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VAM Registration Opens This Week
It's nearly here! The 2018 Vascular Annual Meeting takes a big step forward this week with the opening of housing and registration. Prepare to sign up for VAM, June 20 to 23 in Boston.
Following a full day of postgraduate courses, VESS abstracts, workshops and international programming, abstract-based scientific sessions will open June 21 and continue to June 23. The Exhibit Hall will be open June 21 to 22.
Catch the highlights of this year's annual meeting here.
It's nearly here! The 2018 Vascular Annual Meeting takes a big step forward this week with the opening of housing and registration. Prepare to sign up for VAM, June 20 to 23 in Boston.
Following a full day of postgraduate courses, VESS abstracts, workshops and international programming, abstract-based scientific sessions will open June 21 and continue to June 23. The Exhibit Hall will be open June 21 to 22.
Catch the highlights of this year's annual meeting here.
It's nearly here! The 2018 Vascular Annual Meeting takes a big step forward this week with the opening of housing and registration. Prepare to sign up for VAM, June 20 to 23 in Boston.
Following a full day of postgraduate courses, VESS abstracts, workshops and international programming, abstract-based scientific sessions will open June 21 and continue to June 23. The Exhibit Hall will be open June 21 to 22.
Catch the highlights of this year's annual meeting here.
Drug approved to treat newly diagnosed MM in China
The China Food and Drug Administration (CFDA) has approved lenalidomide (Revlimid®) to treat patients with newly diagnosed multiple myeloma (MM).
The drug is now approved for use in combination with dexamethasone to treat adults with previously untreated MM who are not eligible for transplant.
Lenalidomide was first approved by the CFDA in 2013 for use in combination with dexamethasone to treat adults with MM who had received at least one prior therapy.
“In China, where the incidence of multiple myeloma is on the rise due to an aging population and improved diagnosis, we are hopeful that newly diagnosed patients will have a meaningful long-term benefit from this approval,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene, the company marketing lenalidomide as Revlimid in China under an exclusive license from Celgene Corporation.
Trial results
The CFDA’s decision to expand the approval of lenalidomide is based on results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology in November 2016.
The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.
Patients were randomized to receive:
- Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535), known as the “continuous Rd group”
- 18 cycles of Rd (Rd18) for 72 weeks (n=541), known as the “Rd18 group”
- Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).
In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.
The median progression-free survival was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, progression-free survival rates were 33%, 14%, and 13%, respectively.
The median overall survival was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, overall survival rates were 60%, 57%, and 51%, respectively.
The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.
Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.
The China Food and Drug Administration (CFDA) has approved lenalidomide (Revlimid®) to treat patients with newly diagnosed multiple myeloma (MM).
The drug is now approved for use in combination with dexamethasone to treat adults with previously untreated MM who are not eligible for transplant.
Lenalidomide was first approved by the CFDA in 2013 for use in combination with dexamethasone to treat adults with MM who had received at least one prior therapy.
“In China, where the incidence of multiple myeloma is on the rise due to an aging population and improved diagnosis, we are hopeful that newly diagnosed patients will have a meaningful long-term benefit from this approval,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene, the company marketing lenalidomide as Revlimid in China under an exclusive license from Celgene Corporation.
Trial results
The CFDA’s decision to expand the approval of lenalidomide is based on results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology in November 2016.
The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.
Patients were randomized to receive:
- Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535), known as the “continuous Rd group”
- 18 cycles of Rd (Rd18) for 72 weeks (n=541), known as the “Rd18 group”
- Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).
In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.
The median progression-free survival was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, progression-free survival rates were 33%, 14%, and 13%, respectively.
The median overall survival was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, overall survival rates were 60%, 57%, and 51%, respectively.
The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.
Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.
The China Food and Drug Administration (CFDA) has approved lenalidomide (Revlimid®) to treat patients with newly diagnosed multiple myeloma (MM).
The drug is now approved for use in combination with dexamethasone to treat adults with previously untreated MM who are not eligible for transplant.
Lenalidomide was first approved by the CFDA in 2013 for use in combination with dexamethasone to treat adults with MM who had received at least one prior therapy.
“In China, where the incidence of multiple myeloma is on the rise due to an aging population and improved diagnosis, we are hopeful that newly diagnosed patients will have a meaningful long-term benefit from this approval,” said John V. Oyler, founder, chief executive officer, and chairman of BeiGene, the company marketing lenalidomide as Revlimid in China under an exclusive license from Celgene Corporation.
Trial results
The CFDA’s decision to expand the approval of lenalidomide is based on results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology in November 2016.
The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.
