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Customized brain stimulation: New hope for severe depression
Personalized deep brain stimulation (DBS) appears to rapidly and effectively improve symptoms of treatment-resistant depression, new research suggests.
In a proof-of-concept study, investigators identified specific brain activity patterns responsible for a single patient’s severe depression and customized a DBS protocol to modulate the patterns. Results showed rapid and sustained improvement in depression scores.
“This study points the way to a new paradigm that is desperately needed in psychiatry,” Andrew Krystal, PhD, Weill Institute for Neurosciences, University of California, San Francisco, said in a news release.
“ by identifying and modulating the circuit in her brain that’s uniquely associated with her symptoms,” Dr. Krystal added.
The findings were published online Oct. 4 in Nature Medicine.
Closed-loop, on-demand stimulation
The patient was a 36-year-old woman with longstanding, severe, and treatment-resistant major depressive disorder. She was unresponsive to multiple antidepressant combinations and electroconvulsive therapy.
The researchers used intracranial electrophysiology and focal electrical stimulation to identify the specific pattern of electrical brain activity that correlated with her depressed mood.
They identified the right ventral striatum – which is involved in emotion, motivation, and reward – as the stimulation site that led to consistent, sustained, and dose-dependent improvement of symptoms and served as the neural biomarker.
In addition, the investigators identified a neural activity pattern in the amygdala that predicted both the mood symptoms, symptom severity, and stimulation efficacy.
The patient was implanted with the Food and Drug Administration–approved NeuroPace RNS System. The device was placed in the right hemisphere. A single sensing lead was positioned in the amygdala and the second stimulation lead was placed in the ventral striatum.
When the sensing lead detected the activity pattern associated with depression, the other lead delivered a tiny dose (1 milliampere/1 mA) of electricity for 6 seconds, which altered the neural activity and relieved mood symptoms.
Remission achieved
Once this personalized, closed-loop therapy was fully operational, the patient’s depression score on the Montgomery-Åsberg Depression Rating Scale (MADRS) dropped from 33 before turning treatment ON to 14 at the first ON-treatment assessment carried out after 12 days of stimulation. The score dropped below 10, representing remission, several months later.
The treatment also rapidly improved symptom severity, as measured daily with Hamilton Depression Rating Scale (HAMD-6) and visual analog scales.
“Success was predicated on a clinical mapping stage before chronic device placement, a strategy that has been utilized in epilepsy to map seizure foci in a personalized manner but has not previously been performed in other neuropsychiatric conditions,” the investigators wrote.
This patient represents “one of the first examples of precision psychiatry – a treatment tailored to an individual,” the study’s lead author, Katherine Scangos, MD, also with UCSF Weill Institute, said in an interview.
She added that the treatment “was personally tailored both spatially,” meaning at the brain location, and temporally – the time it was delivered.
“This is the first time a neural biomarker has been used to automatically trigger therapeutic stimulation in depression as a successful long-term treatment,” said Dr. Scangos. However, “we have a lot of work left to do,” she added.
“This study provides proof-of-principle that we can utilize a multimodal brain mapping approach to identify a personalized depression circuit and target that circuit with successful treatment. We will need to test the approach in more patients before we can determine its efficacy,” Dr. Scangos said.
First reliable biomarker in psychiatry
In a statement from the UK nonprofit Science Media Centre, Vladimir Litvak, PhD, with the Wellcome Centre for Human Neuroimaging, University College London, said that the study is interesting, noting that it is from “one of the leading groups in the field.”
The fact that depression symptoms can be treated in some patients by electrical stimulation of the ventral striatum is not new, Dr. Litvak said. However, what is “exciting” is that the authors identified a particular neural activity pattern in the amygdala as a reliable predictor of both symptom severity and stimulation effectiveness, he noted.
“Patterns of brain activity correlated with disease symptoms when testing over a large group of patients are commonly discovered. But there are just a handful of examples of patterns that are reliable enough to be predictive on a short time scale in a single patient,” said Dr. Litvak, who was not associated with the research.
“Furthermore, to my knowledge, this is the first example of such a reliable biomarker for psychiatric symptoms. The other examples were all for neurological disorders such as Parkinson’s disease, dystonia, and epilepsy,” he added.
He cautioned that this is a single case, but “if reproduced in additional patients, it will bring at least some psychiatric conditions into the domain of brain diseases that can be characterized and diagnosed objectively rather than based on symptoms alone.”
Dr. Litvak pointed out two other critical aspects of the study: the use of exploratory recordings and stimulation to determine the most effective treatment strategy, and the use of a closed-loop device that stimulates only when detecting the amygdala biomarker.
“It is hard to say based on this single case how important these will be in the future. There is no comparison to constant stimulation that might have worked as well because the implanted device used in the study is not suitable for that,” Dr. Litvak said.
It should also be noted that implanting multiple depth electrodes at different brain sites is a “traumatic invasive procedure only reserved to date for severe cases of drug-resistant epilepsy,” he said. “Furthermore, it only allows [researchers] to test a small number of candidate sites, so it relies heavily on prior knowledge.
“Once clinicians know better what to look for, it might be possible to avoid this procedure altogether by using noninvasive methods,” such as functional MRI or EEG, to match the right treatment option to a patient, Dr. Litvak concluded.
The research was funded by the National Institutes of Health, the Brain & Behavior Research Foundation, and the Ray and Dagmar Dolby Family Fund through the department of psychiatry at UCSF. Dr. Scangos has reported no relevant financial relationships. A complete list of author disclosures is available in the original article. Dr. Litvak is participating in a research funding application to search for electrophysiological biomarkers of depression symptoms using invasive recordings.
A version of this article first appeared on Medscape.com.
Personalized deep brain stimulation (DBS) appears to rapidly and effectively improve symptoms of treatment-resistant depression, new research suggests.
In a proof-of-concept study, investigators identified specific brain activity patterns responsible for a single patient’s severe depression and customized a DBS protocol to modulate the patterns. Results showed rapid and sustained improvement in depression scores.
“This study points the way to a new paradigm that is desperately needed in psychiatry,” Andrew Krystal, PhD, Weill Institute for Neurosciences, University of California, San Francisco, said in a news release.
“ by identifying and modulating the circuit in her brain that’s uniquely associated with her symptoms,” Dr. Krystal added.
The findings were published online Oct. 4 in Nature Medicine.
Closed-loop, on-demand stimulation
The patient was a 36-year-old woman with longstanding, severe, and treatment-resistant major depressive disorder. She was unresponsive to multiple antidepressant combinations and electroconvulsive therapy.
The researchers used intracranial electrophysiology and focal electrical stimulation to identify the specific pattern of electrical brain activity that correlated with her depressed mood.
They identified the right ventral striatum – which is involved in emotion, motivation, and reward – as the stimulation site that led to consistent, sustained, and dose-dependent improvement of symptoms and served as the neural biomarker.
In addition, the investigators identified a neural activity pattern in the amygdala that predicted both the mood symptoms, symptom severity, and stimulation efficacy.
The patient was implanted with the Food and Drug Administration–approved NeuroPace RNS System. The device was placed in the right hemisphere. A single sensing lead was positioned in the amygdala and the second stimulation lead was placed in the ventral striatum.
When the sensing lead detected the activity pattern associated with depression, the other lead delivered a tiny dose (1 milliampere/1 mA) of electricity for 6 seconds, which altered the neural activity and relieved mood symptoms.
Remission achieved
Once this personalized, closed-loop therapy was fully operational, the patient’s depression score on the Montgomery-Åsberg Depression Rating Scale (MADRS) dropped from 33 before turning treatment ON to 14 at the first ON-treatment assessment carried out after 12 days of stimulation. The score dropped below 10, representing remission, several months later.
The treatment also rapidly improved symptom severity, as measured daily with Hamilton Depression Rating Scale (HAMD-6) and visual analog scales.
“Success was predicated on a clinical mapping stage before chronic device placement, a strategy that has been utilized in epilepsy to map seizure foci in a personalized manner but has not previously been performed in other neuropsychiatric conditions,” the investigators wrote.
This patient represents “one of the first examples of precision psychiatry – a treatment tailored to an individual,” the study’s lead author, Katherine Scangos, MD, also with UCSF Weill Institute, said in an interview.
She added that the treatment “was personally tailored both spatially,” meaning at the brain location, and temporally – the time it was delivered.
“This is the first time a neural biomarker has been used to automatically trigger therapeutic stimulation in depression as a successful long-term treatment,” said Dr. Scangos. However, “we have a lot of work left to do,” she added.
“This study provides proof-of-principle that we can utilize a multimodal brain mapping approach to identify a personalized depression circuit and target that circuit with successful treatment. We will need to test the approach in more patients before we can determine its efficacy,” Dr. Scangos said.
First reliable biomarker in psychiatry
In a statement from the UK nonprofit Science Media Centre, Vladimir Litvak, PhD, with the Wellcome Centre for Human Neuroimaging, University College London, said that the study is interesting, noting that it is from “one of the leading groups in the field.”
The fact that depression symptoms can be treated in some patients by electrical stimulation of the ventral striatum is not new, Dr. Litvak said. However, what is “exciting” is that the authors identified a particular neural activity pattern in the amygdala as a reliable predictor of both symptom severity and stimulation effectiveness, he noted.
“Patterns of brain activity correlated with disease symptoms when testing over a large group of patients are commonly discovered. But there are just a handful of examples of patterns that are reliable enough to be predictive on a short time scale in a single patient,” said Dr. Litvak, who was not associated with the research.
“Furthermore, to my knowledge, this is the first example of such a reliable biomarker for psychiatric symptoms. The other examples were all for neurological disorders such as Parkinson’s disease, dystonia, and epilepsy,” he added.
He cautioned that this is a single case, but “if reproduced in additional patients, it will bring at least some psychiatric conditions into the domain of brain diseases that can be characterized and diagnosed objectively rather than based on symptoms alone.”
Dr. Litvak pointed out two other critical aspects of the study: the use of exploratory recordings and stimulation to determine the most effective treatment strategy, and the use of a closed-loop device that stimulates only when detecting the amygdala biomarker.
“It is hard to say based on this single case how important these will be in the future. There is no comparison to constant stimulation that might have worked as well because the implanted device used in the study is not suitable for that,” Dr. Litvak said.
It should also be noted that implanting multiple depth electrodes at different brain sites is a “traumatic invasive procedure only reserved to date for severe cases of drug-resistant epilepsy,” he said. “Furthermore, it only allows [researchers] to test a small number of candidate sites, so it relies heavily on prior knowledge.
“Once clinicians know better what to look for, it might be possible to avoid this procedure altogether by using noninvasive methods,” such as functional MRI or EEG, to match the right treatment option to a patient, Dr. Litvak concluded.
The research was funded by the National Institutes of Health, the Brain & Behavior Research Foundation, and the Ray and Dagmar Dolby Family Fund through the department of psychiatry at UCSF. Dr. Scangos has reported no relevant financial relationships. A complete list of author disclosures is available in the original article. Dr. Litvak is participating in a research funding application to search for electrophysiological biomarkers of depression symptoms using invasive recordings.
A version of this article first appeared on Medscape.com.
Personalized deep brain stimulation (DBS) appears to rapidly and effectively improve symptoms of treatment-resistant depression, new research suggests.
In a proof-of-concept study, investigators identified specific brain activity patterns responsible for a single patient’s severe depression and customized a DBS protocol to modulate the patterns. Results showed rapid and sustained improvement in depression scores.
“This study points the way to a new paradigm that is desperately needed in psychiatry,” Andrew Krystal, PhD, Weill Institute for Neurosciences, University of California, San Francisco, said in a news release.
“ by identifying and modulating the circuit in her brain that’s uniquely associated with her symptoms,” Dr. Krystal added.
The findings were published online Oct. 4 in Nature Medicine.
Closed-loop, on-demand stimulation
The patient was a 36-year-old woman with longstanding, severe, and treatment-resistant major depressive disorder. She was unresponsive to multiple antidepressant combinations and electroconvulsive therapy.
The researchers used intracranial electrophysiology and focal electrical stimulation to identify the specific pattern of electrical brain activity that correlated with her depressed mood.
They identified the right ventral striatum – which is involved in emotion, motivation, and reward – as the stimulation site that led to consistent, sustained, and dose-dependent improvement of symptoms and served as the neural biomarker.
In addition, the investigators identified a neural activity pattern in the amygdala that predicted both the mood symptoms, symptom severity, and stimulation efficacy.
The patient was implanted with the Food and Drug Administration–approved NeuroPace RNS System. The device was placed in the right hemisphere. A single sensing lead was positioned in the amygdala and the second stimulation lead was placed in the ventral striatum.
When the sensing lead detected the activity pattern associated with depression, the other lead delivered a tiny dose (1 milliampere/1 mA) of electricity for 6 seconds, which altered the neural activity and relieved mood symptoms.
Remission achieved
Once this personalized, closed-loop therapy was fully operational, the patient’s depression score on the Montgomery-Åsberg Depression Rating Scale (MADRS) dropped from 33 before turning treatment ON to 14 at the first ON-treatment assessment carried out after 12 days of stimulation. The score dropped below 10, representing remission, several months later.
The treatment also rapidly improved symptom severity, as measured daily with Hamilton Depression Rating Scale (HAMD-6) and visual analog scales.
“Success was predicated on a clinical mapping stage before chronic device placement, a strategy that has been utilized in epilepsy to map seizure foci in a personalized manner but has not previously been performed in other neuropsychiatric conditions,” the investigators wrote.
This patient represents “one of the first examples of precision psychiatry – a treatment tailored to an individual,” the study’s lead author, Katherine Scangos, MD, also with UCSF Weill Institute, said in an interview.
She added that the treatment “was personally tailored both spatially,” meaning at the brain location, and temporally – the time it was delivered.
“This is the first time a neural biomarker has been used to automatically trigger therapeutic stimulation in depression as a successful long-term treatment,” said Dr. Scangos. However, “we have a lot of work left to do,” she added.
“This study provides proof-of-principle that we can utilize a multimodal brain mapping approach to identify a personalized depression circuit and target that circuit with successful treatment. We will need to test the approach in more patients before we can determine its efficacy,” Dr. Scangos said.
First reliable biomarker in psychiatry
In a statement from the UK nonprofit Science Media Centre, Vladimir Litvak, PhD, with the Wellcome Centre for Human Neuroimaging, University College London, said that the study is interesting, noting that it is from “one of the leading groups in the field.”
The fact that depression symptoms can be treated in some patients by electrical stimulation of the ventral striatum is not new, Dr. Litvak said. However, what is “exciting” is that the authors identified a particular neural activity pattern in the amygdala as a reliable predictor of both symptom severity and stimulation effectiveness, he noted.
“Patterns of brain activity correlated with disease symptoms when testing over a large group of patients are commonly discovered. But there are just a handful of examples of patterns that are reliable enough to be predictive on a short time scale in a single patient,” said Dr. Litvak, who was not associated with the research.
“Furthermore, to my knowledge, this is the first example of such a reliable biomarker for psychiatric symptoms. The other examples were all for neurological disorders such as Parkinson’s disease, dystonia, and epilepsy,” he added.
He cautioned that this is a single case, but “if reproduced in additional patients, it will bring at least some psychiatric conditions into the domain of brain diseases that can be characterized and diagnosed objectively rather than based on symptoms alone.”
Dr. Litvak pointed out two other critical aspects of the study: the use of exploratory recordings and stimulation to determine the most effective treatment strategy, and the use of a closed-loop device that stimulates only when detecting the amygdala biomarker.
“It is hard to say based on this single case how important these will be in the future. There is no comparison to constant stimulation that might have worked as well because the implanted device used in the study is not suitable for that,” Dr. Litvak said.
It should also be noted that implanting multiple depth electrodes at different brain sites is a “traumatic invasive procedure only reserved to date for severe cases of drug-resistant epilepsy,” he said. “Furthermore, it only allows [researchers] to test a small number of candidate sites, so it relies heavily on prior knowledge.
