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Migraine device expands treatment possibilities
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AUSTIN, TEX – Migraine treatment and prevention is challenging in any population, but some present even more difficulties. Pregnant women and pediatric patients are two such groups where physicians and patients may be hesitant to use drugs.
Neuromodulation devices are proven alternatives to medical interventions, and the remote electrical neuromodulation device Nerivio (Theranica) was cleared by the Food and Drug Administration for acute treatment of migraine patients aged 12 and over in 2021. In March 2023, the agency expanded the clearance to include prevention of migration in adolescents aged 12 and over as well as adults.
Two studies presented at the annual meeting of the American Headache Society showed The latter study yielded similar findings to adults and was used by FDA in its decision to expand the device’s indication in adolescents in 2023, according to Teshamae Monteith, MD, who presented the study at a poster session.
The device, worn on the arm, allows the user to modulate the intensity of the stimulation so that it activates nociceptive pain receptors, but not in a painful way. “Each [patient] raises the intensity until it feels strong, yet comfortable, and when that happens, they activate the nociceptive receptors and the arm sends a signal all the way back up to the brainstem, where the pain control area is. Activating it causes the release of neurotransmitters that inhibit pain. That inhibition is a global pain inhibition mechanism, which causes inhibition of the migraine pain, and also the symptoms associated with migraine like photophobia and vomiting,” said Alit Stark-Inbar, PhD, who presented the study of treatment of pregnant women during a poster session.
Declining treatment days over time in adolescents
Dr. Monteith’s team studied high-frequency remote electrical neuromodulation device use in adolescents who had migraine on 10 days or more per month. They also required at least three treatment days in months 2 and 3 to control for the possibility that patients might stop using the device because they couldn’t afford it or for some reason other than efficacy or because their migraines went away.
The study included 83 adolescents aged 12-17 (mean, 15.9 years, 89% female). In the first month of use, the mean number of migraine treatment days was 12.6, which dropped to 9.0 in month 2 (P < .001), and 7.4 in month 3 (P < .001 from month 2). At 2 hours after treatment, 61.9% had pain relief, 24.5% had freedom from pain, 67.4% had functional disability relief, and 41.3% had functional disability freedom.
“It parallels the findings of the randomized, sham-controlled study in adults. The safety profile was excellent with just one person complaining of minor discomfort of the arm that resolved after treatment. The combination of the exceedingly safe profile and the likelihood of efficacy based on using monthly migraine treatment days as a proxy, the FDA decided to clear this for an adolescent indication,” said Dr. Monteith, associate professor of clinical neurology and chief of the headache division at the University of Miami.
The device design is convenient, according to Dr. Monteith. “The arm is just an easy place to stimulate. It’s a wearable device, and it’s 45 minutes [of treatment] and it’s app controlled. You know adolescents like their technology. They can track their symptoms here, and there’s some biobehavioral power to this because they can do biobehavioral exercises in addition to receiving the simulation,” she said.
The fact that the device is discrete is also an advantage for adolescents in school. “You have to go to the nurse to get your medication versus a device, you can just put it on, it’s easy, no one sees it, and no one’s making fun of you,” said Dr. Monteith.
Advantages for adolescents
The device offers a useful alternative to medication, according to Alan M. Rapoport, MD, who was asked for comment on the adolescent study. “I’d rather not give medication and certainly not preventive medication to an adolescent,” he said. He noted that over-the-counter acute care migraine medications such as aspirin or acetaminophen and combination medications with caffeine, as well as prescription medications such as triptans, “all have possible side effects, and when used to an increased extent can even cause medication overuse headache, increasing the severity and frequency of headache and migraine days per month,” Dr. Rapoport said. Using an effective device with almost no side effects is preferable to any of these acute care medications, especially if there are several headaches a month,” he said. Some newer medications that block calcitonin gene-related peptide might be quite effective when they are approved for adolescents, and should have few adverse events, he added.
In the past, Dr. Rapoport has favored biofeedback training for acute and especially preventive treatment of migraine in adolescents. “[Remote electrical neuromodulation] seems to do just as well, children enjoy it, and it’s easier for a patient to do at home,” said Dr. Rapoport.
Biofeedback training is usually taught to patients by a PhD psychologist. Once the patients have been on the biofeedback equipment and learn the techniques, they can practice on their own at home without equipment. “This new device treatment using Nerivio for acute care and prevention of migraine in adults and children 12 and older, where they can easily apply the device in almost any situation, whether they are at home or possibly even in school or out and about, looks very promising,” said Dr. Rapoport. It is quite effective and has almost no adverse events, which is what you really want, especially for adolescents,” he said.
Also asked to comment on the study of remote electrical neuromodulation use in adolescents, Abraham Avi Ashkenazi, MD, director of the Headache Clinic at Shaare Zedek Medical Center in Jerusalem, who attended the session, was enthusiastic, and said he has begun using it in his own practice. “It shows that remote electrical neuromodulation can not only be effective for the acute migraine attack, but also has a potential preventive effect on future migraine attacks. [This] actually makes sense, because we know that the more migraine attacks a person has, the more likely they are to progress to a more chronic form of the disease,” he said in an interview.
Asked what distinguishes REN from other neuromodulation therapies such as vagus nerve stimulation or transcranial magnetic stimulation (TMS), Dr. Ashkenazi said: “It’s just a different way of modulating the brain system via a different mechanism. In both ways, though, the advantage is that there are literally no adverse effects, as opposed to drug treatment.”
An alternative during pregnancy
Adolescents aren’t the only population where there is reluctance to use medication. Physicians have been prescribing the device for pregnant women, who are reluctant to take medication due to concerns effects on the fetus. However, pregnant women were not included in the pivotal studies. “They expect it to be safe. This study was done in order to validate that assumption. We reached out to women who either used the device during pregnancy or women from the same database who started it using afterwards, but did not use it during the pregnancy,” said Dr. Stark-Inbar, vice president of medical information at Theranica.
The study included 140 women, 59 in the remote electrical neuromodulation device group and 81 controls. The primary endpoint was gestational age, which was 38 weeks and 5 days in the remote electrical neuromodulation device group and 39 weeks among controls (P = .150). There were no significant between-group differences with respect to newborn birth weight, miscarriage rate, preterm birth rate, birth defect rate, developmental milestone rate, or emergency department visit rate.
Dr. Monteith and Dr. Ashkenazi have no relevant financial disclosures. Dr. Rapoport advises AbbVie, Biohaven, Cala Health, Dr. Reddy’s, Pfizer, Satsuma, Teva Pharmaceutical Industries, and Theranica. He is on the speakers bureau of AbbVie, Dr. Reddy’s, Impel, Pfizer and Teva Pharmaceutical Industries. Dr. Rapoport is the editor-in-chief of Neurology Reviews and on the editorial board of CNS Drugs.
AT AHS 2023
Combo treatment eases nausea and vomiting of pregnancy
. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
. While the benefit of either agent was clinically small for moderate to severe symptoms, the combination showed numerically larger and potentially more meaningful benefit, according to a team led by Xiao-Ke Wu, MD, PhD, of the department of obstetrics and gynecology at First Affiliated Hospital, Heilongjiang University of Chinese Medicine, and Heilongjiang Provincial Hospital in Harbin, China.
The treatments found small reductions in symptoms of less than one point to 1.6 points on an emesis scale. Nevertheless, Dr. Wu’s group wrote online June 19 in Annals of Internal Medicine that the finding “is especially significant because there is a pressing need to establish a pregnancy-safe treatment regimen and an integrative guideline for managing severe NVP.”
NVP affects as many as 85% of pregnant women, 80%-90% of whom have only mild symptoms, the authors noted. However, severe NVP and hyperemesis gravidarum, or HG, develop in about 10%. “Unfortunately, as many as 10% of wanted pregnancies with severe NVP or HG are terminated because of intolerable and untreatable symptoms and complications,” Dr. Wu told this news organization. And antiemetics may be underprescribed by general practitioners because of concerns about potential teratogenic effects, he said.
“Our findings suggest that either acupuncture or doxylamine-pyridoxine alone is a suitable for treating moderate to severe NVP, and a combination of both can be used to treat severe NVP and HG,” Dr. Wu said.
Commenting on the study but not involved in it, Catherine S. Stika, MD, a clinical professor of ob.gyn. at Northwestern University in Chicago, said the results suggest these two therapies are more suited to mild than severe symptoms. “But an RCT is important to do in order to support the use of these therapies since they’re not as widely accepted as they ought to be,” she said in an interview.
According to Dr. Stika, many pregnant women are reluctant to take drugs at all or participate in drug studies, “so the combination of nonpharmaceutical/pharmaceutical treatment might be a bit more appealing.” She noted that some women have such severe nausea they are literally starving and so weak they are bedridden or even hospitalized.
Both treatments have been recommended for some time, and the American College of Obstetricians and Gynecologists’ 2018 practice bulletin recommends acupuncture for mild nausea.
Design
The randomized, double-blind, placebo-controled 2x2 factorial trial was conducted at 13 tertiary-care hospitals in mainland China from June 2020 to February 2022. The researchers recruited 352 women in early pregnancy with moderate to severe NVP. The mean age of participants was about 29 years and the mean gestational age was about 9 weeks.
Participants were randomized into four 14-day treatment groups: active acupuncture for 30 minutes a day plus the antihistamine-vitamin B6 agent doxylamine-pyridoxine; sham acupuncture for 30 minutes daily plus doxylamine-pyridoxine; active acupuncture plus placebo; and sham acupuncture plus placebo.
The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at day 15 relative to baseline with a score of less than 6 indicating mild NVP, 6-12 indicating moderate NVP, and 13 or higher indicating severe NVP. Secondary outcomes ranged from quality of life and adverse events to maternal and perinatal complications. Acupuncture and combined treatment yielded larger though still small reductions in PUQE score, compared with control treatments. The mean differences were as follows: acupuncture, –.07; 95% confidence interval, 1.3-0.1); doxylamine-pyridoxine, –1.0: 95% CI, 1.6-0.4); combination of both, –1.6; 95% CI, 2.2-0.9). No significant interaction was detected between the interventions (P = .69).Compared with placebo treatments, pharmaceutical therapy resulted in more somnolence, while active acupuncture led to more frequent dyspnea, bruising, itching, and pain. A higher risk of babies born small for gestational age was observed in mothers who took doxylamine-pyridoxine versus placebo: odds ratio, 3.8; 95% CI, 1-14.1). Neither the placebo effects of the sham interventions nor the natural regression of symptoms experienced by many women were evaluated.
Suited to milder symptoms?
Dr. Stika called the study well-designed and well-written but cited several limitations, including the small cohort, the minor symptom improvement, and the lack of a comparator group receiving neither sham nor active treatment.
“Compared with sham combination treatments, the active combination arm was only about a point and a half better,” she said. “And would some women have got better over the 2 weeks anyway with no intervention at all? A large percentage of women with NVP do improve on their own.”
And in terms of acceptability to U.S. women, she cautioned, “The study cohort was entirely Chinese, and this is a population that already accepts acupuncture treatment.”
Countered Dr. Wu, “Medical care provided by licensed acupuncturists is approved in many countries. Certainly, it is ready to be prescribed by physicians when a pregnant patient is seeking NVP treatment.”
Dr. Stika stressed that these therapies are suited to milder NV, and would “barely take edge off severe symptoms,” for which a patient might have to “go up to a big gun like the antiemetic Zofran” (ondansetron). She is currently involved in a National Institutes of Health–funded clinical trial of the antidepressant mirtazapine (Remeron) for NVP.
Matthew Carroll, MD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, noted that doxylamine-pyridoxine is already an effective treatment for NVP, but in his experience it is often "not enough" to help patients deal with symptoms.
"Many patients are hesitant to take additional medications," he said. "If acupuncture can be safely done in pregnancy, then it seems a reasonable option as an adjuvant treatment for NVP. I think there is a cohort of pregnant people in the US who would be excited to try a complementary and nonpharmaceutical treatment option. Unfortunately, complementary therapies are rarely evaluated at a systems level for safety and so they are hard to recommend for obstetricians in the US," he added.
Dr. Carroll, who was not involved in the study. noted that "studies like this can help us counsel patients who may be seeking these treatments even if not approved or recommended by ACOG."
This study was funded by the National Key R&D Program of China and the Project of Heilongjiang Province “TouYan” Innovation Team. Support also came from the National Clinical Research Base of Chinese Medicine, the Heilongjiang Provincial Clinical Research Centre for Ovary Diseases, and the 2023 Capability Improvement Project for Evidence-based Assessment of Traditional Chinese Medicine.
Study coauthor Ben Willem J. Mol, MD, PhD, reported consulting fees from ObsEva and Merck and travel fees from Merck.
Dr. Stika and Dr. Carroll had no competing interests to disclose.
FROM ANNALS OF INTERNAL MEDICINE
A ‘one-stop shop’: New guidance on hormones and aging
The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.
The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.
“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.
During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”
The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.
“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
Not designed to be read all at once
In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.
“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.
In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.
Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”
“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.
However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.
“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”
During the briefing, Dr. Cappola noted that the document need not be read all at once.
