Outpatient laparoscopic surgery for uncomplicated appendicitis can be safely implemented in a large county hospital that serves a poor, underserved population, findings from a prospective, observational trial have shown.

Outpatient appendectomy has gradually gained acceptance in the United States, and numerous studies support the practice. David R. Rosen, MD, of the University of Southern California, Los Angeles, and his colleagues considered the possible advantages of outpatient laparoscopic appendectomy for their institution, such as decreased length of stay, decreased costs, and fewer admissions.

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Outpatient laparoscopic surgery for uncomplicated appendicitis can be safely implemented in a large county hospital that serves a poor, underserved population, findings from a prospective, observational trial have shown.

Outpatient appendectomy has gradually gained acceptance in the United States, and numerous studies support the practice. David R. Rosen, MD, of the University of Southern California, Los Angeles, and his colleagues considered the possible advantages of outpatient laparoscopic appendectomy for their institution, such as decreased length of stay, decreased costs, and fewer admissions.

[email protected]

Outpatient laparoscopic surgery for uncomplicated appendicitis can be safely implemented in a large county hospital that serves a poor, underserved population, findings from a prospective, observational trial have shown.

Outpatient appendectomy has gradually gained acceptance in the United States, and numerous studies support the practice. David R. Rosen, MD, of the University of Southern California, Los Angeles, and his colleagues considered the possible advantages of outpatient laparoscopic appendectomy for their institution, such as decreased length of stay, decreased costs, and fewer admissions.

[email protected]

BOSTON – Showing patients videos of themselves having apneic episodes may convince them to use continuous positive airway pressure (CPAP), suggests the first results of an ongoing randomized clinical trial.

The investigators based their research project design on a previous pilot study that showed improved adherence to CPAP in patients who were shown videos of themselves sleeping while participating in a sleep study, Mark S. Aloia, PhD, said in a presentation at the annual meeting of the Associated Professional Sleep Societies.

In the new study, patients who had been recently diagnosed with sleep apnea were randomly assigned to participate in one of the three treatment groups. All three groups received sleep apnea and CPAP education prior to the use of CPAP. One group also watched videos of themselves sleeping, snoring, and gasping for air, and another group watched videos of a stranger sleeping and having apneic events.

copyright designer491/Thinkstock

The study is supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Aloia disclosed that he is a paid employee of Phillips, but that the study used both Phillips and ResMed CPAP devices.

[email protected]

BOSTON – Showing patients videos of themselves having apneic episodes may convince them to use continuous positive airway pressure (CPAP), suggests the first results of an ongoing randomized clinical trial.

The investigators based their research project design on a previous pilot study that showed improved adherence to CPAP in patients who were shown videos of themselves sleeping while participating in a sleep study, Mark S. Aloia, PhD, said in a presentation at the annual meeting of the Associated Professional Sleep Societies.

In the new study, patients who had been recently diagnosed with sleep apnea were randomly assigned to participate in one of the three treatment groups. All three groups received sleep apnea and CPAP education prior to the use of CPAP. One group also watched videos of themselves sleeping, snoring, and gasping for air, and another group watched videos of a stranger sleeping and having apneic events.

copyright designer491/Thinkstock

The study is supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Aloia disclosed that he is a paid employee of Phillips, but that the study used both Phillips and ResMed CPAP devices.

[email protected]

BOSTON – Showing patients videos of themselves having apneic episodes may convince them to use continuous positive airway pressure (CPAP), suggests the first results of an ongoing randomized clinical trial.

The investigators based their research project design on a previous pilot study that showed improved adherence to CPAP in patients who were shown videos of themselves sleeping while participating in a sleep study, Mark S. Aloia, PhD, said in a presentation at the annual meeting of the Associated Professional Sleep Societies.

In the new study, patients who had been recently diagnosed with sleep apnea were randomly assigned to participate in one of the three treatment groups. All three groups received sleep apnea and CPAP education prior to the use of CPAP. One group also watched videos of themselves sleeping, snoring, and gasping for air, and another group watched videos of a stranger sleeping and having apneic events.

copyright designer491/Thinkstock

The study is supported by a grant from the National Heart, Lung, and Blood Institute. Dr. Aloia disclosed that he is a paid employee of Phillips, but that the study used both Phillips and ResMed CPAP devices.

[email protected]

SAN DIEGO – The atypical antipsychotic drug clozapine is the standard of care for patients with treatment-resistant schizophrenia, but about half do not see an adequate response.

At the annual meeting of the American Psychiatric Association, Randall F. White, MD, presented an algorithm for clozapine-resistant patients intended to simplify and clarify a path forward. He also presented outcome data from a cohort of patients managed using this approach.

The algorithm recommends electroconvulsive therapy if there is inadequate response to clozapine alone or with fluvoxamine, which sometimes is used to boost clozapine serum level, especially in patients who are heavy smokers. If ECT fails to reduce symptoms or the patient refuses it, topiramate, aripiprazole, or sulpiride may be added to clozapine treatment, said Dr. White of the University of British Columbia, Vancouver.

And finally, if psychosis persists, certain patients should be offered cognitive-behavioral therapy with a psychologist trained in helping people with psychosis, Dr. White and his colleagues advise.

Dr. White said in an interview that the idea for a systematic approach to clozapine resistance came from clinical experience of the British Columbia Psychosis Program, which specializes in patients with severe schizophrenia and treatment resistance.

“About half of our patients come to us already on clozapine and aren’t getting better, so we needed to figure out a coherent approach to help them,” he said, noting that there is no current standard of care and that many “come to us already on four or five medications, and it can seem a bit random.”

When these patients are admitted, “we try to simplify their treatment and figure out what’s going on, and then offer ECT if appropriate,” he said.

Dr. White presented data from a cohort of patients assessed at the program between 2012 and 2017, of which 114 were taking clozapine at admission and had a diagnosis of schizophrenia or schizoaffective disorder.

To be considered clozapine-resistant, patients had to be taking 500 mg or more for at least 60 days, yet have persistent positive symptoms and moderate to severe impairment. Dr. White and his colleagues identified 20 patients with clozapine resistance. Of these, eight were offered ECT, and three accepted. At the time of discharge, 16 patients remained on clozapine with or without fluvoxamine. Four patients were treated with the recommended adjunctive agents aripiprazole or sulpiride and five with other agents.

Dr. White said the three agents recommended in the algorithm were determined by literature reviews, including meta-analyses of randomized trials. Several commonly used adjunctive agents to clozapine, including risperidone, were ruled out, for lack of evidence in this patient group.

Sulpiride, one of the drugs recommended in the algorithm, is not marketed in North America, and in Canada is accessible only by special arrangement. The evidence for aripiprazole, meanwhile, “is not stupendous,” Dr. White said, “but there’s a signal.”

The topiramate recommendation is based on results from a 2016 meta-analysis of randomized controlled trials. “Topiramate has a possible advantage of ameliorating metabolic problems,” Dr. White said, and the meta-analysis showed a significant effect size in improving positive and negative symptoms. However, he noted, on rare occasions, it has been seen to exacerbate psychosis.