“Once clinicians know better what to look for, it might be possible to avoid this procedure altogether by using noninvasive methods,” such as functional MRI or EEG, to match the right treatment option to a patient, Dr. Litvak concluded.
The research was funded by the National Institutes of Health, the Brain & Behavior Research Foundation, and the Ray and Dagmar Dolby Family Fund through the department of psychiatry at UCSF. Dr. Scangos has reported no relevant financial relationships. A complete list of author disclosures is available in the original article. Dr. Litvak is participating in a research funding application to search for electrophysiological biomarkers of depression symptoms using invasive recordings.
A version of this article first appeared on Medscape.com.
USPSTF update: Screen young asymptomatic women for chlamydia and gonorrhea
But evidence for screening men remains insufficient, task force says
The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.
Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.
As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.
With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.
In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.
The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.
The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).
While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.
Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).
Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.
“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.
In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”
They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.
“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.
In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.
“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”
In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.
“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.
This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.
But evidence for screening men remains insufficient, task force says
But evidence for screening men remains insufficient, task force says
The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.
Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.
As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.
With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.
In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.
The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.
The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).
While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.
Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).
Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.
“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.
In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”
They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.
“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.
In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.
“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”
In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.
“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.
This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.
The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.
Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.
As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.
With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.
In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.
The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.
The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).
While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.
Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).
Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.
“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.
In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”
They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.
“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.
In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.
“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”
In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.
“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.
This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.
FROM JAMA
Mediterranean diet tied to less severe erectile dysfunction
In an observational study of 250 middle-aged men with hypertension and erectile dysfunction, those whose eating patterns more closely matched a Mediterranean diet had significantly higher testosterone levels, better exercise capacity, and better erectile performance than their peers.
In addition, more closely following a Mediterranean diet – which emphasizes eating fruit, vegetables, whole grains, and olive oil, with modest consumption of dairy products and limited red meat – was associated with better coronary blood flow and less arterial stiffness, all after adjusting for age, body mass index, type 2 diabetes, statin use, and smoking.
Athanasios Angelis, MD, First Cardiology Clinic, Hippokration Hospital, School of Medicine, University of Athens, presented the study at the annual congress of the European Society of Cardiology.
“While we did not examine mechanisms,” Dr. Angelis said in a press release from the ESC, “it seems plausible that this dietary pattern may improve fitness and erectile performance by enhancing function of the blood vessels and limiting the fall in testosterone that occurs in midlife.”
“The findings suggest that the Mediterranean diet could play a role in maintaining several parameters of vascular health and quality of life and in middle-aged men with hypertension and erectile dysfunction,” he concluded.
“A Mediterranean diet may help erectile dysfunction by improving endothelial physiology,” Dr. Angelis said in an interview. “We suggest the Mediterranean diet as a basic parameter of hypertension and erectile dysfunction treatment. We advise all our patients to be careful regarding salt consumption and to try to exercise regularly.”
“Depending on the severity of the erectile dysfunction, we may suggest only lifestyle changes (e.g., quit smoking), at least for the beginning, or combination with medication,” consisting of phosphodiesterase type 5 (PDE5) inhibitors such as Viagra.
A ‘first-choice’ diet for men with ED, low T, high CVD risk?
This research “adds to the growing evidence that a Mediterranean diet is protective against erectile dysfunction,” said Joseph Whittaker, MSc, a clinical nutritionist from the University of Worcester (England) and coauthor of a related meta-analysis about dietary fat and testosterone.
This way of eating “also improves cardiovascular health, so it could become a low-risk, first choice treatment for these three pathologies (low testosterone, erectile dysfunction, increased risk of CVD), which so commonly coexist,” he wrote in an email.
“However, most of the research to date is observational,” he cautioned, which often has a “healthy user bias,” that is, the men eating a Mediterranean diet are probably health-conscious individuals, with other healthy habits such as exercise, good sleep, low stress, etc. “So, was it the diet, the healthy habits, or both?”
Randomized studies are needed to replicate the positive results of observational studies like this one, Mr. Whittaker added. In the meantime, “a Mediterranean diet will probably improve your health anyway,” he noted, “so trying it for the purposes of erectile function (before starting drugs) is a viable option.”
Previous research has shown that dietary fat and olive oil may boost testosterone levels, Mr. Whittaker noted, and nuts have also been shown to improve erectile function.
“So, the increase in healthy fats – mono- and polyunsaturated fatty acids (MUFAs and PUFAs, respectively) – on the Mediterranean diet is probably responsible for these benefits,” he speculated.
Middle-aged hypertensive men with ED
Men with hypertension are twice as likely to have erectile dysfunction as their peers with normal blood pressure, according to background information in the ESC press release.
Erectile dysfunction is thought to be a disorder of the small arteries, which lose their ability to dilate and increase blood flow. Declining testosterone levels in middle age also contribute to weakened erectile performance.
Physical fitness is linked with longer life in men with hypertension, and the Mediterranean diet is associated with lower blood pressure and fewer heart attacks and strokes in individuals at high cardiovascular risk.
Therefore, Dr. Angelis and colleagues aimed to see if greater adherence to a Mediterranean diet was associated with better exercise capacity, testosterone levels, coronary flow reserve, and erectile performance in middle-aged hypertensive men with erectile dysfunction.
Participants were a mean age of 56. They had a treadmill test to determine their exercise capacity, expressed as metabolic equivalent of tasks (METs), and a blood test to determine testosterone levels.
They replied to two questionnaires: a food questionnaire to determine a Mediterranean Diet score (range, 0-55, where higher scores indicate greater adherence to a Mediterranean diet) and a Sexual Health Inventory for Men (SHIM) questionnaire (score range, 0-25, where higher scores indicate better erectile performance).
Researchers used echocardiography to determine participants’ coronary flow reserve, a measure of the cardiovascular system’s ability to increase blood flow when needed. They used a SphygmoCor device to determine participants’ augmentation index and central pulse pressure, measures of arterial stiffness.
The men with a higher Mediterranean diet score (>29) had better erectile performance (SHIM scores > 14), as well as higher testosterone levels, higher coronary flow reserve, and less arterial stiffness than the other men.
The fitter men with greater exercise capacity (>10 METs) were more likely to adhere to a Mediterranean diet (scores > 25), and they also had better erectile performance (SHIM scores > 12), higher testosterone levels, greater coronary flow reserve, and less arterial stiffness than the other men.
The study did not receive any funding. The study authors and Mr. Whittaker have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an observational study of 250 middle-aged men with hypertension and erectile dysfunction, those whose eating patterns more closely matched a Mediterranean diet had significantly higher testosterone levels, better exercise capacity, and better erectile performance than their peers.
In addition, more closely following a Mediterranean diet – which emphasizes eating fruit, vegetables, whole grains, and olive oil, with modest consumption of dairy products and limited red meat – was associated with better coronary blood flow and less arterial stiffness, all after adjusting for age, body mass index, type 2 diabetes, statin use, and smoking.
Athanasios Angelis, MD, First Cardiology Clinic, Hippokration Hospital, School of Medicine, University of Athens, presented the study at the annual congress of the European Society of Cardiology.
“While we did not examine mechanisms,” Dr. Angelis said in a press release from the ESC, “it seems plausible that this dietary pattern may improve fitness and erectile performance by enhancing function of the blood vessels and limiting the fall in testosterone that occurs in midlife.”
“The findings suggest that the Mediterranean diet could play a role in maintaining several parameters of vascular health and quality of life and in middle-aged men with hypertension and erectile dysfunction,” he concluded.
“A Mediterranean diet may help erectile dysfunction by improving endothelial physiology,” Dr. Angelis said in an interview. “We suggest the Mediterranean diet as a basic parameter of hypertension and erectile dysfunction treatment. We advise all our patients to be careful regarding salt consumption and to try to exercise regularly.”
“Depending on the severity of the erectile dysfunction, we may suggest only lifestyle changes (e.g., quit smoking), at least for the beginning, or combination with medication,” consisting of phosphodiesterase type 5 (PDE5) inhibitors such as Viagra.
A ‘first-choice’ diet for men with ED, low T, high CVD risk?
This research “adds to the growing evidence that a Mediterranean diet is protective against erectile dysfunction,” said Joseph Whittaker, MSc, a clinical nutritionist from the University of Worcester (England) and coauthor of a related meta-analysis about dietary fat and testosterone.
This way of eating “also improves cardiovascular health, so it could become a low-risk, first choice treatment for these three pathologies (low testosterone, erectile dysfunction, increased risk of CVD), which so commonly coexist,” he wrote in an email.
“However, most of the research to date is observational,” he cautioned, which often has a “healthy user bias,” that is, the men eating a Mediterranean diet are probably health-conscious individuals, with other healthy habits such as exercise, good sleep, low stress, etc. “So, was it the diet, the healthy habits, or both?”
Randomized studies are needed to replicate the positive results of observational studies like this one, Mr. Whittaker added. In the meantime, “a Mediterranean diet will probably improve your health anyway,” he noted, “so trying it for the purposes of erectile function (before starting drugs) is a viable option.”
Previous research has shown that dietary fat and olive oil may boost testosterone levels, Mr. Whittaker noted, and nuts have also been shown to improve erectile function.
“So, the increase in healthy fats – mono- and polyunsaturated fatty acids (MUFAs and PUFAs, respectively) – on the Mediterranean diet is probably responsible for these benefits,” he speculated.
Middle-aged hypertensive men with ED
Men with hypertension are twice as likely to have erectile dysfunction as their peers with normal blood pressure, according to background information in the ESC press release.
Erectile dysfunction is thought to be a disorder of the small arteries, which lose their ability to dilate and increase blood flow. Declining testosterone levels in middle age also contribute to weakened erectile performance.
Physical fitness is linked with longer life in men with hypertension, and the Mediterranean diet is associated with lower blood pressure and fewer heart attacks and strokes in individuals at high cardiovascular risk.
Therefore, Dr. Angelis and colleagues aimed to see if greater adherence to a Mediterranean diet was associated with better exercise capacity, testosterone levels, coronary flow reserve, and erectile performance in middle-aged hypertensive men with erectile dysfunction.
Participants were a mean age of 56. They had a treadmill test to determine their exercise capacity, expressed as metabolic equivalent of tasks (METs), and a blood test to determine testosterone levels.
They replied to two questionnaires: a food questionnaire to determine a Mediterranean Diet score (range, 0-55, where higher scores indicate greater adherence to a Mediterranean diet) and a Sexual Health Inventory for Men (SHIM) questionnaire (score range, 0-25, where higher scores indicate better erectile performance).
Researchers used echocardiography to determine participants’ coronary flow reserve, a measure of the cardiovascular system’s ability to increase blood flow when needed. They used a SphygmoCor device to determine participants’ augmentation index and central pulse pressure, measures of arterial stiffness.
The men with a higher Mediterranean diet score (>29) had better erectile performance (SHIM scores > 14), as well as higher testosterone levels, higher coronary flow reserve, and less arterial stiffness than the other men.
The fitter men with greater exercise capacity (>10 METs) were more likely to adhere to a Mediterranean diet (scores > 25), and they also had better erectile performance (SHIM scores > 12), higher testosterone levels, greater coronary flow reserve, and less arterial stiffness than the other men.
The study did not receive any funding. The study authors and Mr. Whittaker have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an observational study of 250 middle-aged men with hypertension and erectile dysfunction, those whose eating patterns more closely matched a Mediterranean diet had significantly higher testosterone levels, better exercise capacity, and better erectile performance than their peers.
In addition, more closely following a Mediterranean diet – which emphasizes eating fruit, vegetables, whole grains, and olive oil, with modest consumption of dairy products and limited red meat – was associated with better coronary blood flow and less arterial stiffness, all after adjusting for age, body mass index, type 2 diabetes, statin use, and smoking.
Athanasios Angelis, MD, First Cardiology Clinic, Hippokration Hospital, School of Medicine, University of Athens, presented the study at the annual congress of the European Society of Cardiology.
“While we did not examine mechanisms,” Dr. Angelis said in a press release from the ESC, “it seems plausible that this dietary pattern may improve fitness and erectile performance by enhancing function of the blood vessels and limiting the fall in testosterone that occurs in midlife.”
“The findings suggest that the Mediterranean diet could play a role in maintaining several parameters of vascular health and quality of life and in middle-aged men with hypertension and erectile dysfunction,” he concluded.
“A Mediterranean diet may help erectile dysfunction by improving endothelial physiology,” Dr. Angelis said in an interview. “We suggest the Mediterranean diet as a basic parameter of hypertension and erectile dysfunction treatment. We advise all our patients to be careful regarding salt consumption and to try to exercise regularly.”
“Depending on the severity of the erectile dysfunction, we may suggest only lifestyle changes (e.g., quit smoking), at least for the beginning, or combination with medication,” consisting of phosphodiesterase type 5 (PDE5) inhibitors such as Viagra.
A ‘first-choice’ diet for men with ED, low T, high CVD risk?
This research “adds to the growing evidence that a Mediterranean diet is protective against erectile dysfunction,” said Joseph Whittaker, MSc, a clinical nutritionist from the University of Worcester (England) and coauthor of a related meta-analysis about dietary fat and testosterone.
This way of eating “also improves cardiovascular health, so it could become a low-risk, first choice treatment for these three pathologies (low testosterone, erectile dysfunction, increased risk of CVD), which so commonly coexist,” he wrote in an email.
“However, most of the research to date is observational,” he cautioned, which often has a “healthy user bias,” that is, the men eating a Mediterranean diet are probably health-conscious individuals, with other healthy habits such as exercise, good sleep, low stress, etc. “So, was it the diet, the healthy habits, or both?”
Randomized studies are needed to replicate the positive results of observational studies like this one, Mr. Whittaker added. In the meantime, “a Mediterranean diet will probably improve your health anyway,” he noted, “so trying it for the purposes of erectile function (before starting drugs) is a viable option.”
Previous research has shown that dietary fat and olive oil may boost testosterone levels, Mr. Whittaker noted, and nuts have also been shown to improve erectile function.
“So, the increase in healthy fats – mono- and polyunsaturated fatty acids (MUFAs and PUFAs, respectively) – on the Mediterranean diet is probably responsible for these benefits,” he speculated.
Middle-aged hypertensive men with ED
Men with hypertension are twice as likely to have erectile dysfunction as their peers with normal blood pressure, according to background information in the ESC press release.
Erectile dysfunction is thought to be a disorder of the small arteries, which lose their ability to dilate and increase blood flow. Declining testosterone levels in middle age also contribute to weakened erectile performance.
Physical fitness is linked with longer life in men with hypertension, and the Mediterranean diet is associated with lower blood pressure and fewer heart attacks and strokes in individuals at high cardiovascular risk.
Therefore, Dr. Angelis and colleagues aimed to see if greater adherence to a Mediterranean diet was associated with better exercise capacity, testosterone levels, coronary flow reserve, and erectile performance in middle-aged hypertensive men with erectile dysfunction.
Participants were a mean age of 56. They had a treadmill test to determine their exercise capacity, expressed as metabolic equivalent of tasks (METs), and a blood test to determine testosterone levels.
They replied to two questionnaires: a food questionnaire to determine a Mediterranean Diet score (range, 0-55, where higher scores indicate greater adherence to a Mediterranean diet) and a Sexual Health Inventory for Men (SHIM) questionnaire (score range, 0-25, where higher scores indicate better erectile performance).
Researchers used echocardiography to determine participants’ coronary flow reserve, a measure of the cardiovascular system’s ability to increase blood flow when needed. They used a SphygmoCor device to determine participants’ augmentation index and central pulse pressure, measures of arterial stiffness.
The men with a higher Mediterranean diet score (>29) had better erectile performance (SHIM scores > 14), as well as higher testosterone levels, higher coronary flow reserve, and less arterial stiffness than the other men.
