Federal Practitioner

Two diabetes management devices that aid in the precision of insulin delivery have been recently cleared by the Food and Drug Administration.

On March 2, the FDA cleared the Android version of Bigfoot Biomedical’s Unity Mobile App for use with its system of smart pen caps that are compatible with different disposable insulin pens for administering both long-acting and rapid-acting insulin.

The system, which has been compatible with iOS devices since May 2021, is “the first and only FDA-cleared smart injection system that turns CGM [continuous glucose monitoring] data into dosing recommendations displayed right on the pen cap for people using multiple daily [insulin] injection therapy,” according to a company statement.

The Bigfoot app allows users to input and review provider treatment recommendations, displays current glucose ranges, and delivers real-time alerts.

Once it is commercially launched, the Android phone application will be available via the Google Play Store. “Given that 41% of U.S. smartphone users choose Android devices, this clearance enables expanded access to a large group of people with diabetes,” the company said.

On March 6, the FDA cleared the Abbott FreeStyle Libre 2 and FreeStyle Libre 3 devices as “integrated” CGM sensors. This means that they can now be used as components in automated insulin delivery systems, along with insulin pumps and connectivity software.

Abbott is working with insulin pump manufacturers Insulet and Tandem in the United States for integration with the FreeStyle Libre versions 2 and 3. Outside the United States, the Libre 3 is already authorized to work with mylife Loop from Ypsomed and CamDiab in Germany. Further launches are expected in the United Kingdom, Switzerland, and the Netherlands later this year.

The modified FreeStyle Libre 2 and FreeStyle Libre 3 sensors have been cleared for use by patients as young as age 2 years and for up to 15 days, in contrast to the previous versions, which were available for patients as young as 4 years for use up to 14 days. The FDA has cleared all Libre sensors – 2 and 3, current and future versions – for use by pregnant women with any type of diabetes.

The modified sensors will be available in the United States later this year and will eventually replace the Libre sensors in current use, the company said in a statement.

“The FreeStyle Libre portfolio is still the most affordable CGM on the market,” an Abbott representative said in an interview.

A version of this article first appeared on Medscape.com.

Two diabetes management devices that aid in the precision of insulin delivery have been recently cleared by the Food and Drug Administration.

On March 2, the FDA cleared the Android version of Bigfoot Biomedical’s Unity Mobile App for use with its system of smart pen caps that are compatible with different disposable insulin pens for administering both long-acting and rapid-acting insulin.

The system, which has been compatible with iOS devices since May 2021, is “the first and only FDA-cleared smart injection system that turns CGM [continuous glucose monitoring] data into dosing recommendations displayed right on the pen cap for people using multiple daily [insulin] injection therapy,” according to a company statement.

The Bigfoot app allows users to input and review provider treatment recommendations, displays current glucose ranges, and delivers real-time alerts.

Once it is commercially launched, the Android phone application will be available via the Google Play Store. “Given that 41% of U.S. smartphone users choose Android devices, this clearance enables expanded access to a large group of people with diabetes,” the company said.

On March 6, the FDA cleared the Abbott FreeStyle Libre 2 and FreeStyle Libre 3 devices as “integrated” CGM sensors. This means that they can now be used as components in automated insulin delivery systems, along with insulin pumps and connectivity software.

Abbott is working with insulin pump manufacturers Insulet and Tandem in the United States for integration with the FreeStyle Libre versions 2 and 3. Outside the United States, the Libre 3 is already authorized to work with mylife Loop from Ypsomed and CamDiab in Germany. Further launches are expected in the United Kingdom, Switzerland, and the Netherlands later this year.

The modified FreeStyle Libre 2 and FreeStyle Libre 3 sensors have been cleared for use by patients as young as age 2 years and for up to 15 days, in contrast to the previous versions, which were available for patients as young as 4 years for use up to 14 days. The FDA has cleared all Libre sensors – 2 and 3, current and future versions – for use by pregnant women with any type of diabetes.

The modified sensors will be available in the United States later this year and will eventually replace the Libre sensors in current use, the company said in a statement.

“The FreeStyle Libre portfolio is still the most affordable CGM on the market,” an Abbott representative said in an interview.

A version of this article first appeared on Medscape.com.

Two diabetes management devices that aid in the precision of insulin delivery have been recently cleared by the Food and Drug Administration.

On March 2, the FDA cleared the Android version of Bigfoot Biomedical’s Unity Mobile App for use with its system of smart pen caps that are compatible with different disposable insulin pens for administering both long-acting and rapid-acting insulin.

The system, which has been compatible with iOS devices since May 2021, is “the first and only FDA-cleared smart injection system that turns CGM [continuous glucose monitoring] data into dosing recommendations displayed right on the pen cap for people using multiple daily [insulin] injection therapy,” according to a company statement.

The Bigfoot app allows users to input and review provider treatment recommendations, displays current glucose ranges, and delivers real-time alerts.

Once it is commercially launched, the Android phone application will be available via the Google Play Store. “Given that 41% of U.S. smartphone users choose Android devices, this clearance enables expanded access to a large group of people with diabetes,” the company said.

On March 6, the FDA cleared the Abbott FreeStyle Libre 2 and FreeStyle Libre 3 devices as “integrated” CGM sensors. This means that they can now be used as components in automated insulin delivery systems, along with insulin pumps and connectivity software.

Abbott is working with insulin pump manufacturers Insulet and Tandem in the United States for integration with the FreeStyle Libre versions 2 and 3. Outside the United States, the Libre 3 is already authorized to work with mylife Loop from Ypsomed and CamDiab in Germany. Further launches are expected in the United Kingdom, Switzerland, and the Netherlands later this year.

The modified FreeStyle Libre 2 and FreeStyle Libre 3 sensors have been cleared for use by patients as young as age 2 years and for up to 15 days, in contrast to the previous versions, which were available for patients as young as 4 years for use up to 14 days. The FDA has cleared all Libre sensors – 2 and 3, current and future versions – for use by pregnant women with any type of diabetes.

The modified sensors will be available in the United States later this year and will eventually replace the Libre sensors in current use, the company said in a statement.

“The FreeStyle Libre portfolio is still the most affordable CGM on the market,” an Abbott representative said in an interview.

A version of this article first appeared on Medscape.com.

The American Psychiatric Association has released updated practice guidelines for the management of eating disorders, the first update in 16 years.

The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.

“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”

Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.

The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.

The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.

The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.

Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.

“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.

A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.

The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.

The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.

A version of this article first appeared on Medscape.com.

The American Psychiatric Association has released updated practice guidelines for the management of eating disorders, the first update in 16 years.

The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.

“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”

Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.

The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.

The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.

The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.

Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.

“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.

A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.

The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.

The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.

A version of this article first appeared on Medscape.com.

The American Psychiatric Association has released updated practice guidelines for the management of eating disorders, the first update in 16 years.

The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.

“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”

Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.

The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.

The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.

The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.

Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.

“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.

A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.

The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.

The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.

A version of this article first appeared on Medscape.com.

An incisionless surgical procedure that uses focused ultrasound ablation (FUSA) to target the globus pallidus internus of patients with Parkinson’s disease significantly reduced tremors and improved mobility for those with advanced disease, new research shows.

The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.

Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.

On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.

“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”

The study was published online in the New England Journal of Medicine.
 

Strong response

For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.

The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.

Patients in the control group underwent an identical procedure with the sonication energy disabled.

The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.

At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).

When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.

Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
 

‘Unforgiving’ area of the brain

While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.

The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”

“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”

By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.

Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
 

More study is needed

Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.

The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.

But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.

“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.

One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.

Investigators plan to probe these questions in future trials.

“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”

The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.

A version of this article originally appeared on Medscape.com.

An incisionless surgical procedure that uses focused ultrasound ablation (FUSA) to target the globus pallidus internus of patients with Parkinson’s disease significantly reduced tremors and improved mobility for those with advanced disease, new research shows.

The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.

Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.

On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.

“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”

The study was published online in the New England Journal of Medicine.
 

Strong response

For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.

The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.

Patients in the control group underwent an identical procedure with the sonication energy disabled.

The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.

At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).

When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.

Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
 

‘Unforgiving’ area of the brain

While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.

The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”

“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”

By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.

Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
 

More study is needed

Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.

The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.

But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.

“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.

One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.

Investigators plan to probe these questions in future trials.

“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”

The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.

A version of this article originally appeared on Medscape.com.

An incisionless surgical procedure that uses focused ultrasound ablation (FUSA) to target the globus pallidus internus of patients with Parkinson’s disease significantly reduced tremors and improved mobility for those with advanced disease, new research shows.

The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.

Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.

On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.

“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”

The study was published online in the New England Journal of Medicine.
 

Strong response

For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.

The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.

Patients in the control group underwent an identical procedure with the sonication energy disabled.

The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.

At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).

When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.

Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
 

‘Unforgiving’ area of the brain

While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.

The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”

“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”

By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.

Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
 

More study is needed

Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.

The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.

But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.

“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.

One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.

Investigators plan to probe these questions in future trials.

“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”

The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.

A version of this article originally appeared on Medscape.com.

Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.

“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.

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“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.

Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.

In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.

“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”

He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.” 

For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.

They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.

On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.

Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).

Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).

Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004).  Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).

After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.

After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
 

‘Closer monitoring needed’

“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”

He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.

“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”

He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001). 

“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”

Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.

“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
 

Jury still out

Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”

Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.  

“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said. 

“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.

The authors of the study reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.

“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.

a_namenko/Getty Images

“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.

Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.

In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.

“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”

He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.” 

For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.

They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.

On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.

Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).

Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).

Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004).  Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).

After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.

After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
 

‘Closer monitoring needed’

“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”

He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.

“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”

He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001). 

“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”

Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.

“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
 

Jury still out

Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”

Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.  