Patients were randomized to receive:
- Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535), known as the “continuous Rd group”
- 18 cycles of Rd (Rd18) for 72 weeks (n=541), known as the “Rd18 group”
- Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).
In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.
The median progression-free survival was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, progression-free survival rates were 33%, 14%, and 13%, respectively.
The median overall survival was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, overall survival rates were 60%, 57%, and 51%, respectively.
The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.
Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.
Does boosting inhaled glucocorticoids avoid asthma exacerbations?
in preventing the exacerbation from occurring, according to the results of two trials in adults and children.
Presented at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization and simultaneously published in the March 3 online edition of the New England Journal of Medicine, one study explored the effect of quadrupling the inhaled glucocorticoid dose in adults and adolescents with asthma, while the other looked at quintupling the dose in children.
At 1 year, there was a significantly lower incidence of severe asthma exacerbations in the group who used the higher dose of inhaled glucocorticoids (45% vs. 52%; hazard ratio, 0.80; P = .001) after adjusting for age, sex, and peak flow measures at randomization.
Researchers also saw a lower percentage of participants using systemic glucocorticoids in the quadruple-dose group compared with the normal-dose group (33% vs. 40%), and the quadruple-dose group also showed a 14% lower incidence of unscheduled health care consultations.
At the end of the 12-month follow-up, the estimated mean total dose of inhaled glucocorticoids was 385 mg in the quadruple-dose group and 328 mg in the normal-dose group.
The most common serious adverse event was hospitalization for asthma, which occurred three times in the quadruple-dose group and 18 times in the normal-dose group. However the incidence of oral candidiasis and dysphonia – both potentially treatment related – was significantly higher in the quadruple-dose group (36 events vs. 9 events).
Overall, the number needed to treat with the quadruple dose to prevent one severe asthma exacerbation was 15.
“Given the potential benefit with respect to preventing exacerbations and in view of the toxic effects of inhaled glucocorticoids and the biases that may have been introduced by the absence of blinding, individual practitioners, patients, and guideline committees will need to consider whether the magnitude of the reduction achieved is clinically meaningful,” wrote Tricia McKeever, PhD, from the department of epidemiology and public health at the University of Nottingham (United Kingdom) and her coauthors.
The second study, which was double blinded, investigated whether quintupling the dose of inhaled glucocorticoids might avoid exacerbations in children. They randomized 254 children who had mild-moderate persistent asthma and had had at least one exacerbation treated with systemic glucocorticoids in the previous year to manage “yellow zone” early warning signs with either normal dose or five times their usual dose of inhaled glucocorticoids.
The rate of severe asthma exacerbations did not differ significantly between the quintuple-dose and normal-dose groups at the 1-year follow-up (0.48 vs. 0.37; P = 0.3), nor did the time to the first severe exacerbation or the rate of emergency department or urgent care visits.
The four hospitalizations for asthma all occurred in the high-dose group. However, there was a lower growth rate seen in children in the high-dose group than in the low-dose group (5.43 cm/yr vs. 5.65 cm/yr; P = .06). There were no significant differences between the two groups in other adverse events.
However, Daniel J. Jackson, MD, and his coauthors noted that there were fewer yellow zone episodes and fewer exacerbations in both groups than they had anticipated.
“It is important to recognize that our findings are specific to school-age children with mild-to-moderate persistent asthma regularly treated with daily low-dose inhaled glucocorticoids (with good adherence),” wrote Dr. Jackson from the department of pediatrics at the University of Wisconsin–Madison and his coauthors.
The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees and other funding and support from the pharmaceutical industry outside the submitted work.
The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health.
SOURCE: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.
These two trials address the important question of whether substantial escalation of regularly used inhaled glucocorticoids prevents exacerbations if started at the first sign of deterioration, as this so-called yellow zone has long been thought the perfect time to initiate more aggressive care. However glucocorticoids have serious side effects, and there is some preclinical evidence that they may enhance viral replication
One trial shows that escalating dose in this yellow zone does not prevent exacerbations in children with the early signs of asthma instability. The second trial is more complex and more controversial, as the open-label design may have biased the outcome, and the degree of benefit is debatable.
Together, these studies suggest that high doses of inhaled glucocorticoids either do not prevent exacerbations or only do so in a small subgroup of patients with as-yet-undefined baseline and exacerbation characteristics.
Philip G. Bardin, PhD, is from the Monash Lung and Sleep Unit at the Monash University Medical Centre in Melbourne, Australia. These comments are taken from an accompanying editorial (N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMe1800152). Dr. Bardin reported personal fees from GlaxoSmithKline outside the submitted work.
