Clinician Reviews

Christina Chambers, PhD, MPH, who runs the MotherToBaby Pregnancy Studies research center at the University of California, San Diego, has found most pregnant women to be “entirely altruistic” about sharing their experiences with drug treatment during pregnancy.

Christina Chambers

This is good news for the growth of more information about the safety of biologics and other drugs during pregnancy. Pregnancy outcomes data are increasingly emerging – particularly for tumor necrosis factor (TNF) inhibitors – but dermatologists, rheumatologists, and their female patients with psoriasis and psoriatic arthritis (PsA) want much more.

And women’s participation in the MotherToBaby studies conducted by the nonprofit Organization of Teratology Information Specialists (OTIS) is key, say physicians who are treating women of reproductive age. OTIS is now listed in drug labeling as the “pregnancy registry” contact for many of the medications they may be discussing with patients.

Dr. Chambers said that most women appreciate “that participating in a study may not help her with her pregnancy, but it can help her sister or her friend or someone else who has these same questions in planning a pregnancy of ‘Can I stay on my treatment?’ or, in the case of an unplanned pregnancy, ‘Should I be concerned?’ ”

OTIS has enrolled women with psoriasis and/or PsA in studies of nine medications, most of them biologics (both TNF-alpha blockers and newer anti-interleukin agents).

Four of the studies – those evaluating etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), and ustekinumab (Stelara) – are now closed to enrollment with analyses either underway or completed. The other five are currently enrolling patients and involve treatment with certolizumab pegol (Cimzia), tildrakizumab (Ilumya), apremilast (Otezla), guselkumab (Tremfya), and tofacitinib (Xeljanz).

Lisa R. Sammaritano, MD, a rheumatologist at the Hospital for Special Surgery, New York, who led the development of the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases, recommends to some of her patients that they contact OTIS. “Their pregnancy registry studies have added important information to the field over the years,” she said.

Most recently, a study of the anti–TNF-alpha medication adalimumab that began in 2004 in pregnant patients with RA and Crohn’s disease culminated in a 2019 PLOS ONE paper reporting no associations between exposure to the medication and an increased risk of adverse outcomes. The outcomes studied were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, prenatal and postnatal growth deficiency, serious or opportunistic infections, and malignancies.

An analysis is underway of adalimumab exposure in women with PsA – a patient subset that was added after the study started. But in the meantime, Dr. Chambers said, the 2019 research article is relevant to questions of drug safety across indications.

OTIS’s MothertoBaby studies are structured as prospective cohort studies. Dr. Chambers, a perinatal epidemiologist, is president of OTIS, which recruits women who have an exposure to the medication under study – at least one dose, for any length of time. And in most cases, it also recruits women with the underlying condition but no exposure and healthy women without the condition to represent the general population.

It’s the disease-matched comparison group that makes OTIS’s studies different from traditional pregnancy registries involving “a simple exposure series and outcomes that are described in the context of what you’d expect in the general population,” said Dr. Chambers, professor in the department of pediatrics, as well as family and preventative medicine, at UCSD and codirector of the Center for Better Beginnings at that university. “Many maternal conditions themselves [or their comorbidities] carry some risk of adverse outcomes in pregnancy.”

The OTIS studies typically involve at least 100 exposed pregnancies and a similar number of unexposed pregnancies; some have cohorts of 200-300.

The recently published study of adalimumab, for instance, included 257 women with exposure to the drug and 120 women in a disease comparison group with no exposure. In addition to finding no associations between drug exposure and adverse outcomes, the study found that women with RA or Crohn’s were at increased risk of preterm delivery, irrespective of adalimumab exposure.

“There’s insufficient [power with any of these numbers] to come to the conclusion that a drug is safe,” she said. “But what we have been able to say [through our studies] is that we’ve looked carefully at the whole array of outcomes ... and we don’t see anything unusual. That early view can be reassuring” until large population-based studies or claims analyses become possible.

Dr. Sammaritano, also with Weill Cornell Medicine, New York, said that she does not recommend registry participation for patients who stop biologics at the diagnosis of pregnancy. Since “the start of IgG antibody transfer during pregnancy is about 16 weeks,” she worries that including these patients might lead to falsely reassuring findings. “We are most interested in [knowing the outcomes of] patients who must continue the drugs through pregnancy,” she said.

Dr. Chambers, however, said that in her view, placental transfer is not a requirement for a medication to have some effect on the outcome of pregnancy. “The outcome could be influenced by an effect of the medication that doesn’t require placental transfer or require placental transfer in large amounts,” she said. “So it’s relevant to examine exposures that have occurred only in the first trimester, and this is especially true for the outcome of major birth defects, most of which are initiated in the first trimester.”

The MotherToBaby studies typically include both early, short exposures and longer exposures, she said. “And certainly, duration of use is a factor that we do consider in looking at specific outcomes such as growth, preterm delivery, and risk of serious or opportunistic infections.”

(In the published study of adalimumab, 65.3% of women in the medication-exposed cohort used the medication in all three trimesters, 10.5% in the first and second trimesters, and 22.4% in the first trimester only.)

Women participating in the MotherToBaby studies complete two to four interviews during pregnancy and may be interviewed again after delivery. They are asked for their permission to share a copy of their medical records – and their baby’s medical records – and their babies receive a follow-up pediatric exam by a pediatrician with expertise in dysmorphology/genetics (who is blinded to exposure status), most commonly in the participant’s home. Providers are not asked to enter any data.

Oklahoma Medical Research Foundation

Eliza Chakravarty, MD, a rheumatologist with the Oklahoma Medical Research Foundation in Oklahoma City who treats patients with PsA who are pregnant or considering pregnancy, said that her referrals for research participation “have been mostly to MothertoBaby.”

“Most drug companies [in the autoimmune space] are now contracting with them [for their pregnancy exposure research],” she said. “I really like that it’s become so centralized.”

She tells patients that many questions can be answered through research, that their experience matters, and that “there are benefits” to the extra pediatric examination. “I give them the information and let them decide whether or not they want to call [MotherToBaby],” she said. “I don’t want to impose. I want to make them aware.”

Dr. Chambers emphasizes to patients and physicians that the studies are strictly observational and do not require any changes in personal or medical regimens. “When people hear the word ‘research’ they think of clinical trials. We’re saying, you and your provider do everything you normally would do, just let us observe what happens during your pregnancy.”

Physicians should assure patients, moreover, that “just because the drug is being studied doesn’t mean there’s a known risk or even a suspected risk,” she said.

The MotherToBaby studies receive funding from the pharmaceutical companies, which are required by the Food and Drug Administration to conduct pregnancy exposure registries for medications used during pregnancy or in women of reproductive age. OTIS has an independent advisory board, however, and independently analyzes and publishes its findings. Progress reports are shared with the pharmaceutical companies, and in turn, the FDA, Dr. Chambers said.


To refer patients for MotherToBaby studies, physicians can use an online referral form found on the MothertoBaby web site, a service of OTIS, or call the pregnancy studies team at 877-311-8972 to provide them with the patient’s name or number. Patients may also be given the number and advised to consider calling. MotherToBaby offers medication fact sheets that answer questions about exposures during pregnancy and breastfeeding, and runs a free and confidential teratogen counseling service: 866-626-6847.
 

Christina Chambers, PhD, MPH, who runs the MotherToBaby Pregnancy Studies research center at the University of California, San Diego, has found most pregnant women to be “entirely altruistic” about sharing their experiences with drug treatment during pregnancy.

Christina Chambers

This is good news for the growth of more information about the safety of biologics and other drugs during pregnancy. Pregnancy outcomes data are increasingly emerging – particularly for tumor necrosis factor (TNF) inhibitors – but dermatologists, rheumatologists, and their female patients with psoriasis and psoriatic arthritis (PsA) want much more.

And women’s participation in the MotherToBaby studies conducted by the nonprofit Organization of Teratology Information Specialists (OTIS) is key, say physicians who are treating women of reproductive age. OTIS is now listed in drug labeling as the “pregnancy registry” contact for many of the medications they may be discussing with patients.

Dr. Chambers said that most women appreciate “that participating in a study may not help her with her pregnancy, but it can help her sister or her friend or someone else who has these same questions in planning a pregnancy of ‘Can I stay on my treatment?’ or, in the case of an unplanned pregnancy, ‘Should I be concerned?’ ”

OTIS has enrolled women with psoriasis and/or PsA in studies of nine medications, most of them biologics (both TNF-alpha blockers and newer anti-interleukin agents).

Four of the studies – those evaluating etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), and ustekinumab (Stelara) – are now closed to enrollment with analyses either underway or completed. The other five are currently enrolling patients and involve treatment with certolizumab pegol (Cimzia), tildrakizumab (Ilumya), apremilast (Otezla), guselkumab (Tremfya), and tofacitinib (Xeljanz).

Lisa R. Sammaritano, MD, a rheumatologist at the Hospital for Special Surgery, New York, who led the development of the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases, recommends to some of her patients that they contact OTIS. “Their pregnancy registry studies have added important information to the field over the years,” she said.

Most recently, a study of the anti–TNF-alpha medication adalimumab that began in 2004 in pregnant patients with RA and Crohn’s disease culminated in a 2019 PLOS ONE paper reporting no associations between exposure to the medication and an increased risk of adverse outcomes. The outcomes studied were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, prenatal and postnatal growth deficiency, serious or opportunistic infections, and malignancies.

An analysis is underway of adalimumab exposure in women with PsA – a patient subset that was added after the study started. But in the meantime, Dr. Chambers said, the 2019 research article is relevant to questions of drug safety across indications.

OTIS’s MothertoBaby studies are structured as prospective cohort studies. Dr. Chambers, a perinatal epidemiologist, is president of OTIS, which recruits women who have an exposure to the medication under study – at least one dose, for any length of time. And in most cases, it also recruits women with the underlying condition but no exposure and healthy women without the condition to represent the general population.

It’s the disease-matched comparison group that makes OTIS’s studies different from traditional pregnancy registries involving “a simple exposure series and outcomes that are described in the context of what you’d expect in the general population,” said Dr. Chambers, professor in the department of pediatrics, as well as family and preventative medicine, at UCSD and codirector of the Center for Better Beginnings at that university. “Many maternal conditions themselves [or their comorbidities] carry some risk of adverse outcomes in pregnancy.”