The fitter men with greater exercise capacity (>10 METs) were more likely to adhere to a Mediterranean diet (scores > 25), and they also had better erectile performance (SHIM scores > 12), higher testosterone levels, greater coronary flow reserve, and less arterial stiffness than the other men.
The study did not receive any funding. The study authors and Mr. Whittaker have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ESC CONGRESS 2021
Although inconclusive, CV safety study of cancer therapy attracts attention
The first global trial to compare the cardiovascular (CV) safety of two therapies for prostate cancer proved inconclusive because of inadequate enrollment and events, but the study is a harbinger of growth in the emerging specialty of cardio-oncology, according to experts.
“Many new cancer agents have extended patient survival, yet some of these agents have significant potential cardiovascular toxicity,” said Renato D. Lopes, MD, in presenting a study at the annual congress of the European Society of Cardiology.
In the context of improving survival in patients with or at risk for both cancer and cardiovascular disease, he suggested that the prostate cancer study he led could be “a model for interdisciplinary collaboration” needed to address the relative and sometimes competing risks of these disease states.
This point was seconded by several pioneers in cardio-oncology who participated in the discussion of the results of the trial, called PRONOUNCE.
“We know many drugs in oncology increase cardiovascular risk, so these are the types of trials we need,” according Thomas M. Suter, MD, who leads the cardio-oncology service at the University Hospital, Berne, Switzerland. He was the ESC-invited discussant for PRONOUNCE.
More than 100 centers in 12 countries involved
In PRONOUNCE, 545 patients with prostate cancer and established atherosclerotic cardiovascular disease were randomized to degarelix, a gonadotropin-releasing hormone antagonist, or leuprolide, a GnRH agonist. The patients were enrolled at 113 participating centers in 12 countries. All of the patients had an indication for an androgen-deprivation therapy (ADT).
In numerous previous studies, “ADT has been associated with higher CV morbidity and mortality, particularly in men with preexisting CV disease,” explained Dr. Lopes, but the relative cardiovascular safety of GnRH agonists relative to GnRH antagonists has been “controversial.”
The PRONOUNCE study was designed to resolve this issue, but the study was terminated early because of slow enrollment (not related to the COVID-19 pandemic). The planned enrollment was 900 patients.
In addition, the rate of major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, or death, was lower over the course of follow-up than anticipated in the study design.
No significant difference on primary endpoint
At the end of 12 months, MACE occurred in 11 (4.1%) of patients randomized to leuprolide and 15 (5.5%) of those randomized to degarelix. The greater hazard ratio for MACE in the degarelix group did not approach statistical significance (hazard ratio, 1.28; P = .53).
As a result, the question of the relative CV safety of these drugs “remains unresolved,” according to Dr. Lopes, professor of medicine at Duke University Medical Center, Durham, N.C.
This does not diminish the need to answer this question. In the addition to the fact that cancer is a malignancy primarily of advancing age when CV disease is prevalent – the mean age in this study was 73 years and 44% were over age 75 – it is often an indolent disease with long periods of survival, according to Dr. Lopes. About half of prostate cancer patients have concomitant CV disease, and about half will receive ADT at some point in their treatment.
In patients receiving ADT, leuprolide is far more commonly used than GnRH antagonists, which are offered in only about 4% of patients, according to data cited by Dr. Lopes. The underlying hypothesis of this study was that leuprolide is associated with greater CV risk, which might have been relevant to a risk-benefit calculation, if the hypothesis had been confirmed.
Cancer drugs can increase CV risk
Based on experimental data, “there is concern the leuprolide is involved in plaque destabilization,” said Dr. Lopes, but he noted that ADTs in general are associated with adverse metabolic changes, including increases in LDL cholesterol, insulin resistance, and body fat, all of which could be relevant to CV risk.
It is the improving rates of survival for prostate cancer as well for other types of cancer that have increased attention to the potential for cancer drugs to increase CV risk, another major cause of early mortality. For these competing risks, objective data are needed to evaluate a relative risk-to-benefit ratio for treatment choices.
This dilemma led the ESC to recently establish its Council on Cardio-Oncology, and many centers around the world are also creating interdisciplinary groups to guide treatment choices for patients with both diseases.
“You will certainly get a lot of referrals,” said Rudolf de Boer, MD, professor of translational cardiology, University Medical Center, Groningen, Netherlands. Basing his remark on his own experience starting a cardio-oncology clinic at his institution, he called this work challenging and agreed that the need for objective data is urgent.
“We need data to provide common ground on which to judge relative risks,” Dr. de Boer said. He also praised the PRONOUNCE investigators for their efforts even if the data failed to answer the question posed.
The PRONOUNCE results were published online in Circulation at the time of Dr. Lopes’s presentation.
The study received funding from Ferring Pharmaceuticals. Dr. Lopes reports financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi. Dr. Suter reports financial relationships with Boehringer Ingelheim, GlaxoSmithKline, and Roche. Dr. de Boer reports financial relationships with AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche.
The first global trial to compare the cardiovascular (CV) safety of two therapies for prostate cancer proved inconclusive because of inadequate enrollment and events, but the study is a harbinger of growth in the emerging specialty of cardio-oncology, according to experts.
“Many new cancer agents have extended patient survival, yet some of these agents have significant potential cardiovascular toxicity,” said Renato D. Lopes, MD, in presenting a study at the annual congress of the European Society of Cardiology.
In the context of improving survival in patients with or at risk for both cancer and cardiovascular disease, he suggested that the prostate cancer study he led could be “a model for interdisciplinary collaboration” needed to address the relative and sometimes competing risks of these disease states.
This point was seconded by several pioneers in cardio-oncology who participated in the discussion of the results of the trial, called PRONOUNCE.
“We know many drugs in oncology increase cardiovascular risk, so these are the types of trials we need,” according Thomas M. Suter, MD, who leads the cardio-oncology service at the University Hospital, Berne, Switzerland. He was the ESC-invited discussant for PRONOUNCE.
More than 100 centers in 12 countries involved
In PRONOUNCE, 545 patients with prostate cancer and established atherosclerotic cardiovascular disease were randomized to degarelix, a gonadotropin-releasing hormone antagonist, or leuprolide, a GnRH agonist. The patients were enrolled at 113 participating centers in 12 countries. All of the patients had an indication for an androgen-deprivation therapy (ADT).
In numerous previous studies, “ADT has been associated with higher CV morbidity and mortality, particularly in men with preexisting CV disease,” explained Dr. Lopes, but the relative cardiovascular safety of GnRH agonists relative to GnRH antagonists has been “controversial.”
The PRONOUNCE study was designed to resolve this issue, but the study was terminated early because of slow enrollment (not related to the COVID-19 pandemic). The planned enrollment was 900 patients.
In addition, the rate of major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, or death, was lower over the course of follow-up than anticipated in the study design.
No significant difference on primary endpoint
At the end of 12 months, MACE occurred in 11 (4.1%) of patients randomized to leuprolide and 15 (5.5%) of those randomized to degarelix. The greater hazard ratio for MACE in the degarelix group did not approach statistical significance (hazard ratio, 1.28; P = .53).
As a result, the question of the relative CV safety of these drugs “remains unresolved,” according to Dr. Lopes, professor of medicine at Duke University Medical Center, Durham, N.C.
This does not diminish the need to answer this question. In the addition to the fact that cancer is a malignancy primarily of advancing age when CV disease is prevalent – the mean age in this study was 73 years and 44% were over age 75 – it is often an indolent disease with long periods of survival, according to Dr. Lopes. About half of prostate cancer patients have concomitant CV disease, and about half will receive ADT at some point in their treatment.
In patients receiving ADT, leuprolide is far more commonly used than GnRH antagonists, which are offered in only about 4% of patients, according to data cited by Dr. Lopes. The underlying hypothesis of this study was that leuprolide is associated with greater CV risk, which might have been relevant to a risk-benefit calculation, if the hypothesis had been confirmed.
Cancer drugs can increase CV risk
Based on experimental data, “there is concern the leuprolide is involved in plaque destabilization,” said Dr. Lopes, but he noted that ADTs in general are associated with adverse metabolic changes, including increases in LDL cholesterol, insulin resistance, and body fat, all of which could be relevant to CV risk.
It is the improving rates of survival for prostate cancer as well for other types of cancer that have increased attention to the potential for cancer drugs to increase CV risk, another major cause of early mortality. For these competing risks, objective data are needed to evaluate a relative risk-to-benefit ratio for treatment choices.
This dilemma led the ESC to recently establish its Council on Cardio-Oncology, and many centers around the world are also creating interdisciplinary groups to guide treatment choices for patients with both diseases.
“You will certainly get a lot of referrals,” said Rudolf de Boer, MD, professor of translational cardiology, University Medical Center, Groningen, Netherlands. Basing his remark on his own experience starting a cardio-oncology clinic at his institution, he called this work challenging and agreed that the need for objective data is urgent.
“We need data to provide common ground on which to judge relative risks,” Dr. de Boer said. He also praised the PRONOUNCE investigators for their efforts even if the data failed to answer the question posed.
The PRONOUNCE results were published online in Circulation at the time of Dr. Lopes’s presentation.
The study received funding from Ferring Pharmaceuticals. Dr. Lopes reports financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi. Dr. Suter reports financial relationships with Boehringer Ingelheim, GlaxoSmithKline, and Roche. Dr. de Boer reports financial relationships with AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche.
The first global trial to compare the cardiovascular (CV) safety of two therapies for prostate cancer proved inconclusive because of inadequate enrollment and events, but the study is a harbinger of growth in the emerging specialty of cardio-oncology, according to experts.
“Many new cancer agents have extended patient survival, yet some of these agents have significant potential cardiovascular toxicity,” said Renato D. Lopes, MD, in presenting a study at the annual congress of the European Society of Cardiology.
In the context of improving survival in patients with or at risk for both cancer and cardiovascular disease, he suggested that the prostate cancer study he led could be “a model for interdisciplinary collaboration” needed to address the relative and sometimes competing risks of these disease states.
This point was seconded by several pioneers in cardio-oncology who participated in the discussion of the results of the trial, called PRONOUNCE.
“We know many drugs in oncology increase cardiovascular risk, so these are the types of trials we need,” according Thomas M. Suter, MD, who leads the cardio-oncology service at the University Hospital, Berne, Switzerland. He was the ESC-invited discussant for PRONOUNCE.
More than 100 centers in 12 countries involved
In PRONOUNCE, 545 patients with prostate cancer and established atherosclerotic cardiovascular disease were randomized to degarelix, a gonadotropin-releasing hormone antagonist, or leuprolide, a GnRH agonist. The patients were enrolled at 113 participating centers in 12 countries. All of the patients had an indication for an androgen-deprivation therapy (ADT).
In numerous previous studies, “ADT has been associated with higher CV morbidity and mortality, particularly in men with preexisting CV disease,” explained Dr. Lopes, but the relative cardiovascular safety of GnRH agonists relative to GnRH antagonists has been “controversial.”
The PRONOUNCE study was designed to resolve this issue, but the study was terminated early because of slow enrollment (not related to the COVID-19 pandemic). The planned enrollment was 900 patients.
In addition, the rate of major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, or death, was lower over the course of follow-up than anticipated in the study design.
No significant difference on primary endpoint
At the end of 12 months, MACE occurred in 11 (4.1%) of patients randomized to leuprolide and 15 (5.5%) of those randomized to degarelix. The greater hazard ratio for MACE in the degarelix group did not approach statistical significance (hazard ratio, 1.28; P = .53).
As a result, the question of the relative CV safety of these drugs “remains unresolved,” according to Dr. Lopes, professor of medicine at Duke University Medical Center, Durham, N.C.
This does not diminish the need to answer this question. In the addition to the fact that cancer is a malignancy primarily of advancing age when CV disease is prevalent – the mean age in this study was 73 years and 44% were over age 75 – it is often an indolent disease with long periods of survival, according to Dr. Lopes. About half of prostate cancer patients have concomitant CV disease, and about half will receive ADT at some point in their treatment.
In patients receiving ADT, leuprolide is far more commonly used than GnRH antagonists, which are offered in only about 4% of patients, according to data cited by Dr. Lopes. The underlying hypothesis of this study was that leuprolide is associated with greater CV risk, which might have been relevant to a risk-benefit calculation, if the hypothesis had been confirmed.
Cancer drugs can increase CV risk
Based on experimental data, “there is concern the leuprolide is involved in plaque destabilization,” said Dr. Lopes, but he noted that ADTs in general are associated with adverse metabolic changes, including increases in LDL cholesterol, insulin resistance, and body fat, all of which could be relevant to CV risk.
It is the improving rates of survival for prostate cancer as well for other types of cancer that have increased attention to the potential for cancer drugs to increase CV risk, another major cause of early mortality. For these competing risks, objective data are needed to evaluate a relative risk-to-benefit ratio for treatment choices.
This dilemma led the ESC to recently establish its Council on Cardio-Oncology, and many centers around the world are also creating interdisciplinary groups to guide treatment choices for patients with both diseases.
“You will certainly get a lot of referrals,” said Rudolf de Boer, MD, professor of translational cardiology, University Medical Center, Groningen, Netherlands. Basing his remark on his own experience starting a cardio-oncology clinic at his institution, he called this work challenging and agreed that the need for objective data is urgent.
“We need data to provide common ground on which to judge relative risks,” Dr. de Boer said. He also praised the PRONOUNCE investigators for their efforts even if the data failed to answer the question posed.
The PRONOUNCE results were published online in Circulation at the time of Dr. Lopes’s presentation.
The study received funding from Ferring Pharmaceuticals. Dr. Lopes reports financial relationships with Bristol-Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi. Dr. Suter reports financial relationships with Boehringer Ingelheim, GlaxoSmithKline, and Roche. Dr. de Boer reports financial relationships with AstraZeneca, Abbott, Bristol-Myers Squibb, Novartis, Novo Nordisk, and Roche.
FROM ESC 2021
‘Countdown to zero’: Endocrine disruptors and worldwide sperm counts
In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.
Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.
Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.
But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.
According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.
Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”
As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.
According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.
It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.
Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.
In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.
Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.
Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.
Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.
But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.
According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.
Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”
As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.
According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.
It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.
Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.
In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.
Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
In medical school, I remember thinking that telling a patient “you have cancer” would be the most professionally challenging phrase I would ever utter. And don’t get me wrong – it certainly isn’t easy; but, compared with telling someone “you are infertile,” it’s a cakewalk.
Maybe it’s because people “have” cancer and cancer is something you “fight.” Or maybe because, unlike infertility, cancer has become a part of public life (think lapel pins and support groups) and is now easier to accept. On the other hand, someone “is” infertile. The condition is a source of embarrassment for the couple and is often hidden from society.
Here’s another concerning point of contrast: While the overall rate of cancer death has declined since the early 1990s, infertility is increasing. Reports now show that one in six couples have problems conceiving and the use of assisted reproductive technologies is increasing by 5%-10% per year. Many theories exist to explain these trends, chief among them the rise in average maternal age and the increasing incidence of obesity, as well as various other male- and female-specific factors.
But interestingly, recent data suggest that the most male of all male-specific factors – total sperm count – may be specifically to blame.
According to a recent meta-analysis, the average total sperm count in men declined by 59.3% between 1973 and 2011. While these data certainly have limitations – including the exclusion of non-English publications, the reliance on total sperm count and not sperm motility, and the potential bias of those patients willing to give a semen sample – the overall trend nevertheless seems to be clearly downward. What’s more concerning, if you believe the data presented, is that there does not appear to be a leveling off of the downward curve in total sperm count.
Think about that last statement. At the current rate of decline, the average sperm count will be zero in 2045. One of the lead authors on the meta-analysis, Hagai Levine, MD, MPH, goes so far as to state, “We should hope for the best and prepare for the worst.”