These two trials address the important question of whether substantial escalation of regularly used inhaled glucocorticoids prevents exacerbations if started at the first sign of deterioration, as this so-called yellow zone has long been thought the perfect time to initiate more aggressive care. However glucocorticoids have serious side effects, and there is some preclinical evidence that they may enhance viral replication
One trial shows that escalating dose in this yellow zone does not prevent exacerbations in children with the early signs of asthma instability. The second trial is more complex and more controversial, as the open-label design may have biased the outcome, and the degree of benefit is debatable.
Together, these studies suggest that high doses of inhaled glucocorticoids either do not prevent exacerbations or only do so in a small subgroup of patients with as-yet-undefined baseline and exacerbation characteristics.
Philip G. Bardin, PhD, is from the Monash Lung and Sleep Unit at the Monash University Medical Centre in Melbourne, Australia. These comments are taken from an accompanying editorial (N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMe1800152). Dr. Bardin reported personal fees from GlaxoSmithKline outside the submitted work.
These two trials address the important question of whether substantial escalation of regularly used inhaled glucocorticoids prevents exacerbations if started at the first sign of deterioration, as this so-called yellow zone has long been thought the perfect time to initiate more aggressive care. However glucocorticoids have serious side effects, and there is some preclinical evidence that they may enhance viral replication
One trial shows that escalating dose in this yellow zone does not prevent exacerbations in children with the early signs of asthma instability. The second trial is more complex and more controversial, as the open-label design may have biased the outcome, and the degree of benefit is debatable.
Together, these studies suggest that high doses of inhaled glucocorticoids either do not prevent exacerbations or only do so in a small subgroup of patients with as-yet-undefined baseline and exacerbation characteristics.
Philip G. Bardin, PhD, is from the Monash Lung and Sleep Unit at the Monash University Medical Centre in Melbourne, Australia. These comments are taken from an accompanying editorial (N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMe1800152). Dr. Bardin reported personal fees from GlaxoSmithKline outside the submitted work.
in preventing the exacerbation from occurring, according to the results of two trials in adults and children.
Presented at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization and simultaneously published in the March 3 online edition of the New England Journal of Medicine, one study explored the effect of quadrupling the inhaled glucocorticoid dose in adults and adolescents with asthma, while the other looked at quintupling the dose in children.
At 1 year, there was a significantly lower incidence of severe asthma exacerbations in the group who used the higher dose of inhaled glucocorticoids (45% vs. 52%; hazard ratio, 0.80; P = .001) after adjusting for age, sex, and peak flow measures at randomization.
Researchers also saw a lower percentage of participants using systemic glucocorticoids in the quadruple-dose group compared with the normal-dose group (33% vs. 40%), and the quadruple-dose group also showed a 14% lower incidence of unscheduled health care consultations.
At the end of the 12-month follow-up, the estimated mean total dose of inhaled glucocorticoids was 385 mg in the quadruple-dose group and 328 mg in the normal-dose group.
The most common serious adverse event was hospitalization for asthma, which occurred three times in the quadruple-dose group and 18 times in the normal-dose group. However the incidence of oral candidiasis and dysphonia – both potentially treatment related – was significantly higher in the quadruple-dose group (36 events vs. 9 events).
Overall, the number needed to treat with the quadruple dose to prevent one severe asthma exacerbation was 15.
“Given the potential benefit with respect to preventing exacerbations and in view of the toxic effects of inhaled glucocorticoids and the biases that may have been introduced by the absence of blinding, individual practitioners, patients, and guideline committees will need to consider whether the magnitude of the reduction achieved is clinically meaningful,” wrote Tricia McKeever, PhD, from the department of epidemiology and public health at the University of Nottingham (United Kingdom) and her coauthors.
The second study, which was double blinded, investigated whether quintupling the dose of inhaled glucocorticoids might avoid exacerbations in children. They randomized 254 children who had mild-moderate persistent asthma and had had at least one exacerbation treated with systemic glucocorticoids in the previous year to manage “yellow zone” early warning signs with either normal dose or five times their usual dose of inhaled glucocorticoids.
The rate of severe asthma exacerbations did not differ significantly between the quintuple-dose and normal-dose groups at the 1-year follow-up (0.48 vs. 0.37; P = 0.3), nor did the time to the first severe exacerbation or the rate of emergency department or urgent care visits.
The four hospitalizations for asthma all occurred in the high-dose group. However, there was a lower growth rate seen in children in the high-dose group than in the low-dose group (5.43 cm/yr vs. 5.65 cm/yr; P = .06). There were no significant differences between the two groups in other adverse events.
However, Daniel J. Jackson, MD, and his coauthors noted that there were fewer yellow zone episodes and fewer exacerbations in both groups than they had anticipated.