The OTIS studies typically involve at least 100 exposed pregnancies and a similar number of unexposed pregnancies; some have cohorts of 200-300.

The recently published study of adalimumab, for instance, included 257 women with exposure to the drug and 120 women in a disease comparison group with no exposure. In addition to finding no associations between drug exposure and adverse outcomes, the study found that women with RA or Crohn’s were at increased risk of preterm delivery, irrespective of adalimumab exposure.

“There’s insufficient [power with any of these numbers] to come to the conclusion that a drug is safe,” she said. “But what we have been able to say [through our studies] is that we’ve looked carefully at the whole array of outcomes ... and we don’t see anything unusual. That early view can be reassuring” until large population-based studies or claims analyses become possible.

Dr. Sammaritano, also with Weill Cornell Medicine, New York, said that she does not recommend registry participation for patients who stop biologics at the diagnosis of pregnancy. Since “the start of IgG antibody transfer during pregnancy is about 16 weeks,” she worries that including these patients might lead to falsely reassuring findings. “We are most interested in [knowing the outcomes of] patients who must continue the drugs through pregnancy,” she said.

Dr. Chambers, however, said that in her view, placental transfer is not a requirement for a medication to have some effect on the outcome of pregnancy. “The outcome could be influenced by an effect of the medication that doesn’t require placental transfer or require placental transfer in large amounts,” she said. “So it’s relevant to examine exposures that have occurred only in the first trimester, and this is especially true for the outcome of major birth defects, most of which are initiated in the first trimester.”

The MotherToBaby studies typically include both early, short exposures and longer exposures, she said. “And certainly, duration of use is a factor that we do consider in looking at specific outcomes such as growth, preterm delivery, and risk of serious or opportunistic infections.”

(In the published study of adalimumab, 65.3% of women in the medication-exposed cohort used the medication in all three trimesters, 10.5% in the first and second trimesters, and 22.4% in the first trimester only.)

Women participating in the MotherToBaby studies complete two to four interviews during pregnancy and may be interviewed again after delivery. They are asked for their permission to share a copy of their medical records – and their baby’s medical records – and their babies receive a follow-up pediatric exam by a pediatrician with expertise in dysmorphology/genetics (who is blinded to exposure status), most commonly in the participant’s home. Providers are not asked to enter any data.

Oklahoma Medical Research Foundation

Eliza Chakravarty, MD, a rheumatologist with the Oklahoma Medical Research Foundation in Oklahoma City who treats patients with PsA who are pregnant or considering pregnancy, said that her referrals for research participation “have been mostly to MothertoBaby.”

“Most drug companies [in the autoimmune space] are now contracting with them [for their pregnancy exposure research],” she said. “I really like that it’s become so centralized.”

She tells patients that many questions can be answered through research, that their experience matters, and that “there are benefits” to the extra pediatric examination. “I give them the information and let them decide whether or not they want to call [MotherToBaby],” she said. “I don’t want to impose. I want to make them aware.”

Dr. Chambers emphasizes to patients and physicians that the studies are strictly observational and do not require any changes in personal or medical regimens. “When people hear the word ‘research’ they think of clinical trials. We’re saying, you and your provider do everything you normally would do, just let us observe what happens during your pregnancy.”

Physicians should assure patients, moreover, that “just because the drug is being studied doesn’t mean there’s a known risk or even a suspected risk,” she said.

The MotherToBaby studies receive funding from the pharmaceutical companies, which are required by the Food and Drug Administration to conduct pregnancy exposure registries for medications used during pregnancy or in women of reproductive age. OTIS has an independent advisory board, however, and independently analyzes and publishes its findings. Progress reports are shared with the pharmaceutical companies, and in turn, the FDA, Dr. Chambers said.


To refer patients for MotherToBaby studies, physicians can use an online referral form found on the MothertoBaby web site, a service of OTIS, or call the pregnancy studies team at 877-311-8972 to provide them with the patient’s name or number. Patients may also be given the number and advised to consider calling. MotherToBaby offers medication fact sheets that answer questions about exposures during pregnancy and breastfeeding, and runs a free and confidential teratogen counseling service: 866-626-6847.
 

Christina Chambers, PhD, MPH, who runs the MotherToBaby Pregnancy Studies research center at the University of California, San Diego, has found most pregnant women to be “entirely altruistic” about sharing their experiences with drug treatment during pregnancy.

Christina Chambers

This is good news for the growth of more information about the safety of biologics and other drugs during pregnancy. Pregnancy outcomes data are increasingly emerging – particularly for tumor necrosis factor (TNF) inhibitors – but dermatologists, rheumatologists, and their female patients with psoriasis and psoriatic arthritis (PsA) want much more.

And women’s participation in the MotherToBaby studies conducted by the nonprofit Organization of Teratology Information Specialists (OTIS) is key, say physicians who are treating women of reproductive age. OTIS is now listed in drug labeling as the “pregnancy registry” contact for many of the medications they may be discussing with patients.

Dr. Chambers said that most women appreciate “that participating in a study may not help her with her pregnancy, but it can help her sister or her friend or someone else who has these same questions in planning a pregnancy of ‘Can I stay on my treatment?’ or, in the case of an unplanned pregnancy, ‘Should I be concerned?’ ”

OTIS has enrolled women with psoriasis and/or PsA in studies of nine medications, most of them biologics (both TNF-alpha blockers and newer anti-interleukin agents).

Four of the studies – those evaluating etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), and ustekinumab (Stelara) – are now closed to enrollment with analyses either underway or completed. The other five are currently enrolling patients and involve treatment with certolizumab pegol (Cimzia), tildrakizumab (Ilumya), apremilast (Otezla), guselkumab (Tremfya), and tofacitinib (Xeljanz).

Lisa R. Sammaritano, MD, a rheumatologist at the Hospital for Special Surgery, New York, who led the development of the American College of Rheumatology’s first guideline for the management of reproductive health in rheumatic and musculoskeletal diseases, recommends to some of her patients that they contact OTIS. “Their pregnancy registry studies have added important information to the field over the years,” she said.

Most recently, a study of the anti–TNF-alpha medication adalimumab that began in 2004 in pregnant patients with RA and Crohn’s disease culminated in a 2019 PLOS ONE paper reporting no associations between exposure to the medication and an increased risk of adverse outcomes. The outcomes studied were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, prenatal and postnatal growth deficiency, serious or opportunistic infections, and malignancies.

An analysis is underway of adalimumab exposure in women with PsA – a patient subset that was added after the study started. But in the meantime, Dr. Chambers said, the 2019 research article is relevant to questions of drug safety across indications.

OTIS’s MothertoBaby studies are structured as prospective cohort studies. Dr. Chambers, a perinatal epidemiologist, is president of OTIS, which recruits women who have an exposure to the medication under study – at least one dose, for any length of time. And in most cases, it also recruits women with the underlying condition but no exposure and healthy women without the condition to represent the general population.

It’s the disease-matched comparison group that makes OTIS’s studies different from traditional pregnancy registries involving “a simple exposure series and outcomes that are described in the context of what you’d expect in the general population,” said Dr. Chambers, professor in the department of pediatrics, as well as family and preventative medicine, at UCSD and codirector of the Center for Better Beginnings at that university. “Many maternal conditions themselves [or their comorbidities] carry some risk of adverse outcomes in pregnancy.”

The OTIS studies typically involve at least 100 exposed pregnancies and a similar number of unexposed pregnancies; some have cohorts of 200-300.

The recently published study of adalimumab, for instance, included 257 women with exposure to the drug and 120 women in a disease comparison group with no exposure. In addition to finding no associations between drug exposure and adverse outcomes, the study found that women with RA or Crohn’s were at increased risk of preterm delivery, irrespective of adalimumab exposure.

“There’s insufficient [power with any of these numbers] to come to the conclusion that a drug is safe,” she said. “But what we have been able to say [through our studies] is that we’ve looked carefully at the whole array of outcomes ... and we don’t see anything unusual. That early view can be reassuring” until large population-based studies or claims analyses become possible.

Dr. Sammaritano, also with Weill Cornell Medicine, New York, said that she does not recommend registry participation for patients who stop biologics at the diagnosis of pregnancy. Since “the start of IgG antibody transfer during pregnancy is about 16 weeks,” she worries that including these patients might lead to falsely reassuring findings. “We are most interested in [knowing the outcomes of] patients who must continue the drugs through pregnancy,” she said.

Dr. Chambers, however, said that in her view, placental transfer is not a requirement for a medication to have some effect on the outcome of pregnancy. “The outcome could be influenced by an effect of the medication that doesn’t require placental transfer or require placental transfer in large amounts,” she said. “So it’s relevant to examine exposures that have occurred only in the first trimester, and this is especially true for the outcome of major birth defects, most of which are initiated in the first trimester.”

The MotherToBaby studies typically include both early, short exposures and longer exposures, she said. “And certainly, duration of use is a factor that we do consider in looking at specific outcomes such as growth, preterm delivery, and risk of serious or opportunistic infections.”

(In the published study of adalimumab, 65.3% of women in the medication-exposed cohort used the medication in all three trimesters, 10.5% in the first and second trimesters, and 22.4% in the first trimester only.)

Women participating in the MotherToBaby studies complete two to four interviews during pregnancy and may be interviewed again after delivery. They are asked for their permission to share a copy of their medical records – and their baby’s medical records – and their babies receive a follow-up pediatric exam by a pediatrician with expertise in dysmorphology/genetics (who is blinded to exposure status), most commonly in the participant’s home. Providers are not asked to enter any data.

Oklahoma Medical Research Foundation

Eliza Chakravarty, MD, a rheumatologist with the Oklahoma Medical Research Foundation in Oklahoma City who treats patients with PsA who are pregnant or considering pregnancy, said that her referrals for research participation “have been mostly to MothertoBaby.”

“Most drug companies [in the autoimmune space] are now contracting with them [for their pregnancy exposure research],” she said. “I really like that it’s become so centralized.”

She tells patients that many questions can be answered through research, that their experience matters, and that “there are benefits” to the extra pediatric examination. “I give them the information and let them decide whether or not they want to call [MotherToBaby],” she said. “I don’t want to impose. I want to make them aware.”

