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DIY nerve stimulation effective in episodic migraine
results from a phase 3 study show.
This is great news for headache patients who want to explore nondrug treatment options, said study investigator Deena E. Kuruvilla, MD, neurologist and headache specialist at the Westport Headache Institute, Connecticut.
She added that such devices “aren’t always part of the conversation when we’re discussing preventive and acute treatments with our patients. Making this a regular part of the conversation might be helpful to patients.”
The findings were presented at ANA 2021: 146th Annual Meeting of the American Neurological Association (ANA), which was held online.
A key therapeutic target
The randomized, double-blind trial compared E-TNS with sham stimulation for the acute treatment of migraine.
The E-TNS device (Verum Cefaly Abortive Program) stimulates the supraorbital nerve in the forehead. “This nerve is a branch of the trigeminal nerve, which is thought to be the key player in migraine pathophysiology,” Dr. Kuruvilla noted.
The device has been cleared by the U.S. Food and Drug Administration for acute and preventive treatment of migraine.
During a run-in period before randomization, patients were asked to keep a detailed headache diary and to become comfortable using the trial device to treat an acute migraine attack at home.
The study enrolled 538 adult patients at 10 centers. The patients were aged 18 to 65 years, and they had been having episodic migraines, with or without aura, for at least a year. The participants had to have received a migraine diagnosis before age 50, and they had to be experiencing an attack of migraine 2 to 8 days per month.
The patients used the device only for a migraine of at least moderate intensity that was accompanied by at least one migraine-associated symptom, such as photophobia, phonophobia, or nausea. They were asked not to take rescue medication prior to or during a therapy session.
Study participants applied either neurostimulation or sham stimulation for a continuous 2-hour period within 4 hours of a migraine attack over the 2-month study period.
The two primary endpoints were pain freedom and freedom from the most bothersome migraine-associated symptoms at 2 hours.
Compared to sham treatment, active stimulation was more effective in achieving pain freedom (P = .043) and freedom from the most bothersome migraine-associated symptom (P = .001) at 2 hours.
“So the study did meet both primary endpoints with statistical significance,” said Dr. Kuruvilla.
The five secondary endpoints included pain relief at 2 hours; absence of all migraine-associated symptoms at 2 hours; use of rescue medication within 24 hours; sustained pain freedom at 24 hours; and sustained pain relief at 24 hours.
All but one of these endpoints reached statistical significance, showing superiority for the active intervention. The only exception was in regard to use of rescue medication.
The most common adverse event (AE) was forehead paresthesia, discomfort, or burning, which was more common in the active-treatment group than in the sham-treatment group (P = .009). There were four cases of nausea or vomiting in the active-treatment group and none in the sham-treatment group. There were no serious AEs.
Available over the counter
Both moderators of the headache poster tour that featured this study – Justin C. McArthur, MBBS, from Johns Hopkins University, Baltimore, and Steven Galetta, MD, from NYU Grossman School of Medicine – praised the presentation.
Dr. Galetta questioned whether patients were receiving preventive therapies. Dr. Kuruvilla said that the patients were allowed to enter the trial while taking preventive therapies, including antiepileptic treatments, blood pressure medications, and antidepressants, but that they had to be receiving stable doses.
The investigators didn’t distinguish between participants who were taking preventive therapies and those who weren’t, she said. “The aim was really to look at acute treatment for migraine,” and patients taking such medication “had been stable on their regimen for a pretty prolonged period of time.”
Dr. McArthur asked about the origin of the nausea some patients experienced.
It was difficult to determine whether the nausea was an aspect of an individual patient’s migraine attack or was an effect of the stimulation, said Dr. Kuruvilla. She noted that some patients found the vibrating sensation from the device uncomfortable and that nausea could be associated with pain at the site.
The device costs $300 to $400 (U.S.) and is available over the counter.
Dr. Kuruvilla is a consultant for Cefaly, Neurolief, Theranica, Now What Media, and Kx Advisors. She is on the speakers bureau for AbbVie/Allergan, Amgen/Novartis, Lilly, the American Headache Society, Biohaven, and CME meeting, and she is on an advisory board at AbbVie/Allergan, Lilly, Theranica, and Amgen/Novartis. She is editor and associate editor of Healthline and is an author for WebMD/Medscape, Healthline.
A version of this article first appeared on Medscape.com.
results from a phase 3 study show.
This is great news for headache patients who want to explore nondrug treatment options, said study investigator Deena E. Kuruvilla, MD, neurologist and headache specialist at the Westport Headache Institute, Connecticut.
She added that such devices “aren’t always part of the conversation when we’re discussing preventive and acute treatments with our patients. Making this a regular part of the conversation might be helpful to patients.”
The findings were presented at ANA 2021: 146th Annual Meeting of the American Neurological Association (ANA), which was held online.
A key therapeutic target
The randomized, double-blind trial compared E-TNS with sham stimulation for the acute treatment of migraine.
The E-TNS device (Verum Cefaly Abortive Program) stimulates the supraorbital nerve in the forehead. “This nerve is a branch of the trigeminal nerve, which is thought to be the key player in migraine pathophysiology,” Dr. Kuruvilla noted.
The device has been cleared by the U.S. Food and Drug Administration for acute and preventive treatment of migraine.
During a run-in period before randomization, patients were asked to keep a detailed headache diary and to become comfortable using the trial device to treat an acute migraine attack at home.
The study enrolled 538 adult patients at 10 centers. The patients were aged 18 to 65 years, and they had been having episodic migraines, with or without aura, for at least a year. The participants had to have received a migraine diagnosis before age 50, and they had to be experiencing an attack of migraine 2 to 8 days per month.
The patients used the device only for a migraine of at least moderate intensity that was accompanied by at least one migraine-associated symptom, such as photophobia, phonophobia, or nausea. They were asked not to take rescue medication prior to or during a therapy session.
Study participants applied either neurostimulation or sham stimulation for a continuous 2-hour period within 4 hours of a migraine attack over the 2-month study period.
The two primary endpoints were pain freedom and freedom from the most bothersome migraine-associated symptoms at 2 hours.
Compared to sham treatment, active stimulation was more effective in achieving pain freedom (P = .043) and freedom from the most bothersome migraine-associated symptom (P = .001) at 2 hours.
“So the study did meet both primary endpoints with statistical significance,” said Dr. Kuruvilla.
The five secondary endpoints included pain relief at 2 hours; absence of all migraine-associated symptoms at 2 hours; use of rescue medication within 24 hours; sustained pain freedom at 24 hours; and sustained pain relief at 24 hours.
All but one of these endpoints reached statistical significance, showing superiority for the active intervention. The only exception was in regard to use of rescue medication.
The most common adverse event (AE) was forehead paresthesia, discomfort, or burning, which was more common in the active-treatment group than in the sham-treatment group (P = .009). There were four cases of nausea or vomiting in the active-treatment group and none in the sham-treatment group. There were no serious AEs.
Available over the counter
Both moderators of the headache poster tour that featured this study – Justin C. McArthur, MBBS, from Johns Hopkins University, Baltimore, and Steven Galetta, MD, from NYU Grossman School of Medicine – praised the presentation.
Dr. Galetta questioned whether patients were receiving preventive therapies. Dr. Kuruvilla said that the patients were allowed to enter the trial while taking preventive therapies, including antiepileptic treatments, blood pressure medications, and antidepressants, but that they had to be receiving stable doses.
The investigators didn’t distinguish between participants who were taking preventive therapies and those who weren’t, she said. “The aim was really to look at acute treatment for migraine,” and patients taking such medication “had been stable on their regimen for a pretty prolonged period of time.”
Dr. McArthur asked about the origin of the nausea some patients experienced.
It was difficult to determine whether the nausea was an aspect of an individual patient’s migraine attack or was an effect of the stimulation, said Dr. Kuruvilla. She noted that some patients found the vibrating sensation from the device uncomfortable and that nausea could be associated with pain at the site.
The device costs $300 to $400 (U.S.) and is available over the counter.
Dr. Kuruvilla is a consultant for Cefaly, Neurolief, Theranica, Now What Media, and Kx Advisors. She is on the speakers bureau for AbbVie/Allergan, Amgen/Novartis, Lilly, the American Headache Society, Biohaven, and CME meeting, and she is on an advisory board at AbbVie/Allergan, Lilly, Theranica, and Amgen/Novartis. She is editor and associate editor of Healthline and is an author for WebMD/Medscape, Healthline.
A version of this article first appeared on Medscape.com.
results from a phase 3 study show.
This is great news for headache patients who want to explore nondrug treatment options, said study investigator Deena E. Kuruvilla, MD, neurologist and headache specialist at the Westport Headache Institute, Connecticut.
She added that such devices “aren’t always part of the conversation when we’re discussing preventive and acute treatments with our patients. Making this a regular part of the conversation might be helpful to patients.”
The findings were presented at ANA 2021: 146th Annual Meeting of the American Neurological Association (ANA), which was held online.
A key therapeutic target
The randomized, double-blind trial compared E-TNS with sham stimulation for the acute treatment of migraine.
The E-TNS device (Verum Cefaly Abortive Program) stimulates the supraorbital nerve in the forehead. “This nerve is a branch of the trigeminal nerve, which is thought to be the key player in migraine pathophysiology,” Dr. Kuruvilla noted.
The device has been cleared by the U.S. Food and Drug Administration for acute and preventive treatment of migraine.
During a run-in period before randomization, patients were asked to keep a detailed headache diary and to become comfortable using the trial device to treat an acute migraine attack at home.
The study enrolled 538 adult patients at 10 centers. The patients were aged 18 to 65 years, and they had been having episodic migraines, with or without aura, for at least a year. The participants had to have received a migraine diagnosis before age 50, and they had to be experiencing an attack of migraine 2 to 8 days per month.
The patients used the device only for a migraine of at least moderate intensity that was accompanied by at least one migraine-associated symptom, such as photophobia, phonophobia, or nausea. They were asked not to take rescue medication prior to or during a therapy session.
Study participants applied either neurostimulation or sham stimulation for a continuous 2-hour period within 4 hours of a migraine attack over the 2-month study period.
The two primary endpoints were pain freedom and freedom from the most bothersome migraine-associated symptoms at 2 hours.
Compared to sham treatment, active stimulation was more effective in achieving pain freedom (P = .043) and freedom from the most bothersome migraine-associated symptom (P = .001) at 2 hours.
“So the study did meet both primary endpoints with statistical significance,” said Dr. Kuruvilla.
The five secondary endpoints included pain relief at 2 hours; absence of all migraine-associated symptoms at 2 hours; use of rescue medication within 24 hours; sustained pain freedom at 24 hours; and sustained pain relief at 24 hours.