“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said. 

“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.

The authors of the study reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Consumption of a low-carbohydrate, high-fat diet, dubbed a “keto-like” diet, was associated with an increase in LDL levels and a twofold increase in the risk for future cardiovascular events, in a new observational study.

“To our knowledge this is the first study to demonstrate an association between a carbohydrate-restricted dietary platform and greater risk of atherosclerotic cardiovascular disease,” said study investigator Iulia Iatan, MD, PhD, University of British Columbia, Vancouver.

a_namenko/Getty Images

“Hypercholesterolemia occurring during a low-carb, high-fat diet should not be assumed to be benign,” she concluded.

Dr. Iatan presented the study March 5 at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

The presentation received much media attention, with headlines implying a causal relationship with cardiac events based on these observational results. But lipid expert Steven Nissen, MD, of the Cleveland Clinic, warned against paying much attention to the headlines or to the study’s conclusions.

In an interview, Dr. Nissen pointed out that the LDL increase in the “keto-like” diet group was relatively small and “certainly not enough to produce a doubling in cardiovascular risk.

“The people who were on the ‘keto-like’ diet in this study were different than those who were on the standard diet,” he said. “Those on the ‘keto-like’ diet were on it for a reason – they were more overweight, they had a higher incidence of diabetes, so their risk profile was completely different. Even though the researchers tried to adjust for other cardiovascular risk factors, there will be unmeasured confounding in a study like this.”

He said he doesn’t think this study “answers any significant questions in a way that we want to have them answered. I’m not a big fan of this type of diet, but I don’t think it doubles the risk of adverse cardiovascular events, and I don’t think this study tells us one way or another.” 

For the study, Dr. Iatan and colleagues defined a low-carbohydrate, high-fat diet as consisting of no more than 25% of total daily energy from carbohydrates and more than 45% of total daily calories from fat. This is somewhat higher in carbohydrates and lower in fat than a strict ketogenic diet but could be thought of as a ‘keto-like’ diet.

They analyzed data from the UK Biobank, a large-scale prospective database with health information from over half a million people living in the United Kingdom who were followed for at least 10 years.

On enrollment in the Biobank, participants completed a one-time, self-reported 24-hour diet questionnaire and, at the same time, had blood drawn to check their levels of cholesterol. The researchers identified 305 participants whose questionnaire responses indicated that they followed a low-carbohydrate, high-fat diet. These participants were matched by age and sex with 1,220 individuals who reported being on a standard diet.

Of the study population, 73% were women and the average age was 54 years. Those on a low carbohydrate/high fat diet had a higher average body mass index (27.7 vs. 26.7) and a higher incidence of diabetes (4.9% vs. 1.7%).

Results showed that compared with participants on a standard diet, those on the “keto-like” diet had significantly higher levels of both LDL cholesterol and apolipoprotein B (ApoB).

Levels of LDL were 3.80 mmol/L (147 mg/dL) in the keto-like group vs. 3.64 mmol/L (141 mg/dL) in the standard group (P = .004).  Levels of ApoB were 1.09 g/L (109 mg/dL) in the keto-like group and 1.04 g/L (104 mg/dL) in the standard group (P < .001).

After an average of 11.8 years of follow-up, 9.8% of participants on the low-carbohydrate/high-fat diet vs. 4.3% in the standard diet group experienced one of the events included in the composite event endpoint: Angina, myocardial infarction, coronary artery disease, ischemic stroke, peripheral arterial disease, or coronary/carotid revascularization.

After adjustment for other risk factors for heart disease – diabetes, hypertension, obesity, and smoking – individuals on a low-carbohydrate, high-fat diet were found to have a twofold risk of having a cardiovascular event (HR, 2.18; P < .001).
 

‘Closer monitoring needed’

“Our results have shown, I think for the first time, that there is an association between this increasingly popular dietary pattern and high LDL cholesterol and an increased future risk of cardiovascular events,” senior author Liam Brunham, MD, of the University of British Columbia, said in an interview. “This is concerning as there are many people out there following this type of diet, and I think it suggests there is a need for closer monitoring of these people.”

He explained that while it would be expected for cholesterol levels to rise on a high-fat diet, “there has been a perception by some that this is not worrisome as it is reflecting certain metabolic changes. What we’ve shown in this study is that if your cholesterol does increase significantly on this diet then you should not assume that this is not a problem.

“For some people with diabetes this diet can help lower blood sugar and some people can lose weight on it,” he noted, “but what our data show is that there is a subgroup of people who experience high levels of LDL and ApoB and that seems to be driving the risk.”

He pointed out that overall the mean level of LDL was only slightly increased in the individuals on the low-carb/high-fat diet but severe high cholesterol (more than 5 mmol/L or 190 mg/dL) was about doubled in that group (10% vs. 5%). And these patients had a sixfold increase in risk of cardiovascular disease (P < .001). 

“This suggests that there is a subgroup of people who are susceptible to this exacerbation of hypercholesterolemia in response to a low-carb/high-fat diet.”

Dr. Brunham said his advice would be that if people choose to follow this diet, they should have their cholesterol monitored, and manage their cardiovascular risk factors.

“I wouldn’t say it is not appropriate to follow this diet based on this study,” he added. “This is just an observational study. It is not definitive. But if people do want to follow this dietary pattern because they feel there would be some benefits, then they should be aware of the potential risks and take steps to mitigate those risks.”
 

Jury still out

Dr. Nissen said in his view “the jury was still out” on this type of diet. “I’m open to the possibility that, particularly in the short run, a ‘keto-like’ diet may help some people lose weight and that’s a good thing. But I do not generally recommend this type of diet.”

Rather, he advises patients to follow a Mediterranean diet, which has been proven to reduce cardiovascular events in a randomized study, the PREDIMED trial.  

“We can’t make decisions on what type of diet to recommend to patients based on observational studies like this where there is a lot of subtlety missing. But when studies like this are reported, the mass media seize on it. That’s not the way the public needs to be educated,” Dr. Nissen said. 

“We refer to this type of study as hypothesis-generating. It raises a hypothesis. It doesn’t answer the question. It is worth looking at the question of whether a ketogenic-like diet is harmful. We don’t know at present, and I don’t think we know any more after this study,” he added.

The authors of the study reported no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Patients with advanced renal cell carcinoma who are taking a tyrosine kinase inhibitor (TKI) to prolong their lives will typically keep going without a break until the disease progresses or toxicities such as severe fatigue and diarrhea become intolerable.

That might soon change with the publication of a unique study. Lasting 10 years, the phase 3 STAR trial involved 920 patients across 60 cancer centers. These patients had advanced kidney cancer and were taking either sunitinib (Sutent) or pazopanib (Votrient).

The results showed that taking an occasional respite from TKI therapy had little impact on the patient’s survival.

The study was published online in The Lancet Oncology.

The study was funded by the United Kingdom’s National Institute for Health and Care Research because drug companies never run studies on how to reduce the use of their drug, commented lead author Janet Brown, MD, of the University of Sheffield (England).

“We rely on the NIHR to do these important trials that … companies wouldn’t do,” she commented to this news organization.

Commenting on the rationale for STAR, coauthor Jenny Hewison, PhD, of Leeds (England) University School of Medicine, explained that patients often find it difficult to tolerate TKIs. “Although these patients are getting the best treatment that we can offer them, it’s very demanding. … It could make them feel tired, quite unwell. And there can be a range of other effects including sickness and diarrhea.”

As an example, 77% of patients in the pivotal trial of sunitinib in kidney cancer experienced grade 3 or 4 adverse events such as hypertension (13%), fatigue (15%), diarrhea (10%) and hand-foot syndrome (8%).

Both sunitinib and pazopanib carry label warnings of severe and fatal hepatotoxicity.

Also, in contrast to conventional chemotherapy, which is usually given in a finite number of courses, treatment with TKIs carries on indefinitely.

“It feels like you’re taking [TKIs] for the whole of the rest of your life,” said Dr. Brown.
 

Study details

The STAR trial, an open-label, noninferiority, randomized controlled study, is the first phase 3 study of treatment breaks in renal cell carcinoma. The participants had inoperable locoregional or metastatic clear cell renal cell carcinoma (ccRCC) and had received no systemic therapy for advanced disease.

They were randomly assigned before TKI treatment to a conventional continuation strategy or a drug-free interval approach. The treating physician decided whether a patient would take sunitinib or pazopanib.

All participants took their drugs for four cycles (6 weeks each cycle). At the 24-week point, those with a complete response, partial response, or stable disease began their randomized assignment.

Individuals who took a break continued until their disease progressed, at which point therapy was resumed. They could take further treatment breaks once their disease was back under control. The group on continuous treatment kept going until disease progression or intolerable toxicities. Median follow up was 58 months.

In both the per-protocol and intent-to-treat (ITT) populations, overall survival was 28 months for the people who received continuous treatment vs. 27 months for those who took a break. Statistical noninferiority was established in the ITT population but not in the per-protocol population.

The median length of all treatment breaks was 87 days. Many people took two or more breaks; one patient took nine breaks overall. The breaks were popular: only 3% of participants who were meant to stop therapy withdrew from the study in order to continue their treatment.

Said Dr. Hewison: “In the very early days of planning the study there were some doubts as to whether it would succeed because of potential unwillingness of people to stop treatment for a while.”

Dr. Brown agreed: “People did worry about that initially, but it actually seemed to be more the other way around. By that time – 6 months – people were relieved to be there. …We actually had some people from the other arm asking, could they also have a break?”

To understand better the benefits of treatment breaks to patients, Janine Bestall, PhD, a senior research fellow in applied health research at the University of Leeds, conducted a qualitative study in parallel with the main trial.