Dr. White said few of the treatment-resistant patients seen in his program have had a course of ECT despite evidence of benefit. “Instead of ECT, they usually are put on multiple medications,” he said. “Admittedly, getting some of these patients to accept ECT isn’t easy.”

Because the program is designed to keep patients for 6 or more months as needed, “we have the luxury of time,” Dr. White said, to allow for the discontinuation of extraneous medicines and for an ECT trial if indicated.

“I know that in other hospitals, and other health care settings, they don’t have that – they have to figure out what to do quickly. And ECT is not the quickest treatment.”

Offering cognitive-behavioral therapy to people with psychosis is possible, he stressed, and supported by evidence from at least one study. “In this population, it’s challenging,” he acknowledged. “I don’t think I’d do it concurrently with ECT but as an alternative to or after ECT.”

Dr. White disclosed no conflicts of interest related to his research.

SAN DIEGO – The atypical antipsychotic drug clozapine is the standard of care for patients with treatment-resistant schizophrenia, but about half do not see an adequate response.

At the annual meeting of the American Psychiatric Association, Randall F. White, MD, presented an algorithm for clozapine-resistant patients intended to simplify and clarify a path forward. He also presented outcome data from a cohort of patients managed using this approach.

The algorithm recommends electroconvulsive therapy if there is inadequate response to clozapine alone or with fluvoxamine, which sometimes is used to boost clozapine serum level, especially in patients who are heavy smokers. If ECT fails to reduce symptoms or the patient refuses it, topiramate, aripiprazole, or sulpiride may be added to clozapine treatment, said Dr. White of the University of British Columbia, Vancouver.

And finally, if psychosis persists, certain patients should be offered cognitive-behavioral therapy with a psychologist trained in helping people with psychosis, Dr. White and his colleagues advise.

Dr. White said in an interview that the idea for a systematic approach to clozapine resistance came from clinical experience of the British Columbia Psychosis Program, which specializes in patients with severe schizophrenia and treatment resistance.

“About half of our patients come to us already on clozapine and aren’t getting better, so we needed to figure out a coherent approach to help them,” he said, noting that there is no current standard of care and that many “come to us already on four or five medications, and it can seem a bit random.”

When these patients are admitted, “we try to simplify their treatment and figure out what’s going on, and then offer ECT if appropriate,” he said.

Dr. White presented data from a cohort of patients assessed at the program between 2012 and 2017, of which 114 were taking clozapine at admission and had a diagnosis of schizophrenia or schizoaffective disorder.

To be considered clozapine-resistant, patients had to be taking 500 mg or more for at least 60 days, yet have persistent positive symptoms and moderate to severe impairment. Dr. White and his colleagues identified 20 patients with clozapine resistance. Of these, eight were offered ECT, and three accepted. At the time of discharge, 16 patients remained on clozapine with or without fluvoxamine. Four patients were treated with the recommended adjunctive agents aripiprazole or sulpiride and five with other agents.

Dr. White said the three agents recommended in the algorithm were determined by literature reviews, including meta-analyses of randomized trials. Several commonly used adjunctive agents to clozapine, including risperidone, were ruled out, for lack of evidence in this patient group.

Sulpiride, one of the drugs recommended in the algorithm, is not marketed in North America, and in Canada is accessible only by special arrangement. The evidence for aripiprazole, meanwhile, “is not stupendous,” Dr. White said, “but there’s a signal.”

The topiramate recommendation is based on results from a 2016 meta-analysis of randomized controlled trials. “Topiramate has a possible advantage of ameliorating metabolic problems,” Dr. White said, and the meta-analysis showed a significant effect size in improving positive and negative symptoms. However, he noted, on rare occasions, it has been seen to exacerbate psychosis.

Dr. White said few of the treatment-resistant patients seen in his program have had a course of ECT despite evidence of benefit. “Instead of ECT, they usually are put on multiple medications,” he said. “Admittedly, getting some of these patients to accept ECT isn’t easy.”

Because the program is designed to keep patients for 6 or more months as needed, “we have the luxury of time,” Dr. White said, to allow for the discontinuation of extraneous medicines and for an ECT trial if indicated.

“I know that in other hospitals, and other health care settings, they don’t have that – they have to figure out what to do quickly. And ECT is not the quickest treatment.”

Offering cognitive-behavioral therapy to people with psychosis is possible, he stressed, and supported by evidence from at least one study. “In this population, it’s challenging,” he acknowledged. “I don’t think I’d do it concurrently with ECT but as an alternative to or after ECT.”

Dr. White disclosed no conflicts of interest related to his research.

SAN DIEGO – The atypical antipsychotic drug clozapine is the standard of care for patients with treatment-resistant schizophrenia, but about half do not see an adequate response.

At the annual meeting of the American Psychiatric Association, Randall F. White, MD, presented an algorithm for clozapine-resistant patients intended to simplify and clarify a path forward. He also presented outcome data from a cohort of patients managed using this approach.

The algorithm recommends electroconvulsive therapy if there is inadequate response to clozapine alone or with fluvoxamine, which sometimes is used to boost clozapine serum level, especially in patients who are heavy smokers. If ECT fails to reduce symptoms or the patient refuses it, topiramate, aripiprazole, or sulpiride may be added to clozapine treatment, said Dr. White of the University of British Columbia, Vancouver.

And finally, if psychosis persists, certain patients should be offered cognitive-behavioral therapy with a psychologist trained in helping people with psychosis, Dr. White and his colleagues advise.

Dr. White said in an interview that the idea for a systematic approach to clozapine resistance came from clinical experience of the British Columbia Psychosis Program, which specializes in patients with severe schizophrenia and treatment resistance.

“About half of our patients come to us already on clozapine and aren’t getting better, so we needed to figure out a coherent approach to help them,” he said, noting that there is no current standard of care and that many “come to us already on four or five medications, and it can seem a bit random.”

When these patients are admitted, “we try to simplify their treatment and figure out what’s going on, and then offer ECT if appropriate,” he said.

Dr. White presented data from a cohort of patients assessed at the program between 2012 and 2017, of which 114 were taking clozapine at admission and had a diagnosis of schizophrenia or schizoaffective disorder.

To be considered clozapine-resistant, patients had to be taking 500 mg or more for at least 60 days, yet have persistent positive symptoms and moderate to severe impairment. Dr. White and his colleagues identified 20 patients with clozapine resistance. Of these, eight were offered ECT, and three accepted. At the time of discharge, 16 patients remained on clozapine with or without fluvoxamine. Four patients were treated with the recommended adjunctive agents aripiprazole or sulpiride and five with other agents.

Dr. White said the three agents recommended in the algorithm were determined by literature reviews, including meta-analyses of randomized trials. Several commonly used adjunctive agents to clozapine, including risperidone, were ruled out, for lack of evidence in this patient group.

Sulpiride, one of the drugs recommended in the algorithm, is not marketed in North America, and in Canada is accessible only by special arrangement. The evidence for aripiprazole, meanwhile, “is not stupendous,” Dr. White said, “but there’s a signal.”

