A Maryland-based physician assistant was sentenced to 37 months in federal prison for conspiracy to distribute and dispense oxycodone, fentanyl, methadone, and alprazolam at a pain management clinic.

Niyazz/ThinkStock

A U.S. District Judge sentenced William Soyke, 68, of Hanover, Penn., for acting outside the scope of professional practice and not for a legitimate medical purpose, according to the U.S. Attorney’s Office in Maryland. The 37-month prison term will be followed by 3 years of supervised release.

According to the plea agreement, Mr. Soyke worked as a physician assistant with Rosen-Hoffberg Rehabilitation and Pain Management from 2011 to 2018, where he treated patients during follow-up doctor appointments. As a physician assistant, Mr. Soyke had privileges to prescribe controlled substance medications, but was required to operate under a delegation agreement with the Rosen-Hoffberg owners.  

In his plea, Mr. Soyke said that he believed the owners, Norman Rosen, MD, and Howard Hoffberg, MD, prescribed excessive levels of opioids. Despite Mr. Soyke’s attempts to lower patient’s prescription doses, both doctors overruled the PA’s opinion, according to the plea agreement. Also, if another health care provider within the practice declined to treat a patient because of the patient’s aberrant behavior – such as failing a drug screening test for illicit drugs or selling their prescriptions – Dr. Rosen and Dr. Hoffberg would assume that patient’s care, the report continued.

As stated in the plea agreement, Mr. Sokye was aware that many of the patients presenting to Rosen-Hoffberg Rehabilitation and Pain Management did not have a legitimate medical need for the oxycodone, fentanyl, alprazolam, and methadone they were being prescribed. Nevertheless, Mr. Soyke issued prescriptions for these drugs to patients without a legitimate medical need and outside the bounds of acceptable medical practice, according to the release.

Mr. Soyke also admitted that in several instances he engaged in sexual, physical contact with female patients who were attempting to get prescriptions, the plea agreement stated. Specifically, Mr. Soyke asked some female customers to engage in a range of motion test, and while they were bending over, he would position himself behind them such that his genitalia would rub against the customers’ buttocks through their clothes. These patients often submitted to this sexual abuse for fear of not getting the medications to which they were addicted, according to the press release.

Although the female patients complained to Dr. Rosen and Dr. Hoffberg about Mr. Soyke’s behavior, the doctors did not fire Mr. Soyke because the PA saw the largest number of patients at the practice and generated significant revenue, according to federal officials.

Dr. Hoffberg, the associate medical director and part-owner of the practice, pleaded guilty in June to accepting kickbacks from pharmaceutical company Insys Therapeutics in exchange for prescribing an opioid drug called Subsys (a fentanyl sublingual spray) marketed by Insys for breakthrough pain in cancer patients for off-label purposes. He will be sentenced in September and faces a maximum of 5 years in federal prison.

Mr. Soyke pled guilty to a federal drug charge in July 2019. In announcing the guilty plea then, U.S. Attorney Robert Hur said, “Opioid overdoses are killing thousands of Marylanders each year, and opioid addiction is fueled by health care providers who prescribe drugs for people without a legitimate medical need. Doctors and other medical professionals who irresponsibly write opioid prescriptions are acting like street-corner drug pushers.”

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

A Maryland-based physician assistant was sentenced to 37 months in federal prison for conspiracy to distribute and dispense oxycodone, fentanyl, methadone, and alprazolam at a pain management clinic.

Niyazz/ThinkStock

A U.S. District Judge sentenced William Soyke, 68, of Hanover, Penn., for acting outside the scope of professional practice and not for a legitimate medical purpose, according to the U.S. Attorney’s Office in Maryland. The 37-month prison term will be followed by 3 years of supervised release.

According to the plea agreement, Mr. Soyke worked as a physician assistant with Rosen-Hoffberg Rehabilitation and Pain Management from 2011 to 2018, where he treated patients during follow-up doctor appointments. As a physician assistant, Mr. Soyke had privileges to prescribe controlled substance medications, but was required to operate under a delegation agreement with the Rosen-Hoffberg owners.  

In his plea, Mr. Soyke said that he believed the owners, Norman Rosen, MD, and Howard Hoffberg, MD, prescribed excessive levels of opioids. Despite Mr. Soyke’s attempts to lower patient’s prescription doses, both doctors overruled the PA’s opinion, according to the plea agreement. Also, if another health care provider within the practice declined to treat a patient because of the patient’s aberrant behavior – such as failing a drug screening test for illicit drugs or selling their prescriptions – Dr. Rosen and Dr. Hoffberg would assume that patient’s care, the report continued.

As stated in the plea agreement, Mr. Sokye was aware that many of the patients presenting to Rosen-Hoffberg Rehabilitation and Pain Management did not have a legitimate medical need for the oxycodone, fentanyl, alprazolam, and methadone they were being prescribed. Nevertheless, Mr. Soyke issued prescriptions for these drugs to patients without a legitimate medical need and outside the bounds of acceptable medical practice, according to the release.

Mr. Soyke also admitted that in several instances he engaged in sexual, physical contact with female patients who were attempting to get prescriptions, the plea agreement stated. Specifically, Mr. Soyke asked some female customers to engage in a range of motion test, and while they were bending over, he would position himself behind them such that his genitalia would rub against the customers’ buttocks through their clothes. These patients often submitted to this sexual abuse for fear of not getting the medications to which they were addicted, according to the press release.

Although the female patients complained to Dr. Rosen and Dr. Hoffberg about Mr. Soyke’s behavior, the doctors did not fire Mr. Soyke because the PA saw the largest number of patients at the practice and generated significant revenue, according to federal officials.

Dr. Hoffberg, the associate medical director and part-owner of the practice, pleaded guilty in June to accepting kickbacks from pharmaceutical company Insys Therapeutics in exchange for prescribing an opioid drug called Subsys (a fentanyl sublingual spray) marketed by Insys for breakthrough pain in cancer patients for off-label purposes. He will be sentenced in September and faces a maximum of 5 years in federal prison.

Mr. Soyke pled guilty to a federal drug charge in July 2019. In announcing the guilty plea then, U.S. Attorney Robert Hur said, “Opioid overdoses are killing thousands of Marylanders each year, and opioid addiction is fueled by health care providers who prescribe drugs for people without a legitimate medical need. Doctors and other medical professionals who irresponsibly write opioid prescriptions are acting like street-corner drug pushers.”

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

A Maryland-based physician assistant was sentenced to 37 months in federal prison for conspiracy to distribute and dispense oxycodone, fentanyl, methadone, and alprazolam at a pain management clinic.

Niyazz/ThinkStock

A U.S. District Judge sentenced William Soyke, 68, of Hanover, Penn., for acting outside the scope of professional practice and not for a legitimate medical purpose, according to the U.S. Attorney’s Office in Maryland. The 37-month prison term will be followed by 3 years of supervised release.

According to the plea agreement, Mr. Soyke worked as a physician assistant with Rosen-Hoffberg Rehabilitation and Pain Management from 2011 to 2018, where he treated patients during follow-up doctor appointments. As a physician assistant, Mr. Soyke had privileges to prescribe controlled substance medications, but was required to operate under a delegation agreement with the Rosen-Hoffberg owners.  

In his plea, Mr. Soyke said that he believed the owners, Norman Rosen, MD, and Howard Hoffberg, MD, prescribed excessive levels of opioids. Despite Mr. Soyke’s attempts to lower patient’s prescription doses, both doctors overruled the PA’s opinion, according to the plea agreement. Also, if another health care provider within the practice declined to treat a patient because of the patient’s aberrant behavior – such as failing a drug screening test for illicit drugs or selling their prescriptions – Dr. Rosen and Dr. Hoffberg would assume that patient’s care, the report continued.

As stated in the plea agreement, Mr. Sokye was aware that many of the patients presenting to Rosen-Hoffberg Rehabilitation and Pain Management did not have a legitimate medical need for the oxycodone, fentanyl, alprazolam, and methadone they were being prescribed. Nevertheless, Mr. Soyke issued prescriptions for these drugs to patients without a legitimate medical need and outside the bounds of acceptable medical practice, according to the release.

Mr. Soyke also admitted that in several instances he engaged in sexual, physical contact with female patients who were attempting to get prescriptions, the plea agreement stated. Specifically, Mr. Soyke asked some female customers to engage in a range of motion test, and while they were bending over, he would position himself behind them such that his genitalia would rub against the customers’ buttocks through their clothes. These patients often submitted to this sexual abuse for fear of not getting the medications to which they were addicted, according to the press release.

Although the female patients complained to Dr. Rosen and Dr. Hoffberg about Mr. Soyke’s behavior, the doctors did not fire Mr. Soyke because the PA saw the largest number of patients at the practice and generated significant revenue, according to federal officials.

Dr. Hoffberg, the associate medical director and part-owner of the practice, pleaded guilty in June to accepting kickbacks from pharmaceutical company Insys Therapeutics in exchange for prescribing an opioid drug called Subsys (a fentanyl sublingual spray) marketed by Insys for breakthrough pain in cancer patients for off-label purposes. He will be sentenced in September and faces a maximum of 5 years in federal prison.

Mr. Soyke pled guilty to a federal drug charge in July 2019. In announcing the guilty plea then, U.S. Attorney Robert Hur said, “Opioid overdoses are killing thousands of Marylanders each year, and opioid addiction is fueled by health care providers who prescribe drugs for people without a legitimate medical need. Doctors and other medical professionals who irresponsibly write opioid prescriptions are acting like street-corner drug pushers.”

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

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

Patients on immunosuppressive or immunomodulatory therapy should receive a third dose of either the Pfizer-BioNTech COVID-19 vaccine or the Moderna COVID-19 vaccine at least 28 days after the second dose of either of these two mRNA vaccines, according to updated recommendations from the American College of Rheumatology.

Mongkolchon Akesin/Getty Images

The update follows the Centers for Disease Control and Prevention’s recommendation that certain immunocompromised patients receive a third dose of an mRNA vaccine to reduce their risk of contracting COVID-19.

Individuals receiving the Pfizer vaccine must be aged 12 years and older, while those receiving the Moderna vaccine must be 18 years and older, the ACR emphasized.

“These statements were based upon a dearth of high-quality data and are not intended to replace clinical judgment,” the authors wrote. “Modifications made to treatment plans, particularly in complex rheumatic disease patients, are highly disease, patient, geography, and time specific and, therefore, must be individualized as part of a shared decision-making process.”

The task force recommended using the same mRNA vaccine booster as the patient received for their initial two-dose series when possible, but notes that either mRNA vaccine is acceptable, and recommends the mRNA vaccine for patients who have yet to receive any vaccine because of the availability of the booster. The task force emphasized that they achieved no consensus on recommending a booster mRNA vaccine to patients who received a single dose of Johnson & Johnson vaccine because the safety data are uncertain.

The updated guidance also identifies the Food and Drug Administration’s emergency use authorization in August for the use of REGEN-COV monoclonal antibody treatment for emergency postexposure prophylaxis for COVID-19 in adults and adolescents aged 12 years and older who weigh at least 40 kg and are at increased risk for severe COVID-19, which includes patients receiving immunosuppressive or immunomodulatory therapies other than hydroxychloroquine. Patients who have been exposed to an individual with COVID-19 should discuss this treatment with their health care provider as an added precaution; however, the guidance emphasized that the prophylactic treatment is not a substitute for COVID-19 vaccination.

The recommendations advise clinicians to counsel their patients to refrain from taking certain immunomodulatory or immunosuppressive medications for 1-2 weeks after booster vaccination if disease activity allows, with the exception of glucocorticoids and anticytokines such as tumor necrosis factor inhibitors and others including interleukin-17, IL-12/23, IL-23, IL-1R, IL-6R antagonists, for which the task force did not achieve a consensus recommendation.

The guidance notes that patients on rituximab or other anti-CD20 medications “should discuss the optimal timing [of the booster] with their rheumatology provider” and that some practitioners measure CD19 B cells as a tool with which to time the booster and subsequent rituximab dosing. For those who elect to dose without such information, or for whom such measurement is not available or feasible, provide the booster 2-4 weeks before next anticipated rituximab dose (e.g., at month 5.0 or 5.5 for patients on an every-6-month rituximab dosing schedule).”

There was strong consensus from the task force that health care providers “should not routinely order any lab testing (e.g., antibody tests for IgM and/or IgG to spike or nucleocapsid proteins) to assess immunity to COVID-19 post vaccination, nor to assess the need for vaccination in a yet-unvaccinated person.”

“The updated information from the ACR addresses not only booster vaccination but also other important and practical issues facing rheumatology providers and their patients related to the pandemic,” said task force chair Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, in an ACR statement announcing the updates.

“Although the guidance is issued in light of the best evidence available, the science regarding COVID-19 vaccination as it affects the practice of rheumatology is undergoing rapid evolution,” he noted. “We need direct evidence such as that from randomized trials to inform the best practices of what we can do to protect our patients from SARS-CoV-2.”

The update retains the current recommendations that rheumatology patients follow all public health guidelines regarding physical distancing and other preventive measures following vaccination, but the task force did not recommend exceeding current public health guidance. “The appropriateness for continued preventive measures (e.g., masking, physical distancing) should be discussed with patients as their rheumatology providers deem appropriate,” they wrote.

The full updated version of the ACR’s COVID-19 Vaccine Clinical Guidance for Patients with Rheumatic and Musculoskeletal Diseases will be published in Arthritis & Rheumatology. The summary was developed by the ACR COVID-19 Vaccine Clinical Guidance Task Force, which included 9 rheumatologists, 2 infectious disease specialists, and 2 public health experts with current or past employment history with the CDC.

The ACR encourages clinicians with questions or concerns to email [email protected] for support.

Background: Many articles have been published on sepsis and mortality in ICUs, but there are not many analyzing outcomes in patients with infections, nor types of infections. More information on the infection rate, types of infection, and possible impact on mortality should heighten awareness of infection effects, as well as guide resource allocation and help direct policy development for diagnosis and treatment.

Despite limitations related to being an observational study, 24-hour point evaluation, a centrally controlled database, and different geographic locations, this study elucidated the world-wide prevalence of ICU infection and high hospital-in mortality in those patients.

Bottom line: There is a high prevalence of infection in ICUs: 43%-60% depending on location. This is associated with 30% in-hospital mortality.

Citation: Vincent J-L et al. Prevalance and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020 Mar 24;323(15):1478-87.

Dr. Rogozinska is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Many articles have been published on sepsis and mortality in ICUs, but there are not many analyzing outcomes in patients with infections, nor types of infections. More information on the infection rate, types of infection, and possible impact on mortality should heighten awareness of infection effects, as well as guide resource allocation and help direct policy development for diagnosis and treatment.

Despite limitations related to being an observational study, 24-hour point evaluation, a centrally controlled database, and different geographic locations, this study elucidated the world-wide prevalence of ICU infection and high hospital-in mortality in those patients.

Bottom line: There is a high prevalence of infection in ICUs: 43%-60% depending on location. This is associated with 30% in-hospital mortality.

Citation: Vincent J-L et al. Prevalance and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020 Mar 24;323(15):1478-87.

Dr. Rogozinska is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

Background: Many articles have been published on sepsis and mortality in ICUs, but there are not many analyzing outcomes in patients with infections, nor types of infections. More information on the infection rate, types of infection, and possible impact on mortality should heighten awareness of infection effects, as well as guide resource allocation and help direct policy development for diagnosis and treatment.

Despite limitations related to being an observational study, 24-hour point evaluation, a centrally controlled database, and different geographic locations, this study elucidated the world-wide prevalence of ICU infection and high hospital-in mortality in those patients.

