in which electrodes are inserted into targeted areas of the brain and alter the neural impulses and physiology to relieve neuropsychiatric symptoms and, thus, modulate neural structure and function.
Up to one-third of veterans with PTSD also may have a substance use disorder. Pary and colleagues review the research on another trend in mental health treatment that is fast becoming a best practice: the integrated, coordinated treatment of co-occurring substance use and mental health disorders. This approach provides a comprehensive look at the diagnosis and treatment of depression and bipolar disorder coexistent with alcohol use disorder with both psycho- and pharmacotherapy.
Through its unique primary care psychiatry clinics, the VA has pioneered integrated care for individuals with serious mental illness and chronic medical conditions that may result in frequent hospitalization and increased overall health care utilization. Gill and colleagues emphasize the urgency and importance of these efforts given the increasing number of active-duty service members and veterans who served in Iraq and Afghanistan and are diagnosed with mental and physical conditions. Their outcomes data suggest that directing outpatient resources to patients with specific demographic and clinical factors may be beneficial.
The challenges of providing team-based care to patients with mental health disorders is borne out in the research of Lee and colleagues. Their examination of the risk of hospitalization for patients with PTSD who have been treated with benzodiazepine and opioids is a reminder of the challenge of treating patients with multiple comorbidities. The authors caution that prescribers should “limit benzodiazepine and opioid use in this population and consider safer nonpharmacologic and pharmacologic treatment options when possible.”
Many of these trends coalesce in my discussion with Larry Davis, MD, Distinguished Professor of Neurology at the University of New Mexico School of Medicine and Chief of Neurology at the New Mexico VA Health Care System. Dr. Davis describes a successful teleneurology program that treats patients in underserved rural areas in New Mexico and Colorado. He also touts the benefits of teleneurology to address the shortage of neurologists. Many of the most common and serious neurologic conditions, such as epilepsy, Alzheimer, and Parkinson, are managed through a teleneurology program that includes education and support for patients and caregivers.
The articles in this special issue reflect a number of emerging trends in federal practice. The first is that the optimal delivery of mental health clinical care as well as the conduct of cutting-edge clinical research are most often inter- and multidisciplinary collaborations. A background in public and military service instills the experience and training to maximize teamwork in the health care professionals of the VA, DoD, and PHS. Pharmacists, neuropsychologists, psychiatrists, social workers, nurses, and others come together to advance the science and scholarship that are the backbone for building efficacious patient-centered health care. Just as important, most of these articles reflect a partnership between VA and academic medical centers. The knowledge and skill of each partner amplifies the other to produce novel insights, which can be readily translated into treatment progress that benefits patients.
A case in point: Neurology and psychiatry have historically been different disciplines. However, some thought leaders recently suggested that the explosion of neuroscience has narrowed the gap between the specialties to a single field, as demonstrated by Langevin and colleagues. The authors propose the use of deep brain stimulation to treat patients with posttraumatic stress disorder (PTSD). Deep brain stimulation is a process in which electrodes are inserted into targeted areas of the brain and alter the neural impulses and physiology to relieve neuropsychiatric symptoms and, thus, modulate neural structure and function.
Up to one-third of veterans with PTSD also may have a substance use disorder. Pary and colleagues review the research on another trend in mental health treatment that is fast becoming a best practice: the integrated, coordinated treatment of co-occurring substance use and mental health disorders. This approach provides a comprehensive look at the diagnosis and treatment of depression and bipolar disorder coexistent with alcohol use disorder with both psycho- and pharmacotherapy.
Through its unique primary care psychiatry clinics, the VA has pioneered integrated care for individuals with serious mental illness and chronic medical conditions that may result in frequent hospitalization and increased overall health care utilization. Gill and colleagues emphasize the urgency and importance of these efforts given the increasing number of active-duty service members and veterans who served in Iraq and Afghanistan and are diagnosed with mental and physical conditions. Their outcomes data suggest that directing outpatient resources to patients with specific demographic and clinical factors may be beneficial.
The challenges of providing team-based care to patients with mental health disorders is borne out in the research of Lee and colleagues. Their examination of the risk of hospitalization for patients with PTSD who have been treated with benzodiazepine and opioids is a reminder of the challenge of treating patients with multiple comorbidities. The authors caution that prescribers should “limit benzodiazepine and opioid use in this population and consider safer nonpharmacologic and pharmacologic treatment options when possible.”
Many of these trends coalesce in my discussion with Larry Davis, MD, Distinguished Professor of Neurology at the University of New Mexico School of Medicine and Chief of Neurology at the New Mexico VA Health Care System. Dr. Davis describes a successful teleneurology program that treats patients in underserved rural areas in New Mexico and Colorado. He also touts the benefits of teleneurology to address the shortage of neurologists. Many of the most common and serious neurologic conditions, such as epilepsy, Alzheimer, and Parkinson, are managed through a teleneurology program that includes education and support for patients and caregivers.
Potential link between varicose veins and VTE, PAD
People with varicose veins may have an increased risk of venous thromboembolism (VTE) and peripheral artery disease (PAD), according to a new study.
The data suggested patients with varicose veins had a 5-fold higher risk of deep vein thrombosis (DVT) and roughly twice the risk of pulmonary embolism (PE) and PAD as patients without varicose veins.
Investigators said these results suggest an increased risk of DVT among patients with varicose veins, but “the findings for PE and PAD are less clear due to the potential for confounding.”
Pei-Chun Chen, PhD, of China Medical University in Taichung, Taiwan, and colleagues reported these findings in JAMA.
The team conducted this research using claims data in Taiwan’s National Health Insurance program. They assessed the risk of DVT, PE, and PAD in 212,984 patients with varicose veins and 212,984 control subjects. Patients and controls were matched by age, sex, and calendar year.
All study subjects were enrolled from 2001 to 2013 and followed through 2014.
Among the patients with varicose veins, the median duration of follow-up was 7.5 years for DVT, 7.8 years for PE, and 7.3 years for PAD. For controls, the median follow-up was 7.6 years for DVT, 7.7 years for PE, and 7.4 years for PAD.
Results
The incidence rate for DVT was 6.55 per 1000 person-years for patients with varicose veins (n=10,360) and 1.23 per 1000 person-years for controls (n=1980). The absolute risk difference (ARD) was 5.32.
The incidence rate for PE was 0.48 per 1000 person-years for patients with varicose veins (n=793) and 0.28 per 1000 person-years for controls (n=451). The ARD was 0.20.
The incidence rate for PAD was 10.73 per 1000 person-years for patients with varicose veins (n=16,615) and 6.22 for controls (n=9709). The ARD was 4.51.
The hazard ratios (for the varicose-veins group compared to controls) were 5.30 for DVT, 1.73 for PE, and 1.72 for PAD.
The investigators also calculated hazard ratios in a model adjusted for sex, age, index year, number of outpatient visits during the year before index date, and comorbidities. Comorbidities included hypertension, diabetes, chronic obstructive pulmonary disease, hyperlipidemia, malignancy, heart failure, ischemic heart disease, stroke, and chronic renal insufficiency.
In this adjusted model, the hazard ratios were 5.39 for DVT, 1.75 for PE, and 1.76 for PAD.
Limitations
The investigators said this study had several limitations.
First, the data did not include information for patients who didn’t seek medical care for varicose veins. Therefore, the results may reflect only the risk of VTE and PAD among patients with more severe varicose veins.
And the investigators were not able to examine whether the severity of varicose veins played a role in the risk of VTE or PAD.
In addition, information on some potential confounders, such as smoking and obesity, was not available. And the magnitude of the association between varicose veins and PE/PAD was small, so the association the investigators observed could be due to residual or unmeasured confounding.
The investigators also noted that diagnostic evaluations for PAD are more likely to occur in patients with varicose veins, which could partially explain the observed association between varicose veins and PAD.
