Pregnant women who have even mild sleep apnea should be treated for their sleep-disordered breathing given what is known about associated risks for hypertensive disorders of pregnancy and gestational diabetes, Carolyn M. D’Ambrosio, MS, MD, FCCP, said at the virtual annual meeting of the Associated Professional Sleep Societies.

“This is the current standard of care,” Dr. D’Ambrosio said. “Although guidelines on this issue are not hard and fast, I’d say that knowing what we know about the risk of adverse [maternal] outcomes, we should all try to treat these problems as soon as they’re identified” and then repeat polysomnography or home sleep testing 3-6 months post partum to “be sure the sleep-disordered breathing has resolved.”

Estimates of obstructive sleep apnea (OSA) prevalence range from approximately 9% in the first trimester to 20% in the third trimester. Yet recognizing the significance of OSA in pregnant women and identifying women for testing remains a major challenge. “Most women won’t [report sleep problems] because it’s pretty much common folklore that you don’t sleep well when you’re pregnant,” said Dr. D’Ambrosio, associate professor of medicine at Harvard Medical School, Boston, and current past-chair of the Women’s Lung Health Network for CHEST.

Many obstetricians and obstetrics providers, meanwhile, do not adequately screen. Typical screening tools like the Epworth Sleepiness Scale have low sensitivity and specificity during pregnancy, which means that inquiries about sleepiness, snoring, and disruptions in sleep are important, as is attention to potential risks for OSA posed by obesity, chronic hypertension, and neck circumference.

Only about a quarter of women in the United States snore during pregnancy, she noted. Snoring prevalence does increase as pregnancy progresses, reaching up to almost 50% in during the third trimester in some studies.

A four-variable screening tool reported almost 10 years ago for pregnant women is reliable for gauging risk, Dr. D’Ambrosio said. The model considers self-reported frequent snoring (more than three times/week), chronic hypertension, advanced maternal age, and a pregestational body mass index of at least 30 kg/m². “If these [factors] are present, the patient is at significant risk for OSA and should be strongly considered for testing,” she said.

Home sleep apnea testing (HSAT) is validated for pregnant women but “it can underestimate,” she said. “If you get a negative result and [have clinical suspicion], then don’t stop there.”

And considering that the prevalence of OSA – at all levels of severity – increases as pregnancy progresses, it’s important to continue talking about sleep with patients who have frequent snoring, for instance, but negative sleep test results early in pregnancy. “They could develop [OSA] as time goes on,” she said.
 

Associated risk factors

Independent associations between sleep-disordered breathing and adverse maternal outcomes were demonstrated in a prospective cohort study published several years ago of 3,705 women who underwent HSAT in early and mid-pregnancy. The adjusted odds ratios for preeclampsia when sleep-disordered breathing (an apnea-hypopnea index of ≥5) was present early in pregnancy and in mid-pregnancy were 1.94 and 1.95, respectively.

For hypertensive disorders of pregnancy more broadly, the ORs were 1.46 and 1.73, and for gestational diabetes, the ORs were 3.47 and 2.79.

“Faced with the question about why it’s important to diagnosis and treat OSA [during pregnancy] since the pregnancy will be over in a few months, I go to this study,” Dr. D’Ambrosio said. “Waiting until the end of pregnancy is not safe. There are increased risks of very serious conditions if sleep apnea is there and it’s not treated.”

Another study demonstrating a link between OSA and maternal outcomes looked over 1.5 million deliveries in the United States and found a significantly higher prevalence of gestational diabetes (OR, 2.08), gestational hypertension (OR, 1.77), preeclampsia (OR, 2.07), and eclampsia (OR, 2.70) in pregnant women with OSA than without, after adjusting for maternal obesity. Associations remained significant after adjusting for a more comprehensive list of covariates.

Multiple potential casual pathways are at play, Dr. D’Ambrosio said. Short sleep duration decreases leptin and increases ghrelin levels, for instance, and sleep fragmentation activates the HPA axis and increases cortisol. Intermittent hypoxemia affects sympathetic activity, and intrathoracic pressure swings cause increased oxidative stress and systemic inflammation.

The resulting endothelial dysfunction, glucose dysfunction, and dyslipidemia can drive the adverse maternal outcomes documented in these studies, she said, noting that the adverse outcomes can have long-term cardiovascular consequences.

Continuous positive airway pressure therapy is well tolerated in pregnancy, and given pregnancy’s continual weight change, auto-titrating CPAP may be the best option, she said.

There is “some limited data that treatment improves maternal outcomes, and we’re still working on trying to get better data and more solid recommendations,” Dr. D’Ambrosio said. There currently are no guidelines covering the diagnosis and management of OSA during pregnancy.

“We’ve come a long way ... but we still have more to do,” she said. “We have a long way to go to getting [OSA in pregnant women] well recognized, with screening techniques and diagnosis.”

Asked after the meeting about Dr. D’Ambrosio’s messages, Anita Rajagopal, MD, said that OSA screening during pregnancy needs to be improved through more collaboration “with our ob.gyn. and primary care colleagues.”

Too often, she said, “the signs and symptoms of OSA in pregnancy are written off as ‘just harmless snoring’ while in fact the patient has treatable sleep disordered breathing with potential adverse effects.” Dr. Rajagopal is department medical director for sleep medicine at Community Physician Network and medical director of the Community Health Network Sleep-Wake Disorders Center, both in Indianapolis.

Dr. D’Ambrosio reported that she has no potential conflicts of interest related to the material she presented, and Dr. Rajagopal stated she has no potential conflicts of interest.

Pregnant women who have even mild sleep apnea should be treated for their sleep-disordered breathing given what is known about associated risks for hypertensive disorders of pregnancy and gestational diabetes, Carolyn M. D’Ambrosio, MS, MD, FCCP, said at the virtual annual meeting of the Associated Professional Sleep Societies.

“This is the current standard of care,” Dr. D’Ambrosio said. “Although guidelines on this issue are not hard and fast, I’d say that knowing what we know about the risk of adverse [maternal] outcomes, we should all try to treat these problems as soon as they’re identified” and then repeat polysomnography or home sleep testing 3-6 months post partum to “be sure the sleep-disordered breathing has resolved.”

Estimates of obstructive sleep apnea (OSA) prevalence range from approximately 9% in the first trimester to 20% in the third trimester. Yet recognizing the significance of OSA in pregnant women and identifying women for testing remains a major challenge. “Most women won’t [report sleep problems] because it’s pretty much common folklore that you don’t sleep well when you’re pregnant,” said Dr. D’Ambrosio, associate professor of medicine at Harvard Medical School, Boston, and current past-chair of the Women’s Lung Health Network for CHEST.

Many obstetricians and obstetrics providers, meanwhile, do not adequately screen. Typical screening tools like the Epworth Sleepiness Scale have low sensitivity and specificity during pregnancy, which means that inquiries about sleepiness, snoring, and disruptions in sleep are important, as is attention to potential risks for OSA posed by obesity, chronic hypertension, and neck circumference.

Only about a quarter of women in the United States snore during pregnancy, she noted. Snoring prevalence does increase as pregnancy progresses, reaching up to almost 50% in during the third trimester in some studies.

A four-variable screening tool reported almost 10 years ago for pregnant women is reliable for gauging risk, Dr. D’Ambrosio said. The model considers self-reported frequent snoring (more than three times/week), chronic hypertension, advanced maternal age, and a pregestational body mass index of at least 30 kg/m². “If these [factors] are present, the patient is at significant risk for OSA and should be strongly considered for testing,” she said.

Home sleep apnea testing (HSAT) is validated for pregnant women but “it can underestimate,” she said. “If you get a negative result and [have clinical suspicion], then don’t stop there.”

And considering that the prevalence of OSA – at all levels of severity – increases as pregnancy progresses, it’s important to continue talking about sleep with patients who have frequent snoring, for instance, but negative sleep test results early in pregnancy. “They could develop [OSA] as time goes on,” she said.
 

Associated risk factors

Independent associations between sleep-disordered breathing and adverse maternal outcomes were demonstrated in a prospective cohort study published several years ago of 3,705 women who underwent HSAT in early and mid-pregnancy. The adjusted odds ratios for preeclampsia when sleep-disordered breathing (an apnea-hypopnea index of ≥5) was present early in pregnancy and in mid-pregnancy were 1.94 and 1.95, respectively.

For hypertensive disorders of pregnancy more broadly, the ORs were 1.46 and 1.73, and for gestational diabetes, the ORs were 3.47 and 2.79.

“Faced with the question about why it’s important to diagnosis and treat OSA [during pregnancy] since the pregnancy will be over in a few months, I go to this study,” Dr. D’Ambrosio said. “Waiting until the end of pregnancy is not safe. There are increased risks of very serious conditions if sleep apnea is there and it’s not treated.”

Another study demonstrating a link between OSA and maternal outcomes looked over 1.5 million deliveries in the United States and found a significantly higher prevalence of gestational diabetes (OR, 2.08), gestational hypertension (OR, 1.77), preeclampsia (OR, 2.07), and eclampsia (OR, 2.70) in pregnant women with OSA than without, after adjusting for maternal obesity. Associations remained significant after adjusting for a more comprehensive list of covariates.

Multiple potential casual pathways are at play, Dr. D’Ambrosio said. Short sleep duration decreases leptin and increases ghrelin levels, for instance, and sleep fragmentation activates the HPA axis and increases cortisol. Intermittent hypoxemia affects sympathetic activity, and intrathoracic pressure swings cause increased oxidative stress and systemic inflammation.

The resulting endothelial dysfunction, glucose dysfunction, and dyslipidemia can drive the adverse maternal outcomes documented in these studies, she said, noting that the adverse outcomes can have long-term cardiovascular consequences.

Continuous positive airway pressure therapy is well tolerated in pregnancy, and given pregnancy’s continual weight change, auto-titrating CPAP may be the best option, she said.

There is “some limited data that treatment improves maternal outcomes, and we’re still working on trying to get better data and more solid recommendations,” Dr. D’Ambrosio said. There currently are no guidelines covering the diagnosis and management of OSA during pregnancy.

“We’ve come a long way ... but we still have more to do,” she said. “We have a long way to go to getting [OSA in pregnant women] well recognized, with screening techniques and diagnosis.”

Asked after the meeting about Dr. D’Ambrosio’s messages, Anita Rajagopal, MD, said that OSA screening during pregnancy needs to be improved through more collaboration “with our ob.gyn. and primary care colleagues.”

Too often, she said, “the signs and symptoms of OSA in pregnancy are written off as ‘just harmless snoring’ while in fact the patient has treatable sleep disordered breathing with potential adverse effects.” Dr. Rajagopal is department medical director for sleep medicine at Community Physician Network and medical director of the Community Health Network Sleep-Wake Disorders Center, both in Indianapolis.

Dr. D’Ambrosio reported that she has no potential conflicts of interest related to the material she presented, and Dr. Rajagopal stated she has no potential conflicts of interest.

Pregnant women who have even mild sleep apnea should be treated for their sleep-disordered breathing given what is known about associated risks for hypertensive disorders of pregnancy and gestational diabetes, Carolyn M. D’Ambrosio, MS, MD, FCCP, said at the virtual annual meeting of the Associated Professional Sleep Societies.

“This is the current standard of care,” Dr. D’Ambrosio said. “Although guidelines on this issue are not hard and fast, I’d say that knowing what we know about the risk of adverse [maternal] outcomes, we should all try to treat these problems as soon as they’re identified” and then repeat polysomnography or home sleep testing 3-6 months post partum to “be sure the sleep-disordered breathing has resolved.”

Estimates of obstructive sleep apnea (OSA) prevalence range from approximately 9% in the first trimester to 20% in the third trimester. Yet recognizing the significance of OSA in pregnant women and identifying women for testing remains a major challenge. “Most women won’t [report sleep problems] because it’s pretty much common folklore that you don’t sleep well when you’re pregnant,” said Dr. D’Ambrosio, associate professor of medicine at Harvard Medical School, Boston, and current past-chair of the Women’s Lung Health Network for CHEST.

Many obstetricians and obstetrics providers, meanwhile, do not adequately screen. Typical screening tools like the Epworth Sleepiness Scale have low sensitivity and specificity during pregnancy, which means that inquiries about sleepiness, snoring, and disruptions in sleep are important, as is attention to potential risks for OSA posed by obesity, chronic hypertension, and neck circumference.

Only about a quarter of women in the United States snore during pregnancy, she noted. Snoring prevalence does increase as pregnancy progresses, reaching up to almost 50% in during the third trimester in some studies.

A four-variable screening tool reported almost 10 years ago for pregnant women is reliable for gauging risk, Dr. D’Ambrosio said. The model considers self-reported frequent snoring (more than three times/week), chronic hypertension, advanced maternal age, and a pregestational body mass index of at least 30 kg/m². “If these [factors] are present, the patient is at significant risk for OSA and should be strongly considered for testing,” she said.

Home sleep apnea testing (HSAT) is validated for pregnant women but “it can underestimate,” she said. “If you get a negative result and [have clinical suspicion], then don’t stop there.”

And considering that the prevalence of OSA – at all levels of severity – increases as pregnancy progresses, it’s important to continue talking about sleep with patients who have frequent snoring, for instance, but negative sleep test results early in pregnancy. “They could develop [OSA] as time goes on,” she said.
 

Associated risk factors

Independent associations between sleep-disordered breathing and adverse maternal outcomes were demonstrated in a prospective cohort study published several years ago of 3,705 women who underwent HSAT in early and mid-pregnancy. The adjusted odds ratios for preeclampsia when sleep-disordered breathing (an apnea-hypopnea index of ≥5) was present early in pregnancy and in mid-pregnancy were 1.94 and 1.95, respectively.