Bottom line: There is a high prevalence of infection in ICUs: 43%-60% depending on location. This is associated with 30% in-hospital mortality.

Citation: Vincent J-L et al. Prevalance and outcomes of infection among patients in intensive care units in 2017. JAMA. 2020 Mar 24;323(15):1478-87.

Dr. Rogozinska is a hospitalist and assistant professor of medicine at UK HealthCare, Lexington, Ky.

An internist will never forget the dark secret his patient revealed during a routine visit – or the grim aftermath. 

The patient, who had a progressive, incurable neurological condition, confided that he planned to kill himself. The patient intended to conceal the true manner and make the death look natural.

“[He planned to do it] very carefully at home so no one would know,” said the internist, who remains anonymous. “[He shared] the methods he would use.”

Perhaps more shocking than the patient’s confession was the physician’s response. 

“He did not require my help to do what he planned, and I did not try to stop him,” said the internist. “I reported his death as ‘natural causes’ and never told anyone.”

The account comes from a response to Medscape’s 2020 Ethics Report in which physicians were asked about their toughest ethical dilemmas. Many physicians shared secrets and dilemmas that have haunted them for years.  An ob.gyn., for instance, wrote about struggling with whether to tell a father that his newborn baby was not his genetic child. The newborn had a blood type that made it impossible for the father to be biologically related to the infant, the anonymous doctor wrote.

“I told the wife who then informed me she had a lover,” the ob.gyn. said. “I never told the husband.”

It’s uncertain whether carrying the burden of such hidden knowledge affected the physicians involved in these cases. However, in general, secrets can weigh heavily on the minds of those who keep them and can contribute to stress, said Malia Mason, PhD, a psychologist and dean of research at Columbia Business School in New York. Holding onto secrets can cause depression and anxiety, research shows. The more often people think about the secret, the greater the impact, according to a recent study coauthored by Dr. Mason.

“Keeping a secret diminishes well-being,” Dr. Mason said. “It makes people feel socially distant. It lowers relationship satisfaction, and it leads people to feel inauthentic. The reason that secrets do this is because people think about them all the time. The more you think about it, the more you see these consequences.”

Feelings that stem from a secret depend on the content. The more immoral a secret is thought to be, the more people feel ashamed, according to a 2021 analysis of thousands of secrets, reported by Michael L. Slepian, PhD, and Alex Koch, PhD. However, secrets more related to a person’s profession are often internalized differently, the study found. The more a secret fell higher on the profession/goal-oriented dimension, the more people felt they had insight into the secret, according to the analysis. For example, having clear thinking about the secret and/or knowing how to handle it. 

“The more shame participants felt from their secret, the more they indicated the secret hurt their well-being,” Dr. Slepian and Dr. Koch wrote in the study. “The more insight participants felt they had into their secret, the less they indicated the secret hurt their well-being.”
 

Suspicious deaths exposed after investigations

The internist’s account of keeping his patient’s suicide a secret raises many questions, such as how the patient masked his manner of death. The internist did not share any more details about the incident. 

Suicides are among the most challenging manners of deaths to certify, according to James Gill, MD, a pathologist and president of the National Association of Medical Examiners. Death investigators must demonstrate intent, meaning the individuals caused the injury to intentionally harm themselves. Fewer than half of people who die by suicide leave a note, Dr. Gill said, so investigators can’t rely on the absence or the presence of a note in making their determination.

A decedent who had cancer or a severe neurological disorder presents further challenges, said Dr. Gill, who serves as chief medical examiner for the state of Connecticut.

“These [deaths] may not be unexpected and may not be reported to the medical examiner/coroner,” Dr. Gill said. “If there is no suspicion and the treating doctor is willing to sign the death certificate, the death will not come under the jurisdiction of the medical examiner.”

Dr. Gill recalled a death his colleague once investigated that appeared to be natural but emerged as something else after a deeper look. 

A woman with metastatic breast cancer was about to be discharged from a hospital into hospice the next morning. The night before, she had a “going away” party with friends who came to visit her in the hospital. Shortly after the friends left, the woman was found dead. Because of her condition, she could have died at any time, Dr. Gill said, but she also had a history of depression and hospital staff were suspicious. The death was reported to the medical examiner’s office.

Toxicology testing found markedly elevated concentrations of phenytoin and pentobarbital, neither of which were prescribed during her hospital stay. Dr. Gill said it turned out that the woman and her friends worked at a veterinarian’s office, and the medication they used to euthanize dogs was a combination of phenytoin and pentobarbital.

“The death was certified as a homicide because of the direct actions of another, but a reasonable argument could be made for suicide,” Dr. Gill said.

In a similar case reported in the journal Science & Justice, a 64-year-old cardiologist was found lifeless by his wife after he collapsed near the stairs of his home. Next to his body was a bottle of whiskey and two cups, one that appeared to be used for the alcohol and one with a yellowish liquid smelling of honey. The wife reported that her husband always drank whiskey with honey before bed. The death was initially classified as natural, but after vehement protest by the family, a forensic autopsy was performed. 

Prior to the autopsy, death investigators learned the decedent, who was a well-known and successful practitioner in his community, had Parkinson’s disease. At times, he could not sign his prescriptions because of the increasing tremor in his hands, according to the case study. Investigators learned the patient’s mother had also suffered from Parkinson’s, and that her son had witnessed her decline. 

The autopsy revealed only nonspecific lesions such as acute stasis of the viscera, moderate pulmonary and cerebral edema, and moderate generalized atheromatosis. Histological examinations did not yield any unusual findings.

An analysis of the beverage containers detected pentobarbital in the yellowish syrup residue of the second cup. Testing of the doctor’s peripheral blood revealed the presence of a metabolite of pentobarbital, ethanol, and traces of phenobarbital. In addition, a urine analysis showed the presence of venlafaxine, an antidepressant, as well as the benzophenone of lorazepam, a sedating benzodiazepine, and metoclopramide, an antiemetic.

Lead author C. Brandt-Casadevall, MD, and colleagues wrote that the levels were clearly compatible with a scenario of a pentobarbital overdose with a lethal outcome.

“... It is obvious that the victim attempted to hide his suicide from his family circle,” Dr. Brandt-Casadevall and colleagues wrote. “Thus, we obtained no evidence indicating that he might have spoken at any point of putting an end to his life. There was no written note. The victim did not wait to be alone at home. Instead, he committed his act in a routine situation: his wife was watching television late at night and he was upstairs, presumably going to sleep. Thus, he had one to two hours at his disposal, and he ingested a very fast-acting drug which would make any attempt at reanimation impossible, even after a brief period of time. This may have induced the physician in charge to believe that the cause of death was cardiac origin, a likely hypothesis given the age of the victim.”
 

What to do when a terminally ill patient talks suicide

When a terminally ill patient expresses the desire to end his or her life, it’s important to understand that desire is often a result of existential suffering, a sense of hopelessness, and lack of social support, said Lynn A. Jansen, PhD, a bioethicist at the University of Arizona in Tucson.

“The duty of beneficence requires that physicians attempt to provide the support and care that is needed,” said Dr. Jansen. “Here, interdisciplinary teamwork is important and should be utilized. Physicians should refer patients to professionals, such as social workers, pastoral care, psychologists, etc., who are better able to address these issues.”

The rate of desire for a hastened death among terminally ill patients ranges from 17% to 45%, depending on the population studied and how the desire is evaluated, according to an analysis in the Primary Care Companion to the Journal of Clinical Psychiatry. In one study, 14% of about 130 palliative care patients with cancer had a strong desire to quicken the dying process.

In addition, patients with neurologic disorders have a significantly higher suicide rate than that of those without neurologic disorders, a recent JAMA study found. About 1 in 150 patients diagnosed with a neurological disorder dies by suicide, the analysis determined. 

A tricky point to remember is that a desire by a terminally ill patient to hasten his or her death by suicide should not be taken by itself to indicate depression, Dr. Jansen noted.

“In principle, such patients can make an autonomous decision to end their lives,” she said. “However, the expression of such a desire is very often associated with depression and forms of suffering that can be effectively addressed by the health care team.”

Physicians can also explore other avenues with the patient such as palliative care or making sure adequate pain relief is available, added Robert Klitzman, MD, professor of psychiatry and academic director of the master of science in bioethics program at Columbia University, New York.

“If they are saying it’s because they are distressed, ethically, a doctor can and should find ways to decrease their distress,” he said.

Of course, those who practice in the U.S. jurisdictions that have physician-assisted-dying laws have different legal and ethical elements to consider. Physicians in these areas have no ethical duty to participate in the process, Dr. Jansen said, but they have a duty to refer patients who express a desire to pursue physician aid-in-dying to another provider who can assist them.

Physician aid-in-dying laws vary somewhat so it’s important that physicians in these areas be aware of their specific statute, Dr. Klitzman said. California, Colorado, Hawaii, Maine, New Jersey, New Mexico, Oregon, Vermont, Washington, and the District of Columbia have these laws.

“In these states, if a terminally ill patient says they don’t want to live anymore, a physician would first decide if this is a result of depression or if it’s a request for physician aid-in-dying,” he said. “Even then, in most cases, the patient would be evaluated by not one, but two different health professionals at two different points. We want to see if it is a consistent decision that the person has made that they want physician aid-in-dying, and not just that they’ve had a bad day or a setback in their treatment.”

In the case of the internist who told no one of his patient’s suicide plan, Dr. Klitzman said he would have dug deeper into the patient’s mindset.

“Not knowing anything about the patient or the doctor, I would have responded differently,” he said. “I think a physician should address why a patient feels that way. They may feel their pain is unbearable, and we potentially offer more pain relief. Maybe the patient shows evidence of having depression, which may be treatable [with medication]. The patient would then feel better and be able to spend quality time with family and loved ones, make sure their affairs are in order, and have a chance to say goodbye.”

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

An internist will never forget the dark secret his patient revealed during a routine visit – or the grim aftermath. 

The patient, who had a progressive, incurable neurological condition, confided that he planned to kill himself. The patient intended to conceal the true manner and make the death look natural.

“[He planned to do it] very carefully at home so no one would know,” said the internist, who remains anonymous. “[He shared] the methods he would use.”

Perhaps more shocking than the patient’s confession was the physician’s response. 

“He did not require my help to do what he planned, and I did not try to stop him,” said the internist. “I reported his death as ‘natural causes’ and never told anyone.”

The account comes from a response to Medscape’s 2020 Ethics Report in which physicians were asked about their toughest ethical dilemmas. Many physicians shared secrets and dilemmas that have haunted them for years.  An ob.gyn., for instance, wrote about struggling with whether to tell a father that his newborn baby was not his genetic child. The newborn had a blood type that made it impossible for the father to be biologically related to the infant, the anonymous doctor wrote.

“I told the wife who then informed me she had a lover,” the ob.gyn. said. “I never told the husband.”

It’s uncertain whether carrying the burden of such hidden knowledge affected the physicians involved in these cases. However, in general, secrets can weigh heavily on the minds of those who keep them and can contribute to stress, said Malia Mason, PhD, a psychologist and dean of research at Columbia Business School in New York. Holding onto secrets can cause depression and anxiety, research shows. The more often people think about the secret, the greater the impact, according to a recent study coauthored by Dr. Mason.

“Keeping a secret diminishes well-being,” Dr. Mason said. “It makes people feel socially distant. It lowers relationship satisfaction, and it leads people to feel inauthentic. The reason that secrets do this is because people think about them all the time. The more you think about it, the more you see these consequences.”

Feelings that stem from a secret depend on the content. The more immoral a secret is thought to be, the more people feel ashamed, according to a 2021 analysis of thousands of secrets, reported by Michael L. Slepian, PhD, and Alex Koch, PhD. However, secrets more related to a person’s profession are often internalized differently, the study found. The more a secret fell higher on the profession/goal-oriented dimension, the more people felt they had insight into the secret, according to the analysis. For example, having clear thinking about the secret and/or knowing how to handle it. 

“The more shame participants felt from their secret, the more they indicated the secret hurt their well-being,” Dr. Slepian and Dr. Koch wrote in the study. “The more insight participants felt they had into their secret, the less they indicated the secret hurt their well-being.”
 

Suspicious deaths exposed after investigations

The internist’s account of keeping his patient’s suicide a secret raises many questions, such as how the patient masked his manner of death. The internist did not share any more details about the incident. 

Suicides are among the most challenging manners of deaths to certify, according to James Gill, MD, a pathologist and president of the National Association of Medical Examiners. Death investigators must demonstrate intent, meaning the individuals caused the injury to intentionally harm themselves. Fewer than half of people who die by suicide leave a note, Dr. Gill said, so investigators can’t rely on the absence or the presence of a note in making their determination.

A decedent who had cancer or a severe neurological disorder presents further challenges, said Dr. Gill, who serves as chief medical examiner for the state of Connecticut.

“These [deaths] may not be unexpected and may not be reported to the medical examiner/coroner,” Dr. Gill said. “If there is no suspicion and the treating doctor is willing to sign the death certificate, the death will not come under the jurisdiction of the medical examiner.”

Dr. Gill recalled a death his colleague once investigated that appeared to be natural but emerged as something else after a deeper look. 

A woman with metastatic breast cancer was about to be discharged from a hospital into hospice the next morning. The night before, she had a “going away” party with friends who came to visit her in the hospital. Shortly after the friends left, the woman was found dead. Because of her condition, she could have died at any time, Dr. Gill said, but she also had a history of depression and hospital staff were suspicious. The death was reported to the medical examiner’s office.

Toxicology testing found markedly elevated concentrations of phenytoin and pentobarbital, neither of which were prescribed during her hospital stay. Dr. Gill said it turned out that the woman and her friends worked at a veterinarian’s office, and the medication they used to euthanize dogs was a combination of phenytoin and pentobarbital.

“The death was certified as a homicide because of the direct actions of another, but a reasonable argument could be made for suicide,” Dr. Gill said.

In a similar case reported in the journal Science & Justice, a 64-year-old cardiologist was found lifeless by his wife after he collapsed near the stairs of his home. Next to his body was a bottle of whiskey and two cups, one that appeared to be used for the alcohol and one with a yellowish liquid smelling of honey. The wife reported that her husband always drank whiskey with honey before bed. The death was initially classified as natural, but after vehement protest by the family, a forensic autopsy was performed. 

Prior to the autopsy, death investigators learned the decedent, who was a well-known and successful practitioner in his community, had Parkinson’s disease. At times, he could not sign his prescriptions because of the increasing tremor in his hands, according to the case study. Investigators learned the patient’s mother had also suffered from Parkinson’s, and that her son had witnessed her decline. 

The autopsy revealed only nonspecific lesions such as acute stasis of the viscera, moderate pulmonary and cerebral edema, and moderate generalized atheromatosis. Histological examinations did not yield any unusual findings.

An analysis of the beverage containers detected pentobarbital in the yellowish syrup residue of the second cup. Testing of the doctor’s peripheral blood revealed the presence of a metabolite of pentobarbital, ethanol, and traces of phenobarbital. In addition, a urine analysis showed the presence of venlafaxine, an antidepressant, as well as the benzophenone of lorazepam, a sedating benzodiazepine, and metoclopramide, an antiemetic.

Lead author C. Brandt-Casadevall, MD, and colleagues wrote that the levels were clearly compatible with a scenario of a pentobarbital overdose with a lethal outcome.