Dr. Chambers emphasizes to patients and physicians that the studies are strictly observational and do not require any changes in personal or medical regimens. “When people hear the word ‘research’ they think of clinical trials. We’re saying, you and your provider do everything you normally would do, just let us observe what happens during your pregnancy.”

Physicians should assure patients, moreover, that “just because the drug is being studied doesn’t mean there’s a known risk or even a suspected risk,” she said.

The MotherToBaby studies receive funding from the pharmaceutical companies, which are required by the Food and Drug Administration to conduct pregnancy exposure registries for medications used during pregnancy or in women of reproductive age. OTIS has an independent advisory board, however, and independently analyzes and publishes its findings. Progress reports are shared with the pharmaceutical companies, and in turn, the FDA, Dr. Chambers said.


To refer patients for MotherToBaby studies, physicians can use an online referral form found on the MothertoBaby web site, a service of OTIS, or call the pregnancy studies team at 877-311-8972 to provide them with the patient’s name or number. Patients may also be given the number and advised to consider calling. MotherToBaby offers medication fact sheets that answer questions about exposures during pregnancy and breastfeeding, and runs a free and confidential teratogen counseling service: 866-626-6847.
 

Jun Yang, MBBS, had watched as her father, who had battled hypertension for decades, ended up on four medications that still couldn’t bring his blood pressure to a healthy level. The cardiovascular endocrinologist then ran some tests, and soon thereafter her father had his blood pressure optimized on just one targeted medication.

Courtesy Dr. Jun Yang

Dr. Yang’s father was found to have a hormonal condition known as primary aldosteronism (PA) as the cause of his hypertension.

It turns out that PA is not as rare as once thought.

An eye-catching report in Annals of Internal Medicine this spring of an unexpectedly high prevalence of primary aldosteronism among a diverse cross section of U.S. patients with hypertension has raised issues that could dramatically change the way doctors in America, and elsewhere, assess and manage high blood pressure.

Foremost is the question of whether primary care physicians – the clinicians at the front line for diagnosing and initially treating most patients with hypertension – will absorb and act on this new evidence. For them, aldosteronism doesn’t automatically come to mind when they see high numbers on a BP monitor, and yet this latest research found that up to a third of all 726 patients in the study who were diagnosed with hypertension and with high urinary salt levels had PA.

That translates to a roughly three- to fivefold increase over standard prevalence estimates, and is a ”game changer” for how clinicians should approach hypertension management and PA diagnosis going forward, said John W. Funder, MD, in an editorial accompanying the Annals study.

Long considered relatively uncommon, hypertension driven by an excess of the hormone aldosterone, often because of an adenoma on the adrenal gland, is not the same as conventional “essential” hypertension. The former benefits from early diagnosis because its treatment is completely different – close to half of all PA patients can be treated definitively and quickly with surgical removal of an adenoma from one side of the adrenal gland.

For other PA patients, who have bilateral adrenal hyperplasia that is impossible to resolve surgically, treatment with drugs called mineralocorticoid receptor antagonists (MRAs), such as spironolactone, is needed because they target the hormonal cause of the high BP.

But what usually happens is that a patient with PA is mistakenly diagnosed with essential hypertension, in which the classic approach to treatment is to start with one regular antihypertensive drug, and add on further ones from different drug classes if blood pressure is not adequately controlled. When patients are taking three drugs, without adequate control, they are labeled as having “resistant hypertension.”

But in the case of PA, none of these conventional antihypertensives work, and the process of continuing to monitor and add different drugs wastes time, during which patients deteriorate.

“We need to change the culture of waiting for hypertension to be resistant and have patients riddled with end-organ damage,” due to years of persistently high BP and excess aldosterone “before we look for a secondary cause” like PA, declared Dr. Yang, of Hudson Institute of Medical Research and Monash University in Melbourne, during an interview.

So early diagnosis and prompt treatment of PA is key.

In addition to boosting the public health importance of early PA detection in hypertensive patients, the new up-sized PA prevalence numbers throw a spotlight on primary care physicians (PCPs) as key players who will need to apply the findings to practice on a public health scale.

These novel results create a need for “new guidelines, and a radically revised game plan with the key role of PCPs” emphasized in future management of patients with hypertension, said Dr. Funder, a professor of medicine at Monash University, in a second recent editorial in Hypertension.

“Buy-in by PCPs is essential,” agrees Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville, and a coauthor of the new study.

But he too acknowledges that this presents a major challenge. PCPs and internists, who diagnose a lot of hypertension, are “not used to thinking about aldosterone,” he said in an interview, encapsulating the key problem faced by proponents of earlier and more widespread PA assessment.

This dilemma looms as a “huge public health issue,” Dr. Carey warned.
 

‘We’re a long way from getting’ PCPs to buy in to PA screening

Will PCPs grow more comfortable with screening patients for PA themselves, or might they become more willing to refer hypertensive individuals for assessment at an expert center?

One skeptic is Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg. The finding about high PA prevalence in patients with hypertension “is brand new, [and] the message needs to get to PCPs,” he said. But, “We’re a long way from getting it” to them. “I don’t know how to do that. It will be a tough sell.”

In addition, repositioning MRAs as an earlier option for many hypertensive patients won’t be easy either, because “we’ll never have outcome-trial data for MRAs,” given that they are now generic drugs, he noted.

“No clinical trial data show [MRAs] are first-line drugs,” said Dr. Feldman, who explained that, instead, MRAs are considered “go-to drugs” for patients with treatment-resistant hypertension, a niche therapeutic area. Results from the PATHWAY-2 trial published 5 years ago in Lancet showed “spironolactone was clearly the most effective treatment for the condition,” according to the report authors.

But even among patients with resistant hypertension, screening for PA dramatically lags despite being enshrined in guidelines.

“PCPs should start checking aldosterone-to-renin ratios [a widely used PA screen] in all patients with resistant hypertension or hypertension with hypokalemia, and then refer patients to specialists for testing and management,” said Jordana B. Cohen, MD, a nephrologist and hypertension researcher at the University of Pennsylvania in Philadelphia.

But recent studies of U.S. patient populations with clinical characteristics that meet existing criteria for PA screening showed that just 1%-2% of these individuals underwent an initial PA assessment, she noted, citing reports in the journals Surgery and Hypertension.

“We need to prioritize improving screening in these high-risk patients,” she stressed in an interview.

This illustrates that, in some respects, the new prevalence numbers are beside the point, because PA has been going unscreened and overlooked far too often even in the context of historical, lower prevalence rates, said Dr. Yang.

“The key point is that approximately 1 in 10 people with hypertension, and even more with resistant hypertension, have a form of the disease that is worse than essential hypertension but is routinely missed at present” and is also highly treatable.

“Evidence for the need for increased awareness of PA has been building for 2 decades,” stressed Dr. Yang, who has coauthored several commentaries and reviews that have bemoaned PA’s underappreciated status.
 

Interest in partnering with PCPs on guidance grows

One potential solution is to have endocrinologists and hypertension specialists’ partner with PCPs to come up with diagnostic and management recommendations. Both Dr. Funder and Dr. Carey are opinion leaders regarding the role of aldosterone in hypertension, and both were coauthors of the 2016 Endocrine Society guideline for PA assessment and management published in the Journal of Clinical Endocrinology & Metabolism , with Dr. Funder chairing the writing panel.

Now approaching its fifth year in effect, this guideline is “due for revision,” and “my hope is that we’ll be able to partner with one or more PCP organizations to come up with a version of the guideline targeted to PCPs,” Dr. Carey said.

He voiced interest in working on this with the American College of Physicians, which represents U.S. internal medicine physicians, and the American Academy of Family Physicians.

“We definitely need a partnership and educational efforts to get the word out from these organizations and not from a specialty society,” said Dr. Carey.

Dr. Funder said he has submitted a proposal to the Endocrine Society for a guidelines update he would chair with Dr. Carey’s assistance and with a diverse writing group that includes PCPs. Dr. Carey said that ideally this panel would write and release a revised guideline in 2021.

“Several of us are chomping at the bit to get this done,” he noted.

But participation by the ACP and AAFP remain uncertain as of September 2020. When approached about this, an ACP spokesperson said the organization had no comment. A spokesperson for the AAFP said, “It’s too early to tell if we will partner with any other organizations to develop guidelines specific to excess aldosterone, and how such guidelines might be received by our members.”

Recent history shows little cooperation between ACP, AAFP, and what might be termed the U.S. hypertension “establishment.” For example, when the American College of Cardiology and the American Heart Association released their most recent essential hypertension management guidelines in Hypertension in 2018, it was never adopted by ACP or AAFP.

The latter two organizations continue to endorse a higher BP threshold for diagnosing hypertension, and higher treatment targets set by alternative expert panels to those of the AHA/ACC.
 

Collaboration feasible, although PCPs overworked

Dr. Carey hopes that this episode will not preclude agreement over PA screening.

“I think it is still possible to partner with [the ACP and AAFP],” he observed, adding that he believes high PA prevalence among hypertensive patients and its consequences when unrecognized is “noncontentious.”

But he acknowledges that other, substantial hurdles also exist, notably the “overwhelming workload” that American PCPs already face.

David O’Gurek, MD, a family and community medicine physician at the Lewis Katz School of Medicine of Temple University in Philadelphia, agrees that a revamped approach to PA screening developed cooperatively between PCPs and specialists is an important goal and potentially feasible despite prior disagreements. “There has to be room for collaboration,” he said, but also emphasized the need for developing policies based on a systematic evidence review and a focus on patient-centered outcomes.

“We’re certainly missing patients with PA, but there needs to be greater clarity and standardization about the most appropriate screening approach and cutoff level” for flagging patients who need specialized assessment, Dr. O’Gurek said in an interview.

The current endocrinology literature also shows that experts remain divided on how best to accomplish this.

And some hypertension specialists question whether existing evidence is conclusive enough to warrant revised guidelines.

Dr. Cohen, the nephrologist and hypertension researcher, said that, while the recent prevalence report in Annals of Internal Medicine is “intriguing, hypothesis-generating information that suggests we are missing many cases of hyperaldosteronism in routine care,” she nevertheless believes that “we need additional data to be able to truly understand the breadth and implications of the findings.”

William C. Cushman, MD, a hypertension management specialist at the University of Tennessee Health Science Center in Memphis, agrees.

