Video

In this video, Dr. Nadeem Baig of Allied Digestive Health in West Long Branck, N.J., discusses why he chose private practice gastroenterology and how his organization works with industry to support its mission of providing the best care for patients. Dr. Baig shares his insights into what early career physicians should consider when working with industry throughout their careers.

He has no financial conflicts relative to the topics in this video.

Vidyard Video

In this video, Dr. Nadeem Baig of Allied Digestive Health in West Long Branck, N.J., discusses why he chose private practice gastroenterology and how his organization works with industry to support its mission of providing the best care for patients. Dr. Baig shares his insights into what early career physicians should consider when working with industry throughout their careers.

He has no financial conflicts relative to the topics in this video.

Vidyard Video

In this video, Dr. Nadeem Baig of Allied Digestive Health in West Long Branck, N.J., discusses why he chose private practice gastroenterology and how his organization works with industry to support its mission of providing the best care for patients. Dr. Baig shares his insights into what early career physicians should consider when working with industry throughout their careers.

He has no financial conflicts relative to the topics in this video.

Vidyard Video

Matt Aldrich, MD, is an anesthesiologist and medical director of critical care at UCSF Health in San Francisco. Robert Wachter, MD,MHM, spoke with him about critical care issues in COVID-19, including clinical presentation, PPE in the ICU, whether the health system has enough ventilators for a surge, and ethical dilemmas that ICUs may face during the pandemic.

Matt Aldrich, MD, is an anesthesiologist and medical director of critical care at UCSF Health in San Francisco. Robert Wachter, MD,MHM, spoke with him about critical care issues in COVID-19, including clinical presentation, PPE in the ICU, whether the health system has enough ventilators for a surge, and ethical dilemmas that ICUs may face during the pandemic.

Matt Aldrich, MD, is an anesthesiologist and medical director of critical care at UCSF Health in San Francisco. Robert Wachter, MD,MHM, spoke with him about critical care issues in COVID-19, including clinical presentation, PPE in the ICU, whether the health system has enough ventilators for a surge, and ethical dilemmas that ICUs may face during the pandemic.

Annie Luetkemeyer, MD, professor of infectious diseases at UCSF, is an expert on the treatment of viral infections. Robert Wachter, MD, MHM, chair of the UCSF Department of Medicine, interviewed her about the evidence behind potential treatments for COVID-19 (including chloroquine/hydroxychloroquine, remdesivir, and others), as well as how to assess new and existing drugs in a pandemic.

Annie Luetkemeyer, MD, professor of infectious diseases at UCSF, is an expert on the treatment of viral infections. Robert Wachter, MD, MHM, chair of the UCSF Department of Medicine, interviewed her about the evidence behind potential treatments for COVID-19 (including chloroquine/hydroxychloroquine, remdesivir, and others), as well as how to assess new and existing drugs in a pandemic.

Annie Luetkemeyer, MD, professor of infectious diseases at UCSF, is an expert on the treatment of viral infections. Robert Wachter, MD, MHM, chair of the UCSF Department of Medicine, interviewed her about the evidence behind potential treatments for COVID-19 (including chloroquine/hydroxychloroquine, remdesivir, and others), as well as how to assess new and existing drugs in a pandemic.

Robert Wachter, MD, MHM, chair of the department of medicine at UCSF, interviewed Armond Esmaili, MD, a hospitalist and assistant professor of medicine at UCSF, who is the leader of the Respiratory Isolation Unit at UCSF Medical Center, where the institution's COVID-19 and rule-out COVID-19 patients are being cohorted.

Robert Wachter, MD, MHM, chair of the department of medicine at UCSF, interviewed Armond Esmaili, MD, a hospitalist and assistant professor of medicine at UCSF, who is the leader of the Respiratory Isolation Unit at UCSF Medical Center, where the institution's COVID-19 and rule-out COVID-19 patients are being cohorted.

Robert Wachter, MD, MHM, chair of the department of medicine at UCSF, interviewed Armond Esmaili, MD, a hospitalist and assistant professor of medicine at UCSF, who is the leader of the Respiratory Isolation Unit at UCSF Medical Center, where the institution's COVID-19 and rule-out COVID-19 patients are being cohorted.

LA JOLLA, CALIF. – Physicians and other medical professionals who routinely foster empathic connections with patients may be helping themselves steer clear of burnout.

That’s what iconic actor Alan Alda suggested during a media briefing at Scripps Research on Jan. 16, 2020.

