DENVER – Adding therapies such as acupuncture, electrophysical stimulation, or other interventions to standard exercise therapy does not appear to offer much benefit in pain relief or physical function for patients with knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress. The findings were also published in the Cochrane Database of Systematic Reviews in October 2022.

“The results do not support the use of adjunctive therapies when we add them to exercise for pain, physical function, or quality of life, when compared against placebo, adjunctive therapy, and exercise,” Helen P. French, PhD, told attendees at the meeting sponsored by the Osteoarthritis Research Society International. The findings were similar for pain and physical function when comparing adjunctive therapies with exercise against exercise alone, said Dr. French, an associate professor in physiotherapy at the Royal College of Surgeons, Dublin, except that patients using adjunctive therapies reported feeling greater improvement in their global assessments.

Exercise is recommended as a core treatment for osteoarthritis, but some patients or clinicians may be interested in supplementing that therapy with acupuncture, heat therapy, electromagnetic fields, transcutaneous electrical nerve stimulation, braces/orthotics, and other interventions. Various Cochrane Reviews of the evidence exist for these interventions in treating chronic pain in general but not for their use as adjunctive therapies in addition to exercise for osteoarthritis pain.

Researchers therefore assessed the evidence for improvement in pain, physical function, and quality of life for two sets of comparisons: adjunctive therapies plus exercise versus exercise alone, and adjunctive therapies with exercise versus placebo adjunctive therapy with exercise. The review excluded studies looking at medications or supplements.

Pain was assessed with the Numeric Pain Rating Scale (NPRS, 0-10), with an improvement of at least 2 points (15% improvement) representing the minimum clinically important difference (MCID). Physical function was assessed with the Western Ontario and McMaster Universities Arthritis Index (WOMAC, 0-68), with 6 points (15%) considered the MCID, and quality of life was assessed with the SF-36 (0-100), with 6 points (12%) as the MCID.

The researchers identified trials on knee osteoarthritis that included an overall 6,508 participants with an average age ranging from 52 to 83 years. A total of 36 studies evaluated electrophysical agents. Another seven looked at manual therapies; four looked at acupuncture/dry needling or taping; three looked at psychological, dietary, or “whole body vibration” therapies; and two evaluated spa or peloid therapy. Only one trial evaluated foot insoles.

Nearly all the studies (98%) assessed pain, and most (87%) assessed physical function. Only about one in five (21%) assessed quality of life. The improvement in pain from adding adjunctive therapies to exercise, compared with placebo therapies plus exercise, was 0.77 points, or just under a 10% improvement, which fell short of the 15% MCID. Physical function improvement similarly fell short, with an average improvement of 5 points (12%).

In comparisons of exercise plus adjunctive therapies against exercise alone, the improvement from the additional interventions was even lower. Pain improvement was 0.41 points (7%), and physical function improvement was 2.8 points (9%). However, patients’ perceptions told a different story: 37% more patients who were using an adjunctive therapy reported feeling that the therapies were successful, compared with patients undergoing exercise therapy alone.

Adverse events were poorly reported in the trials, with only 10 trials reporting them at all, and the researchers found no significant difference in adverse events among the studies reporting them. The most common adverse events were increased pain in the joint with the osteoarthritis, pain elsewhere, or swelling and inflammation. It’s unclear, however, whether the pain, swelling, and inflammation were related to the interventions and how serious these effects might have been.

Michelle Hall, PhD, an associate professor in the department of physiotherapy at the University of Melbourne, comoderated the session with this presentation and found it interesting that more than one-third of patients perceived that they did better with the additional therapies even though improvement didn’t bear out in their pain or physical function assessments.

“But the other part of that was that the studies were of poor quality, so we can’t say with confidence, ‘Don’t do this therapy because it’s not going to work,’ ” Dr. Hall said in an interview. She said she personally would probably discourage patients from those therapies, “but I don’t think the evidence is there for everybody to do that,” she added.

Martin Van Der Esch, PhD, of Reade Centre of Rehabilitation and Rheumatology in Amsterdam, also comoderated the discussion and had more concerns about the use of adjunctive therapies in light of the study’s findings. He said in an interview that he tended to believe the patients’ overall self-reported improvement is likely a placebo effect, and he sees potential harm in that effect. If the pain is not truly decreasing as patients continue using those therapies, then the pain may become a more stable part of the nervous system, “so I think they need to do an intervention which really has evidence in reducing pain, an active approach that means exercising in the right way,” Dr. Van Der Esch said. If patients are undergoing therapy whose primary benefit is a placebo effect, “the pain will prolong and become more fixed in the nervous system,” shifting the patients toward greater risk of the pain becoming chronic, he said.

“I want to emphasize that we have an ethical role to our management, and it’s not ethical to give treatments which have no response and no pain relief except that the patient or the professional believes it will have an effect,” Dr. Van Der Esch said.

The research did not involve outside funding. Dr. French, Dr. Hall, and Dr. Van Der Esch reported having no relevant financial relationships.

DENVER – Adding therapies such as acupuncture, electrophysical stimulation, or other interventions to standard exercise therapy does not appear to offer much benefit in pain relief or physical function for patients with knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress. The findings were also published in the Cochrane Database of Systematic Reviews in October 2022.

“The results do not support the use of adjunctive therapies when we add them to exercise for pain, physical function, or quality of life, when compared against placebo, adjunctive therapy, and exercise,” Helen P. French, PhD, told attendees at the meeting sponsored by the Osteoarthritis Research Society International. The findings were similar for pain and physical function when comparing adjunctive therapies with exercise against exercise alone, said Dr. French, an associate professor in physiotherapy at the Royal College of Surgeons, Dublin, except that patients using adjunctive therapies reported feeling greater improvement in their global assessments.

Exercise is recommended as a core treatment for osteoarthritis, but some patients or clinicians may be interested in supplementing that therapy with acupuncture, heat therapy, electromagnetic fields, transcutaneous electrical nerve stimulation, braces/orthotics, and other interventions. Various Cochrane Reviews of the evidence exist for these interventions in treating chronic pain in general but not for their use as adjunctive therapies in addition to exercise for osteoarthritis pain.

Researchers therefore assessed the evidence for improvement in pain, physical function, and quality of life for two sets of comparisons: adjunctive therapies plus exercise versus exercise alone, and adjunctive therapies with exercise versus placebo adjunctive therapy with exercise. The review excluded studies looking at medications or supplements.

Pain was assessed with the Numeric Pain Rating Scale (NPRS, 0-10), with an improvement of at least 2 points (15% improvement) representing the minimum clinically important difference (MCID). Physical function was assessed with the Western Ontario and McMaster Universities Arthritis Index (WOMAC, 0-68), with 6 points (15%) considered the MCID, and quality of life was assessed with the SF-36 (0-100), with 6 points (12%) as the MCID.

The researchers identified trials on knee osteoarthritis that included an overall 6,508 participants with an average age ranging from 52 to 83 years. A total of 36 studies evaluated electrophysical agents. Another seven looked at manual therapies; four looked at acupuncture/dry needling or taping; three looked at psychological, dietary, or “whole body vibration” therapies; and two evaluated spa or peloid therapy. Only one trial evaluated foot insoles.

Nearly all the studies (98%) assessed pain, and most (87%) assessed physical function. Only about one in five (21%) assessed quality of life. The improvement in pain from adding adjunctive therapies to exercise, compared with placebo therapies plus exercise, was 0.77 points, or just under a 10% improvement, which fell short of the 15% MCID. Physical function improvement similarly fell short, with an average improvement of 5 points (12%).

In comparisons of exercise plus adjunctive therapies against exercise alone, the improvement from the additional interventions was even lower. Pain improvement was 0.41 points (7%), and physical function improvement was 2.8 points (9%). However, patients’ perceptions told a different story: 37% more patients who were using an adjunctive therapy reported feeling that the therapies were successful, compared with patients undergoing exercise therapy alone.

Adverse events were poorly reported in the trials, with only 10 trials reporting them at all, and the researchers found no significant difference in adverse events among the studies reporting them. The most common adverse events were increased pain in the joint with the osteoarthritis, pain elsewhere, or swelling and inflammation. It’s unclear, however, whether the pain, swelling, and inflammation were related to the interventions and how serious these effects might have been.

Michelle Hall, PhD, an associate professor in the department of physiotherapy at the University of Melbourne, comoderated the session with this presentation and found it interesting that more than one-third of patients perceived that they did better with the additional therapies even though improvement didn’t bear out in their pain or physical function assessments.

“But the other part of that was that the studies were of poor quality, so we can’t say with confidence, ‘Don’t do this therapy because it’s not going to work,’ ” Dr. Hall said in an interview. She said she personally would probably discourage patients from those therapies, “but I don’t think the evidence is there for everybody to do that,” she added.

Martin Van Der Esch, PhD, of Reade Centre of Rehabilitation and Rheumatology in Amsterdam, also comoderated the discussion and had more concerns about the use of adjunctive therapies in light of the study’s findings. He said in an interview that he tended to believe the patients’ overall self-reported improvement is likely a placebo effect, and he sees potential harm in that effect. If the pain is not truly decreasing as patients continue using those therapies, then the pain may become a more stable part of the nervous system, “so I think they need to do an intervention which really has evidence in reducing pain, an active approach that means exercising in the right way,” Dr. Van Der Esch said. If patients are undergoing therapy whose primary benefit is a placebo effect, “the pain will prolong and become more fixed in the nervous system,” shifting the patients toward greater risk of the pain becoming chronic, he said.

“I want to emphasize that we have an ethical role to our management, and it’s not ethical to give treatments which have no response and no pain relief except that the patient or the professional believes it will have an effect,” Dr. Van Der Esch said.

The research did not involve outside funding. Dr. French, Dr. Hall, and Dr. Van Der Esch reported having no relevant financial relationships.

DENVER – Adding therapies such as acupuncture, electrophysical stimulation, or other interventions to standard exercise therapy does not appear to offer much benefit in pain relief or physical function for patients with knee osteoarthritis, according to a study presented at the OARSI 2023 World Congress. The findings were also published in the Cochrane Database of Systematic Reviews in October 2022.

“The results do not support the use of adjunctive therapies when we add them to exercise for pain, physical function, or quality of life, when compared against placebo, adjunctive therapy, and exercise,” Helen P. French, PhD, told attendees at the meeting sponsored by the Osteoarthritis Research Society International. The findings were similar for pain and physical function when comparing adjunctive therapies with exercise against exercise alone, said Dr. French, an associate professor in physiotherapy at the Royal College of Surgeons, Dublin, except that patients using adjunctive therapies reported feeling greater improvement in their global assessments.

Exercise is recommended as a core treatment for osteoarthritis, but some patients or clinicians may be interested in supplementing that therapy with acupuncture, heat therapy, electromagnetic fields, transcutaneous electrical nerve stimulation, braces/orthotics, and other interventions. Various Cochrane Reviews of the evidence exist for these interventions in treating chronic pain in general but not for their use as adjunctive therapies in addition to exercise for osteoarthritis pain.

Researchers therefore assessed the evidence for improvement in pain, physical function, and quality of life for two sets of comparisons: adjunctive therapies plus exercise versus exercise alone, and adjunctive therapies with exercise versus placebo adjunctive therapy with exercise. The review excluded studies looking at medications or supplements.

Pain was assessed with the Numeric Pain Rating Scale (NPRS, 0-10), with an improvement of at least 2 points (15% improvement) representing the minimum clinically important difference (MCID). Physical function was assessed with the Western Ontario and McMaster Universities Arthritis Index (WOMAC, 0-68), with 6 points (15%) considered the MCID, and quality of life was assessed with the SF-36 (0-100), with 6 points (12%) as the MCID.

The researchers identified trials on knee osteoarthritis that included an overall 6,508 participants with an average age ranging from 52 to 83 years. A total of 36 studies evaluated electrophysical agents. Another seven looked at manual therapies; four looked at acupuncture/dry needling or taping; three looked at psychological, dietary, or “whole body vibration” therapies; and two evaluated spa or peloid therapy. Only one trial evaluated foot insoles.

Nearly all the studies (98%) assessed pain, and most (87%) assessed physical function. Only about one in five (21%) assessed quality of life. The improvement in pain from adding adjunctive therapies to exercise, compared with placebo therapies plus exercise, was 0.77 points, or just under a 10% improvement, which fell short of the 15% MCID. Physical function improvement similarly fell short, with an average improvement of 5 points (12%).

In comparisons of exercise plus adjunctive therapies against exercise alone, the improvement from the additional interventions was even lower. Pain improvement was 0.41 points (7%), and physical function improvement was 2.8 points (9%). However, patients’ perceptions told a different story: 37% more patients who were using an adjunctive therapy reported feeling that the therapies were successful, compared with patients undergoing exercise therapy alone.

Adverse events were poorly reported in the trials, with only 10 trials reporting them at all, and the researchers found no significant difference in adverse events among the studies reporting them. The most common adverse events were increased pain in the joint with the osteoarthritis, pain elsewhere, or swelling and inflammation. It’s unclear, however, whether the pain, swelling, and inflammation were related to the interventions and how serious these effects might have been.

Michelle Hall, PhD, an associate professor in the department of physiotherapy at the University of Melbourne, comoderated the session with this presentation and found it interesting that more than one-third of patients perceived that they did better with the additional therapies even though improvement didn’t bear out in their pain or physical function assessments.