“... It is obvious that the victim attempted to hide his suicide from his family circle,” Dr. Brandt-Casadevall and colleagues wrote. “Thus, we obtained no evidence indicating that he might have spoken at any point of putting an end to his life. There was no written note. The victim did not wait to be alone at home. Instead, he committed his act in a routine situation: his wife was watching television late at night and he was upstairs, presumably going to sleep. Thus, he had one to two hours at his disposal, and he ingested a very fast-acting drug which would make any attempt at reanimation impossible, even after a brief period of time. This may have induced the physician in charge to believe that the cause of death was cardiac origin, a likely hypothesis given the age of the victim.”
 

What to do when a terminally ill patient talks suicide

When a terminally ill patient expresses the desire to end his or her life, it’s important to understand that desire is often a result of existential suffering, a sense of hopelessness, and lack of social support, said Lynn A. Jansen, PhD, a bioethicist at the University of Arizona in Tucson.

“The duty of beneficence requires that physicians attempt to provide the support and care that is needed,” said Dr. Jansen. “Here, interdisciplinary teamwork is important and should be utilized. Physicians should refer patients to professionals, such as social workers, pastoral care, psychologists, etc., who are better able to address these issues.”

The rate of desire for a hastened death among terminally ill patients ranges from 17% to 45%, depending on the population studied and how the desire is evaluated, according to an analysis in the Primary Care Companion to the Journal of Clinical Psychiatry. In one study, 14% of about 130 palliative care patients with cancer had a strong desire to quicken the dying process.

In addition, patients with neurologic disorders have a significantly higher suicide rate than that of those without neurologic disorders, a recent JAMA study found. About 1 in 150 patients diagnosed with a neurological disorder dies by suicide, the analysis determined. 

A tricky point to remember is that a desire by a terminally ill patient to hasten his or her death by suicide should not be taken by itself to indicate depression, Dr. Jansen noted.

“In principle, such patients can make an autonomous decision to end their lives,” she said. “However, the expression of such a desire is very often associated with depression and forms of suffering that can be effectively addressed by the health care team.”

Physicians can also explore other avenues with the patient such as palliative care or making sure adequate pain relief is available, added Robert Klitzman, MD, professor of psychiatry and academic director of the master of science in bioethics program at Columbia University, New York.

“If they are saying it’s because they are distressed, ethically, a doctor can and should find ways to decrease their distress,” he said.

Of course, those who practice in the U.S. jurisdictions that have physician-assisted-dying laws have different legal and ethical elements to consider. Physicians in these areas have no ethical duty to participate in the process, Dr. Jansen said, but they have a duty to refer patients who express a desire to pursue physician aid-in-dying to another provider who can assist them.

Physician aid-in-dying laws vary somewhat so it’s important that physicians in these areas be aware of their specific statute, Dr. Klitzman said. California, Colorado, Hawaii, Maine, New Jersey, New Mexico, Oregon, Vermont, Washington, and the District of Columbia have these laws.

“In these states, if a terminally ill patient says they don’t want to live anymore, a physician would first decide if this is a result of depression or if it’s a request for physician aid-in-dying,” he said. “Even then, in most cases, the patient would be evaluated by not one, but two different health professionals at two different points. We want to see if it is a consistent decision that the person has made that they want physician aid-in-dying, and not just that they’ve had a bad day or a setback in their treatment.”

In the case of the internist who told no one of his patient’s suicide plan, Dr. Klitzman said he would have dug deeper into the patient’s mindset.

“Not knowing anything about the patient or the doctor, I would have responded differently,” he said. “I think a physician should address why a patient feels that way. They may feel their pain is unbearable, and we potentially offer more pain relief. Maybe the patient shows evidence of having depression, which may be treatable [with medication]. The patient would then feel better and be able to spend quality time with family and loved ones, make sure their affairs are in order, and have a chance to say goodbye.”

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

An internist will never forget the dark secret his patient revealed during a routine visit – or the grim aftermath. 

The patient, who had a progressive, incurable neurological condition, confided that he planned to kill himself. The patient intended to conceal the true manner and make the death look natural.

“[He planned to do it] very carefully at home so no one would know,” said the internist, who remains anonymous. “[He shared] the methods he would use.”

Perhaps more shocking than the patient’s confession was the physician’s response. 

“He did not require my help to do what he planned, and I did not try to stop him,” said the internist. “I reported his death as ‘natural causes’ and never told anyone.”

The account comes from a response to Medscape’s 2020 Ethics Report in which physicians were asked about their toughest ethical dilemmas. Many physicians shared secrets and dilemmas that have haunted them for years.  An ob.gyn., for instance, wrote about struggling with whether to tell a father that his newborn baby was not his genetic child. The newborn had a blood type that made it impossible for the father to be biologically related to the infant, the anonymous doctor wrote.

“I told the wife who then informed me she had a lover,” the ob.gyn. said. “I never told the husband.”

It’s uncertain whether carrying the burden of such hidden knowledge affected the physicians involved in these cases. However, in general, secrets can weigh heavily on the minds of those who keep them and can contribute to stress, said Malia Mason, PhD, a psychologist and dean of research at Columbia Business School in New York. Holding onto secrets can cause depression and anxiety, research shows. The more often people think about the secret, the greater the impact, according to a recent study coauthored by Dr. Mason.

“Keeping a secret diminishes well-being,” Dr. Mason said. “It makes people feel socially distant. It lowers relationship satisfaction, and it leads people to feel inauthentic. The reason that secrets do this is because people think about them all the time. The more you think about it, the more you see these consequences.”

Feelings that stem from a secret depend on the content. The more immoral a secret is thought to be, the more people feel ashamed, according to a 2021 analysis of thousands of secrets, reported by Michael L. Slepian, PhD, and Alex Koch, PhD. However, secrets more related to a person’s profession are often internalized differently, the study found. The more a secret fell higher on the profession/goal-oriented dimension, the more people felt they had insight into the secret, according to the analysis. For example, having clear thinking about the secret and/or knowing how to handle it. 

“The more shame participants felt from their secret, the more they indicated the secret hurt their well-being,” Dr. Slepian and Dr. Koch wrote in the study. “The more insight participants felt they had into their secret, the less they indicated the secret hurt their well-being.”
 

Suspicious deaths exposed after investigations

The internist’s account of keeping his patient’s suicide a secret raises many questions, such as how the patient masked his manner of death. The internist did not share any more details about the incident. 

Suicides are among the most challenging manners of deaths to certify, according to James Gill, MD, a pathologist and president of the National Association of Medical Examiners. Death investigators must demonstrate intent, meaning the individuals caused the injury to intentionally harm themselves. Fewer than half of people who die by suicide leave a note, Dr. Gill said, so investigators can’t rely on the absence or the presence of a note in making their determination.

A decedent who had cancer or a severe neurological disorder presents further challenges, said Dr. Gill, who serves as chief medical examiner for the state of Connecticut.

“These [deaths] may not be unexpected and may not be reported to the medical examiner/coroner,” Dr. Gill said. “If there is no suspicion and the treating doctor is willing to sign the death certificate, the death will not come under the jurisdiction of the medical examiner.”

Dr. Gill recalled a death his colleague once investigated that appeared to be natural but emerged as something else after a deeper look. 

A woman with metastatic breast cancer was about to be discharged from a hospital into hospice the next morning. The night before, she had a “going away” party with friends who came to visit her in the hospital. Shortly after the friends left, the woman was found dead. Because of her condition, she could have died at any time, Dr. Gill said, but she also had a history of depression and hospital staff were suspicious. The death was reported to the medical examiner’s office.

Toxicology testing found markedly elevated concentrations of phenytoin and pentobarbital, neither of which were prescribed during her hospital stay. Dr. Gill said it turned out that the woman and her friends worked at a veterinarian’s office, and the medication they used to euthanize dogs was a combination of phenytoin and pentobarbital.

“The death was certified as a homicide because of the direct actions of another, but a reasonable argument could be made for suicide,” Dr. Gill said.

In a similar case reported in the journal Science & Justice, a 64-year-old cardiologist was found lifeless by his wife after he collapsed near the stairs of his home. Next to his body was a bottle of whiskey and two cups, one that appeared to be used for the alcohol and one with a yellowish liquid smelling of honey. The wife reported that her husband always drank whiskey with honey before bed. The death was initially classified as natural, but after vehement protest by the family, a forensic autopsy was performed. 

Prior to the autopsy, death investigators learned the decedent, who was a well-known and successful practitioner in his community, had Parkinson’s disease. At times, he could not sign his prescriptions because of the increasing tremor in his hands, according to the case study. Investigators learned the patient’s mother had also suffered from Parkinson’s, and that her son had witnessed her decline. 

The autopsy revealed only nonspecific lesions such as acute stasis of the viscera, moderate pulmonary and cerebral edema, and moderate generalized atheromatosis. Histological examinations did not yield any unusual findings.

An analysis of the beverage containers detected pentobarbital in the yellowish syrup residue of the second cup. Testing of the doctor’s peripheral blood revealed the presence of a metabolite of pentobarbital, ethanol, and traces of phenobarbital. In addition, a urine analysis showed the presence of venlafaxine, an antidepressant, as well as the benzophenone of lorazepam, a sedating benzodiazepine, and metoclopramide, an antiemetic.

Lead author C. Brandt-Casadevall, MD, and colleagues wrote that the levels were clearly compatible with a scenario of a pentobarbital overdose with a lethal outcome.

“... It is obvious that the victim attempted to hide his suicide from his family circle,” Dr. Brandt-Casadevall and colleagues wrote. “Thus, we obtained no evidence indicating that he might have spoken at any point of putting an end to his life. There was no written note. The victim did not wait to be alone at home. Instead, he committed his act in a routine situation: his wife was watching television late at night and he was upstairs, presumably going to sleep. Thus, he had one to two hours at his disposal, and he ingested a very fast-acting drug which would make any attempt at reanimation impossible, even after a brief period of time. This may have induced the physician in charge to believe that the cause of death was cardiac origin, a likely hypothesis given the age of the victim.”
 

What to do when a terminally ill patient talks suicide

When a terminally ill patient expresses the desire to end his or her life, it’s important to understand that desire is often a result of existential suffering, a sense of hopelessness, and lack of social support, said Lynn A. Jansen, PhD, a bioethicist at the University of Arizona in Tucson.

“The duty of beneficence requires that physicians attempt to provide the support and care that is needed,” said Dr. Jansen. “Here, interdisciplinary teamwork is important and should be utilized. Physicians should refer patients to professionals, such as social workers, pastoral care, psychologists, etc., who are better able to address these issues.”

The rate of desire for a hastened death among terminally ill patients ranges from 17% to 45%, depending on the population studied and how the desire is evaluated, according to an analysis in the Primary Care Companion to the Journal of Clinical Psychiatry. In one study, 14% of about 130 palliative care patients with cancer had a strong desire to quicken the dying process.

In addition, patients with neurologic disorders have a significantly higher suicide rate than that of those without neurologic disorders, a recent JAMA study found. About 1 in 150 patients diagnosed with a neurological disorder dies by suicide, the analysis determined. 

A tricky point to remember is that a desire by a terminally ill patient to hasten his or her death by suicide should not be taken by itself to indicate depression, Dr. Jansen noted.

“In principle, such patients can make an autonomous decision to end their lives,” she said. “However, the expression of such a desire is very often associated with depression and forms of suffering that can be effectively addressed by the health care team.”

Physicians can also explore other avenues with the patient such as palliative care or making sure adequate pain relief is available, added Robert Klitzman, MD, professor of psychiatry and academic director of the master of science in bioethics program at Columbia University, New York.

“If they are saying it’s because they are distressed, ethically, a doctor can and should find ways to decrease their distress,” he said.

Of course, those who practice in the U.S. jurisdictions that have physician-assisted-dying laws have different legal and ethical elements to consider. Physicians in these areas have no ethical duty to participate in the process, Dr. Jansen said, but they have a duty to refer patients who express a desire to pursue physician aid-in-dying to another provider who can assist them.

Physician aid-in-dying laws vary somewhat so it’s important that physicians in these areas be aware of their specific statute, Dr. Klitzman said. California, Colorado, Hawaii, Maine, New Jersey, New Mexico, Oregon, Vermont, Washington, and the District of Columbia have these laws.

“In these states, if a terminally ill patient says they don’t want to live anymore, a physician would first decide if this is a result of depression or if it’s a request for physician aid-in-dying,” he said. “Even then, in most cases, the patient would be evaluated by not one, but two different health professionals at two different points. We want to see if it is a consistent decision that the person has made that they want physician aid-in-dying, and not just that they’ve had a bad day or a setback in their treatment.”

In the case of the internist who told no one of his patient’s suicide plan, Dr. Klitzman said he would have dug deeper into the patient’s mindset.

“Not knowing anything about the patient or the doctor, I would have responded differently,” he said. “I think a physician should address why a patient feels that way. They may feel their pain is unbearable, and we potentially offer more pain relief. Maybe the patient shows evidence of having depression, which may be treatable [with medication]. The patient would then feel better and be able to spend quality time with family and loved ones, make sure their affairs are in order, and have a chance to say goodbye.”

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

MRI results may not be effective at indicating disability for patients with secondary progressive multiple sclerosis (SPMS), new research suggests. Analysis from the phase 3 ASCEND trial of nearly 900 patients showed that MRI measures were not associated with worsening of scores on the Expanded Disability Status Scale (EDSS), the most widely used physical outcome measure.

The few associations that were shown between MRI measures and clinical outcomes “were with the newer and possibly more sensitive outcomes” – the Timed 25-Foot Walk (T25FW) and Nine-Hole Peg Test (NHPT), wrote the investigators, led by Marcus W. Koch, MD, PhD, associate professor of neurology in the MS program at the University of Calgary, Canada.

However, “it is unclear if these associations are clinically meaningful,” they added.

Worsening on the NHPT at 48 weeks was associated with a 0.86% loss in normalized brain volume; worsening at 96 weeks was associated with a 1.47% loss.

The findings were published online July 26 in the Multiple Sclerosis Journal.
 

ASCEND data analysis

Although brain volume loss occurs in all forms of MS, it is believed to be particularly relevant in SPMS. Clinical trials often use MRI measures of brain volume as endpoints, likely on the assumption that these measures indicate worsening disability.

However, brain volume loss proceeds slowly. Changes that occur during the typical 2-year study period may not be associated with significant physical or cognitive disability.

In the current study, investigators examined data from the ASCEND trial, which assessed the use of natalizumab for patients with SPMS, to examine these potential associations. Eligible participants in ASCEND were between ages 18 and 58 years, had had SPMS for 2 or more years, had had disability progression during the previous year, and had an EDSS score between 3.0 and 6.5 at baseline.

Participants underwent gadolinium-enhanced cranial MRI at screening and at 24, 48, 72, and 96 weeks. MRI outcomes included normalized brain volume, normalized cortical gray matter volume, and normalized whole gray matter volume. The ASCEND investigators also examined the number and volume of T2 and contrast-enhancing lesions.

The study’s clinical outcomes included scores on the EDSS, T25FW, and NHPT, which were administered at baseline and every 12 weeks thereafter. Participants also underwent the Symbol Digit Modalities Test (SDMT), which is a cognitive assessment, at baseline and every 4 weeks thereafter. In addition, 3-month confirmed disability progression was measured every 12 weeks.
 

Few significant associations

The investigators’ analysis included 889 patients (61.9% women; median age, 48 years). The median EDSS score at screening was 6.

Brain volume measures decreased consistently during follow-up. Mean volume loss at 96 weeks was about 1%. In contrast, T2 lesion volume changed little during follow-up. The cumulative number of contrast-enhancing lesions and the cumulative number of new or newly enlarging T2 lesions increased steadily during follow-up.