“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.
Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.
The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.
“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.
During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”
The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.
“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
Not designed to be read all at once
In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.
“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.
In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.
Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”
“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.
However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.
“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”
During the briefing, Dr. Cappola noted that the document need not be read all at once.
“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.
Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The idea of the statement “is to be complete, but also to clarify some misunderstandings. ...We tried to be very clear in the language about what we know, where we can go, where we shouldn’t go, and what we still need to learn,” statement coauthor Cynthia A. Stuenkel, MD, of the University of California, San Diego, said in an interview.
The document is divided into nine parts or axes: growth hormone, adrenal, ovarian, testicular, thyroid, osteoporosis, vitamin D deficiency, type 2 diabetes, and water metabolism. Each section covers natural history and observational data in older individuals, available therapies, clinical trial data on efficacy and safety in older individuals, bulleted “key points,” and research gaps.
“Hormones and Aging: An Endocrine Society Scientific Statement” was presented at the annual meeting of the Endocrine Society and published online in the Journal of Clinical Endocrinology & Metabolism.
During a press briefing, writing group chair Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia, said the goal is to “provide a really concise summary across each of these areas. ... There are multiple hormonal changes that occur with age, so we really couldn’t limit ourselves to just one gland or the few that we commonly think about. We wanted to cover all the axes.”
The statement tackles several controversial areas, including hormone therapy for menopausal symptoms in women and hypogonadal symptoms in men, diabetes treatment goals in older adults, distinguishing between age-associated changes in thyroid function and early hypothyroidism, and vitamin D supplementation in older adults.
“Hormones have these almost mythical qualities to some people. ... ‘If I just had my hormones back the way they were, it would all work out.’ What we want to do is make sure that patients are being treated appropriately and that their symptoms are being heard and managed and ascribed to the appropriate problems and not necessarily to hormonal problems when they are not. ... Part of what we need to do is [provide] the evidence that we have, which includes evidence of when not to prescribe as well as [when] to prescribe,” Dr. Cappola said.
Not designed to be read all at once
In the menopause section, for example, one “key point” is that menopausal symptoms are common, vary in degree and bother, and can be effectively treated with a variety of therapies proven effective in randomized clinical trials. Another key point is that menopausal hormone therapy is safest for women who are younger than 60 years and less than 10 years since starting menopause.
“It’s almost 20 years since the original Women’s Health Initiative, and that led to an incredible falloff of prescribing hormone therapy and a falloff in teaching of our students, residents, fellows, and practitioners about [menopausal] hormone therapy. ... Hopefully, by issuing this kind of aging statement it gets people to read, think, and learn more. And, hopefully, we can improve the education of physicians. ... Menopause is a universal experience. Clinicians should know about it,” noted Dr. Stuenkel, who chaired the menopause section writing panel.
In the type 2 diabetes section, in the bullet points it is noted that oral glucose tolerance testing may reveal abnormal glucose status in older adults that are not picked up with hemoglobin A1c or fasting glucose levels and that glycemic targets should be individualized.
Asked to comment on the statement, Michele Bellantoni, MD, said: “This was a huge undertaking because there are so many areas of expertise here. I thought they did a very good job of reviewing the literature and showing each of the different hormonal axes. ... It’s a good go-to review.”
“I thought it was a very good attempt to catalog and provide opportunities for policy, and particularly at [the National Institutes of Health], as they look at funding to show where are these gaps and to support appropriate research. I think the most important aspect to come of this is identifying research gaps for funding opportunities. I very much support that,” noted Dr. Bellantoni, who is clinical director of the division of geriatric medicine at Johns Hopkins University, Baltimore.
However, she also said that the 40-page document might be a bit much for busy clinicians, despite the bullet points at the end of each section.
“I would love to see an editorial that puts into perspective the take-home messages or a subsequent article that distills this into every day practice of care of older adults, both preventative and treatment care. ... I think that would be so useful.”
During the briefing, Dr. Cappola noted that the document need not be read all at once.
“It ended up being a large document, but you should not be intimidated by it because each section is only about 2,000 words. So, it’s really a kind of one-stop shop to be able to look across all these axes at once. We also wanted people to think about the common themes that occur across all these axes when considering what’s going on right now and for future research,” she said.
Dr. Stuenkel, Dr. Cappola, and Dr. Bellantoni reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ENDO 2023
A new nonhormonal option for menopausal hot flashes: What prescribers should know
This transcript has been edited for clarity.
Hello. I am Dr. JoAnn Pinkerton, professor of obstetrics and gynecology at the University of Virginia and a North American Menopause Society–credentialed menopause specialist.
I am excited to tell you about a brand-new, just-approved non-estrogen therapy for treatment of menopausal symptoms. . The manufacturer, Astellas, is expected to make fezolinetant available at pharmacies before the end of this year. This medication binds to and blocks the neurokinin 3 (NK3) receptor, which plays a role in regulating body temperature, leading to a reduction in hot flashes.
For women suffering from frequent moderate to severe hot flashes, fezolinetant is an exciting breakthrough in women’s health as it is a highly effective nonhormonal treatment that reduces hot flashes and improves quality of life.
In two phase 3 clinical trials (Johnson et al. and Lederman et al.), fezolinetant 45 mg reduced the frequency of vasomotor symptoms by about 65%, significantly more than placebo, and similar to the 75% reduction seen with hormone therapy. Fezolinetant’s efficacy becomes evident within 1 week, reducing both frequency and severity of hot flashes.
With respect to side effects, 1%-2% of the menopausal women participating in clinical trials reported adverse events, including headaches, abdominal pain, diarrhea, insomnia, back pain, hot flushes, and reversible elevated hepatic transaminases. Serious adverse events were infrequent.
Subgroup analysis of data presented at ACOG’s 2023 annual meeting noted fezolinetant’s effectiveness among diverse populations, including White or Black race, body mass index of 30 or higher, those younger or older than age 55, smokers, former smokers, and never smokers, in U.S. as well as in European trial participants.
With respect to safety, a 52-week placebo-controlled safety trial confirmed safety for this time period. Adverse effects on the endometrium were neither seen nor expected, as fezolinetant is a centrally acting non–estrogen-containing medication. In addition, no loss of bone density was seen.
Prior trials of neurokinin receptor antagonists suggested the potential for hepatotoxicity. Increases in ALT or AST noted in one of the phase 3 trials of fezolinetant were described as asymptomatic, isolated, intermittent, or transient and returned to baseline during treatment or after discontinuation. However, the FDA placed a warning about liver injury potential. Package labeling recommends baseline liver function tests before starting fezolinetant and at 3, 6, and 9 months. In addition, concomitant use of moderate CYP1A2 inhibitors, including many antidepressants and cimetidine, should be avoided.
As with other recently approved medications, I am concerned that high cost could prevent appropriate candidates from having access.
Until now, the FDA had approved only one nonhormone therapy for vasomotor symptoms, 7.5 mg paroxetine salt. However, neither this formulation nor off-label use of other SSRIs, SNRIs, gabapentinoids, oxybutynin, or clonidine are as effective as hormone therapy or fezolinetant for moderate to severe vasomotor symptoms.
For women with bothersome menopausal hot flashes who can’t or choose not to use hormone therapy, including those with estrogen-sensitive breast or uterine cancers, fezolinetant offers a much-needed, highly effective, safe, nonhormone/non-estrogen option to treat their hot flashes.
The FDA approved it for treating vasomotor symptoms of menopause (hot flashes and night sweats) but it also appears to improve sleep disruption, mood, and quality of life.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. I am Dr. JoAnn Pinkerton, professor of obstetrics and gynecology at the University of Virginia and a North American Menopause Society–credentialed menopause specialist.
I am excited to tell you about a brand-new, just-approved non-estrogen therapy for treatment of menopausal symptoms. . The manufacturer, Astellas, is expected to make fezolinetant available at pharmacies before the end of this year. This medication binds to and blocks the neurokinin 3 (NK3) receptor, which plays a role in regulating body temperature, leading to a reduction in hot flashes.
For women suffering from frequent moderate to severe hot flashes, fezolinetant is an exciting breakthrough in women’s health as it is a highly effective nonhormonal treatment that reduces hot flashes and improves quality of life.
In two phase 3 clinical trials (Johnson et al. and Lederman et al.), fezolinetant 45 mg reduced the frequency of vasomotor symptoms by about 65%, significantly more than placebo, and similar to the 75% reduction seen with hormone therapy. Fezolinetant’s efficacy becomes evident within 1 week, reducing both frequency and severity of hot flashes.
With respect to side effects, 1%-2% of the menopausal women participating in clinical trials reported adverse events, including headaches, abdominal pain, diarrhea, insomnia, back pain, hot flushes, and reversible elevated hepatic transaminases. Serious adverse events were infrequent.
Subgroup analysis of data presented at ACOG’s 2023 annual meeting noted fezolinetant’s effectiveness among diverse populations, including White or Black race, body mass index of 30 or higher, those younger or older than age 55, smokers, former smokers, and never smokers, in U.S. as well as in European trial participants.
With respect to safety, a 52-week placebo-controlled safety trial confirmed safety for this time period. Adverse effects on the endometrium were neither seen nor expected, as fezolinetant is a centrally acting non–estrogen-containing medication. In addition, no loss of bone density was seen.
Prior trials of neurokinin receptor antagonists suggested the potential for hepatotoxicity. Increases in ALT or AST noted in one of the phase 3 trials of fezolinetant were described as asymptomatic, isolated, intermittent, or transient and returned to baseline during treatment or after discontinuation. However, the FDA placed a warning about liver injury potential. Package labeling recommends baseline liver function tests before starting fezolinetant and at 3, 6, and 9 months. In addition, concomitant use of moderate CYP1A2 inhibitors, including many antidepressants and cimetidine, should be avoided.
As with other recently approved medications, I am concerned that high cost could prevent appropriate candidates from having access.
Until now, the FDA had approved only one nonhormone therapy for vasomotor symptoms, 7.5 mg paroxetine salt. However, neither this formulation nor off-label use of other SSRIs, SNRIs, gabapentinoids, oxybutynin, or clonidine are as effective as hormone therapy or fezolinetant for moderate to severe vasomotor symptoms.
For women with bothersome menopausal hot flashes who can’t or choose not to use hormone therapy, including those with estrogen-sensitive breast or uterine cancers, fezolinetant offers a much-needed, highly effective, safe, nonhormone/non-estrogen option to treat their hot flashes.
The FDA approved it for treating vasomotor symptoms of menopause (hot flashes and night sweats) but it also appears to improve sleep disruption, mood, and quality of life.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hello. I am Dr. JoAnn Pinkerton, professor of obstetrics and gynecology at the University of Virginia and a North American Menopause Society–credentialed menopause specialist.
I am excited to tell you about a brand-new, just-approved non-estrogen therapy for treatment of menopausal symptoms. . The manufacturer, Astellas, is expected to make fezolinetant available at pharmacies before the end of this year. This medication binds to and blocks the neurokinin 3 (NK3) receptor, which plays a role in regulating body temperature, leading to a reduction in hot flashes.
For women suffering from frequent moderate to severe hot flashes, fezolinetant is an exciting breakthrough in women’s health as it is a highly effective nonhormonal treatment that reduces hot flashes and improves quality of life.
In two phase 3 clinical trials (Johnson et al. and Lederman et al.), fezolinetant 45 mg reduced the frequency of vasomotor symptoms by about 65%, significantly more than placebo, and similar to the 75% reduction seen with hormone therapy. Fezolinetant’s efficacy becomes evident within 1 week, reducing both frequency and severity of hot flashes.
With respect to side effects, 1%-2% of the menopausal women participating in clinical trials reported adverse events, including headaches, abdominal pain, diarrhea, insomnia, back pain, hot flushes, and reversible elevated hepatic transaminases. Serious adverse events were infrequent.
Subgroup analysis of data presented at ACOG’s 2023 annual meeting noted fezolinetant’s effectiveness among diverse populations, including White or Black race, body mass index of 30 or higher, those younger or older than age 55, smokers, former smokers, and never smokers, in U.S. as well as in European trial participants.
With respect to safety, a 52-week placebo-controlled safety trial confirmed safety for this time period. Adverse effects on the endometrium were neither seen nor expected, as fezolinetant is a centrally acting non–estrogen-containing medication. In addition, no loss of bone density was seen.
Prior trials of neurokinin receptor antagonists suggested the potential for hepatotoxicity. Increases in ALT or AST noted in one of the phase 3 trials of fezolinetant were described as asymptomatic, isolated, intermittent, or transient and returned to baseline during treatment or after discontinuation. However, the FDA placed a warning about liver injury potential. Package labeling recommends baseline liver function tests before starting fezolinetant and at 3, 6, and 9 months. In addition, concomitant use of moderate CYP1A2 inhibitors, including many antidepressants and cimetidine, should be avoided.
As with other recently approved medications, I am concerned that high cost could prevent appropriate candidates from having access.
Until now, the FDA had approved only one nonhormone therapy for vasomotor symptoms, 7.5 mg paroxetine salt. However, neither this formulation nor off-label use of other SSRIs, SNRIs, gabapentinoids, oxybutynin, or clonidine are as effective as hormone therapy or fezolinetant for moderate to severe vasomotor symptoms.