Changing existing practice guidelines “really needs randomized, controlled trials demonstrating a difference in long-term outcomes, ideally major cardiovascular outcomes,” that result from broader PA screening, he said.

Dr. Carey concurs that more evidence is needed to confirm the Annals report, but is confident this evidence will be in hand by the time a guideline-revision panel meets in 2021.
 

Australian model of PCPs screening for PA could be implemented in United States

An example of what might be possible when PCPs, endocrinologists, and hypertension specialists work together to make PA screening more accessible can be found in Melbourne, at the Endocrine Hypertension Service of Monash Health, in association with the Hudson Institute of Medical Research.

This began operating in July 2016, cofounded by Dr. Yang, whose experiences with her own father made her sensitive to the issue.

The service’s aim is to “address the underdiagnosis of PA, and to offer a streamlined diagnostic service for patients with hypertension,” with an “extensive outreach program” targeted to regional PCPs that, among other messages, encourages them to screen patients for PA when blood pressures exceed 140/90 mm Hg.

During its first 3 years of operation, the service saw 267 patients, with PA diagnosed in 135 and ruled out in 73 patients.

Notably, the proportion of these patients referred from PCPs jumped from 21% of 70 patients during the first year of operation to 47% of 70 patients during year 2, and 52% of 127 patients during the third year, ending in July 2019, said Dr. Yang, who continues to help run the service.

During the first year, a scant 3% of referred patients had recently diagnosed hypertension, but this rose to 14% during the second year, and to 19% during the most recent year with data available.

The median duration of diagnosed hypertension among referred patients fell from 11 years during year 1, to 7 years during year 3.

Service clinicians diagnosed 37 patients with unilateral adenomas, and removed them from 23 patients with four more awaiting surgery and the remaining 10 opting instead for medical management. Another 95 patients went on therapy with a MRA, and during the most recent year studied all patients who began a MRA regimen had a partial or complete clinical response.

Dr. Carey said the “creative program represents a model for implementation in U.S. practice.

Dr. Funder, Dr. Carey, Dr. Feldman, Dr. Yang, Dr. Cohen, and Dr. O’Gurek had no relevant disclosures. Dr. Cushman has been a consultant to Novartis, received personal fees from Sanofi, and research funding from Eli Lilly.

[email protected]

Jun Yang, MBBS, had watched as her father, who had battled hypertension for decades, ended up on four medications that still couldn’t bring his blood pressure to a healthy level. The cardiovascular endocrinologist then ran some tests, and soon thereafter her father had his blood pressure optimized on just one targeted medication.

Courtesy Dr. Jun Yang

Dr. Yang’s father was found to have a hormonal condition known as primary aldosteronism (PA) as the cause of his hypertension.

It turns out that PA is not as rare as once thought.

An eye-catching report in Annals of Internal Medicine this spring of an unexpectedly high prevalence of primary aldosteronism among a diverse cross section of U.S. patients with hypertension has raised issues that could dramatically change the way doctors in America, and elsewhere, assess and manage high blood pressure.

Foremost is the question of whether primary care physicians – the clinicians at the front line for diagnosing and initially treating most patients with hypertension – will absorb and act on this new evidence. For them, aldosteronism doesn’t automatically come to mind when they see high numbers on a BP monitor, and yet this latest research found that up to a third of all 726 patients in the study who were diagnosed with hypertension and with high urinary salt levels had PA.

That translates to a roughly three- to fivefold increase over standard prevalence estimates, and is a ”game changer” for how clinicians should approach hypertension management and PA diagnosis going forward, said John W. Funder, MD, in an editorial accompanying the Annals study.

Long considered relatively uncommon, hypertension driven by an excess of the hormone aldosterone, often because of an adenoma on the adrenal gland, is not the same as conventional “essential” hypertension. The former benefits from early diagnosis because its treatment is completely different – close to half of all PA patients can be treated definitively and quickly with surgical removal of an adenoma from one side of the adrenal gland.

For other PA patients, who have bilateral adrenal hyperplasia that is impossible to resolve surgically, treatment with drugs called mineralocorticoid receptor antagonists (MRAs), such as spironolactone, is needed because they target the hormonal cause of the high BP.

But what usually happens is that a patient with PA is mistakenly diagnosed with essential hypertension, in which the classic approach to treatment is to start with one regular antihypertensive drug, and add on further ones from different drug classes if blood pressure is not adequately controlled. When patients are taking three drugs, without adequate control, they are labeled as having “resistant hypertension.”

But in the case of PA, none of these conventional antihypertensives work, and the process of continuing to monitor and add different drugs wastes time, during which patients deteriorate.

“We need to change the culture of waiting for hypertension to be resistant and have patients riddled with end-organ damage,” due to years of persistently high BP and excess aldosterone “before we look for a secondary cause” like PA, declared Dr. Yang, of Hudson Institute of Medical Research and Monash University in Melbourne, during an interview.

So early diagnosis and prompt treatment of PA is key.

In addition to boosting the public health importance of early PA detection in hypertensive patients, the new up-sized PA prevalence numbers throw a spotlight on primary care physicians (PCPs) as key players who will need to apply the findings to practice on a public health scale.

These novel results create a need for “new guidelines, and a radically revised game plan with the key role of PCPs” emphasized in future management of patients with hypertension, said Dr. Funder, a professor of medicine at Monash University, in a second recent editorial in Hypertension.

“Buy-in by PCPs is essential,” agrees Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville, and a coauthor of the new study.

But he too acknowledges that this presents a major challenge. PCPs and internists, who diagnose a lot of hypertension, are “not used to thinking about aldosterone,” he said in an interview, encapsulating the key problem faced by proponents of earlier and more widespread PA assessment.

This dilemma looms as a “huge public health issue,” Dr. Carey warned.
 

‘We’re a long way from getting’ PCPs to buy in to PA screening

Will PCPs grow more comfortable with screening patients for PA themselves, or might they become more willing to refer hypertensive individuals for assessment at an expert center?

One skeptic is Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg. The finding about high PA prevalence in patients with hypertension “is brand new, [and] the message needs to get to PCPs,” he said. But, “We’re a long way from getting it” to them. “I don’t know how to do that. It will be a tough sell.”

In addition, repositioning MRAs as an earlier option for many hypertensive patients won’t be easy either, because “we’ll never have outcome-trial data for MRAs,” given that they are now generic drugs, he noted.

“No clinical trial data show [MRAs] are first-line drugs,” said Dr. Feldman, who explained that, instead, MRAs are considered “go-to drugs” for patients with treatment-resistant hypertension, a niche therapeutic area. Results from the PATHWAY-2 trial published 5 years ago in Lancet showed “spironolactone was clearly the most effective treatment for the condition,” according to the report authors.

But even among patients with resistant hypertension, screening for PA dramatically lags despite being enshrined in guidelines.

“PCPs should start checking aldosterone-to-renin ratios [a widely used PA screen] in all patients with resistant hypertension or hypertension with hypokalemia, and then refer patients to specialists for testing and management,” said Jordana B. Cohen, MD, a nephrologist and hypertension researcher at the University of Pennsylvania in Philadelphia.

But recent studies of U.S. patient populations with clinical characteristics that meet existing criteria for PA screening showed that just 1%-2% of these individuals underwent an initial PA assessment, she noted, citing reports in the journals Surgery and Hypertension.

“We need to prioritize improving screening in these high-risk patients,” she stressed in an interview.

This illustrates that, in some respects, the new prevalence numbers are beside the point, because PA has been going unscreened and overlooked far too often even in the context of historical, lower prevalence rates, said Dr. Yang.

“The key point is that approximately 1 in 10 people with hypertension, and even more with resistant hypertension, have a form of the disease that is worse than essential hypertension but is routinely missed at present” and is also highly treatable.

“Evidence for the need for increased awareness of PA has been building for 2 decades,” stressed Dr. Yang, who has coauthored several commentaries and reviews that have bemoaned PA’s underappreciated status.
 

Interest in partnering with PCPs on guidance grows

One potential solution is to have endocrinologists and hypertension specialists’ partner with PCPs to come up with diagnostic and management recommendations. Both Dr. Funder and Dr. Carey are opinion leaders regarding the role of aldosterone in hypertension, and both were coauthors of the 2016 Endocrine Society guideline for PA assessment and management published in the Journal of Clinical Endocrinology & Metabolism , with Dr. Funder chairing the writing panel.

Now approaching its fifth year in effect, this guideline is “due for revision,” and “my hope is that we’ll be able to partner with one or more PCP organizations to come up with a version of the guideline targeted to PCPs,” Dr. Carey said.

He voiced interest in working on this with the American College of Physicians, which represents U.S. internal medicine physicians, and the American Academy of Family Physicians.

“We definitely need a partnership and educational efforts to get the word out from these organizations and not from a specialty society,” said Dr. Carey.

Dr. Funder said he has submitted a proposal to the Endocrine Society for a guidelines update he would chair with Dr. Carey’s assistance and with a diverse writing group that includes PCPs. Dr. Carey said that ideally this panel would write and release a revised guideline in 2021.

“Several of us are chomping at the bit to get this done,” he noted.

But participation by the ACP and AAFP remain uncertain as of September 2020. When approached about this, an ACP spokesperson said the organization had no comment. A spokesperson for the AAFP said, “It’s too early to tell if we will partner with any other organizations to develop guidelines specific to excess aldosterone, and how such guidelines might be received by our members.”

Recent history shows little cooperation between ACP, AAFP, and what might be termed the U.S. hypertension “establishment.” For example, when the American College of Cardiology and the American Heart Association released their most recent essential hypertension management guidelines in Hypertension in 2018, it was never adopted by ACP or AAFP.

The latter two organizations continue to endorse a higher BP threshold for diagnosing hypertension, and higher treatment targets set by alternative expert panels to those of the AHA/ACC.
 

Collaboration feasible, although PCPs overworked

Dr. Carey hopes that this episode will not preclude agreement over PA screening.

“I think it is still possible to partner with [the ACP and AAFP],” he observed, adding that he believes high PA prevalence among hypertensive patients and its consequences when unrecognized is “noncontentious.”

But he acknowledges that other, substantial hurdles also exist, notably the “overwhelming workload” that American PCPs already face.