All but one of these endpoints reached statistical significance, showing superiority for the active intervention. The only exception was in regard to use of rescue medication.
The most common adverse event (AE) was forehead paresthesia, discomfort, or burning, which was more common in the active-treatment group than in the sham-treatment group (P = .009). There were four cases of nausea or vomiting in the active-treatment group and none in the sham-treatment group. There were no serious AEs.
Available over the counter
Both moderators of the headache poster tour that featured this study – Justin C. McArthur, MBBS, from Johns Hopkins University, Baltimore, and Steven Galetta, MD, from NYU Grossman School of Medicine – praised the presentation.
Dr. Galetta questioned whether patients were receiving preventive therapies. Dr. Kuruvilla said that the patients were allowed to enter the trial while taking preventive therapies, including antiepileptic treatments, blood pressure medications, and antidepressants, but that they had to be receiving stable doses.
The investigators didn’t distinguish between participants who were taking preventive therapies and those who weren’t, she said. “The aim was really to look at acute treatment for migraine,” and patients taking such medication “had been stable on their regimen for a pretty prolonged period of time.”
Dr. McArthur asked about the origin of the nausea some patients experienced.
It was difficult to determine whether the nausea was an aspect of an individual patient’s migraine attack or was an effect of the stimulation, said Dr. Kuruvilla. She noted that some patients found the vibrating sensation from the device uncomfortable and that nausea could be associated with pain at the site.
The device costs $300 to $400 (U.S.) and is available over the counter.
Dr. Kuruvilla is a consultant for Cefaly, Neurolief, Theranica, Now What Media, and Kx Advisors. She is on the speakers bureau for AbbVie/Allergan, Amgen/Novartis, Lilly, the American Headache Society, Biohaven, and CME meeting, and she is on an advisory board at AbbVie/Allergan, Lilly, Theranica, and Amgen/Novartis. She is editor and associate editor of Healthline and is an author for WebMD/Medscape, Healthline.
A version of this article first appeared on Medscape.com.
FROM ANA
Life-threatening paradoxical bronchospasm may escape recognition in patients with COPD or asthma
according to a researcher who reviewed spirometry test results from U.S. military veterans.
Nearly 1.5% of the tests met the criteria for paradoxical bronchospasm, which refers to airway constriction that may rapidly occur after inhalation of a short-acting beta2 agonist (SABA) such as albuterol.
However, none of those reports alluded to paradoxical bronchospasm, said investigator Malvika Kaul, MD, fellow in the department of pulmonary and critical care at the University of Illinois at Chicago and the Jesse Brown Veterans Affairs Medical Center, also in Chicago.
“Paradoxical bronchospasm was neither recognized nor reported in any spirometry test results,” Dr. Kaul said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
By recognizing paradoxical bronchospasm, health care providers could address its clinical implications and identify potential alternative management options, according to Dr. Kaul.
“We hope in the future, education of clinicians about this phenomena is emphasized,” Dr. Kaul said in her presentation.
Recognizing paradoxical bronchospasm
In an interview, Dr. Kaul said she began researching paradoxical bronchospasm after encountering a patient who had an acute reaction to albuterol during a pulmonary function test.
“I was not taught about it, and I wasn’t recognizing that pattern very frequently in my patients,” she said.
Prescribing information for Food and Drug Administration–approved SABAs include a warning that life-threatening paradoxical bronchospasm may occur, said Dr. Kaul.
If paradoxical bronchospasm occurs, the patient should discontinue the medication immediately and start on alternative therapy, according to the available prescribing information for albuterol sulfate.
Paradoxical bronchospasm has been linked to worsened respiratory outcomes, including more frequent exacerbations, in patients with obstructive lung diseases, according to Dr. Kaul.
Two previous large studies pegged the prevalence of paradoxical bronchospasm at around 4.5% in patients with COPD or asthma, but “it has not been reported or addressed in high-risk population, such as veterans who have high prevalence of obstructive lung diseases like COPD,” Dr. Kaul said.
Latest study results
Dr. Kaul described a retrospective analysis of 1,150 pre- and postbronchodilator spirometry tests conducted in patients with COPD or asthma at the Jesse Brown VA Medical Center between 2017 and 2020.
A positive paradoxical bronchodilator response was defined as a decrease of least 12% and 200 mL in forced expiratory volume in 1 second and forced vital capacity from baseline after four puffs of albuterol were inhaled, Dr. Kaul said.
Out of 18 reviewed spirometry results that met the criteria, none of the test results reported or recognized paradoxical bronchospasm, according to Dr. Kaul.
Those meeting the criteria were predominantly COPD patients, according to Dr. Kaul, who said 12 had an underlying diagnosis COPD, 4 had asthma, and 2 had COPD and asthma.
Of the 18 patients, 13 were African American, and all but 1 of the 18 patients had a current or past smoking history, according to reported data.
A history of obstructive sleep apnea was reported in nine patients, and history of gastroesophageal reflux disease was also reported in nine patients. Eleven patients had emphysema.
Greater awareness needed
Results of this study emphasize the need to recognize potential cases paradoxical bronchospasm in clinical practice, as well as a need for more research, according to Allen J. Blaivas, DO, FCCP, chair of the CHEST Airway Disorders NetWork.
“It’s something to be on the alert for, and certainly be aware that, if your patient is telling you that they feel worse, we shouldn’t just pooh-pooh it,” said Dr. Blaivas, who is medical director of the intensive care unit at the East Orange campus of the VA New Jersey Health Care System.
Further research could focus on breaking down whether patients with suspected paradoxical bronchospasm are using metered-dose inhalers or nebulizers, whether or not they are also taking inhaled corticosteroids, and whether prospective testing can confirm paradoxical bronchospasm in patients who report tightness after using a SABA, he said in an interview.
Dr. Kaul and coauthor Israel Rubinstein, MD had no relevant relationships to disclose. Dr. Blaivas had no relevant relationships to disclose.
according to a researcher who reviewed spirometry test results from U.S. military veterans.
Nearly 1.5% of the tests met the criteria for paradoxical bronchospasm, which refers to airway constriction that may rapidly occur after inhalation of a short-acting beta2 agonist (SABA) such as albuterol.
However, none of those reports alluded to paradoxical bronchospasm, said investigator Malvika Kaul, MD, fellow in the department of pulmonary and critical care at the University of Illinois at Chicago and the Jesse Brown Veterans Affairs Medical Center, also in Chicago.
“Paradoxical bronchospasm was neither recognized nor reported in any spirometry test results,” Dr. Kaul said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
By recognizing paradoxical bronchospasm, health care providers could address its clinical implications and identify potential alternative management options, according to Dr. Kaul.
“We hope in the future, education of clinicians about this phenomena is emphasized,” Dr. Kaul said in her presentation.
Recognizing paradoxical bronchospasm
In an interview, Dr. Kaul said she began researching paradoxical bronchospasm after encountering a patient who had an acute reaction to albuterol during a pulmonary function test.
“I was not taught about it, and I wasn’t recognizing that pattern very frequently in my patients,” she said.
Prescribing information for Food and Drug Administration–approved SABAs include a warning that life-threatening paradoxical bronchospasm may occur, said Dr. Kaul.
If paradoxical bronchospasm occurs, the patient should discontinue the medication immediately and start on alternative therapy, according to the available prescribing information for albuterol sulfate.
Paradoxical bronchospasm has been linked to worsened respiratory outcomes, including more frequent exacerbations, in patients with obstructive lung diseases, according to Dr. Kaul.
Two previous large studies pegged the prevalence of paradoxical bronchospasm at around 4.5% in patients with COPD or asthma, but “it has not been reported or addressed in high-risk population, such as veterans who have high prevalence of obstructive lung diseases like COPD,” Dr. Kaul said.
Latest study results
Dr. Kaul described a retrospective analysis of 1,150 pre- and postbronchodilator spirometry tests conducted in patients with COPD or asthma at the Jesse Brown VA Medical Center between 2017 and 2020.
A positive paradoxical bronchodilator response was defined as a decrease of least 12% and 200 mL in forced expiratory volume in 1 second and forced vital capacity from baseline after four puffs of albuterol were inhaled, Dr. Kaul said.
Out of 18 reviewed spirometry results that met the criteria, none of the test results reported or recognized paradoxical bronchospasm, according to Dr. Kaul.
Those meeting the criteria were predominantly COPD patients, according to Dr. Kaul, who said 12 had an underlying diagnosis COPD, 4 had asthma, and 2 had COPD and asthma.
Of the 18 patients, 13 were African American, and all but 1 of the 18 patients had a current or past smoking history, according to reported data.
A history of obstructive sleep apnea was reported in nine patients, and history of gastroesophageal reflux disease was also reported in nine patients. Eleven patients had emphysema.
Greater awareness needed
Results of this study emphasize the need to recognize potential cases paradoxical bronchospasm in clinical practice, as well as a need for more research, according to Allen J. Blaivas, DO, FCCP, chair of the CHEST Airway Disorders NetWork.
“It’s something to be on the alert for, and certainly be aware that, if your patient is telling you that they feel worse, we shouldn’t just pooh-pooh it,” said Dr. Blaivas, who is medical director of the intensive care unit at the East Orange campus of the VA New Jersey Health Care System.
Further research could focus on breaking down whether patients with suspected paradoxical bronchospasm are using metered-dose inhalers or nebulizers, whether or not they are also taking inhaled corticosteroids, and whether prospective testing can confirm paradoxical bronchospasm in patients who report tightness after using a SABA, he said in an interview.
Dr. Kaul and coauthor Israel Rubinstein, MD had no relevant relationships to disclose. Dr. Blaivas had no relevant relationships to disclose.
according to a researcher who reviewed spirometry test results from U.S. military veterans.
Nearly 1.5% of the tests met the criteria for paradoxical bronchospasm, which refers to airway constriction that may rapidly occur after inhalation of a short-acting beta2 agonist (SABA) such as albuterol.
However, none of those reports alluded to paradoxical bronchospasm, said investigator Malvika Kaul, MD, fellow in the department of pulmonary and critical care at the University of Illinois at Chicago and the Jesse Brown Veterans Affairs Medical Center, also in Chicago.
“Paradoxical bronchospasm was neither recognized nor reported in any spirometry test results,” Dr. Kaul said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
By recognizing paradoxical bronchospasm, health care providers could address its clinical implications and identify potential alternative management options, according to Dr. Kaul.
“We hope in the future, education of clinicians about this phenomena is emphasized,” Dr. Kaul said in her presentation.
Recognizing paradoxical bronchospasm
In an interview, Dr. Kaul said she began researching paradoxical bronchospasm after encountering a patient who had an acute reaction to albuterol during a pulmonary function test.