For women with bothersome menopausal hot flashes who can’t or choose not to use hormone therapy, including those with estrogen-sensitive breast or uterine cancers, fezolinetant offers a much-needed, highly effective, safe, nonhormone/non-estrogen option to treat their hot flashes.
The FDA approved it for treating vasomotor symptoms of menopause (hot flashes and night sweats) but it also appears to improve sleep disruption, mood, and quality of life.
A version of this article first appeared on Medscape.com.
PCOS associated with shorter lifespan
CHICAGO –
In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.
PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.
“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.
“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.
Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”
And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.
Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”
“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”
Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.
He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”
Women with PCOS lose a year of life
The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.
The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).
Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).
In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).
One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.
Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.
CHICAGO –
In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.
PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.
“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.
“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.
Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”
And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.
Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”
“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”
Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.
He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”
Women with PCOS lose a year of life
The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.
The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).
Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).
In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).
One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.
Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.
CHICAGO –
In the study, involving nearly 10,000 women with PCOS and matched controls from Finland, women with PCOS died on average a year earlier than their age-matched counterparts, primarily from diseases of the circulatory system, cancer, and diabetes.
PCOS is the most common endocrine disorder of reproductive-age women, of whom about 50%-70% also have obesity.
“I think we need to acknowledge that this is a health burden and not just a reproductive problem. In many cases we deal with the reproductive problem, and then these women are left alone. … So I think the message is we need to look beyond the reproductive outcomes, which are … really good. We can manage that,” said Terhi T. Piltonen, MD, PhD, during a press briefing held June 15 at the annual meeting of the Endocrine Society.
“I think the difficult part is [managing] the lifelong health for these women and supporting them to achieve the best health they can get. We need a multidisciplinary effort and to put more resources into the research,” added Dr. Piltonen, professor in the departments of ob.gyn. and reproductive endocrinology at the University of Oulu, Finland.
Indeed, Punith Kempegowda, MD, PhD, of the University of Birmingham (England) observed: “In our medical schools in the U.K., over 5 years, students get 45 minutes [of education] on PCOS, and they’re expected to learn about it.”
And over the last 20 years, funding for research into the condition has totaled less than a half percent of overall medical funding. “And we’re talking about 10% of all women. …We need to acknowledge it and educate people more. We need more published studies to understand more about it,” he noted.
Asked to comment, Greg Dodell, MD, owner and president of Central Park Endocrinology, New York, said: “PCOS is about a lot more than fertility, and that may not be the goal or on the mind of a woman at the time they start having symptoms of PCOS or get the diagnosis.”
“PCOS is largely a metabolic condition rooted in insulin resistance, and therefore, the potential clinical outcomes, including mortality, are important to recognize.”
Dr. Dodell, who has a special interest in PCOS, advised that, for women with the condition, “focus on reducing insulin resistance with health-promoting behaviors and medications as needed. Data demonstrate that improving fitness, irrespective of a change in weight, can improve metabolic markers.” And, he advised that these women be routinely screened for mental health issues.
He also noted, “PCOS occurs across the size spectrum, but those patients in larger bodies may face weight stigma which has negative health consequences. These patients may avoid going to doctors for routine health screenings, so it is an important issue to continue to address.”
Women with PCOS lose a year of life
The new data come from 9,839 women with PCOS and 70,705 age- and region-matched controls from the Finnish Care Register for Health Care. The group with PCOS had been diagnosed at a mean age of 27 years.
The mean follow-up time was 13.1 years in both groups, during which 1,003 controls and 177 women with PCOS died. The mean age at death was 51.4 years for the PCOS group versus 52.6 years for the control women, a significant difference (P < .001).
Causes of death that were significantly higher among the women with PCOS versus controls after adjustments were cancer (hazard ratio, 1.39), and diseases of the circulatory system (1.68).
In more specific subcategories, after adjustment for education, the women with PCOS had increased mortality from nonischemic diseases, such as hypertensive heart disease, pulmonary embolism, etc. (HR, 2.06), and diabetes (HR, 2.85).
One study limitation was the inability to adjust for body mass index, Dr. Piltonen noted.
Dr. Piltonen, Dr. Kempegowda, and Dr. Dodell have no disclosures.
AT ENDO 2023
Did ob.gyn. residencies take a hit from abortion bans?
Emilee Gibson, MD, recently graduated from Southern Illinois University, Springfield, and starts her ob.gyn. residency at Vanderbilt University Medical Center in Nashville, Tenn., later this month. Abortion is permitted in Illinois but banned in Tennessee, a factor she weighed cautiously when she applied for residencies.
Dr. Gibson told this news organization that medical students, not just those interested in ob.gyn., are starting to think more about what it means to move to a state where it might be difficult to access abortion care. “Just from a personal standpoint, that’s a little scary.”
The Supreme Court’s decision to overturn Roe v. Wade abortion rights last June threatened to derail ob.gyns. in training from pursuing the specialty or locating in states that have banned or limited abortion.
, but some industry leaders, residents, and medical students say it may be too early to judge the full impact of the ruling because most students were already far along in their decision and application for a 2023 residency position.
At this point, some ob.gyn. students are planning careers on the basis of whether they have family ties in a particular state, whether limiting their search might hurt their potential to match in a competitive specialty, and whether their faith in the family planning and abortion training being offered by a program outweighs the drawbacks of being in a state with abortion bans or restrictions.
Lucy Brown, MD, a recent graduate of Indiana University, Indianapolis, said in an interview that she’d be “very nervous” about living and practicing in abortion-restricted Indiana if she were ready to start a family.
Dr. Brown said that she mostly limited applications in the recent Match to ob.gyn. residencies in states that protected abortion rights. Though she applied to a program in her home state of Kentucky, she noted that it – along with a program in Missouri – was very low on her rank list because of their abortion restrictions.
Ultimately, Dr. Brown matched at Johns Hopkins University, Baltimore, where she will receive abortion training and assist with abortions throughout her residency. Maryland’s abortion rights status was a big attraction, she said. “Abortion is integrated into every aspect of the education.”
By the numbers
For students applying to residencies this summer, evaluating the state legislative landscape is a little clearer than it was 1 year ago but is still evolving. As of June 1, 56 ob.gyn. residency programs and more than 1,100 medical residents are in states with the most restrictive bans in the country (19% of all programs), according to the Bixby Center for Reproductive Health at the University of California, San Francisco.
In terms of the latest abortion laws: 14 states banned abortion, 2 states banned abortion between 6 and 12 weeks, and 9 states banned abortion between 15 and 22 weeks, whereas abortion is legal in 25 states and Washington, according to a recent analysis by the Kaiser Family Foundation.
The impact on residencies? The Association of American Medical Colleges recently reported a 2% drop in the number of U.S. MD seniors who applied to residencies and a 5% decline in the number of seniors who applied to ob.gyn. residencies. In states where abortion was banned, the number of senior applicants to ob.gyn. programs dropped by more than 10%, according to AAMC’s Research and Action Institute.
“U.S. MD seniors appear, in general, more likely to avoid states where abortions are banned,” said Atul Grover, MD, PhD, executive director of the Research and Action Institute. “That’s a big difference between states where there are abortion bans and gestational limits and states with no bans or limits; it’s almost twice as large,” Dr. Grover said in an interview. “The question is: Was it a 1-year blip or something that will be the beginning of a trend?”
In a statement to this news organization, officials from the American College of Obstetricians and Gynecologists and the Association of Professors of Gynecology and Obstetrics said that they were aware of the AAMC data but needed to further evaluate the impact of the Dobbs ruling.
A survey released at ACOG’s annual meeting in May found that 58% of third- and fourth-year medical students were unlikely to apply to a residency program in a state with abortion restrictions. Conducted after the Dobbs ruling last year, the survey found that future physicians are choosing where to attend residency according to state abortion policies, indicating that access to abortion care is changing the landscape of medical practice.
“For personal as well as professional reasons, reproductive health care access is now a key factor in residency match decisions as a result of Dobbs,” lead author Ariana Traub, MPH, said. She studies at Emory University, Atlanta, where abortion is restricted.
“Many students, including myself, struggle when trying to decide whether to stay in restricted states where the need is greatest (highest maternal mortality, infant mortality, lower number of physicians), versus going to an unrestricted state” for more comprehensive training and care, Ms. Traub said. “Regardless of this decision, Dobbs and subsequent abortion laws are making students question what matters most and how they can provide the best care.”
In another recently published survey, University of Miami fourth-year student Morgan Levy, MD, MPH, and colleagues found that 77% of students would prefer to apply to a residency program in a state that preserves access to abortion. Ensuring access to those services for themselves or a family member was a key factor, according to the paper published in the Journal of General Internal Medicine.
For Dr. Levy, who recently graduated from a school in abortion-restricted Florida and will soon apply to ob.gyn. residencies, the Dobbs decision made her more committed to becoming an ob.gyn., an interest she’s had since college, she said.
“I do not intend to limit my search,” Dr. Levy said in an interview. “In the states where there are restrictions in place, it’s really important to make sure that people are getting good care,” she said.
Differing perspective
Though survey and anecdotal data show that students and residents expressing hesitation about states with bans or restrictive laws, it appears that most who applied to residency programs during the 2023 Match did not shy away from those states. Almost all the open ob.gyn. residency positions were filled, according to the National Resident Matching Program.
There was no change in how U.S. MD seniors applying for 2023 residency ranked programs on the basis of whether abortion was legal, limited, or banned in the state where a program was based, Donna Lamb, DHSc, MBA, BSN, president and CEO of the NRMP, said.
“We’re seeing what we’ve seen over the past 5 years, and that is a very high fill rate, a very high rate of preference for ob.gyn., and not a heck of a lot of change,” Dr. Lamb said, noting that ob.gyn. programs continue to be very competitive. “We have more applicants than we have positions available,” she said.
In the most recent Match, there were 2,100 applicants (more than half U.S. MD seniors) for about 1,500 slots, with 1,499 initial matches, according to NRMP data. The overall fill rate was 99.7% after the Supplemental Offer and Assistance Program and Electronic Residency Applications process, NRMP reported. The results are similar to what NRMP reported as its previous all-time high year for ob.gyn. placements.
There was a dip in applicants from 2022 to 2023, even though the slots available stayed the same, but it was not markedly different from the previous 5 years, Dr. Lamb said.
“While the Dobbs decision may, indeed, have impacted applicant and application numbers to residency programs, interventions such as signaling may also contribute to the decrease in numbers of applications submitted as well,” AnnaMarie Connolly, MD, ACOG chief of education and academic affairs, and Arthur Ollendorff, MD, APOG president, said in a statement to this news organization.
For the first time in 2022, Match Day applicants were required to “signal” interest in a particular program in an effort to reduce the number of applications and cost to medical students, they noted.
Personal view
When it was time for Dr. Gibson to apply for ob.gyn. residencies, she wondered: Where do you apply in this landscape? But she did not limit her applications: “If I don’t apply to Indiana, Missouri, Tennessee, Wisconsin, Iowa, I’m taking a lot of really great programs off the table.” She did not want to hurt her chances for a match in a competitive specialty, she said.
“Being in Tennessee is going to give me a very different, unique opportunity to hopefully do a lot of advocacy and lobbying and hopefully have my voice heard in maybe a different way than [in Illinois],” Dr. Gibson added.
Cassie Crifase, MPH, a fourth-year student at the University of Wisconsin–Madison applying to ob.gyn. residencies in next year’s Match, said in an interview that she’s concerned about the health risk of living in a state with abortion restrictions. Wisconsin is one of those.
“My list skews toward programs that are in abortion-protected states, but I also am applying to some programs that are in restricted states.” Those states would have to help her meet the Accreditation Council for Graduate Medical Education training requirements. And, she said, she’d want to know if she could still advocate for abortion access in the state.
Sereena Jivraj, a third-year medical student at Texas Christian University in Fort Worth, said that she won’t apply to programs in Alabama, Mississippi, Arkansas, and other nearby states with abortion restrictions. However, Texas is still on her list. “I’m from Texas, my family lives in Texas, and I go to school in Fort Worth, so I have made those connections,” Ms. Jivraj said.
Student advisers generally encourage ob.gyn. hopefuls to apply to 60-100 programs to ensure that they will match, Ms. Jivraj said. “How are you supposed to apply to 100 programs if many of them fall within states with high restrictions?”
What the future holds
Ms. Jivraj said that she’s concerned about what the future holds, especially if the law does not change in Texas. “I don’t want to go to work every day wondering if I’m going to go to jail for something that I say,” she said.
Dr. Crifase has similar fears. “I want to be able to provide the best care for my patients and that would require being able to do those procedures without having to have my first thought be: Is this legal?”
“Things feel very volatile and uncertain,” Pamela Merritt, executive director of the nonprofit Medical Students for Choice in Philadelphia, where abortion is permitted, said. “What we’re asking medical students to do right now is to envision a future in a profession, a lifetime of providing care, where the policies and procedures and standards of the profession are under attack by 26 state legislatures and the federal court system,” she said.