“But the other part of that was that the studies were of poor quality, so we can’t say with confidence, ‘Don’t do this therapy because it’s not going to work,’ ” Dr. Hall said in an interview. She said she personally would probably discourage patients from those therapies, “but I don’t think the evidence is there for everybody to do that,” she added.

Martin Van Der Esch, PhD, of Reade Centre of Rehabilitation and Rheumatology in Amsterdam, also comoderated the discussion and had more concerns about the use of adjunctive therapies in light of the study’s findings. He said in an interview that he tended to believe the patients’ overall self-reported improvement is likely a placebo effect, and he sees potential harm in that effect. If the pain is not truly decreasing as patients continue using those therapies, then the pain may become a more stable part of the nervous system, “so I think they need to do an intervention which really has evidence in reducing pain, an active approach that means exercising in the right way,” Dr. Van Der Esch said. If patients are undergoing therapy whose primary benefit is a placebo effect, “the pain will prolong and become more fixed in the nervous system,” shifting the patients toward greater risk of the pain becoming chronic, he said.

“I want to emphasize that we have an ethical role to our management, and it’s not ethical to give treatments which have no response and no pain relief except that the patient or the professional believes it will have an effect,” Dr. Van Der Esch said.

The research did not involve outside funding. Dr. French, Dr. Hall, and Dr. Van Der Esch reported having no relevant financial relationships.

Sudden cardiac arrest (SCA) due to commotio cordis occurs more frequently in non–sport-related settings than is commonly thought, resulting in lower rates of resuscitation and increased mortality, especially among young women, a new review suggests.

The condition is rare, caused by an often fatal arrhythmia secondary to a blunt, nonpenetrating impact over the precordium, without direct structural damage to the heart itself. Common causes in nonsport settings include assault, motor vehicle accidents (MVAs), and daily activities such as occupational accidents.

“We found a stark difference in mortality outcomes between non–sport-related commotio cordis compared to sport-related events,” at 88% vs. 66%, Han S. Lim, MBBS, PhD, of the University of Melbourne, and Austin Health, Heidelberg, Australia, told this news organization. “Rates of cardiopulmonary resuscitation (CPR) (27% vs. 97%) and defibrillation (17% vs. 81%) were considerably lower in the non–sport-related events.”

“Although still being male-predominant, of concern, we saw a higher proportion of females in non–sport-related commotio cordis due to assault, MVAs, and other activities,” he noted. Such events may occur “in secluded domestic settings, may not be witnessed, or may occur as intentional harm, whereby the witness could also be the perpetrator, reducing the likelihood of prompt diagnosis, CPR, and defibrillation administration.”

The study was published online in JACC: Clinical Electrophysiology.
 

Young women affected

Dr. Lim and colleagues searched the literature through 2021 for all cases of commotio cordis. Three hundred and thirty-four cases from among 53 citations were included in the analysis; of those, 121 (36%) occurred in non–sport-related settings, including assault (76%), MVAs (7%), and daily activities (16%). “Daily activities” comprised activities that were expected in a person’s day-to-day routine such as falls, play fighting (in children), and occupational accidents.

Non–sport-related cases primarily involved nonprojectile etiologies (95%), including bodily contact (79%), such as impacts from fists, feet, and knees; impacts with handlebars or steering wheels; and solid stick-like weapons and flat surfaces.

Sport-related cases involved a significantly higher proportion of projectiles (94% vs. 5%) and occurred across a range of sports, mostly at the competitive level (66%).

Both sport-related and non–sport-related commotio cordis affected a similar younger demographic (mean age, 19; mostly males). No statistically significant differences between the two groups were seen with regard to previous cardiac history or family history of cardiac disease, or in arrhythmias on electrocardiogram, biomarkers, or imaging findings.

However, in non–sport-related events, the proportion of females affected was significantly higher (13% vs. 2%), as was mortality (88% vs. 66%). Rates were lower for CPR (27% vs. 97%) and defibrillation use (17% vs. 81%), and resuscitation was more commonly delayed beyond 3 minutes (80% vs. 5%).

The finding that more than a third of reported cases were non–sport-related “is higher than previously reported, and included data from 15 different countries,” the authors noted.

Study limitations included the use of data only from published studies, inclusion of a case series limited to fatal cases, small sample sizes, and lack of consistent reporting of demographic data, mechanisms, investigation results, management, and outcomes.
 

Increased awareness ‘essential’

Dr. Lim and colleagues concluded that increased awareness of non–sport-related commotio cordis is “essential” for early recognition, resuscitation, and mortality reduction. 

Jim Cheung, MD, chair of the American College of Cardiology’s electrophysiology section, “completely agrees.” Greater awareness among the general population could reduce barriers to CPR and automated external defibrillator (AED) use, he said, which in turn, can lead to improved survival.

Furthermore, Dr. Cheung added, “This study underscores the importance of ensuring that non–cardiology-trained physicians such as emergency medicine physicians and trauma surgeons who might encounter patients with non–sports-related commotio cordis recognize the entity during the course of treatment.”

Because the review relied only on published cases, “it may not represent the true breadth of cases that are occurring in the real world,” he noted. “I suspect that cases that occur outside of sports-related activities, such as MVAs and assault, are more likely to be underreported and that the true proportion of non–sports-related commotio cordis may be significantly higher than 36%.” Increased reporting of cases as part of an international commotio cordis registry would help provide additional insights, he suggested.

“There is a common misperception that SCA only occurs among older patients and patients with known coronary artery disease or heart failure,” he said. “For us to move the needle on improving SCA survival, we will need to tackle the problem from multiple angles including increasing public awareness, training the public on CPR and AED use, and improving access to AEDs by addressing structural barriers.”

Dr. Cheung pointed to ongoing efforts by nonprofit, patient-driven organizations such as the SADS Foundation and Omar Carter Foundation, and professional societies such as the American College of Cardiology, the American Heart Association, and Heart Rhythm Society, to direct public awareness campaigns and legislative proposals to address this problem.

Similar efforts are underway among cardiac societies and SCA awareness groups in Australia, Dr. Lim said.

No funding or relevant financial relationships were disclosed.
 

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

Sudden cardiac arrest (SCA) due to commotio cordis occurs more frequently in non–sport-related settings than is commonly thought, resulting in lower rates of resuscitation and increased mortality, especially among young women, a new review suggests.

The condition is rare, caused by an often fatal arrhythmia secondary to a blunt, nonpenetrating impact over the precordium, without direct structural damage to the heart itself. Common causes in nonsport settings include assault, motor vehicle accidents (MVAs), and daily activities such as occupational accidents.

“We found a stark difference in mortality outcomes between non–sport-related commotio cordis compared to sport-related events,” at 88% vs. 66%, Han S. Lim, MBBS, PhD, of the University of Melbourne, and Austin Health, Heidelberg, Australia, told this news organization. “Rates of cardiopulmonary resuscitation (CPR) (27% vs. 97%) and defibrillation (17% vs. 81%) were considerably lower in the non–sport-related events.”

“Although still being male-predominant, of concern, we saw a higher proportion of females in non–sport-related commotio cordis due to assault, MVAs, and other activities,” he noted. Such events may occur “in secluded domestic settings, may not be witnessed, or may occur as intentional harm, whereby the witness could also be the perpetrator, reducing the likelihood of prompt diagnosis, CPR, and defibrillation administration.”

The study was published online in JACC: Clinical Electrophysiology.
 

Young women affected

Dr. Lim and colleagues searched the literature through 2021 for all cases of commotio cordis. Three hundred and thirty-four cases from among 53 citations were included in the analysis; of those, 121 (36%) occurred in non–sport-related settings, including assault (76%), MVAs (7%), and daily activities (16%). “Daily activities” comprised activities that were expected in a person’s day-to-day routine such as falls, play fighting (in children), and occupational accidents.

Non–sport-related cases primarily involved nonprojectile etiologies (95%), including bodily contact (79%), such as impacts from fists, feet, and knees; impacts with handlebars or steering wheels; and solid stick-like weapons and flat surfaces.

Sport-related cases involved a significantly higher proportion of projectiles (94% vs. 5%) and occurred across a range of sports, mostly at the competitive level (66%).

Both sport-related and non–sport-related commotio cordis affected a similar younger demographic (mean age, 19; mostly males). No statistically significant differences between the two groups were seen with regard to previous cardiac history or family history of cardiac disease, or in arrhythmias on electrocardiogram, biomarkers, or imaging findings.

However, in non–sport-related events, the proportion of females affected was significantly higher (13% vs. 2%), as was mortality (88% vs. 66%). Rates were lower for CPR (27% vs. 97%) and defibrillation use (17% vs. 81%), and resuscitation was more commonly delayed beyond 3 minutes (80% vs. 5%).

The finding that more than a third of reported cases were non–sport-related “is higher than previously reported, and included data from 15 different countries,” the authors noted.

Study limitations included the use of data only from published studies, inclusion of a case series limited to fatal cases, small sample sizes, and lack of consistent reporting of demographic data, mechanisms, investigation results, management, and outcomes.
 

Increased awareness ‘essential’

Dr. Lim and colleagues concluded that increased awareness of non–sport-related commotio cordis is “essential” for early recognition, resuscitation, and mortality reduction. 

Jim Cheung, MD, chair of the American College of Cardiology’s electrophysiology section, “completely agrees.” Greater awareness among the general population could reduce barriers to CPR and automated external defibrillator (AED) use, he said, which in turn, can lead to improved survival.

Furthermore, Dr. Cheung added, “This study underscores the importance of ensuring that non–cardiology-trained physicians such as emergency medicine physicians and trauma surgeons who might encounter patients with non–sports-related commotio cordis recognize the entity during the course of treatment.”

Because the review relied only on published cases, “it may not represent the true breadth of cases that are occurring in the real world,” he noted. “I suspect that cases that occur outside of sports-related activities, such as MVAs and assault, are more likely to be underreported and that the true proportion of non–sports-related commotio cordis may be significantly higher than 36%.” Increased reporting of cases as part of an international commotio cordis registry would help provide additional insights, he suggested.

“There is a common misperception that SCA only occurs among older patients and patients with known coronary artery disease or heart failure,” he said. “For us to move the needle on improving SCA survival, we will need to tackle the problem from multiple angles including increasing public awareness, training the public on CPR and AED use, and improving access to AEDs by addressing structural barriers.”

Dr. Cheung pointed to ongoing efforts by nonprofit, patient-driven organizations such as the SADS Foundation and Omar Carter Foundation, and professional societies such as the American College of Cardiology, the American Heart Association, and Heart Rhythm Society, to direct public awareness campaigns and legislative proposals to address this problem.

Similar efforts are underway among cardiac societies and SCA awareness groups in Australia, Dr. Lim said.

No funding or relevant financial relationships were disclosed.
 

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

Sudden cardiac arrest (SCA) due to commotio cordis occurs more frequently in non–sport-related settings than is commonly thought, resulting in lower rates of resuscitation and increased mortality, especially among young women, a new review suggests.

The condition is rare, caused by an often fatal arrhythmia secondary to a blunt, nonpenetrating impact over the precordium, without direct structural damage to the heart itself. Common causes in nonsport settings include assault, motor vehicle accidents (MVAs), and daily activities such as occupational accidents.

“We found a stark difference in mortality outcomes between non–sport-related commotio cordis compared to sport-related events,” at 88% vs. 66%, Han S. Lim, MBBS, PhD, of the University of Melbourne, and Austin Health, Heidelberg, Australia, told this news organization. “Rates of cardiopulmonary resuscitation (CPR) (27% vs. 97%) and defibrillation (17% vs. 81%) were considerably lower in the non–sport-related events.”

“Although still being male-predominant, of concern, we saw a higher proportion of females in non–sport-related commotio cordis due to assault, MVAs, and other activities,” he noted. Such events may occur “in secluded domestic settings, may not be witnessed, or may occur as intentional harm, whereby the witness could also be the perpetrator, reducing the likelihood of prompt diagnosis, CPR, and defibrillation administration.”

The study was published online in JACC: Clinical Electrophysiology.
 

Young women affected

Dr. Lim and colleagues searched the literature through 2021 for all cases of commotio cordis. Three hundred and thirty-four cases from among 53 citations were included in the analysis; of those, 121 (36%) occurred in non–sport-related settings, including assault (76%), MVAs (7%), and daily activities (16%). “Daily activities” comprised activities that were expected in a person’s day-to-day routine such as falls, play fighting (in children), and occupational accidents.

Non–sport-related cases primarily involved nonprojectile etiologies (95%), including bodily contact (79%), such as impacts from fists, feet, and knees; impacts with handlebars or steering wheels; and solid stick-like weapons and flat surfaces.

Sport-related cases involved a significantly higher proportion of projectiles (94% vs. 5%) and occurred across a range of sports, mostly at the competitive level (66%).

Both sport-related and non–sport-related commotio cordis affected a similar younger demographic (mean age, 19; mostly males). No statistically significant differences between the two groups were seen with regard to previous cardiac history or family history of cardiac disease, or in arrhythmias on electrocardiogram, biomarkers, or imaging findings.

However, in non–sport-related events, the proportion of females affected was significantly higher (13% vs. 2%), as was mortality (88% vs. 66%). Rates were lower for CPR (27% vs. 97%) and defibrillation use (17% vs. 81%), and resuscitation was more commonly delayed beyond 3 minutes (80% vs. 5%).

The finding that more than a third of reported cases were non–sport-related “is higher than previously reported, and included data from 15 different countries,” the authors noted.