David O’Gurek, MD, a family and community medicine physician at the Lewis Katz School of Medicine of Temple University in Philadelphia, agrees that a revamped approach to PA screening developed cooperatively between PCPs and specialists is an important goal and potentially feasible despite prior disagreements. “There has to be room for collaboration,” he said, but also emphasized the need for developing policies based on a systematic evidence review and a focus on patient-centered outcomes.

“We’re certainly missing patients with PA, but there needs to be greater clarity and standardization about the most appropriate screening approach and cutoff level” for flagging patients who need specialized assessment, Dr. O’Gurek said in an interview.

The current endocrinology literature also shows that experts remain divided on how best to accomplish this.

And some hypertension specialists question whether existing evidence is conclusive enough to warrant revised guidelines.

Dr. Cohen, the nephrologist and hypertension researcher, said that, while the recent prevalence report in Annals of Internal Medicine is “intriguing, hypothesis-generating information that suggests we are missing many cases of hyperaldosteronism in routine care,” she nevertheless believes that “we need additional data to be able to truly understand the breadth and implications of the findings.”

William C. Cushman, MD, a hypertension management specialist at the University of Tennessee Health Science Center in Memphis, agrees.

Changing existing practice guidelines “really needs randomized, controlled trials demonstrating a difference in long-term outcomes, ideally major cardiovascular outcomes,” that result from broader PA screening, he said.

Dr. Carey concurs that more evidence is needed to confirm the Annals report, but is confident this evidence will be in hand by the time a guideline-revision panel meets in 2021.
 

Australian model of PCPs screening for PA could be implemented in United States

An example of what might be possible when PCPs, endocrinologists, and hypertension specialists work together to make PA screening more accessible can be found in Melbourne, at the Endocrine Hypertension Service of Monash Health, in association with the Hudson Institute of Medical Research.

This began operating in July 2016, cofounded by Dr. Yang, whose experiences with her own father made her sensitive to the issue.

The service’s aim is to “address the underdiagnosis of PA, and to offer a streamlined diagnostic service for patients with hypertension,” with an “extensive outreach program” targeted to regional PCPs that, among other messages, encourages them to screen patients for PA when blood pressures exceed 140/90 mm Hg.

During its first 3 years of operation, the service saw 267 patients, with PA diagnosed in 135 and ruled out in 73 patients.

Notably, the proportion of these patients referred from PCPs jumped from 21% of 70 patients during the first year of operation to 47% of 70 patients during year 2, and 52% of 127 patients during the third year, ending in July 2019, said Dr. Yang, who continues to help run the service.

During the first year, a scant 3% of referred patients had recently diagnosed hypertension, but this rose to 14% during the second year, and to 19% during the most recent year with data available.

The median duration of diagnosed hypertension among referred patients fell from 11 years during year 1, to 7 years during year 3.

Service clinicians diagnosed 37 patients with unilateral adenomas, and removed them from 23 patients with four more awaiting surgery and the remaining 10 opting instead for medical management. Another 95 patients went on therapy with a MRA, and during the most recent year studied all patients who began a MRA regimen had a partial or complete clinical response.

Dr. Carey said the “creative program represents a model for implementation in U.S. practice.

Dr. Funder, Dr. Carey, Dr. Feldman, Dr. Yang, Dr. Cohen, and Dr. O’Gurek had no relevant disclosures. Dr. Cushman has been a consultant to Novartis, received personal fees from Sanofi, and research funding from Eli Lilly.

[email protected]

Jun Yang, MBBS, had watched as her father, who had battled hypertension for decades, ended up on four medications that still couldn’t bring his blood pressure to a healthy level. The cardiovascular endocrinologist then ran some tests, and soon thereafter her father had his blood pressure optimized on just one targeted medication.

Courtesy Dr. Jun Yang

Dr. Yang’s father was found to have a hormonal condition known as primary aldosteronism (PA) as the cause of his hypertension.

It turns out that PA is not as rare as once thought.

An eye-catching report in Annals of Internal Medicine this spring of an unexpectedly high prevalence of primary aldosteronism among a diverse cross section of U.S. patients with hypertension has raised issues that could dramatically change the way doctors in America, and elsewhere, assess and manage high blood pressure.

Foremost is the question of whether primary care physicians – the clinicians at the front line for diagnosing and initially treating most patients with hypertension – will absorb and act on this new evidence. For them, aldosteronism doesn’t automatically come to mind when they see high numbers on a BP monitor, and yet this latest research found that up to a third of all 726 patients in the study who were diagnosed with hypertension and with high urinary salt levels had PA.

That translates to a roughly three- to fivefold increase over standard prevalence estimates, and is a ”game changer” for how clinicians should approach hypertension management and PA diagnosis going forward, said John W. Funder, MD, in an editorial accompanying the Annals study.

Long considered relatively uncommon, hypertension driven by an excess of the hormone aldosterone, often because of an adenoma on the adrenal gland, is not the same as conventional “essential” hypertension. The former benefits from early diagnosis because its treatment is completely different – close to half of all PA patients can be treated definitively and quickly with surgical removal of an adenoma from one side of the adrenal gland.

For other PA patients, who have bilateral adrenal hyperplasia that is impossible to resolve surgically, treatment with drugs called mineralocorticoid receptor antagonists (MRAs), such as spironolactone, is needed because they target the hormonal cause of the high BP.

But what usually happens is that a patient with PA is mistakenly diagnosed with essential hypertension, in which the classic approach to treatment is to start with one regular antihypertensive drug, and add on further ones from different drug classes if blood pressure is not adequately controlled. When patients are taking three drugs, without adequate control, they are labeled as having “resistant hypertension.”

But in the case of PA, none of these conventional antihypertensives work, and the process of continuing to monitor and add different drugs wastes time, during which patients deteriorate.

“We need to change the culture of waiting for hypertension to be resistant and have patients riddled with end-organ damage,” due to years of persistently high BP and excess aldosterone “before we look for a secondary cause” like PA, declared Dr. Yang, of Hudson Institute of Medical Research and Monash University in Melbourne, during an interview.

So early diagnosis and prompt treatment of PA is key.

In addition to boosting the public health importance of early PA detection in hypertensive patients, the new up-sized PA prevalence numbers throw a spotlight on primary care physicians (PCPs) as key players who will need to apply the findings to practice on a public health scale.

These novel results create a need for “new guidelines, and a radically revised game plan with the key role of PCPs” emphasized in future management of patients with hypertension, said Dr. Funder, a professor of medicine at Monash University, in a second recent editorial in Hypertension.

“Buy-in by PCPs is essential,” agrees Robert M. Carey, MD, a cardiovascular endocrinologist and professor of medicine at the University of Virginia in Charlottesville, and a coauthor of the new study.

But he too acknowledges that this presents a major challenge. PCPs and internists, who diagnose a lot of hypertension, are “not used to thinking about aldosterone,” he said in an interview, encapsulating the key problem faced by proponents of earlier and more widespread PA assessment.

This dilemma looms as a “huge public health issue,” Dr. Carey warned.
 

‘We’re a long way from getting’ PCPs to buy in to PA screening

Will PCPs grow more comfortable with screening patients for PA themselves, or might they become more willing to refer hypertensive individuals for assessment at an expert center?

One skeptic is Ross D. Feldman, MD, a hypertension-management researcher and professor of medicine at the University of Manitoba in Winnipeg. The finding about high PA prevalence in patients with hypertension “is brand new, [and] the message needs to get to PCPs,” he said. But, “We’re a long way from getting it” to them. “I don’t know how to do that. It will be a tough sell.”

In addition, repositioning MRAs as an earlier option for many hypertensive patients won’t be easy either, because “we’ll never have outcome-trial data for MRAs,” given that they are now generic drugs, he noted.

“No clinical trial data show [MRAs] are first-line drugs,” said Dr. Feldman, who explained that, instead, MRAs are considered “go-to drugs” for patients with treatment-resistant hypertension, a niche therapeutic area. Results from the PATHWAY-2 trial published 5 years ago in Lancet showed “spironolactone was clearly the most effective treatment for the condition,” according to the report authors.

But even among patients with resistant hypertension, screening for PA dramatically lags despite being enshrined in guidelines.

“PCPs should start checking aldosterone-to-renin ratios [a widely used PA screen] in all patients with resistant hypertension or hypertension with hypokalemia, and then refer patients to specialists for testing and management,” said Jordana B. Cohen, MD, a nephrologist and hypertension researcher at the University of Pennsylvania in Philadelphia.

But recent studies of U.S. patient populations with clinical characteristics that meet existing criteria for PA screening showed that just 1%-2% of these individuals underwent an initial PA assessment, she noted, citing reports in the journals Surgery and Hypertension.

“We need to prioritize improving screening in these high-risk patients,” she stressed in an interview.

This illustrates that, in some respects, the new prevalence numbers are beside the point, because PA has been going unscreened and overlooked far too often even in the context of historical, lower prevalence rates, said Dr. Yang.

“The key point is that approximately 1 in 10 people with hypertension, and even more with resistant hypertension, have a form of the disease that is worse than essential hypertension but is routinely missed at present” and is also highly treatable.

“Evidence for the need for increased awareness of PA has been building for 2 decades,” stressed Dr. Yang, who has coauthored several commentaries and reviews that have bemoaned PA’s underappreciated status.
 

Interest in partnering with PCPs on guidance grows

One potential solution is to have endocrinologists and hypertension specialists’ partner with PCPs to come up with diagnostic and management recommendations. Both Dr. Funder and Dr. Carey are opinion leaders regarding the role of aldosterone in hypertension, and both were coauthors of the 2016 Endocrine Society guideline for PA assessment and management published in the Journal of Clinical Endocrinology & Metabolism , with Dr. Funder chairing the writing panel.

Now approaching its fifth year in effect, this guideline is “due for revision,” and “my hope is that we’ll be able to partner with one or more PCP organizations to come up with a version of the guideline targeted to PCPs,” Dr. Carey said.

He voiced interest in working on this with the American College of Physicians, which represents U.S. internal medicine physicians, and the American Academy of Family Physicians.

“We definitely need a partnership and educational efforts to get the word out from these organizations and not from a specialty society,” said Dr. Carey.