“I don’t think you’re going to see people as willing to take risk.” She added that if someone matches to a program and then has regrets, “You can’t easily jump from residency program to residency program.”
Dr. Levy believes that the impact of the Dobbs decision is “definitely going to be a more common question of applicants to their potential programs.”
Applicants undoubtedly are thinking about how abortion restrictions or bans might affect their own health or that of their partners or families, she said. In a 2022 survey, Dr. Levy and colleagues reported that abortion is not uncommon among physicians, with 11.5% of the 1,566 respondents who had been pregnant saying they had at least one therapeutic abortion.
Students are also considering the potential ramification of a ban on emergency contraception and laws that criminalize physicians’ provision of abortion care, Dr. Levy said. Another complicating factor is individuals’ family ties or roots in specific geographic areas, she said.
Prospective residents will also have a lot of questions about how they will receive family planning training, Dr. Levy commented. “If you’re somewhere that you can’t really provide full-spectrum reproductive health care, then the question will become: How is the program going to provide that training?”
A version of this article first appeared on Medscape.com.
Emilee Gibson, MD, recently graduated from Southern Illinois University, Springfield, and starts her ob.gyn. residency at Vanderbilt University Medical Center in Nashville, Tenn., later this month. Abortion is permitted in Illinois but banned in Tennessee, a factor she weighed cautiously when she applied for residencies.
Dr. Gibson told this news organization that medical students, not just those interested in ob.gyn., are starting to think more about what it means to move to a state where it might be difficult to access abortion care. “Just from a personal standpoint, that’s a little scary.”
The Supreme Court’s decision to overturn Roe v. Wade abortion rights last June threatened to derail ob.gyns. in training from pursuing the specialty or locating in states that have banned or limited abortion.
, but some industry leaders, residents, and medical students say it may be too early to judge the full impact of the ruling because most students were already far along in their decision and application for a 2023 residency position.
At this point, some ob.gyn. students are planning careers on the basis of whether they have family ties in a particular state, whether limiting their search might hurt their potential to match in a competitive specialty, and whether their faith in the family planning and abortion training being offered by a program outweighs the drawbacks of being in a state with abortion bans or restrictions.
Lucy Brown, MD, a recent graduate of Indiana University, Indianapolis, said in an interview that she’d be “very nervous” about living and practicing in abortion-restricted Indiana if she were ready to start a family.
Dr. Brown said that she mostly limited applications in the recent Match to ob.gyn. residencies in states that protected abortion rights. Though she applied to a program in her home state of Kentucky, she noted that it – along with a program in Missouri – was very low on her rank list because of their abortion restrictions.
Ultimately, Dr. Brown matched at Johns Hopkins University, Baltimore, where she will receive abortion training and assist with abortions throughout her residency. Maryland’s abortion rights status was a big attraction, she said. “Abortion is integrated into every aspect of the education.”
By the numbers
For students applying to residencies this summer, evaluating the state legislative landscape is a little clearer than it was 1 year ago but is still evolving. As of June 1, 56 ob.gyn. residency programs and more than 1,100 medical residents are in states with the most restrictive bans in the country (19% of all programs), according to the Bixby Center for Reproductive Health at the University of California, San Francisco.
In terms of the latest abortion laws: 14 states banned abortion, 2 states banned abortion between 6 and 12 weeks, and 9 states banned abortion between 15 and 22 weeks, whereas abortion is legal in 25 states and Washington, according to a recent analysis by the Kaiser Family Foundation.
The impact on residencies? The Association of American Medical Colleges recently reported a 2% drop in the number of U.S. MD seniors who applied to residencies and a 5% decline in the number of seniors who applied to ob.gyn. residencies. In states where abortion was banned, the number of senior applicants to ob.gyn. programs dropped by more than 10%, according to AAMC’s Research and Action Institute.
“U.S. MD seniors appear, in general, more likely to avoid states where abortions are banned,” said Atul Grover, MD, PhD, executive director of the Research and Action Institute. “That’s a big difference between states where there are abortion bans and gestational limits and states with no bans or limits; it’s almost twice as large,” Dr. Grover said in an interview. “The question is: Was it a 1-year blip or something that will be the beginning of a trend?”
In a statement to this news organization, officials from the American College of Obstetricians and Gynecologists and the Association of Professors of Gynecology and Obstetrics said that they were aware of the AAMC data but needed to further evaluate the impact of the Dobbs ruling.
A survey released at ACOG’s annual meeting in May found that 58% of third- and fourth-year medical students were unlikely to apply to a residency program in a state with abortion restrictions. Conducted after the Dobbs ruling last year, the survey found that future physicians are choosing where to attend residency according to state abortion policies, indicating that access to abortion care is changing the landscape of medical practice.
“For personal as well as professional reasons, reproductive health care access is now a key factor in residency match decisions as a result of Dobbs,” lead author Ariana Traub, MPH, said. She studies at Emory University, Atlanta, where abortion is restricted.
“Many students, including myself, struggle when trying to decide whether to stay in restricted states where the need is greatest (highest maternal mortality, infant mortality, lower number of physicians), versus going to an unrestricted state” for more comprehensive training and care, Ms. Traub said. “Regardless of this decision, Dobbs and subsequent abortion laws are making students question what matters most and how they can provide the best care.”
In another recently published survey, University of Miami fourth-year student Morgan Levy, MD, MPH, and colleagues found that 77% of students would prefer to apply to a residency program in a state that preserves access to abortion. Ensuring access to those services for themselves or a family member was a key factor, according to the paper published in the Journal of General Internal Medicine.
For Dr. Levy, who recently graduated from a school in abortion-restricted Florida and will soon apply to ob.gyn. residencies, the Dobbs decision made her more committed to becoming an ob.gyn., an interest she’s had since college, she said.
“I do not intend to limit my search,” Dr. Levy said in an interview. “In the states where there are restrictions in place, it’s really important to make sure that people are getting good care,” she said.
Differing perspective
Though survey and anecdotal data show that students and residents expressing hesitation about states with bans or restrictive laws, it appears that most who applied to residency programs during the 2023 Match did not shy away from those states. Almost all the open ob.gyn. residency positions were filled, according to the National Resident Matching Program.
There was no change in how U.S. MD seniors applying for 2023 residency ranked programs on the basis of whether abortion was legal, limited, or banned in the state where a program was based, Donna Lamb, DHSc, MBA, BSN, president and CEO of the NRMP, said.
“We’re seeing what we’ve seen over the past 5 years, and that is a very high fill rate, a very high rate of preference for ob.gyn., and not a heck of a lot of change,” Dr. Lamb said, noting that ob.gyn. programs continue to be very competitive. “We have more applicants than we have positions available,” she said.
In the most recent Match, there were 2,100 applicants (more than half U.S. MD seniors) for about 1,500 slots, with 1,499 initial matches, according to NRMP data. The overall fill rate was 99.7% after the Supplemental Offer and Assistance Program and Electronic Residency Applications process, NRMP reported. The results are similar to what NRMP reported as its previous all-time high year for ob.gyn. placements.
There was a dip in applicants from 2022 to 2023, even though the slots available stayed the same, but it was not markedly different from the previous 5 years, Dr. Lamb said.
“While the Dobbs decision may, indeed, have impacted applicant and application numbers to residency programs, interventions such as signaling may also contribute to the decrease in numbers of applications submitted as well,” AnnaMarie Connolly, MD, ACOG chief of education and academic affairs, and Arthur Ollendorff, MD, APOG president, said in a statement to this news organization.
For the first time in 2022, Match Day applicants were required to “signal” interest in a particular program in an effort to reduce the number of applications and cost to medical students, they noted.
Personal view
When it was time for Dr. Gibson to apply for ob.gyn. residencies, she wondered: Where do you apply in this landscape? But she did not limit her applications: “If I don’t apply to Indiana, Missouri, Tennessee, Wisconsin, Iowa, I’m taking a lot of really great programs off the table.” She did not want to hurt her chances for a match in a competitive specialty, she said.
“Being in Tennessee is going to give me a very different, unique opportunity to hopefully do a lot of advocacy and lobbying and hopefully have my voice heard in maybe a different way than [in Illinois],” Dr. Gibson added.
Cassie Crifase, MPH, a fourth-year student at the University of Wisconsin–Madison applying to ob.gyn. residencies in next year’s Match, said in an interview that she’s concerned about the health risk of living in a state with abortion restrictions. Wisconsin is one of those.
“My list skews toward programs that are in abortion-protected states, but I also am applying to some programs that are in restricted states.” Those states would have to help her meet the Accreditation Council for Graduate Medical Education training requirements. And, she said, she’d want to know if she could still advocate for abortion access in the state.
Sereena Jivraj, a third-year medical student at Texas Christian University in Fort Worth, said that she won’t apply to programs in Alabama, Mississippi, Arkansas, and other nearby states with abortion restrictions. However, Texas is still on her list. “I’m from Texas, my family lives in Texas, and I go to school in Fort Worth, so I have made those connections,” Ms. Jivraj said.
Student advisers generally encourage ob.gyn. hopefuls to apply to 60-100 programs to ensure that they will match, Ms. Jivraj said. “How are you supposed to apply to 100 programs if many of them fall within states with high restrictions?”
What the future holds
Ms. Jivraj said that she’s concerned about what the future holds, especially if the law does not change in Texas. “I don’t want to go to work every day wondering if I’m going to go to jail for something that I say,” she said.
Dr. Crifase has similar fears. “I want to be able to provide the best care for my patients and that would require being able to do those procedures without having to have my first thought be: Is this legal?”
“Things feel very volatile and uncertain,” Pamela Merritt, executive director of the nonprofit Medical Students for Choice in Philadelphia, where abortion is permitted, said. “What we’re asking medical students to do right now is to envision a future in a profession, a lifetime of providing care, where the policies and procedures and standards of the profession are under attack by 26 state legislatures and the federal court system,” she said.
“I don’t think you’re going to see people as willing to take risk.” She added that if someone matches to a program and then has regrets, “You can’t easily jump from residency program to residency program.”
Dr. Levy believes that the impact of the Dobbs decision is “definitely going to be a more common question of applicants to their potential programs.”
Applicants undoubtedly are thinking about how abortion restrictions or bans might affect their own health or that of their partners or families, she said. In a 2022 survey, Dr. Levy and colleagues reported that abortion is not uncommon among physicians, with 11.5% of the 1,566 respondents who had been pregnant saying they had at least one therapeutic abortion.
Students are also considering the potential ramification of a ban on emergency contraception and laws that criminalize physicians’ provision of abortion care, Dr. Levy said. Another complicating factor is individuals’ family ties or roots in specific geographic areas, she said.
Prospective residents will also have a lot of questions about how they will receive family planning training, Dr. Levy commented. “If you’re somewhere that you can’t really provide full-spectrum reproductive health care, then the question will become: How is the program going to provide that training?”
A version of this article first appeared on Medscape.com.
Emilee Gibson, MD, recently graduated from Southern Illinois University, Springfield, and starts her ob.gyn. residency at Vanderbilt University Medical Center in Nashville, Tenn., later this month. Abortion is permitted in Illinois but banned in Tennessee, a factor she weighed cautiously when she applied for residencies.
Dr. Gibson told this news organization that medical students, not just those interested in ob.gyn., are starting to think more about what it means to move to a state where it might be difficult to access abortion care. “Just from a personal standpoint, that’s a little scary.”
The Supreme Court’s decision to overturn Roe v. Wade abortion rights last June threatened to derail ob.gyns. in training from pursuing the specialty or locating in states that have banned or limited abortion.
, but some industry leaders, residents, and medical students say it may be too early to judge the full impact of the ruling because most students were already far along in their decision and application for a 2023 residency position.
At this point, some ob.gyn. students are planning careers on the basis of whether they have family ties in a particular state, whether limiting their search might hurt their potential to match in a competitive specialty, and whether their faith in the family planning and abortion training being offered by a program outweighs the drawbacks of being in a state with abortion bans or restrictions.
Lucy Brown, MD, a recent graduate of Indiana University, Indianapolis, said in an interview that she’d be “very nervous” about living and practicing in abortion-restricted Indiana if she were ready to start a family.
Dr. Brown said that she mostly limited applications in the recent Match to ob.gyn. residencies in states that protected abortion rights. Though she applied to a program in her home state of Kentucky, she noted that it – along with a program in Missouri – was very low on her rank list because of their abortion restrictions.
Ultimately, Dr. Brown matched at Johns Hopkins University, Baltimore, where she will receive abortion training and assist with abortions throughout her residency. Maryland’s abortion rights status was a big attraction, she said. “Abortion is integrated into every aspect of the education.”
By the numbers
For students applying to residencies this summer, evaluating the state legislative landscape is a little clearer than it was 1 year ago but is still evolving. As of June 1, 56 ob.gyn. residency programs and more than 1,100 medical residents are in states with the most restrictive bans in the country (19% of all programs), according to the Bixby Center for Reproductive Health at the University of California, San Francisco.
In terms of the latest abortion laws: 14 states banned abortion, 2 states banned abortion between 6 and 12 weeks, and 9 states banned abortion between 15 and 22 weeks, whereas abortion is legal in 25 states and Washington, according to a recent analysis by the Kaiser Family Foundation.