Vidyard Video

“There’s a tremendous pressure on doctors now to have shorter and shorter visits with their patients,” said the 83-year-old Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016 for his work as a champion of science. “A lot of that time is taken up with recording on a computer, which can only put pressure on the doctor.”

Practicing empathy, he continued, “kind of opens people up to one another, which inspirits them.”

Mr. Alda appeared on the research campus to announce that Scripps Research will serve as the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at Stony Brook (N.Y.) University, a nonprofit organization that Mr. Alda helped found in 2009.

“This will be a center where people can come to get training in effective communication,” Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards, told an audience of scientists and medical professionals prior to the media briefing.

“It’s an experiential kind of training,” he explained. “We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that, when you get a diagnosis, your life is over,” said Mr. Alda, who played army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H.”

“Under the burden of that belief, some people won’t tell their family or workplace colleagues,” he said. “There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

[email protected]

LA JOLLA, CALIF. – Physicians and other medical professionals who routinely foster empathic connections with patients may be helping themselves steer clear of burnout.

That’s what iconic actor Alan Alda suggested during a media briefing at Scripps Research on Jan. 16, 2020.

Vidyard Video

“There’s a tremendous pressure on doctors now to have shorter and shorter visits with their patients,” said the 83-year-old Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016 for his work as a champion of science. “A lot of that time is taken up with recording on a computer, which can only put pressure on the doctor.”

Practicing empathy, he continued, “kind of opens people up to one another, which inspirits them.”

Mr. Alda appeared on the research campus to announce that Scripps Research will serve as the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at Stony Brook (N.Y.) University, a nonprofit organization that Mr. Alda helped found in 2009.

“This will be a center where people can come to get training in effective communication,” Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards, told an audience of scientists and medical professionals prior to the media briefing.

“It’s an experiential kind of training,” he explained. “We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that, when you get a diagnosis, your life is over,” said Mr. Alda, who played army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H.”

“Under the burden of that belief, some people won’t tell their family or workplace colleagues,” he said. “There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

[email protected]

LA JOLLA, CALIF. – Physicians and other medical professionals who routinely foster empathic connections with patients may be helping themselves steer clear of burnout.

That’s what iconic actor Alan Alda suggested during a media briefing at Scripps Research on Jan. 16, 2020.

Vidyard Video

“There’s a tremendous pressure on doctors now to have shorter and shorter visits with their patients,” said the 83-year-old Mr. Alda, who received the Public Welfare Medal from the National Academy of Sciences in 2016 for his work as a champion of science. “A lot of that time is taken up with recording on a computer, which can only put pressure on the doctor.”

Practicing empathy, he continued, “kind of opens people up to one another, which inspirits them.”

Mr. Alda appeared on the research campus to announce that Scripps Research will serve as the new West Coast home of Alda Communication Training, which will work in tandem with the Alan Alda Center for Communicating Science at Stony Brook (N.Y.) University, a nonprofit organization that Mr. Alda helped found in 2009.

“This will be a center where people can come to get training in effective communication,” Mr. Alda, who is the winner of six Emmy Awards and six Golden Globe awards, told an audience of scientists and medical professionals prior to the media briefing.

“It’s an experiential kind of training,” he explained. “We don’t give tips. We don’t give lectures. We put you through exercises that are fun and actually make you laugh, but turn you into a better communicator, so you’re better able to connect to the people you’re talking to.”

During a question-and-answer session, Mr. Alda opened up about his Parkinson’s disease, which he said was diagnosed about 5 years ago. In 2018, he decided to speak publicly about his diagnosis for the first time.

“The reason was that I wanted to communicate to people who had recently been diagnosed not to believe or give into the stereotype that, when you get a diagnosis, your life is over,” said Mr. Alda, who played army surgeon “Hawkeye” Pierce on the TV series “M*A*S*H.”

“Under the burden of that belief, some people won’t tell their family or workplace colleagues,” he said. “There are exercises you can do and medications you can take to prolong the time it takes before Parkinson’s gets much more serious. It’s not to diminish the fact that it can get really bad; but to think that your life is over as soon as you get a diagnosis is wrong.”

The first 2-day training session at Scripps Research will be held in June 2020. Additional sessions are scheduled to take place in October and December. Registration is available at aldacommunicationtraining.com/workshops.