The topiramate recommendation is based on results from a 2016 meta-analysis of randomized controlled trials. “Topiramate has a possible advantage of ameliorating metabolic problems,” Dr. White said, and the meta-analysis showed a significant effect size in improving positive and negative symptoms. However, he noted, on rare occasions, it has been seen to exacerbate psychosis.

Dr. White said few of the treatment-resistant patients seen in his program have had a course of ECT despite evidence of benefit. “Instead of ECT, they usually are put on multiple medications,” he said. “Admittedly, getting some of these patients to accept ECT isn’t easy.”

Because the program is designed to keep patients for 6 or more months as needed, “we have the luxury of time,” Dr. White said, to allow for the discontinuation of extraneous medicines and for an ECT trial if indicated.

“I know that in other hospitals, and other health care settings, they don’t have that – they have to figure out what to do quickly. And ECT is not the quickest treatment.”

Offering cognitive-behavioral therapy to people with psychosis is possible, he stressed, and supported by evidence from at least one study. “In this population, it’s challenging,” he acknowledged. “I don’t think I’d do it concurrently with ECT but as an alternative to or after ECT.”

Dr. White disclosed no conflicts of interest related to his research.

Cognitively normal seniors with brain amyloid experienced accelerated cognitive decline over as few as 3-4 years, compared with those who had no brain amyloid at baseline.

At 4 years’ follow-up, prodromal Alzheimer’s disease (AD) had developed in 32% of amyloid-positive people and 15% of the amyloid-normal people – a 16.9% difference. Extrapolating the limited 10-year data they collected, the authors projected that after a decade, 88% of the amyloid-positive cohort would have progressed, compared with 29% of the amyloid-normal cohort.

graphicsdunia4you/Thinkstock

[email protected]

On Twitter @Alz_gal

Cognitively normal seniors with brain amyloid experienced accelerated cognitive decline over as few as 3-4 years, compared with those who had no brain amyloid at baseline.

At 4 years’ follow-up, prodromal Alzheimer’s disease (AD) had developed in 32% of amyloid-positive people and 15% of the amyloid-normal people – a 16.9% difference. Extrapolating the limited 10-year data they collected, the authors projected that after a decade, 88% of the amyloid-positive cohort would have progressed, compared with 29% of the amyloid-normal cohort.

graphicsdunia4you/Thinkstock

[email protected]

On Twitter @Alz_gal

Cognitively normal seniors with brain amyloid experienced accelerated cognitive decline over as few as 3-4 years, compared with those who had no brain amyloid at baseline.

At 4 years’ follow-up, prodromal Alzheimer’s disease (AD) had developed in 32% of amyloid-positive people and 15% of the amyloid-normal people – a 16.9% difference. Extrapolating the limited 10-year data they collected, the authors projected that after a decade, 88% of the amyloid-positive cohort would have progressed, compared with 29% of the amyloid-normal cohort.

graphicsdunia4you/Thinkstock

[email protected]

On Twitter @Alz_gal

SAN DIEGO – In the 3 months before their atherosclerotic cardiovascular event, 40% of high-risk patients with diabetes received no prescription for lipid-lowering therapy, researchers reported at the annual scientific sessions of the American Diabetes Association.

Underprescribing of high-intensity statins was also “particularly apparent for patients with diabetes mellitus alone, although rates improved somewhat over follow-up,” Sarah S. Cohen, PhD, of EpidStat Institute in Ann Arbor, Mich., said in a late-breaking poster. The findings highlight the need to educate providers and patients on the importance of addressing cardiovascular risk factors and disease in the diabetes setting, she wrote with her associates from the Mayo Clinic and Amgen.

Hypertension and dyslipidemia are classic companions of type 2 diabetes and “clear risk factors” for atherosclerotic cardiovascular disease (ASCVD), according to 2017 care guidelines from the American Diabetes Association.

“Diabetes itself confers independent risk,” the guidelines add. To characterize real-world use of lipid-lowering therapies in patients with diabetes, ASCVD, or both conditions, Dr. Cohen and her associates analyzed electronic medical records from more than 7,400 adults in Minnesota with new-onset type 2 diabetes mellitus or ASCVD, or incident ASCVD and existing diabetes between 2005 and 2012. During this period, about 4,500 patients were diagnosed with diabetes and another 570 patients with an existing diagnosis of diabetes were diagnosed with ASCVD based on incident myocardial infarction, unstable angina, stroke, or revascularization. An additional 2,300 patients had ASCVD alone.

Patients with existing diabetes and incident ASCVD tended to be in their 70s, two-thirds had used tobacco, 31% were overweight, and 54% were obese, the investigators found. Nonetheless, 40% of patients received no lipid-lowering therapy in the 3 months before the ASCVD event and 90% received no high-intensity statins. Three months after the event, 75% of patients were on lipid-lowering therapy and 64% were on moderate- or high-intensity statins. Patients with incident diabetes alone tended to be in their late 50s, about 60% had used tobacco, and two-thirds were obese. Only 34%, however, were prescribed moderate or high-intensity statins within 3 months after their diabetes diagnosis, and this proportion rose to just 46% at 2 years.

Diabetes is known to boost the risk of cardiovascular disease, but incident diabetes seldom triggered a prescription for lipid-lowering therapy in this cohort, the researchers concluded. Incident ASCVD was much more likely to elicit a prescription, but comorbid diabetes did not further improve the chances of receiving guideline-recommended therapy.

The ADA recommends screening for and treating modifiable CVD risk factors even in the prediabetes setting. For patients with clinical diabetes, providers should evaluate history of dyslipidemia, obtain a fasting lipid profile, and recommend lifestyle changes to address glycemic, blood pressure, and lipid goals, ADA guidelines state. In addition, comorbid diabetes and ASCVD merit high-intensity statin therapy, and diabetic patients with additional risk factors for CVD merit consideration of moderate- or high-intensity statin therapy, according to the recommendations.

The researchers lacked data on prescription fill rates, so they might have overestimated the proportion of patients taking lipid-lowering therapies, they noted. They also had no data on reasons for not prescribing lipid-lowering therapies.

Amgen and the National Institute on Aging provided funding. Dr. Cohen disclosed research funding from Amgen, which makes evolocumab, a lipid-lowering drug. She had no other conflicts of interest.
 

[email protected]

SAN DIEGO – In the 3 months before their atherosclerotic cardiovascular event, 40% of high-risk patients with diabetes received no prescription for lipid-lowering therapy, researchers reported at the annual scientific sessions of the American Diabetes Association.

Underprescribing of high-intensity statins was also “particularly apparent for patients with diabetes mellitus alone, although rates improved somewhat over follow-up,” Sarah S. Cohen, PhD, of EpidStat Institute in Ann Arbor, Mich., said in a late-breaking poster. The findings highlight the need to educate providers and patients on the importance of addressing cardiovascular risk factors and disease in the diabetes setting, she wrote with her associates from the Mayo Clinic and Amgen.

Hypertension and dyslipidemia are classic companions of type 2 diabetes and “clear risk factors” for atherosclerotic cardiovascular disease (ASCVD), according to 2017 care guidelines from the American Diabetes Association.