For an increasing number of participants, scores on the EDSS, NHPT, and T25FW worsened significantly during follow-up. Performance on SDMT, however, changed little. Of all the clinical measures, the NHPT was most consistently associated with MRI measures.

Among patients whose NHPT score worsened at 48 weeks, there was greater loss of normalized brain volume (0.86%, P = .02), normalized cortical gray matter volume (1.15%, P = .03), and normalized whole gray matter volume (1.08%, P = .03) than among those whose NHPT score did not worsen.

Among patients whose NHPT score worsened at 96 weeks, there was greater normalized brain volume loss (1.47%, P = .002), greater increase in T2 lesion volume (4.68%, P = .02), and a greater number of cumulative new or newly enlarging T2 lesions (7.81, P = .03) than those whose NHPT score did not worsen.

After adjusting the data for covariables, the investigators found few significant associations between MRI measures and clinical outcomes. Worsening on the EDSS and SDMT was not associated with any MRI outcome.
 

Important disability contributors missed

The odds ratio of 3-month confirmed worsening on the T25FW at 96 weeks was 2.25 for patients with more than 10 cumulative new or newly enlarging T2 lesions (P = .03). The OR of 3-month confirmed worsening on the NHPT at 96 weeks was 3.04 for patients with more than 10 such lesions (P = .03).

Greater normalized brain volume loss at 48 weeks was associated with a greater risk for worsening disability on the NHPT at 48 and 96 weeks. For patients with a volume loss greater than 1.5%, the OR of worsening NHPT at 96 weeks was 4.69 (P = .05).

Although previous cross-sectional studies have shown correlations between brain volume and cognitive dysfunction, the current investigators found no association between change in SDMT performance and MRI measures.

From the ASCEND dataset, they found that performance on the SDMT unexpectedly improved with time, perhaps because of a practice effect.

“The SDMT may therefore not adequately reflect the steady cognitive decline that people with SPMS experience,” the investigators wrote.

The lack of association between MRI measures and clinical outcomes may indicate that traditional MRI does not measure important contributors to disability, they noted.

“Although the investigated volume measures in this study are currently the most commonly used in clinical trials, newer MRI metrics such as thalamic or corpus callosum atrophy may have a closer relation to clinical outcome,” they added.
 

‘Interesting and provocative’

Commenting on the findings, E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children, Toronto, called the study “interesting and provocative.”

“Other studies previously have shown associations between disability and progression, but many have been cross-sectional,” said Dr. Yeh, who was not involved with the research.

The current study is longitudinal and analyzes carefully documented follow-up data from a clinical trial, she noted. However, the 2-year follow-up period was short, considering the pace at which whole brain volume change occurs, Dr. Yeh said.

Some patients with MS have greater brain volume loss than others. Because of this variability, researchers often examine a population’s average brain volume loss. “When you look at averages, it makes it more difficult to understand if the larger brain volume losses are actually associated with change,” said Dr. Yeh.

She noted that because the study population had high EDSS scores at baseline, it is not surprising that the NHPT and the T25FW were more strongly associated with change in brain volume than the EDSS was. Large changes in EDSS score probably did not occur during follow-up, she added.

“We’ll continue to use the EDSS, because it’s what we have,” said Dr. Yeh. However, newer measures, such as the NHPT and the T25FW, may provide better information, she said. Similarly, composite measures of cognition, such as the Brief International Cognitive Assessment for MS, may be superior to the SDMT but take longer to administer.

“We need to look more deeply at which MRI measures are the best for predicting outcome and that correlate well in a short period of time,” said Dr. Yeh.

These measures could include specific regional brain volumes “and more advanced measures that look at axonal injury or axonal loss.” Studies with longer follow-up are also necessary, she concluded.

The investigators and Dr. Yeh have reported no relevant financial relationships.

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

MRI results may not be effective at indicating disability for patients with secondary progressive multiple sclerosis (SPMS), new research suggests. Analysis from the phase 3 ASCEND trial of nearly 900 patients showed that MRI measures were not associated with worsening of scores on the Expanded Disability Status Scale (EDSS), the most widely used physical outcome measure.

The few associations that were shown between MRI measures and clinical outcomes “were with the newer and possibly more sensitive outcomes” – the Timed 25-Foot Walk (T25FW) and Nine-Hole Peg Test (NHPT), wrote the investigators, led by Marcus W. Koch, MD, PhD, associate professor of neurology in the MS program at the University of Calgary, Canada.

However, “it is unclear if these associations are clinically meaningful,” they added.

Worsening on the NHPT at 48 weeks was associated with a 0.86% loss in normalized brain volume; worsening at 96 weeks was associated with a 1.47% loss.

The findings were published online July 26 in the Multiple Sclerosis Journal.
 

ASCEND data analysis

Although brain volume loss occurs in all forms of MS, it is believed to be particularly relevant in SPMS. Clinical trials often use MRI measures of brain volume as endpoints, likely on the assumption that these measures indicate worsening disability.

However, brain volume loss proceeds slowly. Changes that occur during the typical 2-year study period may not be associated with significant physical or cognitive disability.

In the current study, investigators examined data from the ASCEND trial, which assessed the use of natalizumab for patients with SPMS, to examine these potential associations. Eligible participants in ASCEND were between ages 18 and 58 years, had had SPMS for 2 or more years, had had disability progression during the previous year, and had an EDSS score between 3.0 and 6.5 at baseline.

Participants underwent gadolinium-enhanced cranial MRI at screening and at 24, 48, 72, and 96 weeks. MRI outcomes included normalized brain volume, normalized cortical gray matter volume, and normalized whole gray matter volume. The ASCEND investigators also examined the number and volume of T2 and contrast-enhancing lesions.

The study’s clinical outcomes included scores on the EDSS, T25FW, and NHPT, which were administered at baseline and every 12 weeks thereafter. Participants also underwent the Symbol Digit Modalities Test (SDMT), which is a cognitive assessment, at baseline and every 4 weeks thereafter. In addition, 3-month confirmed disability progression was measured every 12 weeks.
 

Few significant associations

The investigators’ analysis included 889 patients (61.9% women; median age, 48 years). The median EDSS score at screening was 6.

Brain volume measures decreased consistently during follow-up. Mean volume loss at 96 weeks was about 1%. In contrast, T2 lesion volume changed little during follow-up. The cumulative number of contrast-enhancing lesions and the cumulative number of new or newly enlarging T2 lesions increased steadily during follow-up.

For an increasing number of participants, scores on the EDSS, NHPT, and T25FW worsened significantly during follow-up. Performance on SDMT, however, changed little. Of all the clinical measures, the NHPT was most consistently associated with MRI measures.

Among patients whose NHPT score worsened at 48 weeks, there was greater loss of normalized brain volume (0.86%, P = .02), normalized cortical gray matter volume (1.15%, P = .03), and normalized whole gray matter volume (1.08%, P = .03) than among those whose NHPT score did not worsen.

Among patients whose NHPT score worsened at 96 weeks, there was greater normalized brain volume loss (1.47%, P = .002), greater increase in T2 lesion volume (4.68%, P = .02), and a greater number of cumulative new or newly enlarging T2 lesions (7.81, P = .03) than those whose NHPT score did not worsen.

After adjusting the data for covariables, the investigators found few significant associations between MRI measures and clinical outcomes. Worsening on the EDSS and SDMT was not associated with any MRI outcome.
 

Important disability contributors missed

The odds ratio of 3-month confirmed worsening on the T25FW at 96 weeks was 2.25 for patients with more than 10 cumulative new or newly enlarging T2 lesions (P = .03). The OR of 3-month confirmed worsening on the NHPT at 96 weeks was 3.04 for patients with more than 10 such lesions (P = .03).

Greater normalized brain volume loss at 48 weeks was associated with a greater risk for worsening disability on the NHPT at 48 and 96 weeks. For patients with a volume loss greater than 1.5%, the OR of worsening NHPT at 96 weeks was 4.69 (P = .05).

Although previous cross-sectional studies have shown correlations between brain volume and cognitive dysfunction, the current investigators found no association between change in SDMT performance and MRI measures.

From the ASCEND dataset, they found that performance on the SDMT unexpectedly improved with time, perhaps because of a practice effect.

“The SDMT may therefore not adequately reflect the steady cognitive decline that people with SPMS experience,” the investigators wrote.

The lack of association between MRI measures and clinical outcomes may indicate that traditional MRI does not measure important contributors to disability, they noted.

“Although the investigated volume measures in this study are currently the most commonly used in clinical trials, newer MRI metrics such as thalamic or corpus callosum atrophy may have a closer relation to clinical outcome,” they added.
 

‘Interesting and provocative’

Commenting on the findings, E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children, Toronto, called the study “interesting and provocative.”

“Other studies previously have shown associations between disability and progression, but many have been cross-sectional,” said Dr. Yeh, who was not involved with the research.

The current study is longitudinal and analyzes carefully documented follow-up data from a clinical trial, she noted. However, the 2-year follow-up period was short, considering the pace at which whole brain volume change occurs, Dr. Yeh said.

Some patients with MS have greater brain volume loss than others. Because of this variability, researchers often examine a population’s average brain volume loss. “When you look at averages, it makes it more difficult to understand if the larger brain volume losses are actually associated with change,” said Dr. Yeh.

She noted that because the study population had high EDSS scores at baseline, it is not surprising that the NHPT and the T25FW were more strongly associated with change in brain volume than the EDSS was. Large changes in EDSS score probably did not occur during follow-up, she added.

“We’ll continue to use the EDSS, because it’s what we have,” said Dr. Yeh. However, newer measures, such as the NHPT and the T25FW, may provide better information, she said. Similarly, composite measures of cognition, such as the Brief International Cognitive Assessment for MS, may be superior to the SDMT but take longer to administer.

“We need to look more deeply at which MRI measures are the best for predicting outcome and that correlate well in a short period of time,” said Dr. Yeh.

These measures could include specific regional brain volumes “and more advanced measures that look at axonal injury or axonal loss.” Studies with longer follow-up are also necessary, she concluded.

The investigators and Dr. Yeh have reported no relevant financial relationships.

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

MRI results may not be effective at indicating disability for patients with secondary progressive multiple sclerosis (SPMS), new research suggests. Analysis from the phase 3 ASCEND trial of nearly 900 patients showed that MRI measures were not associated with worsening of scores on the Expanded Disability Status Scale (EDSS), the most widely used physical outcome measure.

The few associations that were shown between MRI measures and clinical outcomes “were with the newer and possibly more sensitive outcomes” – the Timed 25-Foot Walk (T25FW) and Nine-Hole Peg Test (NHPT), wrote the investigators, led by Marcus W. Koch, MD, PhD, associate professor of neurology in the MS program at the University of Calgary, Canada.

However, “it is unclear if these associations are clinically meaningful,” they added.

Worsening on the NHPT at 48 weeks was associated with a 0.86% loss in normalized brain volume; worsening at 96 weeks was associated with a 1.47% loss.

The findings were published online July 26 in the Multiple Sclerosis Journal.
 

ASCEND data analysis

Although brain volume loss occurs in all forms of MS, it is believed to be particularly relevant in SPMS. Clinical trials often use MRI measures of brain volume as endpoints, likely on the assumption that these measures indicate worsening disability.

However, brain volume loss proceeds slowly. Changes that occur during the typical 2-year study period may not be associated with significant physical or cognitive disability.

In the current study, investigators examined data from the ASCEND trial, which assessed the use of natalizumab for patients with SPMS, to examine these potential associations. Eligible participants in ASCEND were between ages 18 and 58 years, had had SPMS for 2 or more years, had had disability progression during the previous year, and had an EDSS score between 3.0 and 6.5 at baseline.

Participants underwent gadolinium-enhanced cranial MRI at screening and at 24, 48, 72, and 96 weeks. MRI outcomes included normalized brain volume, normalized cortical gray matter volume, and normalized whole gray matter volume. The ASCEND investigators also examined the number and volume of T2 and contrast-enhancing lesions.

The study’s clinical outcomes included scores on the EDSS, T25FW, and NHPT, which were administered at baseline and every 12 weeks thereafter. Participants also underwent the Symbol Digit Modalities Test (SDMT), which is a cognitive assessment, at baseline and every 4 weeks thereafter. In addition, 3-month confirmed disability progression was measured every 12 weeks.
 

Few significant associations

The investigators’ analysis included 889 patients (61.9% women; median age, 48 years). The median EDSS score at screening was 6.

Brain volume measures decreased consistently during follow-up. Mean volume loss at 96 weeks was about 1%. In contrast, T2 lesion volume changed little during follow-up. The cumulative number of contrast-enhancing lesions and the cumulative number of new or newly enlarging T2 lesions increased steadily during follow-up.

For an increasing number of participants, scores on the EDSS, NHPT, and T25FW worsened significantly during follow-up. Performance on SDMT, however, changed little. Of all the clinical measures, the NHPT was most consistently associated with MRI measures.

Among patients whose NHPT score worsened at 48 weeks, there was greater loss of normalized brain volume (0.86%, P = .02), normalized cortical gray matter volume (1.15%, P = .03), and normalized whole gray matter volume (1.08%, P = .03) than among those whose NHPT score did not worsen.

Among patients whose NHPT score worsened at 96 weeks, there was greater normalized brain volume loss (1.47%, P = .002), greater increase in T2 lesion volume (4.68%, P = .02), and a greater number of cumulative new or newly enlarging T2 lesions (7.81, P = .03) than those whose NHPT score did not worsen.

After adjusting the data for covariables, the investigators found few significant associations between MRI measures and clinical outcomes. Worsening on the EDSS and SDMT was not associated with any MRI outcome.
 

Important disability contributors missed

The odds ratio of 3-month confirmed worsening on the T25FW at 96 weeks was 2.25 for patients with more than 10 cumulative new or newly enlarging T2 lesions (P = .03). The OR of 3-month confirmed worsening on the NHPT at 96 weeks was 3.04 for patients with more than 10 such lesions (P = .03).

Greater normalized brain volume loss at 48 weeks was associated with a greater risk for worsening disability on the NHPT at 48 and 96 weeks. For patients with a volume loss greater than 1.5%, the OR of worsening NHPT at 96 weeks was 4.69 (P = .05).

Although previous cross-sectional studies have shown correlations between brain volume and cognitive dysfunction, the current investigators found no association between change in SDMT performance and MRI measures.

From the ASCEND dataset, they found that performance on the SDMT unexpectedly improved with time, perhaps because of a practice effect.

“The SDMT may therefore not adequately reflect the steady cognitive decline that people with SPMS experience,” the investigators wrote.

The lack of association between MRI measures and clinical outcomes may indicate that traditional MRI does not measure important contributors to disability, they noted.

“Although the investigated volume measures in this study are currently the most commonly used in clinical trials, newer MRI metrics such as thalamic or corpus callosum atrophy may have a closer relation to clinical outcome,” they added.
 

‘Interesting and provocative’

Commenting on the findings, E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children, Toronto, called the study “interesting and provocative.”

“Other studies previously have shown associations between disability and progression, but many have been cross-sectional,” said Dr. Yeh, who was not involved with the research.

The current study is longitudinal and analyzes carefully documented follow-up data from a clinical trial, she noted. However, the 2-year follow-up period was short, considering the pace at which whole brain volume change occurs, Dr. Yeh said.

Some patients with MS have greater brain volume loss than others. Because of this variability, researchers often examine a population’s average brain volume loss. “When you look at averages, it makes it more difficult to understand if the larger brain volume losses are actually associated with change,” said Dr. Yeh.