Summing up the patients’ experiences, Dr. Bestall said the drug-free periods “gave them more time.”

Dr. Bestall quoted one patient who said: “I know that things can happen and it grows back, but you’ve always got the buffer there knowing that you can go back and get help. But you actually lead a normal life and the advantage is, yeah, you can go on holiday, you can actually do more things in the garden, cleaning up, painting, whatever needs doing, you do it.”

Dr. Brown said, “I had a lady who, when she was on the trial, had four breaks in total, one when her daughter got married, and [she said] that was really nice for her to do all the shopping and all the normal things that you do, and not be on something that was making her tired and causing sore hands and diarrhea.” 

The drug-free interval strategy provided annual cost savings of 3,235 pounds sterling ($3,850) and a noninferior quality-adjusted life-year (QALY) benefit in both the ITT and per-protocol populations.

Serious adverse reactions occurred in 9% of patients in the treatment-break group versus 12% of the continuous-treatment group.

The authors of the study concluded, “Treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma.”
 

Changes in treatment strategies

The STAR trial started recruiting in January 2012.

Since that time, immunotherapy has taken over as first-line treatment for many patients with advanced ccRCC in both the United Kingdom and the United States.

However, TKIs still have a place. The NCCN Kidney Cancer 2022 Guidelines recommend both sunitinib and pazopanib as options for first-line therapy in advanced disease. The 2022 ASCO Metastatic ccRCC guidelines recommend either drug as first-line treatment in combination with an immune checkpoint inhibitor or in monotherapy if there are “coexisting medical problems.”

In the United States, intermittent sunitinib in metastatic RCC was tested in a small study in 2017 with little activity in the literature since then. The authors, led by Moshe Ornstein, MD, from the Cleveland Clinic, concluded at the time that sunitinib treatment breaks were feasible and “clinical efficacy does not seem to be compromised.” Dr. Ornstein was approached for comment on this latest U.K. study but declined.

Back in the United Kingdom, the results of STAR arrived just in time.

Said Dr. Brown: “This has … been really helpful in the U.K. in the pandemic when people said, can these patients have extra breaks? At the worst of the pandemic we were able to say, sure, if it’s stable, we can keep them off for 3-6 months. …And so that’s already had a powerful impact.”

Dr. Brown concluded, “I think what the trial does allow us to do, as individual oncologists, is to look at the patients that this might be suitable for – it won’t be everybody – and to say yes, it’s okay to personalize things.”

The study was funded by the U.K.’s National Institute for Health and Care Research. Dr. Bestall reported no relevant financial relationships. Dr. Hewison reported funding to her institution from the NIHR Health Technology Assessment. Dr. Brown reports having served as a consultant or adviser for Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; honoraria from Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; research funding paid to their institution from the National Institute for Health and Care Research; and travel expenses from Ipsen. Other coauthors reported numerous relationships with industry.

A version of this article first appeared on Medscape.com.

Patients with advanced renal cell carcinoma who are taking a tyrosine kinase inhibitor (TKI) to prolong their lives will typically keep going without a break until the disease progresses or toxicities such as severe fatigue and diarrhea become intolerable.

That might soon change with the publication of a unique study. Lasting 10 years, the phase 3 STAR trial involved 920 patients across 60 cancer centers. These patients had advanced kidney cancer and were taking either sunitinib (Sutent) or pazopanib (Votrient).

The results showed that taking an occasional respite from TKI therapy had little impact on the patient’s survival.

The study was published online in The Lancet Oncology.

The study was funded by the United Kingdom’s National Institute for Health and Care Research because drug companies never run studies on how to reduce the use of their drug, commented lead author Janet Brown, MD, of the University of Sheffield (England).

“We rely on the NIHR to do these important trials that … companies wouldn’t do,” she commented to this news organization.

Commenting on the rationale for STAR, coauthor Jenny Hewison, PhD, of Leeds (England) University School of Medicine, explained that patients often find it difficult to tolerate TKIs. “Although these patients are getting the best treatment that we can offer them, it’s very demanding. … It could make them feel tired, quite unwell. And there can be a range of other effects including sickness and diarrhea.”

As an example, 77% of patients in the pivotal trial of sunitinib in kidney cancer experienced grade 3 or 4 adverse events such as hypertension (13%), fatigue (15%), diarrhea (10%) and hand-foot syndrome (8%).

Both sunitinib and pazopanib carry label warnings of severe and fatal hepatotoxicity.

Also, in contrast to conventional chemotherapy, which is usually given in a finite number of courses, treatment with TKIs carries on indefinitely.

“It feels like you’re taking [TKIs] for the whole of the rest of your life,” said Dr. Brown.
 

Study details

The STAR trial, an open-label, noninferiority, randomized controlled study, is the first phase 3 study of treatment breaks in renal cell carcinoma. The participants had inoperable locoregional or metastatic clear cell renal cell carcinoma (ccRCC) and had received no systemic therapy for advanced disease.

They were randomly assigned before TKI treatment to a conventional continuation strategy or a drug-free interval approach. The treating physician decided whether a patient would take sunitinib or pazopanib.

All participants took their drugs for four cycles (6 weeks each cycle). At the 24-week point, those with a complete response, partial response, or stable disease began their randomized assignment.

Individuals who took a break continued until their disease progressed, at which point therapy was resumed. They could take further treatment breaks once their disease was back under control. The group on continuous treatment kept going until disease progression or intolerable toxicities. Median follow up was 58 months.

In both the per-protocol and intent-to-treat (ITT) populations, overall survival was 28 months for the people who received continuous treatment vs. 27 months for those who took a break. Statistical noninferiority was established in the ITT population but not in the per-protocol population.

The median length of all treatment breaks was 87 days. Many people took two or more breaks; one patient took nine breaks overall. The breaks were popular: only 3% of participants who were meant to stop therapy withdrew from the study in order to continue their treatment.

Said Dr. Hewison: “In the very early days of planning the study there were some doubts as to whether it would succeed because of potential unwillingness of people to stop treatment for a while.”

Dr. Brown agreed: “People did worry about that initially, but it actually seemed to be more the other way around. By that time – 6 months – people were relieved to be there. …We actually had some people from the other arm asking, could they also have a break?”

To understand better the benefits of treatment breaks to patients, Janine Bestall, PhD, a senior research fellow in applied health research at the University of Leeds, conducted a qualitative study in parallel with the main trial.

Summing up the patients’ experiences, Dr. Bestall said the drug-free periods “gave them more time.”

Dr. Bestall quoted one patient who said: “I know that things can happen and it grows back, but you’ve always got the buffer there knowing that you can go back and get help. But you actually lead a normal life and the advantage is, yeah, you can go on holiday, you can actually do more things in the garden, cleaning up, painting, whatever needs doing, you do it.”

Dr. Brown said, “I had a lady who, when she was on the trial, had four breaks in total, one when her daughter got married, and [she said] that was really nice for her to do all the shopping and all the normal things that you do, and not be on something that was making her tired and causing sore hands and diarrhea.” 

The drug-free interval strategy provided annual cost savings of 3,235 pounds sterling ($3,850) and a noninferior quality-adjusted life-year (QALY) benefit in both the ITT and per-protocol populations.

Serious adverse reactions occurred in 9% of patients in the treatment-break group versus 12% of the continuous-treatment group.

The authors of the study concluded, “Treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma.”
 

Changes in treatment strategies

The STAR trial started recruiting in January 2012.

Since that time, immunotherapy has taken over as first-line treatment for many patients with advanced ccRCC in both the United Kingdom and the United States.

However, TKIs still have a place. The NCCN Kidney Cancer 2022 Guidelines recommend both sunitinib and pazopanib as options for first-line therapy in advanced disease. The 2022 ASCO Metastatic ccRCC guidelines recommend either drug as first-line treatment in combination with an immune checkpoint inhibitor or in monotherapy if there are “coexisting medical problems.”

In the United States, intermittent sunitinib in metastatic RCC was tested in a small study in 2017 with little activity in the literature since then. The authors, led by Moshe Ornstein, MD, from the Cleveland Clinic, concluded at the time that sunitinib treatment breaks were feasible and “clinical efficacy does not seem to be compromised.” Dr. Ornstein was approached for comment on this latest U.K. study but declined.

Back in the United Kingdom, the results of STAR arrived just in time.

Said Dr. Brown: “This has … been really helpful in the U.K. in the pandemic when people said, can these patients have extra breaks? At the worst of the pandemic we were able to say, sure, if it’s stable, we can keep them off for 3-6 months. …And so that’s already had a powerful impact.”

Dr. Brown concluded, “I think what the trial does allow us to do, as individual oncologists, is to look at the patients that this might be suitable for – it won’t be everybody – and to say yes, it’s okay to personalize things.”

The study was funded by the U.K.’s National Institute for Health and Care Research. Dr. Bestall reported no relevant financial relationships. Dr. Hewison reported funding to her institution from the NIHR Health Technology Assessment. Dr. Brown reports having served as a consultant or adviser for Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; honoraria from Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; research funding paid to their institution from the National Institute for Health and Care Research; and travel expenses from Ipsen. Other coauthors reported numerous relationships with industry.

A version of this article first appeared on Medscape.com.

Patients with advanced renal cell carcinoma who are taking a tyrosine kinase inhibitor (TKI) to prolong their lives will typically keep going without a break until the disease progresses or toxicities such as severe fatigue and diarrhea become intolerable.

That might soon change with the publication of a unique study. Lasting 10 years, the phase 3 STAR trial involved 920 patients across 60 cancer centers. These patients had advanced kidney cancer and were taking either sunitinib (Sutent) or pazopanib (Votrient).

The results showed that taking an occasional respite from TKI therapy had little impact on the patient’s survival.