For hypertensive disorders of pregnancy more broadly, the ORs were 1.46 and 1.73, and for gestational diabetes, the ORs were 3.47 and 2.79.

“Faced with the question about why it’s important to diagnosis and treat OSA [during pregnancy] since the pregnancy will be over in a few months, I go to this study,” Dr. D’Ambrosio said. “Waiting until the end of pregnancy is not safe. There are increased risks of very serious conditions if sleep apnea is there and it’s not treated.”

Another study demonstrating a link between OSA and maternal outcomes looked over 1.5 million deliveries in the United States and found a significantly higher prevalence of gestational diabetes (OR, 2.08), gestational hypertension (OR, 1.77), preeclampsia (OR, 2.07), and eclampsia (OR, 2.70) in pregnant women with OSA than without, after adjusting for maternal obesity. Associations remained significant after adjusting for a more comprehensive list of covariates.

Multiple potential casual pathways are at play, Dr. D’Ambrosio said. Short sleep duration decreases leptin and increases ghrelin levels, for instance, and sleep fragmentation activates the HPA axis and increases cortisol. Intermittent hypoxemia affects sympathetic activity, and intrathoracic pressure swings cause increased oxidative stress and systemic inflammation.

The resulting endothelial dysfunction, glucose dysfunction, and dyslipidemia can drive the adverse maternal outcomes documented in these studies, she said, noting that the adverse outcomes can have long-term cardiovascular consequences.

Continuous positive airway pressure therapy is well tolerated in pregnancy, and given pregnancy’s continual weight change, auto-titrating CPAP may be the best option, she said.

There is “some limited data that treatment improves maternal outcomes, and we’re still working on trying to get better data and more solid recommendations,” Dr. D’Ambrosio said. There currently are no guidelines covering the diagnosis and management of OSA during pregnancy.

“We’ve come a long way ... but we still have more to do,” she said. “We have a long way to go to getting [OSA in pregnant women] well recognized, with screening techniques and diagnosis.”

Asked after the meeting about Dr. D’Ambrosio’s messages, Anita Rajagopal, MD, said that OSA screening during pregnancy needs to be improved through more collaboration “with our ob.gyn. and primary care colleagues.”

Too often, she said, “the signs and symptoms of OSA in pregnancy are written off as ‘just harmless snoring’ while in fact the patient has treatable sleep disordered breathing with potential adverse effects.” Dr. Rajagopal is department medical director for sleep medicine at Community Physician Network and medical director of the Community Health Network Sleep-Wake Disorders Center, both in Indianapolis.

Dr. D’Ambrosio reported that she has no potential conflicts of interest related to the material she presented, and Dr. Rajagopal stated she has no potential conflicts of interest.

Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.

Results from two new phase 3 trials show that the investigational drug ublituximab (TG Therapeutics), a novel glycoengineered anti-CD20 monoclonal antibody, significantly reduced the annualized relapse rate (ARR) and MRI parameters compared with teriflunomide in patients with relapsing forms of MS.

The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

‘Glycoengineered’ antibody

If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.

There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.

For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.

Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.

The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.

Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
 

Primary outcomes met

For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).

In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).

One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”

It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.

From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.

Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.

There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).

The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
 

A life changer?

Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”

The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.

The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.

If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.

However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”

Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.

“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.

He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.

Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.

The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
 

Striking improvement

When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”

Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.

He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”

Dr. Steinman is a consultant for TG Therapeutics.

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

Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.

Results from two new phase 3 trials show that the investigational drug ublituximab (TG Therapeutics), a novel glycoengineered anti-CD20 monoclonal antibody, significantly reduced the annualized relapse rate (ARR) and MRI parameters compared with teriflunomide in patients with relapsing forms of MS.

The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

‘Glycoengineered’ antibody

If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.

There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.

For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.

Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.

The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.

Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
 

Primary outcomes met

For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).

In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).

One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”

It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.

From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.

Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.

There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).

The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
 

A life changer?

Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”

The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.

The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.

If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.

However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”

Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.

“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.

He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.

Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.

The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
 

Striking improvement

When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”

Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.

He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”

Dr. Steinman is a consultant for TG Therapeutics.

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

Patients with multiple sclerosis (MS) may soon have another less expensive, more convenient treatment option compared with other agents in the same drug class, new research suggests.

Results from two new phase 3 trials show that the investigational drug ublituximab (TG Therapeutics), a novel glycoengineered anti-CD20 monoclonal antibody, significantly reduced the annualized relapse rate (ARR) and MRI parameters compared with teriflunomide in patients with relapsing forms of MS.

The positive results suggest “another strong and reasonably safe medication might be available to increase the repertoire of effective medicines that we can offer MS patients,” said Lawrence Steinman, MD, professor of neurology, Stanford (Calif.) University. “These are delightful data in my opinion,” he added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

‘Glycoengineered’ antibody

If approved by the U.S. Food and Drug Administration, ublituximab would become the only glycoengineered anti-CD20 monoclonal antibody for MS. Glycoengineering involves changing protein-associated carbohydrates to alter pharmacokinetic properties.

There are currently two approved anti-CD20 agents for MS, but both require 4-hour infusions. For many patients, this means “at least half their day is shot,” Dr. Steinman said. “A lot of people don’t want to or can’t miss a half day of work.” Ublituximab can be infused more rapidly, he noted.

For the study, the investigators analyzed data from the ULTIMATE I and ULTIMATE II studies, which included 1,089 mostly White patients with MS. Almost all participants had the relapsing-remitting form of the disease and were between 18 and 55 years of age (average age, 36 years). Their scores on the Expanded Disability Status Scale (EDSS) were from 0 to 5.5, and they had been neurologically stable for at least 30 days prior to screening.

Participants were required to have experienced two or more relapses within the previous 2 years or one or more relapses in the year prior and/or had one gadolinium-enhancing lesion in the year prior to screening.

The study population was mostly from the Ukraine and Russia. It is more difficult to recruit patients into MS drug studies in the United States and Western Europe because many patients in these countries are already receiving approved drugs, which deters enrollment, explained Dr. Steinman.

Investigators randomly assigned the participants to receive the investigational drug or 14 mg of oral teriflunomide, a drug that blocks the proliferation of immune cells, once daily. The ublituximab group received an initial infusion of 150 mg over 4 hours and then a 1-hour infusion of 450 mg every 6 months over the course of the 96-week study.
 

Primary outcomes met

For ULTIMATE I, the primary outcome was ARR. Results showed that this rate was 0.076 for the ublituximab group and 0.188 for the teriflunomide group, resulting in a 60% relative reduction (adjusted ARR ratio, 0.406; 95% confidence interval, 0.268-0.615; P < .0001).

In ULTIMATE II, the ARR was 0.091 for ublituximab and 0.178 for teriflunomide, for a relative reduction of 49% (ARR ratio, 0.509; 95% CI, 0.330-0.784; P = .0022).

One way of interpreting these data is that patients are likely to have only one relapse in 10 years, said Dr. Steinman. “So that was very good news.”

It is not clear why relative reductions for ARR differed between the two studies; “probably the real number is somewhere between 60% and 49%,” Dr. Steinman said.

From MRI scans, the total number of relevant lesions was reduced by 97% with ublituximab compared with teriflunomide in ULTIMATE I and by 96% in trial II.

Another “piece of really good news” from the studies is that the drug led to a significant improvement in disability, rather than “just slowing it down,” Dr. Steinman noted.

There was a 116% increased chance of confirmed disability improvement (CDI) with ublituximab versus teriflunomide in the first trial (P = .003) and a 103% increased chance of CDI in the second trial (P = .0026).

The percentage of patients who had no evidence of disease activity was 198% for the patients who received the trial drug in comparison with the control group in trial I and 277% in trial II (P < .0001 for both trials).
 

A life changer?

Dr. Steinman said the “robust” findings suggest that patients with MS “won’t have a relapse and will improve. Those are two pretty good messages for somebody with this wretched disease.”

The investigational drug was generally well tolerated. The percentage of adverse events (AEs) with the study drug was about the same as with the comparator. About 9.5% of the ublituximab group had a serious AE, compared with 6.2% of the teriflunomide group.

The ublituximab group had more infections (4.0% vs. 2.6%), which Dr. Steinman said is not surprising because the drug is a potent immune suppressant. “It’s an unfortunate consequence of this kind of strong biologic that knocks down a whole arm of the immune system. The wonder to me is that these are still rather infrequent,” he said.

If approved, “it will be interesting to see how regulatory agencies handle this in terms of risk mitigation,” said Dr. Steinman. He added that a warning label might be a consideration.

However, the safety of this drug “is certainly acceptable,” said Dr. Steinman. “In general, this drug is not that different from the other drugs in the class of anti-CD20s.”

Dr. Steinman noted that he understands why some patients prefer an oral drug and may have an “aversion to getting stuck with a needle,” but he pointed out that teriflunomide has some drawbacks. For example, it tends to thin hair.

“For people who have had relapses, people who are unable to do what they want to in life – attend school, hold down jobs, exercise – this new drug could really be life changing,” he said.

He added that he would “strongly urge” his own family and relatives, if they had MS, to take one of the anti-CD20 drugs.

Ublituximab also has a number of advantages over the other agents in the same class. Not only does it work well, have an acceptable safety profile, and require a shorter infusion time, but it could also be less costly, Dr. Steinman noted. “The company has said it intends to come in at a lower price point,” he said.

The company is now planning to prepare a biological license application for use in MS. Interestingly, the drug, in combination with umbralisib (Ukoniq), is already under review by the FDA for use in chronic lymphoctytic leukemia and small lymphocytic lymphoma.
 

Striking improvement

When session chair Marcello Moccio, MD, Multiple Sclerosis Clinical Care and Research Center, Federico II University, Naples, Italy, asked Dr. Steinman to elaborate on the “very strong effect” of the drug with regard to improving disability, Dr. Steinman said the improvement was “striking.”

Being able to talk to patients about possible improvement rather than about delaying disability “is really gratifying” and provides a “much more constructive and optimistic outlook,” he said.

He noted that as physicians improve their management of patients with MS “and are paying attention to things that we haven’t over the years, like vitamin D and even mental health,” disability progression management “is getting better.”

Dr. Steinman is a consultant for TG Therapeutics.

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

Clinicians who struggle to get dupilumab approved for their patients with moderate to severe atopic dermatitis (AD) are not alone.

Bruce Jancin/MDedge News

This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).

“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”

Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.

When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
 

Starting patients on dupilumab

Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”

She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”

If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
 

Data on effectiveness

Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.

In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.

What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.

While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.

Clinicians who struggle to get dupilumab approved for their patients with moderate to severe atopic dermatitis (AD) are not alone.

Bruce Jancin/MDedge News

This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).

“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”

Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.

When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
 

Starting patients on dupilumab

Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”

She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”

If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
 

Data on effectiveness

Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.

In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.

What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.

While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.

Clinicians who struggle to get dupilumab approved for their patients with moderate to severe atopic dermatitis (AD) are not alone.

Bruce Jancin/MDedge News

This scenario was illustrated in a 2020 retrospective study of 179 adults with AD who were cared for at the University of Pittsburgh Medical Center, which found that 37% did not start dupilumab, mainly due to insurance denial (19%) and high copay (11%).

“We’ve all seen this in our practice,” Amy S. Paller, MD, said during the Revolutionizing Atopic Dermatitis symposium. “We’ve also seen the denials until we get step therapy in there, so if I have a child whom I want to treat with dupilumab for safety reasons, I don’t like being told that I’m going to have to use cyclosporine or methotrexate or a medication that I think may have higher risks and certainly [would] require blood monitoring–yet that’s the state for some patients.”

Dupilumab, an interleukin-4 receptor alpha antagonist, is approved for treatment of moderate to severe AD in patients ages 6 and older.

When working to obtain insurance approval of dupilumab, Dr. Paller reminded dermatologists to document that the patient has moderate to severe AD “and document the negative effect on quality of life in order to try to help make it easier to get these medications for our patients.”
 

Starting patients on dupilumab

Dr. Paller, the Walter J. Hamlin Chair and Professor of Dermatology at Northwestern University, Chicago, said that if patients are on another systemic medication prior to starting dupilumab, she allows a transition period of 1-2 months. “Don’t just stop that drug because it’s ‘not working,’ ” she said. “I usually do a full dose for the first month, and a half dose for the next month before starting dupilumab. Also, don’t stop the use of topical corticosteroids. They can increase treatment response by 10%-20%, even when patients are on dupilumab.”

She recommends a 3- to 4-month trial of dupilumab while monitoring changes in disease severity, itch, and quality of life. “Usually there’s evidence of early improvement by 2 months in those who are going to do well enough to stay on the drug by about 4 months out,” she said. “In my experience, most pediatric patients do very well. In those with an inadequate response, about 50% will do better if you can increase the dose or frequency. Flares can still occur in those who do well. I usually push topicals when that happens.”

If patients respond well after starting dupilumab, Dr. Paller recommends that they continue on the drug for at least a year before considering a taper with the hope of “resetting” the immune system and having sustained improvement off drug. “Some parents and patients don’t want to stop the drug,” but for those who do, she tells them that she does not want to abruptly stop treatment, but to “space out the dosing” instead. “If someone is pretty much clear with the medication and is able to continue with topicals as you dial down, that’s great. But don’t even think about taking them off if somebody’s not clear or virtually clear, particularly if they start to flare with lower frequency.”
 

Data on effectiveness

Real-world data suggest that the effectiveness of dupilumab is similar to the efficacy seen in clinical trials. For example, a recently published systematic review and meta-analysis of 3,303 AD patients on dupilumab found that after 16 weeks of therapy, 60% achieved a 75% improvement in the Eczema Area and Severity (EASI75) score, and 27% achieved an EASI90. In a Dutch study of 210 adults treated with dupilumab for 52 weeks, enrolled in a Dutch registry, the mean percent reduction in EASI score was 70% at 16 weeks and 76.6% by 52 weeks.