Furthermore, cases of DVT, PE, and PAD could have been misclassified.
People with varicose veins may have an increased risk of venous thromboembolism (VTE) and peripheral artery disease (PAD), according to a new study.
The data suggested patients with varicose veins had a 5-fold higher risk of deep vein thrombosis (DVT) and roughly twice the risk of pulmonary embolism (PE) and PAD as patients without varicose veins.
Investigators said these results suggest an increased risk of DVT among patients with varicose veins, but “the findings for PE and PAD are less clear due to the potential for confounding.”
Pei-Chun Chen, PhD, of China Medical University in Taichung, Taiwan, and colleagues reported these findings in JAMA.
The team conducted this research using claims data in Taiwan’s National Health Insurance program. They assessed the risk of DVT, PE, and PAD in 212,984 patients with varicose veins and 212,984 control subjects. Patients and controls were matched by age, sex, and calendar year.
All study subjects were enrolled from 2001 to 2013 and followed through 2014.
Among the patients with varicose veins, the median duration of follow-up was 7.5 years for DVT, 7.8 years for PE, and 7.3 years for PAD. For controls, the median follow-up was 7.6 years for DVT, 7.7 years for PE, and 7.4 years for PAD.
Results
The incidence rate for DVT was 6.55 per 1000 person-years for patients with varicose veins (n=10,360) and 1.23 per 1000 person-years for controls (n=1980). The absolute risk difference (ARD) was 5.32.
The incidence rate for PE was 0.48 per 1000 person-years for patients with varicose veins (n=793) and 0.28 per 1000 person-years for controls (n=451). The ARD was 0.20.
The incidence rate for PAD was 10.73 per 1000 person-years for patients with varicose veins (n=16,615) and 6.22 for controls (n=9709). The ARD was 4.51.
The hazard ratios (for the varicose-veins group compared to controls) were 5.30 for DVT, 1.73 for PE, and 1.72 for PAD.
The investigators also calculated hazard ratios in a model adjusted for sex, age, index year, number of outpatient visits during the year before index date, and comorbidities. Comorbidities included hypertension, diabetes, chronic obstructive pulmonary disease, hyperlipidemia, malignancy, heart failure, ischemic heart disease, stroke, and chronic renal insufficiency.
In this adjusted model, the hazard ratios were 5.39 for DVT, 1.75 for PE, and 1.76 for PAD.
Limitations
The investigators said this study had several limitations.
First, the data did not include information for patients who didn’t seek medical care for varicose veins. Therefore, the results may reflect only the risk of VTE and PAD among patients with more severe varicose veins.
And the investigators were not able to examine whether the severity of varicose veins played a role in the risk of VTE or PAD.
In addition, information on some potential confounders, such as smoking and obesity, was not available. And the magnitude of the association between varicose veins and PE/PAD was small, so the association the investigators observed could be due to residual or unmeasured confounding.
The investigators also noted that diagnostic evaluations for PAD are more likely to occur in patients with varicose veins, which could partially explain the observed association between varicose veins and PAD.
Furthermore, cases of DVT, PE, and PAD could have been misclassified.
People with varicose veins may have an increased risk of venous thromboembolism (VTE) and peripheral artery disease (PAD), according to a new study.
The data suggested patients with varicose veins had a 5-fold higher risk of deep vein thrombosis (DVT) and roughly twice the risk of pulmonary embolism (PE) and PAD as patients without varicose veins.
Investigators said these results suggest an increased risk of DVT among patients with varicose veins, but “the findings for PE and PAD are less clear due to the potential for confounding.”
Pei-Chun Chen, PhD, of China Medical University in Taichung, Taiwan, and colleagues reported these findings in JAMA.
The team conducted this research using claims data in Taiwan’s National Health Insurance program. They assessed the risk of DVT, PE, and PAD in 212,984 patients with varicose veins and 212,984 control subjects. Patients and controls were matched by age, sex, and calendar year.
All study subjects were enrolled from 2001 to 2013 and followed through 2014.
Among the patients with varicose veins, the median duration of follow-up was 7.5 years for DVT, 7.8 years for PE, and 7.3 years for PAD. For controls, the median follow-up was 7.6 years for DVT, 7.7 years for PE, and 7.4 years for PAD.
Results
The incidence rate for DVT was 6.55 per 1000 person-years for patients with varicose veins (n=10,360) and 1.23 per 1000 person-years for controls (n=1980). The absolute risk difference (ARD) was 5.32.
The incidence rate for PE was 0.48 per 1000 person-years for patients with varicose veins (n=793) and 0.28 per 1000 person-years for controls (n=451). The ARD was 0.20.
The incidence rate for PAD was 10.73 per 1000 person-years for patients with varicose veins (n=16,615) and 6.22 for controls (n=9709). The ARD was 4.51.
The hazard ratios (for the varicose-veins group compared to controls) were 5.30 for DVT, 1.73 for PE, and 1.72 for PAD.
The investigators also calculated hazard ratios in a model adjusted for sex, age, index year, number of outpatient visits during the year before index date, and comorbidities. Comorbidities included hypertension, diabetes, chronic obstructive pulmonary disease, hyperlipidemia, malignancy, heart failure, ischemic heart disease, stroke, and chronic renal insufficiency.
In this adjusted model, the hazard ratios were 5.39 for DVT, 1.75 for PE, and 1.76 for PAD.
Limitations
The investigators said this study had several limitations.
First, the data did not include information for patients who didn’t seek medical care for varicose veins. Therefore, the results may reflect only the risk of VTE and PAD among patients with more severe varicose veins.
And the investigators were not able to examine whether the severity of varicose veins played a role in the risk of VTE or PAD.
In addition, information on some potential confounders, such as smoking and obesity, was not available. And the magnitude of the association between varicose veins and PE/PAD was small, so the association the investigators observed could be due to residual or unmeasured confounding.
The investigators also noted that diagnostic evaluations for PAD are more likely to occur in patients with varicose veins, which could partially explain the observed association between varicose veins and PAD.
Furthermore, cases of DVT, PE, and PAD could have been misclassified.
MS medication withdrawn because of safety concerns
Citing concerns about safety, Biogen and AbbVie announced March 2 that they will be withdrawing daclizumab (Zinbryta) from worldwide markets. Daclizumab has known risks, so it was usually prescribed only for people with relapsing multiple sclerosis who had tried two or more other medications that hadn’t worked well enough.
Reports of inflammatory encephalitis and meningoencephalitis led the European Medicines Agency to initiate an Article 20 referral procedure. In such referrals, a medicine or class of medicines are scientifically assessed because of concerns over safety or quality.
However, Biogen and AbbVie concluded that, because of the complex nature of these reports and how few patients were taking daclizumab, it would be difficult to characterize the nature of the medication’s harms and benefits, so the companies instead have decided to withdraw the medication from the market.
On March 14, the Food and Drug Administration announced that it is conducting a review of similar adverse event reports it has received.
The drug will continue to be available to patients until April 30, 2018. Patients taking daclizumab should not stop taking the drug without talking to their doctor and should contact their doctor if they have any new or unexplained symptoms, the FDA said. More information can be found in the press release.
**Story updated 3/14/2018.
Citing concerns about safety, Biogen and AbbVie announced March 2 that they will be withdrawing daclizumab (Zinbryta) from worldwide markets. Daclizumab has known risks, so it was usually prescribed only for people with relapsing multiple sclerosis who had tried two or more other medications that hadn’t worked well enough.
Reports of inflammatory encephalitis and meningoencephalitis led the European Medicines Agency to initiate an Article 20 referral procedure. In such referrals, a medicine or class of medicines are scientifically assessed because of concerns over safety or quality.
However, Biogen and AbbVie concluded that, because of the complex nature of these reports and how few patients were taking daclizumab, it would be difficult to characterize the nature of the medication’s harms and benefits, so the companies instead have decided to withdraw the medication from the market.