“I was not taught about it, and I wasn’t recognizing that pattern very frequently in my patients,” she said.
Prescribing information for Food and Drug Administration–approved SABAs include a warning that life-threatening paradoxical bronchospasm may occur, said Dr. Kaul.
If paradoxical bronchospasm occurs, the patient should discontinue the medication immediately and start on alternative therapy, according to the available prescribing information for albuterol sulfate.
Paradoxical bronchospasm has been linked to worsened respiratory outcomes, including more frequent exacerbations, in patients with obstructive lung diseases, according to Dr. Kaul.
Two previous large studies pegged the prevalence of paradoxical bronchospasm at around 4.5% in patients with COPD or asthma, but “it has not been reported or addressed in high-risk population, such as veterans who have high prevalence of obstructive lung diseases like COPD,” Dr. Kaul said.
Latest study results
Dr. Kaul described a retrospective analysis of 1,150 pre- and postbronchodilator spirometry tests conducted in patients with COPD or asthma at the Jesse Brown VA Medical Center between 2017 and 2020.
A positive paradoxical bronchodilator response was defined as a decrease of least 12% and 200 mL in forced expiratory volume in 1 second and forced vital capacity from baseline after four puffs of albuterol were inhaled, Dr. Kaul said.
Out of 18 reviewed spirometry results that met the criteria, none of the test results reported or recognized paradoxical bronchospasm, according to Dr. Kaul.
Those meeting the criteria were predominantly COPD patients, according to Dr. Kaul, who said 12 had an underlying diagnosis COPD, 4 had asthma, and 2 had COPD and asthma.
Of the 18 patients, 13 were African American, and all but 1 of the 18 patients had a current or past smoking history, according to reported data.
A history of obstructive sleep apnea was reported in nine patients, and history of gastroesophageal reflux disease was also reported in nine patients. Eleven patients had emphysema.
Greater awareness needed
Results of this study emphasize the need to recognize potential cases paradoxical bronchospasm in clinical practice, as well as a need for more research, according to Allen J. Blaivas, DO, FCCP, chair of the CHEST Airway Disorders NetWork.
“It’s something to be on the alert for, and certainly be aware that, if your patient is telling you that they feel worse, we shouldn’t just pooh-pooh it,” said Dr. Blaivas, who is medical director of the intensive care unit at the East Orange campus of the VA New Jersey Health Care System.
Further research could focus on breaking down whether patients with suspected paradoxical bronchospasm are using metered-dose inhalers or nebulizers, whether or not they are also taking inhaled corticosteroids, and whether prospective testing can confirm paradoxical bronchospasm in patients who report tightness after using a SABA, he said in an interview.
Dr. Kaul and coauthor Israel Rubinstein, MD had no relevant relationships to disclose. Dr. Blaivas had no relevant relationships to disclose.
FROM CHEST 2021
Could your patient benefit? New trials in lung cancer
Untreated PD-L1 non–small cell lung cancer (NSCLC). comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.
Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.
Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.
Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.
Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.
Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.
All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).
A version of this article first appeared on Medscape.com.
Untreated PD-L1 non–small cell lung cancer (NSCLC). comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.
Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.
Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.
Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.
Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.
Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.
All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).
A version of this article first appeared on Medscape.com.
Untreated PD-L1 non–small cell lung cancer (NSCLC). comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.
Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.
Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.
Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.
Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.
Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.
All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).
A version of this article first appeared on Medscape.com.
Gut bacteria may fuel prostate cancer treatment resistance
A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.
Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.
A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.
Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.
Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.
But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.
The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.
A version of this article first appeared on WebMD.com.
A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.
Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.
A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.
Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.
Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.
But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.
The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.
A version of this article first appeared on WebMD.com.
A mainstay of treatment for prostate cancer is to deprive it of androgens, the hormones that make it grow. The testes are the main source of these hormones, so treatment can consist of either surgical removal of these organs or use of drugs to block their hormone production.
Over time, some prostate cancers become resistant to these treatments and begin to expand again. As with many cancers that show these behaviors, finding exactly what makes them resistant can be tricky.
A culprit may be bacteria that live in the gut. Researchers found that in castrated mice and in people having androgen deprivation therapy, some of these gut bacteria start producing androgens that are easily taken into the bloodstream. According to these new findings,published in the journal Science, the androgens seem to support the growth of prostate cancer and its resistance to treatment.
Androgen deprivation treatment may also lead to more of these hormone-producing microbes in the gut, the results suggest. Fecal bacterial of people with treatment-resistant prostate cancer also showed a link to lower life expectancy.
Fecal transplants from mice with treatment-resistant prostate cancer could trigger resistance in animals with disease susceptible to these hormones. When these mice received fecal transplants from humans with resistant cancer, the effect was the same: a shift to treatment resistance.
But the converse also was true: Fecal transplants from mice or humans with hormone-susceptible cancer contributed to limiting tumor growth.
The findings may suggest new therapeutic targets: the microbes living in the gut. In mouse studies, the researchers found that when they wiped out these bacteria, the cancer was much slower to progress to treatment resistance. Authors of a commentary accompanying the study say there are other places to look for bacteria that might be making these hormones, too, including the urinary tract or even in the tumor itself.
A version of this article first appeared on WebMD.com.
No advantages to using ADM in implant-based breast reconstruction
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A European study involving 155 women found that the use of acellular dermal matrix (ADM) did not lead to fewer reoperations, nor was it superior in terms of health-related quality of life or patient-reported cosmetic outcomes.
“We feel that women considering implant-based reconstructions for breast cancer should be informed about the lack of evidence supporting its advantage,” said lead author Fredrik Lohmander MD, department of breast and endocrine surgery, section of breast urgery, Karolinska University Hospital, Stockholm.
It is difficult to say generally whether ADM should be used in IBBR, he noted. “We can only conclude from our trial that there is no hard evidence that ADM is beneficial when performing breast reconstructions with implants,” he said in an interview. “In selected patients, ADM might be indicated.”
The study was conducted in Sweden and the United Kingdom. “Mostly because of high costs, ADM in implant-based breast reconstructions in Sweden is not frequently used,” Dr. Lohmander said. “It is slightly more common in the U.K., but much more common in the U.S.A.”
Although biological meshes have received regulatory approval by the U.S. Food and Drug Administration for reconstructive purposes, ADM has not been approved for use in breast reconstruction surgery, and its use in this setting is off label.
The study was published online October 1 in JAMA Network Open.
Any advantage to using mesh device?
Previous studies of ADMs suggested that the mesh device conferred several benefits, including superior cosmetic results, less need for tissue expanders, fewer elective reoperations, and less capsular contracture. The use of a mesh device also enlarges the subpectoral pocket, which allows for larger fixed-volume implants, the authors note.
However, these suggested advantages have not been universally accepted, and the authors note that there have been reports of associated harm, such as higher rates of infection and implant loss.
The new study included 135 women from five centers in Sweden and the United Kingdom. The patients had breast cancer and had planned to undergo mastectomy and immediate IBBR between 2014 and May 2017.
The primary endpoint was the number of repeat surgeries at 2 years.
At the 2-year follow-up, 31 patients (48%) in the ADM group had undergone at least one reoperation on the ipsilateral side, vs 35 (54%) in the control group (P = .54). Results were similar for the contralateral side: 34 (53%) vs 31 (48%).
Two patients in the ADM group and three patients in the control group underwent a risk-reducing mastectomy on the contralateral side. These five surgeries were included in the final analysis.
For nine patients (14%) in the ADM arm, the implant was removed. Four of the removals took place within 6 months after early surgical complications. In the control group, seven patients (11%) underwent implant removal; four were removed within 6 months, owing to early surgical complications.
The secondary endpoint was postoperative health-related quality of life, including perception of body image and satisfaction with cosmetic outcome. There were no significant differences between the two groups.
Some questions remain
Approached for comment on the study, Sameer A. Patel, MD, FACS, chief of plastic and reconstructive surgery at Fox Chase Cancer Center, Philadelphia, noted that the practice of using AMD for breast reconstruction is quite common in the United States, so these data are informative and add to the current understanding of the value of ADM in breast reconstruction. “The study hypothesized that the use of ADM would reduce the number of reoperations within the first 24 months, which it did not,” he said. “This is despite the fact that the ADM group had a significantly higher number of direct-to-implant reconstructions.”
Importantly, the study showed that patient-reported outcomes, as opposed to surgeon’s evaluation of outcomes, were also not different for the most part between the two groups, Dr. Patel pointed out. “The only exception of small favorable advantage in the ADM group was for fitting bras,” he said.
However, there were limitations to the study’s endpoint. “I would add that there are some purported advantages of using ADM, such as reduction in postoperative pain and reduction in length of hospital stay, which are not evaluated by this study,” Patel explained. “Also, I am not certain that they can conclude from this study that capsular contracture is not reduced, because it is not designed to evaluate that.”
But the biggest limitation is one that study authors point out in their discussion at the end of the article, he added. “The use of prepectoral reconstruction is rapidly replacing the dual plane reconstruction that this paper used in the ADM group,” Dr. Patel said. “The role of ADM in prepectoral reconstruction is somewhat different than in the dual plane reconstruction, and so these results may not necessarily be extrapolated to prepectoral reconstruction.”
The study was funded with grants from the Swedish Breast Cancer Association and Stockholm City Council. The trial was initiated by Karolinska University Hospital and Karolinska Institutet. Acelity (an Allergan company) supplied the study with acellular dermal matrix meshes. Dr. Lohmander and Dr. Patel have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Dupilumab-improved lung function lasts in children with moderate to severe asthma
Add-on treatment with dupilumab may improve lung function in children aged 6-11 years with uncontrolled moderate to severe type 2 inflammatory asthma, results from a randomized, placebo-controlled, phase 3 study show.
Improvements in lung function parameters were observed as early as 2 weeks and persisted over the 52-week treatment period among children in the LIBERTY ASTHMA VOYAGE study, according to investigator Leonard B. Bacharier, MD, of Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn.
“Dupilumab led to clinically meaningful rapid and sustained improvements in lung function parameters,” Dr. Bacharier said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
The improvements in forced expiratory volume in 1 second (FEV1) and other measures reported for children with moderate to severe asthma who have the type 2 phenotype, which is the most common driver of pediatric asthma, according to Dr. Bacharier.
“Many children with moderate to severe asthma have abnormal lung function, and this can be a risk factor for future lung disease in adulthood,” Dr. Bacharier said in his presentation.
The VOYAGE continues
The findings presented at the meeting build on another report earlier this year from the LIBERTY ASTHMA VOYAGE study demonstrating that add-on dupilumab treatment led to a significant improvement versus placebo in FEV1 up to 12 weeks.