“Diabetes itself confers independent risk,” the guidelines add. To characterize real-world use of lipid-lowering therapies in patients with diabetes, ASCVD, or both conditions, Dr. Cohen and her associates analyzed electronic medical records from more than 7,400 adults in Minnesota with new-onset type 2 diabetes mellitus or ASCVD, or incident ASCVD and existing diabetes between 2005 and 2012. During this period, about 4,500 patients were diagnosed with diabetes and another 570 patients with an existing diagnosis of diabetes were diagnosed with ASCVD based on incident myocardial infarction, unstable angina, stroke, or revascularization. An additional 2,300 patients had ASCVD alone.

Patients with existing diabetes and incident ASCVD tended to be in their 70s, two-thirds had used tobacco, 31% were overweight, and 54% were obese, the investigators found. Nonetheless, 40% of patients received no lipid-lowering therapy in the 3 months before the ASCVD event and 90% received no high-intensity statins. Three months after the event, 75% of patients were on lipid-lowering therapy and 64% were on moderate- or high-intensity statins. Patients with incident diabetes alone tended to be in their late 50s, about 60% had used tobacco, and two-thirds were obese. Only 34%, however, were prescribed moderate or high-intensity statins within 3 months after their diabetes diagnosis, and this proportion rose to just 46% at 2 years.

Diabetes is known to boost the risk of cardiovascular disease, but incident diabetes seldom triggered a prescription for lipid-lowering therapy in this cohort, the researchers concluded. Incident ASCVD was much more likely to elicit a prescription, but comorbid diabetes did not further improve the chances of receiving guideline-recommended therapy.

The ADA recommends screening for and treating modifiable CVD risk factors even in the prediabetes setting. For patients with clinical diabetes, providers should evaluate history of dyslipidemia, obtain a fasting lipid profile, and recommend lifestyle changes to address glycemic, blood pressure, and lipid goals, ADA guidelines state. In addition, comorbid diabetes and ASCVD merit high-intensity statin therapy, and diabetic patients with additional risk factors for CVD merit consideration of moderate- or high-intensity statin therapy, according to the recommendations.

The researchers lacked data on prescription fill rates, so they might have overestimated the proportion of patients taking lipid-lowering therapies, they noted. They also had no data on reasons for not prescribing lipid-lowering therapies.

Amgen and the National Institute on Aging provided funding. Dr. Cohen disclosed research funding from Amgen, which makes evolocumab, a lipid-lowering drug. She had no other conflicts of interest.
 

[email protected]

SAN DIEGO – In the 3 months before their atherosclerotic cardiovascular event, 40% of high-risk patients with diabetes received no prescription for lipid-lowering therapy, researchers reported at the annual scientific sessions of the American Diabetes Association.

Underprescribing of high-intensity statins was also “particularly apparent for patients with diabetes mellitus alone, although rates improved somewhat over follow-up,” Sarah S. Cohen, PhD, of EpidStat Institute in Ann Arbor, Mich., said in a late-breaking poster. The findings highlight the need to educate providers and patients on the importance of addressing cardiovascular risk factors and disease in the diabetes setting, she wrote with her associates from the Mayo Clinic and Amgen.

Hypertension and dyslipidemia are classic companions of type 2 diabetes and “clear risk factors” for atherosclerotic cardiovascular disease (ASCVD), according to 2017 care guidelines from the American Diabetes Association.

“Diabetes itself confers independent risk,” the guidelines add. To characterize real-world use of lipid-lowering therapies in patients with diabetes, ASCVD, or both conditions, Dr. Cohen and her associates analyzed electronic medical records from more than 7,400 adults in Minnesota with new-onset type 2 diabetes mellitus or ASCVD, or incident ASCVD and existing diabetes between 2005 and 2012. During this period, about 4,500 patients were diagnosed with diabetes and another 570 patients with an existing diagnosis of diabetes were diagnosed with ASCVD based on incident myocardial infarction, unstable angina, stroke, or revascularization. An additional 2,300 patients had ASCVD alone.

Patients with existing diabetes and incident ASCVD tended to be in their 70s, two-thirds had used tobacco, 31% were overweight, and 54% were obese, the investigators found. Nonetheless, 40% of patients received no lipid-lowering therapy in the 3 months before the ASCVD event and 90% received no high-intensity statins. Three months after the event, 75% of patients were on lipid-lowering therapy and 64% were on moderate- or high-intensity statins. Patients with incident diabetes alone tended to be in their late 50s, about 60% had used tobacco, and two-thirds were obese. Only 34%, however, were prescribed moderate or high-intensity statins within 3 months after their diabetes diagnosis, and this proportion rose to just 46% at 2 years.

Diabetes is known to boost the risk of cardiovascular disease, but incident diabetes seldom triggered a prescription for lipid-lowering therapy in this cohort, the researchers concluded. Incident ASCVD was much more likely to elicit a prescription, but comorbid diabetes did not further improve the chances of receiving guideline-recommended therapy.

The ADA recommends screening for and treating modifiable CVD risk factors even in the prediabetes setting. For patients with clinical diabetes, providers should evaluate history of dyslipidemia, obtain a fasting lipid profile, and recommend lifestyle changes to address glycemic, blood pressure, and lipid goals, ADA guidelines state. In addition, comorbid diabetes and ASCVD merit high-intensity statin therapy, and diabetic patients with additional risk factors for CVD merit consideration of moderate- or high-intensity statin therapy, according to the recommendations.

The researchers lacked data on prescription fill rates, so they might have overestimated the proportion of patients taking lipid-lowering therapies, they noted. They also had no data on reasons for not prescribing lipid-lowering therapies.

Amgen and the National Institute on Aging provided funding. Dr. Cohen disclosed research funding from Amgen, which makes evolocumab, a lipid-lowering drug. She had no other conflicts of interest.
 

[email protected]

In testimony before the Senate Veterans Affairs Committee, VA Secretary David J. Shulkin, MD, outlined a vision for a revamped Veterans Choice Program that would allow veterans to access an integrated network of private health care providers for services not currently available at the VA. “We believe redesigning community care will result in a strong VA that can meet the special needs of our veteran population,” Shulkin told the committee. “Where VA excels, we want to make sure that the tools exist to continue performing well in those areas…. We need to move from a system where eligibility for community care is based on wait times and geography to one focused on clinical need and quality of care.”

During the hearing, Dr. Shulkin laid out the basic elements of the new Veterans Choice Program. The proposed changes include the following:

1. Shifting from determining eligibility for community care based on wait times and geography to clinical need and quality of care;
2. Streamlining process for veterans to access urgent care when they need it;
3. Creating what VA is calling a "high performing integrated network,” which would include VA; other federal health care providers, such as military treatment facilities and IHS; academic affiliates; and community providers;
4. Coordinating care across all providers; and
5. Adopting recognized industry standards for quality, patient satisfaction, payment models, health care outcomes, and exchange of health information.