On March 14, the Food and Drug Administration announced that it is conducting a review of similar adverse event reports it has received.
The drug will continue to be available to patients until April 30, 2018. Patients taking daclizumab should not stop taking the drug without talking to their doctor and should contact their doctor if they have any new or unexplained symptoms, the FDA said. More information can be found in the press release.
**Story updated 3/14/2018.
Citing concerns about safety, Biogen and AbbVie announced March 2 that they will be withdrawing daclizumab (Zinbryta) from worldwide markets. Daclizumab has known risks, so it was usually prescribed only for people with relapsing multiple sclerosis who had tried two or more other medications that hadn’t worked well enough.
Reports of inflammatory encephalitis and meningoencephalitis led the European Medicines Agency to initiate an Article 20 referral procedure. In such referrals, a medicine or class of medicines are scientifically assessed because of concerns over safety or quality.
However, Biogen and AbbVie concluded that, because of the complex nature of these reports and how few patients were taking daclizumab, it would be difficult to characterize the nature of the medication’s harms and benefits, so the companies instead have decided to withdraw the medication from the market.
On March 14, the Food and Drug Administration announced that it is conducting a review of similar adverse event reports it has received.
The drug will continue to be available to patients until April 30, 2018. Patients taking daclizumab should not stop taking the drug without talking to their doctor and should contact their doctor if they have any new or unexplained symptoms, the FDA said. More information can be found in the press release.
**Story updated 3/14/2018.
FDA alerts doctors to stop administering compounded products
The Food and Drug Administration today alerted physicians to stop administering or providing drugs manufactured by Cantrell Drug, including opioid products and other drugs intended for sterile injection, because the company has failed to ensure quality and sterility in its compounding operations, which could seriously compromise patient safety.
Health care providers should check medical supplies and separate anything produced by Cantrell Drug, which can be identified by finding the company’s name on the label. The FDA also recommended that physicians seek alternative arrangements for medicines and that any patients who have any products made by Cantrell contact their physicians.
So far, the FDA is not aware of any illness or injuries caused by potentially contaminated products from Cantrell, but any that do arise should be reported to the FDA’s MedWatch program.
Read more about this alert in the FDA website.
The Food and Drug Administration today alerted physicians to stop administering or providing drugs manufactured by Cantrell Drug, including opioid products and other drugs intended for sterile injection, because the company has failed to ensure quality and sterility in its compounding operations, which could seriously compromise patient safety.
Health care providers should check medical supplies and separate anything produced by Cantrell Drug, which can be identified by finding the company’s name on the label. The FDA also recommended that physicians seek alternative arrangements for medicines and that any patients who have any products made by Cantrell contact their physicians.
So far, the FDA is not aware of any illness or injuries caused by potentially contaminated products from Cantrell, but any that do arise should be reported to the FDA’s MedWatch program.
Read more about this alert in the FDA website.
The Food and Drug Administration today alerted physicians to stop administering or providing drugs manufactured by Cantrell Drug, including opioid products and other drugs intended for sterile injection, because the company has failed to ensure quality and sterility in its compounding operations, which could seriously compromise patient safety.
Health care providers should check medical supplies and separate anything produced by Cantrell Drug, which can be identified by finding the company’s name on the label. The FDA also recommended that physicians seek alternative arrangements for medicines and that any patients who have any products made by Cantrell contact their physicians.
So far, the FDA is not aware of any illness or injuries caused by potentially contaminated products from Cantrell, but any that do arise should be reported to the FDA’s MedWatch program.
Read more about this alert in the FDA website.
Aspirin may protect against dementia in T2DM
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
ANAHEIM, CALIF. – in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.
The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.
JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.
In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.
During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.
JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).
Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.
She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.
Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”
Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.
Dr. Matsumoto reported having no financial conflicts.
SOURCE: Matsumoto C. AHA scientific sessions.
REPORTING FROM THE AHA SCIENTIFIC SESSIONS
Key clinical point:
Major finding: Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes.
Study details: A multicenter randomized prospective cohort study of 2,536 patients with type 2 diabetes.
Disclosures: The study presenter reported having no financial conflicts.
Source: Matsumoto C. AHA scientific sessions.
Facing the world
***
Edgar is 86. His COPD recently caught up with him, and he needs oxygen. The nasal prongs that deliver it are irritating, but what really bothers him about them is that he won’t attend any activities in his assisted living facility wearing nasal prongs and trailing a tank.
***
Brenda comes in with a large bandage on her forehead. She takes it off to show me a large, jagged, fully-healed scar. Four months ago she gashed her head on an appliance and didn’t get medical help in time to have the wound properly stitched.
“My bangs aren’t thick enough to cover it,” she says. “My daughter asks why I wear a Band-Aid all the time,” says Brenda. But Brenda would rather walk around with a large bandage on her forehead. Just as Edgar won’t let anyone see him sick and diminished, Brenda won’t let anyone see her face damaged.
***
Stella has lymphoma. While she was on chemotherapy, she stayed put at home and avoided crowds to avoid catching someone’s virus. Once chemo was done, she was able to fly to Tallahassee, Fla., to see her new granddaughter Genevieve.
Unfortunately, her lymphoma recurred sooner than she and her doctors had hoped. Now Stella is on a new drug. This seems to be helping, but it puts her back at risk for infections in crowds.
And on planes. “Will you be able to visit Genevieve in Florida?” I ask.
Her husband Ben interjects. “Her doctors say she can,” he said, “but she would have to wear a mask on the plane, and Stella won’t wear a mask.”
***
Malcolm comes in now and then for this and that. This time, he is here for a skin check. At each visit he brings me up to date on an endless family lawsuit over a contested estate. Its subplots could script a whole Netflix series.
When I’m done with the skin check, Malcolm says, “also, I’d like Botox on my forehead.”
“OK,” I say. I don’t ask why, but Malcolm answers anyway.
“The lawsuit is finally coming to a head,” he says. “One of the nephews contesting the will is flying in from Indonesia, and the trial gets underway in Kentucky next week. I never would have started this fight, but since my charming relatives did, I’m in it to win it.”
I wish him luck.
“That’s why I want Botox,” he says. “I’m going to testify, and I want to look my confident best.”
Go, Malcolm!
While we’re talking Botox, I recall Amy, a well-traveled consultant who gave lectures all over.
“I’m curious,” I once asked her. “What do people say to you after you get Botox? Do they notice?”
“That’s interesting,” she said. “When I speak to groups, my face is projected onto large screens. That makes my wrinkles look like the Grand Canyon.
“When I started doing Botox, a man came over to me after a lecture and said, ‘I’ve heard you before, but this time you were, somehow, more cogent and compelling.’
“I thanked him, of course,” said Amy with a smile. “But the speech he was praising was the exact same speech he’d heard the first time.”
***
The rest of us try to put on the best face we can, assisted (in descending order of importance) by: makers of cosmetics, estheticians, dentists, plastic surgeons, and – oh yes – even dermatologists.
Happy to assist!
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
***
Edgar is 86. His COPD recently caught up with him, and he needs oxygen. The nasal prongs that deliver it are irritating, but what really bothers him about them is that he won’t attend any activities in his assisted living facility wearing nasal prongs and trailing a tank.
***
Brenda comes in with a large bandage on her forehead. She takes it off to show me a large, jagged, fully-healed scar. Four months ago she gashed her head on an appliance and didn’t get medical help in time to have the wound properly stitched.
“My bangs aren’t thick enough to cover it,” she says. “My daughter asks why I wear a Band-Aid all the time,” says Brenda. But Brenda would rather walk around with a large bandage on her forehead. Just as Edgar won’t let anyone see him sick and diminished, Brenda won’t let anyone see her face damaged.
***
Stella has lymphoma. While she was on chemotherapy, she stayed put at home and avoided crowds to avoid catching someone’s virus. Once chemo was done, she was able to fly to Tallahassee, Fla., to see her new granddaughter Genevieve.