[email protected]

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

[email protected]

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

[email protected]

ORLANDO – There’s now mature data surrounding the use of chimeric antigen receptor (CAR) T-cell therapy in lymphoma, and the annual meeting of the American Society of Hematology brought forth additional information from real-world studies, insights about what is driving relapse, and promising data on mantle cell lymphoma.

Vidyard Video

During a video roundtable at the meeting, experts discussed some of the CAR T-cell studies presented at ASH and what those findings mean in practice. The roundtable participants included Brian Hill, MD, of the Cleveland Clinic Taussig Cancer Center; Frederick L. Locke, MD, of the Moffit Cancer Center in Tampa, Fla.; and Peter Riedell, MD, of the University of Chicago.

Among the studies highlighted by the panel was the Transcend NHL 001 study (Abstract 241), which looked at third-line use of lisocabtagene maraleucel (liso-cel) in patients with diffuse large B-cell lymphoma, transformed follicular lymphoma, and other indolent non-Hodgkin lymphoma subtypes. More than 300 patients were enrolled, and liso-cel met all primary and secondary efficacy endpoints, with an overall response rate of more than 70%. The notable take-home point from the study was the safety profile, Dr. Riedell noted. Liso-cel was associated with a lower rate of cytokine release syndrome and neurologic toxicity, compared with the currently approved products.

Since patients in the study had a lower incidence and later onset of cytokine release syndrome, liso-cel could be a candidate for outpatient administration, Dr. Locke said. However, doing that would require “significant infrastructure” in hospitals and clinics to properly support patients, especially given that the treatment-related mortality on the study was similar to approved CAR T-cell products at about 3%. “You have to be ready to admit the patient to the hospital very rapidly, and you have to have the providers and the nurses who are vigilant when the patient is not in the hospital,” he said.

Another notable study presented at ASH examined the characteristics and outcomes of patients receiving bridging therapy while awaiting treatment with axicabtagene ciloleucel (Abstract 245). This real-world study adds interesting information to the field because, in some of the studies that were pivotal to the approval of CAR T-cell therapy, bridging therapy was not allowed, Dr. Locke said.

In this analysis, researchers found that the overall survival was worse among patients who received bridging. This finding suggests that patients who received bridging therapy had a different biology or that the therapy itself may have had an effect on the host or tumor microenvironment that affected the efficacy of the CAR T-cell therapy, the researchers reported.

The panel also highlighted the Zuma-2 study, which looked at KTE-X19, an anti-CD19 CAR T-cell therapy, among more than 70 patients with relapsed/refractory mantle cell lymphoma who had failed treatment with a Bruton’s tyrosine kinase inhibitor (Abstract 754). “This was, I thought, kind of a sleeper study at ASH,” said Dr. Hill, who was one of the authors of the study.

The overall response rate was 93% with about two-thirds of patients achieving a complete response. Researchers found that the response was consistent across subgroups, including Ki-67 and patients with prior use of steroids or bridging therapy. Dr. Locke, who was also a study author, said the results are a “game changer.”

“I’m very excited about it,” Dr. Riedell said, noting that these are patients without a lot of treatment options.

The panel also discussed other studies from ASH, including an analysis of tumor tissue samples from patients in the ZUMA-1 trial who had responded and subsequently relapsed (Abstract 203); a multicenter prospective analysis of circulating tumor DNA in diffuse large B-cell lymphoma patients who had relapsed after treatment with axicabtagene ciloleucel (Abstract 884); and the early use of corticosteroids to prevent toxicities in patients in cohort 4 of the ZUMA-1 trial (Abstract 243).

Dr. Hill reported consulting with Juno/Celgene/BMS and Novartis and research and consulting for Kite/Gilead. Dr. Locke reported consulting for Cellular Biomedicine Group and being a scientific adviser to Kite/Gilead, Novartis, Celgene/BMS, GammaDelta Therapeutics, Calibr, and Allogene. Dr. Riedell reported consulting for Bayer and Verastem, consulting for and research funding from Novartis and BMS/Celgene, and consulting for, research funding from, and speaking for Kite.

[email protected]

Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

[email protected]

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

[email protected]

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

Successful deep brain stimulation of the subthalamic nucleus may have unforeseen effects on the ability to swim in some patients with Parkinson’s disease, according to findings from a case series of nine patients published in Neurology.

All nine patients in the report were experienced swimmers, including two who competed in several competition-level races. They reported losing their ability to swim after successful deep brain stimulation of the subthalamic nucleus (STN-DBS) procedures. The Neurology paper focuses on three of the patients.