Study limitations included the use of data only from published studies, inclusion of a case series limited to fatal cases, small sample sizes, and lack of consistent reporting of demographic data, mechanisms, investigation results, management, and outcomes.
 

Increased awareness ‘essential’

Dr. Lim and colleagues concluded that increased awareness of non–sport-related commotio cordis is “essential” for early recognition, resuscitation, and mortality reduction. 

Jim Cheung, MD, chair of the American College of Cardiology’s electrophysiology section, “completely agrees.” Greater awareness among the general population could reduce barriers to CPR and automated external defibrillator (AED) use, he said, which in turn, can lead to improved survival.

Furthermore, Dr. Cheung added, “This study underscores the importance of ensuring that non–cardiology-trained physicians such as emergency medicine physicians and trauma surgeons who might encounter patients with non–sports-related commotio cordis recognize the entity during the course of treatment.”

Because the review relied only on published cases, “it may not represent the true breadth of cases that are occurring in the real world,” he noted. “I suspect that cases that occur outside of sports-related activities, such as MVAs and assault, are more likely to be underreported and that the true proportion of non–sports-related commotio cordis may be significantly higher than 36%.” Increased reporting of cases as part of an international commotio cordis registry would help provide additional insights, he suggested.

“There is a common misperception that SCA only occurs among older patients and patients with known coronary artery disease or heart failure,” he said. “For us to move the needle on improving SCA survival, we will need to tackle the problem from multiple angles including increasing public awareness, training the public on CPR and AED use, and improving access to AEDs by addressing structural barriers.”

Dr. Cheung pointed to ongoing efforts by nonprofit, patient-driven organizations such as the SADS Foundation and Omar Carter Foundation, and professional societies such as the American College of Cardiology, the American Heart Association, and Heart Rhythm Society, to direct public awareness campaigns and legislative proposals to address this problem.

Similar efforts are underway among cardiac societies and SCA awareness groups in Australia, Dr. Lim said.

No funding or relevant financial relationships were disclosed.
 

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

Diets consisting of high-quality – but not low-quality – plant-based foods and lower intakes of animal products may lower the risks for cancer, heart disease, and early death, new research suggests.

The prospective cohort study used data from more than 120,000 middle-aged adults followed for over 10 years in the UK Biobank. Those who consumed a healthful plant-based diet – with higher amounts of foods such as fruits, vegetables, legumes, whole grains, and nuts – and lower intakes of animal products, sugary drinks, and refined grains had a 16% lower risk of dying during follow-up, compared with those with the lowest intakes of the healthful plant-based foods.

By contrast, an unhealthy plant-based diet was associated with a 23% higher total mortality risk.

“Not all plant-based diets are created equally. Our data provide evidence to support the notion that for health benefits the plant-based sources need to be whole grains, fruits and vegetables, legumes, nuts, etc., rather than processed plant-based foods,” study coauthor Aedín Cassidy, PhD, of Queen’s University, Belfast, Northern Ireland, said in an interview.

She added: “We do not necessarily need to radically shift diets to vegan or vegetarian regimens, but rather to switch proportions on the plate to incorporate more healthful plant-based foods, fish, and leaner cuts of meat into our habitual diet. This would have benefits for both individual health and planetary health.”

The findings were published online in JAMA Network Open by Alysha S. Thompson, MSc, also at Queen’s University, and colleagues.
 

High- vs. low-quality plant-based diets linked to better outcomes

The UK Biobank is a population-based, prospective study that included more than 500,000 participants aged 40-69 years at the time of recruitment between 2006 and 2010 at 22 centers in England, Scotland, and Wales. The current study included 126,395 individuals; slightly over half (55.9%) are women.

Food intake data were collected for at least two 24-hour periods to create both “healthful” and “unhealthful” plant-based diet indexes (PDIs). These included 17 food groups: whole grains, fruits, vegetables, nuts, legumes and vegetarian protein alternatives, tea and coffee, fruit juices, refined grains, potatoes, sugar-sweetened beverages, sweets and desserts, animal fat, dairy, eggs, fish or seafood, meat, and miscellaneous animal-derived foods. Data on oils weren’t available.

Higher scores on the healthful PDI and unhealthful PDI were scored positively or negatively based on quantities of those foods consumed.

Participants were then ranked in quartiles for portions of each food group and assigned scores between 2 (lowest-intake category) and 5 (highest).

During a follow-up of 10.6-12.2 years, there were 698 deaths attributed to cardiovascular disease, 3,275 deaths caused by cancer, 6,890 individuals who experienced a cardiovascular incident, and 8,939 with incident cancer.

Another 4,751 experienced an incident fracture, which was evaluated because of the concern that diets low in animal protein might lead to insufficient vitamin B and calcium intake.

After adjustment for confounding factors, the hazard ratio for all-cause mortality in individuals with the highest healthful PDI score quartile compared with the lowest quartile was 0.84.

At the same time, the HR for all-cause mortality for those with the highest versus lowest unhealthful PDI scores was 1.23, and for cancer-related mortality was 1.19. All were statistically significant (P = .004).

Similarly, greater healthy plant-based diet adherence was associated with a significantly lower risk of being diagnosed with any cancer (HR, 0.93; P = .03), while higher unhealthful PDI scores yielded a higher risk (HR, 1.10; P = .004).

Moreover, higher healthy PDI scores were associated with lower risks for total cardiovascular incident risks (HR, 0.92; P = .007), as well as for the individual events of ischemic stroke (HR, 0.84; P = .08) and MI (HR, 0.86; P = .004). Higher unhealthy PDI scores were similarly associated with greater risks for those outcomes, with an overall HR of 1.21 (P = .004).

No associations were found between either healthful PDI or unhealthful PDI and total or site-specific fracture risk.

And because 91.3% of the UK Biobank study population was White, “future studies among more racially, ethnically, and culturally diverse populations are needed to assess the risk of major chronic disease in relation to [plant-based diets],” the authors wrote.

Dr. Cassidy and Ms. Thompson reported no relevant financial relationships.

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

Diets consisting of high-quality – but not low-quality – plant-based foods and lower intakes of animal products may lower the risks for cancer, heart disease, and early death, new research suggests.

The prospective cohort study used data from more than 120,000 middle-aged adults followed for over 10 years in the UK Biobank. Those who consumed a healthful plant-based diet – with higher amounts of foods such as fruits, vegetables, legumes, whole grains, and nuts – and lower intakes of animal products, sugary drinks, and refined grains had a 16% lower risk of dying during follow-up, compared with those with the lowest intakes of the healthful plant-based foods.

By contrast, an unhealthy plant-based diet was associated with a 23% higher total mortality risk.

“Not all plant-based diets are created equally. Our data provide evidence to support the notion that for health benefits the plant-based sources need to be whole grains, fruits and vegetables, legumes, nuts, etc., rather than processed plant-based foods,” study coauthor Aedín Cassidy, PhD, of Queen’s University, Belfast, Northern Ireland, said in an interview.

She added: “We do not necessarily need to radically shift diets to vegan or vegetarian regimens, but rather to switch proportions on the plate to incorporate more healthful plant-based foods, fish, and leaner cuts of meat into our habitual diet. This would have benefits for both individual health and planetary health.”

The findings were published online in JAMA Network Open by Alysha S. Thompson, MSc, also at Queen’s University, and colleagues.
 

High- vs. low-quality plant-based diets linked to better outcomes

The UK Biobank is a population-based, prospective study that included more than 500,000 participants aged 40-69 years at the time of recruitment between 2006 and 2010 at 22 centers in England, Scotland, and Wales. The current study included 126,395 individuals; slightly over half (55.9%) are women.

Food intake data were collected for at least two 24-hour periods to create both “healthful” and “unhealthful” plant-based diet indexes (PDIs). These included 17 food groups: whole grains, fruits, vegetables, nuts, legumes and vegetarian protein alternatives, tea and coffee, fruit juices, refined grains, potatoes, sugar-sweetened beverages, sweets and desserts, animal fat, dairy, eggs, fish or seafood, meat, and miscellaneous animal-derived foods. Data on oils weren’t available.

Higher scores on the healthful PDI and unhealthful PDI were scored positively or negatively based on quantities of those foods consumed.

Participants were then ranked in quartiles for portions of each food group and assigned scores between 2 (lowest-intake category) and 5 (highest).

During a follow-up of 10.6-12.2 years, there were 698 deaths attributed to cardiovascular disease, 3,275 deaths caused by cancer, 6,890 individuals who experienced a cardiovascular incident, and 8,939 with incident cancer.

Another 4,751 experienced an incident fracture, which was evaluated because of the concern that diets low in animal protein might lead to insufficient vitamin B and calcium intake.

After adjustment for confounding factors, the hazard ratio for all-cause mortality in individuals with the highest healthful PDI score quartile compared with the lowest quartile was 0.84.

At the same time, the HR for all-cause mortality for those with the highest versus lowest unhealthful PDI scores was 1.23, and for cancer-related mortality was 1.19. All were statistically significant (P = .004).

Similarly, greater healthy plant-based diet adherence was associated with a significantly lower risk of being diagnosed with any cancer (HR, 0.93; P = .03), while higher unhealthful PDI scores yielded a higher risk (HR, 1.10; P = .004).

Moreover, higher healthy PDI scores were associated with lower risks for total cardiovascular incident risks (HR, 0.92; P = .007), as well as for the individual events of ischemic stroke (HR, 0.84; P = .08) and MI (HR, 0.86; P = .004). Higher unhealthy PDI scores were similarly associated with greater risks for those outcomes, with an overall HR of 1.21 (P = .004).

No associations were found between either healthful PDI or unhealthful PDI and total or site-specific fracture risk.

And because 91.3% of the UK Biobank study population was White, “future studies among more racially, ethnically, and culturally diverse populations are needed to assess the risk of major chronic disease in relation to [plant-based diets],” the authors wrote.

Dr. Cassidy and Ms. Thompson reported no relevant financial relationships.

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

Diets consisting of high-quality – but not low-quality – plant-based foods and lower intakes of animal products may lower the risks for cancer, heart disease, and early death, new research suggests.

The prospective cohort study used data from more than 120,000 middle-aged adults followed for over 10 years in the UK Biobank. Those who consumed a healthful plant-based diet – with higher amounts of foods such as fruits, vegetables, legumes, whole grains, and nuts – and lower intakes of animal products, sugary drinks, and refined grains had a 16% lower risk of dying during follow-up, compared with those with the lowest intakes of the healthful plant-based foods.

By contrast, an unhealthy plant-based diet was associated with a 23% higher total mortality risk.

“Not all plant-based diets are created equally. Our data provide evidence to support the notion that for health benefits the plant-based sources need to be whole grains, fruits and vegetables, legumes, nuts, etc., rather than processed plant-based foods,” study coauthor Aedín Cassidy, PhD, of Queen’s University, Belfast, Northern Ireland, said in an interview.

She added: “We do not necessarily need to radically shift diets to vegan or vegetarian regimens, but rather to switch proportions on the plate to incorporate more healthful plant-based foods, fish, and leaner cuts of meat into our habitual diet. This would have benefits for both individual health and planetary health.”

The findings were published online in JAMA Network Open by Alysha S. Thompson, MSc, also at Queen’s University, and colleagues.
 

High- vs. low-quality plant-based diets linked to better outcomes

The UK Biobank is a population-based, prospective study that included more than 500,000 participants aged 40-69 years at the time of recruitment between 2006 and 2010 at 22 centers in England, Scotland, and Wales. The current study included 126,395 individuals; slightly over half (55.9%) are women.

Food intake data were collected for at least two 24-hour periods to create both “healthful” and “unhealthful” plant-based diet indexes (PDIs). These included 17 food groups: whole grains, fruits, vegetables, nuts, legumes and vegetarian protein alternatives, tea and coffee, fruit juices, refined grains, potatoes, sugar-sweetened beverages, sweets and desserts, animal fat, dairy, eggs, fish or seafood, meat, and miscellaneous animal-derived foods. Data on oils weren’t available.

Higher scores on the healthful PDI and unhealthful PDI were scored positively or negatively based on quantities of those foods consumed.

Participants were then ranked in quartiles for portions of each food group and assigned scores between 2 (lowest-intake category) and 5 (highest).

During a follow-up of 10.6-12.2 years, there were 698 deaths attributed to cardiovascular disease, 3,275 deaths caused by cancer, 6,890 individuals who experienced a cardiovascular incident, and 8,939 with incident cancer.

Another 4,751 experienced an incident fracture, which was evaluated because of the concern that diets low in animal protein might lead to insufficient vitamin B and calcium intake.

After adjustment for confounding factors, the hazard ratio for all-cause mortality in individuals with the highest healthful PDI score quartile compared with the lowest quartile was 0.84.

At the same time, the HR for all-cause mortality for those with the highest versus lowest unhealthful PDI scores was 1.23, and for cancer-related mortality was 1.19. All were statistically significant (P = .004).

Similarly, greater healthy plant-based diet adherence was associated with a significantly lower risk of being diagnosed with any cancer (HR, 0.93; P = .03), while higher unhealthful PDI scores yielded a higher risk (HR, 1.10; P = .004).

Moreover, higher healthy PDI scores were associated with lower risks for total cardiovascular incident risks (HR, 0.92; P = .007), as well as for the individual events of ischemic stroke (HR, 0.84; P = .08) and MI (HR, 0.86; P = .004). Higher unhealthy PDI scores were similarly associated with greater risks for those outcomes, with an overall HR of 1.21 (P = .004).