In addition, there was at least a 4-point improvement in the Patient-Oriented Eczema Measure (POEM) score and at least a 4-point improvement in the Itch Numeric Rating Scale (NRS), said Dr. Paller, who was not involved in the study. “These patient-reported improvements were seen very early on,” she noted.

What about drug survival at 1 year? In a retrospective cohort study that drew from insurance databases, 1,963 adults given dupilumab were studied for a mean of 315 days. The rate of persistence was 92% at 6 months and 77% at 12 months. “That means that it’s still effective,” Dr. Paller said.

While that is a short period of time, she compared these results with long-term survival of nonsteroid systemic immunosuppressants such as cyclosporine, referring to a study of adults with AD treated with systemic immunosuppressants, which found “a 32% persistence rate at 12 months in drugs that require more monitoring, so more burden.”

Dr. Paller disclosed that she is a consultant to and/or an investigator for dupilumab (Dupixent) manufacturers Regeneron and Sanofi, AbbVie, Arena, Bausch, Bristol Myers Squibb, Dermavant, Eli Lilly, Incyte, Forte, LEO Pharma, LifeMax, Pfizer, and RAPT Therapeutics.

Obesity hypoventilation syndrome (OHS) is bound to be increasing because of the rising obesity epidemic but is underrecognized and “frequently underdiagnosed,” Saiprakash B. Venkateshiah, MD, said at the virtual annual meeting of the Associated Professional Sleep Societies.

The condition, which can cause significant morbidity and mortality, is defined by the combination of obesity and awake alveolar hypoventilation (PaCO₂ ≥45 mm Hg), with the exclusion of alternate causes of hypoventilation. Sleep-disordered breathing (SDB) is almost universally present, with approximately 90% of individuals with OHS also having obstructive sleep apnea (OSA), most often severe, and approximately 10% having sleep-related hypoventilation, or a “pure hypoventilation subtype, if you will,” said Dr. Venkateshiah, assistant professor of medicine at Emory University, Atlanta.

The prevalence of OHS in the general population is unknown, but its prevalence in patients who present for the evaluation of SDB has ranged from 8%-20% across multiple studies, he said. Up to 40% of patients with OHS present for the first time with acute hypercapnic respiratory failure, which has an in-hospital mortality of 18%.

Postmenopausal women appear to have a higher prevalence, compared with premenopausal women and men, he noted, and women appear to be more likely than men to present with the clinical phenotype of OHS without associated OSA.

The arterial blood gas measurement needed to document alveolar hypoventilation and definitively diagnosis OHA is a “simple and economical test,” he said, “but it is logistically very difficult to obtain [these measurements] routinely in all patients in the clinic ... and is one of the reasons why OSH is underdiagnosed.”
 

Guideline advice

A practice guideline published in 2019 by the American Thoracic Society suggests that, for obese patients with SDB and a low to moderate probability of having OSH, a serum bicarbonate level be measured first. “In patients with serum bicarbonate less than 27 mmol/L, clinicians might forgo measuring PaCO₂, as the diagnosis in them is very unlikely,” Dr. Venkateshiah said, referring to the guideline. “In patients with a serum bicarbonate greater than 27, you might need to measure PaCO₂ to confirm or rule out the diagnosis of OHS.”

(Patients strongly suspected of having OHS, with more than a low to moderate probability – those in whom arterial blood gases should be measured – are “usually severely obese with typical signs and symptoms such as dyspnea, nocturia, lower-extremity edema, excessive daytime sleepiness, fatigue, loud disruptive snoring, witnessed apneas, as well as mild hypoxemia during wake and/or significant hypoxemia during sleep,” the ATS guideline says.)

The guideline panel considered the use of oxygen saturation measured with pulse oximetry during wakefulness to screen for OHS and decided to advise against it because of the paucity of evidence-based literature, Dr. Venkateshiah noted. (In making its five conditional recommendations, the guideline panel cited an overall very low quality of evidence.)

Symptoms of OHS overlap with those of OSA (for example, daytime hypersomnolence, witnessed apneas, loud snoring, and morning headaches), so “symptoms alone cannot be used to discriminate between the two disorders,” he advised. Signs of OHS commonly seen in clinical exams, however, are low resting daytime oxygen saturations and lower-extremity edema. A sleep study, he added, is needed to document and characterize SDB in patients with OHS.

Positive airway pressure therapy is the first-line treatment for OHS, and long-term outcomes of patients with OHS on PAP treatment are significantly better, compared with untreated individuals. There is no strong evidence to recommend one form of PAP therapy over another for patients with OHS and concomitant severe OSA, he said, but “the bottom line” from both short- and long-term randomized clinical trials comparing CPAP with noninvasive ventilation “is that CPAP is equivalent to noninvasive ventilation as far as outcomes are concerned.”

The ATS guideline panel recommends continuous positive airway pressure therapy for patients with OHS and severe OSA. And for OHS with nonsevere OSA, bilevel PAP is traditionally used – including pure hypoventilators, Dr. Venkateshiah said.

Weight-loss interventions are paramount, since “the primary driver of OHS is obesity,” he said at the meeting. There are only a few studies that have looked at bariatric surgery in patients with OHS, he said, “but they did note significant improvements in gas exchange, sleep apnea, lung volumes and pulmonary hypertension.”

The ATS guideline suggests weight-loss interventions that produce sustained weight loss of 25%-30% of the actual body weight. Such interventions are “most likely required to achieve resolution of hypoventilation,” Dr. Venkateshiah said.
 

OHS vs. COPD

In a separate presentation on OHS, Michelle Cao, DO, clinical associate professor at Stanford (Calif.) University, emphasized the importance of distinguishing the patient with OHS from the patient with hypercapnic chronic obstructive pulmonary disease (COPD). Spirometry and the flow volume curve can help rule out hypercapnic COPD and other conditions that cause daytime hypoventilation.

A study published in 2016 of 600 hospitalized patients determined to have unequivocal OHS found that 43% had been misdiagnosed as having COPD and none had been previously diagnosed with OHS, Dr. Cao noted. Patients in the study had a mean age of 58 and a mean body mass index of 48.2 kg/m²; 64% were women.

Dr. Venkateshiah and Dr. Cao had no relevant disclosures.

Obesity hypoventilation syndrome (OHS) is bound to be increasing because of the rising obesity epidemic but is underrecognized and “frequently underdiagnosed,” Saiprakash B. Venkateshiah, MD, said at the virtual annual meeting of the Associated Professional Sleep Societies.

The condition, which can cause significant morbidity and mortality, is defined by the combination of obesity and awake alveolar hypoventilation (PaCO₂ ≥45 mm Hg), with the exclusion of alternate causes of hypoventilation. Sleep-disordered breathing (SDB) is almost universally present, with approximately 90% of individuals with OHS also having obstructive sleep apnea (OSA), most often severe, and approximately 10% having sleep-related hypoventilation, or a “pure hypoventilation subtype, if you will,” said Dr. Venkateshiah, assistant professor of medicine at Emory University, Atlanta.

The prevalence of OHS in the general population is unknown, but its prevalence in patients who present for the evaluation of SDB has ranged from 8%-20% across multiple studies, he said. Up to 40% of patients with OHS present for the first time with acute hypercapnic respiratory failure, which has an in-hospital mortality of 18%.

Postmenopausal women appear to have a higher prevalence, compared with premenopausal women and men, he noted, and women appear to be more likely than men to present with the clinical phenotype of OHS without associated OSA.

The arterial blood gas measurement needed to document alveolar hypoventilation and definitively diagnosis OHA is a “simple and economical test,” he said, “but it is logistically very difficult to obtain [these measurements] routinely in all patients in the clinic ... and is one of the reasons why OSH is underdiagnosed.”
 

Guideline advice

A practice guideline published in 2019 by the American Thoracic Society suggests that, for obese patients with SDB and a low to moderate probability of having OSH, a serum bicarbonate level be measured first. “In patients with serum bicarbonate less than 27 mmol/L, clinicians might forgo measuring PaCO₂, as the diagnosis in them is very unlikely,” Dr. Venkateshiah said, referring to the guideline. “In patients with a serum bicarbonate greater than 27, you might need to measure PaCO₂ to confirm or rule out the diagnosis of OHS.”

(Patients strongly suspected of having OHS, with more than a low to moderate probability – those in whom arterial blood gases should be measured – are “usually severely obese with typical signs and symptoms such as dyspnea, nocturia, lower-extremity edema, excessive daytime sleepiness, fatigue, loud disruptive snoring, witnessed apneas, as well as mild hypoxemia during wake and/or significant hypoxemia during sleep,” the ATS guideline says.)

The guideline panel considered the use of oxygen saturation measured with pulse oximetry during wakefulness to screen for OHS and decided to advise against it because of the paucity of evidence-based literature, Dr. Venkateshiah noted. (In making its five conditional recommendations, the guideline panel cited an overall very low quality of evidence.)

Symptoms of OHS overlap with those of OSA (for example, daytime hypersomnolence, witnessed apneas, loud snoring, and morning headaches), so “symptoms alone cannot be used to discriminate between the two disorders,” he advised. Signs of OHS commonly seen in clinical exams, however, are low resting daytime oxygen saturations and lower-extremity edema. A sleep study, he added, is needed to document and characterize SDB in patients with OHS.

Positive airway pressure therapy is the first-line treatment for OHS, and long-term outcomes of patients with OHS on PAP treatment are significantly better, compared with untreated individuals. There is no strong evidence to recommend one form of PAP therapy over another for patients with OHS and concomitant severe OSA, he said, but “the bottom line” from both short- and long-term randomized clinical trials comparing CPAP with noninvasive ventilation “is that CPAP is equivalent to noninvasive ventilation as far as outcomes are concerned.”

The ATS guideline panel recommends continuous positive airway pressure therapy for patients with OHS and severe OSA. And for OHS with nonsevere OSA, bilevel PAP is traditionally used – including pure hypoventilators, Dr. Venkateshiah said.

Weight-loss interventions are paramount, since “the primary driver of OHS is obesity,” he said at the meeting. There are only a few studies that have looked at bariatric surgery in patients with OHS, he said, “but they did note significant improvements in gas exchange, sleep apnea, lung volumes and pulmonary hypertension.”

The ATS guideline suggests weight-loss interventions that produce sustained weight loss of 25%-30% of the actual body weight. Such interventions are “most likely required to achieve resolution of hypoventilation,” Dr. Venkateshiah said.
 

OHS vs. COPD

In a separate presentation on OHS, Michelle Cao, DO, clinical associate professor at Stanford (Calif.) University, emphasized the importance of distinguishing the patient with OHS from the patient with hypercapnic chronic obstructive pulmonary disease (COPD). Spirometry and the flow volume curve can help rule out hypercapnic COPD and other conditions that cause daytime hypoventilation.

A study published in 2016 of 600 hospitalized patients determined to have unequivocal OHS found that 43% had been misdiagnosed as having COPD and none had been previously diagnosed with OHS, Dr. Cao noted. Patients in the study had a mean age of 58 and a mean body mass index of 48.2 kg/m²; 64% were women.

Dr. Venkateshiah and Dr. Cao had no relevant disclosures.

Obesity hypoventilation syndrome (OHS) is bound to be increasing because of the rising obesity epidemic but is underrecognized and “frequently underdiagnosed,” Saiprakash B. Venkateshiah, MD, said at the virtual annual meeting of the Associated Professional Sleep Societies.

The condition, which can cause significant morbidity and mortality, is defined by the combination of obesity and awake alveolar hypoventilation (PaCO₂ ≥45 mm Hg), with the exclusion of alternate causes of hypoventilation. Sleep-disordered breathing (SDB) is almost universally present, with approximately 90% of individuals with OHS also having obstructive sleep apnea (OSA), most often severe, and approximately 10% having sleep-related hypoventilation, or a “pure hypoventilation subtype, if you will,” said Dr. Venkateshiah, assistant professor of medicine at Emory University, Atlanta.

The prevalence of OHS in the general population is unknown, but its prevalence in patients who present for the evaluation of SDB has ranged from 8%-20% across multiple studies, he said. Up to 40% of patients with OHS present for the first time with acute hypercapnic respiratory failure, which has an in-hospital mortality of 18%.

Postmenopausal women appear to have a higher prevalence, compared with premenopausal women and men, he noted, and women appear to be more likely than men to present with the clinical phenotype of OHS without associated OSA.

The arterial blood gas measurement needed to document alveolar hypoventilation and definitively diagnosis OHA is a “simple and economical test,” he said, “but it is logistically very difficult to obtain [these measurements] routinely in all patients in the clinic ... and is one of the reasons why OSH is underdiagnosed.”
 

Guideline advice

A practice guideline published in 2019 by the American Thoracic Society suggests that, for obese patients with SDB and a low to moderate probability of having OSH, a serum bicarbonate level be measured first. “In patients with serum bicarbonate less than 27 mmol/L, clinicians might forgo measuring PaCO₂, as the diagnosis in them is very unlikely,” Dr. Venkateshiah said, referring to the guideline. “In patients with a serum bicarbonate greater than 27, you might need to measure PaCO₂ to confirm or rule out the diagnosis of OHS.”

(Patients strongly suspected of having OHS, with more than a low to moderate probability – those in whom arterial blood gases should be measured – are “usually severely obese with typical signs and symptoms such as dyspnea, nocturia, lower-extremity edema, excessive daytime sleepiness, fatigue, loud disruptive snoring, witnessed apneas, as well as mild hypoxemia during wake and/or significant hypoxemia during sleep,” the ATS guideline says.)