She noted that because the study population had high EDSS scores at baseline, it is not surprising that the NHPT and the T25FW were more strongly associated with change in brain volume than the EDSS was. Large changes in EDSS score probably did not occur during follow-up, she added.

“We’ll continue to use the EDSS, because it’s what we have,” said Dr. Yeh. However, newer measures, such as the NHPT and the T25FW, may provide better information, she said. Similarly, composite measures of cognition, such as the Brief International Cognitive Assessment for MS, may be superior to the SDMT but take longer to administer.

“We need to look more deeply at which MRI measures are the best for predicting outcome and that correlate well in a short period of time,” said Dr. Yeh.

These measures could include specific regional brain volumes “and more advanced measures that look at axonal injury or axonal loss.” Studies with longer follow-up are also necessary, she concluded.

The investigators and Dr. Yeh have reported no relevant financial relationships.

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

Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.

©rootstocks/Thinkstock

“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.

WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.

The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.

Study results

The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:

• Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
• LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
• Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
• Total LDL cholesterol particles, a reduction of 4.3%.
• Small LDL cholesterol particle number, a 6.1% decrease.

“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.

Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).

Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”

Potential study limitations

Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.

Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”

Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”

Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”

The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.

Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.

©rootstocks/Thinkstock

“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.

WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.

The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.

Study results

The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:

• Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
• LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
• Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
• Total LDL cholesterol particles, a reduction of 4.3%.
• Small LDL cholesterol particle number, a 6.1% decrease.

“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.

Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).

Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”

Potential study limitations

Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.

Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”

Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”

Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”

The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.

Healthy elderly people who ate a walnut-supplemented diet for 2 years showed significant reductions in LDL cholesterol, according to a randomized study that used imaging to evaluate lipid changes.

©rootstocks/Thinkstock

“Regularly eating walnuts will lower your LDL cholesterol and improve the quality of LDL particles, rendering them less prone to enter the arterial wall and build up atherosclerosis, and this will occur without unwanted weight gain in spite of the high-fat – healthy vegetable fat, though – content of walnuts,” Emilio Ros, MD, PhD, senior author of the Walnuts and Healthy Aging (WAHA) study, said in an interview.

WAHA is a parallel-group, randomized, controlled trial that followed 636 patients over 2 years at centers in Loma Linda, Calif., and Barcelona. They were randomly assigned to either a walnut-free or walnut-supplemented diet, and every 2 months they were underwent nuclear magnetic resonance spectroscopy and recorded their compliance, toleration, medication changes, and body weight.

The researchers reported “significantly decreased” total cholesterol, LDL cholesterol and intermediate-density lipoprotein cholesterol, along with reductions in total LDL cholesterol particles and small LDL cholesterol particle number in patients on a walnut-supplemented diet, compared with controls. However, triglycerides and HDL cholesterol were unaffected.

Study results

The study reported mean reductions in the following lipid categories among what the researchers called the “walnut group”:

• Total cholesterol, –8.5 mg/dL (95% confidence interval, –11.2 to –5.4), a 4.4% mean reduction.
• LDL-C, –4.3 mg/dL (95% CI, –6.6 to –1.6), a 3.6% reduction.
• Intermediate-density lipoprotein cholesterol, –1.3 mg/dL (95% CI, –1.5 to –1.0] for a 16.8% reduction.
• Total LDL cholesterol particles, a reduction of 4.3%.
• Small LDL cholesterol particle number, a 6.1% decrease.

“WAHA is the largest and longest randomized nut trial to date, which overcomes power limitations of former trials, smaller and of shorter duration,” said Dr. Ros, of the lipid clinic, endocrinology, nutrition service at the Hospital Clinic Villarroel at the University of Barcelona. He noted that studies he has participated in have already shown that the walnut-supplemented diet had beneficial effects on blood pressure, systemic inflammation and endothelial function.

Other strengths of the study, he said, were that it recruited patients from two distinct locations and that it retained 90% of participants over 2 years (the study started out with 708 participants).

Christie Ballantyne, MD, concurred that the size and duration of the study are worth noting. “People always have questions about what they should eat,” said Dr. Ballantyne, chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston, said in an interview. “It’s very difficult to do nutritional studies. Most studies are small and short term, so it’s unusual to have study that’s large with 2 years of follow-up. This is a larger-than-usual study.”

Potential study limitations

Dr. Ros did acknowledge some limitations of the study. Participants weren’t blinded, the feeding setting wasn’t controlled, and participants were generally healthy and had average normal lipid profiles because they were taking statins, which may explain the modest lipid improvements in the study. “LDL cholesterol lowering by nuts is related to baseline levels, hence the reduction observed in our study was modest,” he said.

Additionally, because the study group was elderly, the results don’t apply to younger people. “Yet,” Dr. Ros added, “we know from many prior studies that nuts in general and walnuts in particular will lower blood cholesterol regardless of age.”

Dr. Ballantyne noted that the use of nuclear magnetic resonance spectroscopy to evaluate lipid levels involves a methodology that isn’t as systematic or as standardized as the typical lipid profile, and that different systems use proprietary software to interpret results. “That’s a little bit of an issue,” he said. “What exactly do the numbers mean?”

Overall, though, Dr. Ballantyne said the study is a significant addition to the literature. “The study is large, well done, and it confirms the benefits of something we’ve been telling patients is a good choice. It’s useful because there’s so much noise. It is important because there’s tremendous confusion and misinformation about what’s really healthy to eat.”

The study was supported by a grant from the California Walnut Commission (CWC), from which Dr. Ros and two coauthors received research funding through their institutions. Dr. Ros also reported receiving compensation from CWC and serves on a CWC advisory council. The other authors have no relationships to disclose. The WAHA study was supported by a grant from the CWC, from which Dr. Ros and some coinvestigators have received research funding through their institutions. Dr. Ballantyne has no relevant relationships to disclose.

Perhaps short, asymptomatic bouts of atrial fibrillation (AFib) that show up on long-term, continuous monitoring aren’t worth hunting for just so oral anticoagulation (OAC) can be started, even in elderly people with other stroke risk factors.

That’s a potential message from a randomized trial that tested an AFib screening strategy relying on an implantable loop recorder (ILR) in older adults without AFib but with other stroke risk factors who were invited to participate. OAC was recommended to any participant found with even a short bout of the arrhythmia (that is, any lasting 6 minutes or longer).

More than three times as many in the monitoring group compared to a standard-care cohort were found to have AFib, and nearly all were put on OAC. In fact, monitored participants were almost three times as likely to be put on OAC (P < .0001) compared with controls.

But it didn’t make any apparent difference to outcomes. The risk for stroke or systemic embolism did not significantly differ between the two groups over more than 5 years in the trial of about 6,000 participants, called LOOP.

“This result was seen despite a high proportion of atrial fibrillation detection, and a high acceptance of anticoagulation therapy, and might imply that not all atrial fibrillation is worth screening for, and not all screen-detected atrial fibrillation merits anticoagulation,” contend the authors of the LOOP report, simultaneously published in The Lancet and presented Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021.

“The rates of bleeding were modest, despite the low threshold for anticoagulation,” and was not significantly different between the two groups, Jesper H. Svendsen, MD, DMSc, Copenhagen University Hospital, Denmark, said at a media briefing before his presentation of the trial at the congress. He is lead author on the Lancet report.

At least 6 minutes of AFib was identified in more than 30% of the ILR-monitored patients, and about 90% of those were started on OAC, Dr. Svendsen observed.

But one take-home message from LOOP, he said in an interview, is that “short-lasting episodes” of AFib do not necessarily pose an untoward risk for stroke compared with AFib revealed by intermittent monitoring, which “primarily identifies longer-lasting atrial fibrillation episodes. So short-lasting episodes are probably not as serious as long-lasting.”

The LOOP trial “teaches us that perhaps short-lasting asymptomatic episodes may not benefit from being screened or found,” said Stefan James, MD, PhD, Uppsala University, Sweden. However, that may not be the case when the monitored individual is symptomatic or has longer-lasting AFib episodes, he said in an interview. “But certainly, this study teaches us that we need to understand much better the relationship between short episodes versus symptoms versus medical outcomes.”

In LOOP, 6,004 people aged 70-90 years without AFib but with at least one other stroke risk factor, which could include hypertension, diabetes, a history of stroke, or heart failure, were implanted with an ILR, the Reveal LINQ (Medtronic).

They were randomly assigned at four centers in Denmark to a monitoring group or a usual care group in a 1:3 ratio. Overwhelmingly, most had hypertension. Almost half the population were women.

OAC was recommended for all persons in the monitoring group who showed an episode of AFib lasting at least 6 minutes.

Atrial fibrillation was diagnosed in 31.8% of the 1,501 participants in the monitored group and 12.2% of the 4,503 assigned to usual care, for a hazard ratio (HR) of 3.17 (95% confidence interval, 2.81-3.59; P < .0001).

OAC was started in 29.7% of monitored participants and 13.1% of the control cohort, for an HR of 2.72 (95% CI, 2.41-3.08; P < .0001).

There were 315 strokes and three systemic arterial embolisms observed in the entire trial, for primary endpoint rates of 4.5% in the ILR monitoring group and 5.6% in the control group (HR, 0.80; 95% CI, 0.61-1.05; P = .11). Adding transient ischemic attack (TIA) or cardiovascular death to the endpoint did not make for a significant difference. The rates of major bleeding were 4.3% and 3.5%, respectively (P = .11).

“In general, the findings were consistent across subgroups,” including by age, sex, diabetes and heart failure status, stroke history, antiplatelet therapy, renal function, and even CHA2DS2–VASc score, Dr. Svendsen noted.

But, he said, participants in the highest tertile for baseline systolic blood pressure (BP), at least 157 mm Hg, “seemed to benefit from being screened,” with a 49% reduction in risk for the primary endpoint (P = .0066). The interaction between systolic BP and outcome was significant (P = .007).

Only 9.3% of participants in LOOP did not have a baseline diagnosis of hypertension and so had to have another risk factor to enroll, the published report notes. However, the significant interaction with systolic BP “suggests that patients with dysregulated hypertension could benefit from this type of screening and concomitant anticoagulation.”

“There is a tight association between our primary endpoint and hypertension,” Dr. Svendsen said in an interview. “But I think it’s very important to say that this subgroup analysis is only hypothesis-generating.”

An editorial accompanying the LOOP publication suggests, in line with Dr. Svendsen’s proposal, that “shorter atrial fibrillation episodes found by long-term ILRs might not have the same stroke risk as atrial fibrillation detected through single-timepoint or less intense monitoring.”

If much of the paroxysmal AFib observed in LOOP and other studies with similar monitoring methods “is not the actual cause of stroke and is instead predominantly a risk marker, further research is warranted to establish whether a different screening focus and treatment paradigm are required to prevent stroke and other vascular brain injury related to atrial fibrillation,” wrote editorialists Ben Freedman, MBBS, PhD, and Nicole Lowres, BPhty, PhD, University of Sydney, Australia.

LOOP was partially supported by Medtronic. Dr. Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic in relation to this work and outside the submitted work. Disclosures for the other authors are in the report. Dr. Freedman reports grants to the Heart Research Institute, speakers fees and nonfinancial support from the Bristol-Myers Squibb–Pfizer Alliance, speakers fees and nonfinancial support from Daiichi Sankyo, nonfinancial support from AliveCor, and speakers fees and nonfinancial support from Omron unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation. Dr. Lowres reports grants to the Heart Research Institute from the Bristol-Myers Squibb–Pfizer Alliance unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation.

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

Perhaps short, asymptomatic bouts of atrial fibrillation (AFib) that show up on long-term, continuous monitoring aren’t worth hunting for just so oral anticoagulation (OAC) can be started, even in elderly people with other stroke risk factors.

That’s a potential message from a randomized trial that tested an AFib screening strategy relying on an implantable loop recorder (ILR) in older adults without AFib but with other stroke risk factors who were invited to participate. OAC was recommended to any participant found with even a short bout of the arrhythmia (that is, any lasting 6 minutes or longer).

More than three times as many in the monitoring group compared to a standard-care cohort were found to have AFib, and nearly all were put on OAC. In fact, monitored participants were almost three times as likely to be put on OAC (P < .0001) compared with controls.

But it didn’t make any apparent difference to outcomes. The risk for stroke or systemic embolism did not significantly differ between the two groups over more than 5 years in the trial of about 6,000 participants, called LOOP.

“This result was seen despite a high proportion of atrial fibrillation detection, and a high acceptance of anticoagulation therapy, and might imply that not all atrial fibrillation is worth screening for, and not all screen-detected atrial fibrillation merits anticoagulation,” contend the authors of the LOOP report, simultaneously published in The Lancet and presented Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021.

“The rates of bleeding were modest, despite the low threshold for anticoagulation,” and was not significantly different between the two groups, Jesper H. Svendsen, MD, DMSc, Copenhagen University Hospital, Denmark, said at a media briefing before his presentation of the trial at the congress. He is lead author on the Lancet report.

At least 6 minutes of AFib was identified in more than 30% of the ILR-monitored patients, and about 90% of those were started on OAC, Dr. Svendsen observed.

But one take-home message from LOOP, he said in an interview, is that “short-lasting episodes” of AFib do not necessarily pose an untoward risk for stroke compared with AFib revealed by intermittent monitoring, which “primarily identifies longer-lasting atrial fibrillation episodes. So short-lasting episodes are probably not as serious as long-lasting.”

The LOOP trial “teaches us that perhaps short-lasting asymptomatic episodes may not benefit from being screened or found,” said Stefan James, MD, PhD, Uppsala University, Sweden. However, that may not be the case when the monitored individual is symptomatic or has longer-lasting AFib episodes, he said in an interview. “But certainly, this study teaches us that we need to understand much better the relationship between short episodes versus symptoms versus medical outcomes.”

In LOOP, 6,004 people aged 70-90 years without AFib but with at least one other stroke risk factor, which could include hypertension, diabetes, a history of stroke, or heart failure, were implanted with an ILR, the Reveal LINQ (Medtronic).

They were randomly assigned at four centers in Denmark to a monitoring group or a usual care group in a 1:3 ratio. Overwhelmingly, most had hypertension. Almost half the population were women.

OAC was recommended for all persons in the monitoring group who showed an episode of AFib lasting at least 6 minutes.

Atrial fibrillation was diagnosed in 31.8% of the 1,501 participants in the monitored group and 12.2% of the 4,503 assigned to usual care, for a hazard ratio (HR) of 3.17 (95% confidence interval, 2.81-3.59; P < .0001).

OAC was started in 29.7% of monitored participants and 13.1% of the control cohort, for an HR of 2.72 (95% CI, 2.41-3.08; P < .0001).

There were 315 strokes and three systemic arterial embolisms observed in the entire trial, for primary endpoint rates of 4.5% in the ILR monitoring group and 5.6% in the control group (HR, 0.80; 95% CI, 0.61-1.05; P = .11). Adding transient ischemic attack (TIA) or cardiovascular death to the endpoint did not make for a significant difference. The rates of major bleeding were 4.3% and 3.5%, respectively (P = .11).

“In general, the findings were consistent across subgroups,” including by age, sex, diabetes and heart failure status, stroke history, antiplatelet therapy, renal function, and even CHA2DS2–VASc score, Dr. Svendsen noted.

But, he said, participants in the highest tertile for baseline systolic blood pressure (BP), at least 157 mm Hg, “seemed to benefit from being screened,” with a 49% reduction in risk for the primary endpoint (P = .0066). The interaction between systolic BP and outcome was significant (P = .007).