No associations were found between either healthful PDI or unhealthful PDI and total or site-specific fracture risk.

And because 91.3% of the UK Biobank study population was White, “future studies among more racially, ethnically, and culturally diverse populations are needed to assess the risk of major chronic disease in relation to [plant-based diets],” the authors wrote.

Dr. Cassidy and Ms. Thompson reported no relevant financial relationships.

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

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

Taking 8,000 steps or more for just 1 or 2 days a week was linked to a significant reduction in all-cause and cardiovascular mortality, according to a study of about 3,000 adults.

Previous research has shown lower mortality rates among individuals who walk consistently, especially those who log at least 8,000 steps daily, but the benefit of intense walking just once or twice a week on long-term health outcomes has not been examined, wrote Kosuke Inoue, MD, of Kyoto University, Japan, and colleagues.

iStock/thinkstockphotos

In a study published in JAMA Network Open, the researchers reviewed 10-year follow-up data for 3,101 adults aged 20 years and older who were part of the 2005 and 2006 National Health and Nutrition Examination Survey (NHANES).

The participants were asked to wear accelerometers to track their steps for 7 consecutive days. The researchers assessed the dose-response relationship between days of taking 8,000 steps or more (about 4 miles) during 1 week, and the primary outcome of all-cause mortality risk after 10 years. Cardiovascular mortality risk after 10 years was a secondary outcome.

The mean age of the participants was 50.5 years and 51% were women. The breakdown by ethnicity was 51% White, 21% Black, 24% Hispanic, and 4% other races/ethnicities. A total of 632 individuals took 8,000 steps or more 0 days a week, 532 took at least 8,000 steps 1-2 days per week, and 1,937 took at least 8,000 steps 3-7 days a week.

During the 10-year follow-up period, overall all-cause mortality was 14.2% and cardiovascular mortality was 5.3% across all step groups.

In an adjusted analysis, individuals who took at least 8,000 steps 1-2 days a week had a 14.9% lower all-cause mortality risk compared with those who never reached 8,000 daily steps. This difference was similar to the 16.5% reduced mortality risk for those who took at least 8,000 steps 3-7 days a week.

Similarly, compared with the group with no days of at least 8,000 steps, cardiovascular mortality risk was 8.1% lower for those who took 8,000 steps 1-2 days per week and 8.4% lower for those who took at least 8,000 steps 3-7 days per week. The decreased mortality risk plateaued at 3-4 days.

These patterns in reduced all-cause mortality risk persisted in a stratified analysis by age (younger than 65 years and 65 years and older) and sex. Similar patterns in reduced mortality also emerged when the researchers used different thresholds of daily steps, such as a minimum of 10,000 steps instead of 8,000. The adjusted all-cause mortality for groups who took at least 10,000 steps 1-2 days a week, 3-7 days a week, and no days a week were 8.1%, 7.3%, and 16.7%, respectively, with corresponding cardiovascular mortality risks of 2.4%, 2.3%, and 7.0%, respectively.

“Given the simplicity and ease of counting daily steps, our findings indicate that the recommended number of steps taken on as few as 1 to 2 days per week may be a feasible option for individuals who are striving to achieve some health benefits through adhering to a recommended daily step count but are unable to accomplish this on a daily basis,” the researchers wrote in their discussion.

The findings were limited by several factors including the use daily step measures for 1 week only at baseline, with no data on how physical activity changes might impact mortality risk, the researchers noted. Other limitations included possible accelerometer error and misclassification of activity, possible selection bias, and lack of data on cause-specific mortality outside of cardiovascular death, they said.

However, the results were strengthened by the use of accelerometers as objective measures of activity and by the availability of 10-year follow-up data for nearly 100% of the participants, they said.

“Although our findings might suffer from residual confounding that should be addressed in future research, they suggest that people may receive substantial health benefits even if a sufficient number of steps are taken on only a couple days of the week,” they concluded.
 

Proceed with caution

The current study findings should be interpreted cautiously in light of the potential unmeasured confounding factors and selection bias that often occur in studies of physical activity, James Sawalla Guseh, MD, of Massachusetts General Hospital, and Jose F. Figueroa, MD, of Harvard T.H. Chan School of Public Health, Boston, wrote in an accompanying editorial.

The results support previous studies showing some longevity benefits with “weekend warrior” patterns of intense physical activity for only a couple of days; however, “the body of evidence for sporadic activity is not as robust as the evidence for sustained and regular aerobic activity,” the authors emphasized.

The editorial authors also highlighted the limitations of the current study, including the observational design and significant differences in demographics and comorbidities between the 1- to 2-days of 8,000 steps exercise group and the 0-day group, as well as the reliance on only a week’s worth of data to infer 10 years’ mortality.

Although the data are consistent with previous observations that increased exercise volume reduces mortality, more research is needed, as the current study findings may not reflect other dimensions of health, including neurological health, they said.

Despite the need for cautious interpretation of the results, the current study “supports the emerging and popular idea that step counting, which does not require consideration of exercise duration or intensity, can offer guidance toward robust and favorable health outcomes,” and may inform step-based activity goals to improve public health, the editorialists wrote.

The study was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, the Japan Endocrine Society, and the Meiji Yasuda Life Foundation of Health and Welfare. Dr. Inoue also was supported by the Program for the Development of Next-Generation Leading Scientists With Global Insight sponsored by the Ministry of Education, Culture, Sports, Science and Technology, Japan. The other researchers had no relevant financial conflicts to disclose. The editorial authors had no financial conflicts to disclose.

A biopsy showed a markedly elastotic dermis consisting of a palisading granulomatous inflammatory infiltrate and numerous multinucleated histiocytes (Figure). These histopathologic findings along with the clinical presentation confirmed a diagnosis of annular elastolytic granuloma (AEG). Treatment consisting of 3 months of oral minocycline, 2 months of oral doxycycline, and clobetasol ointment all failed. At that point, oral hydroxychloroquine was recommended. Our patient was lost to follow-up by dermatology, then subsequently was placed on hydroxychloroquine by rheumatology to treat both the osteoarthritis and AEG. A follow-up appointment with dermatology was planned for 3 months to monitor hydroxychloroquine treatment and monitor treatment progress; however, she did not follow-up or seek further treatment.

Annular elastolytic granuloma clinically is similar to granuloma annulare (GA), with both presenting as annular plaques surrounded by an elevated border.¹ Although AEG clinically is distinct with hypopigmented atrophied plaque centers,² a biopsy is required to confirm the lack of elastic tissue in zones of atrophy and the presence of multinucleated histiocytes.^1,3 Lesions most commonly are seen clinically on sun-exposed areas in middle-aged White women; however, they rarely have been seen on frequently covered skin.⁴ Our case illustrates the striking photodistribution of AEG, especially on the posterior neck area. The clinical diagnoses of AEG, annular elastolytic giant cell granuloma, and GA in sun-exposed areas are synonymous and can be used interchangeably.^5,6

Pathologies considered in the diagnosis of AEG include but are not limited to tinea corporis, annular lichen planus, erythema annulare centrifugum, and necrobiosis lipoidica. Scaling typically is absent in AEG, while tinea corporis presents with hyphae within the stratum corneum of the plaques.⁷ Papules along the periphery of annular lesions are more typical of annular lichen planus than AEG, and they tend to have a more purple hue.⁸ Erythema annulare centrifugum has annular erythematous plaques similar to those found in AEG but differs with scaling on the inner margins of these plaques. Histopathology presenting with a lymphocytic infiltrate surrounding vasculature and no indication of elastolytic degradation would further indicate a diagnosis of erythema annulare centrifugum.⁹ Histopathology showing necrobiosis, lipid depositions, and vascular wall thickenings is indicative of necrobiosis lipoidica.¹⁰

Similar to GA,¹¹ the cause of AEG is idiopathic.² Annular elastolytic granuloma and GA differ in the fact that elastin degradation is characteristic of AEG compared to collagen degradation in GA. It is suspected that elastin degradation in AEG patients is caused by an immune response triggering phagocytosis of elastin by multinucleated histiocytes.² Actinic damage also is considered a possible cause of elastin fiber degradation in AEG.¹² Granuloma annulare can be ruled out and the diagnosis of AEG confirmed with the absence of elastin fibers and mucin on pathology.¹³

Although there is no established first-line treatment of AEG, successful treatment has been achieved with antimalarial drugs paired with topical steroids.¹⁴ Treatment recommendations for AEG include minocycline, chloroquine, hydroxychloroquine, tranilast, and oral retinoids, as well as oral and topical steroids. In clinical cases where AEG occurs in the setting of a chronic disease such as diabetes mellitus, vascular occlusion, arthritis, or hypertension, treatment of underlying disease has been shown to resolve AEG symptoms.¹⁴

Although light therapy is not common for AEG, UV light radiation has demonstrated success in treating AEG.^15,16 One study showed complete clearance of granulomatous papules after narrowband UVB treatment.¹⁵ Another study showed that 2 patients treated with psoralen plus UVA therapy reached complete clearance of AEG lasting at least 3 months after treatment.¹⁶

A biopsy showed a markedly elastotic dermis consisting of a palisading granulomatous inflammatory infiltrate and numerous multinucleated histiocytes (Figure). These histopathologic findings along with the clinical presentation confirmed a diagnosis of annular elastolytic granuloma (AEG). Treatment consisting of 3 months of oral minocycline, 2 months of oral doxycycline, and clobetasol ointment all failed. At that point, oral hydroxychloroquine was recommended. Our patient was lost to follow-up by dermatology, then subsequently was placed on hydroxychloroquine by rheumatology to treat both the osteoarthritis and AEG. A follow-up appointment with dermatology was planned for 3 months to monitor hydroxychloroquine treatment and monitor treatment progress; however, she did not follow-up or seek further treatment.

Annular elastolytic granuloma clinically is similar to granuloma annulare (GA), with both presenting as annular plaques surrounded by an elevated border.¹ Although AEG clinically is distinct with hypopigmented atrophied plaque centers,² a biopsy is required to confirm the lack of elastic tissue in zones of atrophy and the presence of multinucleated histiocytes.^1,3 Lesions most commonly are seen clinically on sun-exposed areas in middle-aged White women; however, they rarely have been seen on frequently covered skin.⁴ Our case illustrates the striking photodistribution of AEG, especially on the posterior neck area. The clinical diagnoses of AEG, annular elastolytic giant cell granuloma, and GA in sun-exposed areas are synonymous and can be used interchangeably.^5,6

Pathologies considered in the diagnosis of AEG include but are not limited to tinea corporis, annular lichen planus, erythema annulare centrifugum, and necrobiosis lipoidica. Scaling typically is absent in AEG, while tinea corporis presents with hyphae within the stratum corneum of the plaques.⁷ Papules along the periphery of annular lesions are more typical of annular lichen planus than AEG, and they tend to have a more purple hue.⁸ Erythema annulare centrifugum has annular erythematous plaques similar to those found in AEG but differs with scaling on the inner margins of these plaques. Histopathology presenting with a lymphocytic infiltrate surrounding vasculature and no indication of elastolytic degradation would further indicate a diagnosis of erythema annulare centrifugum.⁹ Histopathology showing necrobiosis, lipid depositions, and vascular wall thickenings is indicative of necrobiosis lipoidica.¹⁰

Similar to GA,¹¹ the cause of AEG is idiopathic.² Annular elastolytic granuloma and GA differ in the fact that elastin degradation is characteristic of AEG compared to collagen degradation in GA. It is suspected that elastin degradation in AEG patients is caused by an immune response triggering phagocytosis of elastin by multinucleated histiocytes.² Actinic damage also is considered a possible cause of elastin fiber degradation in AEG.¹² Granuloma annulare can be ruled out and the diagnosis of AEG confirmed with the absence of elastin fibers and mucin on pathology.¹³

Although there is no established first-line treatment of AEG, successful treatment has been achieved with antimalarial drugs paired with topical steroids.¹⁴ Treatment recommendations for AEG include minocycline, chloroquine, hydroxychloroquine, tranilast, and oral retinoids, as well as oral and topical steroids. In clinical cases where AEG occurs in the setting of a chronic disease such as diabetes mellitus, vascular occlusion, arthritis, or hypertension, treatment of underlying disease has been shown to resolve AEG symptoms.¹⁴

Although light therapy is not common for AEG, UV light radiation has demonstrated success in treating AEG.^15,16 One study showed complete clearance of granulomatous papules after narrowband UVB treatment.¹⁵ Another study showed that 2 patients treated with psoralen plus UVA therapy reached complete clearance of AEG lasting at least 3 months after treatment.¹⁶

A biopsy showed a markedly elastotic dermis consisting of a palisading granulomatous inflammatory infiltrate and numerous multinucleated histiocytes (Figure). These histopathologic findings along with the clinical presentation confirmed a diagnosis of annular elastolytic granuloma (AEG). Treatment consisting of 3 months of oral minocycline, 2 months of oral doxycycline, and clobetasol ointment all failed. At that point, oral hydroxychloroquine was recommended. Our patient was lost to follow-up by dermatology, then subsequently was placed on hydroxychloroquine by rheumatology to treat both the osteoarthritis and AEG. A follow-up appointment with dermatology was planned for 3 months to monitor hydroxychloroquine treatment and monitor treatment progress; however, she did not follow-up or seek further treatment.