As a matter of personal philosophy, I’m not a huge fan of end-of-the-world predictions because they tend not to come true (think Montanism back in the 2nd century; the 2012 Mayan calendar scare; or my personal favorite, the Prophet Hen of Leeds). On the other hand, the overall trend of decreased total sperm count in the English-speaking world seems to be true and it raises the interesting question of why.
According to the Mayo Clinic, causes of decreased sperm count include everything from anatomical factors (like varicoceles and ejaculatory issues) and lifestyle issues (such as recreational drugs, weight gain, and emotional stress) to environmental exposures (heavy metal or radiation). The senior author of the aforementioned meta-analysis, Shanna Swan, PhD, has championed another theory: the widespread exposure to endocrine-disrupting chemicals in everyday plastics.
It turns out that at least two chemicals used in the plastics industry, bisphenol A and phthalates, can mimic the effect of estrogen when ingested into the body. Even low levels of these chemicals in our bodies can lead to health problems.
Consider for a moment the presence of plastics in your life: the plastic wrappings on your food, plastic containers for shampoos and beauty products, and even the coatings of our oral supplements. A study by the Centers for Disease Control and Prevention looked at the urine of people participating in the National Health and Nutrition Examination Survey and found detectable concentrations of both of these chemicals in nearly all participants.
In 2045, I intend to be retired. But in the meantime, I think we all need to be aware of the potential impact that various endocrine-disrupting chemicals could be having on humanity. We need more research. If indeed the connection between endocrine disruptors and decreased sperm count is borne out, changes in our environmental exposure to these chemicals need to be made.
Henry Rosevear, MD, is a private-practice urologist based in Colorado Springs. He comes from a long line of doctors, but before entering medicine he served in the U.S. Navy as an officer aboard the USS Pittsburgh, a fast-attack submarine based out of New London, Conn. During his time in the Navy, he served in two deployments to the Persian Gulf, including combat experience as part of Operation Iraqi Freedom. Dr. Rosevear disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.
Nivolumab Plus Cabozantinib Improves Outcomes Compared With Sunitinib for Advanced Renal Cell Carcinoma
Study Overview
Objective. To evaluate the efficacy and safety of the combination of nivolumab plus cabozantinib as compared with sunitinib monotherapy in the treatment of previously untreated advanced renal cell carcinoma (RCC).
Design. Multicenter, international, open-label, randomized, phase 3 trial.
Intervention. Patients were randomized in a 1:1 fashion to 1 of 2 treatment arms:
- Arm A: Nivolumab intravenously 240 mg every 2 weeks plus cabozantinib orally 40 mg once daily.
- Arm B: Sunitinib orally 50 mg daily for 4 weeks, followed by 2 weeks off therapy (6-week cycle).
Randomization was stratified by the International Metastatic RCC Database Consortium prognostic risk score (low-, intermediate-, and high-risk). Treatment was continued until disease progression or development of unacceptable toxic side effects with a maximum of 2-year duration of Nivolumab therapy.
Settings and participants. Adults with previously untreated advanced RCC with a clear cell component were eligible for enrollment. Subjects were excluded if they had active central nervous system metastases or active autoimmune disease.
Main outcome measures. The primary outcome of this study was progression-free survival (PFS) as assessed by an independent review committee. Secondary endpoints included overall survival, objective response rate, safety, and PFS as assessed by investigators. All subgroup analyses were prespecified. Efficacy was assessed in the intention-to-treat population, including all patients who underwent randomization.
Main results. A total of 651 patients underwent randomization: 323 to the nivolumab plus cabozantinib group, and 328 to the sunitinib group. Baseline demographics were balanced. The median follow-up period for overall survival (OS) was 18.1 months. The primary reason for treatment discontinuation in any group was disease progression. PFS as indicated by an independent review committee was significantly longer in the nivolumab plus cabozantinib group compared to the sunitinib group (median 16.6 months vs 8.2 months; hazard ratio [HR] 0.51, P < .001). The median OS was not reached for any group. Overall survival was longer in the nivolumab plus cabozantinib group compared to the sunitinib group (HR 0.60, 95% CI: 0.40-0.89; P = .001). The objective response rate was 55.7% with the nivolumab plus cabozantinib group versus 27.1% with sunitinib (P < .001). The complete response rate was 8% in the nivolumab plus cabozantinib group compared to 4.6% in the sunitinib group. The median time to response was 2.8 months with nivolumab plus cabozantinib and 4.2 months in the sunitinib group, while the median duration of response was 20.2 months and 11.5 months, respectively.
Nearly all patients (about 99% in each group) had an adverse event (AE). Hypertension was the most common side effect, with grade 3 or higher seen in 12.5% in the nivolumab plus cabzantinib group and 13.1% in the sunitinib group. Other grade 3 or higher side effects occurring in at least 10% of patients in any group were hyponatremia, diarrhea, palmar-plantar erythrodysesthesia, hypothyroidism, and fatigue. AEs of any cause leading to discontinuation of the therapy occurred in 19.7% in the nivolumab plus cabzantinib group vs 16.9% of the sunitinib group. One death was considered to be treatment-related (small intestinal perforation) in the nivolumab plus cabozantinib group vs 2 treatment-related deaths with sunitinib (pneumonia and respiratory distress). In the nivolumab plus cabozantinib group, 57% of the patients had a dose reduction of cabozantinib and 52% had a reduction in sunitinib dosage.
Using the Functional Assessment of Cancer Therapy-Kidney Symptoms Index, patients in the nivolumab plus cabozantinib group reported better health-related quality of life and less disease-related symptoms compared to the sunitinib group.
Commentary
The treatment landscape for frontline therapy for patients with advanced RCC has rapidly expanded over the last several years and has revolutionized cancer care. Ushered in by the results from the CheckMate 214 study highlighting the efficacy of dual checkpoint inhibition with nivolumab and ipilimumab in intermediate and poor risk patients, several subsequent trials have demonstrated improved outcomes with combination therapy with immune checkpoint inhibitors and tyrosine-kinase inhibitors (TKI). To date, data from Keynote-426 (pembrolizumab plus axitinib vs sunitinib), Javelin Renal 101 (avelumab plus axitinib vs sunitinib) and the CLEAR trial (lenvatinib plus pembrolizumab vs levatinib plus everolimus vs sunitinib) have demonstrated superiority of immune checkpoint inhibitor/TKI combinations over sunitinb in the first-line setting.1-5
The current phase 3, CheckMate 9ER trial adds yet another dynamic option for patients with advanced clear cell RCC. While cross-trial comparisons are fraught with important caveats, the median PFS of almost 16.6 months and complete response rate of 8% the nivolumab plus cabozantinib group compares favorably with other combinations. Data from the CLEAR study with the combination of lenvatinib and pembrolizumab showed a complete response rate approaching 16%. Importantly, the current study highlights improved quality of life with the combination of cabozantinib and nivolumab compared to sunitinib alone adding to the efficacy and benefits of this combination treatment.
The selection of first line therapy for patients with advanced RCC should be always guided by individual patient characteristics, and any single immune checkpoint inhibitor/TKI combination is not “superior” to any other. Perhaps more importantly is developing an understanding of the overlapping toxicity profiles of checkpoint inhibitors and TKIs. Again, this trial results are consistent with prior studies in terms of the adverse event profile which were not trivial, and almost all patients (99%) experienced AEs. It is important for oncologists to understand the management of the toxicities with these combinations and dose reductions as appropriate. It is worth noting that 19% of patients with nivolumab plus cabozantinib received glucocorticoids for management of immune-related AEs.
While long-term follow-up data will be needed to further understand the durability of response to this combination, nivolumab-cabozantinib represents an exciting new option for patients with advanced clear cell RCC. As we continue to see improvement in outcomes in clear cell histology, further work must focus on optimization of therapy in non-clear cell RCC as this is a population that is not represented in these data sets. Furthermore, future efforts should begin to explore triplet combinations and biomarker driven patient selection for upfront therapy in ordercontinue to improve outcomes in patients with advanced RCC.
Applications for Clinical Practice
The combination of nivolumab plus cabozantinib adds to the growing list of highly active checkpoint inhibitor/TKI combinations for first-line treatment of advanced RCC. With significant higher response rates, improved outcomes, and improvement in the quality of life, this combination will add another standard treatment option for patients with previously untreated advanced RCC.
1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab Versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378(14)1277-1290. doi:10.1056/NEJMoa1712126
2. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714
3. Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21(12):1563-1573. doi:10.1016/S1470-2045(20)30436-8
4. Choueiri TK, Motzer RJ, Rini BI, et al. Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann Oncol. 2020;31:1030-1039. doi:10.1016/j.annonc.2020.04.010
5, Motzer R, Alekseev B, Rha SY, et al. CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716
Study Overview
Objective. To evaluate the efficacy and safety of the combination of nivolumab plus cabozantinib as compared with sunitinib monotherapy in the treatment of previously untreated advanced renal cell carcinoma (RCC).
Design. Multicenter, international, open-label, randomized, phase 3 trial.
Intervention. Patients were randomized in a 1:1 fashion to 1 of 2 treatment arms:
- Arm A: Nivolumab intravenously 240 mg every 2 weeks plus cabozantinib orally 40 mg once daily.
- Arm B: Sunitinib orally 50 mg daily for 4 weeks, followed by 2 weeks off therapy (6-week cycle).
Randomization was stratified by the International Metastatic RCC Database Consortium prognostic risk score (low-, intermediate-, and high-risk). Treatment was continued until disease progression or development of unacceptable toxic side effects with a maximum of 2-year duration of Nivolumab therapy.
Settings and participants. Adults with previously untreated advanced RCC with a clear cell component were eligible for enrollment. Subjects were excluded if they had active central nervous system metastases or active autoimmune disease.
Main outcome measures. The primary outcome of this study was progression-free survival (PFS) as assessed by an independent review committee. Secondary endpoints included overall survival, objective response rate, safety, and PFS as assessed by investigators. All subgroup analyses were prespecified. Efficacy was assessed in the intention-to-treat population, including all patients who underwent randomization.
Main results. A total of 651 patients underwent randomization: 323 to the nivolumab plus cabozantinib group, and 328 to the sunitinib group. Baseline demographics were balanced. The median follow-up period for overall survival (OS) was 18.1 months. The primary reason for treatment discontinuation in any group was disease progression. PFS as indicated by an independent review committee was significantly longer in the nivolumab plus cabozantinib group compared to the sunitinib group (median 16.6 months vs 8.2 months; hazard ratio [HR] 0.51, P < .001). The median OS was not reached for any group. Overall survival was longer in the nivolumab plus cabozantinib group compared to the sunitinib group (HR 0.60, 95% CI: 0.40-0.89; P = .001). The objective response rate was 55.7% with the nivolumab plus cabozantinib group versus 27.1% with sunitinib (P < .001). The complete response rate was 8% in the nivolumab plus cabozantinib group compared to 4.6% in the sunitinib group. The median time to response was 2.8 months with nivolumab plus cabozantinib and 4.2 months in the sunitinib group, while the median duration of response was 20.2 months and 11.5 months, respectively.
Nearly all patients (about 99% in each group) had an adverse event (AE). Hypertension was the most common side effect, with grade 3 or higher seen in 12.5% in the nivolumab plus cabzantinib group and 13.1% in the sunitinib group. Other grade 3 or higher side effects occurring in at least 10% of patients in any group were hyponatremia, diarrhea, palmar-plantar erythrodysesthesia, hypothyroidism, and fatigue. AEs of any cause leading to discontinuation of the therapy occurred in 19.7% in the nivolumab plus cabzantinib group vs 16.9% of the sunitinib group. One death was considered to be treatment-related (small intestinal perforation) in the nivolumab plus cabozantinib group vs 2 treatment-related deaths with sunitinib (pneumonia and respiratory distress). In the nivolumab plus cabozantinib group, 57% of the patients had a dose reduction of cabozantinib and 52% had a reduction in sunitinib dosage.
Using the Functional Assessment of Cancer Therapy-Kidney Symptoms Index, patients in the nivolumab plus cabozantinib group reported better health-related quality of life and less disease-related symptoms compared to the sunitinib group.
Commentary
The treatment landscape for frontline therapy for patients with advanced RCC has rapidly expanded over the last several years and has revolutionized cancer care. Ushered in by the results from the CheckMate 214 study highlighting the efficacy of dual checkpoint inhibition with nivolumab and ipilimumab in intermediate and poor risk patients, several subsequent trials have demonstrated improved outcomes with combination therapy with immune checkpoint inhibitors and tyrosine-kinase inhibitors (TKI). To date, data from Keynote-426 (pembrolizumab plus axitinib vs sunitinib), Javelin Renal 101 (avelumab plus axitinib vs sunitinib) and the CLEAR trial (lenvatinib plus pembrolizumab vs levatinib plus everolimus vs sunitinib) have demonstrated superiority of immune checkpoint inhibitor/TKI combinations over sunitinb in the first-line setting.1-5
The current phase 3, CheckMate 9ER trial adds yet another dynamic option for patients with advanced clear cell RCC. While cross-trial comparisons are fraught with important caveats, the median PFS of almost 16.6 months and complete response rate of 8% the nivolumab plus cabozantinib group compares favorably with other combinations. Data from the CLEAR study with the combination of lenvatinib and pembrolizumab showed a complete response rate approaching 16%. Importantly, the current study highlights improved quality of life with the combination of cabozantinib and nivolumab compared to sunitinib alone adding to the efficacy and benefits of this combination treatment.
The selection of first line therapy for patients with advanced RCC should be always guided by individual patient characteristics, and any single immune checkpoint inhibitor/TKI combination is not “superior” to any other. Perhaps more importantly is developing an understanding of the overlapping toxicity profiles of checkpoint inhibitors and TKIs. Again, this trial results are consistent with prior studies in terms of the adverse event profile which were not trivial, and almost all patients (99%) experienced AEs. It is important for oncologists to understand the management of the toxicities with these combinations and dose reductions as appropriate. It is worth noting that 19% of patients with nivolumab plus cabozantinib received glucocorticoids for management of immune-related AEs.
While long-term follow-up data will be needed to further understand the durability of response to this combination, nivolumab-cabozantinib represents an exciting new option for patients with advanced clear cell RCC. As we continue to see improvement in outcomes in clear cell histology, further work must focus on optimization of therapy in non-clear cell RCC as this is a population that is not represented in these data sets. Furthermore, future efforts should begin to explore triplet combinations and biomarker driven patient selection for upfront therapy in ordercontinue to improve outcomes in patients with advanced RCC.
Applications for Clinical Practice
The combination of nivolumab plus cabozantinib adds to the growing list of highly active checkpoint inhibitor/TKI combinations for first-line treatment of advanced RCC. With significant higher response rates, improved outcomes, and improvement in the quality of life, this combination will add another standard treatment option for patients with previously untreated advanced RCC.
Study Overview
Objective. To evaluate the efficacy and safety of the combination of nivolumab plus cabozantinib as compared with sunitinib monotherapy in the treatment of previously untreated advanced renal cell carcinoma (RCC).
Design. Multicenter, international, open-label, randomized, phase 3 trial.
Intervention. Patients were randomized in a 1:1 fashion to 1 of 2 treatment arms:
- Arm A: Nivolumab intravenously 240 mg every 2 weeks plus cabozantinib orally 40 mg once daily.
- Arm B: Sunitinib orally 50 mg daily for 4 weeks, followed by 2 weeks off therapy (6-week cycle).
Randomization was stratified by the International Metastatic RCC Database Consortium prognostic risk score (low-, intermediate-, and high-risk). Treatment was continued until disease progression or development of unacceptable toxic side effects with a maximum of 2-year duration of Nivolumab therapy.
Settings and participants. Adults with previously untreated advanced RCC with a clear cell component were eligible for enrollment. Subjects were excluded if they had active central nervous system metastases or active autoimmune disease.