Only 9.3% of participants in LOOP did not have a baseline diagnosis of hypertension and so had to have another risk factor to enroll, the published report notes. However, the significant interaction with systolic BP “suggests that patients with dysregulated hypertension could benefit from this type of screening and concomitant anticoagulation.”

“There is a tight association between our primary endpoint and hypertension,” Dr. Svendsen said in an interview. “But I think it’s very important to say that this subgroup analysis is only hypothesis-generating.”

An editorial accompanying the LOOP publication suggests, in line with Dr. Svendsen’s proposal, that “shorter atrial fibrillation episodes found by long-term ILRs might not have the same stroke risk as atrial fibrillation detected through single-timepoint or less intense monitoring.”

If much of the paroxysmal AFib observed in LOOP and other studies with similar monitoring methods “is not the actual cause of stroke and is instead predominantly a risk marker, further research is warranted to establish whether a different screening focus and treatment paradigm are required to prevent stroke and other vascular brain injury related to atrial fibrillation,” wrote editorialists Ben Freedman, MBBS, PhD, and Nicole Lowres, BPhty, PhD, University of Sydney, Australia.

LOOP was partially supported by Medtronic. Dr. Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic in relation to this work and outside the submitted work. Disclosures for the other authors are in the report. Dr. Freedman reports grants to the Heart Research Institute, speakers fees and nonfinancial support from the Bristol-Myers Squibb–Pfizer Alliance, speakers fees and nonfinancial support from Daiichi Sankyo, nonfinancial support from AliveCor, and speakers fees and nonfinancial support from Omron unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation. Dr. Lowres reports grants to the Heart Research Institute from the Bristol-Myers Squibb–Pfizer Alliance unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation.

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

Perhaps short, asymptomatic bouts of atrial fibrillation (AFib) that show up on long-term, continuous monitoring aren’t worth hunting for just so oral anticoagulation (OAC) can be started, even in elderly people with other stroke risk factors.

That’s a potential message from a randomized trial that tested an AFib screening strategy relying on an implantable loop recorder (ILR) in older adults without AFib but with other stroke risk factors who were invited to participate. OAC was recommended to any participant found with even a short bout of the arrhythmia (that is, any lasting 6 minutes or longer).

More than three times as many in the monitoring group compared to a standard-care cohort were found to have AFib, and nearly all were put on OAC. In fact, monitored participants were almost three times as likely to be put on OAC (P < .0001) compared with controls.

But it didn’t make any apparent difference to outcomes. The risk for stroke or systemic embolism did not significantly differ between the two groups over more than 5 years in the trial of about 6,000 participants, called LOOP.

“This result was seen despite a high proportion of atrial fibrillation detection, and a high acceptance of anticoagulation therapy, and might imply that not all atrial fibrillation is worth screening for, and not all screen-detected atrial fibrillation merits anticoagulation,” contend the authors of the LOOP report, simultaneously published in The Lancet and presented Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021.

“The rates of bleeding were modest, despite the low threshold for anticoagulation,” and was not significantly different between the two groups, Jesper H. Svendsen, MD, DMSc, Copenhagen University Hospital, Denmark, said at a media briefing before his presentation of the trial at the congress. He is lead author on the Lancet report.

At least 6 minutes of AFib was identified in more than 30% of the ILR-monitored patients, and about 90% of those were started on OAC, Dr. Svendsen observed.

But one take-home message from LOOP, he said in an interview, is that “short-lasting episodes” of AFib do not necessarily pose an untoward risk for stroke compared with AFib revealed by intermittent monitoring, which “primarily identifies longer-lasting atrial fibrillation episodes. So short-lasting episodes are probably not as serious as long-lasting.”

The LOOP trial “teaches us that perhaps short-lasting asymptomatic episodes may not benefit from being screened or found,” said Stefan James, MD, PhD, Uppsala University, Sweden. However, that may not be the case when the monitored individual is symptomatic or has longer-lasting AFib episodes, he said in an interview. “But certainly, this study teaches us that we need to understand much better the relationship between short episodes versus symptoms versus medical outcomes.”

In LOOP, 6,004 people aged 70-90 years without AFib but with at least one other stroke risk factor, which could include hypertension, diabetes, a history of stroke, or heart failure, were implanted with an ILR, the Reveal LINQ (Medtronic).

They were randomly assigned at four centers in Denmark to a monitoring group or a usual care group in a 1:3 ratio. Overwhelmingly, most had hypertension. Almost half the population were women.

OAC was recommended for all persons in the monitoring group who showed an episode of AFib lasting at least 6 minutes.

Atrial fibrillation was diagnosed in 31.8% of the 1,501 participants in the monitored group and 12.2% of the 4,503 assigned to usual care, for a hazard ratio (HR) of 3.17 (95% confidence interval, 2.81-3.59; P < .0001).

OAC was started in 29.7% of monitored participants and 13.1% of the control cohort, for an HR of 2.72 (95% CI, 2.41-3.08; P < .0001).

There were 315 strokes and three systemic arterial embolisms observed in the entire trial, for primary endpoint rates of 4.5% in the ILR monitoring group and 5.6% in the control group (HR, 0.80; 95% CI, 0.61-1.05; P = .11). Adding transient ischemic attack (TIA) or cardiovascular death to the endpoint did not make for a significant difference. The rates of major bleeding were 4.3% and 3.5%, respectively (P = .11).

“In general, the findings were consistent across subgroups,” including by age, sex, diabetes and heart failure status, stroke history, antiplatelet therapy, renal function, and even CHA2DS2–VASc score, Dr. Svendsen noted.

But, he said, participants in the highest tertile for baseline systolic blood pressure (BP), at least 157 mm Hg, “seemed to benefit from being screened,” with a 49% reduction in risk for the primary endpoint (P = .0066). The interaction between systolic BP and outcome was significant (P = .007).

Only 9.3% of participants in LOOP did not have a baseline diagnosis of hypertension and so had to have another risk factor to enroll, the published report notes. However, the significant interaction with systolic BP “suggests that patients with dysregulated hypertension could benefit from this type of screening and concomitant anticoagulation.”

“There is a tight association between our primary endpoint and hypertension,” Dr. Svendsen said in an interview. “But I think it’s very important to say that this subgroup analysis is only hypothesis-generating.”

An editorial accompanying the LOOP publication suggests, in line with Dr. Svendsen’s proposal, that “shorter atrial fibrillation episodes found by long-term ILRs might not have the same stroke risk as atrial fibrillation detected through single-timepoint or less intense monitoring.”

If much of the paroxysmal AFib observed in LOOP and other studies with similar monitoring methods “is not the actual cause of stroke and is instead predominantly a risk marker, further research is warranted to establish whether a different screening focus and treatment paradigm are required to prevent stroke and other vascular brain injury related to atrial fibrillation,” wrote editorialists Ben Freedman, MBBS, PhD, and Nicole Lowres, BPhty, PhD, University of Sydney, Australia.

LOOP was partially supported by Medtronic. Dr. Svendsen is a member of Medtronic advisory boards and has received speaker honoraria and research grants from Medtronic in relation to this work and outside the submitted work. Disclosures for the other authors are in the report. Dr. Freedman reports grants to the Heart Research Institute, speakers fees and nonfinancial support from the Bristol-Myers Squibb–Pfizer Alliance, speakers fees and nonfinancial support from Daiichi Sankyo, nonfinancial support from AliveCor, and speakers fees and nonfinancial support from Omron unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation. Dr. Lowres reports grants to the Heart Research Institute from the Bristol-Myers Squibb–Pfizer Alliance unrelated to the topic of the editorial but related to atrial fibrillation and screening for atrial fibrillation.

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

Switching from regular salt to a low-sodium salt substitute has major public health benefits, including a reduction in stroke, cardiovascular events, and death, a new landmark study shows.

jirkaejc/Getty Images

The Salt Substitute and Stroke Study (SSaSS) was conducted in 21,000 people with a history of stroke or high blood pressure in rural China, with half of them using a lower-sodium salt substitute instead of regular salt.

Results showed that after 5 years, those using the salt substitute had a 14% reduction in stroke, a 13% reduction in major cardiovascular events, and a 12% reduction in death. These benefits were achieved without any apparent adverse effects.

The trial was presented by Bruce Neal, MB, George Institute for Global Health, Sydney, Australia, on Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“This is one of the largest dietary intervention trials ever conducted and has shown very clear evidence of protection against stroke, cardiovascular events, and premature death, with no adverse effects with a very simple and low-cost intervention,” Dr. Neal concluded. “This is a very easy thing to work into the diet. You just replace regular salt with a substitute that looks and tastes almost identical,” he added.

Addressing the issue of whether these results are generalizable to other populations, Dr. Neal said, “We believe the results are relevant to everyone who eats salt.

“The way the body manages sodium and potassium and their association with blood pressure is highly consistent across different populations,” he said. “Almost everyone, with the exception of a few people with serious kidney disease, should be avoiding salt or switching to a salt substitute and expect to see some benefit of this.”

Commentators at the ESC presentation lauded the study as “magnificent,” with “extraordinary” results and “very powerful implications.”

Designated discussant, hypertension expert Bryan Williams, MD, University College London, said the SSaSS was “probably the most important study with regards to public health that we will see.” He described the reductions in stroke, cardiovascular events, and death as “extraordinary for such a simple intervention.”

Dr. Williams added: “Those who have doubted the benefits of salt restriction must now admit they were wrong. The debate stops here. The data are in. Global health interventions to implement these findings must now begin.”

He also highlighted the large number of events in the trial. “This was a large, pragmatic, long-duration study in a high-risk population, and with 5,000 cardiovascular events it gives enormous power to show benefits.”

Chair of the ESC session, Barbara Casadei, MD, DPhil, John Radcliffe Hospital, Oxford (England), said the SSaSS “will change the way we think about salt and be remembered for years to come.”

Noting that the benefits were seen in all subgroups across the study, Bertram Pitt, MD, University of Michigan, Ann Arbor, was particularly excited about the stroke reduction seen in patients with diabetes, noting that several recent trials of new diabetes drugs have not managed to show a reduction in stroke.

“For patients with diabetes, this is a really important intervention,” he stated.

However, an editorial accompanying the NEJM publication gave a somewhat less enthusiastic response to the study than the ESC commentators.

Julie R. Ingelfinger, MD, deputy editor of the journal, points out that serial monitoring of potassium levels was not performed in the trial, so it is possible that hyperkalemic episodes were not detected, and persons with a history of medical conditions that may be associated with hyperkalemia were not studied.

She also noted that because the salt substitute was distributed to families, it would have been instructive to have data on the household members without risk factors, but no such data were obtained.

“Overall, the SSaSS provides some intriguing hints, but wider effectiveness is hard to predict, given limited generalizability,” she concluded.

Cluster-randomized trial

The SSaSS was an open-label, cluster-randomized trial involving 20,995 people from 600 villages in rural China who had a history of stroke or were 60 years of age or older and had uncontrolled hypertension. Patients with a history of severe kidney disease and those taking potassium supplements or potassium-sparing diuretics were excluded.

They were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (roughly 75% sodium chloride and 25% potassium chloride), or to the control group, in which the participants continued to use regular salt (100% sodium chloride).

Results showed that after a mean follow-up of 4.74 years, systolic blood pressure was reduced by 3.3 mm Hg in the salt substitute group.

The rate of stroke, the primary endpoint, was 29.14 events per 1,000 person-years in the salt substitute group vs. 33.65 events per 1,000 person-years with regular salt (rate ratio, 0.86; 95% confidence interval, 0.77-0.96; P = .006).

The rates of major cardiovascular events were 49.09 events per 1,000 person-years in the salt substitute group vs. 56.29 events per 1,000 person-years in those using regular salt (rate ratio, 0.87; 95% CI, 0.80-0.94; P < .001).

And the rate of death was 39.28 events per 1,000 person-years with the salt substitute vs. 44.61 events per 1,000 person-years with regular salt (rate ratio, 0.88; 95% CI, 0.82-0.95; P < .001).

The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1,000 person-years; rate ratio, 1.04; 95% CI, 0.80-1.37; P = .76).

Dr. Neal reported that 7%-8% of the control group started using salt substitute over the study period, so these results have likely underestimated the true effect of switching to a salt substitute product.

Noting that about 10 million cardiovascular events occur each year in China, he said the study results suggested that using salt substitute instead of regular salt could prevent about 10% of these events.
 

Food manufacturers must make changes

Dr. Neal acknowledged that a limitation of the study was the fact it was conducted in a single country, which would raise issues of generalizability. But he said he believes the results are generalizable to other populations.

Those who would get the most benefit from switching to a salt substitute are those who consume large amounts of discretionary salt – salt added at home at the time of cooking for preservation of food or seasoning. “This is salt that is easy to replace with salt substitute,” Dr. Neal noted.

“There are more than 5 billion people in the world that consume more than 50% of their salt intake as discretionary salt –  mainly in the developing world. These people would expect to get significant health benefits from a switch to salt substitute.”

He pointed out that salt substitute is low cost and is easy to manufacture. “Salt substitutes cost around 50% more than regular salt, but this translates into just a dollar or two per person per year to make the switch.”

Dr. Neal said the results also apply to higher-income countries but must be implemented by governments and food manufactures, as most salt in these countries comes from processed foods.

“This study provides strong evidence to take to the food industry,” he concluded. “We would like to see food manufacturers switch to using salt substitute and for salt substitute products to be widely available on supermarket shelves. We also urge governments to take action to promote use of salt substitutes over regular salt. This could take the form of taxing regular salt or subsidies for use of salt substitutes.”

The SSaSS was supported by grants from the National Health and Medical Research Council of Australia. Dr. Neal reports no disclosures. Dr. Ingelfinger is employed by the New England Journal of Medicine as deputy editor.

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

Switching from regular salt to a low-sodium salt substitute has major public health benefits, including a reduction in stroke, cardiovascular events, and death, a new landmark study shows.

jirkaejc/Getty Images

The Salt Substitute and Stroke Study (SSaSS) was conducted in 21,000 people with a history of stroke or high blood pressure in rural China, with half of them using a lower-sodium salt substitute instead of regular salt.

Results showed that after 5 years, those using the salt substitute had a 14% reduction in stroke, a 13% reduction in major cardiovascular events, and a 12% reduction in death. These benefits were achieved without any apparent adverse effects.

The trial was presented by Bruce Neal, MB, George Institute for Global Health, Sydney, Australia, on Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“This is one of the largest dietary intervention trials ever conducted and has shown very clear evidence of protection against stroke, cardiovascular events, and premature death, with no adverse effects with a very simple and low-cost intervention,” Dr. Neal concluded. “This is a very easy thing to work into the diet. You just replace regular salt with a substitute that looks and tastes almost identical,” he added.

Addressing the issue of whether these results are generalizable to other populations, Dr. Neal said, “We believe the results are relevant to everyone who eats salt.

“The way the body manages sodium and potassium and their association with blood pressure is highly consistent across different populations,” he said. “Almost everyone, with the exception of a few people with serious kidney disease, should be avoiding salt or switching to a salt substitute and expect to see some benefit of this.”

Commentators at the ESC presentation lauded the study as “magnificent,” with “extraordinary” results and “very powerful implications.”

Designated discussant, hypertension expert Bryan Williams, MD, University College London, said the SSaSS was “probably the most important study with regards to public health that we will see.” He described the reductions in stroke, cardiovascular events, and death as “extraordinary for such a simple intervention.”