Annular elastolytic granuloma clinically is similar to granuloma annulare (GA), with both presenting as annular plaques surrounded by an elevated border.¹ Although AEG clinically is distinct with hypopigmented atrophied plaque centers,² a biopsy is required to confirm the lack of elastic tissue in zones of atrophy and the presence of multinucleated histiocytes.^1,3 Lesions most commonly are seen clinically on sun-exposed areas in middle-aged White women; however, they rarely have been seen on frequently covered skin.⁴ Our case illustrates the striking photodistribution of AEG, especially on the posterior neck area. The clinical diagnoses of AEG, annular elastolytic giant cell granuloma, and GA in sun-exposed areas are synonymous and can be used interchangeably.^5,6

Pathologies considered in the diagnosis of AEG include but are not limited to tinea corporis, annular lichen planus, erythema annulare centrifugum, and necrobiosis lipoidica. Scaling typically is absent in AEG, while tinea corporis presents with hyphae within the stratum corneum of the plaques.⁷ Papules along the periphery of annular lesions are more typical of annular lichen planus than AEG, and they tend to have a more purple hue.⁸ Erythema annulare centrifugum has annular erythematous plaques similar to those found in AEG but differs with scaling on the inner margins of these plaques. Histopathology presenting with a lymphocytic infiltrate surrounding vasculature and no indication of elastolytic degradation would further indicate a diagnosis of erythema annulare centrifugum.⁹ Histopathology showing necrobiosis, lipid depositions, and vascular wall thickenings is indicative of necrobiosis lipoidica.¹⁰

Similar to GA,¹¹ the cause of AEG is idiopathic.² Annular elastolytic granuloma and GA differ in the fact that elastin degradation is characteristic of AEG compared to collagen degradation in GA. It is suspected that elastin degradation in AEG patients is caused by an immune response triggering phagocytosis of elastin by multinucleated histiocytes.² Actinic damage also is considered a possible cause of elastin fiber degradation in AEG.¹² Granuloma annulare can be ruled out and the diagnosis of AEG confirmed with the absence of elastin fibers and mucin on pathology.¹³

Although there is no established first-line treatment of AEG, successful treatment has been achieved with antimalarial drugs paired with topical steroids.¹⁴ Treatment recommendations for AEG include minocycline, chloroquine, hydroxychloroquine, tranilast, and oral retinoids, as well as oral and topical steroids. In clinical cases where AEG occurs in the setting of a chronic disease such as diabetes mellitus, vascular occlusion, arthritis, or hypertension, treatment of underlying disease has been shown to resolve AEG symptoms.¹⁴

Although light therapy is not common for AEG, UV light radiation has demonstrated success in treating AEG.^15,16 One study showed complete clearance of granulomatous papules after narrowband UVB treatment.¹⁵ Another study showed that 2 patients treated with psoralen plus UVA therapy reached complete clearance of AEG lasting at least 3 months after treatment.¹⁶

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

DENVER – Using antidepressants to treat osteoarthritis pain can benefit some individuals but appears to have a clinically unimportant reduction in pain when looking at all patients who have tried them, according to a study presented at the OARSI 2023 World Congress. The review was also published in the Cochrane Database of Systematic Reviews in October 2022.

In terms of implications for clinical practice, the findings “seem to suggest there is a subgroup that is more likely to respond to antidepressants,” Anita Wluka, PhD, MBBS, a professor in the School of Public Health and Preventive Medicine at Monash University in Melbourne, told attendees. The findings also raise an important research question: “How can we identify the patient phenotype likely to benefit so we can [minimize the] risk of those adverse events and effects?”

Osteoarthritis pain is heterogeneous, and an estimated 30% of the pain is neuropathic-like, likely including central and peripheral sensitization, Dr. Wluka said. Given that antidepressants affect multiple sites along these pathways, multiple organizations have issued a conditional recommendation for duloxetine in their osteoarthritis guidelines, including OARSI, the European Alliance of Associations for Rheumatology, and the American College of Rheumatology.

The Cochrane Collaboration therefore conducted a systematic review and meta-analysis of research on the benefits and harms of using antidepressants to treat symptomatic knee and hip osteoarthritis. The review included studies through January 2021 whose participants had knee and/or hip osteoarthritis and which compared antidepressant therapy with placebo or another intervention for at least 6 weeks. The authors looked at seven outcomes: overall pain on a 0-10 scale, clinical response (at least a 50% reduction in 24‐hour mean pain), physical function using the Western Ontario and McMaster Universities Arthritis Index (WOMAC), quality of life using the EQ-5D, the proportion of participants withdrawing because of adverse events, the proportion who experienced any adverse events, and the proportion who experienced serious adverse events.

The researchers considered a change on the pain scale of 0.5-1 points to be “slight to small,” a difference above 1 up to 2 to be “moderate,” and a difference greater than 2 points to be “large.” In assessing quality of life function on a scale of 0-100, a slight to small difference was 5-10, a moderate difference was 11-20, and a large difference was above 20.

Of the 18 articles the researchers identified for qualitative synthesis, 9 met the criteria for qualitative synthesis in the meta-analysis, including 7 studies only on the knee and 2 that included the knees and hips. All nine studies compared antidepressants with placebo, with or without NSAIDs. Most focused on serotonin and norepinephrine reuptake inhibitors (SNRIs) – six studies on duloxetine and one on milnacipran – while one included fluvoxamine and one included nortriptyline.

The trials included a combined 2,122 participants who were predominantly female with an average age range of 54-66. Trials ranged from 8 to 16 weeks. Five of the trials carried risk of attrition and reporting bias, and only one trial had low risk of bias across all domains.

In five trials with SNRIs and one trial with tricyclics (nortriptyline) totaling 1,904 participants, 45% of those receiving antidepressants had a clinical response, compared with 29% of patients who received placebo (risk ratio, 1.55; 95% CI, 1.31-1.92). This absolute improvement in pain occurred in 16% more participants taking antidepressants, giving a number needed to treat (NNT) of 6. Average improvement in WOMAC physical function was 10.5 points with placebo and 16.2 points with antidepressants, indicating a “small, clinically unimportant response,” the researchers concluded.

Withdrawals because of adverse events included 11% of the antidepressant group and 5% of the placebo group (RR, 2.15; 95% CI, 1.56-2.87), putting the NNT for a harmful outcome at 17.

For all nine trials together, however, the mean reduction in pain from antidepressants was 2.3 points, compared with 1.7 points with placebo, a statistically significant but ”clinically unimportant improvement,” the researchers concluded. Adverse events occurred in 64% of the antidepressant group, compared with 49% of the placebo group (RR, 1.27; 95% CI, 1.15-1.41), which put the NNT for a harmful outcome at 7. No significant difference in serious adverse events occurred between the groups.

The analysis was limited by the low number of trials, most of which were sponsored by industry and most of which used duloxetine. Further, few of the studies enrolled patients with osteoarthritis of the hip, none assessed medium- or long-term effects, and none stratified the participants for different types of pain (neuropathic-like or central or peripheral pain sensitization).

“My general impression is that there was a statistically significant difference found in favor of duloxetine and the antidepressants,” David J. Hunter, MBBS, PhD, MSc, of the University of Sydney, said after the presentation. “There is a real risk of harm, which I think is important to take into consideration, but at least for me as a clinician and in advising other clinicians, it’s one tool in our armamentarium. I think it’s really important to allow patients to make an informed decision about the potential benefit, the real risk of harm, and the fact that it is quite useful in some patients, and I use it in my clinical practice.”

Jeffrey N. Katz, MD, MS, of Brigham and Women’s Hospital in Boston, said he uses antidepressants in the same way in his practice and that other types of medications, such as TNF inhibitors, also carry risk of harm that may exceed that of antidepressants.

“I’ve had lots of people start duloxetine, and if they stop it, it’s usually because they just don’t tolerate it very well,” Dr. Katz said.

“We don’t want to throw too many things away,” Dr. Hunter added. “Our patients don’t necessarily have a lot of choices here from a pharmacologic perspective, so I think it’s one of those options that I want to keep in my tool kit, and that’s not necessarily going to change.”

The research did not involve outside funding, and Dr. Wluka reported having no industry disclosures. Disclosure information was unavailable for Dr. Katz and Dr. Hunter. The Congress was sponsored by the Osteoarthritis Research Society International.

NEW ORLEANS – Limited treatment options exist for brittle nail syndrome, a heterogeneous abnormality characterized by increased nail plate fragility, with nails that split, flake, crumble, and become soft and lose elasticity.

“The mainstay of treatment is irritant avoidance and moisturization,” Shari R. Lipner, MD, PhD, associate professor of clinical dermatology and director of the nail division at Weill Cornell Medicine, New York, said at the annual meeting of the American Academy of Dermatology. “This works well if patients are religious about doing it.”

Dr. Lipner

Brittle nail syndrome affects about 20% of adults, she said, and is more common in females, particularly those older than age 50. Most cases are idiopathic, but some are secondary to dermatologic diseases including nail psoriasis and nail lichen planus, and systemic diseases such as hyperthyroidism and hypothyroidism. They are more common in patients in certain occupations such as carpentry. “The pathogenesis is poorly understood but is thought to be due to weakened intercellular keratinocyte bridges, decreased cholesterol sulphate in the nail plate, and reduced water content in the nail plate,” Dr. Lipner said.

Key clinical findings include onychoschizia (peeling of the nail plate), onychorrhexis (an increase in the longitudinal ridges and furrows, sometimes leading to splitting), and superficial granulation of keratin. Treatment involves general measures. “You want to treat the underlying cause and recommend that the patient avoid water and irritant exposure,” she said. Her general instructions for affected patients are to wear latex gloves for wet work and cotton gloves for dry work, avoid triclosan-based hand sanitizers, avoid nail cosmetics, minimize nail trauma, and foster moisturization.“It’s important to give these instructions verbally and in written form,” she said. “In our practice, we designed a QR code that links to our patient handout.”

According to Dr. Lipner, the promotion of vitamins and supplements such as biotin, vitamin D, amino acids, and chromium for treating brittle nail syndrome is rampant on the Internet and on social media, but no rigorously designed clinical trials have shown efficacy for any of them. “Very few people are deficient in biotin, except for those with inherited enzyme deficiencies,” and most people “can get all the biotin they need from a regular diet,” she said.

The initial rationale for using biotin for nails comes from the veterinary literature, she continued. In the 1940s, chickens with biotin deficiency developed fissures in their feet and parrot-like beaks. In the 1970s, pigs with biotin deficiency developed friable hooves, which was corrected with biotin supplementation. “By the 1980s it was standard practice to supplement the feet of pigs with biotin,” she said.

In a human trial from 1989, German researchers enrolled 71 patients with brittle nail syndrome who took oral biotin, 2.5 mg daily. Of the 45 patients evaluated, 41 (91%) showed improvement in firmness and hardness of the fingernails over the course of 5.5 months, but there was no good control group, Dr. Lipner said. In a follow-up study, the same German researchers used scanning electron microscopy to evaluate 22 patients with brittle nails who took oral biotin 2.5 mg daily and compared them with 10 patients with normal nails who did not take biotin. They found a 25% increase in nail plate thickness in the biotin group and onychoschizia resolved in 50% of patients who received biotin. “But again, there was no good control group,” Dr. Lipner said.

In a third study on the topic, researchers surveyed 46 patients who presented with onychorrhexis and/or onychoschizia on clinical exam and took 2.5 mg of biotin daily. Of the 35 survey respondents, 63% subjectively reported improvement in their nails at a mean of 2 months. “This is where we are today: There have been studies of only 80 patients that were done 25 years ago,” Dr. Lipner said. “That’s all of our evidence for biotin for the treatment of brittle nail syndrome.”
 

FDA warning about biotin

Additional cause for concern, she continued, is the safety communication issued by the FDA in 2017, stating that the use of biotin may interfere with certain lab tests such as thyroid tests and cardiac enzymes, in some cases leading to death. The safety communication was updated in 2019.

In 2018, Dr. Lipner and colleagues administered an anonymous survey to 447 patients at their clinic asking about their use of biotin supplements. Of the 447 patients, 34% reported current use of biotin. Among biotin users, 7% were aware of the FDA warning, 29% of respondents reported that it was recommended by either a primary care physician or a dermatologist, and 56% underwent laboratory testing while taking biotin. “It’s our duty to warn our patients about the evidence for biotin for treating brittle nails, and about this interference on laboratory tests,” Dr. Lipner said.

Other treatment options for brittle nail syndrome include two lacquers that are available by prescription. One contains hydroxypropyl chitosan, Equisetum arvense, and methylsulphonylmethane; the other contains 16% poly-ureaurethane, but has not been well studied. “These products can be very expensive if not covered by insurance,” Dr. Lipner said.

As an alternative, she recommends Nail Tek CITRA 2 Nail Strengthener, which is available for less than $10 from Walmart and other retailers.

Cyclosporine emulsion also has been studied for brittle nail syndrome, but results to date have been underwhelming. Dr. Lipner and colleagues are exploring the effect of platelet rich plasma for treating brittle nails on the premise that it will improve nail growth and promote healing, in a 16-week trial that has enrolled 10 patients and includes both a Physician Global Improvement Assessment (PGIA) and a Physician Global Assessment (PGA) score. “Our data is being analyzed by three independent nail experts, and we hope to report the findings next year,” she said.