Main outcome measures. The primary outcome of this study was progression-free survival (PFS) as assessed by an independent review committee. Secondary endpoints included overall survival, objective response rate, safety, and PFS as assessed by investigators. All subgroup analyses were prespecified. Efficacy was assessed in the intention-to-treat population, including all patients who underwent randomization.
Main results. A total of 651 patients underwent randomization: 323 to the nivolumab plus cabozantinib group, and 328 to the sunitinib group. Baseline demographics were balanced. The median follow-up period for overall survival (OS) was 18.1 months. The primary reason for treatment discontinuation in any group was disease progression. PFS as indicated by an independent review committee was significantly longer in the nivolumab plus cabozantinib group compared to the sunitinib group (median 16.6 months vs 8.2 months; hazard ratio [HR] 0.51, P < .001). The median OS was not reached for any group. Overall survival was longer in the nivolumab plus cabozantinib group compared to the sunitinib group (HR 0.60, 95% CI: 0.40-0.89; P = .001). The objective response rate was 55.7% with the nivolumab plus cabozantinib group versus 27.1% with sunitinib (P < .001). The complete response rate was 8% in the nivolumab plus cabozantinib group compared to 4.6% in the sunitinib group. The median time to response was 2.8 months with nivolumab plus cabozantinib and 4.2 months in the sunitinib group, while the median duration of response was 20.2 months and 11.5 months, respectively.
Nearly all patients (about 99% in each group) had an adverse event (AE). Hypertension was the most common side effect, with grade 3 or higher seen in 12.5% in the nivolumab plus cabzantinib group and 13.1% in the sunitinib group. Other grade 3 or higher side effects occurring in at least 10% of patients in any group were hyponatremia, diarrhea, palmar-plantar erythrodysesthesia, hypothyroidism, and fatigue. AEs of any cause leading to discontinuation of the therapy occurred in 19.7% in the nivolumab plus cabzantinib group vs 16.9% of the sunitinib group. One death was considered to be treatment-related (small intestinal perforation) in the nivolumab plus cabozantinib group vs 2 treatment-related deaths with sunitinib (pneumonia and respiratory distress). In the nivolumab plus cabozantinib group, 57% of the patients had a dose reduction of cabozantinib and 52% had a reduction in sunitinib dosage.
Using the Functional Assessment of Cancer Therapy-Kidney Symptoms Index, patients in the nivolumab plus cabozantinib group reported better health-related quality of life and less disease-related symptoms compared to the sunitinib group.
Commentary
The treatment landscape for frontline therapy for patients with advanced RCC has rapidly expanded over the last several years and has revolutionized cancer care. Ushered in by the results from the CheckMate 214 study highlighting the efficacy of dual checkpoint inhibition with nivolumab and ipilimumab in intermediate and poor risk patients, several subsequent trials have demonstrated improved outcomes with combination therapy with immune checkpoint inhibitors and tyrosine-kinase inhibitors (TKI). To date, data from Keynote-426 (pembrolizumab plus axitinib vs sunitinib), Javelin Renal 101 (avelumab plus axitinib vs sunitinib) and the CLEAR trial (lenvatinib plus pembrolizumab vs levatinib plus everolimus vs sunitinib) have demonstrated superiority of immune checkpoint inhibitor/TKI combinations over sunitinb in the first-line setting.1-5
The current phase 3, CheckMate 9ER trial adds yet another dynamic option for patients with advanced clear cell RCC. While cross-trial comparisons are fraught with important caveats, the median PFS of almost 16.6 months and complete response rate of 8% the nivolumab plus cabozantinib group compares favorably with other combinations. Data from the CLEAR study with the combination of lenvatinib and pembrolizumab showed a complete response rate approaching 16%. Importantly, the current study highlights improved quality of life with the combination of cabozantinib and nivolumab compared to sunitinib alone adding to the efficacy and benefits of this combination treatment.
The selection of first line therapy for patients with advanced RCC should be always guided by individual patient characteristics, and any single immune checkpoint inhibitor/TKI combination is not “superior” to any other. Perhaps more importantly is developing an understanding of the overlapping toxicity profiles of checkpoint inhibitors and TKIs. Again, this trial results are consistent with prior studies in terms of the adverse event profile which were not trivial, and almost all patients (99%) experienced AEs. It is important for oncologists to understand the management of the toxicities with these combinations and dose reductions as appropriate. It is worth noting that 19% of patients with nivolumab plus cabozantinib received glucocorticoids for management of immune-related AEs.
While long-term follow-up data will be needed to further understand the durability of response to this combination, nivolumab-cabozantinib represents an exciting new option for patients with advanced clear cell RCC. As we continue to see improvement in outcomes in clear cell histology, further work must focus on optimization of therapy in non-clear cell RCC as this is a population that is not represented in these data sets. Furthermore, future efforts should begin to explore triplet combinations and biomarker driven patient selection for upfront therapy in ordercontinue to improve outcomes in patients with advanced RCC.
Applications for Clinical Practice
The combination of nivolumab plus cabozantinib adds to the growing list of highly active checkpoint inhibitor/TKI combinations for first-line treatment of advanced RCC. With significant higher response rates, improved outcomes, and improvement in the quality of life, this combination will add another standard treatment option for patients with previously untreated advanced RCC.
1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab Versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378(14)1277-1290. doi:10.1056/NEJMoa1712126
2. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714
3. Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21(12):1563-1573. doi:10.1016/S1470-2045(20)30436-8
4. Choueiri TK, Motzer RJ, Rini BI, et al. Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann Oncol. 2020;31:1030-1039. doi:10.1016/j.annonc.2020.04.010
5, Motzer R, Alekseev B, Rha SY, et al. CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716
1. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab Versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018;378(14)1277-1290. doi:10.1056/NEJMoa1712126
2. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus Axitinib versus Sunitinib for Advanced Renal-Cell Carcinoma. N Engl J Med. 2019;380(12):1116-1127. doi:10.1056/NEJMoa1816714
3. Powles T, Plimack ER, Soulières D, et al. Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21(12):1563-1573. doi:10.1016/S1470-2045(20)30436-8
4. Choueiri TK, Motzer RJ, Rini BI, et al. Updated efficacy results from the JAVELIN Renal 101 trial: first-line avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma. Ann Oncol. 2020;31:1030-1039. doi:10.1016/j.annonc.2020.04.010
5, Motzer R, Alekseev B, Rha SY, et al. CLEAR Trial Investigators. Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma. N Engl J Med. 2021;384(14):1289-1300. doi:10.1056/NEJMoa2035716
This is not the time to modify a HTN regimen
ILLUSTRATIVE CASE
A 67-year-old man with hypertension that is well controlled on hydrochlorothiazide 25 mg po daily was admitted to the family medicine inpatient service for community-acquired pneumonia requiring antibiotic therapy and oxygen support. Despite improvement in his overall condition, his blood pressure was consistently > 160/90 mm Hg during his hospitalization. He was treated with lisinopril 10 mg po daily in addition to his home medications, which helped achieve recommended blood pressure goals.
Prior to discharge, his blood pressure was noted to be 108/62 mm Hg. He asks if it is necessary to continue this new blood pressure medicine, as his home blood pressure readings had been within the goal set by his primary care physician. Should you continue this new antihypertensive agent at discharge?
Outpatient antihypertensive medication regimens are commonly intensified at hospital discharge in response to transient short-term elevations in blood pressure during inpatient encounters for noncardiac conditions.1,2 This is typically a reflexive response during a hospitalization, despite the unknown long-term, patient-oriented clinical outcomes. These short-term, in-hospital blood pressure elevations may be due to numerous temporary causes, such as stress/anxiety, a pain response, agitation, a medication adverse effect, or volume overload.3
The transition from inpatient to outpatient care is a high-risk period, especially for older adults, as functional status is generally worse at hospital discharge than prehospitalization baseline.4 To compound this problem, adverse drug reactions are a common cause of hospitalization for older adults. Changing blood pressure medications in response to acute physiologic changes during illness may contribute to patient harm. Although observational studies of adverse drug reactions related to blood pressure medications are numerous, researchers have only evaluated adverse drug reactions pertaining to hospital admissions.5-8 This study sought to evaluate the clinical outcomes associated with intensification of antihypertensive regimens at discharge among older adults.
STUDY SUMMARY
Increased risk of readmission, adverse events after intensification at discharge
This retrospective cohort study, which was conducted across multiple
Antihypertensive medication changes at discharge were evaluated using information pulled from VHA pharmacies, combined with clinical data merged from VHA and Medicare claims. Intensification was defined as either adding a new blood pressure medication or a dose increase of more than 20% on a previously prescribed antihypertensive medication. Patients were excluded if they were discharged with a secondary diagnosis that required modifications to a blood pressure medication (such as atrial fibrillation, acute coronary syndrome, or stroke), were hospitalized in the previous 30 days, were admitted from a skilled nursing facility, or received more than 20% of their care (including filling prescriptions) outside the VHA system.
Primary outcomes included hospital readmission or SAEs (falls, syncope, hypotension, serious electrolyte abnormalities, or acute kidney injury) within 30 days or having a cardiovascular event within 1 year of hospital discharge. Secondary outcomes included the change in systolic blood pressure (SBP) within 1 year after discharge. Propensity score matching was used as a balancing factor to create a matched-pairs cohort to compare those receiving blood pressure medication intensification at hospital discharge with those who did not.
Continue to: Intensification of the blood pressure...
Intensification of the blood pressure regimen at hospital discharge was associated with an increased risk in 30-day hospital readmission (hazard ratio [HR] = 1.23; 95% CI, 1.07–1.42; number needed to harm [NNH] = 27) and SAEs (HR = 1.41; 95% CI, 1.06–1.88; NNH = 63). There was no associated reduction in cardiovascular events (HR = 1.18; 95% CI, 0.99–1.40) or change in mean SBP within 1 year after hospital discharge in those who received intensification vs those who did not (mean BP, 134.7 vs 134.4 mm Hg; difference-in-differences estimate = 0.2 mm Hg; 95% CI, −2.0 to 2.4 mm Hg).
WHAT’S NEW
First study on outcomes related to HTN med changes at hospital discharge
This well-designed, retrospective cohort study provides important clinical data to help guide inpatient blood pressure management decisions for patients with noncardiac conditions. No clinical trials up to that time had assessed patient-oriented outcomes when antihypertensive medication regimens were intensified at hospital discharge.
CAVEATS
Study population: Primarily older men with noncardiac conditions
Selected populations benefit from intensive blood pressure control based on specific risk factors and medical conditions. In patients at high risk for cardiovascular disease, without a history of stroke or diabetes, intensive blood pressure control (SBP < 120 mm Hg) improves cardiovascular outcomes and overall survival compared with standard therapy (SBP < 140 mm Hg).9 This retrospective cohort study involved mainly elderly male patients with noncardiac conditions. The study also excluded patients with a secondary diagnosis requiring modifications to an antihypertensive regimen, such as atrial fibrillation, acute coronary syndrome, or cerebrovascular accident. Thus, the findings may not be applicable to these patient populations.
CHALLENGES TO IMPLEMENTATION
Clinicians will need to address individual needs
Physicians have to balance various antihypertensive management strategies, as competing medical specialty society guidelines recommend differing targets for optimal blood pressure control. Given the concern for medicolegal liability and potential harms of therapeutic inertia, inpatient physicians must consider whether hospitalization is the best time to alter medications for long-term outpatient blood pressure control. Finally, the decision to leave blood pressure management to outpatient physicians assumes the patient has a continuity relationship with a primary care medical home.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
1. Anderson TS, Jing B, Auerbach A, et al. Clinical outcomes after intensifying antihypertensive medication regimens among older adults at hospital discharge. JAMA Intern Med. 2019;179:1528-1536.
2. Harris CM, Sridharan A, Landis R, et al. What happens to the medication regimens of older adults during and after an acute hospitalization? J Patient Saf. 2013;9:150-153.
3. Aung WM, Menon SV, Materson BJ. Management of hypertension in hospitalized patients. Hosp Pract (1995). 2015;43:101-106.
4. Covinsky KE, Palmer RM, Fortinsky RH, et al. Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: increased vulnerability with age. J Am Geriatr Soc. 2003;51:451-458.
5. Omer HMRB, Hodson J, Pontefract SK, et al. Inpatient falls in older adults: a cohort study of antihypertensive prescribing pre- and post-fall. BMC Geriatr. 2018;18:58.
6. Alhawassi TM, Krass I, Pont LG. Antihypertensive-related adverse drug reactions among older hospitalized adults. Int J Clin Pharm. 2018;40:428-435.
7. Passarelli MCG, Jacob-Filho W, Figueras A. Adverse drug reactions in an elderly hospitalised population: inappropriate prescription is a leading cause. Drugs Aging. 2005;22:767-777.
8. Beckett NS, Peters R, Fletcher AE, et al; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-1898.
9. SPRINT Research Group; Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116. Published correction appears in N Engl J Med. 2017;377:2506.
ILLUSTRATIVE CASE
A 67-year-old man with hypertension that is well controlled on hydrochlorothiazide 25 mg po daily was admitted to the family medicine inpatient service for community-acquired pneumonia requiring antibiotic therapy and oxygen support. Despite improvement in his overall condition, his blood pressure was consistently > 160/90 mm Hg during his hospitalization. He was treated with lisinopril 10 mg po daily in addition to his home medications, which helped achieve recommended blood pressure goals.
Prior to discharge, his blood pressure was noted to be 108/62 mm Hg. He asks if it is necessary to continue this new blood pressure medicine, as his home blood pressure readings had been within the goal set by his primary care physician. Should you continue this new antihypertensive agent at discharge?
Outpatient antihypertensive medication regimens are commonly intensified at hospital discharge in response to transient short-term elevations in blood pressure during inpatient encounters for noncardiac conditions.1,2 This is typically a reflexive response during a hospitalization, despite the unknown long-term, patient-oriented clinical outcomes. These short-term, in-hospital blood pressure elevations may be due to numerous temporary causes, such as stress/anxiety, a pain response, agitation, a medication adverse effect, or volume overload.3
The transition from inpatient to outpatient care is a high-risk period, especially for older adults, as functional status is generally worse at hospital discharge than prehospitalization baseline.4 To compound this problem, adverse drug reactions are a common cause of hospitalization for older adults. Changing blood pressure medications in response to acute physiologic changes during illness may contribute to patient harm. Although observational studies of adverse drug reactions related to blood pressure medications are numerous, researchers have only evaluated adverse drug reactions pertaining to hospital admissions.5-8 This study sought to evaluate the clinical outcomes associated with intensification of antihypertensive regimens at discharge among older adults.
STUDY SUMMARY
Increased risk of readmission, adverse events after intensification at discharge
This retrospective cohort study, which was conducted across multiple
Antihypertensive medication changes at discharge were evaluated using information pulled from VHA pharmacies, combined with clinical data merged from VHA and Medicare claims. Intensification was defined as either adding a new blood pressure medication or a dose increase of more than 20% on a previously prescribed antihypertensive medication. Patients were excluded if they were discharged with a secondary diagnosis that required modifications to a blood pressure medication (such as atrial fibrillation, acute coronary syndrome, or stroke), were hospitalized in the previous 30 days, were admitted from a skilled nursing facility, or received more than 20% of their care (including filling prescriptions) outside the VHA system.
Primary outcomes included hospital readmission or SAEs (falls, syncope, hypotension, serious electrolyte abnormalities, or acute kidney injury) within 30 days or having a cardiovascular event within 1 year of hospital discharge. Secondary outcomes included the change in systolic blood pressure (SBP) within 1 year after discharge. Propensity score matching was used as a balancing factor to create a matched-pairs cohort to compare those receiving blood pressure medication intensification at hospital discharge with those who did not.
Continue to: Intensification of the blood pressure...