The study was published online in The Lancet Oncology.

The study was funded by the United Kingdom’s National Institute for Health and Care Research because drug companies never run studies on how to reduce the use of their drug, commented lead author Janet Brown, MD, of the University of Sheffield (England).

“We rely on the NIHR to do these important trials that … companies wouldn’t do,” she commented to this news organization.

Commenting on the rationale for STAR, coauthor Jenny Hewison, PhD, of Leeds (England) University School of Medicine, explained that patients often find it difficult to tolerate TKIs. “Although these patients are getting the best treatment that we can offer them, it’s very demanding. … It could make them feel tired, quite unwell. And there can be a range of other effects including sickness and diarrhea.”

As an example, 77% of patients in the pivotal trial of sunitinib in kidney cancer experienced grade 3 or 4 adverse events such as hypertension (13%), fatigue (15%), diarrhea (10%) and hand-foot syndrome (8%).

Both sunitinib and pazopanib carry label warnings of severe and fatal hepatotoxicity.

Also, in contrast to conventional chemotherapy, which is usually given in a finite number of courses, treatment with TKIs carries on indefinitely.

“It feels like you’re taking [TKIs] for the whole of the rest of your life,” said Dr. Brown.
 

Study details

The STAR trial, an open-label, noninferiority, randomized controlled study, is the first phase 3 study of treatment breaks in renal cell carcinoma. The participants had inoperable locoregional or metastatic clear cell renal cell carcinoma (ccRCC) and had received no systemic therapy for advanced disease.

They were randomly assigned before TKI treatment to a conventional continuation strategy or a drug-free interval approach. The treating physician decided whether a patient would take sunitinib or pazopanib.

All participants took their drugs for four cycles (6 weeks each cycle). At the 24-week point, those with a complete response, partial response, or stable disease began their randomized assignment.

Individuals who took a break continued until their disease progressed, at which point therapy was resumed. They could take further treatment breaks once their disease was back under control. The group on continuous treatment kept going until disease progression or intolerable toxicities. Median follow up was 58 months.

In both the per-protocol and intent-to-treat (ITT) populations, overall survival was 28 months for the people who received continuous treatment vs. 27 months for those who took a break. Statistical noninferiority was established in the ITT population but not in the per-protocol population.

The median length of all treatment breaks was 87 days. Many people took two or more breaks; one patient took nine breaks overall. The breaks were popular: only 3% of participants who were meant to stop therapy withdrew from the study in order to continue their treatment.

Said Dr. Hewison: “In the very early days of planning the study there were some doubts as to whether it would succeed because of potential unwillingness of people to stop treatment for a while.”

Dr. Brown agreed: “People did worry about that initially, but it actually seemed to be more the other way around. By that time – 6 months – people were relieved to be there. …We actually had some people from the other arm asking, could they also have a break?”

To understand better the benefits of treatment breaks to patients, Janine Bestall, PhD, a senior research fellow in applied health research at the University of Leeds, conducted a qualitative study in parallel with the main trial.

Summing up the patients’ experiences, Dr. Bestall said the drug-free periods “gave them more time.”

Dr. Bestall quoted one patient who said: “I know that things can happen and it grows back, but you’ve always got the buffer there knowing that you can go back and get help. But you actually lead a normal life and the advantage is, yeah, you can go on holiday, you can actually do more things in the garden, cleaning up, painting, whatever needs doing, you do it.”

Dr. Brown said, “I had a lady who, when she was on the trial, had four breaks in total, one when her daughter got married, and [she said] that was really nice for her to do all the shopping and all the normal things that you do, and not be on something that was making her tired and causing sore hands and diarrhea.” 

The drug-free interval strategy provided annual cost savings of 3,235 pounds sterling ($3,850) and a noninferior quality-adjusted life-year (QALY) benefit in both the ITT and per-protocol populations.

Serious adverse reactions occurred in 9% of patients in the treatment-break group versus 12% of the continuous-treatment group.

The authors of the study concluded, “Treatment breaks might be a feasible and cost-effective option with lifestyle benefits for patients during tyrosine kinase inhibitor therapy in patients with renal cell carcinoma.”
 

Changes in treatment strategies

The STAR trial started recruiting in January 2012.

Since that time, immunotherapy has taken over as first-line treatment for many patients with advanced ccRCC in both the United Kingdom and the United States.

However, TKIs still have a place. The NCCN Kidney Cancer 2022 Guidelines recommend both sunitinib and pazopanib as options for first-line therapy in advanced disease. The 2022 ASCO Metastatic ccRCC guidelines recommend either drug as first-line treatment in combination with an immune checkpoint inhibitor or in monotherapy if there are “coexisting medical problems.”

In the United States, intermittent sunitinib in metastatic RCC was tested in a small study in 2017 with little activity in the literature since then. The authors, led by Moshe Ornstein, MD, from the Cleveland Clinic, concluded at the time that sunitinib treatment breaks were feasible and “clinical efficacy does not seem to be compromised.” Dr. Ornstein was approached for comment on this latest U.K. study but declined.

Back in the United Kingdom, the results of STAR arrived just in time.

Said Dr. Brown: “This has … been really helpful in the U.K. in the pandemic when people said, can these patients have extra breaks? At the worst of the pandemic we were able to say, sure, if it’s stable, we can keep them off for 3-6 months. …And so that’s already had a powerful impact.”

Dr. Brown concluded, “I think what the trial does allow us to do, as individual oncologists, is to look at the patients that this might be suitable for – it won’t be everybody – and to say yes, it’s okay to personalize things.”

The study was funded by the U.K.’s National Institute for Health and Care Research. Dr. Bestall reported no relevant financial relationships. Dr. Hewison reported funding to her institution from the NIHR Health Technology Assessment. Dr. Brown reports having served as a consultant or adviser for Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; honoraria from Novartis, Ipsen, Amgen, Merck Sharp & Dohme, Bristol-Myers Squibb, and Bayer; research funding paid to their institution from the National Institute for Health and Care Research; and travel expenses from Ipsen. Other coauthors reported numerous relationships with industry.

A version of this article first appeared on Medscape.com.

A physician’s specialty can make a difference when it comes to having suicidal thoughts. Doctors who specialize in family medicine, obstetrics-gynecology, and psychiatry reported double the rates of suicidal thoughts than doctors in oncology, rheumatology, and pulmonary medicine, according to Doctors’ Burden: Medscape Physician Suicide Report 2023.

“The specialties with the highest reporting of physician suicidal thoughts are also those with the greatest physician shortages, based on the number of job openings posted by recruiting sites,” said Peter Yellowlees, MD, professor of psychiatry and chief wellness officer at UC Davis Health.

Doctors in those specialties are overworked, which can lead to burnout, he said. “While burnout doesn’t cause depression, it’s correlated with depression and suicidal ideation.”

There’s also a generational divide among physicians who reported suicidal thoughts. Millennials (age 27-41) and Gen-X physicians (age 42-56) were more likely to report these thoughts than were Baby Boomers (age 57-75) and the Silent Generation (age 76-95).

“Younger physicians are more burned out – they may have less control over their lives and less meaning than some older doctors who can do what they want,” said Dr. Yellowlees.

One millennial respondent commented that being on call and being required to chart detailed notes in the EHR has contributed to her burnout. “I’m more impatient and make less time and effort to see my friends and family.”

One Silent Generation respondent commented, “I am semi-retired, I take no call, I work no weekends, I provide anesthesia care in my area of special expertise, I work clinically about 46 days a year. Life is good, particularly compared to my younger colleagues who are working 60-plus hours a week with evening work, weekend work, and call. I feel really sorry for them.”    

When young people enter medical school, they’re quite healthy, with low rates of depression and burnout, said Dr. Yellowlees. Yet, studies have shown that rates of burnout and suicidal thoughts increased within 2 years. “That reflects what happens when a group of idealistic young people hit a horrible system,” he said.
 

Who’s responsible?

Millennials were three times as likely as baby boomers to say that a medical school or health care organization should be responsible when a student or physician commits suicide.

“Young physicians may expect more of their employers than my generation did, which we see in residency programs that have unionized,” said Dr. Yellowlees, a Baby Boomer.

“As more young doctors are employed by health care organizations, they also may expect more resources to be available to them, such as wellness programs,” he added.

Younger doctors also focus more on work-life balance than older doctors, including time off and having hobbies, he said. “They are much more rational in terms of their overall beliefs and expectations than the older generation.”
 

Whom doctors confide in

Nearly 60% of physician-respondents with suicidal thoughts said they confided in a professional or someone they knew. Men were just as likely as women to reach out to a therapist (38%), whereas men were slightly more likely to confide in a family member and women were slightly more likely to confide in a colleague.

“It’s interesting that women are more active in seeking support at work – they often have developed a network of colleagues to support each other’s careers and whom they can confide in,” said Dr. Yellowlees.

He emphasized that 40% of physicians said they didn’t confide in anyone when they had suicidal thoughts. Of those, just over half said they could cope without professional help.

One respondent commented, “It’s just a thought; nothing I would actually do.” Another commented, “Mental health professionals can’t fix the underlying reason for the problem.”

Many doctors were concerned about risking disclosure to their medical boards (42%); that it would show up on their insurance records (33%); and that their colleagues would find out (25%), according to the report.

One respondent commented, “I don’t trust doctors to keep it to themselves.”

Another barrier doctors mentioned was a lack of time to seek help. One commented, “Time. I have none, when am I supposed to find an hour for counseling?”

A version of this article originally appeared on Medscape.com.

A physician’s specialty can make a difference when it comes to having suicidal thoughts. Doctors who specialize in family medicine, obstetrics-gynecology, and psychiatry reported double the rates of suicidal thoughts than doctors in oncology, rheumatology, and pulmonary medicine, according to Doctors’ Burden: Medscape Physician Suicide Report 2023.