Dr. Williams added: “Those who have doubted the benefits of salt restriction must now admit they were wrong. The debate stops here. The data are in. Global health interventions to implement these findings must now begin.”

He also highlighted the large number of events in the trial. “This was a large, pragmatic, long-duration study in a high-risk population, and with 5,000 cardiovascular events it gives enormous power to show benefits.”

Chair of the ESC session, Barbara Casadei, MD, DPhil, John Radcliffe Hospital, Oxford (England), said the SSaSS “will change the way we think about salt and be remembered for years to come.”

Noting that the benefits were seen in all subgroups across the study, Bertram Pitt, MD, University of Michigan, Ann Arbor, was particularly excited about the stroke reduction seen in patients with diabetes, noting that several recent trials of new diabetes drugs have not managed to show a reduction in stroke.

“For patients with diabetes, this is a really important intervention,” he stated.

However, an editorial accompanying the NEJM publication gave a somewhat less enthusiastic response to the study than the ESC commentators.

Julie R. Ingelfinger, MD, deputy editor of the journal, points out that serial monitoring of potassium levels was not performed in the trial, so it is possible that hyperkalemic episodes were not detected, and persons with a history of medical conditions that may be associated with hyperkalemia were not studied.

She also noted that because the salt substitute was distributed to families, it would have been instructive to have data on the household members without risk factors, but no such data were obtained.

“Overall, the SSaSS provides some intriguing hints, but wider effectiveness is hard to predict, given limited generalizability,” she concluded.

Cluster-randomized trial

The SSaSS was an open-label, cluster-randomized trial involving 20,995 people from 600 villages in rural China who had a history of stroke or were 60 years of age or older and had uncontrolled hypertension. Patients with a history of severe kidney disease and those taking potassium supplements or potassium-sparing diuretics were excluded.

They were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (roughly 75% sodium chloride and 25% potassium chloride), or to the control group, in which the participants continued to use regular salt (100% sodium chloride).

Results showed that after a mean follow-up of 4.74 years, systolic blood pressure was reduced by 3.3 mm Hg in the salt substitute group.

The rate of stroke, the primary endpoint, was 29.14 events per 1,000 person-years in the salt substitute group vs. 33.65 events per 1,000 person-years with regular salt (rate ratio, 0.86; 95% confidence interval, 0.77-0.96; P = .006).

The rates of major cardiovascular events were 49.09 events per 1,000 person-years in the salt substitute group vs. 56.29 events per 1,000 person-years in those using regular salt (rate ratio, 0.87; 95% CI, 0.80-0.94; P < .001).

And the rate of death was 39.28 events per 1,000 person-years with the salt substitute vs. 44.61 events per 1,000 person-years with regular salt (rate ratio, 0.88; 95% CI, 0.82-0.95; P < .001).

The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1,000 person-years; rate ratio, 1.04; 95% CI, 0.80-1.37; P = .76).

Dr. Neal reported that 7%-8% of the control group started using salt substitute over the study period, so these results have likely underestimated the true effect of switching to a salt substitute product.

Noting that about 10 million cardiovascular events occur each year in China, he said the study results suggested that using salt substitute instead of regular salt could prevent about 10% of these events.
 

Food manufacturers must make changes

Dr. Neal acknowledged that a limitation of the study was the fact it was conducted in a single country, which would raise issues of generalizability. But he said he believes the results are generalizable to other populations.

Those who would get the most benefit from switching to a salt substitute are those who consume large amounts of discretionary salt – salt added at home at the time of cooking for preservation of food or seasoning. “This is salt that is easy to replace with salt substitute,” Dr. Neal noted.

“There are more than 5 billion people in the world that consume more than 50% of their salt intake as discretionary salt –  mainly in the developing world. These people would expect to get significant health benefits from a switch to salt substitute.”

He pointed out that salt substitute is low cost and is easy to manufacture. “Salt substitutes cost around 50% more than regular salt, but this translates into just a dollar or two per person per year to make the switch.”

Dr. Neal said the results also apply to higher-income countries but must be implemented by governments and food manufactures, as most salt in these countries comes from processed foods.

“This study provides strong evidence to take to the food industry,” he concluded. “We would like to see food manufacturers switch to using salt substitute and for salt substitute products to be widely available on supermarket shelves. We also urge governments to take action to promote use of salt substitutes over regular salt. This could take the form of taxing regular salt or subsidies for use of salt substitutes.”

The SSaSS was supported by grants from the National Health and Medical Research Council of Australia. Dr. Neal reports no disclosures. Dr. Ingelfinger is employed by the New England Journal of Medicine as deputy editor.

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

Switching from regular salt to a low-sodium salt substitute has major public health benefits, including a reduction in stroke, cardiovascular events, and death, a new landmark study shows.

jirkaejc/Getty Images

The Salt Substitute and Stroke Study (SSaSS) was conducted in 21,000 people with a history of stroke or high blood pressure in rural China, with half of them using a lower-sodium salt substitute instead of regular salt.

Results showed that after 5 years, those using the salt substitute had a 14% reduction in stroke, a 13% reduction in major cardiovascular events, and a 12% reduction in death. These benefits were achieved without any apparent adverse effects.

The trial was presented by Bruce Neal, MB, George Institute for Global Health, Sydney, Australia, on Aug. 29 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“This is one of the largest dietary intervention trials ever conducted and has shown very clear evidence of protection against stroke, cardiovascular events, and premature death, with no adverse effects with a very simple and low-cost intervention,” Dr. Neal concluded. “This is a very easy thing to work into the diet. You just replace regular salt with a substitute that looks and tastes almost identical,” he added.

Addressing the issue of whether these results are generalizable to other populations, Dr. Neal said, “We believe the results are relevant to everyone who eats salt.

“The way the body manages sodium and potassium and their association with blood pressure is highly consistent across different populations,” he said. “Almost everyone, with the exception of a few people with serious kidney disease, should be avoiding salt or switching to a salt substitute and expect to see some benefit of this.”

Commentators at the ESC presentation lauded the study as “magnificent,” with “extraordinary” results and “very powerful implications.”

Designated discussant, hypertension expert Bryan Williams, MD, University College London, said the SSaSS was “probably the most important study with regards to public health that we will see.” He described the reductions in stroke, cardiovascular events, and death as “extraordinary for such a simple intervention.”

Dr. Williams added: “Those who have doubted the benefits of salt restriction must now admit they were wrong. The debate stops here. The data are in. Global health interventions to implement these findings must now begin.”

He also highlighted the large number of events in the trial. “This was a large, pragmatic, long-duration study in a high-risk population, and with 5,000 cardiovascular events it gives enormous power to show benefits.”

Chair of the ESC session, Barbara Casadei, MD, DPhil, John Radcliffe Hospital, Oxford (England), said the SSaSS “will change the way we think about salt and be remembered for years to come.”

Noting that the benefits were seen in all subgroups across the study, Bertram Pitt, MD, University of Michigan, Ann Arbor, was particularly excited about the stroke reduction seen in patients with diabetes, noting that several recent trials of new diabetes drugs have not managed to show a reduction in stroke.

“For patients with diabetes, this is a really important intervention,” he stated.

However, an editorial accompanying the NEJM publication gave a somewhat less enthusiastic response to the study than the ESC commentators.

Julie R. Ingelfinger, MD, deputy editor of the journal, points out that serial monitoring of potassium levels was not performed in the trial, so it is possible that hyperkalemic episodes were not detected, and persons with a history of medical conditions that may be associated with hyperkalemia were not studied.

She also noted that because the salt substitute was distributed to families, it would have been instructive to have data on the household members without risk factors, but no such data were obtained.

“Overall, the SSaSS provides some intriguing hints, but wider effectiveness is hard to predict, given limited generalizability,” she concluded.

Cluster-randomized trial

The SSaSS was an open-label, cluster-randomized trial involving 20,995 people from 600 villages in rural China who had a history of stroke or were 60 years of age or older and had uncontrolled hypertension. Patients with a history of severe kidney disease and those taking potassium supplements or potassium-sparing diuretics were excluded.

They were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (roughly 75% sodium chloride and 25% potassium chloride), or to the control group, in which the participants continued to use regular salt (100% sodium chloride).

Results showed that after a mean follow-up of 4.74 years, systolic blood pressure was reduced by 3.3 mm Hg in the salt substitute group.

The rate of stroke, the primary endpoint, was 29.14 events per 1,000 person-years in the salt substitute group vs. 33.65 events per 1,000 person-years with regular salt (rate ratio, 0.86; 95% confidence interval, 0.77-0.96; P = .006).

The rates of major cardiovascular events were 49.09 events per 1,000 person-years in the salt substitute group vs. 56.29 events per 1,000 person-years in those using regular salt (rate ratio, 0.87; 95% CI, 0.80-0.94; P < .001).

And the rate of death was 39.28 events per 1,000 person-years with the salt substitute vs. 44.61 events per 1,000 person-years with regular salt (rate ratio, 0.88; 95% CI, 0.82-0.95; P < .001).

The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1,000 person-years; rate ratio, 1.04; 95% CI, 0.80-1.37; P = .76).

Dr. Neal reported that 7%-8% of the control group started using salt substitute over the study period, so these results have likely underestimated the true effect of switching to a salt substitute product.

Noting that about 10 million cardiovascular events occur each year in China, he said the study results suggested that using salt substitute instead of regular salt could prevent about 10% of these events.
 

Food manufacturers must make changes

Dr. Neal acknowledged that a limitation of the study was the fact it was conducted in a single country, which would raise issues of generalizability. But he said he believes the results are generalizable to other populations.

Those who would get the most benefit from switching to a salt substitute are those who consume large amounts of discretionary salt – salt added at home at the time of cooking for preservation of food or seasoning. “This is salt that is easy to replace with salt substitute,” Dr. Neal noted.

“There are more than 5 billion people in the world that consume more than 50% of their salt intake as discretionary salt –  mainly in the developing world. These people would expect to get significant health benefits from a switch to salt substitute.”

He pointed out that salt substitute is low cost and is easy to manufacture. “Salt substitutes cost around 50% more than regular salt, but this translates into just a dollar or two per person per year to make the switch.”

Dr. Neal said the results also apply to higher-income countries but must be implemented by governments and food manufactures, as most salt in these countries comes from processed foods.

“This study provides strong evidence to take to the food industry,” he concluded. “We would like to see food manufacturers switch to using salt substitute and for salt substitute products to be widely available on supermarket shelves. We also urge governments to take action to promote use of salt substitutes over regular salt. This could take the form of taxing regular salt or subsidies for use of salt substitutes.”

The SSaSS was supported by grants from the National Health and Medical Research Council of Australia. Dr. Neal reports no disclosures. Dr. Ingelfinger is employed by the New England Journal of Medicine as deputy editor.

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

Another trial has added to the movement toward shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).

MDedge News

In the MASTER DAPT trial involving patients at high risk for bleeding who had undergone implantation of a biodegradable-polymer sirolimus-eluting stent, switching from DAPT to single antiplatelet therapy at a median of 34 days after PCI was noninferior to the continuation of DAPT treatment for a median duration of 193 days with regard to the incidence of major adverse cardiac or cerebral events, and was associated with a lower incidence of major or clinically relevant bleeding.

The results of the study were presented by Marco Valgimigli, MD, Cardiocentro Ticino Institute, Lugano, Switzerland, on Aug. 28 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“It has been suggested in previous studies that if patients are at high bleeding risk, then they do not seem to derive ischemic benefit from prolonging DAPT, they just get the increased bleeding risk,” Dr. Valgimigli said. “But this has never been prospectively tested until now.”

He pointed out that patients at high bleeding risk are a large group, representing up to 40% of patients undergoing PCI, and the MASTER DAPT trial included “all-comer” high-bleeding-risk patients with no selection based on ischemic risk.

M. Alexander Otto, MDedge News

The trial was very well received by commentators at the ESC Hot Line presentation.

Chair of the session, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, described the trial as “practice-changing.”

And Robert Byrne, MD, Mater Private Hospital, Dublin, added: “This is a standout trial. We have become more comfortable with abbreviated DAPT in high-bleeding-risk patients, but definite evidence for this has been lacking until now. This study tells us that just 1 month of DAPT appears to be safe in that there was no increase in ischemic complications and there was a clear reduction in bleeding.”

The MASTER DAPT study involved 4,579 patients at high bleeding risk who had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent (Ultimaster, Terumo). Around half the patients had PCI for acute coronary syndrome (ACS) and half had it electively. One month after PCI they were randomly assigned to discontinue DAPT immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy).

The three co-primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding, all assessed cumulatively at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.

Dual antiplatelet therapy consisted of aspirin plus a P2Y12 inhibitor. The choices of the type of P2Y12 inhibitor for DAPT and the type of monotherapy after the discontinuation of DAPT were at the discretion of the investigator. Clopidogrel was the most popular choice, used as monotherapy in 54% of the patients in the abbreviated-therapy group and as part of DAPT in 79% of patients in the standard-therapy group.

Results showed that net adverse clinical events occurred in 7.5% of the abbreviated-therapy group and in 7.7% of the standard-therapy group (difference, –0.23 percentage points; 95% confidence interval, –1.80 to 1.33 percentage points; P < .001 for noninferiority).

Major adverse cardiac or cerebral events occurred in 6.1% of the abbreviated-therapy group and 5.9% of standard therapy group (difference, 0.11 percentage points; 95% CI, –1.29 to 1.51 percentage points; P = .001 for noninferiority).

Reduction in bleeding driven by BARC-2

Major bleeding or clinically relevant nonmajor bleeding occurred in 6.5% in the abbreviated-therapy group and in 9.4% in the standard-therapy group (difference, –2.82 percentage points; 95% CI, –4.40 to –1.24 percentage points; P < .001 for superiority).

“This is a highly statistically significant reduction in bleeding giving a number needed to treat of 35,” Dr. Valgimigli said.

The lower risk for bleeding in the abbreviated-therapy group was mainly due to the lower incidence of clinically relevant nonmajor bleeding events (BARC type 2) in this group than in the standard-therapy group (4.5% vs. 6.8%).

During the discussion, Dr. Byrne pointed out that the most serious type of bleeding (BARC type 3-5) was not reduced in the abbreviated DAPT group.

Dr. Valgimigli responded that the investigators were surprised about that because previous studies indicated that this most serious bleeding would be reduced, but he suggested that this may be explained by the standard group receiving 3-6 months of DAPT rather than a year or more in previous studies. “Having said that, BARC-2 bleeding is not a trivial event,” he added.
 

Can results be applied to other stents?

Dr. Byrne also questioned whether the results can be applied to patients receiving other types of stents – not just Ultimaster, which is not available everywhere. Dr. Valgimigli highlighted the low rate of stent thrombosis seen with the Ultimaster stent and said, “I would be scared to assume these results are reproducible with other stents.”

But Dr. Mehran challenged this view, saying, “I’m not so sure about that. I think we can probably extrapolate.”

In an interview, Dr. Mehran added: “I think this is one of the much-needed studies in our field. For the first time, we have a randomized trial on duration of DAPT in high-bleeding-risk patients. The study was inclusive, and enrolled truly high-bleeding-risk patients, including those on oral anticoagulants.  

“These results show that, although high-bleeding-risk patients are at high risk of ischemic events, just 1 month of DAPT works well for them regardless, by reducing bleeding, net adverse clinical events, and without increasing ischemic events,” she concluded.

In an editorial accompanying the publication, E. Magnus Ohman, MB, from Duke University, Durham, N.C., pointed out the wide CIs in the results, which he said introduced some uncertainly to the findings.