The impact on residencies? The Association of American Medical Colleges recently reported a 2% drop in the number of U.S. MD seniors who applied to residencies and a 5% decline in the number of seniors who applied to ob.gyn. residencies. In states where abortion was banned, the number of senior applicants to ob.gyn. programs dropped by more than 10%, according to AAMC’s Research and Action Institute.
“U.S. MD seniors appear, in general, more likely to avoid states where abortions are banned,” said Atul Grover, MD, PhD, executive director of the Research and Action Institute. “That’s a big difference between states where there are abortion bans and gestational limits and states with no bans or limits; it’s almost twice as large,” Dr. Grover said in an interview. “The question is: Was it a 1-year blip or something that will be the beginning of a trend?”
In a statement to this news organization, officials from the American College of Obstetricians and Gynecologists and the Association of Professors of Gynecology and Obstetrics said that they were aware of the AAMC data but needed to further evaluate the impact of the Dobbs ruling.
A survey released at ACOG’s annual meeting in May found that 58% of third- and fourth-year medical students were unlikely to apply to a residency program in a state with abortion restrictions. Conducted after the Dobbs ruling last year, the survey found that future physicians are choosing where to attend residency according to state abortion policies, indicating that access to abortion care is changing the landscape of medical practice.
“For personal as well as professional reasons, reproductive health care access is now a key factor in residency match decisions as a result of Dobbs,” lead author Ariana Traub, MPH, said. She studies at Emory University, Atlanta, where abortion is restricted.
“Many students, including myself, struggle when trying to decide whether to stay in restricted states where the need is greatest (highest maternal mortality, infant mortality, lower number of physicians), versus going to an unrestricted state” for more comprehensive training and care, Ms. Traub said. “Regardless of this decision, Dobbs and subsequent abortion laws are making students question what matters most and how they can provide the best care.”
In another recently published survey, University of Miami fourth-year student Morgan Levy, MD, MPH, and colleagues found that 77% of students would prefer to apply to a residency program in a state that preserves access to abortion. Ensuring access to those services for themselves or a family member was a key factor, according to the paper published in the Journal of General Internal Medicine.
For Dr. Levy, who recently graduated from a school in abortion-restricted Florida and will soon apply to ob.gyn. residencies, the Dobbs decision made her more committed to becoming an ob.gyn., an interest she’s had since college, she said.
“I do not intend to limit my search,” Dr. Levy said in an interview. “In the states where there are restrictions in place, it’s really important to make sure that people are getting good care,” she said.
Differing perspective
Though survey and anecdotal data show that students and residents expressing hesitation about states with bans or restrictive laws, it appears that most who applied to residency programs during the 2023 Match did not shy away from those states. Almost all the open ob.gyn. residency positions were filled, according to the National Resident Matching Program.
There was no change in how U.S. MD seniors applying for 2023 residency ranked programs on the basis of whether abortion was legal, limited, or banned in the state where a program was based, Donna Lamb, DHSc, MBA, BSN, president and CEO of the NRMP, said.
“We’re seeing what we’ve seen over the past 5 years, and that is a very high fill rate, a very high rate of preference for ob.gyn., and not a heck of a lot of change,” Dr. Lamb said, noting that ob.gyn. programs continue to be very competitive. “We have more applicants than we have positions available,” she said.
In the most recent Match, there were 2,100 applicants (more than half U.S. MD seniors) for about 1,500 slots, with 1,499 initial matches, according to NRMP data. The overall fill rate was 99.7% after the Supplemental Offer and Assistance Program and Electronic Residency Applications process, NRMP reported. The results are similar to what NRMP reported as its previous all-time high year for ob.gyn. placements.
There was a dip in applicants from 2022 to 2023, even though the slots available stayed the same, but it was not markedly different from the previous 5 years, Dr. Lamb said.
“While the Dobbs decision may, indeed, have impacted applicant and application numbers to residency programs, interventions such as signaling may also contribute to the decrease in numbers of applications submitted as well,” AnnaMarie Connolly, MD, ACOG chief of education and academic affairs, and Arthur Ollendorff, MD, APOG president, said in a statement to this news organization.
For the first time in 2022, Match Day applicants were required to “signal” interest in a particular program in an effort to reduce the number of applications and cost to medical students, they noted.
Personal view
When it was time for Dr. Gibson to apply for ob.gyn. residencies, she wondered: Where do you apply in this landscape? But she did not limit her applications: “If I don’t apply to Indiana, Missouri, Tennessee, Wisconsin, Iowa, I’m taking a lot of really great programs off the table.” She did not want to hurt her chances for a match in a competitive specialty, she said.
“Being in Tennessee is going to give me a very different, unique opportunity to hopefully do a lot of advocacy and lobbying and hopefully have my voice heard in maybe a different way than [in Illinois],” Dr. Gibson added.
Cassie Crifase, MPH, a fourth-year student at the University of Wisconsin–Madison applying to ob.gyn. residencies in next year’s Match, said in an interview that she’s concerned about the health risk of living in a state with abortion restrictions. Wisconsin is one of those.
“My list skews toward programs that are in abortion-protected states, but I also am applying to some programs that are in restricted states.” Those states would have to help her meet the Accreditation Council for Graduate Medical Education training requirements. And, she said, she’d want to know if she could still advocate for abortion access in the state.
Sereena Jivraj, a third-year medical student at Texas Christian University in Fort Worth, said that she won’t apply to programs in Alabama, Mississippi, Arkansas, and other nearby states with abortion restrictions. However, Texas is still on her list. “I’m from Texas, my family lives in Texas, and I go to school in Fort Worth, so I have made those connections,” Ms. Jivraj said.
Student advisers generally encourage ob.gyn. hopefuls to apply to 60-100 programs to ensure that they will match, Ms. Jivraj said. “How are you supposed to apply to 100 programs if many of them fall within states with high restrictions?”
What the future holds
Ms. Jivraj said that she’s concerned about what the future holds, especially if the law does not change in Texas. “I don’t want to go to work every day wondering if I’m going to go to jail for something that I say,” she said.
Dr. Crifase has similar fears. “I want to be able to provide the best care for my patients and that would require being able to do those procedures without having to have my first thought be: Is this legal?”
“Things feel very volatile and uncertain,” Pamela Merritt, executive director of the nonprofit Medical Students for Choice in Philadelphia, where abortion is permitted, said. “What we’re asking medical students to do right now is to envision a future in a profession, a lifetime of providing care, where the policies and procedures and standards of the profession are under attack by 26 state legislatures and the federal court system,” she said.
“I don’t think you’re going to see people as willing to take risk.” She added that if someone matches to a program and then has regrets, “You can’t easily jump from residency program to residency program.”
Dr. Levy believes that the impact of the Dobbs decision is “definitely going to be a more common question of applicants to their potential programs.”
Applicants undoubtedly are thinking about how abortion restrictions or bans might affect their own health or that of their partners or families, she said. In a 2022 survey, Dr. Levy and colleagues reported that abortion is not uncommon among physicians, with 11.5% of the 1,566 respondents who had been pregnant saying they had at least one therapeutic abortion.
Students are also considering the potential ramification of a ban on emergency contraception and laws that criminalize physicians’ provision of abortion care, Dr. Levy said. Another complicating factor is individuals’ family ties or roots in specific geographic areas, she said.
Prospective residents will also have a lot of questions about how they will receive family planning training, Dr. Levy commented. “If you’re somewhere that you can’t really provide full-spectrum reproductive health care, then the question will become: How is the program going to provide that training?”
A version of this article first appeared on Medscape.com.
Novel agent promising for major depression: Phase 3 data
TOPLINE
Patients who received zuranolone 50 mg/d demonstrated significantly greater improvement in depressive symptoms than those who received placebo, with a rapid onset of effect.
METHODOLOGY
The Food and Drug Administration has accepted filing of a new drug application for zuranolone, a neuroactive steroid that targets g-aminobutyric acid type A receptors (GABAAR), for the treatment of major depressive disorder (MDD) and postpartum depression.
The study included 543 mostly White female patients with MDD. The mean age of the patients was 40 years. Participants were randomly assigned to receive oral zuranolone 50 mg or placebo once daily for 14 days.
About 30% of patients were taking an antidepressant.
The primary endpoint was change in Hamilton Depression Rating Scale (HAM-D) score at day 15.
TAKEAWAY
The zuranolone group showed significantly greater improvement in depressive symptoms at 15 days compared with the placebo group (least square mean [LSM] change on HAM-D, –14.1, vs. –12.3; P = .01; Cohen’s d = 0.23).
Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).
Results favored zuranolone regardless of the use of antidepressant therapies.
Patients with anxiety who received the active drug experienced improvement in anxiety symptoms compared to the patients who received placebo.
The drug was well tolerated, and there were no new safety findings. The most common treatment-emergent adverse events were somnolence and headache. There was no weight gain, sexual dysfunction, withdrawal symptoms, or increased suicidal ideation or behavior.
IN PRACTICE
The study adds to evidence suggesting zuranolone is a promising novel therapy for treating MDD, the authors noted.
STUDY DETAILS
The study was conducted by Anita H. Clayton, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, and colleagues. It was published online May 3 in The American Journal of Psychiatry.
LIMITATIONS
The study was short term, and the patient population was severely depressed at study entry, which may limit application to those with mild or moderate symptoms. There was a robust placebo response, possibly partly due to the COVID-19 pandemic, when there was an increase in depressive symptoms in the U.S. population, and so frequent in-person visits may have led to an improvement in symptoms even if the patient was receiving placebo.
DISCLOSURES
The study was funded by Sage Therapeutics and Biogen.
A version of this article first appeared on Medscape.com.
TOPLINE
Patients who received zuranolone 50 mg/d demonstrated significantly greater improvement in depressive symptoms than those who received placebo, with a rapid onset of effect.
METHODOLOGY
The Food and Drug Administration has accepted filing of a new drug application for zuranolone, a neuroactive steroid that targets g-aminobutyric acid type A receptors (GABAAR), for the treatment of major depressive disorder (MDD) and postpartum depression.
The study included 543 mostly White female patients with MDD. The mean age of the patients was 40 years. Participants were randomly assigned to receive oral zuranolone 50 mg or placebo once daily for 14 days.
About 30% of patients were taking an antidepressant.
The primary endpoint was change in Hamilton Depression Rating Scale (HAM-D) score at day 15.
TAKEAWAY
The zuranolone group showed significantly greater improvement in depressive symptoms at 15 days compared with the placebo group (least square mean [LSM] change on HAM-D, –14.1, vs. –12.3; P = .01; Cohen’s d = 0.23).
Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).
Results favored zuranolone regardless of the use of antidepressant therapies.
Patients with anxiety who received the active drug experienced improvement in anxiety symptoms compared to the patients who received placebo.
The drug was well tolerated, and there were no new safety findings. The most common treatment-emergent adverse events were somnolence and headache. There was no weight gain, sexual dysfunction, withdrawal symptoms, or increased suicidal ideation or behavior.
IN PRACTICE
The study adds to evidence suggesting zuranolone is a promising novel therapy for treating MDD, the authors noted.
STUDY DETAILS
The study was conducted by Anita H. Clayton, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, and colleagues. It was published online May 3 in The American Journal of Psychiatry.
LIMITATIONS
The study was short term, and the patient population was severely depressed at study entry, which may limit application to those with mild or moderate symptoms. There was a robust placebo response, possibly partly due to the COVID-19 pandemic, when there was an increase in depressive symptoms in the U.S. population, and so frequent in-person visits may have led to an improvement in symptoms even if the patient was receiving placebo.
DISCLOSURES
The study was funded by Sage Therapeutics and Biogen.
A version of this article first appeared on Medscape.com.
TOPLINE
Patients who received zuranolone 50 mg/d demonstrated significantly greater improvement in depressive symptoms than those who received placebo, with a rapid onset of effect.
METHODOLOGY
The Food and Drug Administration has accepted filing of a new drug application for zuranolone, a neuroactive steroid that targets g-aminobutyric acid type A receptors (GABAAR), for the treatment of major depressive disorder (MDD) and postpartum depression.
The study included 543 mostly White female patients with MDD. The mean age of the patients was 40 years. Participants were randomly assigned to receive oral zuranolone 50 mg or placebo once daily for 14 days.
About 30% of patients were taking an antidepressant.
The primary endpoint was change in Hamilton Depression Rating Scale (HAM-D) score at day 15.
TAKEAWAY
The zuranolone group showed significantly greater improvement in depressive symptoms at 15 days compared with the placebo group (least square mean [LSM] change on HAM-D, –14.1, vs. –12.3; P = .01; Cohen’s d = 0.23).
Improvements were observed on day 3, the earliest assessment, and were sustained at all subsequent visits during the treatment and follow-up period (through day 42).
Results favored zuranolone regardless of the use of antidepressant therapies.
Patients with anxiety who received the active drug experienced improvement in anxiety symptoms compared to the patients who received placebo.