Dr. Funder said he has submitted a proposal to the Endocrine Society for a guidelines update he would chair with Dr. Carey’s assistance and with a diverse writing group that includes PCPs. Dr. Carey said that ideally this panel would write and release a revised guideline in 2021.

“Several of us are chomping at the bit to get this done,” he noted.

But participation by the ACP and AAFP remain uncertain as of September 2020. When approached about this, an ACP spokesperson said the organization had no comment. A spokesperson for the AAFP said, “It’s too early to tell if we will partner with any other organizations to develop guidelines specific to excess aldosterone, and how such guidelines might be received by our members.”

Recent history shows little cooperation between ACP, AAFP, and what might be termed the U.S. hypertension “establishment.” For example, when the American College of Cardiology and the American Heart Association released their most recent essential hypertension management guidelines in Hypertension in 2018, it was never adopted by ACP or AAFP.

The latter two organizations continue to endorse a higher BP threshold for diagnosing hypertension, and higher treatment targets set by alternative expert panels to those of the AHA/ACC.
 

Collaboration feasible, although PCPs overworked

Dr. Carey hopes that this episode will not preclude agreement over PA screening.

“I think it is still possible to partner with [the ACP and AAFP],” he observed, adding that he believes high PA prevalence among hypertensive patients and its consequences when unrecognized is “noncontentious.”

But he acknowledges that other, substantial hurdles also exist, notably the “overwhelming workload” that American PCPs already face.

David O’Gurek, MD, a family and community medicine physician at the Lewis Katz School of Medicine of Temple University in Philadelphia, agrees that a revamped approach to PA screening developed cooperatively between PCPs and specialists is an important goal and potentially feasible despite prior disagreements. “There has to be room for collaboration,” he said, but also emphasized the need for developing policies based on a systematic evidence review and a focus on patient-centered outcomes.

“We’re certainly missing patients with PA, but there needs to be greater clarity and standardization about the most appropriate screening approach and cutoff level” for flagging patients who need specialized assessment, Dr. O’Gurek said in an interview.

The current endocrinology literature also shows that experts remain divided on how best to accomplish this.

And some hypertension specialists question whether existing evidence is conclusive enough to warrant revised guidelines.

Dr. Cohen, the nephrologist and hypertension researcher, said that, while the recent prevalence report in Annals of Internal Medicine is “intriguing, hypothesis-generating information that suggests we are missing many cases of hyperaldosteronism in routine care,” she nevertheless believes that “we need additional data to be able to truly understand the breadth and implications of the findings.”

William C. Cushman, MD, a hypertension management specialist at the University of Tennessee Health Science Center in Memphis, agrees.

Changing existing practice guidelines “really needs randomized, controlled trials demonstrating a difference in long-term outcomes, ideally major cardiovascular outcomes,” that result from broader PA screening, he said.

Dr. Carey concurs that more evidence is needed to confirm the Annals report, but is confident this evidence will be in hand by the time a guideline-revision panel meets in 2021.
 

Australian model of PCPs screening for PA could be implemented in United States

An example of what might be possible when PCPs, endocrinologists, and hypertension specialists work together to make PA screening more accessible can be found in Melbourne, at the Endocrine Hypertension Service of Monash Health, in association with the Hudson Institute of Medical Research.

This began operating in July 2016, cofounded by Dr. Yang, whose experiences with her own father made her sensitive to the issue.

The service’s aim is to “address the underdiagnosis of PA, and to offer a streamlined diagnostic service for patients with hypertension,” with an “extensive outreach program” targeted to regional PCPs that, among other messages, encourages them to screen patients for PA when blood pressures exceed 140/90 mm Hg.

During its first 3 years of operation, the service saw 267 patients, with PA diagnosed in 135 and ruled out in 73 patients.

Notably, the proportion of these patients referred from PCPs jumped from 21% of 70 patients during the first year of operation to 47% of 70 patients during year 2, and 52% of 127 patients during the third year, ending in July 2019, said Dr. Yang, who continues to help run the service.

During the first year, a scant 3% of referred patients had recently diagnosed hypertension, but this rose to 14% during the second year, and to 19% during the most recent year with data available.

The median duration of diagnosed hypertension among referred patients fell from 11 years during year 1, to 7 years during year 3.

Service clinicians diagnosed 37 patients with unilateral adenomas, and removed them from 23 patients with four more awaiting surgery and the remaining 10 opting instead for medical management. Another 95 patients went on therapy with a MRA, and during the most recent year studied all patients who began a MRA regimen had a partial or complete clinical response.

Dr. Carey said the “creative program represents a model for implementation in U.S. practice.

Dr. Funder, Dr. Carey, Dr. Feldman, Dr. Yang, Dr. Cohen, and Dr. O’Gurek had no relevant disclosures. Dr. Cushman has been a consultant to Novartis, received personal fees from Sanofi, and research funding from Eli Lilly.

[email protected]

Objective neuropsychological tests can be used to subclassify the cognitive symptoms present in patients with major depression into three patterns having implications for treatment responsiveness, Gitte Moos Knudsen, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

“Our data highlight the importance of assessing and targeting cognitive symptoms,” said Dr. Knudsen, the ECNP president and professor of neurology at the University of Copenhagen.

She was a coauthor of the Danish NeuroPharm study, in which 92 antidepressant-free patients with moderate or severe major depressive disorder and 103 healthy controls completed a comprehensive neuropsychological test battery. The testing included a validation study of the EMOTICOM test battery, a novel neuropsychological test battery developed specifically to assess what has been called “hot” cognition, such as emotion processing, social cognition, and affective verbal memory.

Overall, the depressed patients collectively showed moderate increases in measures of guilt and shame, moderate deficits in working and verbal memory, moderately slowed reaction time, and mild to moderate negative affective bias, compared with controls. No correlation was found between performance on any of the individual cognitive domains and depression severity as measured using the Hamilton Depression Rating Scale, underscoring the concept that cognitive impairment is a distinct component of depressive pathology rather than an extension of the classic mood and somatic symptoms of major depression.

Cluster analysis revealed three distinct patterns of cognitive impairment in the study population. Unlike the individual cognitive domains, these cognitive clusters did correlate with depression severity. The implication is that neuropsychological testing may identify large subgroups of patients with major depression who may benefit from augmentation of antidepressant medication with treatments targeting impaired cognition, as they become available.

Investigators classified 38 of the 92 patients with major depressive disorder as falling within Cluster A. That is, they exhibited marked deficits in hot cognition expressed in a greatly impaired ability to accurately identify facial emotions on photographs, with resultant high scores for emotion recognition bias and emotion misattribution bias. This impairment in hot cognition was accompanied by minimal guilt and shame and little or no deficits in the cold cognitive domains of verbal and working memory.

Cluster B, composed of 28 patients, was characterized by generally good cognitive function, with positive biases in emotion processing, near-normal guilt and shame ratings, but moderate deficits across the cold cognition domains, making for a mirror image of Cluster A.

The 26 patients in Cluster C demonstrated large deficits in both the hot and cold cognition domains, with particularly pronounced guilt and shame scores.

The three clusters didn’t differ in terms of age or sex. However, patients in Cluster C had significantly more severe core depressive symptoms as measured by Hamilton scores than in Clusters A and B.

This analysis from the NeuroPharm study was cross-sectional. Dr. Knudsen cited a recent large Chinese longitudinal study to underscore how the prevalence of patient-reported cognitive deficits in major depressive disorder is high. And while those deficits decrease over time, they nonetheless remain substantial after 6 months on antidepressant therapy.

That study included 598 Chinese outpatients with major depressive disorder. At baseline, 77% had cognitive symptoms as evidenced by a total score of 21 or more on the self-rated Perceived Deficits Questionnaire–Depression (PDQ-D). One month after going on antidepressant monotherapy, the prevalence of cognitive symptoms had dropped to 59%. At 2 months, the rate was 45%. And at month 6, a PDQ-D score of 21 or greater was still present in 32.4% of patients. High baseline PDQ-D scores were associated with worse clinical outcomes, including a lower treatment response rate at 1 month and a lower remission rate at 2 months. Moreover, high PDQ-D scores at 2 months were associated with lower remission and higher relapse rates at 6 months.

Dr. Knudsen reported having no financial conflicts regarding the NeuroPharm study, which was conducted free of commercial support. She serves as an adviser to Sage Therapeutics and Sanos.

[email protected]

Objective neuropsychological tests can be used to subclassify the cognitive symptoms present in patients with major depression into three patterns having implications for treatment responsiveness, Gitte Moos Knudsen, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

“Our data highlight the importance of assessing and targeting cognitive symptoms,” said Dr. Knudsen, the ECNP president and professor of neurology at the University of Copenhagen.

She was a coauthor of the Danish NeuroPharm study, in which 92 antidepressant-free patients with moderate or severe major depressive disorder and 103 healthy controls completed a comprehensive neuropsychological test battery. The testing included a validation study of the EMOTICOM test battery, a novel neuropsychological test battery developed specifically to assess what has been called “hot” cognition, such as emotion processing, social cognition, and affective verbal memory.

Overall, the depressed patients collectively showed moderate increases in measures of guilt and shame, moderate deficits in working and verbal memory, moderately slowed reaction time, and mild to moderate negative affective bias, compared with controls. No correlation was found between performance on any of the individual cognitive domains and depression severity as measured using the Hamilton Depression Rating Scale, underscoring the concept that cognitive impairment is a distinct component of depressive pathology rather than an extension of the classic mood and somatic symptoms of major depression.

Cluster analysis revealed three distinct patterns of cognitive impairment in the study population. Unlike the individual cognitive domains, these cognitive clusters did correlate with depression severity. The implication is that neuropsychological testing may identify large subgroups of patients with major depression who may benefit from augmentation of antidepressant medication with treatments targeting impaired cognition, as they become available.

Investigators classified 38 of the 92 patients with major depressive disorder as falling within Cluster A. That is, they exhibited marked deficits in hot cognition expressed in a greatly impaired ability to accurately identify facial emotions on photographs, with resultant high scores for emotion recognition bias and emotion misattribution bias. This impairment in hot cognition was accompanied by minimal guilt and shame and little or no deficits in the cold cognitive domains of verbal and working memory.

Cluster B, composed of 28 patients, was characterized by generally good cognitive function, with positive biases in emotion processing, near-normal guilt and shame ratings, but moderate deficits across the cold cognition domains, making for a mirror image of Cluster A.