“It is important to recognize that our findings are specific to school-age children with mild-to-moderate persistent asthma regularly treated with daily low-dose inhaled glucocorticoids (with good adherence),” wrote Dr. Jackson from the department of pediatrics at the University of Wisconsin–Madison and his coauthors.
The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees and other funding and support from the pharmaceutical industry outside the submitted work.
The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health.
SOURCE: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.
in preventing the exacerbation from occurring, according to the results of two trials in adults and children.
Presented at the joint congress of the American Academy of Allergy, Asthma, and Immunology and the World Asthma Organization and simultaneously published in the March 3 online edition of the New England Journal of Medicine, one study explored the effect of quadrupling the inhaled glucocorticoid dose in adults and adolescents with asthma, while the other looked at quintupling the dose in children.
At 1 year, there was a significantly lower incidence of severe asthma exacerbations in the group who used the higher dose of inhaled glucocorticoids (45% vs. 52%; hazard ratio, 0.80; P = .001) after adjusting for age, sex, and peak flow measures at randomization.
Researchers also saw a lower percentage of participants using systemic glucocorticoids in the quadruple-dose group compared with the normal-dose group (33% vs. 40%), and the quadruple-dose group also showed a 14% lower incidence of unscheduled health care consultations.
At the end of the 12-month follow-up, the estimated mean total dose of inhaled glucocorticoids was 385 mg in the quadruple-dose group and 328 mg in the normal-dose group.
The most common serious adverse event was hospitalization for asthma, which occurred three times in the quadruple-dose group and 18 times in the normal-dose group. However the incidence of oral candidiasis and dysphonia – both potentially treatment related – was significantly higher in the quadruple-dose group (36 events vs. 9 events).
Overall, the number needed to treat with the quadruple dose to prevent one severe asthma exacerbation was 15.
“Given the potential benefit with respect to preventing exacerbations and in view of the toxic effects of inhaled glucocorticoids and the biases that may have been introduced by the absence of blinding, individual practitioners, patients, and guideline committees will need to consider whether the magnitude of the reduction achieved is clinically meaningful,” wrote Tricia McKeever, PhD, from the department of epidemiology and public health at the University of Nottingham (United Kingdom) and her coauthors.
The second study, which was double blinded, investigated whether quintupling the dose of inhaled glucocorticoids might avoid exacerbations in children. They randomized 254 children who had mild-moderate persistent asthma and had had at least one exacerbation treated with systemic glucocorticoids in the previous year to manage “yellow zone” early warning signs with either normal dose or five times their usual dose of inhaled glucocorticoids.
The rate of severe asthma exacerbations did not differ significantly between the quintuple-dose and normal-dose groups at the 1-year follow-up (0.48 vs. 0.37; P = 0.3), nor did the time to the first severe exacerbation or the rate of emergency department or urgent care visits.
The four hospitalizations for asthma all occurred in the high-dose group. However, there was a lower growth rate seen in children in the high-dose group than in the low-dose group (5.43 cm/yr vs. 5.65 cm/yr; P = .06). There were no significant differences between the two groups in other adverse events.
However, Daniel J. Jackson, MD, and his coauthors noted that there were fewer yellow zone episodes and fewer exacerbations in both groups than they had anticipated.
“It is important to recognize that our findings are specific to school-age children with mild-to-moderate persistent asthma regularly treated with daily low-dose inhaled glucocorticoids (with good adherence),” wrote Dr. Jackson from the department of pediatrics at the University of Wisconsin–Madison and his coauthors.
The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees and other funding and support from the pharmaceutical industry outside the submitted work.
The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health.
SOURCE: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.
FROM AAAAI/WAO JOINT CONGRESS
Key clinical point: Escalating the dose of inhaled glucocorticoids at the first early warnings of an asthma exacerbation may not significantly reduce the likelihood of the exacerbation occurring.
Major finding: Fifteen individuals would need to quadruple their dose of inhaled glucocorticoids to avoid one asthma exacerbation.
Data source: Two randomized, controlled trials in 1,992 adolescents and adults and 254 children with asthma.
Disclosures: The first study was supported by the National Institute for Health Research. Six authors declared grants, personal fees, and other funding and support from the pharmaceutical industry outside the submitted work. The second study was supported by the National Heart, Lung, and Blood Institute. Fifteen authors declared grants, personal fees, and other funding from the pharmaceutical industry, as well as other private industry, outside the submitted work. Several also declared grants from organizations including the National Institutes of Health. No other conflicts of interest were declared.
Sources: McKeeve T et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJMoa1714257; Jackson DJ et al. N Engl J Med. 2018 Mar 3. doi: 10.1056/NEJM0a1710988.
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.