Intensification of the blood pressure regimen at hospital discharge was associated with an increased risk in 30-day hospital readmission (hazard ratio [HR] = 1.23; 95% CI, 1.07–1.42; number needed to harm [NNH] = 27) and SAEs (HR = 1.41; 95% CI, 1.06–1.88; NNH = 63). There was no associated reduction in cardiovascular events (HR = 1.18; 95% CI, 0.99–1.40) or change in mean SBP within 1 year after hospital discharge in those who received intensification vs those who did not (mean BP, 134.7 vs 134.4 mm Hg; difference-in-differences estimate = 0.2 mm Hg; 95% CI, −2.0 to 2.4 mm Hg).
WHAT’S NEW
First study on outcomes related to HTN med changes at hospital discharge
This well-designed, retrospective cohort study provides important clinical data to help guide inpatient blood pressure management decisions for patients with noncardiac conditions. No clinical trials up to that time had assessed patient-oriented outcomes when antihypertensive medication regimens were intensified at hospital discharge.
CAVEATS
Study population: Primarily older men with noncardiac conditions
Selected populations benefit from intensive blood pressure control based on specific risk factors and medical conditions. In patients at high risk for cardiovascular disease, without a history of stroke or diabetes, intensive blood pressure control (SBP < 120 mm Hg) improves cardiovascular outcomes and overall survival compared with standard therapy (SBP < 140 mm Hg).9 This retrospective cohort study involved mainly elderly male patients with noncardiac conditions. The study also excluded patients with a secondary diagnosis requiring modifications to an antihypertensive regimen, such as atrial fibrillation, acute coronary syndrome, or cerebrovascular accident. Thus, the findings may not be applicable to these patient populations.
CHALLENGES TO IMPLEMENTATION
Clinicians will need to address individual needs
Physicians have to balance various antihypertensive management strategies, as competing medical specialty society guidelines recommend differing targets for optimal blood pressure control. Given the concern for medicolegal liability and potential harms of therapeutic inertia, inpatient physicians must consider whether hospitalization is the best time to alter medications for long-term outpatient blood pressure control. Finally, the decision to leave blood pressure management to outpatient physicians assumes the patient has a continuity relationship with a primary care medical home.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
A 67-year-old man with hypertension that is well controlled on hydrochlorothiazide 25 mg po daily was admitted to the family medicine inpatient service for community-acquired pneumonia requiring antibiotic therapy and oxygen support. Despite improvement in his overall condition, his blood pressure was consistently > 160/90 mm Hg during his hospitalization. He was treated with lisinopril 10 mg po daily in addition to his home medications, which helped achieve recommended blood pressure goals.
Prior to discharge, his blood pressure was noted to be 108/62 mm Hg. He asks if it is necessary to continue this new blood pressure medicine, as his home blood pressure readings had been within the goal set by his primary care physician. Should you continue this new antihypertensive agent at discharge?
Outpatient antihypertensive medication regimens are commonly intensified at hospital discharge in response to transient short-term elevations in blood pressure during inpatient encounters for noncardiac conditions.1,2 This is typically a reflexive response during a hospitalization, despite the unknown long-term, patient-oriented clinical outcomes. These short-term, in-hospital blood pressure elevations may be due to numerous temporary causes, such as stress/anxiety, a pain response, agitation, a medication adverse effect, or volume overload.3
The transition from inpatient to outpatient care is a high-risk period, especially for older adults, as functional status is generally worse at hospital discharge than prehospitalization baseline.4 To compound this problem, adverse drug reactions are a common cause of hospitalization for older adults. Changing blood pressure medications in response to acute physiologic changes during illness may contribute to patient harm. Although observational studies of adverse drug reactions related to blood pressure medications are numerous, researchers have only evaluated adverse drug reactions pertaining to hospital admissions.5-8 This study sought to evaluate the clinical outcomes associated with intensification of antihypertensive regimens at discharge among older adults.
STUDY SUMMARY
Increased risk of readmission, adverse events after intensification at discharge
This retrospective cohort study, which was conducted across multiple
Antihypertensive medication changes at discharge were evaluated using information pulled from VHA pharmacies, combined with clinical data merged from VHA and Medicare claims. Intensification was defined as either adding a new blood pressure medication or a dose increase of more than 20% on a previously prescribed antihypertensive medication. Patients were excluded if they were discharged with a secondary diagnosis that required modifications to a blood pressure medication (such as atrial fibrillation, acute coronary syndrome, or stroke), were hospitalized in the previous 30 days, were admitted from a skilled nursing facility, or received more than 20% of their care (including filling prescriptions) outside the VHA system.
Primary outcomes included hospital readmission or SAEs (falls, syncope, hypotension, serious electrolyte abnormalities, or acute kidney injury) within 30 days or having a cardiovascular event within 1 year of hospital discharge. Secondary outcomes included the change in systolic blood pressure (SBP) within 1 year after discharge. Propensity score matching was used as a balancing factor to create a matched-pairs cohort to compare those receiving blood pressure medication intensification at hospital discharge with those who did not.
Continue to: Intensification of the blood pressure...
Intensification of the blood pressure regimen at hospital discharge was associated with an increased risk in 30-day hospital readmission (hazard ratio [HR] = 1.23; 95% CI, 1.07–1.42; number needed to harm [NNH] = 27) and SAEs (HR = 1.41; 95% CI, 1.06–1.88; NNH = 63). There was no associated reduction in cardiovascular events (HR = 1.18; 95% CI, 0.99–1.40) or change in mean SBP within 1 year after hospital discharge in those who received intensification vs those who did not (mean BP, 134.7 vs 134.4 mm Hg; difference-in-differences estimate = 0.2 mm Hg; 95% CI, −2.0 to 2.4 mm Hg).
WHAT’S NEW
First study on outcomes related to HTN med changes at hospital discharge
This well-designed, retrospective cohort study provides important clinical data to help guide inpatient blood pressure management decisions for patients with noncardiac conditions. No clinical trials up to that time had assessed patient-oriented outcomes when antihypertensive medication regimens were intensified at hospital discharge.
CAVEATS
Study population: Primarily older men with noncardiac conditions
Selected populations benefit from intensive blood pressure control based on specific risk factors and medical conditions. In patients at high risk for cardiovascular disease, without a history of stroke or diabetes, intensive blood pressure control (SBP < 120 mm Hg) improves cardiovascular outcomes and overall survival compared with standard therapy (SBP < 140 mm Hg).9 This retrospective cohort study involved mainly elderly male patients with noncardiac conditions. The study also excluded patients with a secondary diagnosis requiring modifications to an antihypertensive regimen, such as atrial fibrillation, acute coronary syndrome, or cerebrovascular accident. Thus, the findings may not be applicable to these patient populations.
CHALLENGES TO IMPLEMENTATION
Clinicians will need to address individual needs
Physicians have to balance various antihypertensive management strategies, as competing medical specialty society guidelines recommend differing targets for optimal blood pressure control. Given the concern for medicolegal liability and potential harms of therapeutic inertia, inpatient physicians must consider whether hospitalization is the best time to alter medications for long-term outpatient blood pressure control. Finally, the decision to leave blood pressure management to outpatient physicians assumes the patient has a continuity relationship with a primary care medical home.
ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.
1. Anderson TS, Jing B, Auerbach A, et al. Clinical outcomes after intensifying antihypertensive medication regimens among older adults at hospital discharge. JAMA Intern Med. 2019;179:1528-1536.
2. Harris CM, Sridharan A, Landis R, et al. What happens to the medication regimens of older adults during and after an acute hospitalization? J Patient Saf. 2013;9:150-153.
3. Aung WM, Menon SV, Materson BJ. Management of hypertension in hospitalized patients. Hosp Pract (1995). 2015;43:101-106.
4. Covinsky KE, Palmer RM, Fortinsky RH, et al. Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: increased vulnerability with age. J Am Geriatr Soc. 2003;51:451-458.
5. Omer HMRB, Hodson J, Pontefract SK, et al. Inpatient falls in older adults: a cohort study of antihypertensive prescribing pre- and post-fall. BMC Geriatr. 2018;18:58.
6. Alhawassi TM, Krass I, Pont LG. Antihypertensive-related adverse drug reactions among older hospitalized adults. Int J Clin Pharm. 2018;40:428-435.
7. Passarelli MCG, Jacob-Filho W, Figueras A. Adverse drug reactions in an elderly hospitalised population: inappropriate prescription is a leading cause. Drugs Aging. 2005;22:767-777.
8. Beckett NS, Peters R, Fletcher AE, et al; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-1898.
9. SPRINT Research Group; Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116. Published correction appears in N Engl J Med. 2017;377:2506.
1. Anderson TS, Jing B, Auerbach A, et al. Clinical outcomes after intensifying antihypertensive medication regimens among older adults at hospital discharge. JAMA Intern Med. 2019;179:1528-1536.
2. Harris CM, Sridharan A, Landis R, et al. What happens to the medication regimens of older adults during and after an acute hospitalization? J Patient Saf. 2013;9:150-153.
3. Aung WM, Menon SV, Materson BJ. Management of hypertension in hospitalized patients. Hosp Pract (1995). 2015;43:101-106.
4. Covinsky KE, Palmer RM, Fortinsky RH, et al. Loss of independence in activities of daily living in older adults hospitalized with medical illnesses: increased vulnerability with age. J Am Geriatr Soc. 2003;51:451-458.
5. Omer HMRB, Hodson J, Pontefract SK, et al. Inpatient falls in older adults: a cohort study of antihypertensive prescribing pre- and post-fall. BMC Geriatr. 2018;18:58.
6. Alhawassi TM, Krass I, Pont LG. Antihypertensive-related adverse drug reactions among older hospitalized adults. Int J Clin Pharm. 2018;40:428-435.
7. Passarelli MCG, Jacob-Filho W, Figueras A. Adverse drug reactions in an elderly hospitalised population: inappropriate prescription is a leading cause. Drugs Aging. 2005;22:767-777.
8. Beckett NS, Peters R, Fletcher AE, et al; HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-1898.
9. SPRINT Research Group; Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116. Published correction appears in N Engl J Med. 2017;377:2506.
PRACTICE CHANGER
Avoid intensifying antihypertensive medication regimens at hospital discharge in older adults; making such changes increases the risk of serious adverse events (SAEs) and hospital readmission within 30 days without reducing the risk of serious cardiovascular events at 1 year post discharge.
STRENGTH OF RECOMMENDATION
B: Based on a large retrospective cohort study evaluating patient-oriented outcomes.1
Anderson TS, Jing B, Auerbach A, et al. Clinical outcomes after intensifying antihypertensive medication regimens among older adults at hospital discharge. JAMA Intern Med. 2019;179:1528-1536.
Testosterone replacement shows CV benefit in hypogonadal men
Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.
The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.
In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.
The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.
“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.
He presented the new data at the 2021 annual congress of the European Association of Urology.
Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”
Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.
“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
Registry study
The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.
At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.
The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.
The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).
All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.
Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”
No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.
The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.
In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.
The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.
“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.
He presented the new data at the 2021 annual congress of the European Association of Urology.
Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”
Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.
“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
Registry study
The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.
At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.
The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.
The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).
All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.
Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”
No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Data from a long-term study suggest that testosterone replacement therapy (TRT) for men with hypogonadism may reduce the risk for major adverse cardiovascular events. Previous studies have yielded conflicting results on whether there is a benefit.
The latest results come from a study of 805 men with hypogonadism from Germany and Qatar who were followed for nearly a decade. For those who received parenteral testosterone 1,000 mg every 12 weeks, there were improvements in classical cardiovascular risk factors, such as obesity, lipid level, and inflammatory markers, whereas among those who chose not to take testosterone (control patients), all of these factors worsened.
In addition, there were only 16 deaths among patients in the TRT group, and none of the deaths were from myocardial infarction or stroke. In contrast, there were 74 deaths among the control patients, as well as 70 cases of MI and 59 strokes.
The men in the study were all at relatively high risk for cardiovascular adverse events. In the TRT group, the mean Framingham Risk score was 15.5; in the control group, it was 15.8. This translates into mean 10-year risks of 22.7% and 23.5%, respectively.
“Given that all these men would normally have been expected to suffer a heart attack or stroke in the next 5-10 years with no other intervention, it was a real surprise to see no cardiovascular events at all in the group on testosterone therapy. It’s clear that this treatment can significantly reduce the risks in this particular group,” commented lead investigator Omar Aboumarzouk, MD, from Hamad Medical in Doha, Qatar.
He presented the new data at the 2021 annual congress of the European Association of Urology.
Dr. Aboumarzouk emphasized, however, that, “while men need testosterone for certain psychological and biological functions, only those with low levels who display other symptoms are likely to benefit from testosterone therapy.”
Maarten Albersen, MD, a urologist at the University of Leuven (Belgium), who was not involved in the study, noted that, although the study showed a reduction in major adverse cardiovascular events and mortality among the men who received TRT, the risk scores were in the intermediate range, and the men in the TRT group were slightly younger and were at slightly lower risk at baseline.
“The study was long enough to see differences in the rate of cardiovascular events. However, the numbers involved and the fact that the trial was not randomized mean it’s still difficult to draw any hard conclusions,” he said.
Registry study
The data came from a cumulative registry study begun in 2004 to assess the long-term efficacy and safety of TRT every 3 months in men with hypogonadism. The study, conducted in Bremen, Dresden, and Muenster in Germany, as well as in Doha, Qatar, is ongoing.
At total of 805 men were enrolled; 412 received TRT, and 393 declined testosterone replacement and served as control patients.
The investigators reported 10-year data. Statistical models controlled for age, body mass index, smoking, alcohol, total and HDL cholesterol level, systolic blood pressure, and type 2 diabetes.
The median age at baseline was lower among those in the TRT arm, at 57.7 years versus 63.7 years for control patients (P < .001).
All classical cardiovascular risk factors, including obesity, glycemic control, lipid pattern, and C-reactive protein, improved in the TRT group and worsened in the control group.
Dr. Albersen noted that “a new trial is now underway, aiming to recruit 6,000 participants, and this should provide definitive answers on the cardiovascular risks or even benefits of hormone therapy in men with low testosterone.”
No funding source for the study was reported. Dr. Aboumarzouk and Dr. Albersen have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Most U.S. adults age 50+ report good health: Survey
a nonprofit hospice/advanced illness care organization based in Virginia.
Among the respondents, 41% said their health was very good or excellent.
However, the ratings differed largely by race, employment status, and income.
Employment status was also associated with a significant difference in the way people viewed their health at the top tier and bottom tier.
The middle tier (“good” health) was reported similarly (from 33% to 37%) whether a person was employed, retired, or not employed. However, employed respondents were much more likely to report they had “excellent” or “very good” health (51% vs. 44% for retirees and 21% for the not employed).
Conversely, those who were not employed were far more likely to report “fair” or “poor” health (45%) than those who were employed (13%) or retired (20%).
Similarly, respondents with incomes of less than $50,000 were three times more likely to report their health as “fair” or “poor” than were those with incomes of more than $100,000 (36% vs. 12%).
WebMD/CCH surveyed 3,464 U.S. residents ages 50 and older between Aug. 13 and Nov. 9, 2020. WebMD.com readers were randomly invited to take a 10-minute online survey.
Aging at home a priority
The survey also highlighted a strong preference for aging in place, says Steve Cone, chief of communications and philanthropy at CCH.
“More now than ever before, thanks to the COVID experience, baby boomers and their children really believe that’s the holy grail,” he says.
Mr. Cone notes that the quick spread of COVID-19 through some nursing homes early in the pandemic likely has strengthened people’s resolve to live out their lives in their own homes.
The survey indicated that 85% of people aged 50+ who are living in their own home, a family member’s home, or a loved one’s home responded that it is “very important” or “important” to stay in their home as they age.
When asked what services they would need to continue their living situation, the most common responses were housekeeping, home repair services, and transportation (listed as needs by 35% to 45% of respondents). Regarding changes they would have to make to feel safe in their home as they age, installing grab bars and/or safety rails in the bath/shower was the most popular answer (50%).