“The specialties with the highest reporting of physician suicidal thoughts are also those with the greatest physician shortages, based on the number of job openings posted by recruiting sites,” said Peter Yellowlees, MD, professor of psychiatry and chief wellness officer at UC Davis Health.

Doctors in those specialties are overworked, which can lead to burnout, he said. “While burnout doesn’t cause depression, it’s correlated with depression and suicidal ideation.”

There’s also a generational divide among physicians who reported suicidal thoughts. Millennials (age 27-41) and Gen-X physicians (age 42-56) were more likely to report these thoughts than were Baby Boomers (age 57-75) and the Silent Generation (age 76-95).

“Younger physicians are more burned out – they may have less control over their lives and less meaning than some older doctors who can do what they want,” said Dr. Yellowlees.

One millennial respondent commented that being on call and being required to chart detailed notes in the EHR has contributed to her burnout. “I’m more impatient and make less time and effort to see my friends and family.”

One Silent Generation respondent commented, “I am semi-retired, I take no call, I work no weekends, I provide anesthesia care in my area of special expertise, I work clinically about 46 days a year. Life is good, particularly compared to my younger colleagues who are working 60-plus hours a week with evening work, weekend work, and call. I feel really sorry for them.”    

When young people enter medical school, they’re quite healthy, with low rates of depression and burnout, said Dr. Yellowlees. Yet, studies have shown that rates of burnout and suicidal thoughts increased within 2 years. “That reflects what happens when a group of idealistic young people hit a horrible system,” he said.
 

Who’s responsible?

Millennials were three times as likely as baby boomers to say that a medical school or health care organization should be responsible when a student or physician commits suicide.

“Young physicians may expect more of their employers than my generation did, which we see in residency programs that have unionized,” said Dr. Yellowlees, a Baby Boomer.

“As more young doctors are employed by health care organizations, they also may expect more resources to be available to them, such as wellness programs,” he added.

Younger doctors also focus more on work-life balance than older doctors, including time off and having hobbies, he said. “They are much more rational in terms of their overall beliefs and expectations than the older generation.”
 

Whom doctors confide in

Nearly 60% of physician-respondents with suicidal thoughts said they confided in a professional or someone they knew. Men were just as likely as women to reach out to a therapist (38%), whereas men were slightly more likely to confide in a family member and women were slightly more likely to confide in a colleague.

“It’s interesting that women are more active in seeking support at work – they often have developed a network of colleagues to support each other’s careers and whom they can confide in,” said Dr. Yellowlees.

He emphasized that 40% of physicians said they didn’t confide in anyone when they had suicidal thoughts. Of those, just over half said they could cope without professional help.

One respondent commented, “It’s just a thought; nothing I would actually do.” Another commented, “Mental health professionals can’t fix the underlying reason for the problem.”

Many doctors were concerned about risking disclosure to their medical boards (42%); that it would show up on their insurance records (33%); and that their colleagues would find out (25%), according to the report.

One respondent commented, “I don’t trust doctors to keep it to themselves.”

Another barrier doctors mentioned was a lack of time to seek help. One commented, “Time. I have none, when am I supposed to find an hour for counseling?”

A version of this article originally appeared on Medscape.com.

A physician’s specialty can make a difference when it comes to having suicidal thoughts. Doctors who specialize in family medicine, obstetrics-gynecology, and psychiatry reported double the rates of suicidal thoughts than doctors in oncology, rheumatology, and pulmonary medicine, according to Doctors’ Burden: Medscape Physician Suicide Report 2023.

“The specialties with the highest reporting of physician suicidal thoughts are also those with the greatest physician shortages, based on the number of job openings posted by recruiting sites,” said Peter Yellowlees, MD, professor of psychiatry and chief wellness officer at UC Davis Health.

Doctors in those specialties are overworked, which can lead to burnout, he said. “While burnout doesn’t cause depression, it’s correlated with depression and suicidal ideation.”

There’s also a generational divide among physicians who reported suicidal thoughts. Millennials (age 27-41) and Gen-X physicians (age 42-56) were more likely to report these thoughts than were Baby Boomers (age 57-75) and the Silent Generation (age 76-95).

“Younger physicians are more burned out – they may have less control over their lives and less meaning than some older doctors who can do what they want,” said Dr. Yellowlees.

One millennial respondent commented that being on call and being required to chart detailed notes in the EHR has contributed to her burnout. “I’m more impatient and make less time and effort to see my friends and family.”

One Silent Generation respondent commented, “I am semi-retired, I take no call, I work no weekends, I provide anesthesia care in my area of special expertise, I work clinically about 46 days a year. Life is good, particularly compared to my younger colleagues who are working 60-plus hours a week with evening work, weekend work, and call. I feel really sorry for them.”    

When young people enter medical school, they’re quite healthy, with low rates of depression and burnout, said Dr. Yellowlees. Yet, studies have shown that rates of burnout and suicidal thoughts increased within 2 years. “That reflects what happens when a group of idealistic young people hit a horrible system,” he said.
 

Who’s responsible?

Millennials were three times as likely as baby boomers to say that a medical school or health care organization should be responsible when a student or physician commits suicide.

“Young physicians may expect more of their employers than my generation did, which we see in residency programs that have unionized,” said Dr. Yellowlees, a Baby Boomer.

“As more young doctors are employed by health care organizations, they also may expect more resources to be available to them, such as wellness programs,” he added.

Younger doctors also focus more on work-life balance than older doctors, including time off and having hobbies, he said. “They are much more rational in terms of their overall beliefs and expectations than the older generation.”
 

Whom doctors confide in

Nearly 60% of physician-respondents with suicidal thoughts said they confided in a professional or someone they knew. Men were just as likely as women to reach out to a therapist (38%), whereas men were slightly more likely to confide in a family member and women were slightly more likely to confide in a colleague.

“It’s interesting that women are more active in seeking support at work – they often have developed a network of colleagues to support each other’s careers and whom they can confide in,” said Dr. Yellowlees.

He emphasized that 40% of physicians said they didn’t confide in anyone when they had suicidal thoughts. Of those, just over half said they could cope without professional help.

One respondent commented, “It’s just a thought; nothing I would actually do.” Another commented, “Mental health professionals can’t fix the underlying reason for the problem.”

Many doctors were concerned about risking disclosure to their medical boards (42%); that it would show up on their insurance records (33%); and that their colleagues would find out (25%), according to the report.

One respondent commented, “I don’t trust doctors to keep it to themselves.”

Another barrier doctors mentioned was a lack of time to seek help. One commented, “Time. I have none, when am I supposed to find an hour for counseling?”

A version of this article originally appeared on Medscape.com.

Sales of a best-selling health book by a high-profile University of Southern California, Los Angeles, oncologist have been suspended because of dozens of instances of plagiarism.

The Los Angeles Times reported earlier this week that it identified at least 95 instances of plagiarism by author David B. Agus, MD, in “The Book of Animal Secrets: Nature’s Lessons for a Long and Happy Life.”

According to the LA Times, Dr. Agus copied passages from numerous sources, including The New York Times, National Geographic, Wikipedia, and smaller niche sites. Some instances involved a sentence or two; others involved multiparagraph, word-for-word copying without attribution.

The book by Dr. Agus – who interviews celebrities for a health-related miniseries on Paramount Plus – had reached the top spot on Amazon’s list of best-selling books about animals a week before its planned March 7 release.

Publisher Simon & Schuster released a statement announcing a recall of the book at Dr. Agus’ expense “until a fully revised and corrected edition can be released.”

Dr. Agus included his own statement apologizing “to the scientists and writers whose work or words were used or not fully attributed,” and said he will “rewrite the passages in question with new language, will provide proper and full attribution, and when ready will announce a new publication date.”

“Writers should always be credited for their work, and I deeply regret these mistakes and the lack of rigor in finalizing the book,” he stated, adding that “[t]his book contains important lessons, messages, and guidance about health that I wanted to convey to the readers. I do not want these mistakes to interfere with that effort.”
 

A version of this article first appeared on Medscape.com.

Sales of a best-selling health book by a high-profile University of Southern California, Los Angeles, oncologist have been suspended because of dozens of instances of plagiarism.

The Los Angeles Times reported earlier this week that it identified at least 95 instances of plagiarism by author David B. Agus, MD, in “The Book of Animal Secrets: Nature’s Lessons for a Long and Happy Life.”

According to the LA Times, Dr. Agus copied passages from numerous sources, including The New York Times, National Geographic, Wikipedia, and smaller niche sites. Some instances involved a sentence or two; others involved multiparagraph, word-for-word copying without attribution.

The book by Dr. Agus – who interviews celebrities for a health-related miniseries on Paramount Plus – had reached the top spot on Amazon’s list of best-selling books about animals a week before its planned March 7 release.

Publisher Simon & Schuster released a statement announcing a recall of the book at Dr. Agus’ expense “until a fully revised and corrected edition can be released.”

Dr. Agus included his own statement apologizing “to the scientists and writers whose work or words were used or not fully attributed,” and said he will “rewrite the passages in question with new language, will provide proper and full attribution, and when ready will announce a new publication date.”

“Writers should always be credited for their work, and I deeply regret these mistakes and the lack of rigor in finalizing the book,” he stated, adding that “[t]his book contains important lessons, messages, and guidance about health that I wanted to convey to the readers. I do not want these mistakes to interfere with that effort.”
 

A version of this article first appeared on Medscape.com.

Sales of a best-selling health book by a high-profile University of Southern California, Los Angeles, oncologist have been suspended because of dozens of instances of plagiarism.