Over the past year, major veterans service organizations (VSOs), VA officials, the Commission on Care, and members of the House and Senate have worked together to develop the newly introduced Veterans Choice program. The major stakeholders came together at the hearing to “support the concept of developing an integrated network that combines the strength of the VA health care system with the best of community care to offer seamless access for enrolled veterans,” explained Adrian Atizado, the deputy national legislative director at Disabled American Veterans (DAV) in his prepared remarks.

The joint effort was in part a response to calls from some VA critics to provide veterans with unlimited choice to outside providers or to fully privatize veteran care.

In the hearing, Committee Chairman Johnny Isakson (R-GA) suggested that he would be willing to work with the VA on the changes to the Veterans Choice Program and was largely in support of the effort. “We need to see to it that the VA…is unleashed to provide the highest quality service that it can and make the decisions that it needs to make on the ground at the time we need to make them,” he reported in a release following the hearing. “We need to give them the funding, commitment and resources to be able to do that.”

At the hearing, VSOs praised the VA for its efforts to improve the Veterans Choice Program but still expressed frustration with problems that continue to dog the program. “The VFW [Veterans of Foreign Wars] has also heard from veterans that the breakdown in communication between VA, contractors and Choice providers often delays their care because their Choice doctors do not receive authorization to provide needed treatments,” reported Carlos Fuentes, VFW director national legislative services. “What is concerning is that veterans are left to piece together the entire story or else they do not.”

“While many veterans initially clamored for ‘more Choice’ as a solution to scheduling problems within the VA healthcare system, once this program was implemented, most have not found it to be a solution,” noted Jeff Steele, assistant director national legislative division of The American Legion. “Instead, they have found it to create as many problems as it solves.…What we have found over the past decade, directly interacting with veterans, is that many of the problems veterans encountered with scheduling appointments in VA are mirrored in the civilian community outside VA.

In testimony before the Senate Veterans Affairs Committee, VA Secretary David J. Shulkin, MD, outlined a vision for a revamped Veterans Choice Program that would allow veterans to access an integrated network of private health care providers for services not currently available at the VA. “We believe redesigning community care will result in a strong VA that can meet the special needs of our veteran population,” Shulkin told the committee. “Where VA excels, we want to make sure that the tools exist to continue performing well in those areas…. We need to move from a system where eligibility for community care is based on wait times and geography to one focused on clinical need and quality of care.”

During the hearing, Dr. Shulkin laid out the basic elements of the new Veterans Choice Program. The proposed changes include the following:

1. Shifting from determining eligibility for community care based on wait times and geography to clinical need and quality of care;
2. Streamlining process for veterans to access urgent care when they need it;
3. Creating what VA is calling a "high performing integrated network,” which would include VA; other federal health care providers, such as military treatment facilities and IHS; academic affiliates; and community providers;
4. Coordinating care across all providers; and
5. Adopting recognized industry standards for quality, patient satisfaction, payment models, health care outcomes, and exchange of health information.

Over the past year, major veterans service organizations (VSOs), VA officials, the Commission on Care, and members of the House and Senate have worked together to develop the newly introduced Veterans Choice program. The major stakeholders came together at the hearing to “support the concept of developing an integrated network that combines the strength of the VA health care system with the best of community care to offer seamless access for enrolled veterans,” explained Adrian Atizado, the deputy national legislative director at Disabled American Veterans (DAV) in his prepared remarks.

The joint effort was in part a response to calls from some VA critics to provide veterans with unlimited choice to outside providers or to fully privatize veteran care.

In the hearing, Committee Chairman Johnny Isakson (R-GA) suggested that he would be willing to work with the VA on the changes to the Veterans Choice Program and was largely in support of the effort. “We need to see to it that the VA…is unleashed to provide the highest quality service that it can and make the decisions that it needs to make on the ground at the time we need to make them,” he reported in a release following the hearing. “We need to give them the funding, commitment and resources to be able to do that.”

At the hearing, VSOs praised the VA for its efforts to improve the Veterans Choice Program but still expressed frustration with problems that continue to dog the program. “The VFW [Veterans of Foreign Wars] has also heard from veterans that the breakdown in communication between VA, contractors and Choice providers often delays their care because their Choice doctors do not receive authorization to provide needed treatments,” reported Carlos Fuentes, VFW director national legislative services. “What is concerning is that veterans are left to piece together the entire story or else they do not.”

“While many veterans initially clamored for ‘more Choice’ as a solution to scheduling problems within the VA healthcare system, once this program was implemented, most have not found it to be a solution,” noted Jeff Steele, assistant director national legislative division of The American Legion. “Instead, they have found it to create as many problems as it solves.…What we have found over the past decade, directly interacting with veterans, is that many of the problems veterans encountered with scheduling appointments in VA are mirrored in the civilian community outside VA.

In testimony before the Senate Veterans Affairs Committee, VA Secretary David J. Shulkin, MD, outlined a vision for a revamped Veterans Choice Program that would allow veterans to access an integrated network of private health care providers for services not currently available at the VA. “We believe redesigning community care will result in a strong VA that can meet the special needs of our veteran population,” Shulkin told the committee. “Where VA excels, we want to make sure that the tools exist to continue performing well in those areas…. We need to move from a system where eligibility for community care is based on wait times and geography to one focused on clinical need and quality of care.”

During the hearing, Dr. Shulkin laid out the basic elements of the new Veterans Choice Program. The proposed changes include the following:

1. Shifting from determining eligibility for community care based on wait times and geography to clinical need and quality of care;
2. Streamlining process for veterans to access urgent care when they need it;
3. Creating what VA is calling a "high performing integrated network,” which would include VA; other federal health care providers, such as military treatment facilities and IHS; academic affiliates; and community providers;
4. Coordinating care across all providers; and
5. Adopting recognized industry standards for quality, patient satisfaction, payment models, health care outcomes, and exchange of health information.

Over the past year, major veterans service organizations (VSOs), VA officials, the Commission on Care, and members of the House and Senate have worked together to develop the newly introduced Veterans Choice program. The major stakeholders came together at the hearing to “support the concept of developing an integrated network that combines the strength of the VA health care system with the best of community care to offer seamless access for enrolled veterans,” explained Adrian Atizado, the deputy national legislative director at Disabled American Veterans (DAV) in his prepared remarks.

The joint effort was in part a response to calls from some VA critics to provide veterans with unlimited choice to outside providers or to fully privatize veteran care.

In the hearing, Committee Chairman Johnny Isakson (R-GA) suggested that he would be willing to work with the VA on the changes to the Veterans Choice Program and was largely in support of the effort. “We need to see to it that the VA…is unleashed to provide the highest quality service that it can and make the decisions that it needs to make on the ground at the time we need to make them,” he reported in a release following the hearing. “We need to give them the funding, commitment and resources to be able to do that.”

At the hearing, VSOs praised the VA for its efforts to improve the Veterans Choice Program but still expressed frustration with problems that continue to dog the program. “The VFW [Veterans of Foreign Wars] has also heard from veterans that the breakdown in communication between VA, contractors and Choice providers often delays their care because their Choice doctors do not receive authorization to provide needed treatments,” reported Carlos Fuentes, VFW director national legislative services. “What is concerning is that veterans are left to piece together the entire story or else they do not.”