Unfortunately, her lymphoma recurred sooner than she and her doctors had hoped. Now Stella is on a new drug. This seems to be helping, but it puts her back at risk for infections in crowds.
And on planes. “Will you be able to visit Genevieve in Florida?” I ask.
Her husband Ben interjects. “Her doctors say she can,” he said, “but she would have to wear a mask on the plane, and Stella won’t wear a mask.”
***
Malcolm comes in now and then for this and that. This time, he is here for a skin check. At each visit he brings me up to date on an endless family lawsuit over a contested estate. Its subplots could script a whole Netflix series.
When I’m done with the skin check, Malcolm says, “also, I’d like Botox on my forehead.”
“OK,” I say. I don’t ask why, but Malcolm answers anyway.
“The lawsuit is finally coming to a head,” he says. “One of the nephews contesting the will is flying in from Indonesia, and the trial gets underway in Kentucky next week. I never would have started this fight, but since my charming relatives did, I’m in it to win it.”
I wish him luck.
“That’s why I want Botox,” he says. “I’m going to testify, and I want to look my confident best.”
Go, Malcolm!
While we’re talking Botox, I recall Amy, a well-traveled consultant who gave lectures all over.
“I’m curious,” I once asked her. “What do people say to you after you get Botox? Do they notice?”
“That’s interesting,” she said. “When I speak to groups, my face is projected onto large screens. That makes my wrinkles look like the Grand Canyon.
“When I started doing Botox, a man came over to me after a lecture and said, ‘I’ve heard you before, but this time you were, somehow, more cogent and compelling.’
“I thanked him, of course,” said Amy with a smile. “But the speech he was praising was the exact same speech he’d heard the first time.”
***
The rest of us try to put on the best face we can, assisted (in descending order of importance) by: makers of cosmetics, estheticians, dentists, plastic surgeons, and – oh yes – even dermatologists.
Happy to assist!
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
***
Edgar is 86. His COPD recently caught up with him, and he needs oxygen. The nasal prongs that deliver it are irritating, but what really bothers him about them is that he won’t attend any activities in his assisted living facility wearing nasal prongs and trailing a tank.
***
Brenda comes in with a large bandage on her forehead. She takes it off to show me a large, jagged, fully-healed scar. Four months ago she gashed her head on an appliance and didn’t get medical help in time to have the wound properly stitched.
“My bangs aren’t thick enough to cover it,” she says. “My daughter asks why I wear a Band-Aid all the time,” says Brenda. But Brenda would rather walk around with a large bandage on her forehead. Just as Edgar won’t let anyone see him sick and diminished, Brenda won’t let anyone see her face damaged.
***
Stella has lymphoma. While she was on chemotherapy, she stayed put at home and avoided crowds to avoid catching someone’s virus. Once chemo was done, she was able to fly to Tallahassee, Fla., to see her new granddaughter Genevieve.
Unfortunately, her lymphoma recurred sooner than she and her doctors had hoped. Now Stella is on a new drug. This seems to be helping, but it puts her back at risk for infections in crowds.
And on planes. “Will you be able to visit Genevieve in Florida?” I ask.
Her husband Ben interjects. “Her doctors say she can,” he said, “but she would have to wear a mask on the plane, and Stella won’t wear a mask.”
***
Malcolm comes in now and then for this and that. This time, he is here for a skin check. At each visit he brings me up to date on an endless family lawsuit over a contested estate. Its subplots could script a whole Netflix series.
When I’m done with the skin check, Malcolm says, “also, I’d like Botox on my forehead.”
“OK,” I say. I don’t ask why, but Malcolm answers anyway.
“The lawsuit is finally coming to a head,” he says. “One of the nephews contesting the will is flying in from Indonesia, and the trial gets underway in Kentucky next week. I never would have started this fight, but since my charming relatives did, I’m in it to win it.”
I wish him luck.
“That’s why I want Botox,” he says. “I’m going to testify, and I want to look my confident best.”
Go, Malcolm!
While we’re talking Botox, I recall Amy, a well-traveled consultant who gave lectures all over.
“I’m curious,” I once asked her. “What do people say to you after you get Botox? Do they notice?”
“That’s interesting,” she said. “When I speak to groups, my face is projected onto large screens. That makes my wrinkles look like the Grand Canyon.
“When I started doing Botox, a man came over to me after a lecture and said, ‘I’ve heard you before, but this time you were, somehow, more cogent and compelling.’
“I thanked him, of course,” said Amy with a smile. “But the speech he was praising was the exact same speech he’d heard the first time.”
***
The rest of us try to put on the best face we can, assisted (in descending order of importance) by: makers of cosmetics, estheticians, dentists, plastic surgeons, and – oh yes – even dermatologists.
Happy to assist!
Dr. Rockoff practices dermatology in Brookline, Mass., and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His second book, “Act Like a Doctor, Think Like a Patient,” is available at amazon.com and barnesandnoble.com. Write to him at [email protected].
Acalabrutinib shows less off-target activity in mantle cell lymphoma
A new Bruton tyrosine kinase inhibitor has shown a high response rate and favorable safety profile in the treatment of patients with mantle cell lymphoma.
Researchers reported the results of an open-label, phase 2 study of oral acalabrutinib (100 mg, twice daily) in 124 patients with relapsed or refractory mantle cell lymphoma in The Lancet. Acalabrutinib (Calquence) received accelerated approval from the Food and Drug Administration in October 2017 for treatment of adults with mantle cell lymphoma who have received at least one prior therapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica), which was approved in 2013 for the treatment of mantle cell lymphoma, has been associated with side effects including atrial fibrillation, infections and bleeding, likely due to its off-target activity against other kinases. But acalabrutinib (ACP-196) “is a highly selective, potent BTK inhibitor developed to minimise off-target activity,” wrote Michael Wang, MD, of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, and his colleagues.
After a median follow-up of 15.2 months, 81% of patients in the study achieved an investigator-assessed overall response based on Lugano classification, with 40% achieving a complete response. The results were similar according to an independent review committee evaluation of responses based on CT and PET scans, bone-marrow biopsy specimens, endoscopy results, and clinical data.
There was also a reduction in lymphadenopathy seen in 94% of patients. The patients who showed a complete response took a median of 3.4 months to get there, and the median time to best response was 1.9 months.
The researchers also looked at response rates across a number of prespecified subgroups. Patients with Ann Arbor stage IV disease, those with bone marrow involvement, and those with extranodal disease were less likely to achieve a complete response (29%, 14% and 28% respectively). Patients with lymph nodes 5 cm or larger in diameter showed a 78% response rate.
While the Kaplan-Meier estimated medians for duration of response, progression-free survival, and overall survival were not reached, 87% of patients achieved 12-month overall survival and 67% of patients achieved progression-free survival at 12 months.
Most of the adverse events were grade 1 or 2, and included headache, diarrhea, fatigue, and myalgia.
There were no grade 4 or 5 adverse events, but 10% of patients experienced neutropenia, 9% experienced anemia and 5% experienced pneumonia. There was also one case of grade 3 or worse hemorrhage, but no cases of atrial fibrillation. Lymphocytosis was seen in 31% of patients.
Nearly half of patients (44%) discontinued treatment, mostly because of progressive disease (31%) but 6% discontinued the treatment because of adverse events.
“Overall, treatment with acalabrutinib demonstrated a favourable benefit-risk profile and represents a promising treatment option for patients with relapsed or refractory mantle cell lymphoma,” the researchers wrote. “Data from the ongoing ACE-CL-006 trial directly comparing acalabrutinib with ibrutinib in previously treated patients with high-risk chronic lymphocytic leukaemia will further differentiate the safety profiles of the two treatments.”
The researchers noted a decrease in plasma levels of tumor necrosis factor alpha, the cytokine CXCL13, and other cytokines known to be involved in inflammation and cell trafficking.