But he concluded that: “The findings of Dr. Valgimigli and colleagues are important and move us toward a shorter and simpler antithrombotic strategy after PCI.”

In an interview, Dr. Ohman pointed out that the Ultimaster stent is not available in the United States. “We have to think about whether this stent would perform differently to other third- or fourth-generation stents. I wouldn’t have thought so, but it is hard to say for sure.

“All in all, we are looking at shorter periods of DAPT now after PCI. Several trials have now suggested that is the way to go. The forthcoming U.S. PCI guidelines should put all the studies together and come up with recommendations on different patient groups,” he concluded.  

Several commentators said they would like to see the data on the patients receiving oral anticoagulants in the study before making firm conclusions on how to translate the results into clinical practice. “This is such an important group. It is difficult to interpret the results without this data,” Dr. Ohman noted.  Patients receiving oral anticoagulants, who made up 36% of the study population, will be the subject of a separate report to be presented at the ESC meeting.

The MASTER DAPT trial was supported by Terumo. Dr. Valgimigli reports research grants from Terumo, Abbott, and SMT and consulting or speaker fees from Terumo, Abbott, Daiichi Sankyo, Chiesi, Vesalio, Vifor, Avimedica, Medtronic, Boston Scientific, and AstraZeneca. Dr. Ohman reports grants from Abiomed, grants from Chiesi USA, personal fees from Cara Therapeutics, Genentech, Imbria, Impulse Dynamics, Milestone Pharmaceuticals, XyloCor, Cytokinetics, Dispersol, Otsuka, Pfizer, Cytosorbents, Neurocrine, and Paradigm, outside the submitted work.

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

Another trial has added to the movement toward shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).

MDedge News

In the MASTER DAPT trial involving patients at high risk for bleeding who had undergone implantation of a biodegradable-polymer sirolimus-eluting stent, switching from DAPT to single antiplatelet therapy at a median of 34 days after PCI was noninferior to the continuation of DAPT treatment for a median duration of 193 days with regard to the incidence of major adverse cardiac or cerebral events, and was associated with a lower incidence of major or clinically relevant bleeding.

The results of the study were presented by Marco Valgimigli, MD, Cardiocentro Ticino Institute, Lugano, Switzerland, on Aug. 28 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“It has been suggested in previous studies that if patients are at high bleeding risk, then they do not seem to derive ischemic benefit from prolonging DAPT, they just get the increased bleeding risk,” Dr. Valgimigli said. “But this has never been prospectively tested until now.”

He pointed out that patients at high bleeding risk are a large group, representing up to 40% of patients undergoing PCI, and the MASTER DAPT trial included “all-comer” high-bleeding-risk patients with no selection based on ischemic risk.

M. Alexander Otto, MDedge News

The trial was very well received by commentators at the ESC Hot Line presentation.

Chair of the session, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, described the trial as “practice-changing.”

And Robert Byrne, MD, Mater Private Hospital, Dublin, added: “This is a standout trial. We have become more comfortable with abbreviated DAPT in high-bleeding-risk patients, but definite evidence for this has been lacking until now. This study tells us that just 1 month of DAPT appears to be safe in that there was no increase in ischemic complications and there was a clear reduction in bleeding.”

The MASTER DAPT study involved 4,579 patients at high bleeding risk who had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent (Ultimaster, Terumo). Around half the patients had PCI for acute coronary syndrome (ACS) and half had it electively. One month after PCI they were randomly assigned to discontinue DAPT immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy).

The three co-primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding, all assessed cumulatively at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.

Dual antiplatelet therapy consisted of aspirin plus a P2Y12 inhibitor. The choices of the type of P2Y12 inhibitor for DAPT and the type of monotherapy after the discontinuation of DAPT were at the discretion of the investigator. Clopidogrel was the most popular choice, used as monotherapy in 54% of the patients in the abbreviated-therapy group and as part of DAPT in 79% of patients in the standard-therapy group.

Results showed that net adverse clinical events occurred in 7.5% of the abbreviated-therapy group and in 7.7% of the standard-therapy group (difference, –0.23 percentage points; 95% confidence interval, –1.80 to 1.33 percentage points; P < .001 for noninferiority).

Major adverse cardiac or cerebral events occurred in 6.1% of the abbreviated-therapy group and 5.9% of standard therapy group (difference, 0.11 percentage points; 95% CI, –1.29 to 1.51 percentage points; P = .001 for noninferiority).

Reduction in bleeding driven by BARC-2

Major bleeding or clinically relevant nonmajor bleeding occurred in 6.5% in the abbreviated-therapy group and in 9.4% in the standard-therapy group (difference, –2.82 percentage points; 95% CI, –4.40 to –1.24 percentage points; P < .001 for superiority).

“This is a highly statistically significant reduction in bleeding giving a number needed to treat of 35,” Dr. Valgimigli said.

The lower risk for bleeding in the abbreviated-therapy group was mainly due to the lower incidence of clinically relevant nonmajor bleeding events (BARC type 2) in this group than in the standard-therapy group (4.5% vs. 6.8%).

During the discussion, Dr. Byrne pointed out that the most serious type of bleeding (BARC type 3-5) was not reduced in the abbreviated DAPT group.

Dr. Valgimigli responded that the investigators were surprised about that because previous studies indicated that this most serious bleeding would be reduced, but he suggested that this may be explained by the standard group receiving 3-6 months of DAPT rather than a year or more in previous studies. “Having said that, BARC-2 bleeding is not a trivial event,” he added.
 

Can results be applied to other stents?

Dr. Byrne also questioned whether the results can be applied to patients receiving other types of stents – not just Ultimaster, which is not available everywhere. Dr. Valgimigli highlighted the low rate of stent thrombosis seen with the Ultimaster stent and said, “I would be scared to assume these results are reproducible with other stents.”

But Dr. Mehran challenged this view, saying, “I’m not so sure about that. I think we can probably extrapolate.”

In an interview, Dr. Mehran added: “I think this is one of the much-needed studies in our field. For the first time, we have a randomized trial on duration of DAPT in high-bleeding-risk patients. The study was inclusive, and enrolled truly high-bleeding-risk patients, including those on oral anticoagulants.  

“These results show that, although high-bleeding-risk patients are at high risk of ischemic events, just 1 month of DAPT works well for them regardless, by reducing bleeding, net adverse clinical events, and without increasing ischemic events,” she concluded.

In an editorial accompanying the publication, E. Magnus Ohman, MB, from Duke University, Durham, N.C., pointed out the wide CIs in the results, which he said introduced some uncertainly to the findings.

But he concluded that: “The findings of Dr. Valgimigli and colleagues are important and move us toward a shorter and simpler antithrombotic strategy after PCI.”

In an interview, Dr. Ohman pointed out that the Ultimaster stent is not available in the United States. “We have to think about whether this stent would perform differently to other third- or fourth-generation stents. I wouldn’t have thought so, but it is hard to say for sure.

“All in all, we are looking at shorter periods of DAPT now after PCI. Several trials have now suggested that is the way to go. The forthcoming U.S. PCI guidelines should put all the studies together and come up with recommendations on different patient groups,” he concluded.  

Several commentators said they would like to see the data on the patients receiving oral anticoagulants in the study before making firm conclusions on how to translate the results into clinical practice. “This is such an important group. It is difficult to interpret the results without this data,” Dr. Ohman noted.  Patients receiving oral anticoagulants, who made up 36% of the study population, will be the subject of a separate report to be presented at the ESC meeting.

The MASTER DAPT trial was supported by Terumo. Dr. Valgimigli reports research grants from Terumo, Abbott, and SMT and consulting or speaker fees from Terumo, Abbott, Daiichi Sankyo, Chiesi, Vesalio, Vifor, Avimedica, Medtronic, Boston Scientific, and AstraZeneca. Dr. Ohman reports grants from Abiomed, grants from Chiesi USA, personal fees from Cara Therapeutics, Genentech, Imbria, Impulse Dynamics, Milestone Pharmaceuticals, XyloCor, Cytokinetics, Dispersol, Otsuka, Pfizer, Cytosorbents, Neurocrine, and Paradigm, outside the submitted work.

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

Another trial has added to the movement toward shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).

MDedge News

In the MASTER DAPT trial involving patients at high risk for bleeding who had undergone implantation of a biodegradable-polymer sirolimus-eluting stent, switching from DAPT to single antiplatelet therapy at a median of 34 days after PCI was noninferior to the continuation of DAPT treatment for a median duration of 193 days with regard to the incidence of major adverse cardiac or cerebral events, and was associated with a lower incidence of major or clinically relevant bleeding.

The results of the study were presented by Marco Valgimigli, MD, Cardiocentro Ticino Institute, Lugano, Switzerland, on Aug. 28 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.

“It has been suggested in previous studies that if patients are at high bleeding risk, then they do not seem to derive ischemic benefit from prolonging DAPT, they just get the increased bleeding risk,” Dr. Valgimigli said. “But this has never been prospectively tested until now.”

He pointed out that patients at high bleeding risk are a large group, representing up to 40% of patients undergoing PCI, and the MASTER DAPT trial included “all-comer” high-bleeding-risk patients with no selection based on ischemic risk.

M. Alexander Otto, MDedge News

The trial was very well received by commentators at the ESC Hot Line presentation.

Chair of the session, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai, New York, described the trial as “practice-changing.”

And Robert Byrne, MD, Mater Private Hospital, Dublin, added: “This is a standout trial. We have become more comfortable with abbreviated DAPT in high-bleeding-risk patients, but definite evidence for this has been lacking until now. This study tells us that just 1 month of DAPT appears to be safe in that there was no increase in ischemic complications and there was a clear reduction in bleeding.”

The MASTER DAPT study involved 4,579 patients at high bleeding risk who had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent (Ultimaster, Terumo). Around half the patients had PCI for acute coronary syndrome (ACS) and half had it electively. One month after PCI they were randomly assigned to discontinue DAPT immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy).

The three co-primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding, all assessed cumulatively at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.

Dual antiplatelet therapy consisted of aspirin plus a P2Y12 inhibitor. The choices of the type of P2Y12 inhibitor for DAPT and the type of monotherapy after the discontinuation of DAPT were at the discretion of the investigator. Clopidogrel was the most popular choice, used as monotherapy in 54% of the patients in the abbreviated-therapy group and as part of DAPT in 79% of patients in the standard-therapy group.

Results showed that net adverse clinical events occurred in 7.5% of the abbreviated-therapy group and in 7.7% of the standard-therapy group (difference, –0.23 percentage points; 95% confidence interval, –1.80 to 1.33 percentage points; P < .001 for noninferiority).

Major adverse cardiac or cerebral events occurred in 6.1% of the abbreviated-therapy group and 5.9% of standard therapy group (difference, 0.11 percentage points; 95% CI, –1.29 to 1.51 percentage points; P = .001 for noninferiority).

Reduction in bleeding driven by BARC-2

Major bleeding or clinically relevant nonmajor bleeding occurred in 6.5% in the abbreviated-therapy group and in 9.4% in the standard-therapy group (difference, –2.82 percentage points; 95% CI, –4.40 to –1.24 percentage points; P < .001 for superiority).

“This is a highly statistically significant reduction in bleeding giving a number needed to treat of 35,” Dr. Valgimigli said.

The lower risk for bleeding in the abbreviated-therapy group was mainly due to the lower incidence of clinically relevant nonmajor bleeding events (BARC type 2) in this group than in the standard-therapy group (4.5% vs. 6.8%).

During the discussion, Dr. Byrne pointed out that the most serious type of bleeding (BARC type 3-5) was not reduced in the abbreviated DAPT group.

Dr. Valgimigli responded that the investigators were surprised about that because previous studies indicated that this most serious bleeding would be reduced, but he suggested that this may be explained by the standard group receiving 3-6 months of DAPT rather than a year or more in previous studies. “Having said that, BARC-2 bleeding is not a trivial event,” he added.
 

Can results be applied to other stents?

Dr. Byrne also questioned whether the results can be applied to patients receiving other types of stents – not just Ultimaster, which is not available everywhere. Dr. Valgimigli highlighted the low rate of stent thrombosis seen with the Ultimaster stent and said, “I would be scared to assume these results are reproducible with other stents.”

But Dr. Mehran challenged this view, saying, “I’m not so sure about that. I think we can probably extrapolate.”

In an interview, Dr. Mehran added: “I think this is one of the much-needed studies in our field. For the first time, we have a randomized trial on duration of DAPT in high-bleeding-risk patients. The study was inclusive, and enrolled truly high-bleeding-risk patients, including those on oral anticoagulants.  

“These results show that, although high-bleeding-risk patients are at high risk of ischemic events, just 1 month of DAPT works well for them regardless, by reducing bleeding, net adverse clinical events, and without increasing ischemic events,” she concluded.

In an editorial accompanying the publication, E. Magnus Ohman, MB, from Duke University, Durham, N.C., pointed out the wide CIs in the results, which he said introduced some uncertainly to the findings.

But he concluded that: “The findings of Dr. Valgimigli and colleagues are important and move us toward a shorter and simpler antithrombotic strategy after PCI.”

In an interview, Dr. Ohman pointed out that the Ultimaster stent is not available in the United States. “We have to think about whether this stent would perform differently to other third- or fourth-generation stents. I wouldn’t have thought so, but it is hard to say for sure.

“All in all, we are looking at shorter periods of DAPT now after PCI. Several trials have now suggested that is the way to go. The forthcoming U.S. PCI guidelines should put all the studies together and come up with recommendations on different patient groups,” he concluded.  

Several commentators said they would like to see the data on the patients receiving oral anticoagulants in the study before making firm conclusions on how to translate the results into clinical practice. “This is such an important group. It is difficult to interpret the results without this data,” Dr. Ohman noted.  Patients receiving oral anticoagulants, who made up 36% of the study population, will be the subject of a separate report to be presented at the ESC meeting.

The MASTER DAPT trial was supported by Terumo. Dr. Valgimigli reports research grants from Terumo, Abbott, and SMT and consulting or speaker fees from Terumo, Abbott, Daiichi Sankyo, Chiesi, Vesalio, Vifor, Avimedica, Medtronic, Boston Scientific, and AstraZeneca. Dr. Ohman reports grants from Abiomed, grants from Chiesi USA, personal fees from Cara Therapeutics, Genentech, Imbria, Impulse Dynamics, Milestone Pharmaceuticals, XyloCor, Cytokinetics, Dispersol, Otsuka, Pfizer, Cytosorbents, Neurocrine, and Paradigm, outside the submitted work.

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

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.

Key clinical point: Although rates of principal psoriasis hospitalizations have decreased among patients with psoriasis in the last 2 decades in the United States, hospitalization for non-psoriatic reasons has increased, which may be attributed to increased comorbidity burden driving admissions because of comorbidities.

Major finding: Between 1998 and 2018, the incidence of hospitalizations with either principal or secondary diagnosis of psoriasis increased from 17.9 to 52.0 per 100,000 persons, the proportion of patients with psoriasis hospitalized with psoriasis as principal diagnosis reduced from 4.1% to 1.0%, and those with Charlson Comorbidity Index score of 3 or higher increased from 13.9% to 30.9% (all adjusted P-trend < .0001).

Study details: This was a 21-year longitudinal trend analysis of the National Inpatient Sample database between 1998 and 2018 including adults with a principal or secondary diagnosis of psoriasis.

Disclosures: The study did not receive any funding. The authors declared no conflict of interests.

Source: Edigin E et al. J Eur Acad Dermatol Venereol. 2021 Aug 9. doi: 10.1111/jdv.17590.