The drug was well tolerated, and there were no new safety findings. The most common treatment-emergent adverse events were somnolence and headache. There was no weight gain, sexual dysfunction, withdrawal symptoms, or increased suicidal ideation or behavior.
IN PRACTICE
The study adds to evidence suggesting zuranolone is a promising novel therapy for treating MDD, the authors noted.
STUDY DETAILS
The study was conducted by Anita H. Clayton, MD, department of psychiatry and neurobehavioral sciences, University of Virginia, Charlottesville, and colleagues. It was published online May 3 in The American Journal of Psychiatry.
LIMITATIONS
The study was short term, and the patient population was severely depressed at study entry, which may limit application to those with mild or moderate symptoms. There was a robust placebo response, possibly partly due to the COVID-19 pandemic, when there was an increase in depressive symptoms in the U.S. population, and so frequent in-person visits may have led to an improvement in symptoms even if the patient was receiving placebo.
DISCLOSURES
The study was funded by Sage Therapeutics and Biogen.
A version of this article first appeared on Medscape.com.
Hormone therapies still ‘most effective’ in treating menopausal vasomotor symptoms
Despite new options in non–hormone-based treatments,
This recommendation emerged from an updated position statement from the North American Menopause Society in its first review of the scientific literature since 2015. The statement specifically targets nonhormonal management of symptoms such as hot flashes and night sweats, which occur in as many as 80% of menopausal women but are undertreated. The statement appears in the June issue of the Journal of The North American Menopause Society.
“Women with contraindications or objections to hormone treatment should be informed by professionals of evidence-based effective nonhormone treatment options,” stated a NAMS advisory panel led by Chrisandra L. Shufelt, MD, MS, professor and chair of the division of general internal medicine and associate director of the Women’s Health Research Center at the Mayo Clinic in Jacksonville, Fla. The statement is one of multiple NAMS updates performed at regular intervals, said Dr. Shufelt, also past president of NAMS, in an interview. “But the research has changed, and we wanted to make clinicians aware of new medications. One of our interesting findings was more evidence that off-label use of the nonhormonal overactive bladder drug oxybutynin can lower the rate of hot flashes.”
Dr. Shufelt noted that many of the current update’s findings align with previous research, and stressed that the therapeutic recommendations apply specifically to VMS. “Not all menopause-related symptoms are vasomotor, however,” she said. “While a lot of the lifestyle options such as cooling techniques and exercise are not recommended for controlling hot flashes, diet and exercise changes can be beneficial for other health reasons.”
Although it’s the most effective option for VMS, hormone therapy is not suitable for women with contraindications such as a previous blood clot, an estrogen-dependent cancer, a family history of such cancers, or a personal preference against hormone use, Dr. Shufelt added, so nonhormonal alternatives are important to prevent women from wasting time and money on ineffective remedies. “Women need to know what works and what doesn’t,” she said.
Recommended nonhormonal therapies
Based on a rigorous review of the scientific evidence to date, NAMS found the following therapies to be effective: cognitive-behavioral therapy; clinical hypnosis; SSRIs and serotonin-norepinephrine reuptake inhibitors – which yield mild to moderate improvements; gabapentin – which lessens the frequency and severity of hot flashes; fezolinetant (Veozah), a novel first-in-class neurokinin B antagonist that was Food and Drug Administration–approved in May for VSM; and oxybutynin, an antimuscarinic, anticholinergic drug, that reduces moderate to severe VMS, although long-term use in older adults may be linked to cognitive decline, weight loss, and stellate ganglion block.
Therapies that were ineffective, associated with adverse effects (AEs), or lacking adequate evidence of efficacy and thus not recommended for VMS included: paced respiration; supplemental and herbal remedies such as black cohosh, milk thistle, and evening primrose; cooling techniques; trigger avoidance; exercise and yoga; mindfulness-based intervention and relaxation; suvorexant, a dual orexin-receptor antagonist used for insomnia; soy foods, extracts, and the soy metabolite equol; cannabinoids; acupuncture; calibration of neural oscillations; chiropractics; clonidine, an alpha-2 adrenergic agonist that is associated with significant AEs with no recent evidence of benefit over placebo; dietary modification; and pregabalin – which is associated with significant AEs and has controlled-substance prescribing restrictions.
Ultimately, clinicians should individualize menopause care to each patient. For example, “if a patient says that avoiding caffeine in the morning stops her from having hot flashes in the afternoon, that’s fine,” Dr. Shufelt said.
HT still most effective
“This statement is excellent, comprehensive, and evidence-based,” commented Jill M. Rabin MD, vice chair of education and development, obstetrics and gynecology, at Northshore University Hospital/LIJ Medical Center in Manhasset, N.Y., and professor of obstetrics and gynecology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health in Hempstead, N.Y.
Dr. Rabin, coauthor of Mind Over Bladder was not involved in compiling the statement.
She agreed that hormone therapy is the most effective option for VMS and regularly prescribes it for suitable candidates in different forms depending on the type and severity of menopausal symptoms. As for nonhormonal options, Dr. Rabin added in an interview, some of those not recommended in the current NAMS statement could yet prove to be effective as more data accumulate. Suvorexant may be one to watch, for instance, but currently there are not enough data on its effectiveness.
“It’s really important to keep up on this nonhormonal research,” Dr. Rabin said. “As the population ages, more and more women will be in the peri- and postmenopausal periods and some have medical reasons for not taking hormone therapy.” It’s important to recommend nonhormonal therapies of proven benefit according to current high-level evidence, she said, “but also to keep your ear to the ground about those still under investigation.”
As for the lifestyle and alternative remedies of unproven benefit, Dr. Rabin added, there’s little harm in trying them. “As far as I know, no one’s ever died of relaxation and paced breathing.” In addition, a patient’s interaction with and sense of control over her own physiology provided by these techniques may be beneficial in themselves.
Dr. Shufelt reported grant support from the National Institutes of Health. Numerous authors reported consulting fees from and other financial ties to private-sector companies. Dr. Rabin had no relevant competing interests to disclose with regard to her comments.
Despite new options in non–hormone-based treatments,
This recommendation emerged from an updated position statement from the North American Menopause Society in its first review of the scientific literature since 2015. The statement specifically targets nonhormonal management of symptoms such as hot flashes and night sweats, which occur in as many as 80% of menopausal women but are undertreated. The statement appears in the June issue of the Journal of The North American Menopause Society.
“Women with contraindications or objections to hormone treatment should be informed by professionals of evidence-based effective nonhormone treatment options,” stated a NAMS advisory panel led by Chrisandra L. Shufelt, MD, MS, professor and chair of the division of general internal medicine and associate director of the Women’s Health Research Center at the Mayo Clinic in Jacksonville, Fla. The statement is one of multiple NAMS updates performed at regular intervals, said Dr. Shufelt, also past president of NAMS, in an interview. “But the research has changed, and we wanted to make clinicians aware of new medications. One of our interesting findings was more evidence that off-label use of the nonhormonal overactive bladder drug oxybutynin can lower the rate of hot flashes.”
Dr. Shufelt noted that many of the current update’s findings align with previous research, and stressed that the therapeutic recommendations apply specifically to VMS. “Not all menopause-related symptoms are vasomotor, however,” she said. “While a lot of the lifestyle options such as cooling techniques and exercise are not recommended for controlling hot flashes, diet and exercise changes can be beneficial for other health reasons.”
Although it’s the most effective option for VMS, hormone therapy is not suitable for women with contraindications such as a previous blood clot, an estrogen-dependent cancer, a family history of such cancers, or a personal preference against hormone use, Dr. Shufelt added, so nonhormonal alternatives are important to prevent women from wasting time and money on ineffective remedies. “Women need to know what works and what doesn’t,” she said.
Recommended nonhormonal therapies
Based on a rigorous review of the scientific evidence to date, NAMS found the following therapies to be effective: cognitive-behavioral therapy; clinical hypnosis; SSRIs and serotonin-norepinephrine reuptake inhibitors – which yield mild to moderate improvements; gabapentin – which lessens the frequency and severity of hot flashes; fezolinetant (Veozah), a novel first-in-class neurokinin B antagonist that was Food and Drug Administration–approved in May for VSM; and oxybutynin, an antimuscarinic, anticholinergic drug, that reduces moderate to severe VMS, although long-term use in older adults may be linked to cognitive decline, weight loss, and stellate ganglion block.
Therapies that were ineffective, associated with adverse effects (AEs), or lacking adequate evidence of efficacy and thus not recommended for VMS included: paced respiration; supplemental and herbal remedies such as black cohosh, milk thistle, and evening primrose; cooling techniques; trigger avoidance; exercise and yoga; mindfulness-based intervention and relaxation; suvorexant, a dual orexin-receptor antagonist used for insomnia; soy foods, extracts, and the soy metabolite equol; cannabinoids; acupuncture; calibration of neural oscillations; chiropractics; clonidine, an alpha-2 adrenergic agonist that is associated with significant AEs with no recent evidence of benefit over placebo; dietary modification; and pregabalin – which is associated with significant AEs and has controlled-substance prescribing restrictions.
Ultimately, clinicians should individualize menopause care to each patient. For example, “if a patient says that avoiding caffeine in the morning stops her from having hot flashes in the afternoon, that’s fine,” Dr. Shufelt said.
HT still most effective
“This statement is excellent, comprehensive, and evidence-based,” commented Jill M. Rabin MD, vice chair of education and development, obstetrics and gynecology, at Northshore University Hospital/LIJ Medical Center in Manhasset, N.Y., and professor of obstetrics and gynecology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health in Hempstead, N.Y.
Dr. Rabin, coauthor of Mind Over Bladder was not involved in compiling the statement.
She agreed that hormone therapy is the most effective option for VMS and regularly prescribes it for suitable candidates in different forms depending on the type and severity of menopausal symptoms. As for nonhormonal options, Dr. Rabin added in an interview, some of those not recommended in the current NAMS statement could yet prove to be effective as more data accumulate. Suvorexant may be one to watch, for instance, but currently there are not enough data on its effectiveness.
“It’s really important to keep up on this nonhormonal research,” Dr. Rabin said. “As the population ages, more and more women will be in the peri- and postmenopausal periods and some have medical reasons for not taking hormone therapy.” It’s important to recommend nonhormonal therapies of proven benefit according to current high-level evidence, she said, “but also to keep your ear to the ground about those still under investigation.”
As for the lifestyle and alternative remedies of unproven benefit, Dr. Rabin added, there’s little harm in trying them. “As far as I know, no one’s ever died of relaxation and paced breathing.” In addition, a patient’s interaction with and sense of control over her own physiology provided by these techniques may be beneficial in themselves.
Dr. Shufelt reported grant support from the National Institutes of Health. Numerous authors reported consulting fees from and other financial ties to private-sector companies. Dr. Rabin had no relevant competing interests to disclose with regard to her comments.
Despite new options in non–hormone-based treatments,
This recommendation emerged from an updated position statement from the North American Menopause Society in its first review of the scientific literature since 2015. The statement specifically targets nonhormonal management of symptoms such as hot flashes and night sweats, which occur in as many as 80% of menopausal women but are undertreated. The statement appears in the June issue of the Journal of The North American Menopause Society.
“Women with contraindications or objections to hormone treatment should be informed by professionals of evidence-based effective nonhormone treatment options,” stated a NAMS advisory panel led by Chrisandra L. Shufelt, MD, MS, professor and chair of the division of general internal medicine and associate director of the Women’s Health Research Center at the Mayo Clinic in Jacksonville, Fla. The statement is one of multiple NAMS updates performed at regular intervals, said Dr. Shufelt, also past president of NAMS, in an interview. “But the research has changed, and we wanted to make clinicians aware of new medications. One of our interesting findings was more evidence that off-label use of the nonhormonal overactive bladder drug oxybutynin can lower the rate of hot flashes.”
Dr. Shufelt noted that many of the current update’s findings align with previous research, and stressed that the therapeutic recommendations apply specifically to VMS. “Not all menopause-related symptoms are vasomotor, however,” she said. “While a lot of the lifestyle options such as cooling techniques and exercise are not recommended for controlling hot flashes, diet and exercise changes can be beneficial for other health reasons.”
Although it’s the most effective option for VMS, hormone therapy is not suitable for women with contraindications such as a previous blood clot, an estrogen-dependent cancer, a family history of such cancers, or a personal preference against hormone use, Dr. Shufelt added, so nonhormonal alternatives are important to prevent women from wasting time and money on ineffective remedies. “Women need to know what works and what doesn’t,” she said.
Recommended nonhormonal therapies
Based on a rigorous review of the scientific evidence to date, NAMS found the following therapies to be effective: cognitive-behavioral therapy; clinical hypnosis; SSRIs and serotonin-norepinephrine reuptake inhibitors – which yield mild to moderate improvements; gabapentin – which lessens the frequency and severity of hot flashes; fezolinetant (Veozah), a novel first-in-class neurokinin B antagonist that was Food and Drug Administration–approved in May for VSM; and oxybutynin, an antimuscarinic, anticholinergic drug, that reduces moderate to severe VMS, although long-term use in older adults may be linked to cognitive decline, weight loss, and stellate ganglion block.