“We now have a long term data on this drug as well, showing its efficacy over a period of time,” said Muhammad Adrish, MD, MBA, FCCP, associate professor of pulmonary, critical care and sleep medicine at Baylor College of Medicine, Houston.
“I think that’s pretty exciting, and that’s another step towards precision medicine in treatment of asthma,” Dr. Adrish, who is Vice-Chair of CHEST’s Airways Disorders NetWork Steering Committee and was not involved in the study.
Dupilumab received Food and Drug Administration approval in 2018 as add-on maintenance therapy for the treatment of patients aged 12 years or older with moderate to severe asthma that has an eosinophilic phenotype or that is dependent on oral corticosteroid treatment.
In March 2021, Sanofi and Regeneron announced that the FDA had accepted for review a supplemental Biologics License Application for dupilumab as an add-on treatment in children aged 6-11 years with uncontrolled moderate to severe asthma.
That sBLA is supported by data from the LIBERTY ASTHMA VOYAGE study, Sanofi and Regeneron said.
In results of the phase 3 study that Dr. Bacharier presented in May at the American Thoracic Society International Conference, add-on dupilumab dosed every 2 weeks significant improved percent predicted prebronchodilator FEV1 by an additional 5.21 percentage points versus placebo at week 12.
Dupilumab and the type 2 phenotype
The new data reported at the CHEST meeting come from a prespecified analysis evaluating the impact of dupilumab on lung function over a 52-week treatment period in patients with a T2 inflammatory asthma phenotype.
“Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of T2 inflammation in multiple diseases,” Dr. Bacharier and coinvestigators reported in their study abstract.
Of 408 patients in the study, 350 met the T2 phenotype criteria, including 236 in the dupilumab arm and 114 in the placebo arm.
Patients met T2 phenotype criteria if they had blood eosinophils of at least 150 cells/mcL or fractional exhaled nitric oxide FeNO of at least 20 parts per billion at baseline, investigators said.
Dr. Bacharier and coinvestigators reported on several different endpoints, including absolute and percent predicted prebronchodilator FEV1, percent predicted postbronchodilator FEV1, prebronchodilator forced expiratory flow at 25%-75% of pulmonary volume (FEF25%-75%), and forced vital capacity (FVC).
Dupilumab, when compared with placebo, significantly improved prebronchodilator FEV1 in pediatric patients with uncontrolled moderate to severe type 2 asthma, according to Dr. Bacharier.
“Patients receiving dupilumab experienced rapid improvements by week 2, and this was sustained for up to 52 weeks,” he said.
The prebronchodilator FEV1 improved from baseline for dupilumab versus placebo, with a least squares mean difference of 0.06 L at week 2, which reached 0.17 L by week 52, according to their data. Similarly, postbronchodilator FEV1 improved from baseline for dupilumab, with a least square mean difference versus placebo of 0.09 L at week 52.
Dupilumab compared to placebo also significantly improved percent predicted FEF25%-75%, and percent predicted FVC over the 52-week treatment period, according to Dr. Bacharier.
“Dupilumab led to significant, rapid, and sustained improvements in multiple aspects of lung function in children aged 6-11 years,” Dr. Bacharier added in a CHEST press release that described the findings.
The LIBERTY ASTHMA VOYAGE study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Bacharier provided disclosures related to AstraZeneca, GlaxoSmithKline, Regeneron Pharmaceuticals, Sanofi, CF Foundation, DBV Technologies, NIH, and Vectura.
Add-on treatment with dupilumab may improve lung function in children aged 6-11 years with uncontrolled moderate to severe type 2 inflammatory asthma, results from a randomized, placebo-controlled, phase 3 study show.
Improvements in lung function parameters were observed as early as 2 weeks and persisted over the 52-week treatment period among children in the LIBERTY ASTHMA VOYAGE study, according to investigator Leonard B. Bacharier, MD, of Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn.
“Dupilumab led to clinically meaningful rapid and sustained improvements in lung function parameters,” Dr. Bacharier said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
The improvements in forced expiratory volume in 1 second (FEV1) and other measures reported for children with moderate to severe asthma who have the type 2 phenotype, which is the most common driver of pediatric asthma, according to Dr. Bacharier.
“Many children with moderate to severe asthma have abnormal lung function, and this can be a risk factor for future lung disease in adulthood,” Dr. Bacharier said in his presentation.
The VOYAGE continues
The findings presented at the meeting build on another report earlier this year from the LIBERTY ASTHMA VOYAGE study demonstrating that add-on dupilumab treatment led to a significant improvement versus placebo in FEV1 up to 12 weeks.
“We now have a long term data on this drug as well, showing its efficacy over a period of time,” said Muhammad Adrish, MD, MBA, FCCP, associate professor of pulmonary, critical care and sleep medicine at Baylor College of Medicine, Houston.
“I think that’s pretty exciting, and that’s another step towards precision medicine in treatment of asthma,” Dr. Adrish, who is Vice-Chair of CHEST’s Airways Disorders NetWork Steering Committee and was not involved in the study.
Dupilumab received Food and Drug Administration approval in 2018 as add-on maintenance therapy for the treatment of patients aged 12 years or older with moderate to severe asthma that has an eosinophilic phenotype or that is dependent on oral corticosteroid treatment.
In March 2021, Sanofi and Regeneron announced that the FDA had accepted for review a supplemental Biologics License Application for dupilumab as an add-on treatment in children aged 6-11 years with uncontrolled moderate to severe asthma.
That sBLA is supported by data from the LIBERTY ASTHMA VOYAGE study, Sanofi and Regeneron said.
In results of the phase 3 study that Dr. Bacharier presented in May at the American Thoracic Society International Conference, add-on dupilumab dosed every 2 weeks significant improved percent predicted prebronchodilator FEV1 by an additional 5.21 percentage points versus placebo at week 12.
Dupilumab and the type 2 phenotype
The new data reported at the CHEST meeting come from a prespecified analysis evaluating the impact of dupilumab on lung function over a 52-week treatment period in patients with a T2 inflammatory asthma phenotype.
“Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of T2 inflammation in multiple diseases,” Dr. Bacharier and coinvestigators reported in their study abstract.
Of 408 patients in the study, 350 met the T2 phenotype criteria, including 236 in the dupilumab arm and 114 in the placebo arm.
Patients met T2 phenotype criteria if they had blood eosinophils of at least 150 cells/mcL or fractional exhaled nitric oxide FeNO of at least 20 parts per billion at baseline, investigators said.
Dr. Bacharier and coinvestigators reported on several different endpoints, including absolute and percent predicted prebronchodilator FEV1, percent predicted postbronchodilator FEV1, prebronchodilator forced expiratory flow at 25%-75% of pulmonary volume (FEF25%-75%), and forced vital capacity (FVC).
Dupilumab, when compared with placebo, significantly improved prebronchodilator FEV1 in pediatric patients with uncontrolled moderate to severe type 2 asthma, according to Dr. Bacharier.
“Patients receiving dupilumab experienced rapid improvements by week 2, and this was sustained for up to 52 weeks,” he said.
The prebronchodilator FEV1 improved from baseline for dupilumab versus placebo, with a least squares mean difference of 0.06 L at week 2, which reached 0.17 L by week 52, according to their data. Similarly, postbronchodilator FEV1 improved from baseline for dupilumab, with a least square mean difference versus placebo of 0.09 L at week 52.
Dupilumab compared to placebo also significantly improved percent predicted FEF25%-75%, and percent predicted FVC over the 52-week treatment period, according to Dr. Bacharier.
“Dupilumab led to significant, rapid, and sustained improvements in multiple aspects of lung function in children aged 6-11 years,” Dr. Bacharier added in a CHEST press release that described the findings.
The LIBERTY ASTHMA VOYAGE study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Bacharier provided disclosures related to AstraZeneca, GlaxoSmithKline, Regeneron Pharmaceuticals, Sanofi, CF Foundation, DBV Technologies, NIH, and Vectura.
Add-on treatment with dupilumab may improve lung function in children aged 6-11 years with uncontrolled moderate to severe type 2 inflammatory asthma, results from a randomized, placebo-controlled, phase 3 study show.
Improvements in lung function parameters were observed as early as 2 weeks and persisted over the 52-week treatment period among children in the LIBERTY ASTHMA VOYAGE study, according to investigator Leonard B. Bacharier, MD, of Monroe Carell Jr. Children’s Hospital at Vanderbilt University Medical Center, Nashville, Tenn.
“Dupilumab led to clinically meaningful rapid and sustained improvements in lung function parameters,” Dr. Bacharier said in an online poster presentation at the annual meeting of the American College of Chest Physicians, held virtually this year.
The improvements in forced expiratory volume in 1 second (FEV1) and other measures reported for children with moderate to severe asthma who have the type 2 phenotype, which is the most common driver of pediatric asthma, according to Dr. Bacharier.
“Many children with moderate to severe asthma have abnormal lung function, and this can be a risk factor for future lung disease in adulthood,” Dr. Bacharier said in his presentation.
The VOYAGE continues
The findings presented at the meeting build on another report earlier this year from the LIBERTY ASTHMA VOYAGE study demonstrating that add-on dupilumab treatment led to a significant improvement versus placebo in FEV1 up to 12 weeks.
“We now have a long term data on this drug as well, showing its efficacy over a period of time,” said Muhammad Adrish, MD, MBA, FCCP, associate professor of pulmonary, critical care and sleep medicine at Baylor College of Medicine, Houston.
“I think that’s pretty exciting, and that’s another step towards precision medicine in treatment of asthma,” Dr. Adrish, who is Vice-Chair of CHEST’s Airways Disorders NetWork Steering Committee and was not involved in the study.
Dupilumab received Food and Drug Administration approval in 2018 as add-on maintenance therapy for the treatment of patients aged 12 years or older with moderate to severe asthma that has an eosinophilic phenotype or that is dependent on oral corticosteroid treatment.
In March 2021, Sanofi and Regeneron announced that the FDA had accepted for review a supplemental Biologics License Application for dupilumab as an add-on treatment in children aged 6-11 years with uncontrolled moderate to severe asthma.
That sBLA is supported by data from the LIBERTY ASTHMA VOYAGE study, Sanofi and Regeneron said.
In results of the phase 3 study that Dr. Bacharier presented in May at the American Thoracic Society International Conference, add-on dupilumab dosed every 2 weeks significant improved percent predicted prebronchodilator FEV1 by an additional 5.21 percentage points versus placebo at week 12.
Dupilumab and the type 2 phenotype
The new data reported at the CHEST meeting come from a prespecified analysis evaluating the impact of dupilumab on lung function over a 52-week treatment period in patients with a T2 inflammatory asthma phenotype.
“Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin-4 and -13, key and central drivers of T2 inflammation in multiple diseases,” Dr. Bacharier and coinvestigators reported in their study abstract.
Of 408 patients in the study, 350 met the T2 phenotype criteria, including 236 in the dupilumab arm and 114 in the placebo arm.
Patients met T2 phenotype criteria if they had blood eosinophils of at least 150 cells/mcL or fractional exhaled nitric oxide FeNO of at least 20 parts per billion at baseline, investigators said.
Dr. Bacharier and coinvestigators reported on several different endpoints, including absolute and percent predicted prebronchodilator FEV1, percent predicted postbronchodilator FEV1, prebronchodilator forced expiratory flow at 25%-75% of pulmonary volume (FEF25%-75%), and forced vital capacity (FVC).
Dupilumab, when compared with placebo, significantly improved prebronchodilator FEV1 in pediatric patients with uncontrolled moderate to severe type 2 asthma, according to Dr. Bacharier.
“Patients receiving dupilumab experienced rapid improvements by week 2, and this was sustained for up to 52 weeks,” he said.
The prebronchodilator FEV1 improved from baseline for dupilumab versus placebo, with a least squares mean difference of 0.06 L at week 2, which reached 0.17 L by week 52, according to their data. Similarly, postbronchodilator FEV1 improved from baseline for dupilumab, with a least square mean difference versus placebo of 0.09 L at week 52.
Dupilumab compared to placebo also significantly improved percent predicted FEF25%-75%, and percent predicted FVC over the 52-week treatment period, according to Dr. Bacharier.
“Dupilumab led to significant, rapid, and sustained improvements in multiple aspects of lung function in children aged 6-11 years,” Dr. Bacharier added in a CHEST press release that described the findings.
The LIBERTY ASTHMA VOYAGE study was sponsored by Sanofi and Regeneron Pharmaceuticals. Dr. Bacharier provided disclosures related to AstraZeneca, GlaxoSmithKline, Regeneron Pharmaceuticals, Sanofi, CF Foundation, DBV Technologies, NIH, and Vectura.
FROM CHEST 2021
Better bone builder: High-intensity exercise vs. Pilates
An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.
HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent
Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.
Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.
The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.
“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.
“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.
“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.
Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.
“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.
Compliance stands out, study supports high-intensity exercise
Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.
“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.
“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.
Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.
“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.
“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.
Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
Building on the LIFTMOR and LIFTMOR-M Trials
Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.
The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.
In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).
The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .
The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.
The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.
At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.
Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).
HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.
The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.
Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.
Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.
HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent
Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.
Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.
The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.
“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.
“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.
“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.
Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.
“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.
Compliance stands out, study supports high-intensity exercise
Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.
“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.
“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.
Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.
“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.
“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.
Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
Building on the LIFTMOR and LIFTMOR-M Trials
Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.
The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.
In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).
The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .
The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.
The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.
At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.
Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).
HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.
The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.
Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.
Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
An 8-month high-intensity resistance and impact training program (HiRIT, Onero) led to greater gains in lumbar spine bone mineral density (BMD) and leg/back strength than a low-intensity Pilates-based program (Buff Bones).
These findings are from the Medication and Exercise for Osteoporosis (MEDEX-OP) trial, which included 115 postmenopausal women with low bone mass. Patients were randomly assigned to attend either the HiRIT or Pilates-based exercise program. The participants attended supervised 45-min sessions twice weekly.
HiRIT was better than the low-intensity Pilates-based exercise program for enhancing bone mass, muscle strength, functional performance, and stature, the researchers reported. The low-intensity program did improve function, but to a lesser extent
Of the 115 participants, most (86) were not taking osteoporosis medicine. For the 29 women who were receiving it, the medication appeared to enhance the effect of exercise.
Melanie Fischbacher, PhD candidate, Griffith University, Gold Coast, Australia, presented these findings in an oral session at the annual meeting of the American Society for Bone and Mineral Research; the study was also published in the Journal of Bone and Mineral Research.
The study’s senior author, Belinda R. Beck, PhD, director of the Bone Clinic in Brisbane, Australia, developed the Onero HiRIT program and has licensed it to others in Australia.
“It is a very effective program and we have shown it can be undertaken safely, but it must be supervised because of the heavy weights and high-risk clientele,” Beck stressed to this news organization.
“This is not a program you should just hand to a patient and tell them to do in a gym,” she said.
“Both forms of exercise in our study were beneficial for functional outcomes but Onero improved back extensor strength, mobility and stature considerably more than Buff Bones,” Ms. Fischbacher said in an interview.
Nevertheless, “the contribution of functional capacity to risk of falling and fracture cannot be overstated, and bone medications do not address function,” she noted.
“More trials combining bone medication and bone-targeted exercise are needed,” the researchers concluded.
Compliance stands out, study supports high-intensity exercise
Kristen M. Beavers, PhD, MPH, RD, who was not involved with this research, told this news organization that participant compliance in the study really stands out.
“Compliance to an 8-month, 2 day/week high-intensity resistance training program among older women with low bone mass was quite good in this study [>80%], with very few adverse events reported,” said Dr. Beavers, of the department of health and exercise science, Wake Forest University, Winston Salem, N.C.
“A lot of individuals wouldn’t even consider recommending this type/intensity of exercise to this population, because they are worried it is too risky and/or the uptake will be low,” she said.
Although the benefit in BMD and strength wasn’t seen universally across all bone/muscle outcomes assessed, the findings do reinforce the idea that high-intensity exercise is more efficacious for bone health than low-intensity exercise, she noted.
“The possible additive effect of high-intensity exercise when combined with medication is worth confirming in larger, adequately designed/powered studies,” according to Dr. Beavers.
“The general consensus in the field is that higher-intensity exercise is more osteogenic than low-intensity exercise, but improving muscle mass, quality, and function (including balance) are also important to reduce the risk of falls, which is a major contributor to incident fracture,” she noted.
Exercise, even low-intensity exercise, reduces the risk for falls, as shown in a recent meta-analysis, she added. This is something antiresorptive medications don’t do.
Building on the LIFTMOR and LIFTMOR-M Trials
Previously, the Australian group showed that HiRIT is efficacious and safe for bone formation in individuals with low to very low bone mass – in postmenopausal women in the LIFTMOR study (J Bone Miner Res. 2017 Oct 4 .doi: 10.1002/jbmr.3284), and in men in the LIFTMOR-M study.
The current study compared two exercise programs. The researchers randomly assigned 86 women who were not taking antiresorptive medication to the high-intensity (42) or low-intensity (44) exercise program. They also assigned 29 women who were receiving antiresorptive medication to the high-intensity (15) or low-intensity (14) exercise program.
In the high-intensity exercise plus medication subgroup, the women were taking denosumab (12), risedronate (2) or alendronate (1). In the low-intensity exercise plus medication subgroup, the women were taking denosumab (9), risedronate (1), alendronate (3), or zoledronic acid (1).
The mean age of the women was 64-68 years. The mean lumbar spine T score was –1.5 to –2.3, and the mean femoral neck T score was –1.7 to –2.0 (determined by dual-energy x-ray absorptiometry) .
The HiRIT training program consisted of three free-weight resistance training exercises (deadlift, back squat, overhead press), one high-impact exercise (jump drop), and two balance exercises. The exercises varied each session.
The low-intensity training consisted of bone-specific Pilates-based exercises performed on the mat; standing weight-bearing exercise with 1-kg dumbbells; and impact exercises, such as heel drops and stomping.
At 8 months, compared with women in the low-intensity exercise program, those in the HiRIT program demonstrated greater improvement in lumbar spine BMD (1.9% vs. 0.1%) and stature (0.2 cm vs. 0.0 cm), muscle strength, and functional performance.
Functional performance improved with both exercise programs, but the HiRIT program led to greater leg and back muscle strength and better results in the five times sit-to-stand test (P < .05).
HiRIT plus bone medication improved BMD at the femoral neck and total hip, whereas HiRIT alone did not. Low-intensity exercise plus bone medication improved BMD at the lumbar spine and total hip, whereas low-intensity exercise alone did not.
The retention rate was 90%. The rate of exercise compliance was 83% in the high-intensity group and 82% in the low-intensity group.
Thirty falls were reported by 24 participants (21%). One fracture occurred in each exercise group. Three adverse events occurred in the low-intensity group, and four occurred in the high-intensity group.
Dr. Beck owns the Bone Clinic and sells licenses to the Onero program. The other researchers disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Mixing COVID vaccine boosters may be better option: Study
The study also shows mixing different kinds of vaccines appears to spur the body to make higher levels of virus-blocking antibodies than they would have gotten by boosting with a dose of the vaccine the person already had.
If regulators endorse the study findings, it should make getting a COVID-19 booster as easy as getting a yearly influenza vaccine.
“Currently when you go to do your flu shot nobody asks you what kind you had last year. Nobody cares what you had last year. And we were hoping that that was the same — that we would be able to boost regardless of what you had [previously],” said the study’s senior author, John Beigel, MD, who is associate director for clinical research in the division of microbiology and infectious diseases at the National Institutes of Health.
“But we needed to have the data,” he said.
Studies have suggested that higher antibody levels translate into better protection against disease, though the exact level that confers protection is not yet known.
“The antibody responses are so much higher [with mix and match], it’s really impressive,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville, who was not involved in the study.
Dr. Shaffner said if the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) sign off on the approach, he would especially recommend that people who got the Johnson & Johnson vaccine follow up with a dose of an mRNA vaccine from Pfizer or Moderna.
“It is a broader stimulation of the immune system, and I think that broader stimulation is advantageous,” he said.
Minimal side effects
The preprint study was published late Oct. 13 in medRxiv ahead of peer review, just before a slate of meetings involving vaccine experts that advise the FDA and CDC.
These experts are tasked with trying to figure out whether additional shots of Moderna and Johnson & Johnson vaccines are safe and effective for boosting immunity against COVID-19.
The FDA’s panel is the Vaccines and Related Biological Products Advisory Committee (VRBPAC), and the CDC’s panel is the Advisory Committee on Immunization Practices (ACIP).
During the pandemic, they have been meeting almost in lock step to tackle important vaccine-related questions.
“We got this data out because we knew VRBPAC was coming and we knew ACIP was going to grapple with these issues,” Dr. Beigel said.
He noted that these are just the first results. The study will continue for a year, and the researchers aim to deeply characterize the breadth and depth of the immune response to all nine of the different vaccine combinations included in the study.
The study included 458 participants at 10 study sites around the country who had been fully vaccinated with one of the three COVID-19 vaccines authorized for use in the United States: Moderna, Johnson & Johnson, or Pfizer-BioNTech.