“These findings add to the growing body of evidence indicating that BTK inhibition disrupts the tumour microenvironment, limiting the supply of cytokines and chemokines necessary for complex interactions with stromal and accessory cells important for tumour growth and survival.”
The study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. Several study authors reported grants, personal fees and other support from the pharmaceutical industry, including Acerta Pharma, most outside the submitted work. Several authors were also employees of Acerta and some had acalabrutinib patents pending or issued.
SOURCE: Wang M et al., Lancet. 2018;391:659-67.
A new Bruton tyrosine kinase inhibitor has shown a high response rate and favorable safety profile in the treatment of patients with mantle cell lymphoma.
Researchers reported the results of an open-label, phase 2 study of oral acalabrutinib (100 mg, twice daily) in 124 patients with relapsed or refractory mantle cell lymphoma in The Lancet. Acalabrutinib (Calquence) received accelerated approval from the Food and Drug Administration in October 2017 for treatment of adults with mantle cell lymphoma who have received at least one prior therapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica), which was approved in 2013 for the treatment of mantle cell lymphoma, has been associated with side effects including atrial fibrillation, infections and bleeding, likely due to its off-target activity against other kinases. But acalabrutinib (ACP-196) “is a highly selective, potent BTK inhibitor developed to minimise off-target activity,” wrote Michael Wang, MD, of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, and his colleagues.
After a median follow-up of 15.2 months, 81% of patients in the study achieved an investigator-assessed overall response based on Lugano classification, with 40% achieving a complete response. The results were similar according to an independent review committee evaluation of responses based on CT and PET scans, bone-marrow biopsy specimens, endoscopy results, and clinical data.
There was also a reduction in lymphadenopathy seen in 94% of patients. The patients who showed a complete response took a median of 3.4 months to get there, and the median time to best response was 1.9 months.
The researchers also looked at response rates across a number of prespecified subgroups. Patients with Ann Arbor stage IV disease, those with bone marrow involvement, and those with extranodal disease were less likely to achieve a complete response (29%, 14% and 28% respectively). Patients with lymph nodes 5 cm or larger in diameter showed a 78% response rate.
While the Kaplan-Meier estimated medians for duration of response, progression-free survival, and overall survival were not reached, 87% of patients achieved 12-month overall survival and 67% of patients achieved progression-free survival at 12 months.
Most of the adverse events were grade 1 or 2, and included headache, diarrhea, fatigue, and myalgia.
There were no grade 4 or 5 adverse events, but 10% of patients experienced neutropenia, 9% experienced anemia and 5% experienced pneumonia. There was also one case of grade 3 or worse hemorrhage, but no cases of atrial fibrillation. Lymphocytosis was seen in 31% of patients.
Nearly half of patients (44%) discontinued treatment, mostly because of progressive disease (31%) but 6% discontinued the treatment because of adverse events.
“Overall, treatment with acalabrutinib demonstrated a favourable benefit-risk profile and represents a promising treatment option for patients with relapsed or refractory mantle cell lymphoma,” the researchers wrote. “Data from the ongoing ACE-CL-006 trial directly comparing acalabrutinib with ibrutinib in previously treated patients with high-risk chronic lymphocytic leukaemia will further differentiate the safety profiles of the two treatments.”
The researchers noted a decrease in plasma levels of tumor necrosis factor alpha, the cytokine CXCL13, and other cytokines known to be involved in inflammation and cell trafficking.
“These findings add to the growing body of evidence indicating that BTK inhibition disrupts the tumour microenvironment, limiting the supply of cytokines and chemokines necessary for complex interactions with stromal and accessory cells important for tumour growth and survival.”
The study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. Several study authors reported grants, personal fees and other support from the pharmaceutical industry, including Acerta Pharma, most outside the submitted work. Several authors were also employees of Acerta and some had acalabrutinib patents pending or issued.
SOURCE: Wang M et al., Lancet. 2018;391:659-67.
A new Bruton tyrosine kinase inhibitor has shown a high response rate and favorable safety profile in the treatment of patients with mantle cell lymphoma.
Researchers reported the results of an open-label, phase 2 study of oral acalabrutinib (100 mg, twice daily) in 124 patients with relapsed or refractory mantle cell lymphoma in The Lancet. Acalabrutinib (Calquence) received accelerated approval from the Food and Drug Administration in October 2017 for treatment of adults with mantle cell lymphoma who have received at least one prior therapy.
The Bruton tyrosine kinase (BTK) inhibitor ibrutinib (Imbruvica), which was approved in 2013 for the treatment of mantle cell lymphoma, has been associated with side effects including atrial fibrillation, infections and bleeding, likely due to its off-target activity against other kinases. But acalabrutinib (ACP-196) “is a highly selective, potent BTK inhibitor developed to minimise off-target activity,” wrote Michael Wang, MD, of the department of lymphoma and myeloma at the University of Texas MD Anderson Cancer Center, Houston, and his colleagues.
After a median follow-up of 15.2 months, 81% of patients in the study achieved an investigator-assessed overall response based on Lugano classification, with 40% achieving a complete response. The results were similar according to an independent review committee evaluation of responses based on CT and PET scans, bone-marrow biopsy specimens, endoscopy results, and clinical data.
There was also a reduction in lymphadenopathy seen in 94% of patients. The patients who showed a complete response took a median of 3.4 months to get there, and the median time to best response was 1.9 months.
The researchers also looked at response rates across a number of prespecified subgroups. Patients with Ann Arbor stage IV disease, those with bone marrow involvement, and those with extranodal disease were less likely to achieve a complete response (29%, 14% and 28% respectively). Patients with lymph nodes 5 cm or larger in diameter showed a 78% response rate.
While the Kaplan-Meier estimated medians for duration of response, progression-free survival, and overall survival were not reached, 87% of patients achieved 12-month overall survival and 67% of patients achieved progression-free survival at 12 months.
Most of the adverse events were grade 1 or 2, and included headache, diarrhea, fatigue, and myalgia.
There were no grade 4 or 5 adverse events, but 10% of patients experienced neutropenia, 9% experienced anemia and 5% experienced pneumonia. There was also one case of grade 3 or worse hemorrhage, but no cases of atrial fibrillation. Lymphocytosis was seen in 31% of patients.
Nearly half of patients (44%) discontinued treatment, mostly because of progressive disease (31%) but 6% discontinued the treatment because of adverse events.
“Overall, treatment with acalabrutinib demonstrated a favourable benefit-risk profile and represents a promising treatment option for patients with relapsed or refractory mantle cell lymphoma,” the researchers wrote. “Data from the ongoing ACE-CL-006 trial directly comparing acalabrutinib with ibrutinib in previously treated patients with high-risk chronic lymphocytic leukaemia will further differentiate the safety profiles of the two treatments.”
The researchers noted a decrease in plasma levels of tumor necrosis factor alpha, the cytokine CXCL13, and other cytokines known to be involved in inflammation and cell trafficking.
“These findings add to the growing body of evidence indicating that BTK inhibition disrupts the tumour microenvironment, limiting the supply of cytokines and chemokines necessary for complex interactions with stromal and accessory cells important for tumour growth and survival.”
The study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. Several study authors reported grants, personal fees and other support from the pharmaceutical industry, including Acerta Pharma, most outside the submitted work. Several authors were also employees of Acerta and some had acalabrutinib patents pending or issued.
SOURCE: Wang M et al., Lancet. 2018;391:659-67.
FROM THE LANCET
Key clinical point:
Major finding: Eighty-one percent of patients with relapsed or refractory mantle cell lymphoma showed a partial or complete response to Bruton tyrosine kinase inhibitor acalabrutinib.
Study details: An open-label, phase 2 study in 124 patients with relapsed or refractory mantle cell lymphoma.