The guideline panel considered the use of oxygen saturation measured with pulse oximetry during wakefulness to screen for OHS and decided to advise against it because of the paucity of evidence-based literature, Dr. Venkateshiah noted. (In making its five conditional recommendations, the guideline panel cited an overall very low quality of evidence.)

Symptoms of OHS overlap with those of OSA (for example, daytime hypersomnolence, witnessed apneas, loud snoring, and morning headaches), so “symptoms alone cannot be used to discriminate between the two disorders,” he advised. Signs of OHS commonly seen in clinical exams, however, are low resting daytime oxygen saturations and lower-extremity edema. A sleep study, he added, is needed to document and characterize SDB in patients with OHS.

Positive airway pressure therapy is the first-line treatment for OHS, and long-term outcomes of patients with OHS on PAP treatment are significantly better, compared with untreated individuals. There is no strong evidence to recommend one form of PAP therapy over another for patients with OHS and concomitant severe OSA, he said, but “the bottom line” from both short- and long-term randomized clinical trials comparing CPAP with noninvasive ventilation “is that CPAP is equivalent to noninvasive ventilation as far as outcomes are concerned.”

The ATS guideline panel recommends continuous positive airway pressure therapy for patients with OHS and severe OSA. And for OHS with nonsevere OSA, bilevel PAP is traditionally used – including pure hypoventilators, Dr. Venkateshiah said.

Weight-loss interventions are paramount, since “the primary driver of OHS is obesity,” he said at the meeting. There are only a few studies that have looked at bariatric surgery in patients with OHS, he said, “but they did note significant improvements in gas exchange, sleep apnea, lung volumes and pulmonary hypertension.”

The ATS guideline suggests weight-loss interventions that produce sustained weight loss of 25%-30% of the actual body weight. Such interventions are “most likely required to achieve resolution of hypoventilation,” Dr. Venkateshiah said.
 

OHS vs. COPD

In a separate presentation on OHS, Michelle Cao, DO, clinical associate professor at Stanford (Calif.) University, emphasized the importance of distinguishing the patient with OHS from the patient with hypercapnic chronic obstructive pulmonary disease (COPD). Spirometry and the flow volume curve can help rule out hypercapnic COPD and other conditions that cause daytime hypoventilation.

A study published in 2016 of 600 hospitalized patients determined to have unequivocal OHS found that 43% had been misdiagnosed as having COPD and none had been previously diagnosed with OHS, Dr. Cao noted. Patients in the study had a mean age of 58 and a mean body mass index of 48.2 kg/m²; 64% were women.

Dr. Venkateshiah and Dr. Cao had no relevant disclosures.

Background: In the United States, 5% of the population use half of the annual spending for health care services and 1% account for approximately a quarter of annual spending, considered “superutilizers” of U.S. health care services. The Camden Coalition of Healthcare Providers (the Coalition) developed a model using hospital admission data to identify superutilizers, termed “hotspotting,” which has gained national recognition. Unlike other similar programs, this model targets a more diverse population with higher utilization than other programs that have been studied.
 

Study design: Randomized, controlled trial.

Setting: Two hospitals in Camden, N.J., from June 2, 2014, to March 31, 2018.

Synopsis: Eight-hundred superutilizers (at least one hospital admission at any of the four Camden-area hospital systems in the past 6 months, greater than one chronic medical condition, more than one high-risk traits/conditions) were randomly assigned to the intervention group or usual care. Once enrolled in the hospital, a multidisciplinary team began working with the patient in the intervention group on discharge. Team members conducted home visits, scheduled/took patients to appointments, managed medications, monitored and coached patients in disease-specific self-care, and assisted with applying for social and other assistive programs.

The readmission rate within 180 days after hospital discharge (primary outcome) between groups was not significant, with 62.3% readmitted in the intervention group and 61.7% in the control group. There was also no effect on the defined secondary outcomes (number of readmissions, proportion of patients with more than two readmissions, hospital days, charges, payments received, mortality).

The trial was not powered to detect smaller reductions in readmissions or to analyze effects within specific subgroups.

Bottom line: The addition of the Coalition’s program to patients with very high use of health care services did not decrease hospital readmission rate when compared to usual care.

Citation: Finkelstein A et al. Health care hotspotting – a randomized, controlled trial. N Engl J Med. 2020;382:152-62.

Dr. Trammell-Velasquez is a hospitalist and associate professor of medicine at University of Texas Health, San Antonio.

Background: In the United States, 5% of the population use half of the annual spending for health care services and 1% account for approximately a quarter of annual spending, considered “superutilizers” of U.S. health care services. The Camden Coalition of Healthcare Providers (the Coalition) developed a model using hospital admission data to identify superutilizers, termed “hotspotting,” which has gained national recognition. Unlike other similar programs, this model targets a more diverse population with higher utilization than other programs that have been studied.
 

Study design: Randomized, controlled trial.

Setting: Two hospitals in Camden, N.J., from June 2, 2014, to March 31, 2018.

Synopsis: Eight-hundred superutilizers (at least one hospital admission at any of the four Camden-area hospital systems in the past 6 months, greater than one chronic medical condition, more than one high-risk traits/conditions) were randomly assigned to the intervention group or usual care. Once enrolled in the hospital, a multidisciplinary team began working with the patient in the intervention group on discharge. Team members conducted home visits, scheduled/took patients to appointments, managed medications, monitored and coached patients in disease-specific self-care, and assisted with applying for social and other assistive programs.

The readmission rate within 180 days after hospital discharge (primary outcome) between groups was not significant, with 62.3% readmitted in the intervention group and 61.7% in the control group. There was also no effect on the defined secondary outcomes (number of readmissions, proportion of patients with more than two readmissions, hospital days, charges, payments received, mortality).

The trial was not powered to detect smaller reductions in readmissions or to analyze effects within specific subgroups.

Bottom line: The addition of the Coalition’s program to patients with very high use of health care services did not decrease hospital readmission rate when compared to usual care.

Citation: Finkelstein A et al. Health care hotspotting – a randomized, controlled trial. N Engl J Med. 2020;382:152-62.

Dr. Trammell-Velasquez is a hospitalist and associate professor of medicine at University of Texas Health, San Antonio.

Background: In the United States, 5% of the population use half of the annual spending for health care services and 1% account for approximately a quarter of annual spending, considered “superutilizers” of U.S. health care services. The Camden Coalition of Healthcare Providers (the Coalition) developed a model using hospital admission data to identify superutilizers, termed “hotspotting,” which has gained national recognition. Unlike other similar programs, this model targets a more diverse population with higher utilization than other programs that have been studied.
 

Study design: Randomized, controlled trial.

Setting: Two hospitals in Camden, N.J., from June 2, 2014, to March 31, 2018.

Synopsis: Eight-hundred superutilizers (at least one hospital admission at any of the four Camden-area hospital systems in the past 6 months, greater than one chronic medical condition, more than one high-risk traits/conditions) were randomly assigned to the intervention group or usual care. Once enrolled in the hospital, a multidisciplinary team began working with the patient in the intervention group on discharge. Team members conducted home visits, scheduled/took patients to appointments, managed medications, monitored and coached patients in disease-specific self-care, and assisted with applying for social and other assistive programs.

The readmission rate within 180 days after hospital discharge (primary outcome) between groups was not significant, with 62.3% readmitted in the intervention group and 61.7% in the control group. There was also no effect on the defined secondary outcomes (number of readmissions, proportion of patients with more than two readmissions, hospital days, charges, payments received, mortality).

The trial was not powered to detect smaller reductions in readmissions or to analyze effects within specific subgroups.

Bottom line: The addition of the Coalition’s program to patients with very high use of health care services did not decrease hospital readmission rate when compared to usual care.

Citation: Finkelstein A et al. Health care hotspotting – a randomized, controlled trial. N Engl J Med. 2020;382:152-62.

Dr. Trammell-Velasquez is a hospitalist and associate professor of medicine at University of Texas Health, San Antonio.

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

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

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

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

The contraceptive needs of women who have had in vitro fertilization (IVF) pregnancies are real but are being overlooked, according to study data presented at the Royal College of Obstetricians & Gynaecologists (RCOG) Virtual World Congress 2021.

The interview-based study found that women report not being routinely informed about the chance of spontaneous pregnancy after IVF. “There is scope to follow-up with women after IVF … but information about the chances of spontaneous births and need for contraception isn’t given,” said lead researcher Annette Thwaites, MD, an academic clinical fellow and a senior registrar in Community Sexual and Reproductive Health at Kings College Hospital, London.

“Fertility services, maternity services, and community services could all do more to give women information on contraception postnatally,” Dr. Thwaites said.

“Even if a woman has had IVF previously, a woman shouldn’t lose the right to plan the rest of her family,” she added. “We need to stop shielding these women from the information they really do need.”

Dr. Thwaites first came across the issue around contraception after IVF pregnancy while talking to new mothers in a postnatal ward for another study. Ward staff told her not to enter the rooms with women who had had IVF births, with the implication that these women would not need or want contraception.

With this in mind, Dr. Thwaites and colleagues aimed to better understand the contraceptive needs of women after successful IVF pregnancy to improve service delivery and prevent unplanned and rapid-repeat pregnancies after IVF.

The researchers interviewed 21 women who had spontaneous pregnancies after successful IVF. Participants were aged 35-50 years, the majority were White, British, professional, married for at least 10 years, and living in nuclear families.

Of the spontaneous post-IVF pregnancies in these women, outcomes included single (11) and multiple live births (1 twin), miscarriage (1), ectopic (1) termination of pregnancy (1), and three ongoing pregnancies.  

After IVF pregnancy, most women said that they used no contraception or ineffective contraception and had never had a conversation around contraception after IVF.

The women also reported that spontaneous pregnancy was shocking and not universally welcomed, and interpregnancy intervals were often short.

In addition, comments by these women suggested certain aspects of the IVF experience reinforced their perceptions of subfertility. One is quoted as saying, “It seemed to be this big failure if you were having IVF.” Another said, “It’s bad enough that I’m having to conceive my baby like this.”
 

An unmet need

In her 30 years of practice, Melanie Davies, MD, has seen many women who experience natural pregnancy after IVF. She agrees it is important to address these women’s contraceptive needs but stresses that it needs to be approached carefully.

“It can stir up sensitivities to discuss this issue after having an IVF pregnancy,” said Dr. Davies, a consultant obstetrician and gynecologist at University College London Hospitals, London. “I think many women genuinely think that contraception after IVF just doesn’t apply, but lots of women do have natural pregnancies after IVF. I think women do need this information, but we need to be aware of the sensitivities around this issue, so the way we deliver it is crucial.”

Gwenda Burns, chief executive of the National Patient Charity Fertility Network UK, which supports people before, during, and after fertility treatment, agrees that the process leading up to a successful IVF birth can have lasting effects.

“Fertility struggles and going through fertility treatment can put an enormous strain on both physical and mental health and can have a long-lasting impact,” Ms. Burns said when asked to comment on the new study.

“It is vital that patients receive the right support, guidance, and advice following treatment, including when natural conception may still be possible,” Ms. Burns continued.
 

Growing population

Given the increasing use of IVF in recent years, Dr. Thwaites said the importance of understanding and meeting the contraceptive needs of women post-IVF is increasingly important. Also, people are turning to it earlier and for other reasons, such as women in same sex relationships, single women, pre-implantation genetic testing, and surrogates.

“During the recruitment process for the current study, I came across women who said since their IVF pregnancies they had no idea what they should do about contraception,” Dr. Thwaites said.

But she empathizes with health care professionals too. “I genuinely feel that health care professionals just don’t know how to advise women in this setting, so they avoid the topic of contraception altogether with these women. They are concerned about making women feel awkward or upsetting them. In my experience, there is very little said about IVF and contraception in the same breath.”
 

Women believe subfertility always persists after IVF

Among participants in the study, the causes of the women’s subfertility were wide-ranging and included tubal, anovulatory, male factor, joint, and unexplained, the latter of which affects 25% of couples with fertility issues. In the cohort, women had taken up to 9 years to conceive their first child and one had a donor egg conception.

After IVF, the chance of pregnancy will depend on the reason for the couple’s subfertility. “Given that a huge number of patients these days have unexplained subfertility. This is when there is no absolute cause of infertility identified, and it might not prevent a pregnancy but slows it down,” Dr. Davies said in an interview. “Such couples still have a chance of natural pregnancy.”

Polycystic ovary syndrome as a cause of subfertility is often associated with improvement in fertility after IVF, Dr. Davies noted. “This can improve after a spontaneous pregnancy or after IVF, even if the IVF is not a success, and this is possibly due to needling the ovary.”

Dr. Thwaites added that challenging women’s perceptions of their subfertility is critical if headway is to be made on this topic. Many women have persistent views concerning their subfertility after successful IVF, which may be rooted in previous failed treatment; need for repeat cycles or intracytoplasmic sperm injection (ICSI); low numbers of eggs collected; poor quality embryos; and pregnancy complications, to note some of the most common reasons.

“So many [women] feel that they are very lucky to have had a pregnancy because their journey has been difficult. They might have had a successful pregnancy, but they still hold a sense of personal failure,” said Dr. Thwaites. “Even after spontaneous pregnancy some women said it was a miracle or freak event. [Yet two of these] women had two spontaneous pregnancies.”

Remarkably, even after subsequent spontaneous pregnancy, use of contraception and the most effective methods remained low among participants.

As well as fixed beliefs concerning their subfertility, other barriers to contraception use included a lack of knowledge of likelihood of spontaneous pregnancy; lack of contraceptive experience; and inherent incentives towards shorter interpregnancy intervals (e.g., the convenience and privacy of undergoing further IVF while still on maternity leave and availability of frozen embryos).