All of the patients achieved good to excellent motor control and cut their L-dopa dosage by impressive amounts. But they also lost the ability to coordinate limb movement when in the water, reported Daniel Waldvogel, MD, of the University of Zurich, and associates.

“All found their ability to swim came back immediately, with improved coordination of the limbs,” when stimulation was discontinued, the team noted. But soon after the stimulation ceased, their motor symptoms also rapidly returned, leading all to resume continuous stimulation.

One possible explanation is that STN-DBS does not strongly improve dopamine levels in the supplementary motor area, which controls independent limb movements.

It “may be that DBS affects the supplementary motor area (SMA) differently than levodopa. The SMA is a main output area of the basal ganglia, with connections to the primary motor cortex and the spinal cord,” wrote Dr. Waldvogel and associates. “Functionally, the SMA is thought to be crucial for facilitating independent movements of the limbs, which is a key requirement for swimming.”

Although the SMA also partly manages gait, walking was unaffected in all nine of the patients.

The authors described three patients in more detail:

• Case 1 was a 69-year-old man who was a proficient swimmer before DBS. His Unified Parkinson’s Disease Rating Scale (UPDRS) motor score on medication fell from 28 with dyskinesia before DBS to 17 after DBS, and his levodopa-equivalent dosage declined from 1,570 mg to 920 mg. The man almost drowned after he jumped into a lake and had to be rescued by another swimmer.
• Case 4 was a 59-year-old woman who was an accomplished and competitive swimmer and had been swimming up until the DBS procedure. After DBS, her UPDRS motor score on medication fell from 9 with dyskinesia to 6, and her levodopa-equivalent dosage dropped from 825 mg to 150 mg. She had good motor outcome after DBS but lost the ability to swim. “She regularly practiced swimming with her physiotherapist, but never came close to her previous level,” the authors said.
• Case 5 was a 61-year-old woman who was a competitive swimmer, including swimming across Lake Zurich, and held a lifesaving certification. Her UPDRS motor score on medication fell from 11 with dyskinesia to 9, and her levodopa-equivalent dosage decreased from 800 mg to 180 mg. After DBS, she could swim only a quarter of a kilometer and complained of “awkward posture” during her efforts.

The phenomenon has been reported just one other time by a group from the University of Western Australia. This reported patient was a 68-year-old man with a 5-year history of medication-refractory, tremor-predominant Parkinson’s. He received DBS of the posterior subthalamic area (PSA-DBS).

The patient was a dedicated lap swimmer at his local pool. When he returned to his hobby, “he quickly realized he could not propel himself adequately and that he required assistance to get to safety. In a supervised swimming situation, he was unable to float or perform freestyle, breaststroke, or back stroke. With the stimulator turned off for 30 minutes, he regained swimming ability and lost it when the stimulator was turned on.

The Australian team noted that three similar cases presented to them, but they did not discuss those cases in the paper.

Dr. Waldvogel and coauthors wrote that they might also have unreported cases in their cohort of patients with STN-DBS.

“Our cohort of patients with PD who underwent STN-DBS at the time of this retrospective study consisted of 217 patients, but we did not assess patients systematically for their swimming skills or loss thereof,” the authors said. “Until the mechanism of the reported deterioration of the ability to swim after STN-DBS is elucidated, it is crucial that we advise patients of the potential risk of drowning and the need for a carefully supervised assessment of their swimming skills before going into deep water.”

The report received no funding, and one author disclosed financial relationships with industry.

[email protected]

SOURCE: Waldvogel D et al Neurology. 2019 Nov 27. doi: 10.1212/WNL.0000000000008664.

PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.

Mitchel L. Zoler/MDedge News

“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.

While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.

In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A^1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A_1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.

“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A_1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.

If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.

“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.

The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.

The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.

DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.

[email protected]

SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.

PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.

Mitchel L. Zoler/MDedge News

“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.

While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.

In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A^1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A_1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.

“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A_1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.

If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.

“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.

The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.

The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.

DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.

[email protected]

SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.

PHILADELPHIA – The primary outcome results from the practice-changing DAPA-HF trial gave clinicians strong evidence that the diabetes drug dapagliflozin was equally effective at reducing cardiovascular death and acute exacerbations in patients with heart failure with reduced ejection fraction, whether or not they also had type 2 diabetes. More detailed findings from the 2,605 enrolled patients in DAPA-HF who lacked diabetes (55% of the total study population) have now sealed the deal.