Disclosures: The study was sponsored by Acerta Pharma, a member of the AstraZeneca Group. Several study authors reported grants, personal fees and other support from the pharmaceutical industry, including Acerta Pharma, most outside the submitted work. Several authors were also employees of Acerta and some had acalabrutinib patents pending or issued.
Source: Wang M et al. Lancet. 2018;391:659-67.
Prostate cancer survival similar with EBRT/brachytherapy or surgery, analysts claim
More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).
However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.
“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.
The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.
They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.
Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.
They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).
In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).
The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”
They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.
SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134
Clinicians interpreting this and other retrospective studies using large cancer registry data need to consider:
1) Whether treatment groups are comparable. For most retrospective studies, treatment groups are not comparable. Surgery versus RT is especially difficult to compare. In many studies in various cancers that have compared surgery alone versus surgery plus adjuvant therapy, the latter patients are inherently healthier. The ability or inability of investigators to address these confounding issues is central to assessing the quality of the evidence in a study.
(2) Limitations related to the data elements that are contained in the registry and data accuracy.
(3) Whether the results are believable clinically. If survival is the endpoint in a study, when do the survival curves separate – and is that consistent with the known clinical course of a particular disease? The main advantage of randomized trials is the ability to create comparable patient groups and minimize confounding, which is also the biggest limitation of retrospective studies. In clinical scenarios where multiple randomized trials have consistently confirmed a result (e.g., adding androgen deprivation therapy to RT improves survival for high-risk patients), repeated retrospective analyses asking these same questions that may show either the same or an opposite result are less useful.
Perhaps the biggest challenge in conducting studies using cancer registry data and interpreting their results as researchers and clinicians relates to the personal biases most of us harbor; these biases tempt us to analyze registry data in an attempt to refute clinical trials and to selectively believe studies that provide results supporting our own biases. For each clinician interpreting retrospective results along with or in absence of clinical trial data, recognizing our own biases by following the framework outlined previously to assess the quality and believability of each study can potentially remove the greatest confounder of all.
Ronald C. Chen, MD, MPH, is associate professor of radiation oncology at the University of North Carolina at Chapel Hill. He serves in a consulting or advisory role for Medivation/Astellas, Accuray, and Bayer, and has received research funding from Accuray. His remarks are adapted from an editorial (J Clin Oncol. 2018 Feb 28. doi: 0.1200/JCO.2017.77.5833).
Clinicians interpreting this and other retrospective studies using large cancer registry data need to consider:
1) Whether treatment groups are comparable. For most retrospective studies, treatment groups are not comparable. Surgery versus RT is especially difficult to compare. In many studies in various cancers that have compared surgery alone versus surgery plus adjuvant therapy, the latter patients are inherently healthier. The ability or inability of investigators to address these confounding issues is central to assessing the quality of the evidence in a study.
(2) Limitations related to the data elements that are contained in the registry and data accuracy.
(3) Whether the results are believable clinically. If survival is the endpoint in a study, when do the survival curves separate – and is that consistent with the known clinical course of a particular disease? The main advantage of randomized trials is the ability to create comparable patient groups and minimize confounding, which is also the biggest limitation of retrospective studies. In clinical scenarios where multiple randomized trials have consistently confirmed a result (e.g., adding androgen deprivation therapy to RT improves survival for high-risk patients), repeated retrospective analyses asking these same questions that may show either the same or an opposite result are less useful.
Perhaps the biggest challenge in conducting studies using cancer registry data and interpreting their results as researchers and clinicians relates to the personal biases most of us harbor; these biases tempt us to analyze registry data in an attempt to refute clinical trials and to selectively believe studies that provide results supporting our own biases. For each clinician interpreting retrospective results along with or in absence of clinical trial data, recognizing our own biases by following the framework outlined previously to assess the quality and believability of each study can potentially remove the greatest confounder of all.
Ronald C. Chen, MD, MPH, is associate professor of radiation oncology at the University of North Carolina at Chapel Hill. He serves in a consulting or advisory role for Medivation/Astellas, Accuray, and Bayer, and has received research funding from Accuray. His remarks are adapted from an editorial (J Clin Oncol. 2018 Feb 28. doi: 0.1200/JCO.2017.77.5833).
Clinicians interpreting this and other retrospective studies using large cancer registry data need to consider:
1) Whether treatment groups are comparable. For most retrospective studies, treatment groups are not comparable. Surgery versus RT is especially difficult to compare. In many studies in various cancers that have compared surgery alone versus surgery plus adjuvant therapy, the latter patients are inherently healthier. The ability or inability of investigators to address these confounding issues is central to assessing the quality of the evidence in a study.
(2) Limitations related to the data elements that are contained in the registry and data accuracy.
(3) Whether the results are believable clinically. If survival is the endpoint in a study, when do the survival curves separate – and is that consistent with the known clinical course of a particular disease? The main advantage of randomized trials is the ability to create comparable patient groups and minimize confounding, which is also the biggest limitation of retrospective studies. In clinical scenarios where multiple randomized trials have consistently confirmed a result (e.g., adding androgen deprivation therapy to RT improves survival for high-risk patients), repeated retrospective analyses asking these same questions that may show either the same or an opposite result are less useful.
Perhaps the biggest challenge in conducting studies using cancer registry data and interpreting their results as researchers and clinicians relates to the personal biases most of us harbor; these biases tempt us to analyze registry data in an attempt to refute clinical trials and to selectively believe studies that provide results supporting our own biases. For each clinician interpreting retrospective results along with or in absence of clinical trial data, recognizing our own biases by following the framework outlined previously to assess the quality and believability of each study can potentially remove the greatest confounder of all.
Ronald C. Chen, MD, MPH, is associate professor of radiation oncology at the University of North Carolina at Chapel Hill. He serves in a consulting or advisory role for Medivation/Astellas, Accuray, and Bayer, and has received research funding from Accuray. His remarks are adapted from an editorial (J Clin Oncol. 2018 Feb 28. doi: 0.1200/JCO.2017.77.5833).
More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).
However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.
“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.
The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.
They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.
Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.
They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).
In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).
The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”
They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.
SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134
More fuel for the radiation vs. surgery in prostate cancer debate comes from a study suggesting that patients with high-risk localized prostate cancer treated with external beam radiotherapy (EBRT) plus brachytherapy – with or without androgen deprivation (AD) – have survival rates equivalent to those of patients treated with radical prostatectomy (RP).
However, patients treated with EBRT and androgen deprivation without brachytherapy had significantly worse survival compared with patients treated with surgery, according to Ronald D. Ennis, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, and his colleagues.
“The data reported herein suggest that RT plus brachytherapy with or without AD and RP are associated with similar survival. This finding reinforces the need for patients to seek opinions from both a urologic oncologic surgeon with expertise in RP and a radiation oncologist with expertise in brachytherapy. The natural human tendency for physicians to prefer their modality necessitates this dual consultation approach, preferably in a single joint consultation visit,” the researchers wrote. The report was published in the Journal of Clinical Oncology.
The investigators attempted to control for variables that could influence the results by drawing on data on a large number of patients – 42,765 – who were treated at a large number of facilities across the United States. In addition, they incorporated data on clinical stage and Gleason score for all patients, prostate-specific antigen measurements, comorbidities, and socioeconomic factors that are either known or thought to influence treatment decisions.
They used inverse probability of treatment weight to adjust for imbalances of covariables among the treatment groups, and then created weighted time-dependent Cox proportional hazard models to estimate the effects of each type of treatment on survival.
Their sample included 24,688 patients who underwent RP, 15,435 who received EBRT with AD, and 2,642 who underwent EBRT and brachytherapy with or without AD.
They found no statistical difference in survival between RP and EBRT plus brachytherapy with/without AD in inverse probability of treatment weighted analysis. The hazard ratio for EBRT/brachytherapy was 1.17, but this was not statistically significant (95% confidence interval, 0.88-1.55).