Looking ahead, Dr. Thwaites says there is a clear need to link and/or expand the maternity services dataset to uncover the true rates of post-IVF spontaneous pregnancy.

Dr. Thwaites and Dr. Davies have disclosed no relevant financial relationships.

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

Physical punishment doesn’t improve a child’s behavior or social competence, and in fact, it can make behavior worse, according to a new study published June 28, 2021, in The Lancet.

Spanking and hitting can also harm a child’s development and well-being, the authors wrote.

“Parents hit their children because they think doing so will improve their behavior,” Elizabeth Gershoff, PhD, the senior author and a human development professor at the University of Texas at Austin, told CNN. “Unfortunately for parents who hit, our research found clear and compelling evidence that physical punishment does not improve children’s behavior and instead makes it worse.”

Dr. Gershoff and colleagues reviewed 69 studies from numerous countries, including the United States, United Kingdom, Canada, China, Colombia, Greece, Japan, Switzerland, and Turkey. They focused on spanking and other physical punishment that parents might use to discipline a child, excluding verbal punishment and “severe” physical punishment such as punching or kicking that could be characterized as child abuse.

Some studies in the review found a mix of positive and negative results from spanking. But most of the studies showed a significant negative impact.

In 13 of 19 studies, spanking and other forms of physical punishment created more external negative behaviors over time, including increased aggression, increased antisocial behavior, and increased disruptive behavior at school. Children were more likely to “act out” after being physically punished, regardless of the child’s gender, race, or ethnicity, the authors found.

Several studies found that physical punishment increased signs of oppositional defiant disorder, which is linked with temper tantrums, spitefulness, vindictiveness, argumentative behavior, active defiance, and refusal to follow rules.

Dr. Gershoff and colleagues also looked at the link between how often physical punishment happened and a child’s negative behavior in seven of the studies. In five of those studies, there was a “dose-response effect.”

“In other words, as physical punishment increased in frequency, so did its likelihood of predicting worse outcomes over time,” Dr. Gershoff told CNN.

In addition, the review found that negative behavior wasn’t changed by parenting style. Even if parents had an overall warm and positive parenting style, physical punishment still led to an increase in behavioral issues.

In the United States, all 50 states allow parents to use physical punishment on children, and 19 states still have laws that allow schools to use corporal punishment, CNN reported.

But spanking appears to be declining in the United States, particularly among younger generations, according to a research letter published in JAMA Pediatrics in 2020. About 50% of parents reported spanking a child in 1993, which dropped to 35% in 2017.

The American Academy of Pediatrics issued a policy statement in 2018 in favor of “healthy forms of discipline,” such as positive reinforcement of good behavior, setting limits, and giving consequences such as time-out or taking away toys or privileges. The group recommends against spanking, hitting, slapping, threatening, insulting, humiliating, or shaming children, which can lead to behavioral problems and symptoms of depression in later years.

The AAP also suggests learning from mistakes, both for parents and children.

“Remember that, as a parent, you can give yourself a time out if you feel out of control,” the group wrote in a discipline tip sheet. “When you are feeling better, go back to your child, hug each other, and start over.”

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

Physical punishment doesn’t improve a child’s behavior or social competence, and in fact, it can make behavior worse, according to a new study published June 28, 2021, in The Lancet.

Spanking and hitting can also harm a child’s development and well-being, the authors wrote.

“Parents hit their children because they think doing so will improve their behavior,” Elizabeth Gershoff, PhD, the senior author and a human development professor at the University of Texas at Austin, told CNN. “Unfortunately for parents who hit, our research found clear and compelling evidence that physical punishment does not improve children’s behavior and instead makes it worse.”

Dr. Gershoff and colleagues reviewed 69 studies from numerous countries, including the United States, United Kingdom, Canada, China, Colombia, Greece, Japan, Switzerland, and Turkey. They focused on spanking and other physical punishment that parents might use to discipline a child, excluding verbal punishment and “severe” physical punishment such as punching or kicking that could be characterized as child abuse.

Some studies in the review found a mix of positive and negative results from spanking. But most of the studies showed a significant negative impact.

In 13 of 19 studies, spanking and other forms of physical punishment created more external negative behaviors over time, including increased aggression, increased antisocial behavior, and increased disruptive behavior at school. Children were more likely to “act out” after being physically punished, regardless of the child’s gender, race, or ethnicity, the authors found.

Several studies found that physical punishment increased signs of oppositional defiant disorder, which is linked with temper tantrums, spitefulness, vindictiveness, argumentative behavior, active defiance, and refusal to follow rules.

Dr. Gershoff and colleagues also looked at the link between how often physical punishment happened and a child’s negative behavior in seven of the studies. In five of those studies, there was a “dose-response effect.”

“In other words, as physical punishment increased in frequency, so did its likelihood of predicting worse outcomes over time,” Dr. Gershoff told CNN.

In addition, the review found that negative behavior wasn’t changed by parenting style. Even if parents had an overall warm and positive parenting style, physical punishment still led to an increase in behavioral issues.

In the United States, all 50 states allow parents to use physical punishment on children, and 19 states still have laws that allow schools to use corporal punishment, CNN reported.

But spanking appears to be declining in the United States, particularly among younger generations, according to a research letter published in JAMA Pediatrics in 2020. About 50% of parents reported spanking a child in 1993, which dropped to 35% in 2017.

The American Academy of Pediatrics issued a policy statement in 2018 in favor of “healthy forms of discipline,” such as positive reinforcement of good behavior, setting limits, and giving consequences such as time-out or taking away toys or privileges. The group recommends against spanking, hitting, slapping, threatening, insulting, humiliating, or shaming children, which can lead to behavioral problems and symptoms of depression in later years.

The AAP also suggests learning from mistakes, both for parents and children.

“Remember that, as a parent, you can give yourself a time out if you feel out of control,” the group wrote in a discipline tip sheet. “When you are feeling better, go back to your child, hug each other, and start over.”

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

Physical punishment doesn’t improve a child’s behavior or social competence, and in fact, it can make behavior worse, according to a new study published June 28, 2021, in The Lancet.

Spanking and hitting can also harm a child’s development and well-being, the authors wrote.

“Parents hit their children because they think doing so will improve their behavior,” Elizabeth Gershoff, PhD, the senior author and a human development professor at the University of Texas at Austin, told CNN. “Unfortunately for parents who hit, our research found clear and compelling evidence that physical punishment does not improve children’s behavior and instead makes it worse.”

Dr. Gershoff and colleagues reviewed 69 studies from numerous countries, including the United States, United Kingdom, Canada, China, Colombia, Greece, Japan, Switzerland, and Turkey. They focused on spanking and other physical punishment that parents might use to discipline a child, excluding verbal punishment and “severe” physical punishment such as punching or kicking that could be characterized as child abuse.

Some studies in the review found a mix of positive and negative results from spanking. But most of the studies showed a significant negative impact.

In 13 of 19 studies, spanking and other forms of physical punishment created more external negative behaviors over time, including increased aggression, increased antisocial behavior, and increased disruptive behavior at school. Children were more likely to “act out” after being physically punished, regardless of the child’s gender, race, or ethnicity, the authors found.

Several studies found that physical punishment increased signs of oppositional defiant disorder, which is linked with temper tantrums, spitefulness, vindictiveness, argumentative behavior, active defiance, and refusal to follow rules.

Dr. Gershoff and colleagues also looked at the link between how often physical punishment happened and a child’s negative behavior in seven of the studies. In five of those studies, there was a “dose-response effect.”

“In other words, as physical punishment increased in frequency, so did its likelihood of predicting worse outcomes over time,” Dr. Gershoff told CNN.

In addition, the review found that negative behavior wasn’t changed by parenting style. Even if parents had an overall warm and positive parenting style, physical punishment still led to an increase in behavioral issues.

In the United States, all 50 states allow parents to use physical punishment on children, and 19 states still have laws that allow schools to use corporal punishment, CNN reported.

But spanking appears to be declining in the United States, particularly among younger generations, according to a research letter published in JAMA Pediatrics in 2020. About 50% of parents reported spanking a child in 1993, which dropped to 35% in 2017.

The American Academy of Pediatrics issued a policy statement in 2018 in favor of “healthy forms of discipline,” such as positive reinforcement of good behavior, setting limits, and giving consequences such as time-out or taking away toys or privileges. The group recommends against spanking, hitting, slapping, threatening, insulting, humiliating, or shaming children, which can lead to behavioral problems and symptoms of depression in later years.

The AAP also suggests learning from mistakes, both for parents and children.

“Remember that, as a parent, you can give yourself a time out if you feel out of control,” the group wrote in a discipline tip sheet. “When you are feeling better, go back to your child, hug each other, and start over.”

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

OBSTETRIC ANAL SPHINCTER INJURY: PREVENTION AND REPAIR 

ROBERT L. BARBIERI, MD (EDITORIAL; MAY 2021)

Experience with warm perineal compresses and massage

I have been a midwife for 45 years. I have used warm compresses on the perineum my whole career. I don't need data to tell me it provides comfort. My patients do. 
I don't do much massage of the perineum, only slightly while applying K-Y or another water-soluble gel. 

A slow, controlled extension of the vertex and healthy tissue is the best way to prevent tears. 

Karen Parker, MN, CNM 

Ashland, Oregon 

Dr. Barbieri responds 

I thank Ms. Parker for her clinical recommendation: "Yes to warm compresses" and "Massage of the perineum?" Not so much. 

Continue to: CESAREAN MYOMECTOMY...

ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2021) 

Timely comments on cesarean myomectomy 

Dr. Barbieri's editorial on cesarean myomectomy is very timely, especially the quote from Dr. K.S.J. Olah: "The berating I received was severe and disproportionate to the crime. The rule was that myomectomy performed at cesarean section was not just frowned upon but expressly forbidden." 

I had a very similar experience with panniculectomy and "tummy tuck" as a part of cesarean delivery (CD). Traditionally, a combination of a CD with any other surgical procedures (myomectomy, abdominoplasty, and so on) has not been accepted in the obstetric community. The main reason for such an opinion has been the unfounded fear of complications of combined procedures, including but not limited to infection, hematomas, and poor wound healing. None of these concerns have been supported by studies. Obvious advantages of combining a CD with other surgical procedures, including abdominoplasty, are obvious: the elimination of a second anesthesia, increased patient satisfaction, and no need for a second surgery. 

We reviewed the outcomes in 52 patients who underwent a combination of CD with other procedures (such as panniculectomy, abdominoplasty, hernia repairs, myomectomies, and ovarian biopsies). The postsurgical outcomes included in the analysis were postsurgical fever and the presence of seromas, hematomas, and wound dehiscence.¹ Twelve of our own patients had a panniculectomy during CD performed by a plastic surgeon. While the preoperative complications of panniculectomy may have been well described, there is a paucity of data in women who underwent the cosmetic procedure at the time of CD. We concluded that the performance of a panniculectomy and tummy tuck as part of a CD does not appear to increase surgical complications in patients with a high body mass index. Our preliminary results and call for further studies were received at the American College of Surgeons 2017 meeting in San Diego.² 

Boris Petrikovsky, MD, PhD 

Sunny Island Beach, Florida 

References 

1. Petrikovsky BM, Swancoat S, Zharov EV. Safety of panniculectomy during cesarean section: a prospective, non-randomized study. J Reprod Med. 2019;64:197-200. 
2. Petrikovsky BM. Is the combination of panniculectomy and cesarean section safe? Scientific Poster Presentation-Obstetrics and Gynecology. J Am Coll Surg. 2017;225(4 suppl 2):E130. 

Dr. Barbieri responds 

I agree with Dr. Petrikovsky that advances in the field of obstetrical surgery have been inhibited by a tendency to criticize innovation. Less than 40 years ago, leaders in gynecology did not initially accept the application of minimally invasive gynecology surgical techniques to common gyn procedures including hysterectomy. Every surgical field is rapidly innovating. Obstetrical surgeons should be encouraged to pursue new approaches, as you are doing. We wish you success in your pioneering work. 

Continue to: A CASE OF BV...

A CASE OF BV DURING PREGNANCY: BEST MANAGEMENT APPROACH 

CALLIE FOX REEDER, MD, AND PATRICK DUFF, MD (ID CONSULT; FEBRUARY 2021) 

Secnidazole for treatment of BV 

The article by Drs. Reeder and Duff incorrectly states that there are no single-dose therapeutic options for bacterial vaginosis (BV) in the United States. Secnidazole 2 g single oral dose was approved by the US Food and Drug Administration (FDA) in 2017, and it is now included in the American College of Obstetricians and Gynecologists' (ACOG) clinical management guidelines for the treatment of BV in nonpregnant patients. 

Secnidazole is not contraindicated in pregnancy. In a poster presented at the 2020 ACOG annual clinical meeting, we summarized results of the preclinical studies that were part of the FDA submission.¹ There was no evidence of secnidazole toxicity in fertility and pre- and postnatal reproductive toxicology studies. In addition, there were no adverse developmental outcomes when secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose. These findings are consistent with the observation that no other preclinical studies, or experience from postmarketing use of secnidazole for approved indications, have suggested a risk of adverse effects when using secnidazole in pregnancy. 

Steven E. Chavoustie, MD 

North Miami, Florida 

Reference 

1. Pentikis H, Eder S, Kaufman G, Chavoustie S. Secnidazole, an approved single dose drug for bacterial vaginosis, does not cause reproductive toxicity in animals [16A]. Obstet Gynecol. 2020;135:12S. 