Mitchel L. Zoler/MDedge News

“The relative and absolute reductions in cardiovascular death and hospitalizations or urgent visits for heart failure were substantial, clinically important, and consistent in patients with or without type 2 diabetes,” John McMurray, MD, declared at the American Heart Association scientific sessions as he summarized new trial results that confirmed the initial finding he reported previously.

While the initial report of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) by the study’s lead investigator, Dr. McMurray, was limited to the finding that the relative risk reduction for the study’s primary endpoint was a highly statistically significant 25% in heart failure patients with diabetes and an equally strongly significant 27% relative cut among patients without diabetes (N Engl J Med. 2019 Sep 19;doi: 10.1056/NEJMoa1911303), the new data showed that same consistency across the range of outcomes studied in the trial as well as across the range of glycosylated hemoglobin levels that patients had at study entry.

In an analysis that divided the entire study population of 4,744 patients with heart failure with reduced ejection fraction (HFrEF) into tertiles based on their entry blood level of hemoglobin A^1c, patients with a normal level at or below 5.6% had a 26% relative reduction in the study’s primary endpoint, essentially the same response as the 29% relative cut in adverse events in the tertile of patients with a glycosylated hemoglobin level of 5.7%-5.9% and the relative 28% relative reduction in events in patients diagnosed with type 2 diabetes and having a hemoglobin A_1c of 6.0% or greater, reported Dr. McMurray, professor of cardiology at the University of Glasgow. The results also showed a very benign safety profile in the patients without diabetes, similar to patients with diabetes and to placebo, and with no episodes of major hypoglycemia or diabetic ketoacidosis.

“It’s quite impressive that the result was consistent regardless of the level of hemoglobin A_1c,” commented Larry A. Allen, MD, professor of medicine at the University of Colorado in Aurora and designated discussant for the report. Even though the patients without diabetes constituted just over half of the full DAPA-HF enrollment, the comparison of the effect of dapagliflozin in patients with or without diabetes was prespecified in a trial that enrolled a relatively large number of patients into each of the two subgroups by diabetes status. “I think there a good chance dapagliflozin will get an indication” for treating HFrEF patients without diabetes, Dr. Allen suggested in a video interview.

If the DAPA-HF results persuade the U.S. Food and Drug Administration to grant a supplemental indication to dapagliflozin for use in cutting cardiovascular deaths and acute heart failure exacerbations in patients without diabetes, it would pave the way for health insurers to pay for the drug. Right now, even though Dr. Allen and other heart failure physicians have been impressed by the DAPA-HF findings and are eager to add the drug to the list of agents that HFrEF patients routinely receive, he’s been stymied so far by patients’ out-of pocket cost for using dapagliflozin off-label, roughly $500 a month.

“The DAPA-HF results suggest there is strong reason to consider dapagliflozin for patients without diabetes, and for payers to pay for it. I’m not prescribing dapagliflozin to HFrEF patients without diabetes right now; not because of the data, but because of noncoverage. Payers have not yet caught up with the data,” he said, and they likely will continue to not pay for the drug when used by patients without diabetes until a new labeled indication appears for those patients.

The immediate availability of dapagliflozin (Farxiga) and the two other approved members of the sodium-glucose co-transporter 2 inhibitor class of drugs, empagliflozin (Jardiance) and canagliflozin (Invokana), to treat patients with HFrEF, and the prospect of soon having dapagliflozin and possibly the other drugs in this class to treat patients with HFrEF but without diabetes also raises issues of drug sequencing in these patients and the overall number of drugs that HFrEF patients must now take to be on optimized medical therapy, Dr. Allen noted.

The already-existing lineup of medications for HFrEF patients includes starting on an ACE inhibitor or angiotensin receptor blocker and adding a beta-blocker, a mineralocorticoid receptor antagonist, then swapping out the initial renin-angiotensin system inhibitor for sacubitril/valsartan, and then, on top of all this, adding dapagliflozin or another drug in the same class. It raises questions of what is objectively the best way to introduce all these drugs into patients, and how to do it without subjecting patients to “financial toxicity,” Dr. Allen said during his discussion of the trial’s results.

DAPA-HF was sponsored by AstraZeneca, which markets dapagliflozin (Farxiga). The University of Glasgow received payment from AstraZeneca to compensate for the time Dr. McMurray spent running the study. Dr. Allen has been a consultant to ACI Clinical, Boston Scientific, and Janssen.

[email protected]

SOURCE: McMurray JJV. AHA 19, Late-Breaking Science 1.