Therapies that were ineffective, associated with adverse effects (AEs), or lacking adequate evidence of efficacy and thus not recommended for VMS included: paced respiration; supplemental and herbal remedies such as black cohosh, milk thistle, and evening primrose; cooling techniques; trigger avoidance; exercise and yoga; mindfulness-based intervention and relaxation; suvorexant, a dual orexin-receptor antagonist used for insomnia; soy foods, extracts, and the soy metabolite equol; cannabinoids; acupuncture; calibration of neural oscillations; chiropractics; clonidine, an alpha-2 adrenergic agonist that is associated with significant AEs with no recent evidence of benefit over placebo; dietary modification; and pregabalin – which is associated with significant AEs and has controlled-substance prescribing restrictions.
Ultimately, clinicians should individualize menopause care to each patient. For example, “if a patient says that avoiding caffeine in the morning stops her from having hot flashes in the afternoon, that’s fine,” Dr. Shufelt said.
HT still most effective
“This statement is excellent, comprehensive, and evidence-based,” commented Jill M. Rabin MD, vice chair of education and development, obstetrics and gynecology, at Northshore University Hospital/LIJ Medical Center in Manhasset, N.Y., and professor of obstetrics and gynecology at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell Health in Hempstead, N.Y.
Dr. Rabin, coauthor of Mind Over Bladder was not involved in compiling the statement.
She agreed that hormone therapy is the most effective option for VMS and regularly prescribes it for suitable candidates in different forms depending on the type and severity of menopausal symptoms. As for nonhormonal options, Dr. Rabin added in an interview, some of those not recommended in the current NAMS statement could yet prove to be effective as more data accumulate. Suvorexant may be one to watch, for instance, but currently there are not enough data on its effectiveness.
“It’s really important to keep up on this nonhormonal research,” Dr. Rabin said. “As the population ages, more and more women will be in the peri- and postmenopausal periods and some have medical reasons for not taking hormone therapy.” It’s important to recommend nonhormonal therapies of proven benefit according to current high-level evidence, she said, “but also to keep your ear to the ground about those still under investigation.”
As for the lifestyle and alternative remedies of unproven benefit, Dr. Rabin added, there’s little harm in trying them. “As far as I know, no one’s ever died of relaxation and paced breathing.” In addition, a patient’s interaction with and sense of control over her own physiology provided by these techniques may be beneficial in themselves.
Dr. Shufelt reported grant support from the National Institutes of Health. Numerous authors reported consulting fees from and other financial ties to private-sector companies. Dr. Rabin had no relevant competing interests to disclose with regard to her comments.
FROM THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY
How does psoriasis affect fertility and birth outcomes?
in a U.K. cohort study.
Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.
“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”
To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.
Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.
The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.
Fertility, birth outcomes
When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.
As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.
In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.
However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.
“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”
They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”
Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.
This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.
“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”
The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.
in a U.K. cohort study.
Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.
“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”
To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.
Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.
The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.
Fertility, birth outcomes
When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.
As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.
In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.
However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.
“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”
They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”
Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.
This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.
“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”
The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.
in a U.K. cohort study.
Those are key findings from what is believed to be one of the largest studies to investigate fertility and obstetric outcomes in patients with psoriasis.
“Studies that have examined fertility and pregnancy outcomes in women with psoriasis have reported conflicting findings,” lead author Teng-Chou Chen, PhD, of the Centre for Pharmacoepidemiology and Drug Safety at the University of Manchester (England), and colleagues from the Global Psoriasis Atlas wrote in the study, published in JAMA Dermatology. Most of the studies were small, with under 100 women, “and are thus likely underpowered to detect a difference in pregnancy outcomes. The majority of those studies used disease registry data or lacked a matched comparison group and hence were unable to estimate the association of fertility and adverse pregnancy outcomes in women with psoriasis when compared with the general population.”
To determine fertility rates and birth outcomes in female patients with psoriasis, compared with age- and practice-matched patients without psoriasis, the researchers evaluated EHR data from a large U.K. primary care database, the Clinical Practice Research Datalink GOLD, from 1998 to 2019. They limited the analysis to patients aged 15-44 years and used relevant codes from clinical consultations to identify those with psoriasis. Then, for each patient with psoriasis, the researchers selected five comparators without psoriasis from the same primary care practice and matched for year of birth.
Both sets of patients were followed from the index date to age 45 years, death, transfer out of practice, last date of data collection, or end of the study period (Dec. 31, 2019), whichever came first. Pregnancy records were extracted for both sets of patients, and birth outcomes were categorized as pregnancy loss, live birth, stillbirth, and preterm birth. Adverse pregnancy outcomes were also collected. Finally, Dr. Chen and colleagues used a negative binomial model to examine the association between psoriasis and the fertility rate, and they applied logistic regression to compare the association between psoriasis and obstetric outcomes.
The analysis included 63,681 patients with psoriasis and 318,405 comparators whose median age on the index date was 30 years and who were followed for a median of 4.1 years. Among patients with psoriasis, 5.1% met criteria for moderate to severe disease in the follow-up period. The researchers observed that, compared with their age- and practice-matched counterparts, patients with psoriasis were more likely to be current smokers, alcohol drinkers, or overweight on the index date. They were also more often diagnosed with diabetes, hypertension, inflammatory bowel disease, thyroid disorders, and respiratory diseases such as asthma and chronic obstructive pulmonary disease.
Fertility, birth outcomes
When they looked at fertility outcomes, the researchers found that, compared with their matched peers without psoriasis, those with psoriasis had higher rates of fertility (risk ratio, 1.30; 95% confidence interval, 1.27-1.33; P < .001). But after the researchers stratified patients based on psoriasis severity, those with moderate to severe disease had significantly lower rates of fertility (RR, 0.75; 95% CI, 0.69-0.83; P < .001), compared those who did not have psoriasis.
As for adverse birth outcomes, compared with their matched comparators, pregnancies in patients with psoriasis were less likely to end in a live birth (odds ratio, 0.91; 95% CI, 0.88-0.93; P < .001). They also had a higher risk of pregnancy loss (OR, 1.06; 95% CI, 1.03-1.10; P < .001), most during the first trimester, at a gestation period of under 91 days.
In addition to psoriasis, patients younger than age 20 (OR, 2.04; 95% CI, 1.94-2.15; P < .011) and those aged between 20 and 24 years (OR, 1.35; 95% CI, 1.31-1.40; P < .001) had a higher risk of pregnancy loss, compared with those aged between 25 and 34 years.
However, no increases in the risks of antenatal hemorrhage, preeclampsia, or gestational diabetes were observed in patients with psoriasis, and no statistically significant differences in the odds of stillbirth and preterm birth were found between patients with psoriasis and matched comparators who did not have psoriasis.
“The mechanism to link the higher risk of pregnancy loss in patients with psoriasis is not clear, but there might be potential explanations,” the researchers wrote. “Psoriasis is characterized by the increased activity of [interleukin]-17, IL-23, and tumor necrosis factor–alpha. Those proinflammatory cytokines may negatively affect the placenta and cause impaired fetal growth.”
They recommended that further studies “evaluate the effects of better management of psoriasis and close monitoring during pregnancy on pregnancy loss.” In particular, “patients with psoriasis were more likely to have comorbidities that may be related to poor pregnancy outcomes, and hence increased emphasis of managing comorbidities as part of the routine management plan is also warranted.”
Asked to comment on the study, Alexa B. Kimball, MD, MPH, who has been involved with research on this topic, said that she and other investigators had observed some years ago that fertility rates for women with moderate to severe psoriasis might be lower than expected.
This trend was observed in some psoriasis registries, some pregnancy registries, and in clinical practice, Dr. Kimball, professor of dermatology at Harvard Medical School, Boston, said in an interview. “This study clearly demonstrates that lower fertility rates in the moderate to severe psoriasis population occurs and compels further exploration of the reason why.” The reasons could be biologic, she continued, including difficulty conceiving or an increased risk of miscarriage, sociobehavioral issues, or a combination.
“Behavioral examples could include that some women with moderate to severe psoriasis can flare during pregnancy, which might affect their choice” to become pregnant, Dr. Kimball said. “Stigma may also play a role in how women with moderate to severe psoriasis form relationships. Now that there are much better treatments for moderate to severe psoriasis and better knowledge about managing psoriasis during pregnancy, it will also be important to explore whether these trends change over time.”
The study was funded by the International League of Dermatological Societies on behalf of the Global Psoriasis Atlas. Two of the study authors reported receiving consulting fees and grant support from many pharmaceutical companies. Dr. Kimball disclosed that she serves or has served on several Organization of Teratology Information Specialists advisory board pregnancy registries, is a consultant and investigator for Abbvie, Janssen, Lilly, Bristol-Myers Squibb, Moonlake, UCB, and Amgen; has fellowship funding from Janssen; and serves on the board of Almirall.
FROM JAMA DERMATOLOGY
Guide explains nonsurgical management of major hemorrhage
A new guide offers recommendations for the nonsurgical management of major hemorrhage, which is a challenging clinical problem.
Major hemorrhage is a significant cause of death and can occur in a myriad of clinical settings.
“In Ontario, we’ve been collecting quality metrics on major hemorrhages to try and make sure that a higher percentage of patients gets the best possible care when they are experiencing significant bleeding,” author Jeannie Callum, MD, professor and director of transfusion medicine at Kingston (Ont.) Health Sciences Centre and Queen’s University, also in Kingston, said in an interview. “There were some gaps, so this is our effort to get open, clear information out to the emergency doctors, intensive care unit doctors, the surgeons, and everyone else involved in managing major hemorrhage, to help close these gaps.”
The guide was published in the Canadian Medical Association Journal.
Fast care essential
The guide aims to provide answers, based on the latest research, to questions such as when to activate a massive hemorrhage protocol (MHP), which patients should receive tranexamic acid (TXA), which blood products should be transfused before laboratory results are available, how to monitor the effects of blood transfusion, and when fibrinogen concentrate or prothrombin complex concentrate should be given.
Not all recommendations will be followed, Dr. Callum said, especially in rural hospitals with limited resources. But the guide is adaptable, and rural hospitals can create protocols that are customized to their unique circumstances.
Care must be “perfect and fast” in the first hour of major injury, said Dr. Callum. “You need to get a proclotting drug in that first hour if you have a traumatic or postpartum bleed. You have to make sure your clotting factors never fail you throughout your resuscitation. You have to be fast with the transfusion. You have to monitor for the complications of the transfusion, electrolyte disturbances, and the patient’s temperature dropping. It’s a complicated situation that needs a multidisciplinary team.”
Bleeding affects everybody in medicine, from family doctors in smaller institutions who work in emergency departments to obstetricians and surgeons, she added.
“For people under the age of 45, trauma is the most common cause of death. When people die of trauma, they die of bleeding. So many people experience these extreme bleeds. We believe that some of them might be preventable with faster, more standardized, more aggressive care. That’s why we wrote this review,” said Dr. Callum.
Administer TXA quickly
The first recommendation is to ensure that every hospital has a massive hemorrhage protocol. Such a protocol is vital for the emergency department, operating room, and obstetric unit. “Making sure you’ve got a protocol that is updated every 3 years and adjusted to the local hospital context is essential,” said Dr. Callum.
Smaller hospitals will have to adjust their protocols according to the capabilities of their sites. “Some smaller hospitals do not have platelets in stock and get their platelets from another hospital, so you need to adjust your protocol to what you are able to do. Not every hospital can control bleeding in a trauma patient, so your protocol would be to stabilize and call a helicopter. Make sure all of this is detailed so that implementing it becomes automatic,” said Dr. Callum.
An MHP should be activated for patients with uncontrolled hemorrhage who meet the clinical criteria of the local hospital and are expected to need blood product support and red blood cells.
“Lots of people bleed, but not everybody is bleeding enough that they need a code transfusion,” said Dr. Callum. Most patients with gastrointestinal bleeds caused by NSAID use can be managed with uncrossed matched blood from the local blood bank. “But in patients who need the full code transfusion because they are going to need plasma, clotting factor replacement, and many other drugs, that is when the MHP should be activated. Don’t activate it when you don’t need it, because doing so activates the whole hospital and diverts care away from other patients.”
TXA should be administered as soon as possible after onset of hemorrhage in most patients, with the exception of gastrointestinal hemorrhage, where a benefit has not been shown.
TXA has been a major advance in treating massive bleeding, Dr. Callum said. “TXA was invented by a Japanese husband-and-wife research team. We know that it reduces the death rate in trauma and in postpartum hemorrhage, and it reduces the chance of major bleeding with major surgical procedures. We give it routinely in surgical procedures. If a patient gets TXA within 60 minutes of injury, it dramatically reduces the death rate. And it costs $10 per patient. It’s cheap, it’s easy, it has no side effects. It’s just amazing.”
Future research must address several unanswered questions, said Dr. Callum. These questions include whether prehospital transfusion improves patient outcomes, whether whole blood has a role in the early management of major hemorrhage, and what role factor concentrates play in patients with major bleeding.
‘Optimal recommendations’
Commenting on the document, Bourke Tillmann, MD, PhD, trauma team leader at Sunnybrook Health Sciences Centre and the Ross Tilley Burn Center in Toronto, said: “Overall, I think it is a good overview of MHPs as an approach to major hemorrhage.”