In contrast. EBRT plus AD was associated with significantly worse survival, with a hazard ration of 1.53 (95% CI, 1.22-1.92).
The authors noted that “this finding reinforces the importance of complications, particularly in the urinary, sexual, and bowel domains, in combination with patient priorities and preferences, in determining an individual patient’s optimal choice. Significant data have been published in recent years regarding patient-reported outcomes that should be shared with all new patients to help guide them to their personal optimal treatment.”
They added that for some patients, quality of life may be a more important factor than survival when choosing a treatment modality.
SOURCE: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134
FROM JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: This analysis of cancer registry data suggests that surgery and external beam radiotherapy plus brachytherapy have similar survival outcomes in patients with localized high-risk cancers.
Major finding: The hazard ratio for EBRT/brachytherapy vs. radical prostatectomy was 1.17 and was not statistically significant.
Data source: Retrospective review of data on 42,765 patients with localized high-risk prostate cancer.
Disclosures: No funding source was reported. Coauthor Madhu Mazumdar, PhD, reported National Cancer Institute funding. All other authors had no disclosures.
Source: Ennis et al. J Clin Oncol. 2018 Feb 28. doi: 10.1200/JCO.2017.75.9134.
Experts cite five orthopedic tests that physicians and patients should question
The American Academy of Pediatrics–Section on Orthopaedics and the Pediatric Orthopaedic Society of North America (POSNA) provide the following list:
- Do not order a screening hip ultrasound to rule out developmental hip dysplasia or developmental hip dislocation if the baby has no risk factors and has a clinically stable hip examination.
- Do not order radiographs or advise bracing or surgery for a child less than 8 years of age with simple in-toeing gait.
- Do not order custom orthotics or shoe inserts for a child with minimally symptomatic or asymptomatic flat feet.
- Do not order advanced imaging studies (MRI or CT) for most musculoskeletal conditions in a child until all appropriate clinical, laboratory, and plain radiographic examinations have been completed.
- Do not order follow-up x-rays for buckle (or torus) fractures if they are no longer tender or painful.
This list was developed based on data collected from 2014-2015 from the POSNA Evidence Based Committee and Advocacy Committee. Approximately 20 members of the two committees participated in the process. They submitted five items each from their practices and experience of tests or procedures that they found were commonly overutilized. The items were placed in order of number of times listed by each surgeon; a total of 30 items were submitted. The two committees then agreed on a final list of five procedures, based on frequency of responses and importance of the condition. After the list was reviewed and feedback provided, the POSNA board of directors voted on a final list. The AAP Executive Committee then provided final approval.
The committee noted that the list is provided for informational purposes and is not intended as a substitute for consultation with a physician.
Read the full list with more details here.
The American Academy of Pediatrics–Section on Orthopaedics and the Pediatric Orthopaedic Society of North America (POSNA) provide the following list:
- Do not order a screening hip ultrasound to rule out developmental hip dysplasia or developmental hip dislocation if the baby has no risk factors and has a clinically stable hip examination.
- Do not order radiographs or advise bracing or surgery for a child less than 8 years of age with simple in-toeing gait.
- Do not order custom orthotics or shoe inserts for a child with minimally symptomatic or asymptomatic flat feet.
- Do not order advanced imaging studies (MRI or CT) for most musculoskeletal conditions in a child until all appropriate clinical, laboratory, and plain radiographic examinations have been completed.
- Do not order follow-up x-rays for buckle (or torus) fractures if they are no longer tender or painful.
This list was developed based on data collected from 2014-2015 from the POSNA Evidence Based Committee and Advocacy Committee. Approximately 20 members of the two committees participated in the process. They submitted five items each from their practices and experience of tests or procedures that they found were commonly overutilized. The items were placed in order of number of times listed by each surgeon; a total of 30 items were submitted. The two committees then agreed on a final list of five procedures, based on frequency of responses and importance of the condition. After the list was reviewed and feedback provided, the POSNA board of directors voted on a final list. The AAP Executive Committee then provided final approval.
The committee noted that the list is provided for informational purposes and is not intended as a substitute for consultation with a physician.
Read the full list with more details here.
The American Academy of Pediatrics–Section on Orthopaedics and the Pediatric Orthopaedic Society of North America (POSNA) provide the following list:
- Do not order a screening hip ultrasound to rule out developmental hip dysplasia or developmental hip dislocation if the baby has no risk factors and has a clinically stable hip examination.
- Do not order radiographs or advise bracing or surgery for a child less than 8 years of age with simple in-toeing gait.
- Do not order custom orthotics or shoe inserts for a child with minimally symptomatic or asymptomatic flat feet.
- Do not order advanced imaging studies (MRI or CT) for most musculoskeletal conditions in a child until all appropriate clinical, laboratory, and plain radiographic examinations have been completed.
- Do not order follow-up x-rays for buckle (or torus) fractures if they are no longer tender or painful.
This list was developed based on data collected from 2014-2015 from the POSNA Evidence Based Committee and Advocacy Committee. Approximately 20 members of the two committees participated in the process. They submitted five items each from their practices and experience of tests or procedures that they found were commonly overutilized. The items were placed in order of number of times listed by each surgeon; a total of 30 items were submitted. The two committees then agreed on a final list of five procedures, based on frequency of responses and importance of the condition. After the list was reviewed and feedback provided, the POSNA board of directors voted on a final list. The AAP Executive Committee then provided final approval.
The committee noted that the list is provided for informational purposes and is not intended as a substitute for consultation with a physician.
Read the full list with more details here.
Trial shows ‘signals’ in favor of general anesthesia during EVT for stroke
The provision of general anesthesia during endovascular therapy for acute ischemic stroke patients with large-vessel occlusions did not result in more infarct growth when compared with conscious sedation in a new randomized trial, contrary to previous findings.
Furthermore, the single-center, open-label, blinded-endpoint General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial also reported that patients randomized to the general anesthesia (GA) group had improved functional outcomes on the modified Rankin Scale at 90 days, with a 91% greater likelihood for lower scores than with conscious sedation (CS) (odds ratio, 1.91; 95% confidence interval, 1.03-3.56).
The GOLIATH trial randomized patients to general anesthetic (n = 65) or conscious sedation (n = 63). The average age of the patients was 71.4 years and 48.4% of the cohort were women. The patients’ median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21), and the initial infarct size was also comparable between the GA and CS groups, respectively (median [interquartile range], 10.5 [2.4-23.6] mL vs. 13.3 [5.2-31.1] mL; P = .26)
The trial’s primary endpoint results showed that although final infarct volume was smaller in the GA group, the difference in the volume of infarct growth 48-72 hours after symptom onset among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs. 19.4 [2.4-79.0] mL; P = .10).
“Assuming a normal distribution, the mean infarct growth for CS was 57.4 mL and for GA was 34.1 mL (difference, 23.2 mL; 95% CI, –6.4 to 52.9),” the research team noted.
A higher rate of successful reperfusion in the GA arm appeared to reflect its better clinical outcomes. Successful reperfusion occurred in 76.9% of GA patients, compared with 60.3% of CS patients (P = .04).
There were no clinically meaningful differences in safety endpoints between the two arms. Four patients (6.3%) in the CS group were converted to GA.
Significantly more patients in the GA group than in the CS group experienced a decrease of greater than 20% in mean arterial pressure (MAP) (87.7% vs. 34.9%; P = .001). However, when MAP dropped below 70 mm Hg, the duration was non-significantly longer for CS patients than for GA patients (6.5 [2-13] minutes vs. 2 [1-5.5] minutes; P = .09).
A longer delay from arrival at the neurointerventional suite to groin puncture was also seen for patients in the GA group. But the median difference of 9 minutes was “acceptable in the context of the much longer overall time from stroke onset to treatment and from stroke onset to reperfusion, which was not significantly different between the competing arms,” the authors said.