The Los Angeles Times reported earlier this week that it identified at least 95 instances of plagiarism by author David B. Agus, MD, in “The Book of Animal Secrets: Nature’s Lessons for a Long and Happy Life.”

According to the LA Times, Dr. Agus copied passages from numerous sources, including The New York Times, National Geographic, Wikipedia, and smaller niche sites. Some instances involved a sentence or two; others involved multiparagraph, word-for-word copying without attribution.

The book by Dr. Agus – who interviews celebrities for a health-related miniseries on Paramount Plus – had reached the top spot on Amazon’s list of best-selling books about animals a week before its planned March 7 release.

Publisher Simon & Schuster released a statement announcing a recall of the book at Dr. Agus’ expense “until a fully revised and corrected edition can be released.”

Dr. Agus included his own statement apologizing “to the scientists and writers whose work or words were used or not fully attributed,” and said he will “rewrite the passages in question with new language, will provide proper and full attribution, and when ready will announce a new publication date.”

“Writers should always be credited for their work, and I deeply regret these mistakes and the lack of rigor in finalizing the book,” he stated, adding that “[t]his book contains important lessons, messages, and guidance about health that I wanted to convey to the readers. I do not want these mistakes to interfere with that effort.”
 

A version of this article first appeared on Medscape.com.

Most women with breast cancer undergo primary surgery within 8 weeks of diagnosis and any later may be associated with worse overall survival, according to findings from a case series.

With no national quality metrics delineating optimal breast cancer surgery timing, the researchers recommend surgery before 8 weeks from breast cancer diagnosis.

“This time interval does not appear to have a detrimental association with cancer outcomes and allows for multidisciplinary care,” the researchers, led by Alyssa A. Wiener, MD, from University of Wisconsin–Madison, said.

But, in an accompanying editorial, two surgical oncologists questioned whether faster surgery is always better.

“Efficiency might associate with quality, but doesn’t always ensure it,” Rita Mukhtar, MD, and Laura Esserman, MD, with the division of surgical oncology, University of California, San Francisco, said.

The study and editorial were published online in JAMA Surgery.


 

Optimal timing for surgery?

Some studies have found worse survival outcomes for women who experience delays between breast cancer diagnosis and surgical treatment, but the optimal window for surgery and the point at which surgery becomes less advantageous remain unknown.

Using the National Cancer Database, Dr. Wiener and colleagues identified 373,334 women (median age, 61) who were diagnosed with stage I to stage III ductal or lobular breast cancer from 2010 to 2014 and followed up through 2019.

All women underwent surgery as their first course of treatment. Patients with prior breast cancer, those who had neoadjuvant or experimental therapy or missing receptor information, and those who were diagnosed with breast cancer on the date of their primary surgery were excluded.

Most patients had timely surgery. The median time to surgery was 30 days, and 88% of patients underwent surgery before the 57-day time point.

Only 12% of patients had surgery more than 8 weeks after their diagnosis. Factors associated with longer times to surgery included age younger than 45, having Medicaid or no insurance, and lower household income.

The overall 5-year survival for the cohort was high at 90%. On multivariable analysis, the researchers found no statistically significant association between time to surgery and overall survival when surgery was performed between 0 and 8 weeks.

However, women who had surgery 9 or more weeks after diagnosis had a significantly higher rate of death within 5 years, compared with those who had surgery performed between 0 and 4 weeks (hazard ratio, 1.15; P < .001). Performing surgery up to 9 weeks (57-63 days) post diagnosis also did not appear to be negatively associated with survival.

This study “highlights that time to treatment of breast cancer is important,” said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the study. “Surgery is only one-third of the treatment of breast cancer, so these patients who had longer delays to the OR may have also not started their postsurgery treatments in time.”

In addition, the study found that socioeconomic status – Medicaid or uninsured status and lower household incomes – was associated with longer times to surgery.

“Socioeconomic factors like these may be independently associated with worse outcomes and may contribute to some of the disparities in cancer outcomes observed for resource-limited patients due to delayed care,” the authors said.

Identifying 8 weeks as a goal for time to surgery can help uncover delays associated with socioeconomic factors and provide adequate time for decision-making, the researchers noted.
 

Is faster always better?

Dr. Wiener and colleagues cautioned, however, that their findings should be considered “hypothesis generating,” given that decision-making surrounding breast cancer surgery is complex.

Importantly, the authors noted, tumor characteristics, such as tumor size, nodal status, and receptor subtype, appeared to have a pronounced impact on overall survival, compared with timing of surgery. For instance, compared with a tumor size of 2 cm or fewer, larger tumors – those > 2 cm to ≤ 5 cm and > 5 cm – were associated with worse survival (HR, 1.80 and 2.62, respectively).

“This highlights that tumor biology is the primary driver of patients’ breast cancer outcomes,” the authors noted.

In an accompanying editorial, two surgical oncologists highlighted that faster may not always be better.

For instance, Dr. Mukhtar and Dr. Esserman explained, if a patient with a large node-positive, triple-negative breast cancer receives surgery within a week of diagnosis, “one must question whether this timely care represents quality care, as the opportunity to understand tumor response and affect breast cancer survival has been lost.”

The editorialists noted that time to surgery might also matter very little for indolent, screen-detected cancers, and time to treatment start might matter a lot for fast-growing, interval cancers.

In addition, they questioned whether including the socioeconomic factors highlighted in the overall model would “mitigate the association between time to surgery and survival seen in this study.”

Overall, “operating too soon could indicate lack of quality, while operating too late perhaps reflects lack of access to care,” the editorialists said.

This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Dr. Wiener and Dr. Cate report no relevant financial relationships. Dr. Esserman is a member of the Blue Cross Medical advisory panel, is a board member of the Quantum Leap Healthcare Collaborative, and leads an investigator-initiated vaccine trial for high-risk ductal carcinoma in situ, which is funded by Merck.

A version of this article first appeared on Medscape.com.

Most women with breast cancer undergo primary surgery within 8 weeks of diagnosis and any later may be associated with worse overall survival, according to findings from a case series.

With no national quality metrics delineating optimal breast cancer surgery timing, the researchers recommend surgery before 8 weeks from breast cancer diagnosis.

“This time interval does not appear to have a detrimental association with cancer outcomes and allows for multidisciplinary care,” the researchers, led by Alyssa A. Wiener, MD, from University of Wisconsin–Madison, said.

But, in an accompanying editorial, two surgical oncologists questioned whether faster surgery is always better.

“Efficiency might associate with quality, but doesn’t always ensure it,” Rita Mukhtar, MD, and Laura Esserman, MD, with the division of surgical oncology, University of California, San Francisco, said.

The study and editorial were published online in JAMA Surgery.


 

Optimal timing for surgery?

Some studies have found worse survival outcomes for women who experience delays between breast cancer diagnosis and surgical treatment, but the optimal window for surgery and the point at which surgery becomes less advantageous remain unknown.

Using the National Cancer Database, Dr. Wiener and colleagues identified 373,334 women (median age, 61) who were diagnosed with stage I to stage III ductal or lobular breast cancer from 2010 to 2014 and followed up through 2019.

All women underwent surgery as their first course of treatment. Patients with prior breast cancer, those who had neoadjuvant or experimental therapy or missing receptor information, and those who were diagnosed with breast cancer on the date of their primary surgery were excluded.

Most patients had timely surgery. The median time to surgery was 30 days, and 88% of patients underwent surgery before the 57-day time point.

Only 12% of patients had surgery more than 8 weeks after their diagnosis. Factors associated with longer times to surgery included age younger than 45, having Medicaid or no insurance, and lower household income.

The overall 5-year survival for the cohort was high at 90%. On multivariable analysis, the researchers found no statistically significant association between time to surgery and overall survival when surgery was performed between 0 and 8 weeks.

However, women who had surgery 9 or more weeks after diagnosis had a significantly higher rate of death within 5 years, compared with those who had surgery performed between 0 and 4 weeks (hazard ratio, 1.15; P < .001). Performing surgery up to 9 weeks (57-63 days) post diagnosis also did not appear to be negatively associated with survival.

This study “highlights that time to treatment of breast cancer is important,” said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the study. “Surgery is only one-third of the treatment of breast cancer, so these patients who had longer delays to the OR may have also not started their postsurgery treatments in time.”

In addition, the study found that socioeconomic status – Medicaid or uninsured status and lower household incomes – was associated with longer times to surgery.

“Socioeconomic factors like these may be independently associated with worse outcomes and may contribute to some of the disparities in cancer outcomes observed for resource-limited patients due to delayed care,” the authors said.

Identifying 8 weeks as a goal for time to surgery can help uncover delays associated with socioeconomic factors and provide adequate time for decision-making, the researchers noted.
 

Is faster always better?

Dr. Wiener and colleagues cautioned, however, that their findings should be considered “hypothesis generating,” given that decision-making surrounding breast cancer surgery is complex.

Importantly, the authors noted, tumor characteristics, such as tumor size, nodal status, and receptor subtype, appeared to have a pronounced impact on overall survival, compared with timing of surgery. For instance, compared with a tumor size of 2 cm or fewer, larger tumors – those > 2 cm to ≤ 5 cm and > 5 cm – were associated with worse survival (HR, 1.80 and 2.62, respectively).

“This highlights that tumor biology is the primary driver of patients’ breast cancer outcomes,” the authors noted.

In an accompanying editorial, two surgical oncologists highlighted that faster may not always be better.

For instance, Dr. Mukhtar and Dr. Esserman explained, if a patient with a large node-positive, triple-negative breast cancer receives surgery within a week of diagnosis, “one must question whether this timely care represents quality care, as the opportunity to understand tumor response and affect breast cancer survival has been lost.”