The review also is timely, since Ontario released its MHP guidelines in 2021, he added. “I would have liked to see more about the treatment aspects than just an overview of an MHP. But if you are the person overseeing the emergency department or running the blood bank, these protocols are incredibly useful and incredibly important.”
“This report is a nice and thoughtful overview of best practices in many areas, especially trauma, and makes recommendations that are optimal, although they are not necessarily practical in all centers,” Eric L. Legome, MD, professor and chair of emergency medicine at Mount Sinai West and Mount Sinai Morningside, New York, said in an interview.
“If you’re in a small rural hospital with one lab technician, trying to do all of these things, it will not be possible. These are optimal recommendations that people can use to the best of their ability, but they are not standard of care, because some places will not be able to provide this level of care,” he added. “This paper provides practical, reasonable advice that should be looked at as you are trying to implement transfusion policies and processes, with the understanding that it is not necessarily applicable or practical for very small hospitals in very rural centers that might not have access to these types of products and tools, but it’s a reasonable and nicely written paper.”
No outside funding for the guideline was reported. Dr. Callum has received research funding from Canadian Blood Services and Octapharma. She sits on the nominating committee with the Association for the Advancement of Blood & Biotherapies and on the data safety monitoring boards for the Tranexamic Acid for Subdural Hematoma trial and the Fibrinogen Replacement in Trauma trial. Dr. Tillmann and Dr. Legome reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A new guide offers recommendations for the nonsurgical management of major hemorrhage, which is a challenging clinical problem.
Major hemorrhage is a significant cause of death and can occur in a myriad of clinical settings.
“In Ontario, we’ve been collecting quality metrics on major hemorrhages to try and make sure that a higher percentage of patients gets the best possible care when they are experiencing significant bleeding,” author Jeannie Callum, MD, professor and director of transfusion medicine at Kingston (Ont.) Health Sciences Centre and Queen’s University, also in Kingston, said in an interview. “There were some gaps, so this is our effort to get open, clear information out to the emergency doctors, intensive care unit doctors, the surgeons, and everyone else involved in managing major hemorrhage, to help close these gaps.”
The guide was published in the Canadian Medical Association Journal.
Fast care essential
The guide aims to provide answers, based on the latest research, to questions such as when to activate a massive hemorrhage protocol (MHP), which patients should receive tranexamic acid (TXA), which blood products should be transfused before laboratory results are available, how to monitor the effects of blood transfusion, and when fibrinogen concentrate or prothrombin complex concentrate should be given.
Not all recommendations will be followed, Dr. Callum said, especially in rural hospitals with limited resources. But the guide is adaptable, and rural hospitals can create protocols that are customized to their unique circumstances.
Care must be “perfect and fast” in the first hour of major injury, said Dr. Callum. “You need to get a proclotting drug in that first hour if you have a traumatic or postpartum bleed. You have to make sure your clotting factors never fail you throughout your resuscitation. You have to be fast with the transfusion. You have to monitor for the complications of the transfusion, electrolyte disturbances, and the patient’s temperature dropping. It’s a complicated situation that needs a multidisciplinary team.”
Bleeding affects everybody in medicine, from family doctors in smaller institutions who work in emergency departments to obstetricians and surgeons, she added.
“For people under the age of 45, trauma is the most common cause of death. When people die of trauma, they die of bleeding. So many people experience these extreme bleeds. We believe that some of them might be preventable with faster, more standardized, more aggressive care. That’s why we wrote this review,” said Dr. Callum.
Administer TXA quickly
The first recommendation is to ensure that every hospital has a massive hemorrhage protocol. Such a protocol is vital for the emergency department, operating room, and obstetric unit. “Making sure you’ve got a protocol that is updated every 3 years and adjusted to the local hospital context is essential,” said Dr. Callum.
Smaller hospitals will have to adjust their protocols according to the capabilities of their sites. “Some smaller hospitals do not have platelets in stock and get their platelets from another hospital, so you need to adjust your protocol to what you are able to do. Not every hospital can control bleeding in a trauma patient, so your protocol would be to stabilize and call a helicopter. Make sure all of this is detailed so that implementing it becomes automatic,” said Dr. Callum.
An MHP should be activated for patients with uncontrolled hemorrhage who meet the clinical criteria of the local hospital and are expected to need blood product support and red blood cells.
“Lots of people bleed, but not everybody is bleeding enough that they need a code transfusion,” said Dr. Callum. Most patients with gastrointestinal bleeds caused by NSAID use can be managed with uncrossed matched blood from the local blood bank. “But in patients who need the full code transfusion because they are going to need plasma, clotting factor replacement, and many other drugs, that is when the MHP should be activated. Don’t activate it when you don’t need it, because doing so activates the whole hospital and diverts care away from other patients.”
TXA should be administered as soon as possible after onset of hemorrhage in most patients, with the exception of gastrointestinal hemorrhage, where a benefit has not been shown.
TXA has been a major advance in treating massive bleeding, Dr. Callum said. “TXA was invented by a Japanese husband-and-wife research team. We know that it reduces the death rate in trauma and in postpartum hemorrhage, and it reduces the chance of major bleeding with major surgical procedures. We give it routinely in surgical procedures. If a patient gets TXA within 60 minutes of injury, it dramatically reduces the death rate. And it costs $10 per patient. It’s cheap, it’s easy, it has no side effects. It’s just amazing.”
Future research must address several unanswered questions, said Dr. Callum. These questions include whether prehospital transfusion improves patient outcomes, whether whole blood has a role in the early management of major hemorrhage, and what role factor concentrates play in patients with major bleeding.
‘Optimal recommendations’
Commenting on the document, Bourke Tillmann, MD, PhD, trauma team leader at Sunnybrook Health Sciences Centre and the Ross Tilley Burn Center in Toronto, said: “Overall, I think it is a good overview of MHPs as an approach to major hemorrhage.”
The review also is timely, since Ontario released its MHP guidelines in 2021, he added. “I would have liked to see more about the treatment aspects than just an overview of an MHP. But if you are the person overseeing the emergency department or running the blood bank, these protocols are incredibly useful and incredibly important.”
“This report is a nice and thoughtful overview of best practices in many areas, especially trauma, and makes recommendations that are optimal, although they are not necessarily practical in all centers,” Eric L. Legome, MD, professor and chair of emergency medicine at Mount Sinai West and Mount Sinai Morningside, New York, said in an interview.
“If you’re in a small rural hospital with one lab technician, trying to do all of these things, it will not be possible. These are optimal recommendations that people can use to the best of their ability, but they are not standard of care, because some places will not be able to provide this level of care,” he added. “This paper provides practical, reasonable advice that should be looked at as you are trying to implement transfusion policies and processes, with the understanding that it is not necessarily applicable or practical for very small hospitals in very rural centers that might not have access to these types of products and tools, but it’s a reasonable and nicely written paper.”
No outside funding for the guideline was reported. Dr. Callum has received research funding from Canadian Blood Services and Octapharma. She sits on the nominating committee with the Association for the Advancement of Blood & Biotherapies and on the data safety monitoring boards for the Tranexamic Acid for Subdural Hematoma trial and the Fibrinogen Replacement in Trauma trial. Dr. Tillmann and Dr. Legome reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
A new guide offers recommendations for the nonsurgical management of major hemorrhage, which is a challenging clinical problem.
Major hemorrhage is a significant cause of death and can occur in a myriad of clinical settings.
“In Ontario, we’ve been collecting quality metrics on major hemorrhages to try and make sure that a higher percentage of patients gets the best possible care when they are experiencing significant bleeding,” author Jeannie Callum, MD, professor and director of transfusion medicine at Kingston (Ont.) Health Sciences Centre and Queen’s University, also in Kingston, said in an interview. “There were some gaps, so this is our effort to get open, clear information out to the emergency doctors, intensive care unit doctors, the surgeons, and everyone else involved in managing major hemorrhage, to help close these gaps.”
The guide was published in the Canadian Medical Association Journal.
Fast care essential
The guide aims to provide answers, based on the latest research, to questions such as when to activate a massive hemorrhage protocol (MHP), which patients should receive tranexamic acid (TXA), which blood products should be transfused before laboratory results are available, how to monitor the effects of blood transfusion, and when fibrinogen concentrate or prothrombin complex concentrate should be given.
Not all recommendations will be followed, Dr. Callum said, especially in rural hospitals with limited resources. But the guide is adaptable, and rural hospitals can create protocols that are customized to their unique circumstances.
Care must be “perfect and fast” in the first hour of major injury, said Dr. Callum. “You need to get a proclotting drug in that first hour if you have a traumatic or postpartum bleed. You have to make sure your clotting factors never fail you throughout your resuscitation. You have to be fast with the transfusion. You have to monitor for the complications of the transfusion, electrolyte disturbances, and the patient’s temperature dropping. It’s a complicated situation that needs a multidisciplinary team.”
Bleeding affects everybody in medicine, from family doctors in smaller institutions who work in emergency departments to obstetricians and surgeons, she added.
“For people under the age of 45, trauma is the most common cause of death. When people die of trauma, they die of bleeding. So many people experience these extreme bleeds. We believe that some of them might be preventable with faster, more standardized, more aggressive care. That’s why we wrote this review,” said Dr. Callum.
Administer TXA quickly
The first recommendation is to ensure that every hospital has a massive hemorrhage protocol. Such a protocol is vital for the emergency department, operating room, and obstetric unit. “Making sure you’ve got a protocol that is updated every 3 years and adjusted to the local hospital context is essential,” said Dr. Callum.
Smaller hospitals will have to adjust their protocols according to the capabilities of their sites. “Some smaller hospitals do not have platelets in stock and get their platelets from another hospital, so you need to adjust your protocol to what you are able to do. Not every hospital can control bleeding in a trauma patient, so your protocol would be to stabilize and call a helicopter. Make sure all of this is detailed so that implementing it becomes automatic,” said Dr. Callum.
An MHP should be activated for patients with uncontrolled hemorrhage who meet the clinical criteria of the local hospital and are expected to need blood product support and red blood cells.
“Lots of people bleed, but not everybody is bleeding enough that they need a code transfusion,” said Dr. Callum. Most patients with gastrointestinal bleeds caused by NSAID use can be managed with uncrossed matched blood from the local blood bank. “But in patients who need the full code transfusion because they are going to need plasma, clotting factor replacement, and many other drugs, that is when the MHP should be activated. Don’t activate it when you don’t need it, because doing so activates the whole hospital and diverts care away from other patients.”
TXA should be administered as soon as possible after onset of hemorrhage in most patients, with the exception of gastrointestinal hemorrhage, where a benefit has not been shown.
TXA has been a major advance in treating massive bleeding, Dr. Callum said. “TXA was invented by a Japanese husband-and-wife research team. We know that it reduces the death rate in trauma and in postpartum hemorrhage, and it reduces the chance of major bleeding with major surgical procedures. We give it routinely in surgical procedures. If a patient gets TXA within 60 minutes of injury, it dramatically reduces the death rate. And it costs $10 per patient. It’s cheap, it’s easy, it has no side effects. It’s just amazing.”
Future research must address several unanswered questions, said Dr. Callum. These questions include whether prehospital transfusion improves patient outcomes, whether whole blood has a role in the early management of major hemorrhage, and what role factor concentrates play in patients with major bleeding.
‘Optimal recommendations’
Commenting on the document, Bourke Tillmann, MD, PhD, trauma team leader at Sunnybrook Health Sciences Centre and the Ross Tilley Burn Center in Toronto, said: “Overall, I think it is a good overview of MHPs as an approach to major hemorrhage.”
The review also is timely, since Ontario released its MHP guidelines in 2021, he added. “I would have liked to see more about the treatment aspects than just an overview of an MHP. But if you are the person overseeing the emergency department or running the blood bank, these protocols are incredibly useful and incredibly important.”
“This report is a nice and thoughtful overview of best practices in many areas, especially trauma, and makes recommendations that are optimal, although they are not necessarily practical in all centers,” Eric L. Legome, MD, professor and chair of emergency medicine at Mount Sinai West and Mount Sinai Morningside, New York, said in an interview.
“If you’re in a small rural hospital with one lab technician, trying to do all of these things, it will not be possible. These are optimal recommendations that people can use to the best of their ability, but they are not standard of care, because some places will not be able to provide this level of care,” he added. “This paper provides practical, reasonable advice that should be looked at as you are trying to implement transfusion policies and processes, with the understanding that it is not necessarily applicable or practical for very small hospitals in very rural centers that might not have access to these types of products and tools, but it’s a reasonable and nicely written paper.”
No outside funding for the guideline was reported. Dr. Callum has received research funding from Canadian Blood Services and Octapharma. She sits on the nominating committee with the Association for the Advancement of Blood & Biotherapies and on the data safety monitoring boards for the Tranexamic Acid for Subdural Hematoma trial and the Fibrinogen Replacement in Trauma trial. Dr. Tillmann and Dr. Legome reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM THE CANADIAN MEDICAL ASSOCIATION JOURNAL