The authors said that overall their findings supported GA as a viable anesthetic approach during EVT. “Contrary to numerous nonrandomized studies that have reported better outcomes with CS, the GOLIATH trial shows signals in favor of GA for multiple endpoints,” the research team wrote. “Performing EVT under GA, compared with CS, does not result in worse tissue or clinical outcomes when using a GA protocol that limits the time delay for intubation (less than 10 minutes) and blood pressure level within recommended limits (systolic blood pressure greater than 140 mm Hg and MAP greater than 70 mm Hg).”
The trial was funded by Aarhus University Hospital. One author reported research grants from Penumbra and Neuravi, and another author reported a research grant from Health Research Fund of Central Denmark Region.
SOURCE: Simonsen C et al., JAMA Neurol. 2018 Jan 16. doi: 10.1001/jamaneurol.2017.4474
The provision of general anesthesia during endovascular therapy for acute ischemic stroke patients with large-vessel occlusions did not result in more infarct growth when compared with conscious sedation in a new randomized trial, contrary to previous findings.
Furthermore, the single-center, open-label, blinded-endpoint General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial also reported that patients randomized to the general anesthesia (GA) group had improved functional outcomes on the modified Rankin Scale at 90 days, with a 91% greater likelihood for lower scores than with conscious sedation (CS) (odds ratio, 1.91; 95% confidence interval, 1.03-3.56).
The GOLIATH trial randomized patients to general anesthetic (n = 65) or conscious sedation (n = 63). The average age of the patients was 71.4 years and 48.4% of the cohort were women. The patients’ median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21), and the initial infarct size was also comparable between the GA and CS groups, respectively (median [interquartile range], 10.5 [2.4-23.6] mL vs. 13.3 [5.2-31.1] mL; P = .26)
The trial’s primary endpoint results showed that although final infarct volume was smaller in the GA group, the difference in the volume of infarct growth 48-72 hours after symptom onset among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs. 19.4 [2.4-79.0] mL; P = .10).
“Assuming a normal distribution, the mean infarct growth for CS was 57.4 mL and for GA was 34.1 mL (difference, 23.2 mL; 95% CI, –6.4 to 52.9),” the research team noted.
A higher rate of successful reperfusion in the GA arm appeared to reflect its better clinical outcomes. Successful reperfusion occurred in 76.9% of GA patients, compared with 60.3% of CS patients (P = .04).
There were no clinically meaningful differences in safety endpoints between the two arms. Four patients (6.3%) in the CS group were converted to GA.
Significantly more patients in the GA group than in the CS group experienced a decrease of greater than 20% in mean arterial pressure (MAP) (87.7% vs. 34.9%; P = .001). However, when MAP dropped below 70 mm Hg, the duration was non-significantly longer for CS patients than for GA patients (6.5 [2-13] minutes vs. 2 [1-5.5] minutes; P = .09).
A longer delay from arrival at the neurointerventional suite to groin puncture was also seen for patients in the GA group. But the median difference of 9 minutes was “acceptable in the context of the much longer overall time from stroke onset to treatment and from stroke onset to reperfusion, which was not significantly different between the competing arms,” the authors said.
The authors said that overall their findings supported GA as a viable anesthetic approach during EVT. “Contrary to numerous nonrandomized studies that have reported better outcomes with CS, the GOLIATH trial shows signals in favor of GA for multiple endpoints,” the research team wrote. “Performing EVT under GA, compared with CS, does not result in worse tissue or clinical outcomes when using a GA protocol that limits the time delay for intubation (less than 10 minutes) and blood pressure level within recommended limits (systolic blood pressure greater than 140 mm Hg and MAP greater than 70 mm Hg).”
The trial was funded by Aarhus University Hospital. One author reported research grants from Penumbra and Neuravi, and another author reported a research grant from Health Research Fund of Central Denmark Region.
SOURCE: Simonsen C et al., JAMA Neurol. 2018 Jan 16. doi: 10.1001/jamaneurol.2017.4474
The provision of general anesthesia during endovascular therapy for acute ischemic stroke patients with large-vessel occlusions did not result in more infarct growth when compared with conscious sedation in a new randomized trial, contrary to previous findings.
Furthermore, the single-center, open-label, blinded-endpoint General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial also reported that patients randomized to the general anesthesia (GA) group had improved functional outcomes on the modified Rankin Scale at 90 days, with a 91% greater likelihood for lower scores than with conscious sedation (CS) (odds ratio, 1.91; 95% confidence interval, 1.03-3.56).
The GOLIATH trial randomized patients to general anesthetic (n = 65) or conscious sedation (n = 63). The average age of the patients was 71.4 years and 48.4% of the cohort were women. The patients’ median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21), and the initial infarct size was also comparable between the GA and CS groups, respectively (median [interquartile range], 10.5 [2.4-23.6] mL vs. 13.3 [5.2-31.1] mL; P = .26)
The trial’s primary endpoint results showed that although final infarct volume was smaller in the GA group, the difference in the volume of infarct growth 48-72 hours after symptom onset among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs. 19.4 [2.4-79.0] mL; P = .10).
“Assuming a normal distribution, the mean infarct growth for CS was 57.4 mL and for GA was 34.1 mL (difference, 23.2 mL; 95% CI, –6.4 to 52.9),” the research team noted.
A higher rate of successful reperfusion in the GA arm appeared to reflect its better clinical outcomes. Successful reperfusion occurred in 76.9% of GA patients, compared with 60.3% of CS patients (P = .04).
There were no clinically meaningful differences in safety endpoints between the two arms. Four patients (6.3%) in the CS group were converted to GA.
Significantly more patients in the GA group than in the CS group experienced a decrease of greater than 20% in mean arterial pressure (MAP) (87.7% vs. 34.9%; P = .001). However, when MAP dropped below 70 mm Hg, the duration was non-significantly longer for CS patients than for GA patients (6.5 [2-13] minutes vs. 2 [1-5.5] minutes; P = .09).
A longer delay from arrival at the neurointerventional suite to groin puncture was also seen for patients in the GA group. But the median difference of 9 minutes was “acceptable in the context of the much longer overall time from stroke onset to treatment and from stroke onset to reperfusion, which was not significantly different between the competing arms,” the authors said.
The authors said that overall their findings supported GA as a viable anesthetic approach during EVT. “Contrary to numerous nonrandomized studies that have reported better outcomes with CS, the GOLIATH trial shows signals in favor of GA for multiple endpoints,” the research team wrote. “Performing EVT under GA, compared with CS, does not result in worse tissue or clinical outcomes when using a GA protocol that limits the time delay for intubation (less than 10 minutes) and blood pressure level within recommended limits (systolic blood pressure greater than 140 mm Hg and MAP greater than 70 mm Hg).”
The trial was funded by Aarhus University Hospital. One author reported research grants from Penumbra and Neuravi, and another author reported a research grant from Health Research Fund of Central Denmark Region.
SOURCE: Simonsen C et al., JAMA Neurol. 2018 Jan 16. doi: 10.1001/jamaneurol.2017.4474
FROM JAMA NEUROLOGY
Key clinical point: A new trial shows signals in multiple endpoints in favor of general anesthesia for acute ischemic stroke patients with large-vessel occlusions who undergo endovascular therapy.
Major finding: The difference in the volume of infarct growth 48-72 hours after symptom onset among patients treated under general anesthesia or conscious sedation did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs. 19.4 [2.4-79.0] mL; P = .10).
Study details: The single-center, open-label, blinded-endpoint GOLIATH trial randomized 128 acute ischemic stroke patients to general anesthesia or conscious sedation.
Disclosures: The trial was funded by Aarhus University Hospital. One author reported research grants from Penumbra and Neuravi, and another author reported a research grant from Health Research Fund of Central Denmark Region.
Source: Simonsen C et al. JAMA Neurol. 2018 Jan 16. doi: 10.1001/jamaneurol.2017.4474.