The 26 patients in Cluster C demonstrated large deficits in both the hot and cold cognition domains, with particularly pronounced guilt and shame scores.

The three clusters didn’t differ in terms of age or sex. However, patients in Cluster C had significantly more severe core depressive symptoms as measured by Hamilton scores than in Clusters A and B.

This analysis from the NeuroPharm study was cross-sectional. Dr. Knudsen cited a recent large Chinese longitudinal study to underscore how the prevalence of patient-reported cognitive deficits in major depressive disorder is high. And while those deficits decrease over time, they nonetheless remain substantial after 6 months on antidepressant therapy.

That study included 598 Chinese outpatients with major depressive disorder. At baseline, 77% had cognitive symptoms as evidenced by a total score of 21 or more on the self-rated Perceived Deficits Questionnaire–Depression (PDQ-D). One month after going on antidepressant monotherapy, the prevalence of cognitive symptoms had dropped to 59%. At 2 months, the rate was 45%. And at month 6, a PDQ-D score of 21 or greater was still present in 32.4% of patients. High baseline PDQ-D scores were associated with worse clinical outcomes, including a lower treatment response rate at 1 month and a lower remission rate at 2 months. Moreover, high PDQ-D scores at 2 months were associated with lower remission and higher relapse rates at 6 months.

Dr. Knudsen reported having no financial conflicts regarding the NeuroPharm study, which was conducted free of commercial support. She serves as an adviser to Sage Therapeutics and Sanos.

[email protected]

Objective neuropsychological tests can be used to subclassify the cognitive symptoms present in patients with major depression into three patterns having implications for treatment responsiveness, Gitte Moos Knudsen, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.

“Our data highlight the importance of assessing and targeting cognitive symptoms,” said Dr. Knudsen, the ECNP president and professor of neurology at the University of Copenhagen.

She was a coauthor of the Danish NeuroPharm study, in which 92 antidepressant-free patients with moderate or severe major depressive disorder and 103 healthy controls completed a comprehensive neuropsychological test battery. The testing included a validation study of the EMOTICOM test battery, a novel neuropsychological test battery developed specifically to assess what has been called “hot” cognition, such as emotion processing, social cognition, and affective verbal memory.

Overall, the depressed patients collectively showed moderate increases in measures of guilt and shame, moderate deficits in working and verbal memory, moderately slowed reaction time, and mild to moderate negative affective bias, compared with controls. No correlation was found between performance on any of the individual cognitive domains and depression severity as measured using the Hamilton Depression Rating Scale, underscoring the concept that cognitive impairment is a distinct component of depressive pathology rather than an extension of the classic mood and somatic symptoms of major depression.

Cluster analysis revealed three distinct patterns of cognitive impairment in the study population. Unlike the individual cognitive domains, these cognitive clusters did correlate with depression severity. The implication is that neuropsychological testing may identify large subgroups of patients with major depression who may benefit from augmentation of antidepressant medication with treatments targeting impaired cognition, as they become available.

Investigators classified 38 of the 92 patients with major depressive disorder as falling within Cluster A. That is, they exhibited marked deficits in hot cognition expressed in a greatly impaired ability to accurately identify facial emotions on photographs, with resultant high scores for emotion recognition bias and emotion misattribution bias. This impairment in hot cognition was accompanied by minimal guilt and shame and little or no deficits in the cold cognitive domains of verbal and working memory.

Cluster B, composed of 28 patients, was characterized by generally good cognitive function, with positive biases in emotion processing, near-normal guilt and shame ratings, but moderate deficits across the cold cognition domains, making for a mirror image of Cluster A.

The 26 patients in Cluster C demonstrated large deficits in both the hot and cold cognition domains, with particularly pronounced guilt and shame scores.

The three clusters didn’t differ in terms of age or sex. However, patients in Cluster C had significantly more severe core depressive symptoms as measured by Hamilton scores than in Clusters A and B.

This analysis from the NeuroPharm study was cross-sectional. Dr. Knudsen cited a recent large Chinese longitudinal study to underscore how the prevalence of patient-reported cognitive deficits in major depressive disorder is high. And while those deficits decrease over time, they nonetheless remain substantial after 6 months on antidepressant therapy.

That study included 598 Chinese outpatients with major depressive disorder. At baseline, 77% had cognitive symptoms as evidenced by a total score of 21 or more on the self-rated Perceived Deficits Questionnaire–Depression (PDQ-D). One month after going on antidepressant monotherapy, the prevalence of cognitive symptoms had dropped to 59%. At 2 months, the rate was 45%. And at month 6, a PDQ-D score of 21 or greater was still present in 32.4% of patients. High baseline PDQ-D scores were associated with worse clinical outcomes, including a lower treatment response rate at 1 month and a lower remission rate at 2 months. Moreover, high PDQ-D scores at 2 months were associated with lower remission and higher relapse rates at 6 months.

Dr. Knudsen reported having no financial conflicts regarding the NeuroPharm study, which was conducted free of commercial support. She serves as an adviser to Sage Therapeutics and Sanos.

[email protected]

Brachial plexus injury often is thought to co-occur with shoulder dystocia, but the two complications appear to be unrelated, according to research published in Obstetrics & Gynecology.

dimarik/iStock/Getty Images

Grace J. Johnson, MD, and colleagues at Baylor College of Medicine in Houston performed a medical review of 41,525 deliveries at Texas Children’s Hospital between March 2012 and July 2019, identifying cases of brachial plexus injury, with and without shoulder dystocia, occurring and persisting. The researchers also evaluated whether clinical experience (5 years or fewer, 6-15 years, or more than 15 years since training) and education impacted the risk of children developing shoulder dystocia or brachial plexus injury.

There were 547 cases of shoulder dystocia in 26,163 vaginal births (2.1%) and 9 cases in 15,362 cesarean births (0.06%), while 33 cases of brachial plexus injury occurred overall. Nearly all brachial plexus injuries were in vaginal deliveries (30 cases; 0.1%), while 3 cases occurred in cesarean deliveries (0.02%). Of these, 14 cases (42%) of brachial plexus injury did not co-occur with shoulder dystocia. Brachial plexus injury that persisted to discharge was similar for children with shoulder dystocia (17 of 19 cases; 89%) and without shoulder dystocia (10 of 14 cases; 71%). In the 27 children with persistent brachial plexus injury, 2 of 23 children who received follow-up care continued to experience persistent brachial plexus injury at 9 months (1 case with shoulder dystocia) and 12 months (1 case without shoulder dystocia).

“The frequent co-occurrence of shoulder dystocia and brachial plexus injury coupled with the equally frequent occurrence of isolated brachial plexus injury suggests that both brachial plexus injury and shoulder dystocia often reflect two causally unrelated complications of uterine forces driving a fetus through the birth canal in the presence of disproportion between the passage and the shoulder girdle of the passenger,” Dr. Johnson and colleagues wrote.
 

Results unchanged by clinician experience

Factors that impacted the risk of brachial plexus injury in children without shoulder dystocia were lack of maternal diabetes (0 women vs. 6 women; P = .03) and second-stage labor length (mean 103 minutes vs. 53 minutes; P = .08). Dr. Johnson and colleagues found no significant between-group differences regarding operative delivery, maternal age, or gestational age.

The researchers also examined the experience of the clinician who delivered children with brachial plexus injuries, and discovered there were no significant differences in children who had transient as opposed to persistent brachial plexus injury based on the number of years a clinician had been in practice (P = .97). There also were no significant changes in the “ratios of brachial plexus injury per total deliveries, brachial plexus injury per vaginal deliveries, and brachial plexus injury per shoulder dystocia” despite the presence of education and training for shoulder dystocia.
 

Questions require further study

Torri Metz, MD, MS, a maternal-fetal medicine subspecialist and associate professor of obstetrics and gynecology at University of Utah Health in Salt Lake City, said in an interview that the review by Johnson and colleagues was able to address limitations in previous studies by looking at the medical records of shoulder dystocia cases at a single tertiary care center.

“Brachial plexus injury occurs both with and without a diagnosis of shoulder dystocia. The finding that the non–shoulder dystocia brachial plexus injuries were associated with a longer second stage of labor suggests that these injuries can occur even prior to delivery of the fetal head and are often not related to maneuvers employed by an obstetrician during delivery,” Dr. Metz said.

The findings that brachial plexus injury severity was unrelated to clinician experience suggests “the occurrence, severity, and persistence of brachial plexus injury may be unrelated to maneuvers by the practitioner at the time of delivery,” she said.

Although Johnson et al. found education and training initiatives did not significantly impact the ratio of brachial plexus injury cases, “importantly, there are likely many other benefits to shoulder dystocia simulation including team communication and comfort of the practitioner in an obstetrical emergency. Thus, the conclusion should not be that simulation training should be abandoned,” Dr. Metz explained.

The results of the study should be confirmed in future research, she noted. “Despite looking at all cases of shoulder dystocia at a tertiary center over a 7-year period, the incidence of brachial plexus injury is low enough that only 33 cases were evaluated. As such, many questions about obstetrical management and the risk of brachial plexus injury still require further study,” said Dr. Metz, who was asked to comment on the study.

The authors reported no relevant financial disclosures. Dr. Metz is an editorial board member for Obstetrics and Gynecology. She was not involved in the review of this manuscript or the decision to publish it.

SOURCE: Johnson GJ et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004013.

Brachial plexus injury often is thought to co-occur with shoulder dystocia, but the two complications appear to be unrelated, according to research published in Obstetrics & Gynecology.

dimarik/iStock/Getty Images

Grace J. Johnson, MD, and colleagues at Baylor College of Medicine in Houston performed a medical review of 41,525 deliveries at Texas Children’s Hospital between March 2012 and July 2019, identifying cases of brachial plexus injury, with and without shoulder dystocia, occurring and persisting. The researchers also evaluated whether clinical experience (5 years or fewer, 6-15 years, or more than 15 years since training) and education impacted the risk of children developing shoulder dystocia or brachial plexus injury.