Dr. Lipner reported having no disclosures relevant to her presentation.

NEW ORLEANS – Limited treatment options exist for brittle nail syndrome, a heterogeneous abnormality characterized by increased nail plate fragility, with nails that split, flake, crumble, and become soft and lose elasticity.

“The mainstay of treatment is irritant avoidance and moisturization,” Shari R. Lipner, MD, PhD, associate professor of clinical dermatology and director of the nail division at Weill Cornell Medicine, New York, said at the annual meeting of the American Academy of Dermatology. “This works well if patients are religious about doing it.”

Dr. Lipner

Brittle nail syndrome affects about 20% of adults, she said, and is more common in females, particularly those older than age 50. Most cases are idiopathic, but some are secondary to dermatologic diseases including nail psoriasis and nail lichen planus, and systemic diseases such as hyperthyroidism and hypothyroidism. They are more common in patients in certain occupations such as carpentry. “The pathogenesis is poorly understood but is thought to be due to weakened intercellular keratinocyte bridges, decreased cholesterol sulphate in the nail plate, and reduced water content in the nail plate,” Dr. Lipner said.

Key clinical findings include onychoschizia (peeling of the nail plate), onychorrhexis (an increase in the longitudinal ridges and furrows, sometimes leading to splitting), and superficial granulation of keratin. Treatment involves general measures. “You want to treat the underlying cause and recommend that the patient avoid water and irritant exposure,” she said. Her general instructions for affected patients are to wear latex gloves for wet work and cotton gloves for dry work, avoid triclosan-based hand sanitizers, avoid nail cosmetics, minimize nail trauma, and foster moisturization.“It’s important to give these instructions verbally and in written form,” she said. “In our practice, we designed a QR code that links to our patient handout.”

According to Dr. Lipner, the promotion of vitamins and supplements such as biotin, vitamin D, amino acids, and chromium for treating brittle nail syndrome is rampant on the Internet and on social media, but no rigorously designed clinical trials have shown efficacy for any of them. “Very few people are deficient in biotin, except for those with inherited enzyme deficiencies,” and most people “can get all the biotin they need from a regular diet,” she said.

The initial rationale for using biotin for nails comes from the veterinary literature, she continued. In the 1940s, chickens with biotin deficiency developed fissures in their feet and parrot-like beaks. In the 1970s, pigs with biotin deficiency developed friable hooves, which was corrected with biotin supplementation. “By the 1980s it was standard practice to supplement the feet of pigs with biotin,” she said.

In a human trial from 1989, German researchers enrolled 71 patients with brittle nail syndrome who took oral biotin, 2.5 mg daily. Of the 45 patients evaluated, 41 (91%) showed improvement in firmness and hardness of the fingernails over the course of 5.5 months, but there was no good control group, Dr. Lipner said. In a follow-up study, the same German researchers used scanning electron microscopy to evaluate 22 patients with brittle nails who took oral biotin 2.5 mg daily and compared them with 10 patients with normal nails who did not take biotin. They found a 25% increase in nail plate thickness in the biotin group and onychoschizia resolved in 50% of patients who received biotin. “But again, there was no good control group,” Dr. Lipner said.

In a third study on the topic, researchers surveyed 46 patients who presented with onychorrhexis and/or onychoschizia on clinical exam and took 2.5 mg of biotin daily. Of the 35 survey respondents, 63% subjectively reported improvement in their nails at a mean of 2 months. “This is where we are today: There have been studies of only 80 patients that were done 25 years ago,” Dr. Lipner said. “That’s all of our evidence for biotin for the treatment of brittle nail syndrome.”
 

FDA warning about biotin

Additional cause for concern, she continued, is the safety communication issued by the FDA in 2017, stating that the use of biotin may interfere with certain lab tests such as thyroid tests and cardiac enzymes, in some cases leading to death. The safety communication was updated in 2019.

In 2018, Dr. Lipner and colleagues administered an anonymous survey to 447 patients at their clinic asking about their use of biotin supplements. Of the 447 patients, 34% reported current use of biotin. Among biotin users, 7% were aware of the FDA warning, 29% of respondents reported that it was recommended by either a primary care physician or a dermatologist, and 56% underwent laboratory testing while taking biotin. “It’s our duty to warn our patients about the evidence for biotin for treating brittle nails, and about this interference on laboratory tests,” Dr. Lipner said.

Other treatment options for brittle nail syndrome include two lacquers that are available by prescription. One contains hydroxypropyl chitosan, Equisetum arvense, and methylsulphonylmethane; the other contains 16% poly-ureaurethane, but has not been well studied. “These products can be very expensive if not covered by insurance,” Dr. Lipner said.

As an alternative, she recommends Nail Tek CITRA 2 Nail Strengthener, which is available for less than $10 from Walmart and other retailers.

Cyclosporine emulsion also has been studied for brittle nail syndrome, but results to date have been underwhelming. Dr. Lipner and colleagues are exploring the effect of platelet rich plasma for treating brittle nails on the premise that it will improve nail growth and promote healing, in a 16-week trial that has enrolled 10 patients and includes both a Physician Global Improvement Assessment (PGIA) and a Physician Global Assessment (PGA) score. “Our data is being analyzed by three independent nail experts, and we hope to report the findings next year,” she said.

Dr. Lipner reported having no disclosures relevant to her presentation.

NEW ORLEANS – Limited treatment options exist for brittle nail syndrome, a heterogeneous abnormality characterized by increased nail plate fragility, with nails that split, flake, crumble, and become soft and lose elasticity.

“The mainstay of treatment is irritant avoidance and moisturization,” Shari R. Lipner, MD, PhD, associate professor of clinical dermatology and director of the nail division at Weill Cornell Medicine, New York, said at the annual meeting of the American Academy of Dermatology. “This works well if patients are religious about doing it.”

Dr. Lipner

Brittle nail syndrome affects about 20% of adults, she said, and is more common in females, particularly those older than age 50. Most cases are idiopathic, but some are secondary to dermatologic diseases including nail psoriasis and nail lichen planus, and systemic diseases such as hyperthyroidism and hypothyroidism. They are more common in patients in certain occupations such as carpentry. “The pathogenesis is poorly understood but is thought to be due to weakened intercellular keratinocyte bridges, decreased cholesterol sulphate in the nail plate, and reduced water content in the nail plate,” Dr. Lipner said.

Key clinical findings include onychoschizia (peeling of the nail plate), onychorrhexis (an increase in the longitudinal ridges and furrows, sometimes leading to splitting), and superficial granulation of keratin. Treatment involves general measures. “You want to treat the underlying cause and recommend that the patient avoid water and irritant exposure,” she said. Her general instructions for affected patients are to wear latex gloves for wet work and cotton gloves for dry work, avoid triclosan-based hand sanitizers, avoid nail cosmetics, minimize nail trauma, and foster moisturization.“It’s important to give these instructions verbally and in written form,” she said. “In our practice, we designed a QR code that links to our patient handout.”

According to Dr. Lipner, the promotion of vitamins and supplements such as biotin, vitamin D, amino acids, and chromium for treating brittle nail syndrome is rampant on the Internet and on social media, but no rigorously designed clinical trials have shown efficacy for any of them. “Very few people are deficient in biotin, except for those with inherited enzyme deficiencies,” and most people “can get all the biotin they need from a regular diet,” she said.

The initial rationale for using biotin for nails comes from the veterinary literature, she continued. In the 1940s, chickens with biotin deficiency developed fissures in their feet and parrot-like beaks. In the 1970s, pigs with biotin deficiency developed friable hooves, which was corrected with biotin supplementation. “By the 1980s it was standard practice to supplement the feet of pigs with biotin,” she said.

In a human trial from 1989, German researchers enrolled 71 patients with brittle nail syndrome who took oral biotin, 2.5 mg daily. Of the 45 patients evaluated, 41 (91%) showed improvement in firmness and hardness of the fingernails over the course of 5.5 months, but there was no good control group, Dr. Lipner said. In a follow-up study, the same German researchers used scanning electron microscopy to evaluate 22 patients with brittle nails who took oral biotin 2.5 mg daily and compared them with 10 patients with normal nails who did not take biotin. They found a 25% increase in nail plate thickness in the biotin group and onychoschizia resolved in 50% of patients who received biotin. “But again, there was no good control group,” Dr. Lipner said.

In a third study on the topic, researchers surveyed 46 patients who presented with onychorrhexis and/or onychoschizia on clinical exam and took 2.5 mg of biotin daily. Of the 35 survey respondents, 63% subjectively reported improvement in their nails at a mean of 2 months. “This is where we are today: There have been studies of only 80 patients that were done 25 years ago,” Dr. Lipner said. “That’s all of our evidence for biotin for the treatment of brittle nail syndrome.”
 

FDA warning about biotin

Additional cause for concern, she continued, is the safety communication issued by the FDA in 2017, stating that the use of biotin may interfere with certain lab tests such as thyroid tests and cardiac enzymes, in some cases leading to death. The safety communication was updated in 2019.

In 2018, Dr. Lipner and colleagues administered an anonymous survey to 447 patients at their clinic asking about their use of biotin supplements. Of the 447 patients, 34% reported current use of biotin. Among biotin users, 7% were aware of the FDA warning, 29% of respondents reported that it was recommended by either a primary care physician or a dermatologist, and 56% underwent laboratory testing while taking biotin. “It’s our duty to warn our patients about the evidence for biotin for treating brittle nails, and about this interference on laboratory tests,” Dr. Lipner said.

Other treatment options for brittle nail syndrome include two lacquers that are available by prescription. One contains hydroxypropyl chitosan, Equisetum arvense, and methylsulphonylmethane; the other contains 16% poly-ureaurethane, but has not been well studied. “These products can be very expensive if not covered by insurance,” Dr. Lipner said.

As an alternative, she recommends Nail Tek CITRA 2 Nail Strengthener, which is available for less than $10 from Walmart and other retailers.

Cyclosporine emulsion also has been studied for brittle nail syndrome, but results to date have been underwhelming. Dr. Lipner and colleagues are exploring the effect of platelet rich plasma for treating brittle nails on the premise that it will improve nail growth and promote healing, in a 16-week trial that has enrolled 10 patients and includes both a Physician Global Improvement Assessment (PGIA) and a Physician Global Assessment (PGA) score. “Our data is being analyzed by three independent nail experts, and we hope to report the findings next year,” she said.

Dr. Lipner reported having no disclosures relevant to her presentation.

HER2-positive (HER2+) BC was associated with poor outcomes compared with other BC subtypes. However, the introduction of trastuzumab has drastically changed the treatment paradigm for these patients afflicted with HER2+ BC. The pivotal trials with trastuzumab included only a few patients with lower-risk HER2+ tumors; therefore, it was not clear whether these lower-risk patients can benefit from a de-escalated adjuvant regimen. The phase 2 APT trial prospectively investigated the safety and efficacy of 12 weeks of paclitaxel with trastuzumab, followed by 9 months of trastuzumab monotherapy, in patients with small (≤ 3 cm), node-negative, HER2+ BC. After a median follow-up of 10.8 years, the 10-year invasive disease-free survival was 91.3%, the recurrence-free interval was 96.3%, the overall survival rate was 94.3%, and the BC-specific survival rate was 98.8%.

The researchers also conducted an exploratory analysis in 284 patients using the HER2DX genomic test. This is a single 27-gene expression and clinical feature-based classifier developed for early-stage, HER2+ BC. The tool identified a subset of patients with a high HER2DX score (HERDX score ≥ 32) who might harbor an increased risk for long-term recurrence.

These excellent long-term outcomes from the APT trial support the use of the currently endorsed adjuvant regimen of paclitaxel and trastuzumab in patients with stage I HER2+ BC. Furthermore, the HER2DX risk score, if validated, may provide a promising genomic tool to identify a subset of these patients who are at increased risk for recurrence and therefore may benefit from additional therapy.

Prior studies have noted worse survival outcomes with longer times from BC diagnosis to surgical treatment; however, the specific time interval that is acceptable to wait between diagnosis and surgery is still unclear. A case series study by Weiner and colleagues looked at the association between time from BC diagnosis to primary breast surgery and overall survival. The study looked at 373,334 female patients from the National Cancer Database with stage I-III BC who underwent primary breast surgery. Results showed worse overall survival outcomes when time to surgery was 9 or more weeks compared with surgery between 0 and 4 weeks (hazard ratio 1.15; P < .001). Factors associated with longer times to surgery included younger age, uninsured or Medicaid status, and lower neighborhood household income. On the basis of these findings, surgery before 8 weeks from BC diagnosis appears to be an acceptable time frame to avoid unfavorable survival outcomes and allow for appropriate multidisciplinary care. Furthermore, it is critical to identify potential barriers in a timely manner to prevent prolonged delays in care.

In hormone receptor-positive (HR+) BC, adjuvant endocrine therapy (ET) is usually delayed until after adjuvant radiotherapy, although, the optimal sequence of both therapies is still unknown. The aim of the study by Sutton and colleagues was to assess the association between time from surgery to ET initiation and cancer outcomes in high-risk HR+ patients, particularly those with residual disease after neoadjuvant chemotherapy. The study analysed 179 patients with HR+ BC from a multi-institutional database who received adjuvant radiotherapy, of which 68 patients received adjuvant ET before or during radiotherapy and 111 patients received ET after cessation of radiotherapy. Results showed that an interval of >14 weeks between surgery and the receipt of ET was independently associated with worse recurrence-free survival compared with an interval of 14 or less weeks (hazard ratio 3.20; P = .02). Of interest, the study also showed that patients receiving ET before or during radiation were more likely to experience skin and soft tissue late radiation morbidity, and this was nonsignificantly associated with worse radiation-associated complication-free survival (hazard ratio 1.87; P = .06). Although prior studies have reported that the interval from surgery to ET does not affect cancer outcomes, this was not studied in a high-risk cohort who have received neoadjuvant chemotherapy. Further studies in larger prospective cohorts are needed to validate these findings. At this time, the risks and benefits of concurrent ET with radiation need to be assessed prior to making any treatment recommendations.