Drs. Reeder and Duff respond 

We are very appreciative of Dr. Chavoustie's interest in our article and for his thoughtful assessment of the role of single-dose secnidazole for the treatment of BV. As we noted in our article, this drug has been used extensively in Europe and Asia, but there is much less published experience with the drug in the United States. We pointed out the excellent results reported by Hillier and colleagues with 1-g and 2-g doses of this medication.¹ Dr. Chavoustie is correct in stating that there is no risk of fetal harm based on animal data at up to 4 times the recommended human dose, although the manufacturer recommends discontinuing breastfeeding during, and for 96 hours after, treatment. According to www.goodrx.com, the cost of a single 2-g dose of secnidazole is $325; the cost of a 7-day course of metronidazole is approximately $16. 

Reference 

1. Hillier SL, Nyirjesy P, Waldbaum AS, et al. Secnidazole treatment of bacterial vaginosis: a randomized controlled trial. Obstet Gynecol. 2017;130:379-386. 

Continue to: OPTIMIZING THE USE OF...

ROBERT L. BARBIERI, MD (EDITORIAL; JANUARY 2021) 

Vigilant labor progress aids in oxytocin optimization 

I read with particular interest Dr. Barbieri's editorial on optimizing oxytocin infusion. This topic is relevant for my practice as I am the kind of physician described and I usually get upset when the oxytocin is not managed as I ordered. 

In my opinion, several things need clarification. On our unit, the most significant point of controversy is the definition of tachysystole, mainly when we are using a tocodynamometer and not an internal transducer. 

I contend that it is quite challenging to ascertain the effectiveness of any given labor pattern based only on the number of contractions. Although we joke about "pit to distress," the truth is that contractions need to be "effective," which to me means strong enough to induce cervical changes. 

In my clinical practice, with a tocodynamometer, having 5 contractions that do not produce cervical changes (unless associated with abnormalities of the fetal heart rate tracing) is not a clinically relevant finding as we do not have a way to gauge the strength of such contractions. 

I usually employ a mid-range oxytocin protocol, starting at 4 mU per minute and increasing by 4 mU every 20 minutes. Through 30 years of practicing obstetrics, I have found that this protocol renders excellent results in achieving an efficient labor pattern without jeopardizing fetal well-being. 

On learning about oxytocin's pharmacokinetics, I still support Dr. Rhonda L. Perry and her colleagues' conclusion that, until we learn better about this aspect of oxytocin pharmacology, each woman is her own bioassay.¹ Furthermore, we see this in our daily practice: some patients go into full efficient labor with oxytocin at 4 mU per minute while others at 30 mU per minute do zilch. 

Based on the above, I think that optimization requires close vigilance of the labor and the fetal status at any given time, not determining an oxytocin rate of infusion or dosage. 
We should be observant on evaluating labor progress, and we should not hesitate to use internal pressure catheters when needed to obtain a more accurate evaluation of the labor pattern. 

By examining the patient's labor progress at regular intervals, we also optimize the oxytocin infusion by determining if the infusion is producing the expected cervical changes. 

Tomas Hernandez-Mejia, MD 

Pasco, Washington 

Reference
 
1. Perry RL, Satin AJ, Barth WH, et al. The pharmacokinetics of oxytocin as they apply to labor induction. Am J Obstet Gynecol. 1996;174:1590-1593. 

Dr. Barbieri responds 

I thank Dr. Tomas Hernandez-Mejia for sharing his expertise in utilizing a higher dose of oxytocin to optimize labor and birth. Dr. Hernandez-Mejia's view is supported by the recent publication of a high-quality clinical trial showing that a high-dose oxytocin protocol (initial and incremental rate of 6 mIU/min) did not cause an increase in adverse perinatal outcomes compared with a standard-dose protocol (initial and incremental rate of 2 mIU/min) but slightly shortened the duration of labor.¹ Based on this clinical trial, my conclusion is that the high-dose protocol, if appropriately monitored for excess uterine contractions and fetal heart rate pattern, is safe. 

Reference 

1. Son M, Roy A, Stetson BT, et al. High-dose compared with standard-dose oxytocin regimens to augment labor in nulliparous women: a randomized controlled trial. Obstet Gynecol. 2021;137:991-998. 

Continue to: PREGNANCY OF UNKNOWN...

IRIS G. INSOGNA, MD, AND PAULA C. BRADY, MD (AUGUST 2020) 

I would like to thank Dr. Iris Insogna and Dr. Paula Brady for their very informative article on pregnancy of unknown location. However, please allow me to make a suggestion that will clarify terminology for all practicing ObGyns. 

The medical literature uses the terms cornual pregnancy and interstitial pregnancy interchangeably, although they are actually very different conditions and have significant different implications. Clinicians are often confused about which is an intrauterine pregnancy and which is a true ectopic pregnancy. This confusion was addressed in a 2006 article in Fertility and Sterility, which explains that a cornual pregnancy refers to the implantation and development of a gestation in one of the upper and lateral portions of the uterus.¹ This may occur in a rudimentary horn or in one horn of a septate or bicornuate uterus. Conversely, an interstitial pregnancy is a gestation that implants within the proximal, intramural portion of the fallopian tube that is enveloped by myometrium. Therefore, a cornual pregnancy is actually an intrauterine pregnancy, whereas an interstitial pregnancy is a true ectopic pregnancy. 

I hope that all clinicians will read the article in Fertility and Sterility and adopt this terminology to avoid future confusion and misunderstandings. 

Alan D. Rosen, MD 

Houston, Texas 

Reference 

1. Malinowski A, Bates SK. Semantics and pitfalls in the diagnosis of cornual/interstitial pregnancy. Fertil Steril. 2006;86:1764.e11-1764.e14.

OBSTETRIC ANAL SPHINCTER INJURY: PREVENTION AND REPAIR 

ROBERT L. BARBIERI, MD (EDITORIAL; MAY 2021)

Experience with warm perineal compresses and massage

I have been a midwife for 45 years. I have used warm compresses on the perineum my whole career. I don't need data to tell me it provides comfort. My patients do. 
I don't do much massage of the perineum, only slightly while applying K-Y or another water-soluble gel. 

A slow, controlled extension of the vertex and healthy tissue is the best way to prevent tears. 

Karen Parker, MN, CNM 

Ashland, Oregon 

Dr. Barbieri responds 

I thank Ms. Parker for her clinical recommendation: "Yes to warm compresses" and "Massage of the perineum?" Not so much. 

Continue to: CESAREAN MYOMECTOMY...

ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2021) 

Timely comments on cesarean myomectomy 

Dr. Barbieri's editorial on cesarean myomectomy is very timely, especially the quote from Dr. K.S.J. Olah: "The berating I received was severe and disproportionate to the crime. The rule was that myomectomy performed at cesarean section was not just frowned upon but expressly forbidden." 

I had a very similar experience with panniculectomy and "tummy tuck" as a part of cesarean delivery (CD). Traditionally, a combination of a CD with any other surgical procedures (myomectomy, abdominoplasty, and so on) has not been accepted in the obstetric community. The main reason for such an opinion has been the unfounded fear of complications of combined procedures, including but not limited to infection, hematomas, and poor wound healing. None of these concerns have been supported by studies. Obvious advantages of combining a CD with other surgical procedures, including abdominoplasty, are obvious: the elimination of a second anesthesia, increased patient satisfaction, and no need for a second surgery. 

We reviewed the outcomes in 52 patients who underwent a combination of CD with other procedures (such as panniculectomy, abdominoplasty, hernia repairs, myomectomies, and ovarian biopsies). The postsurgical outcomes included in the analysis were postsurgical fever and the presence of seromas, hematomas, and wound dehiscence.¹ Twelve of our own patients had a panniculectomy during CD performed by a plastic surgeon. While the preoperative complications of panniculectomy may have been well described, there is a paucity of data in women who underwent the cosmetic procedure at the time of CD. We concluded that the performance of a panniculectomy and tummy tuck as part of a CD does not appear to increase surgical complications in patients with a high body mass index. Our preliminary results and call for further studies were received at the American College of Surgeons 2017 meeting in San Diego.² 

Boris Petrikovsky, MD, PhD 

Sunny Island Beach, Florida 

References 

1. Petrikovsky BM, Swancoat S, Zharov EV. Safety of panniculectomy during cesarean section: a prospective, non-randomized study. J Reprod Med. 2019;64:197-200. 
2. Petrikovsky BM. Is the combination of panniculectomy and cesarean section safe? Scientific Poster Presentation-Obstetrics and Gynecology. J Am Coll Surg. 2017;225(4 suppl 2):E130. 

Dr. Barbieri responds 

I agree with Dr. Petrikovsky that advances in the field of obstetrical surgery have been inhibited by a tendency to criticize innovation. Less than 40 years ago, leaders in gynecology did not initially accept the application of minimally invasive gynecology surgical techniques to common gyn procedures including hysterectomy. Every surgical field is rapidly innovating. Obstetrical surgeons should be encouraged to pursue new approaches, as you are doing. We wish you success in your pioneering work. 

Continue to: A CASE OF BV...

A CASE OF BV DURING PREGNANCY: BEST MANAGEMENT APPROACH 

CALLIE FOX REEDER, MD, AND PATRICK DUFF, MD (ID CONSULT; FEBRUARY 2021) 

Secnidazole for treatment of BV 

The article by Drs. Reeder and Duff incorrectly states that there are no single-dose therapeutic options for bacterial vaginosis (BV) in the United States. Secnidazole 2 g single oral dose was approved by the US Food and Drug Administration (FDA) in 2017, and it is now included in the American College of Obstetricians and Gynecologists' (ACOG) clinical management guidelines for the treatment of BV in nonpregnant patients. 

Secnidazole is not contraindicated in pregnancy. In a poster presented at the 2020 ACOG annual clinical meeting, we summarized results of the preclinical studies that were part of the FDA submission.¹ There was no evidence of secnidazole toxicity in fertility and pre- and postnatal reproductive toxicology studies. In addition, there were no adverse developmental outcomes when secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose. These findings are consistent with the observation that no other preclinical studies, or experience from postmarketing use of secnidazole for approved indications, have suggested a risk of adverse effects when using secnidazole in pregnancy. 

Steven E. Chavoustie, MD 

North Miami, Florida 

Reference 

1. Pentikis H, Eder S, Kaufman G, Chavoustie S. Secnidazole, an approved single dose drug for bacterial vaginosis, does not cause reproductive toxicity in animals [16A]. Obstet Gynecol. 2020;135:12S. 

Drs. Reeder and Duff respond 

We are very appreciative of Dr. Chavoustie's interest in our article and for his thoughtful assessment of the role of single-dose secnidazole for the treatment of BV. As we noted in our article, this drug has been used extensively in Europe and Asia, but there is much less published experience with the drug in the United States. We pointed out the excellent results reported by Hillier and colleagues with 1-g and 2-g doses of this medication.¹ Dr. Chavoustie is correct in stating that there is no risk of fetal harm based on animal data at up to 4 times the recommended human dose, although the manufacturer recommends discontinuing breastfeeding during, and for 96 hours after, treatment. According to www.goodrx.com, the cost of a single 2-g dose of secnidazole is $325; the cost of a 7-day course of metronidazole is approximately $16. 

Reference 

1. Hillier SL, Nyirjesy P, Waldbaum AS, et al. Secnidazole treatment of bacterial vaginosis: a randomized controlled trial. Obstet Gynecol. 2017;130:379-386. 

Continue to: OPTIMIZING THE USE OF...

ROBERT L. BARBIERI, MD (EDITORIAL; JANUARY 2021) 

Vigilant labor progress aids in oxytocin optimization 

I read with particular interest Dr. Barbieri's editorial on optimizing oxytocin infusion. This topic is relevant for my practice as I am the kind of physician described and I usually get upset when the oxytocin is not managed as I ordered. 

In my opinion, several things need clarification. On our unit, the most significant point of controversy is the definition of tachysystole, mainly when we are using a tocodynamometer and not an internal transducer. 

I contend that it is quite challenging to ascertain the effectiveness of any given labor pattern based only on the number of contractions. Although we joke about "pit to distress," the truth is that contractions need to be "effective," which to me means strong enough to induce cervical changes. 

In my clinical practice, with a tocodynamometer, having 5 contractions that do not produce cervical changes (unless associated with abnormalities of the fetal heart rate tracing) is not a clinically relevant finding as we do not have a way to gauge the strength of such contractions. 

I usually employ a mid-range oxytocin protocol, starting at 4 mU per minute and increasing by 4 mU every 20 minutes. Through 30 years of practicing obstetrics, I have found that this protocol renders excellent results in achieving an efficient labor pattern without jeopardizing fetal well-being. 

On learning about oxytocin's pharmacokinetics, I still support Dr. Rhonda L. Perry and her colleagues' conclusion that, until we learn better about this aspect of oxytocin pharmacology, each woman is her own bioassay.¹ Furthermore, we see this in our daily practice: some patients go into full efficient labor with oxytocin at 4 mU per minute while others at 30 mU per minute do zilch. 

Based on the above, I think that optimization requires close vigilance of the labor and the fetal status at any given time, not determining an oxytocin rate of infusion or dosage. 
We should be observant on evaluating labor progress, and we should not hesitate to use internal pressure catheters when needed to obtain a more accurate evaluation of the labor pattern. 

By examining the patient's labor progress at regular intervals, we also optimize the oxytocin infusion by determining if the infusion is producing the expected cervical changes. 

Tomas Hernandez-Mejia, MD 

Pasco, Washington 

Reference
 
1. Perry RL, Satin AJ, Barth WH, et al. The pharmacokinetics of oxytocin as they apply to labor induction. Am J Obstet Gynecol. 1996;174:1590-1593. 