The editorialists noted that time to surgery might also matter very little for indolent, screen-detected cancers, and time to treatment start might matter a lot for fast-growing, interval cancers.

In addition, they questioned whether including the socioeconomic factors highlighted in the overall model would “mitigate the association between time to surgery and survival seen in this study.”

Overall, “operating too soon could indicate lack of quality, while operating too late perhaps reflects lack of access to care,” the editorialists said.

This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Dr. Wiener and Dr. Cate report no relevant financial relationships. Dr. Esserman is a member of the Blue Cross Medical advisory panel, is a board member of the Quantum Leap Healthcare Collaborative, and leads an investigator-initiated vaccine trial for high-risk ductal carcinoma in situ, which is funded by Merck.

A version of this article first appeared on Medscape.com.

Most women with breast cancer undergo primary surgery within 8 weeks of diagnosis and any later may be associated with worse overall survival, according to findings from a case series.

With no national quality metrics delineating optimal breast cancer surgery timing, the researchers recommend surgery before 8 weeks from breast cancer diagnosis.

“This time interval does not appear to have a detrimental association with cancer outcomes and allows for multidisciplinary care,” the researchers, led by Alyssa A. Wiener, MD, from University of Wisconsin–Madison, said.

But, in an accompanying editorial, two surgical oncologists questioned whether faster surgery is always better.

“Efficiency might associate with quality, but doesn’t always ensure it,” Rita Mukhtar, MD, and Laura Esserman, MD, with the division of surgical oncology, University of California, San Francisco, said.

The study and editorial were published online in JAMA Surgery.


 

Optimal timing for surgery?

Some studies have found worse survival outcomes for women who experience delays between breast cancer diagnosis and surgical treatment, but the optimal window for surgery and the point at which surgery becomes less advantageous remain unknown.

Using the National Cancer Database, Dr. Wiener and colleagues identified 373,334 women (median age, 61) who were diagnosed with stage I to stage III ductal or lobular breast cancer from 2010 to 2014 and followed up through 2019.

All women underwent surgery as their first course of treatment. Patients with prior breast cancer, those who had neoadjuvant or experimental therapy or missing receptor information, and those who were diagnosed with breast cancer on the date of their primary surgery were excluded.

Most patients had timely surgery. The median time to surgery was 30 days, and 88% of patients underwent surgery before the 57-day time point.

Only 12% of patients had surgery more than 8 weeks after their diagnosis. Factors associated with longer times to surgery included age younger than 45, having Medicaid or no insurance, and lower household income.

The overall 5-year survival for the cohort was high at 90%. On multivariable analysis, the researchers found no statistically significant association between time to surgery and overall survival when surgery was performed between 0 and 8 weeks.

However, women who had surgery 9 or more weeks after diagnosis had a significantly higher rate of death within 5 years, compared with those who had surgery performed between 0 and 4 weeks (hazard ratio, 1.15; P < .001). Performing surgery up to 9 weeks (57-63 days) post diagnosis also did not appear to be negatively associated with survival.

This study “highlights that time to treatment of breast cancer is important,” said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the study. “Surgery is only one-third of the treatment of breast cancer, so these patients who had longer delays to the OR may have also not started their postsurgery treatments in time.”

In addition, the study found that socioeconomic status – Medicaid or uninsured status and lower household incomes – was associated with longer times to surgery.

“Socioeconomic factors like these may be independently associated with worse outcomes and may contribute to some of the disparities in cancer outcomes observed for resource-limited patients due to delayed care,” the authors said.

Identifying 8 weeks as a goal for time to surgery can help uncover delays associated with socioeconomic factors and provide adequate time for decision-making, the researchers noted.
 

Is faster always better?

Dr. Wiener and colleagues cautioned, however, that their findings should be considered “hypothesis generating,” given that decision-making surrounding breast cancer surgery is complex.

Importantly, the authors noted, tumor characteristics, such as tumor size, nodal status, and receptor subtype, appeared to have a pronounced impact on overall survival, compared with timing of surgery. For instance, compared with a tumor size of 2 cm or fewer, larger tumors – those > 2 cm to ≤ 5 cm and > 5 cm – were associated with worse survival (HR, 1.80 and 2.62, respectively).

“This highlights that tumor biology is the primary driver of patients’ breast cancer outcomes,” the authors noted.

In an accompanying editorial, two surgical oncologists highlighted that faster may not always be better.

For instance, Dr. Mukhtar and Dr. Esserman explained, if a patient with a large node-positive, triple-negative breast cancer receives surgery within a week of diagnosis, “one must question whether this timely care represents quality care, as the opportunity to understand tumor response and affect breast cancer survival has been lost.”

The editorialists noted that time to surgery might also matter very little for indolent, screen-detected cancers, and time to treatment start might matter a lot for fast-growing, interval cancers.

In addition, they questioned whether including the socioeconomic factors highlighted in the overall model would “mitigate the association between time to surgery and survival seen in this study.”

Overall, “operating too soon could indicate lack of quality, while operating too late perhaps reflects lack of access to care,” the editorialists said.

This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Dr. Wiener and Dr. Cate report no relevant financial relationships. Dr. Esserman is a member of the Blue Cross Medical advisory panel, is a board member of the Quantum Leap Healthcare Collaborative, and leads an investigator-initiated vaccine trial for high-risk ductal carcinoma in situ, which is funded by Merck.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A new wearable device detects, with a high degree of precision, various types of visual dysfunction, which eventually affects most patients with multiple sclerosis (MS). The device uses advanced digital technology to stimulate the retina and the occipital cortex while also stimulating the eye tracking system, and reports out this data, one of its developers, Jennifer Graves, MD, PhD, director of neuroimmunology research, University of California, San Diego, said in an interview.

“In one paradigm of testing, we can get both sets of information,” which eliminates the complicated equipment set-up used by neuro-ophthalmologists, and makes eye assessments more readily available, she said.

“We can make this accessible for more clinicians and more patients, even eventually having it in an emergency setting or an outpatient clinic setting.”

Dr. Graves discussed this and other next-generation digital tools at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Currently, patients with MS can use accelerometers that determine overall activity level and devices that detect heart rate variability. They can also access mobile apps that track symptoms and medication adherence.
 

Limited sensitivity of current tools

However, current tools used to determine disability in MS are limited. The classification of MS subtypes is largely retrospective, and the preferred Expanded Disability Status Scale (EDSS) is problematic, said Dr. Graves.

For example, she said, the EDSS lacks sensitivity to short-term changes, depends on ambulation, and only poorly captures upper-extremity disability. “We know our patients are experiencing change and we know the tools we have now aren’t capturing that.”

She used the example of a pianist who can no longer play well with her right hand, but this can’t be detected with current tools. A device that uses technology from the gaming and computer control industry “can quantify that” change, said Dr. Graves.

She added that tools in development can detect not only motor and visual dysfunction but also cognitive dysfunction, potentially aiding clinical care and facilitating more rapid trials of disease modifying agents in MS. “Rather than having descriptive terms, these digital tools will help us quantitate change so we can take action.”

The new sensing devices use multiple sensors, including accelerometers, gyroscopes, and surface electrical signals in muscles to capture very precise temporal and textural information related to movement. Their development uses traditional signal processing as well as artificial intelligence approaches.

Dr. Graves’s device, the MSight, captures afferent and efferent visual function with a single mobile brain-computer interface.

At least 80% of patients with MS have some measurable dysfunction in the afferent system that oversees how light from the environment is turned into images in the brain, explained Dr. Graves. The efferent visual system that controls eye movements is also “profoundly impacted by MS” with, again, up to 80% of patients with MS experiencing related dysfunction, she said.

Her new visual system correlates with burden of MS disease, said Dr. Graves. “Having efferent and eye tracking problems correlates with overall disability and walking function.”

The information collected by this new device “tends to be really helpful even in people who don’t appear to be disabled with MS because it’s literally a window into the brain to let us see what’s happening,” said Dr. Graves.

She and her colleagues are testing the MSight device in clinical trials and have a provisional patent for it.
 

Finger and foot taps

Another device her team is developing detects minute changes over several months in finger and toe tap movements that are very difficult for the human eye to capture.

Dr. Graves reported on a cross sectional validation study of 17 patients with MS showing the foot and finger tap measures strongly correlated with the EDSS and patient-reported outcomes (P < .0001). A longitudinal analysis of 68 patients with MS found information on finger and foot taps distinguished those with progressive from those with relapsing MS.

“We found that in patients with progressive MS, the information in the signal we were capturing was changing, whereas someone with relapsing MS had a little bit of that but much less,” said Dr. Graves.

These and other novel, self-contained devices “will provide a set of neurological vital signs that we can put in the hands of clinicians and patients” with MS, as is currently being done in other specialties – for example, cardiology, said Dr. Graves.
 

Intriguing, exciting

In a comment, David Gosselin, PhD, associate professor, department of molecular medicine, Laval University, Quebec City, who cochaired the session featuring next-generation digital tools, said more sensitive monitoring technologies coming down the pipeline are “intriguing and exciting.”

While the devices are still in early development, “the eventual integration of such noninvasive technology that measures subtle limb muscle function has the potential to redefine clinical practice,” said Dr. Gosselin.

“The idea of sampling a patient’s ability to move about on a frequent basis, perhaps even daily, and to generate data profiles over time, certainly hold promise with respect to tracking disease evolution and responses to treatments on a scale not accessible before.”

A more immediate and comprehensive overview of a patient’s response to a treatment “could yield more rapid insights into the effectiveness of novel therapies tested in clinical trials,” said Dr. Gosselin. “This could have profound implications.”

Future digital devices may facilitate monitoring of patients in more remote communities, too, said Dr. Gosselin.