HER2-positive (HER2+) BC was associated with poor outcomes compared with other BC subtypes. However, the introduction of trastuzumab has drastically changed the treatment paradigm for these patients afflicted with HER2+ BC. The pivotal trials with trastuzumab included only a few patients with lower-risk HER2+ tumors; therefore, it was not clear whether these lower-risk patients can benefit from a de-escalated adjuvant regimen. The phase 2 APT trial prospectively investigated the safety and efficacy of 12 weeks of paclitaxel with trastuzumab, followed by 9 months of trastuzumab monotherapy, in patients with small (≤ 3 cm), node-negative, HER2+ BC. After a median follow-up of 10.8 years, the 10-year invasive disease-free survival was 91.3%, the recurrence-free interval was 96.3%, the overall survival rate was 94.3%, and the BC-specific survival rate was 98.8%.

The researchers also conducted an exploratory analysis in 284 patients using the HER2DX genomic test. This is a single 27-gene expression and clinical feature-based classifier developed for early-stage, HER2+ BC. The tool identified a subset of patients with a high HER2DX score (HERDX score ≥ 32) who might harbor an increased risk for long-term recurrence.

These excellent long-term outcomes from the APT trial support the use of the currently endorsed adjuvant regimen of paclitaxel and trastuzumab in patients with stage I HER2+ BC. Furthermore, the HER2DX risk score, if validated, may provide a promising genomic tool to identify a subset of these patients who are at increased risk for recurrence and therefore may benefit from additional therapy.

Prior studies have noted worse survival outcomes with longer times from BC diagnosis to surgical treatment; however, the specific time interval that is acceptable to wait between diagnosis and surgery is still unclear. A case series study by Weiner and colleagues looked at the association between time from BC diagnosis to primary breast surgery and overall survival. The study looked at 373,334 female patients from the National Cancer Database with stage I-III BC who underwent primary breast surgery. Results showed worse overall survival outcomes when time to surgery was 9 or more weeks compared with surgery between 0 and 4 weeks (hazard ratio 1.15; P < .001). Factors associated with longer times to surgery included younger age, uninsured or Medicaid status, and lower neighborhood household income. On the basis of these findings, surgery before 8 weeks from BC diagnosis appears to be an acceptable time frame to avoid unfavorable survival outcomes and allow for appropriate multidisciplinary care. Furthermore, it is critical to identify potential barriers in a timely manner to prevent prolonged delays in care.

In hormone receptor-positive (HR+) BC, adjuvant endocrine therapy (ET) is usually delayed until after adjuvant radiotherapy, although, the optimal sequence of both therapies is still unknown. The aim of the study by Sutton and colleagues was to assess the association between time from surgery to ET initiation and cancer outcomes in high-risk HR+ patients, particularly those with residual disease after neoadjuvant chemotherapy. The study analysed 179 patients with HR+ BC from a multi-institutional database who received adjuvant radiotherapy, of which 68 patients received adjuvant ET before or during radiotherapy and 111 patients received ET after cessation of radiotherapy. Results showed that an interval of >14 weeks between surgery and the receipt of ET was independently associated with worse recurrence-free survival compared with an interval of 14 or less weeks (hazard ratio 3.20; P = .02). Of interest, the study also showed that patients receiving ET before or during radiation were more likely to experience skin and soft tissue late radiation morbidity, and this was nonsignificantly associated with worse radiation-associated complication-free survival (hazard ratio 1.87; P = .06). Although prior studies have reported that the interval from surgery to ET does not affect cancer outcomes, this was not studied in a high-risk cohort who have received neoadjuvant chemotherapy. Further studies in larger prospective cohorts are needed to validate these findings. At this time, the risks and benefits of concurrent ET with radiation need to be assessed prior to making any treatment recommendations.

HER2-positive (HER2+) BC was associated with poor outcomes compared with other BC subtypes. However, the introduction of trastuzumab has drastically changed the treatment paradigm for these patients afflicted with HER2+ BC. The pivotal trials with trastuzumab included only a few patients with lower-risk HER2+ tumors; therefore, it was not clear whether these lower-risk patients can benefit from a de-escalated adjuvant regimen. The phase 2 APT trial prospectively investigated the safety and efficacy of 12 weeks of paclitaxel with trastuzumab, followed by 9 months of trastuzumab monotherapy, in patients with small (≤ 3 cm), node-negative, HER2+ BC. After a median follow-up of 10.8 years, the 10-year invasive disease-free survival was 91.3%, the recurrence-free interval was 96.3%, the overall survival rate was 94.3%, and the BC-specific survival rate was 98.8%.

The researchers also conducted an exploratory analysis in 284 patients using the HER2DX genomic test. This is a single 27-gene expression and clinical feature-based classifier developed for early-stage, HER2+ BC. The tool identified a subset of patients with a high HER2DX score (HERDX score ≥ 32) who might harbor an increased risk for long-term recurrence.

These excellent long-term outcomes from the APT trial support the use of the currently endorsed adjuvant regimen of paclitaxel and trastuzumab in patients with stage I HER2+ BC. Furthermore, the HER2DX risk score, if validated, may provide a promising genomic tool to identify a subset of these patients who are at increased risk for recurrence and therefore may benefit from additional therapy.

Prior studies have noted worse survival outcomes with longer times from BC diagnosis to surgical treatment; however, the specific time interval that is acceptable to wait between diagnosis and surgery is still unclear. A case series study by Weiner and colleagues looked at the association between time from BC diagnosis to primary breast surgery and overall survival. The study looked at 373,334 female patients from the National Cancer Database with stage I-III BC who underwent primary breast surgery. Results showed worse overall survival outcomes when time to surgery was 9 or more weeks compared with surgery between 0 and 4 weeks (hazard ratio 1.15; P < .001). Factors associated with longer times to surgery included younger age, uninsured or Medicaid status, and lower neighborhood household income. On the basis of these findings, surgery before 8 weeks from BC diagnosis appears to be an acceptable time frame to avoid unfavorable survival outcomes and allow for appropriate multidisciplinary care. Furthermore, it is critical to identify potential barriers in a timely manner to prevent prolonged delays in care.

In hormone receptor-positive (HR+) BC, adjuvant endocrine therapy (ET) is usually delayed until after adjuvant radiotherapy, although, the optimal sequence of both therapies is still unknown. The aim of the study by Sutton and colleagues was to assess the association between time from surgery to ET initiation and cancer outcomes in high-risk HR+ patients, particularly those with residual disease after neoadjuvant chemotherapy. The study analysed 179 patients with HR+ BC from a multi-institutional database who received adjuvant radiotherapy, of which 68 patients received adjuvant ET before or during radiotherapy and 111 patients received ET after cessation of radiotherapy. Results showed that an interval of >14 weeks between surgery and the receipt of ET was independently associated with worse recurrence-free survival compared with an interval of 14 or less weeks (hazard ratio 3.20; P = .02). Of interest, the study also showed that patients receiving ET before or during radiation were more likely to experience skin and soft tissue late radiation morbidity, and this was nonsignificantly associated with worse radiation-associated complication-free survival (hazard ratio 1.87; P = .06). Although prior studies have reported that the interval from surgery to ET does not affect cancer outcomes, this was not studied in a high-risk cohort who have received neoadjuvant chemotherapy. Further studies in larger prospective cohorts are needed to validate these findings. At this time, the risks and benefits of concurrent ET with radiation need to be assessed prior to making any treatment recommendations.

Isotretinoin, for severe, nodular acne, comes with complex safety requirements, and on March 28, two Food and Drug Administration advisory committees began a 2-day meeting examining how to relieve some of those burdens for patients, pharmacies, and prescribers.
 

Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.

In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.

In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.

March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
 

Key areas of concern

The meeting focused on several key areas.

The 19-day lockout period

The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.

Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.

She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.

“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.

The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
 

Home testing

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.

Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.

Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.

Documenting counseling patients who cannot get pregnant

Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.

IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.

On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.

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

Isotretinoin, for severe, nodular acne, comes with complex safety requirements, and on March 28, two Food and Drug Administration advisory committees began a 2-day meeting examining how to relieve some of those burdens for patients, pharmacies, and prescribers.
 

Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.

In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.

In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.

March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
 

Key areas of concern

The meeting focused on several key areas.

The 19-day lockout period

The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.

Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.

She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.

“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.

The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
 

Home testing

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.

Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.

Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.

Documenting counseling patients who cannot get pregnant

Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.

IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.

On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.

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

Isotretinoin, for severe, nodular acne, comes with complex safety requirements, and on March 28, two Food and Drug Administration advisory committees began a 2-day meeting examining how to relieve some of those burdens for patients, pharmacies, and prescribers.
 

Isotretinoin, previously called Accutane, is marketed as Absorica, Absorica LD, Claravis, Amnesteem, Myorisan, and Zenatane.

In a joint meeting of the FDA’s Drug Safety and Risk Management Advisory Committee and Dermatologic and Ophthalmic Drugs Advisory Committee, experts addressed ways to improve the modified iPLEDGE Risk Evaluation and Mitigation Strategy (iPLEDGE REMS) for isotretinoin that caused chaos after its rollout at the end of 2021.

In January 2022, problems were multiplying with the program for clinicians, pharmacists, and patients, causing extensive delays and prescription denials. In response, the FDA said it would continue to meet with the Isotretinoin Products Manufacturers Group (IPMG) to resolve problems.

March 28 was the first day of a 2-day meeting addressing what can be done to reduce burden with the iPLEDGE REMS while maintaining safety and preventing fetal exposure to the drug.
 

Key areas of concern

The meeting focused on several key areas.

The 19-day lockout period

The lockout is a current restriction for patients who can become pregnant and do not pick up their first prescription of isotretinoin within the specified 7-day prescription window. Currently, those who miss the window must wait 19 days from the date of the first pregnancy test to take an additional pregnancy test to be eligible to receive the drug.

Lindsey Crist, PharmD, a risk management analyst for the FDA, who presented the FDA review committee’s analysis, acknowledged that the lockout period causes delays in treatment and adds frustration and costs.

She said it’s important to remember that the lockout applies only to the first prescription. “It’s intended as an additional layer of screening to detect pregnancy,” she said.

“At least 12 pregnancies have been identified during the 19-day lockout from March 2017–September of 2022,” she noted.

The FDA is looking to the advisory committee to provide recommendations on whether the lockout period should be changed.
 

Home testing

During the pandemic, iPLEDGE rules have been relaxed from having a pregnancy test done only at a Clinical Laboratory Improvement Amendments–certified laboratory and home pregnancy tests have been allowed. The question now is whether home tests should continue to be allowed.

Ms. Crist said that the FDA’s review committee recommends ending the allowance of home tests, citing insufficient data on use and the discovery of instances of falsification of pregnancy tests.

“One study at an academic medical center reviewed the medical records of 89 patients who used home pregnancy tests while taking isotretinoin during the public health emergency. It found that 15.7% submitted falsified pregnancy test results,” she said.

Ms. Crist added, however, that the review committee recommends allowing the tests to be done in a provider’s office as an alternative.

Documenting counseling patients who cannot get pregnant

Currently, this documentation must be done monthly, primarily to counsel patients against drug sharing or giving blood. Proposed changes include extending the intervals for attestation or eliminating it to reduce burden on clinicians.

IPMG representative Gregory Wedin, PharmD, pharmacovigilance and risk management director for Upsher-Smith Laboratories, said, “while we cannot support eliminating or extending the confirmation interval to a year, the [iPLEDGE] sponsors are agreeable [to] a 120-day confirmation interval.”

He said that while extending to 120 days would reduce burden on prescribers, it comes with risk in reducing oversight by a certified iPLEDGE prescriber and potentially increasing the risk for drug sharing.

“A patient may be more likely to share their drug with another person the further along with therapy they get as their condition improves,” Mr. Wedin said.

On March 29, the panel will hear more recommendations for and against modifications to iPLEDGE REMS and will vote on select modifications at the end of the meeting.

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

However, a combined analysis of two other trials (PlanB and SUCCESS C) did not show a benefit with the addition of anthracycline for most patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer.²Roy and colleagues performed a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, including 1106 women ≥ 66 years of age with node-positive TNBC, of whom 69.3% received adjuvant chemotherapy (N = 767). The use of chemotherapy led to a statistically significant improvement in survival outcomes (3-year cancer-specific survival [CSS] 81.8% vs 71.4%; overall survival 70.7% vs 51.3%). Although the anthracycline/taxane–based therapy did not improve CSS in the overall population vs taxane-based (hazard ratio [HR] 0.94; P = .79), among patients aged ≥ 76 years with four or more positive nodes, there was improvement in CSS with anthracycline/taxane therapy (HR 0.09; P = .02). These data further support the benefits of adjuvant chemotherapy in older patients when indicated; stimulate consideration of nonanthracycline combinations, particularly now with the use of immunotherapy for early TNBC; and highlight the need for inclusion of older individuals in clinical trials.