Dr. Barbieri responds 

I thank Dr. Tomas Hernandez-Mejia for sharing his expertise in utilizing a higher dose of oxytocin to optimize labor and birth. Dr. Hernandez-Mejia's view is supported by the recent publication of a high-quality clinical trial showing that a high-dose oxytocin protocol (initial and incremental rate of 6 mIU/min) did not cause an increase in adverse perinatal outcomes compared with a standard-dose protocol (initial and incremental rate of 2 mIU/min) but slightly shortened the duration of labor.¹ Based on this clinical trial, my conclusion is that the high-dose protocol, if appropriately monitored for excess uterine contractions and fetal heart rate pattern, is safe. 

Reference 

1. Son M, Roy A, Stetson BT, et al. High-dose compared with standard-dose oxytocin regimens to augment labor in nulliparous women: a randomized controlled trial. Obstet Gynecol. 2021;137:991-998. 

Continue to: PREGNANCY OF UNKNOWN...

IRIS G. INSOGNA, MD, AND PAULA C. BRADY, MD (AUGUST 2020) 

I would like to thank Dr. Iris Insogna and Dr. Paula Brady for their very informative article on pregnancy of unknown location. However, please allow me to make a suggestion that will clarify terminology for all practicing ObGyns. 

The medical literature uses the terms cornual pregnancy and interstitial pregnancy interchangeably, although they are actually very different conditions and have significant different implications. Clinicians are often confused about which is an intrauterine pregnancy and which is a true ectopic pregnancy. This confusion was addressed in a 2006 article in Fertility and Sterility, which explains that a cornual pregnancy refers to the implantation and development of a gestation in one of the upper and lateral portions of the uterus.¹ This may occur in a rudimentary horn or in one horn of a septate or bicornuate uterus. Conversely, an interstitial pregnancy is a gestation that implants within the proximal, intramural portion of the fallopian tube that is enveloped by myometrium. Therefore, a cornual pregnancy is actually an intrauterine pregnancy, whereas an interstitial pregnancy is a true ectopic pregnancy. 

I hope that all clinicians will read the article in Fertility and Sterility and adopt this terminology to avoid future confusion and misunderstandings. 

Alan D. Rosen, MD 

Houston, Texas 

Reference 

1. Malinowski A, Bates SK. Semantics and pitfalls in the diagnosis of cornual/interstitial pregnancy. Fertil Steril. 2006;86:1764.e11-1764.e14.

OBSTETRIC ANAL SPHINCTER INJURY: PREVENTION AND REPAIR 

ROBERT L. BARBIERI, MD (EDITORIAL; MAY 2021)

Experience with warm perineal compresses and massage

I have been a midwife for 45 years. I have used warm compresses on the perineum my whole career. I don't need data to tell me it provides comfort. My patients do. 
I don't do much massage of the perineum, only slightly while applying K-Y or another water-soluble gel. 

A slow, controlled extension of the vertex and healthy tissue is the best way to prevent tears. 

Karen Parker, MN, CNM 

Ashland, Oregon 

Dr. Barbieri responds 

I thank Ms. Parker for her clinical recommendation: "Yes to warm compresses" and "Massage of the perineum?" Not so much. 

Continue to: CESAREAN MYOMECTOMY...

ROBERT L. BARBIERI, MD (EDITORIAL; FEBRUARY 2021) 

Timely comments on cesarean myomectomy 

Dr. Barbieri's editorial on cesarean myomectomy is very timely, especially the quote from Dr. K.S.J. Olah: "The berating I received was severe and disproportionate to the crime. The rule was that myomectomy performed at cesarean section was not just frowned upon but expressly forbidden." 

I had a very similar experience with panniculectomy and "tummy tuck" as a part of cesarean delivery (CD). Traditionally, a combination of a CD with any other surgical procedures (myomectomy, abdominoplasty, and so on) has not been accepted in the obstetric community. The main reason for such an opinion has been the unfounded fear of complications of combined procedures, including but not limited to infection, hematomas, and poor wound healing. None of these concerns have been supported by studies. Obvious advantages of combining a CD with other surgical procedures, including abdominoplasty, are obvious: the elimination of a second anesthesia, increased patient satisfaction, and no need for a second surgery. 

We reviewed the outcomes in 52 patients who underwent a combination of CD with other procedures (such as panniculectomy, abdominoplasty, hernia repairs, myomectomies, and ovarian biopsies). The postsurgical outcomes included in the analysis were postsurgical fever and the presence of seromas, hematomas, and wound dehiscence.¹ Twelve of our own patients had a panniculectomy during CD performed by a plastic surgeon. While the preoperative complications of panniculectomy may have been well described, there is a paucity of data in women who underwent the cosmetic procedure at the time of CD. We concluded that the performance of a panniculectomy and tummy tuck as part of a CD does not appear to increase surgical complications in patients with a high body mass index. Our preliminary results and call for further studies were received at the American College of Surgeons 2017 meeting in San Diego.² 

Boris Petrikovsky, MD, PhD 

Sunny Island Beach, Florida 

References 

1. Petrikovsky BM, Swancoat S, Zharov EV. Safety of panniculectomy during cesarean section: a prospective, non-randomized study. J Reprod Med. 2019;64:197-200. 
2. Petrikovsky BM. Is the combination of panniculectomy and cesarean section safe? Scientific Poster Presentation-Obstetrics and Gynecology. J Am Coll Surg. 2017;225(4 suppl 2):E130. 

Dr. Barbieri responds 

I agree with Dr. Petrikovsky that advances in the field of obstetrical surgery have been inhibited by a tendency to criticize innovation. Less than 40 years ago, leaders in gynecology did not initially accept the application of minimally invasive gynecology surgical techniques to common gyn procedures including hysterectomy. Every surgical field is rapidly innovating. Obstetrical surgeons should be encouraged to pursue new approaches, as you are doing. We wish you success in your pioneering work. 

Continue to: A CASE OF BV...

A CASE OF BV DURING PREGNANCY: BEST MANAGEMENT APPROACH 

CALLIE FOX REEDER, MD, AND PATRICK DUFF, MD (ID CONSULT; FEBRUARY 2021) 

Secnidazole for treatment of BV 

The article by Drs. Reeder and Duff incorrectly states that there are no single-dose therapeutic options for bacterial vaginosis (BV) in the United States. Secnidazole 2 g single oral dose was approved by the US Food and Drug Administration (FDA) in 2017, and it is now included in the American College of Obstetricians and Gynecologists' (ACOG) clinical management guidelines for the treatment of BV in nonpregnant patients. 

Secnidazole is not contraindicated in pregnancy. In a poster presented at the 2020 ACOG annual clinical meeting, we summarized results of the preclinical studies that were part of the FDA submission.¹ There was no evidence of secnidazole toxicity in fertility and pre- and postnatal reproductive toxicology studies. In addition, there were no adverse developmental outcomes when secnidazole was administered orally to pregnant rats and rabbits during organogenesis at doses up to 4 times the clinical dose. These findings are consistent with the observation that no other preclinical studies, or experience from postmarketing use of secnidazole for approved indications, have suggested a risk of adverse effects when using secnidazole in pregnancy. 

Steven E. Chavoustie, MD 

North Miami, Florida 

Reference 

1. Pentikis H, Eder S, Kaufman G, Chavoustie S. Secnidazole, an approved single dose drug for bacterial vaginosis, does not cause reproductive toxicity in animals [16A]. Obstet Gynecol. 2020;135:12S. 

Drs. Reeder and Duff respond 

We are very appreciative of Dr. Chavoustie's interest in our article and for his thoughtful assessment of the role of single-dose secnidazole for the treatment of BV. As we noted in our article, this drug has been used extensively in Europe and Asia, but there is much less published experience with the drug in the United States. We pointed out the excellent results reported by Hillier and colleagues with 1-g and 2-g doses of this medication.¹ Dr. Chavoustie is correct in stating that there is no risk of fetal harm based on animal data at up to 4 times the recommended human dose, although the manufacturer recommends discontinuing breastfeeding during, and for 96 hours after, treatment. According to www.goodrx.com, the cost of a single 2-g dose of secnidazole is $325; the cost of a 7-day course of metronidazole is approximately $16. 

Reference 

1. Hillier SL, Nyirjesy P, Waldbaum AS, et al. Secnidazole treatment of bacterial vaginosis: a randomized controlled trial. Obstet Gynecol. 2017;130:379-386. 

Continue to: OPTIMIZING THE USE OF...

ROBERT L. BARBIERI, MD (EDITORIAL; JANUARY 2021) 

Vigilant labor progress aids in oxytocin optimization 

I read with particular interest Dr. Barbieri's editorial on optimizing oxytocin infusion. This topic is relevant for my practice as I am the kind of physician described and I usually get upset when the oxytocin is not managed as I ordered. 

In my opinion, several things need clarification. On our unit, the most significant point of controversy is the definition of tachysystole, mainly when we are using a tocodynamometer and not an internal transducer. 

I contend that it is quite challenging to ascertain the effectiveness of any given labor pattern based only on the number of contractions. Although we joke about "pit to distress," the truth is that contractions need to be "effective," which to me means strong enough to induce cervical changes. 

In my clinical practice, with a tocodynamometer, having 5 contractions that do not produce cervical changes (unless associated with abnormalities of the fetal heart rate tracing) is not a clinically relevant finding as we do not have a way to gauge the strength of such contractions. 

I usually employ a mid-range oxytocin protocol, starting at 4 mU per minute and increasing by 4 mU every 20 minutes. Through 30 years of practicing obstetrics, I have found that this protocol renders excellent results in achieving an efficient labor pattern without jeopardizing fetal well-being. 

On learning about oxytocin's pharmacokinetics, I still support Dr. Rhonda L. Perry and her colleagues' conclusion that, until we learn better about this aspect of oxytocin pharmacology, each woman is her own bioassay.¹ Furthermore, we see this in our daily practice: some patients go into full efficient labor with oxytocin at 4 mU per minute while others at 30 mU per minute do zilch. 

Based on the above, I think that optimization requires close vigilance of the labor and the fetal status at any given time, not determining an oxytocin rate of infusion or dosage. 
We should be observant on evaluating labor progress, and we should not hesitate to use internal pressure catheters when needed to obtain a more accurate evaluation of the labor pattern. 

By examining the patient's labor progress at regular intervals, we also optimize the oxytocin infusion by determining if the infusion is producing the expected cervical changes. 

Tomas Hernandez-Mejia, MD 

Pasco, Washington 

Reference
 
1. Perry RL, Satin AJ, Barth WH, et al. The pharmacokinetics of oxytocin as they apply to labor induction. Am J Obstet Gynecol. 1996;174:1590-1593. 

Dr. Barbieri responds 

I thank Dr. Tomas Hernandez-Mejia for sharing his expertise in utilizing a higher dose of oxytocin to optimize labor and birth. Dr. Hernandez-Mejia's view is supported by the recent publication of a high-quality clinical trial showing that a high-dose oxytocin protocol (initial and incremental rate of 6 mIU/min) did not cause an increase in adverse perinatal outcomes compared with a standard-dose protocol (initial and incremental rate of 2 mIU/min) but slightly shortened the duration of labor.¹ Based on this clinical trial, my conclusion is that the high-dose protocol, if appropriately monitored for excess uterine contractions and fetal heart rate pattern, is safe. 

Reference 

1. Son M, Roy A, Stetson BT, et al. High-dose compared with standard-dose oxytocin regimens to augment labor in nulliparous women: a randomized controlled trial. Obstet Gynecol. 2021;137:991-998. 

Continue to: PREGNANCY OF UNKNOWN...

IRIS G. INSOGNA, MD, AND PAULA C. BRADY, MD (AUGUST 2020) 

I would like to thank Dr. Iris Insogna and Dr. Paula Brady for their very informative article on pregnancy of unknown location. However, please allow me to make a suggestion that will clarify terminology for all practicing ObGyns. 

The medical literature uses the terms cornual pregnancy and interstitial pregnancy interchangeably, although they are actually very different conditions and have significant different implications. Clinicians are often confused about which is an intrauterine pregnancy and which is a true ectopic pregnancy. This confusion was addressed in a 2006 article in Fertility and Sterility, which explains that a cornual pregnancy refers to the implantation and development of a gestation in one of the upper and lateral portions of the uterus.¹ This may occur in a rudimentary horn or in one horn of a septate or bicornuate uterus. Conversely, an interstitial pregnancy is a gestation that implants within the proximal, intramural portion of the fallopian tube that is enveloped by myometrium. Therefore, a cornual pregnancy is actually an intrauterine pregnancy, whereas an interstitial pregnancy is a true ectopic pregnancy. 

I hope that all clinicians will read the article in Fertility and Sterility and adopt this terminology to avoid future confusion and misunderstandings. 

Alan D. Rosen, MD 

Houston, Texas 

Reference 

1. Malinowski A, Bates SK. Semantics and pitfalls in the diagnosis of cornual/interstitial pregnancy. Fertil Steril. 2006;86:1764.e11-1764.e14.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

Frequency or timing of unprotected intercourse within 14 days before IUD placement had no impact on pregnancy if a preplacement pregnancy test was negative, based on data from 655 women who received IUDs.

Many women present for emergency contraception with a history of unprotected intercourse, often beyond the 5-day guidelines for emergency contraception recommended by the World Health Organization, wrote Abena BakenRa, MD, of the University of California, Berkeley, and colleagues. “As such, we lack data on situations in which multiple episodes of unprotected intercourse occurred in the same menstrual cycle of use, especially episodes occurring more than 5 days before emergency contraception use,” the researchers said.

To determine pregnancy risk during a longer period before IUD placement, the researchers reviewed secondary data from a randomized trial of 655 women who received the copper T380A IUD or levonorgestrel 52-mg intrauterine system for emergency contraception. The women were aged 18-35 years and were enrolled at one of six family planning clinics in Utah between August 2016 and December 2019.