Use of telemedicine
Respondents were also asked about their acceptance of telemedicine, and 62% said they would be likely or very likely to engage in virtual visits with a doctor it in the future.
However, the likelihood varied by income level. Specifically, respondents with incomes over $100,000 were significantly more likely to say they would use telemedicine in the future than were those with incomes below $50,000 (74% vs. 60%). They were also more likely to already have used telemedicine.
Although respondents generally embraced telemedicine, they are less confident about some types of monitoring, according to Mr. Cone.
Emergency response (64%) was the leading type of remote monitoring respondents ages 50 and older would allow. Only a minority of respondents would allow the other types of monitoring asked about in the survey.
Close to one-quarter of respondents would not allow any type of monitoring.
Fewer than one-third would allow tracking of medication compliance, refrigerator use, sleep habits, or bathroom use.
People see monitoring of some movements as “Orwellian,” Mr. Cone says.
Knowledge of hospice
The survey findings support the need for more widespread use of hospice so people can stay in their homes as they age, Mr. Cone says.
When illness gets severe, “There’s no reason you have to get rushed to the emergency room or wind up in a hospital,” Mr. Cone says.
He notes that hospice and palliative care can come to patients wherever they reside – in their home, an assisted living center, a nursing home, or even a hospital room.
“That doesn’t mean the physician isn’t involved,” he says. “But working as a team, we can keep them in their homes and their lifestyle intact.”
Patients whose doctors attest that they are likely to live a maximum 6 months are eligible for hospice. But most families wait too long to long to start hospice or palliative care for a patient, Mr. Cone says, and may not be aware of what these services typically cover, including meal preparation and pet care.
In the survey, nearly one-third of respondents said they did not know that palliative care is something that “can be given at any stage of a serious illness” or “provides non-medical services (e.g., patient/family communication, help with insurance issues, scheduling appointments, arranging transportation).”
He notes palliative care and hospice are covered by Medicare and Medicaid and also by most private insurance plans or by individual companies providing the service.
However, health care providers may have to overcome a general reluctance to discuss hospice when sharing options for those severely ill.
The survey showed that while 51% of those 50 and older are at least “slightly interested” in learning more about hospice, a nearly equal number say they are “not at all interested” (49%).
Most using hospice are White
More than 90% of those surveyed reported that aspects of hospice care, including “comfort and relief from pain at the end of patients’ lives,” providing a dedicated care team, and an alternative to other care settings, are “very important” or “important.”
However, national hospice use rates are extremely low for minorities and the LGBTQ community, according to Mr. Cone. Among Medicare hospice recipients, 82% were white, 8.2% Black, 6.7% Hispanic, and 1.8% Asian or Pacific Islander, according to the National Hospice and Palliative Care Organization.
Those numbers signal a need for outreach to those communities with information on what services are available and how to access them, he says.
Health costs top concern
The survey also asked about level of concern regarding matters including family, health, financials, and end-of-life directives and found adults aged 50 and older expressed the greatest amount of concern for health care costs that are not covered by insurance.
More than half (56%) said they were concerned or very concerned about those costs, which was higher than the percentage concerned about losing a spouse (49%).
Respondents were less concerned (“slightly concerned” or “not at all concerned”) about their children living far away, planning end-of life-directives, and falling or having reduced mobility.
A version of this article first appeared on WebMD.com.
a nonprofit hospice/advanced illness care organization based in Virginia.
Among the respondents, 41% said their health was very good or excellent.
However, the ratings differed largely by race, employment status, and income.
Employment status was also associated with a significant difference in the way people viewed their health at the top tier and bottom tier.
The middle tier (“good” health) was reported similarly (from 33% to 37%) whether a person was employed, retired, or not employed. However, employed respondents were much more likely to report they had “excellent” or “very good” health (51% vs. 44% for retirees and 21% for the not employed).
Conversely, those who were not employed were far more likely to report “fair” or “poor” health (45%) than those who were employed (13%) or retired (20%).
Similarly, respondents with incomes of less than $50,000 were three times more likely to report their health as “fair” or “poor” than were those with incomes of more than $100,000 (36% vs. 12%).
WebMD/CCH surveyed 3,464 U.S. residents ages 50 and older between Aug. 13 and Nov. 9, 2020. WebMD.com readers were randomly invited to take a 10-minute online survey.
Aging at home a priority
The survey also highlighted a strong preference for aging in place, says Steve Cone, chief of communications and philanthropy at CCH.
“More now than ever before, thanks to the COVID experience, baby boomers and their children really believe that’s the holy grail,” he says.
Mr. Cone notes that the quick spread of COVID-19 through some nursing homes early in the pandemic likely has strengthened people’s resolve to live out their lives in their own homes.
The survey indicated that 85% of people aged 50+ who are living in their own home, a family member’s home, or a loved one’s home responded that it is “very important” or “important” to stay in their home as they age.
When asked what services they would need to continue their living situation, the most common responses were housekeeping, home repair services, and transportation (listed as needs by 35% to 45% of respondents). Regarding changes they would have to make to feel safe in their home as they age, installing grab bars and/or safety rails in the bath/shower was the most popular answer (50%).
Use of telemedicine
Respondents were also asked about their acceptance of telemedicine, and 62% said they would be likely or very likely to engage in virtual visits with a doctor it in the future.
However, the likelihood varied by income level. Specifically, respondents with incomes over $100,000 were significantly more likely to say they would use telemedicine in the future than were those with incomes below $50,000 (74% vs. 60%). They were also more likely to already have used telemedicine.
Although respondents generally embraced telemedicine, they are less confident about some types of monitoring, according to Mr. Cone.
Emergency response (64%) was the leading type of remote monitoring respondents ages 50 and older would allow. Only a minority of respondents would allow the other types of monitoring asked about in the survey.
Close to one-quarter of respondents would not allow any type of monitoring.
Fewer than one-third would allow tracking of medication compliance, refrigerator use, sleep habits, or bathroom use.
People see monitoring of some movements as “Orwellian,” Mr. Cone says.
Knowledge of hospice
The survey findings support the need for more widespread use of hospice so people can stay in their homes as they age, Mr. Cone says.
When illness gets severe, “There’s no reason you have to get rushed to the emergency room or wind up in a hospital,” Mr. Cone says.
He notes that hospice and palliative care can come to patients wherever they reside – in their home, an assisted living center, a nursing home, or even a hospital room.
“That doesn’t mean the physician isn’t involved,” he says. “But working as a team, we can keep them in their homes and their lifestyle intact.”
Patients whose doctors attest that they are likely to live a maximum 6 months are eligible for hospice. But most families wait too long to long to start hospice or palliative care for a patient, Mr. Cone says, and may not be aware of what these services typically cover, including meal preparation and pet care.
In the survey, nearly one-third of respondents said they did not know that palliative care is something that “can be given at any stage of a serious illness” or “provides non-medical services (e.g., patient/family communication, help with insurance issues, scheduling appointments, arranging transportation).”
He notes palliative care and hospice are covered by Medicare and Medicaid and also by most private insurance plans or by individual companies providing the service.
However, health care providers may have to overcome a general reluctance to discuss hospice when sharing options for those severely ill.
The survey showed that while 51% of those 50 and older are at least “slightly interested” in learning more about hospice, a nearly equal number say they are “not at all interested” (49%).
Most using hospice are White
More than 90% of those surveyed reported that aspects of hospice care, including “comfort and relief from pain at the end of patients’ lives,” providing a dedicated care team, and an alternative to other care settings, are “very important” or “important.”
However, national hospice use rates are extremely low for minorities and the LGBTQ community, according to Mr. Cone. Among Medicare hospice recipients, 82% were white, 8.2% Black, 6.7% Hispanic, and 1.8% Asian or Pacific Islander, according to the National Hospice and Palliative Care Organization.
Those numbers signal a need for outreach to those communities with information on what services are available and how to access them, he says.
Health costs top concern
The survey also asked about level of concern regarding matters including family, health, financials, and end-of-life directives and found adults aged 50 and older expressed the greatest amount of concern for health care costs that are not covered by insurance.
More than half (56%) said they were concerned or very concerned about those costs, which was higher than the percentage concerned about losing a spouse (49%).
Respondents were less concerned (“slightly concerned” or “not at all concerned”) about their children living far away, planning end-of life-directives, and falling or having reduced mobility.
A version of this article first appeared on WebMD.com.
a nonprofit hospice/advanced illness care organization based in Virginia.
Among the respondents, 41% said their health was very good or excellent.
However, the ratings differed largely by race, employment status, and income.
Employment status was also associated with a significant difference in the way people viewed their health at the top tier and bottom tier.
The middle tier (“good” health) was reported similarly (from 33% to 37%) whether a person was employed, retired, or not employed. However, employed respondents were much more likely to report they had “excellent” or “very good” health (51% vs. 44% for retirees and 21% for the not employed).
Conversely, those who were not employed were far more likely to report “fair” or “poor” health (45%) than those who were employed (13%) or retired (20%).
Similarly, respondents with incomes of less than $50,000 were three times more likely to report their health as “fair” or “poor” than were those with incomes of more than $100,000 (36% vs. 12%).
WebMD/CCH surveyed 3,464 U.S. residents ages 50 and older between Aug. 13 and Nov. 9, 2020. WebMD.com readers were randomly invited to take a 10-minute online survey.
Aging at home a priority
The survey also highlighted a strong preference for aging in place, says Steve Cone, chief of communications and philanthropy at CCH.
“More now than ever before, thanks to the COVID experience, baby boomers and their children really believe that’s the holy grail,” he says.
Mr. Cone notes that the quick spread of COVID-19 through some nursing homes early in the pandemic likely has strengthened people’s resolve to live out their lives in their own homes.
The survey indicated that 85% of people aged 50+ who are living in their own home, a family member’s home, or a loved one’s home responded that it is “very important” or “important” to stay in their home as they age.
When asked what services they would need to continue their living situation, the most common responses were housekeeping, home repair services, and transportation (listed as needs by 35% to 45% of respondents). Regarding changes they would have to make to feel safe in their home as they age, installing grab bars and/or safety rails in the bath/shower was the most popular answer (50%).
Use of telemedicine
Respondents were also asked about their acceptance of telemedicine, and 62% said they would be likely or very likely to engage in virtual visits with a doctor it in the future.
However, the likelihood varied by income level. Specifically, respondents with incomes over $100,000 were significantly more likely to say they would use telemedicine in the future than were those with incomes below $50,000 (74% vs. 60%). They were also more likely to already have used telemedicine.
Although respondents generally embraced telemedicine, they are less confident about some types of monitoring, according to Mr. Cone.
Emergency response (64%) was the leading type of remote monitoring respondents ages 50 and older would allow. Only a minority of respondents would allow the other types of monitoring asked about in the survey.
Close to one-quarter of respondents would not allow any type of monitoring.
Fewer than one-third would allow tracking of medication compliance, refrigerator use, sleep habits, or bathroom use.
People see monitoring of some movements as “Orwellian,” Mr. Cone says.
Knowledge of hospice
The survey findings support the need for more widespread use of hospice so people can stay in their homes as they age, Mr. Cone says.
When illness gets severe, “There’s no reason you have to get rushed to the emergency room or wind up in a hospital,” Mr. Cone says.
He notes that hospice and palliative care can come to patients wherever they reside – in their home, an assisted living center, a nursing home, or even a hospital room.
“That doesn’t mean the physician isn’t involved,” he says. “But working as a team, we can keep them in their homes and their lifestyle intact.”
Patients whose doctors attest that they are likely to live a maximum 6 months are eligible for hospice. But most families wait too long to long to start hospice or palliative care for a patient, Mr. Cone says, and may not be aware of what these services typically cover, including meal preparation and pet care.
In the survey, nearly one-third of respondents said they did not know that palliative care is something that “can be given at any stage of a serious illness” or “provides non-medical services (e.g., patient/family communication, help with insurance issues, scheduling appointments, arranging transportation).”
He notes palliative care and hospice are covered by Medicare and Medicaid and also by most private insurance plans or by individual companies providing the service.
However, health care providers may have to overcome a general reluctance to discuss hospice when sharing options for those severely ill.
The survey showed that while 51% of those 50 and older are at least “slightly interested” in learning more about hospice, a nearly equal number say they are “not at all interested” (49%).
Most using hospice are White
More than 90% of those surveyed reported that aspects of hospice care, including “comfort and relief from pain at the end of patients’ lives,” providing a dedicated care team, and an alternative to other care settings, are “very important” or “important.”
However, national hospice use rates are extremely low for minorities and the LGBTQ community, according to Mr. Cone. Among Medicare hospice recipients, 82% were white, 8.2% Black, 6.7% Hispanic, and 1.8% Asian or Pacific Islander, according to the National Hospice and Palliative Care Organization.
Those numbers signal a need for outreach to those communities with information on what services are available and how to access them, he says.
Health costs top concern
The survey also asked about level of concern regarding matters including family, health, financials, and end-of-life directives and found adults aged 50 and older expressed the greatest amount of concern for health care costs that are not covered by insurance.
More than half (56%) said they were concerned or very concerned about those costs, which was higher than the percentage concerned about losing a spouse (49%).
Respondents were less concerned (“slightly concerned” or “not at all concerned”) about their children living far away, planning end-of life-directives, and falling or having reduced mobility.
A version of this article first appeared on WebMD.com.
Postpartum depression affects dads, too
Michael W., a 38-year-old New Jersey–based attorney, and his wife had been excitedly planning for the birth of their baby and were overjoyed when she was born.
But after that, “I found that parenting a newborn was shockingly exhausting. I felt unprepared for the task, overwhelmed by the burden of the 24-hour-schedule and lack of sleep, and I struggled with feelings of inadequacy,” he said in an interview.
Michael never thought he had postpartum depression (PPD), perhaps because the condition is more commonly associated with women. But a study published in the American Journal of Men’s Health suggests that PPD also affects men.
A team of Danish investigators led by researcher Sarah Pedersen, of the department of public health, Aarhus University, extensively interviewed eight fathers with PPD and found their primary experiences involved feelings of being overwhelmed and powerless or inadequate, which sometimes turned into anger and frustration.
“I think one of the most important take-home messages is that practicing clinicians working with new parents should invite fathers to your consultations and engage the fathers as much as possible,” Ms. Pedersen said in an interview.
The findings also contained a message for parents, she says.
“I hope you will support each other and talk about your feelings and how you experience the transition to parenthood – know that it will take time to adjust to your new role,” she said.
Not enough attention
There’s been too little focus on fathers when it comes to PPD, according to Ms. Pedersen.
“During the last decade, several studies have examined the prevalence of PPD in men, and there is rising evidence that paternal PPD is associated with increased risk of long-term adverse behavioral and emotional outcomes in children,” she said.
Nevertheless, only three studies have been based on interviews with fathers who had personal experience with PPD.
“The purpose of our study was, first of all, to explore the lived experience of fathers who had PPD and, secondly, to gain deeper understanding of their help-seeking behavior – barriers to seeking help and facilitators of help-seeking,” Ms. Pedersen said.
The study was based on “semistructured” interviews with eight Danish fathers (ages 29-38 years) who had had PPD, none of whom had a previous history of depression.
All of them had received a formal diagnosis of PPD by a general practitioner or psychologist, and all had sought or received mental health care and considered themselves recovered from depression at the time of the interview.
The researchers used a technique called interpretative phenomenological analysis to analyze the interviews.
This method “aims to produce in-depth examinations of certain phenomena by examining how individuals make meaning of their own life experiences,” the authors wrote.
A ‘radical change’
Of the fathers, five described the period of pregnancy as a “time of happiness, full of positive expectations about fatherhood.”
But “the fathers’ great expectations were later replaced by a very different reality of fatherhood,” the authors wrote, noting that the transition to fatherhood was, in the words of one participant, a “radical change that you just can’t imagine.”