“While many veterans initially clamored for ‘more Choice’ as a solution to scheduling problems within the VA healthcare system, once this program was implemented, most have not found it to be a solution,” noted Jeff Steele, assistant director national legislative division of The American Legion. “Instead, they have found it to create as many problems as it solves.…What we have found over the past decade, directly interacting with veterans, is that many of the problems veterans encountered with scheduling appointments in VA are mirrored in the civilian community outside VA.

Women with severe posttraumatic stress disorder (PTSD) symptoms have a nearly 70% increase in the incidence of cardiovascular disease (CVD), according to a study by researchers from Harvard and Brigham and Women’s Hospital in Boston, Massachusetts, Columbia University in New York, and University of California in San Francisco.

The researchers analyzed data from 49,859 women in the Nurses’ Health Study II. Over 20 years, there were 552 confirmed cases of myocardial infarction or stroke.

Women with 6 to 7 symptoms of trauma and PTSD had the highest risk. Women with trauma but no PTSD symptoms had a 30% higher risk. When women who said illness was their worst trauma were excluded, the risk of CVD doubled among those with trauma and severe PTSD symptoms and increased by 88% in women with trauma and moderate PTSD symptoms.

Strikingly, the researchers also found that when the PTSD symptoms declined so did the CVD risk. The researchers note that CVD risk due to other well-known risk factors, such as smoking, increases with exposure duration declines once the risk factor is eliminated. In this study, for every 5 additional years PTSD symptoms lasted, the odds of CVD were 9% higher.

A “more nuanced understanding” of the role of health behaviors could add insight into how PTSD influences the risk of CVD, the researchers say. They point to studies that have found a link between PTSD and cardiotoxic behaviors such as smoking, drinking, and diet. Physiologic alterations that occur with PTSD symptoms also may play an important role, they suggest, such as changes in neuropeptide Y in response to stress, which might contribute to metabolic syndrome.

Citing “particularly intriguing” findings from a study that found symptoms eventually remitted in 44% of individuals with PTSD, the researchers say providing treatment shortly after PTSD symptoms begin could limit the risk of CVD and, potentially, other disease-related risk.

Source:
Gilsanz P, Winning A, Koenen KC, et al. Psychol Med. 2017;47(8):1370-1378.
doi: 10.1017/S0033291716003378.

Women with severe posttraumatic stress disorder (PTSD) symptoms have a nearly 70% increase in the incidence of cardiovascular disease (CVD), according to a study by researchers from Harvard and Brigham and Women’s Hospital in Boston, Massachusetts, Columbia University in New York, and University of California in San Francisco.

The researchers analyzed data from 49,859 women in the Nurses’ Health Study II. Over 20 years, there were 552 confirmed cases of myocardial infarction or stroke.

Women with 6 to 7 symptoms of trauma and PTSD had the highest risk. Women with trauma but no PTSD symptoms had a 30% higher risk. When women who said illness was their worst trauma were excluded, the risk of CVD doubled among those with trauma and severe PTSD symptoms and increased by 88% in women with trauma and moderate PTSD symptoms.

Strikingly, the researchers also found that when the PTSD symptoms declined so did the CVD risk. The researchers note that CVD risk due to other well-known risk factors, such as smoking, increases with exposure duration declines once the risk factor is eliminated. In this study, for every 5 additional years PTSD symptoms lasted, the odds of CVD were 9% higher.

A “more nuanced understanding” of the role of health behaviors could add insight into how PTSD influences the risk of CVD, the researchers say. They point to studies that have found a link between PTSD and cardiotoxic behaviors such as smoking, drinking, and diet. Physiologic alterations that occur with PTSD symptoms also may play an important role, they suggest, such as changes in neuropeptide Y in response to stress, which might contribute to metabolic syndrome.

Citing “particularly intriguing” findings from a study that found symptoms eventually remitted in 44% of individuals with PTSD, the researchers say providing treatment shortly after PTSD symptoms begin could limit the risk of CVD and, potentially, other disease-related risk.

Source:
Gilsanz P, Winning A, Koenen KC, et al. Psychol Med. 2017;47(8):1370-1378.
doi: 10.1017/S0033291716003378.

Women with severe posttraumatic stress disorder (PTSD) symptoms have a nearly 70% increase in the incidence of cardiovascular disease (CVD), according to a study by researchers from Harvard and Brigham and Women’s Hospital in Boston, Massachusetts, Columbia University in New York, and University of California in San Francisco.

The researchers analyzed data from 49,859 women in the Nurses’ Health Study II. Over 20 years, there were 552 confirmed cases of myocardial infarction or stroke.

Women with 6 to 7 symptoms of trauma and PTSD had the highest risk. Women with trauma but no PTSD symptoms had a 30% higher risk. When women who said illness was their worst trauma were excluded, the risk of CVD doubled among those with trauma and severe PTSD symptoms and increased by 88% in women with trauma and moderate PTSD symptoms.

Strikingly, the researchers also found that when the PTSD symptoms declined so did the CVD risk. The researchers note that CVD risk due to other well-known risk factors, such as smoking, increases with exposure duration declines once the risk factor is eliminated. In this study, for every 5 additional years PTSD symptoms lasted, the odds of CVD were 9% higher.

A “more nuanced understanding” of the role of health behaviors could add insight into how PTSD influences the risk of CVD, the researchers say. They point to studies that have found a link between PTSD and cardiotoxic behaviors such as smoking, drinking, and diet. Physiologic alterations that occur with PTSD symptoms also may play an important role, they suggest, such as changes in neuropeptide Y in response to stress, which might contribute to metabolic syndrome.

Citing “particularly intriguing” findings from a study that found symptoms eventually remitted in 44% of individuals with PTSD, the researchers say providing treatment shortly after PTSD symptoms begin could limit the risk of CVD and, potentially, other disease-related risk.

Source:
Gilsanz P, Winning A, Koenen KC, et al. Psychol Med. 2017;47(8):1370-1378.
doi: 10.1017/S0033291716003378.

When military and VA nurses work side by side—learning from and teaching each other—they benefit and so do their patients. A “unique partnership” between the DoD and VA is proving that at Captain James A. Lovell Federal Health Care Center outside Chicago, Illinois.

The first of its kind facility serves nearly 67,000 active-duty military, military retirees, family members, and veterans. In an article for Health.mil News, U.S. Navy Lt. Nathan Aranas, an active-duty registered nurse (RN) and assistant nurse manager in the emergency department (ED), says, “We learn from local trauma, mental health, and pediatrics and birthing centers, exposing me more to how medicine outside of the military is practiced. It gives me a bigger perspective of how the rest of the country operates as a health care institution.”

Christine Barassi-Jackson, a VA civilian RN, nurse manager in the ED, says “having a combined organization is a great balance that pulls out the best parts of both the Navy and VA.” She leans on Aranas, the article says, to serve as an interpreter with some of the patients. “Knowing more of the Navy culture helps break down walls with the patients and other providers.” Aranas also believes that former active-duty patients may be more at ease with a uniformed nurse “because they understand the lingo.”