In a study published in Obstetrics & Gynecology, the researchers assessed pregnancies at 1 month after IUD placement. All of the women had a confirmed negative urine pregnancy test result immediately before IUD placement.

Overall, 286 women (43.7%) reported multiple episodes of unprotected intercourse, with a median of three episodes. A total of 95 women (14.4%) reported at least one unprotected intercourse episode at 6 days or more prior to IUD placement. No pregnancies were reported among women in either of these categories (0.0% for both). Pregnancy risk was 0.2% among those who reported unprotected intercourse within 5 days of IUD placement.

No pregnancies occurred in those who reported additional episodes of unprotected intercourse at 6-7 days, 6-10 days, or 6-14 days before IUD placement (0% for all).

In both the copper IUD and levonorgestrel groups, 68% and 74%, respectively, of the women reported that all fertile-window unprotected intercourse events occurred in the 5 days prior to IUD placement.

The study findings were limited by several factors including the lack of power for analysis of certain categories of assessment, such as pregnancy rates by timing or frequency, the inclusion of patients only from the state of Utah, and the potential underreporting of unprotected intercourse, the researchers noted. However, the findings were strengthened by the relatively large sample size, and by data on unprotected intercourse before IUD placement in a randomized, controlled trial that included two types of IUDs, they said.

“For these situations with multiple unprotected intercourse episodes and extended time between unprotected intercourse and emergency contraception request, potential users should be informed of the evidence of IUD emergency contraception efficacy, compared with the current state of uncertain data for oral emergency contraception methods,” the researchers said.

“Given the multitude of barriers that may impede timely presentation to care (insurance and cost concerns, difficulty finding a capable health care professional, or sexual assault trauma), these data are critical to patient-centered family planning care,” they concluded.

Data support IUD placement in practice

“Understanding potential barriers to placement of long-acting reversible contraception such as IUDs is essential to expanding access to contraception,” Iris Krishna, MD, of Emory University, Atlanta, said in an interview.

“This study is a secondary analysis of a randomized trial that compared copper versus levonorgestrel IUD placement for emergency contraception. Investigators were able to evaluate frequency and timing of unprotected intercourse up to 14 days prior to IUD placement and prospectively collect data assessing pregnancy risk 1 month after IUD placement,” she said.

The study findings suggest that the risk of pregnancy with unprotected intercourse within 14 days of IUD placement is low overall, and that this risk does not appear to increase with multiple episodes of unprotected intercourse during this time period, Dr. Krishna said. “In general, insertion of an IUD may occur at any time during the menstrual cycle as long as pregnancy may be reasonably excluded and clinicians are encouraged to initiate and place long-acting reversible contraceptives in a single visit, if possible,” she noted. However, “there is a paucity of data on risk of pregnancy when assessing efficacy of IUDs as emergency contraception with episodes of unprotected intercourse more than 5 days prior to IUD placement,” she added.

The study results also suggest that pregnancy risk is similar between women who reported unprotected intercourse within 5 days prior to IUD placement and those who reported unprotected intercourse up to 14 days prior to IUD placement, said Dr. Krishna. “These findings are clinically significant, as they add to our understanding of risk of pregnancy with unprotected intercourse up to 14 days prior to placement of an IUD,” she emphasized.

In practice, the study results “will help clinicians counsel patients on risk of pregnancy after IUD placement for emergency contraception,” said Dr. Krishna. “More studies evaluating risk of pregnancy after IUD placement for emergency contraception with episodes of unprotected intercourse more than 5 days prior to placement are needed to further assess the potential to expand the time frame for IUD use as emergency contraception,” she said. “Reducing barriers to IUD access, especially in setting of emergency contraception, is essential to lowering unintended pregnancy rates in the United States.”

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, as well as the University of Utah Population Health Research Foundation, the National Center for Research Resources, and the National Center for Advancing Translational Sciences at the National Institutes of Health. Several coauthors disclosed grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Office of Research on Women’s Health of the National Institutes of Health. The researchers, as well as Dr. Krishna, had no financial conflicts to disclose.

With vaccination rates increasing and new infections declining, we all hope the worst of the COVID-19 pandemic is over (fingers crossed really tight). Regardless, the post–COVID-19 syndrome pandemic has already begun. What is post–COVID-19 syndrome (or long-haulers or long-COVID)? Is it standard postviral fatigue? Prolonged deconditioning following debilitating illness? Permanent lung or vascular injury? Common sense and past experience say it’s all of these.

In theory, the burden of actual lung injury post COVID-19 should be the easiest to quantify, so let’s discuss what we think we know. I’ve heard experts break post–COVID-19 lung injury into three broad categories:

• Preexisting lung disease that is exacerbated by acute COVID-19 infection.
• Acute COVID-19 infection that causes acute respiratory distress syndrome (ARDS) or other acute lung injury (ALI).
• Non–critically ill acute COVID-19 with residual lung damage and abnormal repair.

These categories are necessarily imprecise, making it challenging to fit some patients neatly into a single definition.

For patients in the first category, management will be dictated largely by the nature of the preexisting lung disease. For those in category two, we already know a lot about what their recovery from ARDS will look like. There’s no longer reason to believe that COVID-19–related ARDS is particularly unique, and all things being equal, lung recovery should mimic that seen with non–COVID-19 ARDS.

It’s going to take patience and time, and beyond targeted rehabilitation it’s not clear that we have anything available to expedite the process.

The third category of patients is the most intriguing. Is there a group of patients who have residual lung injury but didn’t have evident ARDS/ALI during their acute COVID-19 infection? Anecdotally we think so, but we know little about prevalence and less about management. A recent study published in Annals of the American Thoracic Society addresses both issues. In an observational report on patients recovering after being hospitalized with COVID-19 infection, the authors found that 3.6% of patients had residual lung injury that improved with 3 weeks of corticosteroid treatment.

The report is timely and helpful but hardly definitive. It’s observational, and patients required extensive screening and identification by a multidisciplinary committee of experts in interstitial lung disease. Patients were diagnosed as having organizing pneumonia (OP) as their “lung injury” if certain radiographic criteria were met. There were no biopsies. Last, there was no control group. Still, this report is critically important. It tells us that at 6 weeks post discharge, about 3.6% of patients who were hospitalized for COVID-19 will have persistent symptoms, radiographic abnormalities, and a plateau in their recovery.

Beyond that, it tells us little. Did these patients really have OP? It’s impossible to know. The CT findings used to establish the diagnosis are nonspecific. Response to steroids is consistent with OP, but the treatment course was quite short. If truly OP, one would expect a high relapse rate after steroid withdrawal. Patients weren’t followed long enough to monitor recurrence rates. Also, as appropriately discussed in the accompanying editorial, there’s no control group so we can’t know whether the patients treated with steroids would have recovered without treatment. There was objective improvement in lung function for the two to three patients they followed who did not receive steroids. However, it was of lesser magnitude than in the steroid group.

Post–COVID-19 symptoms will remain a challenge for the foreseeable future. More than 30 million patients have been diagnosed with COVID-19 in the United States and close to half will experience persistent dyspnea. Putting the numbers together, I conclude that the vast majority will not have identifiable lung injury that will benefit from steroids. I wish I could prescribe patience to both physicians and patients.

Dr. Holley is associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.
 

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

With vaccination rates increasing and new infections declining, we all hope the worst of the COVID-19 pandemic is over (fingers crossed really tight). Regardless, the post–COVID-19 syndrome pandemic has already begun. What is post–COVID-19 syndrome (or long-haulers or long-COVID)? Is it standard postviral fatigue? Prolonged deconditioning following debilitating illness? Permanent lung or vascular injury? Common sense and past experience say it’s all of these.

In theory, the burden of actual lung injury post COVID-19 should be the easiest to quantify, so let’s discuss what we think we know. I’ve heard experts break post–COVID-19 lung injury into three broad categories:

• Preexisting lung disease that is exacerbated by acute COVID-19 infection.
• Acute COVID-19 infection that causes acute respiratory distress syndrome (ARDS) or other acute lung injury (ALI).
• Non–critically ill acute COVID-19 with residual lung damage and abnormal repair.

These categories are necessarily imprecise, making it challenging to fit some patients neatly into a single definition.

For patients in the first category, management will be dictated largely by the nature of the preexisting lung disease. For those in category two, we already know a lot about what their recovery from ARDS will look like. There’s no longer reason to believe that COVID-19–related ARDS is particularly unique, and all things being equal, lung recovery should mimic that seen with non–COVID-19 ARDS.

It’s going to take patience and time, and beyond targeted rehabilitation it’s not clear that we have anything available to expedite the process.

The third category of patients is the most intriguing. Is there a group of patients who have residual lung injury but didn’t have evident ARDS/ALI during their acute COVID-19 infection? Anecdotally we think so, but we know little about prevalence and less about management. A recent study published in Annals of the American Thoracic Society addresses both issues. In an observational report on patients recovering after being hospitalized with COVID-19 infection, the authors found that 3.6% of patients had residual lung injury that improved with 3 weeks of corticosteroid treatment.

The report is timely and helpful but hardly definitive. It’s observational, and patients required extensive screening and identification by a multidisciplinary committee of experts in interstitial lung disease. Patients were diagnosed as having organizing pneumonia (OP) as their “lung injury” if certain radiographic criteria were met. There were no biopsies. Last, there was no control group. Still, this report is critically important. It tells us that at 6 weeks post discharge, about 3.6% of patients who were hospitalized for COVID-19 will have persistent symptoms, radiographic abnormalities, and a plateau in their recovery.

Beyond that, it tells us little. Did these patients really have OP? It’s impossible to know. The CT findings used to establish the diagnosis are nonspecific. Response to steroids is consistent with OP, but the treatment course was quite short. If truly OP, one would expect a high relapse rate after steroid withdrawal. Patients weren’t followed long enough to monitor recurrence rates. Also, as appropriately discussed in the accompanying editorial, there’s no control group so we can’t know whether the patients treated with steroids would have recovered without treatment. There was objective improvement in lung function for the two to three patients they followed who did not receive steroids. However, it was of lesser magnitude than in the steroid group.

Post–COVID-19 symptoms will remain a challenge for the foreseeable future. More than 30 million patients have been diagnosed with COVID-19 in the United States and close to half will experience persistent dyspnea. Putting the numbers together, I conclude that the vast majority will not have identifiable lung injury that will benefit from steroids. I wish I could prescribe patience to both physicians and patients.

Dr. Holley is associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.
 

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

With vaccination rates increasing and new infections declining, we all hope the worst of the COVID-19 pandemic is over (fingers crossed really tight). Regardless, the post–COVID-19 syndrome pandemic has already begun. What is post–COVID-19 syndrome (or long-haulers or long-COVID)? Is it standard postviral fatigue? Prolonged deconditioning following debilitating illness? Permanent lung or vascular injury? Common sense and past experience say it’s all of these.

In theory, the burden of actual lung injury post COVID-19 should be the easiest to quantify, so let’s discuss what we think we know. I’ve heard experts break post–COVID-19 lung injury into three broad categories:

• Preexisting lung disease that is exacerbated by acute COVID-19 infection.
• Acute COVID-19 infection that causes acute respiratory distress syndrome (ARDS) or other acute lung injury (ALI).
• Non–critically ill acute COVID-19 with residual lung damage and abnormal repair.

These categories are necessarily imprecise, making it challenging to fit some patients neatly into a single definition.

For patients in the first category, management will be dictated largely by the nature of the preexisting lung disease. For those in category two, we already know a lot about what their recovery from ARDS will look like. There’s no longer reason to believe that COVID-19–related ARDS is particularly unique, and all things being equal, lung recovery should mimic that seen with non–COVID-19 ARDS.

It’s going to take patience and time, and beyond targeted rehabilitation it’s not clear that we have anything available to expedite the process.

The third category of patients is the most intriguing. Is there a group of patients who have residual lung injury but didn’t have evident ARDS/ALI during their acute COVID-19 infection? Anecdotally we think so, but we know little about prevalence and less about management. A recent study published in Annals of the American Thoracic Society addresses both issues. In an observational report on patients recovering after being hospitalized with COVID-19 infection, the authors found that 3.6% of patients had residual lung injury that improved with 3 weeks of corticosteroid treatment.

The report is timely and helpful but hardly definitive. It’s observational, and patients required extensive screening and identification by a multidisciplinary committee of experts in interstitial lung disease. Patients were diagnosed as having organizing pneumonia (OP) as their “lung injury” if certain radiographic criteria were met. There were no biopsies. Last, there was no control group. Still, this report is critically important. It tells us that at 6 weeks post discharge, about 3.6% of patients who were hospitalized for COVID-19 will have persistent symptoms, radiographic abnormalities, and a plateau in their recovery.

Beyond that, it tells us little. Did these patients really have OP? It’s impossible to know. The CT findings used to establish the diagnosis are nonspecific. Response to steroids is consistent with OP, but the treatment course was quite short. If truly OP, one would expect a high relapse rate after steroid withdrawal. Patients weren’t followed long enough to monitor recurrence rates. Also, as appropriately discussed in the accompanying editorial, there’s no control group so we can’t know whether the patients treated with steroids would have recovered without treatment. There was objective improvement in lung function for the two to three patients they followed who did not receive steroids. However, it was of lesser magnitude than in the steroid group.

Post–COVID-19 symptoms will remain a challenge for the foreseeable future. More than 30 million patients have been diagnosed with COVID-19 in the United States and close to half will experience persistent dyspnea. Putting the numbers together, I conclude that the vast majority will not have identifiable lung injury that will benefit from steroids. I wish I could prescribe patience to both physicians and patients.

Dr. Holley is associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.
 

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