About 150 study participants were recruited from each group. Everyone in the study had finished their primary series at least 12 weeks before starting the study. None had a prior SARS-CoV-2 infection.
About 50 participants from each vaccine group were randomly assigned to get a third (booster) dose of either the same vaccine as the one they had already received, or a different vaccine, creating nine possible combinations of shots.
About half of study participants reported mild side effects — including pain at the injection site, fatigue, headache, and muscle aches.
Two study participants had serious medical problems during the study, but they were judged to be unrelated to vaccination. One study participant experienced kidney failure after their muscles broke down following a fall. The other experienced cholecystitis, or an inflamed gallbladder.
Up to 1 month after the booster shots, no other serious adverse events were seen.
The study didn’t look at whether people got COVID-19, so it’s not possible to say that they were better protected against disease after their boosters.
Increase in antibodies
But all the groups saw substantial increases in their antibody levels, which is thought to indicate that they were better protected.
Overall, groups that got the same vaccine as their primary series saw 4 to 20-fold increases in their antibody levels. Groups that got different shots than the ones in their primary series got 6 to 76 fold increases in their antibody levels.
People who had originally gotten a Johnson & Johnson vaccine saw far bigger increases in antibodies, and were more likely to see a protective rise in antibodies if they got a second dose of an mRNA vaccine.
Dr. Schaffner noted that European countries had already been mixing the vaccine doses this way, giving people who had received the AstraZeneca vaccine, which is similar to the Johnson & Johnson shot, another dose of an mRNA vaccine.
German Chancellor Angela Merkel received a Moderna vaccine for her second dose after an initial shot of the Oxford-AstraZeneca vaccines, for example.
No safety signals related to mixing vaccines has been seen in countries that routinely use the approach for their initial series.
A version of this article first appeared on Medscape.com.
The study also shows mixing different kinds of vaccines appears to spur the body to make higher levels of virus-blocking antibodies than they would have gotten by boosting with a dose of the vaccine the person already had.
If regulators endorse the study findings, it should make getting a COVID-19 booster as easy as getting a yearly influenza vaccine.
“Currently when you go to do your flu shot nobody asks you what kind you had last year. Nobody cares what you had last year. And we were hoping that that was the same — that we would be able to boost regardless of what you had [previously],” said the study’s senior author, John Beigel, MD, who is associate director for clinical research in the division of microbiology and infectious diseases at the National Institutes of Health.
“But we needed to have the data,” he said.
Studies have suggested that higher antibody levels translate into better protection against disease, though the exact level that confers protection is not yet known.
“The antibody responses are so much higher [with mix and match], it’s really impressive,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville, who was not involved in the study.
Dr. Shaffner said if the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) sign off on the approach, he would especially recommend that people who got the Johnson & Johnson vaccine follow up with a dose of an mRNA vaccine from Pfizer or Moderna.
“It is a broader stimulation of the immune system, and I think that broader stimulation is advantageous,” he said.
Minimal side effects
The preprint study was published late Oct. 13 in medRxiv ahead of peer review, just before a slate of meetings involving vaccine experts that advise the FDA and CDC.
These experts are tasked with trying to figure out whether additional shots of Moderna and Johnson & Johnson vaccines are safe and effective for boosting immunity against COVID-19.
The FDA’s panel is the Vaccines and Related Biological Products Advisory Committee (VRBPAC), and the CDC’s panel is the Advisory Committee on Immunization Practices (ACIP).
During the pandemic, they have been meeting almost in lock step to tackle important vaccine-related questions.
“We got this data out because we knew VRBPAC was coming and we knew ACIP was going to grapple with these issues,” Dr. Beigel said.
He noted that these are just the first results. The study will continue for a year, and the researchers aim to deeply characterize the breadth and depth of the immune response to all nine of the different vaccine combinations included in the study.
The study included 458 participants at 10 study sites around the country who had been fully vaccinated with one of the three COVID-19 vaccines authorized for use in the United States: Moderna, Johnson & Johnson, or Pfizer-BioNTech.
About 150 study participants were recruited from each group. Everyone in the study had finished their primary series at least 12 weeks before starting the study. None had a prior SARS-CoV-2 infection.
About 50 participants from each vaccine group were randomly assigned to get a third (booster) dose of either the same vaccine as the one they had already received, or a different vaccine, creating nine possible combinations of shots.
About half of study participants reported mild side effects — including pain at the injection site, fatigue, headache, and muscle aches.
Two study participants had serious medical problems during the study, but they were judged to be unrelated to vaccination. One study participant experienced kidney failure after their muscles broke down following a fall. The other experienced cholecystitis, or an inflamed gallbladder.
Up to 1 month after the booster shots, no other serious adverse events were seen.
The study didn’t look at whether people got COVID-19, so it’s not possible to say that they were better protected against disease after their boosters.
Increase in antibodies
But all the groups saw substantial increases in their antibody levels, which is thought to indicate that they were better protected.
Overall, groups that got the same vaccine as their primary series saw 4 to 20-fold increases in their antibody levels. Groups that got different shots than the ones in their primary series got 6 to 76 fold increases in their antibody levels.
People who had originally gotten a Johnson & Johnson vaccine saw far bigger increases in antibodies, and were more likely to see a protective rise in antibodies if they got a second dose of an mRNA vaccine.
Dr. Schaffner noted that European countries had already been mixing the vaccine doses this way, giving people who had received the AstraZeneca vaccine, which is similar to the Johnson & Johnson shot, another dose of an mRNA vaccine.
German Chancellor Angela Merkel received a Moderna vaccine for her second dose after an initial shot of the Oxford-AstraZeneca vaccines, for example.
No safety signals related to mixing vaccines has been seen in countries that routinely use the approach for their initial series.
A version of this article first appeared on Medscape.com.
The study also shows mixing different kinds of vaccines appears to spur the body to make higher levels of virus-blocking antibodies than they would have gotten by boosting with a dose of the vaccine the person already had.
If regulators endorse the study findings, it should make getting a COVID-19 booster as easy as getting a yearly influenza vaccine.
“Currently when you go to do your flu shot nobody asks you what kind you had last year. Nobody cares what you had last year. And we were hoping that that was the same — that we would be able to boost regardless of what you had [previously],” said the study’s senior author, John Beigel, MD, who is associate director for clinical research in the division of microbiology and infectious diseases at the National Institutes of Health.
“But we needed to have the data,” he said.
Studies have suggested that higher antibody levels translate into better protection against disease, though the exact level that confers protection is not yet known.
“The antibody responses are so much higher [with mix and match], it’s really impressive,” said William Schaffner, MD, an infectious disease specialist at Vanderbilt University in Nashville, who was not involved in the study.
Dr. Shaffner said if the U.S. Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) sign off on the approach, he would especially recommend that people who got the Johnson & Johnson vaccine follow up with a dose of an mRNA vaccine from Pfizer or Moderna.
“It is a broader stimulation of the immune system, and I think that broader stimulation is advantageous,” he said.
Minimal side effects
The preprint study was published late Oct. 13 in medRxiv ahead of peer review, just before a slate of meetings involving vaccine experts that advise the FDA and CDC.
These experts are tasked with trying to figure out whether additional shots of Moderna and Johnson & Johnson vaccines are safe and effective for boosting immunity against COVID-19.
The FDA’s panel is the Vaccines and Related Biological Products Advisory Committee (VRBPAC), and the CDC’s panel is the Advisory Committee on Immunization Practices (ACIP).
During the pandemic, they have been meeting almost in lock step to tackle important vaccine-related questions.
“We got this data out because we knew VRBPAC was coming and we knew ACIP was going to grapple with these issues,” Dr. Beigel said.
He noted that these are just the first results. The study will continue for a year, and the researchers aim to deeply characterize the breadth and depth of the immune response to all nine of the different vaccine combinations included in the study.
The study included 458 participants at 10 study sites around the country who had been fully vaccinated with one of the three COVID-19 vaccines authorized for use in the United States: Moderna, Johnson & Johnson, or Pfizer-BioNTech.
About 150 study participants were recruited from each group. Everyone in the study had finished their primary series at least 12 weeks before starting the study. None had a prior SARS-CoV-2 infection.
About 50 participants from each vaccine group were randomly assigned to get a third (booster) dose of either the same vaccine as the one they had already received, or a different vaccine, creating nine possible combinations of shots.
About half of study participants reported mild side effects — including pain at the injection site, fatigue, headache, and muscle aches.
Two study participants had serious medical problems during the study, but they were judged to be unrelated to vaccination. One study participant experienced kidney failure after their muscles broke down following a fall. The other experienced cholecystitis, or an inflamed gallbladder.
Up to 1 month after the booster shots, no other serious adverse events were seen.
The study didn’t look at whether people got COVID-19, so it’s not possible to say that they were better protected against disease after their boosters.
Increase in antibodies
But all the groups saw substantial increases in their antibody levels, which is thought to indicate that they were better protected.
Overall, groups that got the same vaccine as their primary series saw 4 to 20-fold increases in their antibody levels. Groups that got different shots than the ones in their primary series got 6 to 76 fold increases in their antibody levels.
People who had originally gotten a Johnson & Johnson vaccine saw far bigger increases in antibodies, and were more likely to see a protective rise in antibodies if they got a second dose of an mRNA vaccine.
Dr. Schaffner noted that European countries had already been mixing the vaccine doses this way, giving people who had received the AstraZeneca vaccine, which is similar to the Johnson & Johnson shot, another dose of an mRNA vaccine.
German Chancellor Angela Merkel received a Moderna vaccine for her second dose after an initial shot of the Oxford-AstraZeneca vaccines, for example.
No safety signals related to mixing vaccines has been seen in countries that routinely use the approach for their initial series.
A version of this article first appeared on Medscape.com.
USPSTF rules out aspirin for over 60s in primary CVD prevention
New draft recommendations from the U.S. Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of cardiovascular disease (CVD) have been released and appear to limit the population in which it should be considered.
“The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit,” the recommendation notes. They conclude that for these patients, the decision to use aspirin “should be an individual one.”
“Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit,” they note.
For older individuals, however, the task force concludes.
The new recommendations were posted online Oct. 12 and will be available for public comment until November 8. Once it is finalized, the recommendation will replace the 2016 USPSTF recommendation on aspirin use to prevent CVD and colorectal cancer (CRC), they note.
In that document, the task force recommended initiating low-dose aspirin for the primary prevention of both CVD and CRC in adults 50-59 years of age who had a 10% or greater 10-year CVD risk, were not at increased risk for bleeding, had a life expectancy of at least 10 years, and were willing to take daily low-dose aspirin for at least 10 years, with the decision to start being an individual one.