Most fathers expressed a feeling of being overwhelmed, and three felt unready for the task, which added to their depression.
“The participants wanted to be emotionally and physically present in their child’s life, but during the time of their depression, these kind-hearted intentions changed into feelings of guilt and inadequacy, as the participants did not feel they had enough energy and mental strength to become the kind of fathers they wanted to be,” the authors wrote.
The fathers mentioned stressors they believed contributed to their PPD, including complications during their partners’ pregnancies, unplanned cesarean birth (three fathers), the partners’ difficulties with breastfeeding (five fathers), and employment-related concerns. Five reported that their partners had postpartum emotional distress.
‘Masculine norms’
A second focus of the research was to examine fathers’ help-seeking behaviors, Ms. Pedersen said.
Ultimately, all the men sought formal help, either from their general practitioners or from a health visitor, with two seeking help right after birth.
Although the men were able to recognize changes in mood and behavior in retrospect, many did not regard them as signs of depression before their diagnosis.
Most had heard of PPD, but primarily as it affects women. Three sought information online about paternal PPD but couldn’t find any.
Four participants described experiencing PPD as “taboo,” based on a “combination of false beliefs, stigma, and masculine norms,” the authors stated, since men “are supposed to be big and strong and take care of everything, and suddenly you can’t.”
The authors reported that seven participants were screened for PPD or depression by a health care professional.
“The screening was an important part of the help-seeking process, as this was the first time two of the fathers were introduced to PPD,” the authors noted.
Although the screening “had the potential to spark conversation” about PPD, it was geared toward women, and some participants did not feel it was relevant to them.
“Future research should focus on identification of educational needs about paternal PPD among both parents, health care professionals, and other professionals taking care of new families,” Ms. Pedersen said.
Michael W. says it would have been helpful if someone had prepared him and his wife for what to expect, or if there had been some type of screening. Also, he advises expectant parents to “get some real-life experience by spending time around a newborn to see what’s involved.”
Different symptoms
“We often talk about mothers suffering from PPD, so it is more normalized for mothers to bring it up or for loved ones to ask mothers about how they are doing physically and psychologically after the birth,” Craig Garfield, MD, an attending physician and founder/director of Family and Child Health innovations at Ann and Robert H. Lurie Children’s Hospital, Chicago, said in an interview.
For fathers, “it is not discussed as commonly, so friends and families don’t often ask dads, and dads don’t know where to turn,” said Dr. Garfield, professor of pediatrics and medical social sciences at Northwestern University, Chicago. He was not involved with the study.
He noted that symptoms in fathers might differ from those of mothers.
“I have seen fathers who are anxious or more moody than they had been prior, or more angry, and I have seen fathers who throw themselves into work or begin drinking more – all related to changes in mood and depressive symptoms in the postnatal period,” he said.
Symptoms in men may last longer than in women. Dr. Garfield’s group published a study in which they surveyed 400 mothers and fathers of premature infants in the neonatal intensive care unit (NICU) about depressive symptoms around the time of NICU admission, at discharge home, and then after 30 days at home.
Roughly one-third of mothers screened positive for depressive symptoms around NICU admission, as did 17% of fathers. But the mothers’ depression scores improved by discharge and 30 days after being home, while the fathers’ remained “essentially unchanged,” he said.
“Further, we found that if doctors were to screen mothers and fathers during the NICU stay – at admission or even at discharge – that would greatly improve their ability to predict who would still have depressive symptoms 1 month after going home.”
Ms. Pedersen agrees that clinicians should incorporate screening for PPD into their practices and be proactive in encouraging fathers to get help.
“Keep pushing,” she advised, as “men rarely seek help, compared to women, in matters of mental health.”
A version of this article first appeared on WebMD.com.
Michael W., a 38-year-old New Jersey–based attorney, and his wife had been excitedly planning for the birth of their baby and were overjoyed when she was born.
But after that, “I found that parenting a newborn was shockingly exhausting. I felt unprepared for the task, overwhelmed by the burden of the 24-hour-schedule and lack of sleep, and I struggled with feelings of inadequacy,” he said in an interview.
Michael never thought he had postpartum depression (PPD), perhaps because the condition is more commonly associated with women. But a study published in the American Journal of Men’s Health suggests that PPD also affects men.
A team of Danish investigators led by researcher Sarah Pedersen, of the department of public health, Aarhus University, extensively interviewed eight fathers with PPD and found their primary experiences involved feelings of being overwhelmed and powerless or inadequate, which sometimes turned into anger and frustration.
“I think one of the most important take-home messages is that practicing clinicians working with new parents should invite fathers to your consultations and engage the fathers as much as possible,” Ms. Pedersen said in an interview.
The findings also contained a message for parents, she says.
“I hope you will support each other and talk about your feelings and how you experience the transition to parenthood – know that it will take time to adjust to your new role,” she said.
Not enough attention
There’s been too little focus on fathers when it comes to PPD, according to Ms. Pedersen.
“During the last decade, several studies have examined the prevalence of PPD in men, and there is rising evidence that paternal PPD is associated with increased risk of long-term adverse behavioral and emotional outcomes in children,” she said.
Nevertheless, only three studies have been based on interviews with fathers who had personal experience with PPD.
“The purpose of our study was, first of all, to explore the lived experience of fathers who had PPD and, secondly, to gain deeper understanding of their help-seeking behavior – barriers to seeking help and facilitators of help-seeking,” Ms. Pedersen said.
The study was based on “semistructured” interviews with eight Danish fathers (ages 29-38 years) who had had PPD, none of whom had a previous history of depression.
All of them had received a formal diagnosis of PPD by a general practitioner or psychologist, and all had sought or received mental health care and considered themselves recovered from depression at the time of the interview.
The researchers used a technique called interpretative phenomenological analysis to analyze the interviews.
This method “aims to produce in-depth examinations of certain phenomena by examining how individuals make meaning of their own life experiences,” the authors wrote.
A ‘radical change’
Of the fathers, five described the period of pregnancy as a “time of happiness, full of positive expectations about fatherhood.”
But “the fathers’ great expectations were later replaced by a very different reality of fatherhood,” the authors wrote, noting that the transition to fatherhood was, in the words of one participant, a “radical change that you just can’t imagine.”
Most fathers expressed a feeling of being overwhelmed, and three felt unready for the task, which added to their depression.
“The participants wanted to be emotionally and physically present in their child’s life, but during the time of their depression, these kind-hearted intentions changed into feelings of guilt and inadequacy, as the participants did not feel they had enough energy and mental strength to become the kind of fathers they wanted to be,” the authors wrote.
The fathers mentioned stressors they believed contributed to their PPD, including complications during their partners’ pregnancies, unplanned cesarean birth (three fathers), the partners’ difficulties with breastfeeding (five fathers), and employment-related concerns. Five reported that their partners had postpartum emotional distress.
‘Masculine norms’
A second focus of the research was to examine fathers’ help-seeking behaviors, Ms. Pedersen said.
Ultimately, all the men sought formal help, either from their general practitioners or from a health visitor, with two seeking help right after birth.
Although the men were able to recognize changes in mood and behavior in retrospect, many did not regard them as signs of depression before their diagnosis.
Most had heard of PPD, but primarily as it affects women. Three sought information online about paternal PPD but couldn’t find any.
Four participants described experiencing PPD as “taboo,” based on a “combination of false beliefs, stigma, and masculine norms,” the authors stated, since men “are supposed to be big and strong and take care of everything, and suddenly you can’t.”
The authors reported that seven participants were screened for PPD or depression by a health care professional.
“The screening was an important part of the help-seeking process, as this was the first time two of the fathers were introduced to PPD,” the authors noted.
Although the screening “had the potential to spark conversation” about PPD, it was geared toward women, and some participants did not feel it was relevant to them.
“Future research should focus on identification of educational needs about paternal PPD among both parents, health care professionals, and other professionals taking care of new families,” Ms. Pedersen said.
Michael W. says it would have been helpful if someone had prepared him and his wife for what to expect, or if there had been some type of screening. Also, he advises expectant parents to “get some real-life experience by spending time around a newborn to see what’s involved.”
Different symptoms
“We often talk about mothers suffering from PPD, so it is more normalized for mothers to bring it up or for loved ones to ask mothers about how they are doing physically and psychologically after the birth,” Craig Garfield, MD, an attending physician and founder/director of Family and Child Health innovations at Ann and Robert H. Lurie Children’s Hospital, Chicago, said in an interview.
For fathers, “it is not discussed as commonly, so friends and families don’t often ask dads, and dads don’t know where to turn,” said Dr. Garfield, professor of pediatrics and medical social sciences at Northwestern University, Chicago. He was not involved with the study.
He noted that symptoms in fathers might differ from those of mothers.
“I have seen fathers who are anxious or more moody than they had been prior, or more angry, and I have seen fathers who throw themselves into work or begin drinking more – all related to changes in mood and depressive symptoms in the postnatal period,” he said.
Symptoms in men may last longer than in women. Dr. Garfield’s group published a study in which they surveyed 400 mothers and fathers of premature infants in the neonatal intensive care unit (NICU) about depressive symptoms around the time of NICU admission, at discharge home, and then after 30 days at home.
Roughly one-third of mothers screened positive for depressive symptoms around NICU admission, as did 17% of fathers. But the mothers’ depression scores improved by discharge and 30 days after being home, while the fathers’ remained “essentially unchanged,” he said.
“Further, we found that if doctors were to screen mothers and fathers during the NICU stay – at admission or even at discharge – that would greatly improve their ability to predict who would still have depressive symptoms 1 month after going home.”
Ms. Pedersen agrees that clinicians should incorporate screening for PPD into their practices and be proactive in encouraging fathers to get help.
“Keep pushing,” she advised, as “men rarely seek help, compared to women, in matters of mental health.”
A version of this article first appeared on WebMD.com.
Michael W., a 38-year-old New Jersey–based attorney, and his wife had been excitedly planning for the birth of their baby and were overjoyed when she was born.
But after that, “I found that parenting a newborn was shockingly exhausting. I felt unprepared for the task, overwhelmed by the burden of the 24-hour-schedule and lack of sleep, and I struggled with feelings of inadequacy,” he said in an interview.
Michael never thought he had postpartum depression (PPD), perhaps because the condition is more commonly associated with women. But a study published in the American Journal of Men’s Health suggests that PPD also affects men.
A team of Danish investigators led by researcher Sarah Pedersen, of the department of public health, Aarhus University, extensively interviewed eight fathers with PPD and found their primary experiences involved feelings of being overwhelmed and powerless or inadequate, which sometimes turned into anger and frustration.
“I think one of the most important take-home messages is that practicing clinicians working with new parents should invite fathers to your consultations and engage the fathers as much as possible,” Ms. Pedersen said in an interview.
The findings also contained a message for parents, she says.
“I hope you will support each other and talk about your feelings and how you experience the transition to parenthood – know that it will take time to adjust to your new role,” she said.
Not enough attention
There’s been too little focus on fathers when it comes to PPD, according to Ms. Pedersen.
“During the last decade, several studies have examined the prevalence of PPD in men, and there is rising evidence that paternal PPD is associated with increased risk of long-term adverse behavioral and emotional outcomes in children,” she said.
Nevertheless, only three studies have been based on interviews with fathers who had personal experience with PPD.
“The purpose of our study was, first of all, to explore the lived experience of fathers who had PPD and, secondly, to gain deeper understanding of their help-seeking behavior – barriers to seeking help and facilitators of help-seeking,” Ms. Pedersen said.
The study was based on “semistructured” interviews with eight Danish fathers (ages 29-38 years) who had had PPD, none of whom had a previous history of depression.
All of them had received a formal diagnosis of PPD by a general practitioner or psychologist, and all had sought or received mental health care and considered themselves recovered from depression at the time of the interview.
The researchers used a technique called interpretative phenomenological analysis to analyze the interviews.
This method “aims to produce in-depth examinations of certain phenomena by examining how individuals make meaning of their own life experiences,” the authors wrote.
A ‘radical change’
Of the fathers, five described the period of pregnancy as a “time of happiness, full of positive expectations about fatherhood.”
But “the fathers’ great expectations were later replaced by a very different reality of fatherhood,” the authors wrote, noting that the transition to fatherhood was, in the words of one participant, a “radical change that you just can’t imagine.”
Most fathers expressed a feeling of being overwhelmed, and three felt unready for the task, which added to their depression.
“The participants wanted to be emotionally and physically present in their child’s life, but during the time of their depression, these kind-hearted intentions changed into feelings of guilt and inadequacy, as the participants did not feel they had enough energy and mental strength to become the kind of fathers they wanted to be,” the authors wrote.
The fathers mentioned stressors they believed contributed to their PPD, including complications during their partners’ pregnancies, unplanned cesarean birth (three fathers), the partners’ difficulties with breastfeeding (five fathers), and employment-related concerns. Five reported that their partners had postpartum emotional distress.
‘Masculine norms’
A second focus of the research was to examine fathers’ help-seeking behaviors, Ms. Pedersen said.
Ultimately, all the men sought formal help, either from their general practitioners or from a health visitor, with two seeking help right after birth.
Although the men were able to recognize changes in mood and behavior in retrospect, many did not regard them as signs of depression before their diagnosis.
Most had heard of PPD, but primarily as it affects women. Three sought information online about paternal PPD but couldn’t find any.
Four participants described experiencing PPD as “taboo,” based on a “combination of false beliefs, stigma, and masculine norms,” the authors stated, since men “are supposed to be big and strong and take care of everything, and suddenly you can’t.”
The authors reported that seven participants were screened for PPD or depression by a health care professional.
“The screening was an important part of the help-seeking process, as this was the first time two of the fathers were introduced to PPD,” the authors noted.
Although the screening “had the potential to spark conversation” about PPD, it was geared toward women, and some participants did not feel it was relevant to them.
“Future research should focus on identification of educational needs about paternal PPD among both parents, health care professionals, and other professionals taking care of new families,” Ms. Pedersen said.
Michael W. says it would have been helpful if someone had prepared him and his wife for what to expect, or if there had been some type of screening. Also, he advises expectant parents to “get some real-life experience by spending time around a newborn to see what’s involved.”
Different symptoms
“We often talk about mothers suffering from PPD, so it is more normalized for mothers to bring it up or for loved ones to ask mothers about how they are doing physically and psychologically after the birth,” Craig Garfield, MD, an attending physician and founder/director of Family and Child Health innovations at Ann and Robert H. Lurie Children’s Hospital, Chicago, said in an interview.
For fathers, “it is not discussed as commonly, so friends and families don’t often ask dads, and dads don’t know where to turn,” said Dr. Garfield, professor of pediatrics and medical social sciences at Northwestern University, Chicago. He was not involved with the study.
He noted that symptoms in fathers might differ from those of mothers.
“I have seen fathers who are anxious or more moody than they had been prior, or more angry, and I have seen fathers who throw themselves into work or begin drinking more – all related to changes in mood and depressive symptoms in the postnatal period,” he said.
Symptoms in men may last longer than in women. Dr. Garfield’s group published a study in which they surveyed 400 mothers and fathers of premature infants in the neonatal intensive care unit (NICU) about depressive symptoms around the time of NICU admission, at discharge home, and then after 30 days at home.
Roughly one-third of mothers screened positive for depressive symptoms around NICU admission, as did 17% of fathers. But the mothers’ depression scores improved by discharge and 30 days after being home, while the fathers’ remained “essentially unchanged,” he said.
“Further, we found that if doctors were to screen mothers and fathers during the NICU stay – at admission or even at discharge – that would greatly improve their ability to predict who would still have depressive symptoms 1 month after going home.”
Ms. Pedersen agrees that clinicians should incorporate screening for PPD into their practices and be proactive in encouraging fathers to get help.
“Keep pushing,” she advised, as “men rarely seek help, compared to women, in matters of mental health.”
A version of this article first appeared on WebMD.com.