Overall, Aranas says, “It’s a great experience for young, active-duty clinicians to have."

When military and VA nurses work side by side—learning from and teaching each other—they benefit and so do their patients. A “unique partnership” between the DoD and VA is proving that at Captain James A. Lovell Federal Health Care Center outside Chicago, Illinois.

The first of its kind facility serves nearly 67,000 active-duty military, military retirees, family members, and veterans. In an article for Health.mil News, U.S. Navy Lt. Nathan Aranas, an active-duty registered nurse (RN) and assistant nurse manager in the emergency department (ED), says, “We learn from local trauma, mental health, and pediatrics and birthing centers, exposing me more to how medicine outside of the military is practiced. It gives me a bigger perspective of how the rest of the country operates as a health care institution.”

Christine Barassi-Jackson, a VA civilian RN, nurse manager in the ED, says “having a combined organization is a great balance that pulls out the best parts of both the Navy and VA.” She leans on Aranas, the article says, to serve as an interpreter with some of the patients. “Knowing more of the Navy culture helps break down walls with the patients and other providers.” Aranas also believes that former active-duty patients may be more at ease with a uniformed nurse “because they understand the lingo.”

Overall, Aranas says, “It’s a great experience for young, active-duty clinicians to have."

When military and VA nurses work side by side—learning from and teaching each other—they benefit and so do their patients. A “unique partnership” between the DoD and VA is proving that at Captain James A. Lovell Federal Health Care Center outside Chicago, Illinois.

The first of its kind facility serves nearly 67,000 active-duty military, military retirees, family members, and veterans. In an article for Health.mil News, U.S. Navy Lt. Nathan Aranas, an active-duty registered nurse (RN) and assistant nurse manager in the emergency department (ED), says, “We learn from local trauma, mental health, and pediatrics and birthing centers, exposing me more to how medicine outside of the military is practiced. It gives me a bigger perspective of how the rest of the country operates as a health care institution.”

Christine Barassi-Jackson, a VA civilian RN, nurse manager in the ED, says “having a combined organization is a great balance that pulls out the best parts of both the Navy and VA.” She leans on Aranas, the article says, to serve as an interpreter with some of the patients. “Knowing more of the Navy culture helps break down walls with the patients and other providers.” Aranas also believes that former active-duty patients may be more at ease with a uniformed nurse “because they understand the lingo.”

Overall, Aranas says, “It’s a great experience for young, active-duty clinicians to have."

Photo © ASCO/Scott Morgan 2017

CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.

Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.

Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.

Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).

“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . .  dramatically improved progression-free survival.”

“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”

Study design

Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.

Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.

They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.

The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.

First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4^th week thereafter.

The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m² on day 1, cycle 1 to 70 mg/m² on day 8 of cycle 1.

Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.

The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).

The study also had an exploratory endpoint of progression-free survival (PFS).

Baseline characteristics

Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.

A little over half were male and most (86%) were white.

A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.

Patient disposition

As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.

Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.

The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).

“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m² by cycle 2 except for 3 patients.”

Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m² at day of the second cycle, and 1 escalated to 70 mg/m² at day 8 of cycle 3.

Ultimately, all patients who remained on study were able to escalate to 70 mg/m².

Safety

The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.

Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).

The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).

The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.

The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.

Serious TEAEs

Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.

All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.

The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.

The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.

Overall, serious TEAEs were consistent with previous reports from KRd studies.

Echocardiogram assessment

Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function.  The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.

One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.

“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”

Infusion times and reactions

Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.

The split-dose infusion time was very similar to that of second and subsequent cycles.

There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.

Response rate

The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.

The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.

PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.

Stem cell harvest and ASCT

“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”

Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 10⁶ cells/kg.

Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.

The investigators believe stem cell yield was consistent with previous KRd studies.

Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."

The study was funded by Janssen Research and Development, LLC. 

*Data presented during the meeting differ from the abstract.

Photo © ASCO/Scott Morgan 2017

CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.

Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.

Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.

Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).

“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . .  dramatically improved progression-free survival.”

“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”

Study design

Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.

Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.

They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.

The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.

First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4^th week thereafter.

The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m² on day 1, cycle 1 to 70 mg/m² on day 8 of cycle 1.

Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.

The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).

The study also had an exploratory endpoint of progression-free survival (PFS).

Baseline characteristics

Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.

A little over half were male and most (86%) were white.

A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.

Patient disposition

As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.

Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.

The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).

“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m² by cycle 2 except for 3 patients.”

Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m² at day of the second cycle, and 1 escalated to 70 mg/m² at day 8 of cycle 3.

Ultimately, all patients who remained on study were able to escalate to 70 mg/m².

Safety

The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.

Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).

The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).

The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.

The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.

Serious TEAEs

Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.

All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.

The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.

The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.

Overall, serious TEAEs were consistent with previous reports from KRd studies.

Echocardiogram assessment

Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function.  The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.

One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.

“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”

Infusion times and reactions

Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.

The split-dose infusion time was very similar to that of second and subsequent cycles.

There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.

Response rate

The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.

The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.

PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.

Stem cell harvest and ASCT

“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”

Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 10⁶ cells/kg.

Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.

The investigators believe stem cell yield was consistent with previous KRd studies.

Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."

The study was funded by Janssen Research and Development, LLC. 

*Data presented during the meeting differ from the abstract.

Photo © ASCO/Scott Morgan 2017

CHICAGO—Results of an open-label phase 1b study of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone (KRd) in newly diagnosed multiple myeloma (MM) patients have shown the combination to be highly effective, with an overall response rate of 100%.

Ninety-one percent of patients achieved a very good partial response (VGPR) or better, and 43% achieved a complete response (CR) or better.

Investigators had hypothesized that rather than using autologous stem cell transplant (ASCT) to improve results of treatment with KRd, the combination could alternatively be improved by incorporating daratumumab into a KRd regimen.

Andrzej Jakubowiak, MD, of the University of Chicago Medical Center in Illinois, presented the findings of the MMY1001 study at the 2017 ASCO Annual Meeting (abstract 8000*).

“I think what was one of the more important developments in myeloma last year,” Dr Jakubowiak said, “was data from randomized studies showing that adding daratumumab to either lenalidomide and dexamethasone in the POLLUX study or bortezomib and dexamethasone, a proteasome inhibitor, in the CASTOR study, improves responses, depth of response, and . . .  dramatically improved progression-free survival.”

“[W]e have now the rationale to potentially combine daratumumab with both an IMiD and proteasome inhibitor,” he explained, “which led to the development of this phase 1b study in which we combined daratumumab with KRd and evaluated tolerability and efficacy.”

Study design

Twenty-two transplant-eligible or -ineligible newly diagnosed MM patients were enrolled on the study.

Treatment duration was planned to be 13 cycles or less and patients had the option to move to transplant after 4 cycles.

They could have no clinically significant cardiac disease and echocardiogram was required prior to transplant.

The dosing schedule was the established dosing schema for daratumumab and KRd with 2 notable differences in the 28-day cycles.

First, the daratumumab dose was a split dose. So patients received 8 mg/kg on days 1-2 of cycle 1, 16 mg/kg a week on cycle 2, 16 mg/kg every 2 weeks on cycles 3 – 6, and every 4^th week thereafter.