However, before these technologies can be introduced on a broad level, several outstanding issues will have to be addressed, the most important being the streams of data they generate, said Dr. Gosselin.

“This clearly has the potential to overwhelm neurologists in the assessment of their patients’ conditions,” he said. “Which information, and in which analyzed forms, truly provides meaningful insights into patients’ conditions will need to be identified, and this will take time.”

Privacy may be an issue, too, said Dr. Gosselin. Some patients may be less inclined to comply with a procedure “that can capture and record their life so extensively.”

And how health care insurance providers can interface with these comprehensive profiles of patients’ lives will also have to be considered, he said.

Dr. Graves has a provisional patent on the MSight device; has received research support from MMSS, Octave, Biogen EMD Serono, Novartis, ATARA Biotherapeutics, and ABM; has served on advisory boards for Bayer, Genentech, and TG therapeutic and a pediatric clinical trial steering committee for Novartis; and has consulted for Google. Dr. Gosselin reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A new wearable device detects, with a high degree of precision, various types of visual dysfunction, which eventually affects most patients with multiple sclerosis (MS). The device uses advanced digital technology to stimulate the retina and the occipital cortex while also stimulating the eye tracking system, and reports out this data, one of its developers, Jennifer Graves, MD, PhD, director of neuroimmunology research, University of California, San Diego, said in an interview.

“In one paradigm of testing, we can get both sets of information,” which eliminates the complicated equipment set-up used by neuro-ophthalmologists, and makes eye assessments more readily available, she said.

“We can make this accessible for more clinicians and more patients, even eventually having it in an emergency setting or an outpatient clinic setting.”

Dr. Graves discussed this and other next-generation digital tools at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Currently, patients with MS can use accelerometers that determine overall activity level and devices that detect heart rate variability. They can also access mobile apps that track symptoms and medication adherence.
 

Limited sensitivity of current tools

However, current tools used to determine disability in MS are limited. The classification of MS subtypes is largely retrospective, and the preferred Expanded Disability Status Scale (EDSS) is problematic, said Dr. Graves.

For example, she said, the EDSS lacks sensitivity to short-term changes, depends on ambulation, and only poorly captures upper-extremity disability. “We know our patients are experiencing change and we know the tools we have now aren’t capturing that.”

She used the example of a pianist who can no longer play well with her right hand, but this can’t be detected with current tools. A device that uses technology from the gaming and computer control industry “can quantify that” change, said Dr. Graves.

She added that tools in development can detect not only motor and visual dysfunction but also cognitive dysfunction, potentially aiding clinical care and facilitating more rapid trials of disease modifying agents in MS. “Rather than having descriptive terms, these digital tools will help us quantitate change so we can take action.”

The new sensing devices use multiple sensors, including accelerometers, gyroscopes, and surface electrical signals in muscles to capture very precise temporal and textural information related to movement. Their development uses traditional signal processing as well as artificial intelligence approaches.

Dr. Graves’s device, the MSight, captures afferent and efferent visual function with a single mobile brain-computer interface.

At least 80% of patients with MS have some measurable dysfunction in the afferent system that oversees how light from the environment is turned into images in the brain, explained Dr. Graves. The efferent visual system that controls eye movements is also “profoundly impacted by MS” with, again, up to 80% of patients with MS experiencing related dysfunction, she said.

Her new visual system correlates with burden of MS disease, said Dr. Graves. “Having efferent and eye tracking problems correlates with overall disability and walking function.”

The information collected by this new device “tends to be really helpful even in people who don’t appear to be disabled with MS because it’s literally a window into the brain to let us see what’s happening,” said Dr. Graves.

She and her colleagues are testing the MSight device in clinical trials and have a provisional patent for it.
 

Finger and foot taps

Another device her team is developing detects minute changes over several months in finger and toe tap movements that are very difficult for the human eye to capture.

Dr. Graves reported on a cross sectional validation study of 17 patients with MS showing the foot and finger tap measures strongly correlated with the EDSS and patient-reported outcomes (P < .0001). A longitudinal analysis of 68 patients with MS found information on finger and foot taps distinguished those with progressive from those with relapsing MS.

“We found that in patients with progressive MS, the information in the signal we were capturing was changing, whereas someone with relapsing MS had a little bit of that but much less,” said Dr. Graves.

These and other novel, self-contained devices “will provide a set of neurological vital signs that we can put in the hands of clinicians and patients” with MS, as is currently being done in other specialties – for example, cardiology, said Dr. Graves.
 

Intriguing, exciting

In a comment, David Gosselin, PhD, associate professor, department of molecular medicine, Laval University, Quebec City, who cochaired the session featuring next-generation digital tools, said more sensitive monitoring technologies coming down the pipeline are “intriguing and exciting.”

While the devices are still in early development, “the eventual integration of such noninvasive technology that measures subtle limb muscle function has the potential to redefine clinical practice,” said Dr. Gosselin.

“The idea of sampling a patient’s ability to move about on a frequent basis, perhaps even daily, and to generate data profiles over time, certainly hold promise with respect to tracking disease evolution and responses to treatments on a scale not accessible before.”

A more immediate and comprehensive overview of a patient’s response to a treatment “could yield more rapid insights into the effectiveness of novel therapies tested in clinical trials,” said Dr. Gosselin. “This could have profound implications.”

Future digital devices may facilitate monitoring of patients in more remote communities, too, said Dr. Gosselin.

However, before these technologies can be introduced on a broad level, several outstanding issues will have to be addressed, the most important being the streams of data they generate, said Dr. Gosselin.

“This clearly has the potential to overwhelm neurologists in the assessment of their patients’ conditions,” he said. “Which information, and in which analyzed forms, truly provides meaningful insights into patients’ conditions will need to be identified, and this will take time.”

Privacy may be an issue, too, said Dr. Gosselin. Some patients may be less inclined to comply with a procedure “that can capture and record their life so extensively.”

And how health care insurance providers can interface with these comprehensive profiles of patients’ lives will also have to be considered, he said.

Dr. Graves has a provisional patent on the MSight device; has received research support from MMSS, Octave, Biogen EMD Serono, Novartis, ATARA Biotherapeutics, and ABM; has served on advisory boards for Bayer, Genentech, and TG therapeutic and a pediatric clinical trial steering committee for Novartis; and has consulted for Google. Dr. Gosselin reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A new wearable device detects, with a high degree of precision, various types of visual dysfunction, which eventually affects most patients with multiple sclerosis (MS). The device uses advanced digital technology to stimulate the retina and the occipital cortex while also stimulating the eye tracking system, and reports out this data, one of its developers, Jennifer Graves, MD, PhD, director of neuroimmunology research, University of California, San Diego, said in an interview.

“In one paradigm of testing, we can get both sets of information,” which eliminates the complicated equipment set-up used by neuro-ophthalmologists, and makes eye assessments more readily available, she said.

“We can make this accessible for more clinicians and more patients, even eventually having it in an emergency setting or an outpatient clinic setting.”

Dr. Graves discussed this and other next-generation digital tools at the annual meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Currently, patients with MS can use accelerometers that determine overall activity level and devices that detect heart rate variability. They can also access mobile apps that track symptoms and medication adherence.
 

Limited sensitivity of current tools

However, current tools used to determine disability in MS are limited. The classification of MS subtypes is largely retrospective, and the preferred Expanded Disability Status Scale (EDSS) is problematic, said Dr. Graves.

For example, she said, the EDSS lacks sensitivity to short-term changes, depends on ambulation, and only poorly captures upper-extremity disability. “We know our patients are experiencing change and we know the tools we have now aren’t capturing that.”

She used the example of a pianist who can no longer play well with her right hand, but this can’t be detected with current tools. A device that uses technology from the gaming and computer control industry “can quantify that” change, said Dr. Graves.

She added that tools in development can detect not only motor and visual dysfunction but also cognitive dysfunction, potentially aiding clinical care and facilitating more rapid trials of disease modifying agents in MS. “Rather than having descriptive terms, these digital tools will help us quantitate change so we can take action.”

The new sensing devices use multiple sensors, including accelerometers, gyroscopes, and surface electrical signals in muscles to capture very precise temporal and textural information related to movement. Their development uses traditional signal processing as well as artificial intelligence approaches.

Dr. Graves’s device, the MSight, captures afferent and efferent visual function with a single mobile brain-computer interface.

At least 80% of patients with MS have some measurable dysfunction in the afferent system that oversees how light from the environment is turned into images in the brain, explained Dr. Graves. The efferent visual system that controls eye movements is also “profoundly impacted by MS” with, again, up to 80% of patients with MS experiencing related dysfunction, she said.

Her new visual system correlates with burden of MS disease, said Dr. Graves. “Having efferent and eye tracking problems correlates with overall disability and walking function.”

The information collected by this new device “tends to be really helpful even in people who don’t appear to be disabled with MS because it’s literally a window into the brain to let us see what’s happening,” said Dr. Graves.

She and her colleagues are testing the MSight device in clinical trials and have a provisional patent for it.
 

Finger and foot taps

Another device her team is developing detects minute changes over several months in finger and toe tap movements that are very difficult for the human eye to capture.

Dr. Graves reported on a cross sectional validation study of 17 patients with MS showing the foot and finger tap measures strongly correlated with the EDSS and patient-reported outcomes (P < .0001). A longitudinal analysis of 68 patients with MS found information on finger and foot taps distinguished those with progressive from those with relapsing MS.

“We found that in patients with progressive MS, the information in the signal we were capturing was changing, whereas someone with relapsing MS had a little bit of that but much less,” said Dr. Graves.

These and other novel, self-contained devices “will provide a set of neurological vital signs that we can put in the hands of clinicians and patients” with MS, as is currently being done in other specialties – for example, cardiology, said Dr. Graves.