Treatment strategies to improve efficacy and minimize toxicity are highly desired for patients with early breast cancer (EBC). As an example, for small, node-negative, HER2-positive tumors, adjuvant systemic therapy with 12 weeks of paclitaxel/trastuzumab followed by continuation of trastuzumab to complete 1 full year has demonstrated excellent survival outcomes at over 10 years of follow-up.³ In the WSG-ADAPT-TP phase 2 trial, 375 patients with hormone receptor–positive , HER2-positive EBC were randomized to receive neoadjuvant T-DM1 (trastuzumab emtansine) with or without endocrine therapy or trastuzumab plus endocrine therapy. Similar 5-year invasive disease-free and overall survival rates were seen between the three arms. Patients who achieved a pathologic complete response (pCR) vs non-pCR had improved 5-year invasive disease-free survival (iDFS) rates (92.7% vs 82.7%; unadjusted HR 0.40). Furthermore, among the 117 patients who achieved pCR, the omission of adjuvant chemotherapy did not compromise survival outcomes (5-year iDFS 93% vs 92.1% for those who had vs those who did not have chemotherapy, respectively; unadjusted HR 1.15) (Harbeck et al). De-escalation approaches should ideally focus on the identification of biomarkers of response and resistance, as well as tools that can help predict patient outcomes and allow modification of therapy in real time. An example of this latter concept is the use of ¹⁸F-FDG-PET to identify patients with HER2-positive EBC who were likely to benefit from a chemotherapy-free dual HER2 blockade (trastuzumab/pertuzumab) treatment approach.⁴

Gynecologic surgery has been shown to reduce the risk for breast cancer,⁵ although the specific type of surgery and the impact of hormone replacement therapy add complexity to understanding the risks and outcomes for women. A prospective cohort, the Sister Study, included 50,701 women without a prior diagnosis of breast cancer but with a biological sister who had breast cancer; of these, 13.8% reported having hysterectomy only and 18.1% reported having bilateral oophorectomy with or without hysterectomy. Bilateral oophorectomy was inversely associated with breast cancer incidence (HR 0.91; 95% CI 0.83-1.00), with comparable results for women receiving estrogen only or combination estrogen plus progestin hormone replacement therapy. Contrary to these findings, having a hysterectomy only showed a positive association with breast cancer incidence (HR 1.12; 95% CI 1.02-1.23), with the strongest association among women who used combination estrogen and progestin therapy (HR 1.25; 95% CI 1.01-1.55) (Lovett et al). The impact of other gynecologic surgeries (such as salpingectomy)⁶ and the timing of the initiation of hormone replacement therapy, as well as the duration, should be investigated in future research.

Additional References

1. Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG oncology). J Clin Oncol. 2017;35:2647e55. doi: 10.1200/JCO.2016.71.4147

2. de Gregorio A, Janni W, Friedl TW, et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022;126:1715-1724. doi: 10.1038/s41416-021-01690-6

3. Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: Final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023;24:273-285. doi: 10.1016/S1470-2045(23)00051-7

4. Pérez-García JM, Gebhart G, Ruiz Borrego M, et al; on behalf of PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an ¹⁸F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): A multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021;22:858-871. doi: 10.1016/S1470-2045(21)00122-4

5. Chow S, Raine-Bennett T, Samant ND, Postlethwaite DA, Holzapfel M. Breast cancer risk after hysterectomy with and without salpingo-oophorectomy for benign indications. Am J Obstet Gynecol. 2020;223:900.e1-900.e7. doi: 10.1016/j.ajog.2020.06.040

6. ACOG Committee Opinion No. 774: Opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet Gynecol. 2019;133:e279-e284. doi: 10.1097/AOG.0000000000003164

However, a combined analysis of two other trials (PlanB and SUCCESS C) did not show a benefit with the addition of anthracycline for most patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer.²Roy and colleagues performed a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, including 1106 women ≥ 66 years of age with node-positive TNBC, of whom 69.3% received adjuvant chemotherapy (N = 767). The use of chemotherapy led to a statistically significant improvement in survival outcomes (3-year cancer-specific survival [CSS] 81.8% vs 71.4%; overall survival 70.7% vs 51.3%). Although the anthracycline/taxane–based therapy did not improve CSS in the overall population vs taxane-based (hazard ratio [HR] 0.94; P = .79), among patients aged ≥ 76 years with four or more positive nodes, there was improvement in CSS with anthracycline/taxane therapy (HR 0.09; P = .02). These data further support the benefits of adjuvant chemotherapy in older patients when indicated; stimulate consideration of nonanthracycline combinations, particularly now with the use of immunotherapy for early TNBC; and highlight the need for inclusion of older individuals in clinical trials.

Treatment strategies to improve efficacy and minimize toxicity are highly desired for patients with early breast cancer (EBC). As an example, for small, node-negative, HER2-positive tumors, adjuvant systemic therapy with 12 weeks of paclitaxel/trastuzumab followed by continuation of trastuzumab to complete 1 full year has demonstrated excellent survival outcomes at over 10 years of follow-up.³ In the WSG-ADAPT-TP phase 2 trial, 375 patients with hormone receptor–positive , HER2-positive EBC were randomized to receive neoadjuvant T-DM1 (trastuzumab emtansine) with or without endocrine therapy or trastuzumab plus endocrine therapy. Similar 5-year invasive disease-free and overall survival rates were seen between the three arms. Patients who achieved a pathologic complete response (pCR) vs non-pCR had improved 5-year invasive disease-free survival (iDFS) rates (92.7% vs 82.7%; unadjusted HR 0.40). Furthermore, among the 117 patients who achieved pCR, the omission of adjuvant chemotherapy did not compromise survival outcomes (5-year iDFS 93% vs 92.1% for those who had vs those who did not have chemotherapy, respectively; unadjusted HR 1.15) (Harbeck et al). De-escalation approaches should ideally focus on the identification of biomarkers of response and resistance, as well as tools that can help predict patient outcomes and allow modification of therapy in real time. An example of this latter concept is the use of ¹⁸F-FDG-PET to identify patients with HER2-positive EBC who were likely to benefit from a chemotherapy-free dual HER2 blockade (trastuzumab/pertuzumab) treatment approach.⁴

Gynecologic surgery has been shown to reduce the risk for breast cancer,⁵ although the specific type of surgery and the impact of hormone replacement therapy add complexity to understanding the risks and outcomes for women. A prospective cohort, the Sister Study, included 50,701 women without a prior diagnosis of breast cancer but with a biological sister who had breast cancer; of these, 13.8% reported having hysterectomy only and 18.1% reported having bilateral oophorectomy with or without hysterectomy. Bilateral oophorectomy was inversely associated with breast cancer incidence (HR 0.91; 95% CI 0.83-1.00), with comparable results for women receiving estrogen only or combination estrogen plus progestin hormone replacement therapy. Contrary to these findings, having a hysterectomy only showed a positive association with breast cancer incidence (HR 1.12; 95% CI 1.02-1.23), with the strongest association among women who used combination estrogen and progestin therapy (HR 1.25; 95% CI 1.01-1.55) (Lovett et al). The impact of other gynecologic surgeries (such as salpingectomy)⁶ and the timing of the initiation of hormone replacement therapy, as well as the duration, should be investigated in future research.

Additional References

1. Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG oncology). J Clin Oncol. 2017;35:2647e55. doi: 10.1200/JCO.2016.71.4147

2. de Gregorio A, Janni W, Friedl TW, et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022;126:1715-1724. doi: 10.1038/s41416-021-01690-6

3. Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: Final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023;24:273-285. doi: 10.1016/S1470-2045(23)00051-7

4. Pérez-García JM, Gebhart G, Ruiz Borrego M, et al; on behalf of PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an ¹⁸F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): A multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021;22:858-871. doi: 10.1016/S1470-2045(21)00122-4

5. Chow S, Raine-Bennett T, Samant ND, Postlethwaite DA, Holzapfel M. Breast cancer risk after hysterectomy with and without salpingo-oophorectomy for benign indications. Am J Obstet Gynecol. 2020;223:900.e1-900.e7. doi: 10.1016/j.ajog.2020.06.040

6. ACOG Committee Opinion No. 774: Opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet Gynecol. 2019;133:e279-e284. doi: 10.1097/AOG.0000000000003164

However, a combined analysis of two other trials (PlanB and SUCCESS C) did not show a benefit with the addition of anthracycline for most patients with human epidermal growth factor receptor 2 (HER2)–negative early breast cancer.²Roy and colleagues performed a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, including 1106 women ≥ 66 years of age with node-positive TNBC, of whom 69.3% received adjuvant chemotherapy (N = 767). The use of chemotherapy led to a statistically significant improvement in survival outcomes (3-year cancer-specific survival [CSS] 81.8% vs 71.4%; overall survival 70.7% vs 51.3%). Although the anthracycline/taxane–based therapy did not improve CSS in the overall population vs taxane-based (hazard ratio [HR] 0.94; P = .79), among patients aged ≥ 76 years with four or more positive nodes, there was improvement in CSS with anthracycline/taxane therapy (HR 0.09; P = .02). These data further support the benefits of adjuvant chemotherapy in older patients when indicated; stimulate consideration of nonanthracycline combinations, particularly now with the use of immunotherapy for early TNBC; and highlight the need for inclusion of older individuals in clinical trials.

Treatment strategies to improve efficacy and minimize toxicity are highly desired for patients with early breast cancer (EBC). As an example, for small, node-negative, HER2-positive tumors, adjuvant systemic therapy with 12 weeks of paclitaxel/trastuzumab followed by continuation of trastuzumab to complete 1 full year has demonstrated excellent survival outcomes at over 10 years of follow-up.³ In the WSG-ADAPT-TP phase 2 trial, 375 patients with hormone receptor–positive , HER2-positive EBC were randomized to receive neoadjuvant T-DM1 (trastuzumab emtansine) with or without endocrine therapy or trastuzumab plus endocrine therapy. Similar 5-year invasive disease-free and overall survival rates were seen between the three arms. Patients who achieved a pathologic complete response (pCR) vs non-pCR had improved 5-year invasive disease-free survival (iDFS) rates (92.7% vs 82.7%; unadjusted HR 0.40). Furthermore, among the 117 patients who achieved pCR, the omission of adjuvant chemotherapy did not compromise survival outcomes (5-year iDFS 93% vs 92.1% for those who had vs those who did not have chemotherapy, respectively; unadjusted HR 1.15) (Harbeck et al). De-escalation approaches should ideally focus on the identification of biomarkers of response and resistance, as well as tools that can help predict patient outcomes and allow modification of therapy in real time. An example of this latter concept is the use of ¹⁸F-FDG-PET to identify patients with HER2-positive EBC who were likely to benefit from a chemotherapy-free dual HER2 blockade (trastuzumab/pertuzumab) treatment approach.⁴

Gynecologic surgery has been shown to reduce the risk for breast cancer,⁵ although the specific type of surgery and the impact of hormone replacement therapy add complexity to understanding the risks and outcomes for women. A prospective cohort, the Sister Study, included 50,701 women without a prior diagnosis of breast cancer but with a biological sister who had breast cancer; of these, 13.8% reported having hysterectomy only and 18.1% reported having bilateral oophorectomy with or without hysterectomy. Bilateral oophorectomy was inversely associated with breast cancer incidence (HR 0.91; 95% CI 0.83-1.00), with comparable results for women receiving estrogen only or combination estrogen plus progestin hormone replacement therapy. Contrary to these findings, having a hysterectomy only showed a positive association with breast cancer incidence (HR 1.12; 95% CI 1.02-1.23), with the strongest association among women who used combination estrogen and progestin therapy (HR 1.25; 95% CI 1.01-1.55) (Lovett et al). The impact of other gynecologic surgeries (such as salpingectomy)⁶ and the timing of the initiation of hormone replacement therapy, as well as the duration, should be investigated in future research.

Additional References

1. Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: The ABC trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG oncology). J Clin Oncol. 2017;35:2647e55. doi: 10.1200/JCO.2016.71.4147

2. de Gregorio A, Janni W, Friedl TW, et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer-a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022;126:1715-1724. doi: 10.1038/s41416-021-01690-6

3. Tolaney SM, Tarantino P, Graham N, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: Final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol. 2023;24:273-285. doi: 10.1016/S1470-2045(23)00051-7

4. Pérez-García JM, Gebhart G, Ruiz Borrego M, et al; on behalf of PHERGain steering committee and trial investigators. Chemotherapy de-escalation using an ¹⁸F-FDG-PET-based pathological response-adapted strategy in patients with HER2-positive early breast cancer (PHERGain): A multicentre, randomised, open-label, non-comparative, phase 2 trial. Lancet Oncol. 2021;22:858-871. doi: 10.1016/S1470-2045(21)00122-4

5. Chow S, Raine-Bennett T, Samant ND, Postlethwaite DA, Holzapfel M. Breast cancer risk after hysterectomy with and without salpingo-oophorectomy for benign indications. Am J Obstet Gynecol. 2020;223:900.e1-900.e7. doi: 10.1016/j.ajog.2020.06.040

6. ACOG Committee Opinion No. 774: Opportunistic salpingectomy as a strategy for epithelial ovarian cancer prevention. Obstet Gynecol. 2019;133:e279-e284. doi: 10.1097/AOG.0000000000003164