The second difference was carfilzomib dosing was a weekly regimen with escalation from 20 mg/m² on day 1, cycle 1 to 70 mg/m² on day 8 of cycle 1.

Lenalidomide (25 mg on days 1-21 of each cycle) and dexamethasone (40 mg/week) were the standard regimens for these drugs.

The primary endpoint was safety and tolerability. The secondary endpoint was overall response rate (ORR), duration of response, time to response, and infusion-related reactions (IRR).

The study also had an exploratory endpoint of progression-free survival (PFS).

Baseline characteristics

Patients were a median age of 59.5 years (range 34 – 74). About two thirds were younger than 65 and one third were between 65 and 75.

A little over half were male and most (86%) were white.

A little more than half (55%) had an ECOG score of 0, 41% were ECOG 1, and 5% were ECOG 2.

Patient disposition

As of the cutoff date of March 24, 8 of the 22 patients enrolled (36%) discontinued treatment: 1 due to an adverse event (AE), 1 due to progressive disease, and 6 patients (27%) proceeded to ASCT.

Dr Jakubowiak pointed out that response was censored at this point for patients who proceeded to transplant.

The median follow-up was 10.8 months (range, 4.0 – 12.5) and the median number of treatment cycles was 11.5 (range, 1.0 – 13.0).

“What is of interest to many of us,” Dr Jakubowiak said, “is that patients were escalated to the planned dose of 70 mg/m² by cycle 2 except for 3 patients.”

Of the 3, 1 discontinued before day 1 of the second cycle due to toxicity, 1 had a dose reduction to 56 mg/m² at day of the second cycle, and 1 escalated to 70 mg/m² at day 8 of cycle 3.

Ultimately, all patients who remained on study were able to escalate to 70 mg/m².

Safety

The hematologic treatment-emergent adverse events (TEAE) generally followed what has been observed in similar studies before, Dr Jakubowiak noted.

Hematologic TEAEs of all grades occurring in 30% or more of patients were lymphopenia (68%), thrombocytopenia (55%), anemia (46%), leukopenia (41%), and neutropenia (32%).

The most common non-hematologic TEAEs of all grades occurring in 30% of patients or more were diarrhea (73%), upper respiratory infection (59%) cough, constipation, and fatigue (50% each), dyspnea and insomnia (46%), nausea, rash, and back pain (41%), muscle spasm (36%), and vomiting, pain in extremity, hyperglycemia, and increased ALT (32%).

The most common grade 3/4 TEAEs were infrequent and many events had none of grade 3/4 severity.

The safety profile is consistent with what was previously reported for daratumumab or KRd, Dr Jakubowiak affirmed.

Serious TEAEs

Serious TEAEs occurred in 10 patients (46%), with many occurring in just 1 patient. Pulmonary embolism (PE) was the most frequent, occurring in 3 patients.

All patients were required to be on aspirin prophylaxis and 1 of the patients who had a PE discontinued therapy.

The number of patients with a serious TEAE reasonably related to an individual study drug were 3 (14%) for daratumumab, 5 (23%) for carfilzomib, 5 (23%) for lenalidomide, and 2 (9%) for dexamethasone.

The TEAEs of interest—tachycardia, congestive heart failure, and hypertension—occurred in a single patient each.

Overall, serious TEAEs were consistent with previous reports from KRd studies.

Echocardiogram assessment

Investigators conducted 30 systemic evaluations on the impact of this regimen on heart function.  The investigators observed no change from baseline through the duration of treatment in patients’ left ventricular ejection fractions.

One patient developed congestive heart failure, possibly related to daratumumab or carfilzomib. This patient resumed treatment with a reduced carfilzomib dose, elected ASCT on study day 113, and ended treatment with a VGPR.

“In all,” Dr Jakubowiak said, “we feel that there is no apparent signal of adverse impact of the addition of daratumumab on cardiac function.”

Infusion times and reactions

Overall, IRRs occurred in 27% of the patients, “which appears lower than with previous daratumumab studies,” Dr Jakubowiak noted. And IRRs occurred more frequently during the first infusion than subsequent infusions.

The split-dose infusion time was very similar to that of second and subsequent cycles.

There were limited events related to infusions. All were grade 1 or 2 and most occurred in only a single patient.

Response rate

The median number of treatment cycles administered was 11.5 (range, 2.0 – 13.0). The best response was 100% PR or better, 91% achieved VGPR or better, 42% CR or better, and 29% a stringent CR.

The depth of response improved with duration of treatment. For example, the sCR rate increased from 5% after 4 cycles to 29% at the end of treatment.

PFS was an exploratory endpoint. One patient progressed at 10.8 months and the 12-month PFS rate was 94% with all patients alive.

Stem cell harvest and ASCT

“For many of us,” Dr Jakubowiak commented, “it’s also of interest how this regimen will impact stem cell harvest.”

Nineteen of 22 patients were deemed to be transplant eligible, and the median number of CD34+ cells collected from them was 10.4 x 10⁶ cells/kg.

Patients had a median of 5 treatment cycles prior to stem cell harvest, and 14 (74%) had a VGPR or better prior to harvest.

The investigators believe stem cell yield was consistent with previous KRd studies.

Dr Jakubowiak commented that the deepening of response over time “is a phenomenon we think is important. . . . In all, the data from this small phase 1b study provide support for further evaluation of this regimen in newly diagnosed myeloma."

The study was funded by Janssen Research and Development, LLC. 

*Data presented during the meeting differ from the abstract.

Clinical Question: What are the risks of nonthoracic MRI in patients with pacemakers or implantable cardioverter-defibrillators (ICD) who are not preapproved by the Food and Drug Administration for MRI scanning?

Background: Implantable cardiovascular devices could suffer heating in MRI magnetic fields leading to cardiac thermal injury and changes in pacing properties. The FDA approves “MRI-conditional devices” deemed safe for MRI, but up to six million patients worldwide (and two million in the United States) have non–MRI conditional devices.

Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.

Clinical Question: What are the risks of nonthoracic MRI in patients with pacemakers or implantable cardioverter-defibrillators (ICD) who are not preapproved by the Food and Drug Administration for MRI scanning?

Background: Implantable cardiovascular devices could suffer heating in MRI magnetic fields leading to cardiac thermal injury and changes in pacing properties. The FDA approves “MRI-conditional devices” deemed safe for MRI, but up to six million patients worldwide (and two million in the United States) have non–MRI conditional devices.

Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.

Clinical Question: What are the risks of nonthoracic MRI in patients with pacemakers or implantable cardioverter-defibrillators (ICD) who are not preapproved by the Food and Drug Administration for MRI scanning?

Background: Implantable cardiovascular devices could suffer heating in MRI magnetic fields leading to cardiac thermal injury and changes in pacing properties. The FDA approves “MRI-conditional devices” deemed safe for MRI, but up to six million patients worldwide (and two million in the United States) have non–MRI conditional devices.

Dr. Frederick is assistant clinical professor in the division of hospital Medicine, department of medicine, University of California, San Diego.