For older and younger patients, they found at that time that the evidence was “insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults younger than age 50 years or adults aged 70 years or older.”
In the new draft document, “the USPSTF has changed the age ranges and grades of its recommendation on aspirin use.” Besides the recommendations for CVD prevention, they have also changed the previous recommendation of aspirin for the prevention of CRC given evidence generated from large primary CVD prevention trials.
“Based on new analyses of the evidence from primary CVD prevention populations, longer-term follow-up data from the Women’s Health Study (WHS) (JE Buring, personal communication, November 23, 2020), and new trial evidence, the USPSTF concluded that the evidence is inadequate that low-dose aspirin use reduces CRC incidence or mortality,” it states.
Optimum dose
On the optimum dose for primary CVD prevention, the task force says the benefit appears similar for a low dose (≤100 mg/d) and all doses that have been studied in CVD prevention trials (50 to 500 mg/d). “A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the United States,” it states.
The USPSTF recommends using the ACC/AHA Pooled Cohort Equations to estimate cardiovascular risk but it points out that these equations are imperfect for risk prediction at the individual level, and suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with >15% or >20% 10-year CVD risk), they note.
“Decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin use. Persons who place a higher value on the potential harms or on the burden of taking a daily preventive medication than the potential benefits may choose not to initiate low-dose aspirin use,” the task force says.
It also points out that the risk for bleeding increases modestly with advancing age. “For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. The net benefits, however, become smaller with advancing age because of an increased risk for bleeding, so modeling data suggest that it may be reasonable to consider stopping aspirin use around age 75 years,” it states.
Systematic review
The updated draft recommendations are based on a new systematic review commissioned by the USPSTF on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD.
The systematic review also investigated the effect of aspirin use on CRC incidence and mortality in primary CVD prevention populations, as well as the harms, particularly bleeding harms, associated with aspirin use.
In addition to the systematic evidence review, the USPSTF commissioned a microsimulation modeling study to assess the net balance of benefits and harms from aspirin use for primary prevention of CVD and CRC, stratified by age, sex, and CVD risk level. Modeling study parameter inputs were informed by the results of the systematic review, and the primary outcomes were net benefits expressed as quality-adjusted life-years and life-years.
The USPSTF found 13 randomized clinical trials (RCTs) that reported on the benefits of aspirin use for the primary prevention of cardiovascular morbidity and mortality. The total number of participants was 161,680, and most trials used low-dose aspirin of 100 mg/d or less or aspirin every other day. The 13 primary prevention trials included a balanced number of male and female participants and included a broad distribution of ages, with mean age ranging from 53 years in the Physicians’ Health Study to 74 years in the ASPREE trial.
This body of evidence shows that aspirin use for primary prevention of CVD is associated with a decreased risk of myocardial infarction and stroke but not cardiovascular mortality or all-cause mortality. Results are quite similar when including studies using all doses of aspirin compared with studies using low-dose aspirin.
The USPSTF reviewed 14 RCTs in CVD primary prevention populations that reported on the bleeding harms of aspirin.
When looking at studies reporting on the harms of low-dose aspirin use (≤100 mg/d), which is most relevant to current practice, a pooled analysis of 10 trials showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding, and a pooled analysis of 11 trials showed a 31% increase in intracranial bleeds in the aspirin group compared with the control group. Low-dose aspirin use was not associated with a statistically significant increase in risk of fatal hemorrhagic stroke.
Data suggested that the increased risk of bleeding associated with aspirin use occurs relatively quickly after initiating aspirin, and data do not suggest that aspirin has a differential relative bleeding risk based on age, sex, presence of diabetes, level of CVD risk, or race or ethnicity. Although the increase in relative risk does not appear to differ based on age, the absolute risk of bleeding, and thus the magnitude of bleeding harm, does increase with age, and more so in adults age 60 years or older, they note.
The microsimulation model to estimate the magnitude of net benefit of low-dose aspirin use incorporated findings from the systematic review.
Modeling data demonstrated that aspirin use in both men and women ages 40-59 years with 10% or greater 10-year CVD risk generally provides a modest net benefit in both quality-adjusted life-years and life-years gained. Initiation of aspirin use in persons aged 60-69 years results in quality-adjusted life-years gained that range from slightly negative to slightly positive depending on CVD risk level, and life-years gained are generally negative.
In persons aged 70-79 years, initiation of aspirin use results in a loss of both quality-adjusted life-years and life-years at essentially all CVD risk levels modeled (ie, up to 20% 10-year CVD risk).
The USPSTF thus determined that aspirin use has a small net benefit in persons aged 40-59 years with 10% or greater 10-year CVD risk, and initiation of aspirin use has no net benefit in persons age 60 years or older.
When looking at net lifetime benefit of continuous aspirin use until stopping at age 65, 70, 75, 80, or 85 years, modeling data suggest that there is generally little incremental lifetime net benefit in continuing aspirin use beyond the age of 75-80 years.
The task force points out that the net benefit of continuing aspirin use by a person in their 60s or 70s is not the same as the net benefit of initiating aspirin use by a person in their 60s or 70s. This is because, in part, of the fact that CVD risk is heavily influenced by age. Persons who meet the eligibility criteria for aspirin use at a younger age (ie, ≥10% 10-year CVD risk in their 40s or 50s) typically have even higher CVD risk by their 60s or 70s compared with persons who first reach a 10% or greater 10-year CVD risk in their 60s or 70s, and may gain more benefit by continuing aspirin use than a person at lower risk might gain by initiating aspirin use, the USPSTF explains.
A version of this article first appeared on Medscape.com.
New draft recommendations from the U.S. Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of cardiovascular disease (CVD) have been released and appear to limit the population in which it should be considered.
“The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit,” the recommendation notes. They conclude that for these patients, the decision to use aspirin “should be an individual one.”
“Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit,” they note.
For older individuals, however, the task force concludes.
The new recommendations were posted online Oct. 12 and will be available for public comment until November 8. Once it is finalized, the recommendation will replace the 2016 USPSTF recommendation on aspirin use to prevent CVD and colorectal cancer (CRC), they note.
In that document, the task force recommended initiating low-dose aspirin for the primary prevention of both CVD and CRC in adults 50-59 years of age who had a 10% or greater 10-year CVD risk, were not at increased risk for bleeding, had a life expectancy of at least 10 years, and were willing to take daily low-dose aspirin for at least 10 years, with the decision to start being an individual one.
For older and younger patients, they found at that time that the evidence was “insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults younger than age 50 years or adults aged 70 years or older.”
In the new draft document, “the USPSTF has changed the age ranges and grades of its recommendation on aspirin use.” Besides the recommendations for CVD prevention, they have also changed the previous recommendation of aspirin for the prevention of CRC given evidence generated from large primary CVD prevention trials.
“Based on new analyses of the evidence from primary CVD prevention populations, longer-term follow-up data from the Women’s Health Study (WHS) (JE Buring, personal communication, November 23, 2020), and new trial evidence, the USPSTF concluded that the evidence is inadequate that low-dose aspirin use reduces CRC incidence or mortality,” it states.
Optimum dose
On the optimum dose for primary CVD prevention, the task force says the benefit appears similar for a low dose (≤100 mg/d) and all doses that have been studied in CVD prevention trials (50 to 500 mg/d). “A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the United States,” it states.
The USPSTF recommends using the ACC/AHA Pooled Cohort Equations to estimate cardiovascular risk but it points out that these equations are imperfect for risk prediction at the individual level, and suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with >15% or >20% 10-year CVD risk), they note.
“Decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin use. Persons who place a higher value on the potential harms or on the burden of taking a daily preventive medication than the potential benefits may choose not to initiate low-dose aspirin use,” the task force says.
It also points out that the risk for bleeding increases modestly with advancing age. “For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. The net benefits, however, become smaller with advancing age because of an increased risk for bleeding, so modeling data suggest that it may be reasonable to consider stopping aspirin use around age 75 years,” it states.
Systematic review
The updated draft recommendations are based on a new systematic review commissioned by the USPSTF on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD.
The systematic review also investigated the effect of aspirin use on CRC incidence and mortality in primary CVD prevention populations, as well as the harms, particularly bleeding harms, associated with aspirin use.
In addition to the systematic evidence review, the USPSTF commissioned a microsimulation modeling study to assess the net balance of benefits and harms from aspirin use for primary prevention of CVD and CRC, stratified by age, sex, and CVD risk level. Modeling study parameter inputs were informed by the results of the systematic review, and the primary outcomes were net benefits expressed as quality-adjusted life-years and life-years.
The USPSTF found 13 randomized clinical trials (RCTs) that reported on the benefits of aspirin use for the primary prevention of cardiovascular morbidity and mortality. The total number of participants was 161,680, and most trials used low-dose aspirin of 100 mg/d or less or aspirin every other day. The 13 primary prevention trials included a balanced number of male and female participants and included a broad distribution of ages, with mean age ranging from 53 years in the Physicians’ Health Study to 74 years in the ASPREE trial.
This body of evidence shows that aspirin use for primary prevention of CVD is associated with a decreased risk of myocardial infarction and stroke but not cardiovascular mortality or all-cause mortality. Results are quite similar when including studies using all doses of aspirin compared with studies using low-dose aspirin.
The USPSTF reviewed 14 RCTs in CVD primary prevention populations that reported on the bleeding harms of aspirin.
When looking at studies reporting on the harms of low-dose aspirin use (≤100 mg/d), which is most relevant to current practice, a pooled analysis of 10 trials showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding, and a pooled analysis of 11 trials showed a 31% increase in intracranial bleeds in the aspirin group compared with the control group. Low-dose aspirin use was not associated with a statistically significant increase in risk of fatal hemorrhagic stroke.
Data suggested that the increased risk of bleeding associated with aspirin use occurs relatively quickly after initiating aspirin, and data do not suggest that aspirin has a differential relative bleeding risk based on age, sex, presence of diabetes, level of CVD risk, or race or ethnicity. Although the increase in relative risk does not appear to differ based on age, the absolute risk of bleeding, and thus the magnitude of bleeding harm, does increase with age, and more so in adults age 60 years or older, they note.
The microsimulation model to estimate the magnitude of net benefit of low-dose aspirin use incorporated findings from the systematic review.
Modeling data demonstrated that aspirin use in both men and women ages 40-59 years with 10% or greater 10-year CVD risk generally provides a modest net benefit in both quality-adjusted life-years and life-years gained. Initiation of aspirin use in persons aged 60-69 years results in quality-adjusted life-years gained that range from slightly negative to slightly positive depending on CVD risk level, and life-years gained are generally negative.
In persons aged 70-79 years, initiation of aspirin use results in a loss of both quality-adjusted life-years and life-years at essentially all CVD risk levels modeled (ie, up to 20% 10-year CVD risk).
The USPSTF thus determined that aspirin use has a small net benefit in persons aged 40-59 years with 10% or greater 10-year CVD risk, and initiation of aspirin use has no net benefit in persons age 60 years or older.
When looking at net lifetime benefit of continuous aspirin use until stopping at age 65, 70, 75, 80, or 85 years, modeling data suggest that there is generally little incremental lifetime net benefit in continuing aspirin use beyond the age of 75-80 years.
The task force points out that the net benefit of continuing aspirin use by a person in their 60s or 70s is not the same as the net benefit of initiating aspirin use by a person in their 60s or 70s. This is because, in part, of the fact that CVD risk is heavily influenced by age. Persons who meet the eligibility criteria for aspirin use at a younger age (ie, ≥10% 10-year CVD risk in their 40s or 50s) typically have even higher CVD risk by their 60s or 70s compared with persons who first reach a 10% or greater 10-year CVD risk in their 60s or 70s, and may gain more benefit by continuing aspirin use than a person at lower risk might gain by initiating aspirin use, the USPSTF explains.
A version of this article first appeared on Medscape.com.
New draft recommendations from the U.S. Preventive Services Task Force (USPSTF) on the use of aspirin for the primary prevention of cardiovascular disease (CVD) have been released and appear to limit the population in which it should be considered.
“The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults ages 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit,” the recommendation notes. They conclude that for these patients, the decision to use aspirin “should be an individual one.”
“Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit,” they note.
For older individuals, however, the task force concludes.
The new recommendations were posted online Oct. 12 and will be available for public comment until November 8. Once it is finalized, the recommendation will replace the 2016 USPSTF recommendation on aspirin use to prevent CVD and colorectal cancer (CRC), they note.
In that document, the task force recommended initiating low-dose aspirin for the primary prevention of both CVD and CRC in adults 50-59 years of age who had a 10% or greater 10-year CVD risk, were not at increased risk for bleeding, had a life expectancy of at least 10 years, and were willing to take daily low-dose aspirin for at least 10 years, with the decision to start being an individual one.
For older and younger patients, they found at that time that the evidence was “insufficient to assess the balance of benefits and harms of initiating aspirin use for the primary prevention of CVD and CRC in adults younger than age 50 years or adults aged 70 years or older.”
In the new draft document, “the USPSTF has changed the age ranges and grades of its recommendation on aspirin use.” Besides the recommendations for CVD prevention, they have also changed the previous recommendation of aspirin for the prevention of CRC given evidence generated from large primary CVD prevention trials.
“Based on new analyses of the evidence from primary CVD prevention populations, longer-term follow-up data from the Women’s Health Study (WHS) (JE Buring, personal communication, November 23, 2020), and new trial evidence, the USPSTF concluded that the evidence is inadequate that low-dose aspirin use reduces CRC incidence or mortality,” it states.
Optimum dose
On the optimum dose for primary CVD prevention, the task force says the benefit appears similar for a low dose (≤100 mg/d) and all doses that have been studied in CVD prevention trials (50 to 500 mg/d). “A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the United States,” it states.
The USPSTF recommends using the ACC/AHA Pooled Cohort Equations to estimate cardiovascular risk but it points out that these equations are imperfect for risk prediction at the individual level, and suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with >15% or >20% 10-year CVD risk), they note.
“Decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin use. Persons who place a higher value on the potential harms or on the burden of taking a daily preventive medication than the potential benefits may choose not to initiate low-dose aspirin use,” the task force says.
It also points out that the risk for bleeding increases modestly with advancing age. “For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. The net benefits, however, become smaller with advancing age because of an increased risk for bleeding, so modeling data suggest that it may be reasonable to consider stopping aspirin use around age 75 years,” it states.
Systematic review
The updated draft recommendations are based on a new systematic review commissioned by the USPSTF on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD.
The systematic review also investigated the effect of aspirin use on CRC incidence and mortality in primary CVD prevention populations, as well as the harms, particularly bleeding harms, associated with aspirin use.
In addition to the systematic evidence review, the USPSTF commissioned a microsimulation modeling study to assess the net balance of benefits and harms from aspirin use for primary prevention of CVD and CRC, stratified by age, sex, and CVD risk level. Modeling study parameter inputs were informed by the results of the systematic review, and the primary outcomes were net benefits expressed as quality-adjusted life-years and life-years.
The USPSTF found 13 randomized clinical trials (RCTs) that reported on the benefits of aspirin use for the primary prevention of cardiovascular morbidity and mortality. The total number of participants was 161,680, and most trials used low-dose aspirin of 100 mg/d or less or aspirin every other day. The 13 primary prevention trials included a balanced number of male and female participants and included a broad distribution of ages, with mean age ranging from 53 years in the Physicians’ Health Study to 74 years in the ASPREE trial.
This body of evidence shows that aspirin use for primary prevention of CVD is associated with a decreased risk of myocardial infarction and stroke but not cardiovascular mortality or all-cause mortality. Results are quite similar when including studies using all doses of aspirin compared with studies using low-dose aspirin.
The USPSTF reviewed 14 RCTs in CVD primary prevention populations that reported on the bleeding harms of aspirin.
When looking at studies reporting on the harms of low-dose aspirin use (≤100 mg/d), which is most relevant to current practice, a pooled analysis of 10 trials showed that aspirin use was associated with a 58% increase in major gastrointestinal bleeding, and a pooled analysis of 11 trials showed a 31% increase in intracranial bleeds in the aspirin group compared with the control group. Low-dose aspirin use was not associated with a statistically significant increase in risk of fatal hemorrhagic stroke.
Data suggested that the increased risk of bleeding associated with aspirin use occurs relatively quickly after initiating aspirin, and data do not suggest that aspirin has a differential relative bleeding risk based on age, sex, presence of diabetes, level of CVD risk, or race or ethnicity. Although the increase in relative risk does not appear to differ based on age, the absolute risk of bleeding, and thus the magnitude of bleeding harm, does increase with age, and more so in adults age 60 years or older, they note.
The microsimulation model to estimate the magnitude of net benefit of low-dose aspirin use incorporated findings from the systematic review.
Modeling data demonstrated that aspirin use in both men and women ages 40-59 years with 10% or greater 10-year CVD risk generally provides a modest net benefit in both quality-adjusted life-years and life-years gained. Initiation of aspirin use in persons aged 60-69 years results in quality-adjusted life-years gained that range from slightly negative to slightly positive depending on CVD risk level, and life-years gained are generally negative.
In persons aged 70-79 years, initiation of aspirin use results in a loss of both quality-adjusted life-years and life-years at essentially all CVD risk levels modeled (ie, up to 20% 10-year CVD risk).
The USPSTF thus determined that aspirin use has a small net benefit in persons aged 40-59 years with 10% or greater 10-year CVD risk, and initiation of aspirin use has no net benefit in persons age 60 years or older.
When looking at net lifetime benefit of continuous aspirin use until stopping at age 65, 70, 75, 80, or 85 years, modeling data suggest that there is generally little incremental lifetime net benefit in continuing aspirin use beyond the age of 75-80 years.
The task force points out that the net benefit of continuing aspirin use by a person in their 60s or 70s is not the same as the net benefit of initiating aspirin use by a person in their 60s or 70s. This is because, in part, of the fact that CVD risk is heavily influenced by age. Persons who meet the eligibility criteria for aspirin use at a younger age (ie, ≥10% 10-year CVD risk in their 40s or 50s) typically have even higher CVD risk by their 60s or 70s compared with persons who first reach a 10% or greater 10-year CVD risk in their 60s or 70s, and may gain more benefit by continuing aspirin use than a person at lower risk might gain by initiating aspirin use, the USPSTF explains.
A version of this article first appeared on Medscape.com.
Synthetic chemical in consumer products linked to early death, study says
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.
Daily exposure to phthalates, which are synthetic chemicals founds in many consumer products, may lead to hundreds of thousands of early deaths each year among older adults in the United States, according to a new study published Oct. 12, 2021, in the peer-reviewed journal Environmental Pollution.
The chemicals are found in hundreds of types of products, including children’s toys, food storage containers, makeup, perfume, and shampoo. In the study, those with the highest levels of phthalates had a greater risk of death from any cause, especially heart disease.
“This study adds to the growing database on the impact of plastics on the human body and bolsters public health and business cases for reducing or eliminating the use of plastics,” Leonardo Trasande, MD, the lead author and a professor of environmental medicine and population health at New York University Langone Health, told CNN.
Dr. Trasande and colleagues measured the urine concentration of phthalates in more than 5,000 adults aged 55-64 and compared the levels with the risk of early death over an average of 10 years. The research team controlled for preexisting heart diseases, diabetes, cancer, poor eating habits, physical activity, body mass, and other known hormone disruptors such as bisphenol A, or BPA, an industrial chemical that’s been used since the 1950s to make certain plastics and resins, according to the Mayo Clinic
The research team found that phthalates could contribute to 91,000-107,000 premature deaths per year in the United States. These early deaths could cost the nation $40 billion to $47 billion each year in lost economic productivity.
Phthalates interrupt the body’s endocrine system and hormone production. Previous studies have found that the chemicals are linked with developmental, reproductive, and immune system problems, according to NYU Langone Health. They’ve also been linked with asthma, childhood obesity, heart issues, and cancer.
“These chemicals have a rap sheet,” Dr. Trasande told CNN. “And the fact of the matter is that when you look at the entire body of evidence, it provides a haunting pattern of concern.”
Phthalates are often called “everywhere chemicals” because they are so common, CNN reported. Also called “plasticizers,” they are added to products to make them more durable, including PVC plumbing, vinyl flooring, medical tubing, garden hoses, food packaging, detergents, clothing, furniture, and automotive materials.
People are often exposed when they breathe contaminated air or consume food that comes into contact with the chemical, according to the Centers for Disease Control and Prevention. Children may be exposed by touching plastic items and putting their hands in their mouth.
Dr. Trasande told CNN that it’s possible to lessen exposure to phthalates and other endocrine disruptors such as BPA by using unscented lotions, laundry detergents, and cleaning supplies, as well as substituting glass, stainless steel, ceramic, and wood for plastic food storage.
“First, avoid plastics as much as you can. Never put plastic containers in the microwave or dishwasher, where the heat can break down the linings so they might be absorbed more readily,” he said. “In addition, cooking at home and reducing your use of processed foods can reduce the levels of the chemical exposures you come in contact with.”
A version of this article first appeared on WebMD.com.