There were 547 cases of shoulder dystocia in 26,163 vaginal births (2.1%) and 9 cases in 15,362 cesarean births (0.06%), while 33 cases of brachial plexus injury occurred overall. Nearly all brachial plexus injuries were in vaginal deliveries (30 cases; 0.1%), while 3 cases occurred in cesarean deliveries (0.02%). Of these, 14 cases (42%) of brachial plexus injury did not co-occur with shoulder dystocia. Brachial plexus injury that persisted to discharge was similar for children with shoulder dystocia (17 of 19 cases; 89%) and without shoulder dystocia (10 of 14 cases; 71%). In the 27 children with persistent brachial plexus injury, 2 of 23 children who received follow-up care continued to experience persistent brachial plexus injury at 9 months (1 case with shoulder dystocia) and 12 months (1 case without shoulder dystocia).

“The frequent co-occurrence of shoulder dystocia and brachial plexus injury coupled with the equally frequent occurrence of isolated brachial plexus injury suggests that both brachial plexus injury and shoulder dystocia often reflect two causally unrelated complications of uterine forces driving a fetus through the birth canal in the presence of disproportion between the passage and the shoulder girdle of the passenger,” Dr. Johnson and colleagues wrote.
 

Results unchanged by clinician experience

Factors that impacted the risk of brachial plexus injury in children without shoulder dystocia were lack of maternal diabetes (0 women vs. 6 women; P = .03) and second-stage labor length (mean 103 minutes vs. 53 minutes; P = .08). Dr. Johnson and colleagues found no significant between-group differences regarding operative delivery, maternal age, or gestational age.

The researchers also examined the experience of the clinician who delivered children with brachial plexus injuries, and discovered there were no significant differences in children who had transient as opposed to persistent brachial plexus injury based on the number of years a clinician had been in practice (P = .97). There also were no significant changes in the “ratios of brachial plexus injury per total deliveries, brachial plexus injury per vaginal deliveries, and brachial plexus injury per shoulder dystocia” despite the presence of education and training for shoulder dystocia.
 

Questions require further study

Torri Metz, MD, MS, a maternal-fetal medicine subspecialist and associate professor of obstetrics and gynecology at University of Utah Health in Salt Lake City, said in an interview that the review by Johnson and colleagues was able to address limitations in previous studies by looking at the medical records of shoulder dystocia cases at a single tertiary care center.

“Brachial plexus injury occurs both with and without a diagnosis of shoulder dystocia. The finding that the non–shoulder dystocia brachial plexus injuries were associated with a longer second stage of labor suggests that these injuries can occur even prior to delivery of the fetal head and are often not related to maneuvers employed by an obstetrician during delivery,” Dr. Metz said.

The findings that brachial plexus injury severity was unrelated to clinician experience suggests “the occurrence, severity, and persistence of brachial plexus injury may be unrelated to maneuvers by the practitioner at the time of delivery,” she said.

Although Johnson et al. found education and training initiatives did not significantly impact the ratio of brachial plexus injury cases, “importantly, there are likely many other benefits to shoulder dystocia simulation including team communication and comfort of the practitioner in an obstetrical emergency. Thus, the conclusion should not be that simulation training should be abandoned,” Dr. Metz explained.

The results of the study should be confirmed in future research, she noted. “Despite looking at all cases of shoulder dystocia at a tertiary center over a 7-year period, the incidence of brachial plexus injury is low enough that only 33 cases were evaluated. As such, many questions about obstetrical management and the risk of brachial plexus injury still require further study,” said Dr. Metz, who was asked to comment on the study.

The authors reported no relevant financial disclosures. Dr. Metz is an editorial board member for Obstetrics and Gynecology. She was not involved in the review of this manuscript or the decision to publish it.

SOURCE: Johnson GJ et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004013.

Brachial plexus injury often is thought to co-occur with shoulder dystocia, but the two complications appear to be unrelated, according to research published in Obstetrics & Gynecology.

dimarik/iStock/Getty Images

Grace J. Johnson, MD, and colleagues at Baylor College of Medicine in Houston performed a medical review of 41,525 deliveries at Texas Children’s Hospital between March 2012 and July 2019, identifying cases of brachial plexus injury, with and without shoulder dystocia, occurring and persisting. The researchers also evaluated whether clinical experience (5 years or fewer, 6-15 years, or more than 15 years since training) and education impacted the risk of children developing shoulder dystocia or brachial plexus injury.

There were 547 cases of shoulder dystocia in 26,163 vaginal births (2.1%) and 9 cases in 15,362 cesarean births (0.06%), while 33 cases of brachial plexus injury occurred overall. Nearly all brachial plexus injuries were in vaginal deliveries (30 cases; 0.1%), while 3 cases occurred in cesarean deliveries (0.02%). Of these, 14 cases (42%) of brachial plexus injury did not co-occur with shoulder dystocia. Brachial plexus injury that persisted to discharge was similar for children with shoulder dystocia (17 of 19 cases; 89%) and without shoulder dystocia (10 of 14 cases; 71%). In the 27 children with persistent brachial plexus injury, 2 of 23 children who received follow-up care continued to experience persistent brachial plexus injury at 9 months (1 case with shoulder dystocia) and 12 months (1 case without shoulder dystocia).

“The frequent co-occurrence of shoulder dystocia and brachial plexus injury coupled with the equally frequent occurrence of isolated brachial plexus injury suggests that both brachial plexus injury and shoulder dystocia often reflect two causally unrelated complications of uterine forces driving a fetus through the birth canal in the presence of disproportion between the passage and the shoulder girdle of the passenger,” Dr. Johnson and colleagues wrote.
 

Results unchanged by clinician experience

Factors that impacted the risk of brachial plexus injury in children without shoulder dystocia were lack of maternal diabetes (0 women vs. 6 women; P = .03) and second-stage labor length (mean 103 minutes vs. 53 minutes; P = .08). Dr. Johnson and colleagues found no significant between-group differences regarding operative delivery, maternal age, or gestational age.

The researchers also examined the experience of the clinician who delivered children with brachial plexus injuries, and discovered there were no significant differences in children who had transient as opposed to persistent brachial plexus injury based on the number of years a clinician had been in practice (P = .97). There also were no significant changes in the “ratios of brachial plexus injury per total deliveries, brachial plexus injury per vaginal deliveries, and brachial plexus injury per shoulder dystocia” despite the presence of education and training for shoulder dystocia.
 

Questions require further study

Torri Metz, MD, MS, a maternal-fetal medicine subspecialist and associate professor of obstetrics and gynecology at University of Utah Health in Salt Lake City, said in an interview that the review by Johnson and colleagues was able to address limitations in previous studies by looking at the medical records of shoulder dystocia cases at a single tertiary care center.

“Brachial plexus injury occurs both with and without a diagnosis of shoulder dystocia. The finding that the non–shoulder dystocia brachial plexus injuries were associated with a longer second stage of labor suggests that these injuries can occur even prior to delivery of the fetal head and are often not related to maneuvers employed by an obstetrician during delivery,” Dr. Metz said.

The findings that brachial plexus injury severity was unrelated to clinician experience suggests “the occurrence, severity, and persistence of brachial plexus injury may be unrelated to maneuvers by the practitioner at the time of delivery,” she said.

Although Johnson et al. found education and training initiatives did not significantly impact the ratio of brachial plexus injury cases, “importantly, there are likely many other benefits to shoulder dystocia simulation including team communication and comfort of the practitioner in an obstetrical emergency. Thus, the conclusion should not be that simulation training should be abandoned,” Dr. Metz explained.

The results of the study should be confirmed in future research, she noted. “Despite looking at all cases of shoulder dystocia at a tertiary center over a 7-year period, the incidence of brachial plexus injury is low enough that only 33 cases were evaluated. As such, many questions about obstetrical management and the risk of brachial plexus injury still require further study,” said Dr. Metz, who was asked to comment on the study.

The authors reported no relevant financial disclosures. Dr. Metz is an editorial board member for Obstetrics and Gynecology. She was not involved in the review of this manuscript or the decision to publish it.

SOURCE: Johnson GJ et al. Obstet Gynecol. 2020 Oct. doi: 10.1097/AOG.0000000000004013.

The cumulative percentage of COVID-19 cases reported in children continues to climb, but “the history behind that cumulative number shows substantial change,” according to a new analysis of state health department data.

As of Sept. 10, the 549,432 cases in children represented 10.0% of all reported COVID-19 cases in the United States following a substantial rise over the course of the pandemic – the figure was 7.7% on July 16 and 3.2% on May 7, Blake Sisk, PhD, of the American Academy of Pediatrics and associates reported Sept. 29 in Pediatrics.

Unlike the cumulative number, the weekly proportion of cases in children fell early in the summer but then started climbing again in late July. “In the last 8 weeks, children represented between 12%-15.9% of new weekly reported cases,” Dr. Sisk and associates wrote.

Despite the increase, however, the proportion of pediatric COVID-19 cases is still well below children’s share of the overall population (22.6%). Also, “it is unclear how much of the increase in child cases is due to increased testing capacity, although CDC data from public and commercial laboratories show the share of all tests administered to children ages 0-17 has remained stable at 5%-7% since late April,” they said.

Data for the current report were drawn from 49 state health department websites (New York state does not report ages for COVID-19 cases), along with New York City, the District of Columbia, Puerto Rico, and Guam. Alabama changed its definition of a child case in August and was not included in the trend analysis (see graph), the investigators explained.

Those data show “substantial variation in case growth by region: in April, a preponderance of cases was in the Northeast. In June, cases surged in the South and West, followed by mid-July increases in the Midwest,” Dr. Sisk and associates said.

The increase among children in Midwest states is ongoing with the number of new cases reaching its highest level yet during the week ending Sept. 10, they reported.

[email protected]

SOURCE: Sisk B et al. Pediatrics. 2020 Sep 29. doi: 10.1542/peds.2020-027425.

The cumulative percentage of COVID-19 cases reported in children continues to climb, but “the history behind that cumulative number shows substantial change,” according to a new analysis of state health department data.

As of Sept. 10, the 549,432 cases in children represented 10.0% of all reported COVID-19 cases in the United States following a substantial rise over the course of the pandemic – the figure was 7.7% on July 16 and 3.2% on May 7, Blake Sisk, PhD, of the American Academy of Pediatrics and associates reported Sept. 29 in Pediatrics.

Unlike the cumulative number, the weekly proportion of cases in children fell early in the summer but then started climbing again in late July. “In the last 8 weeks, children represented between 12%-15.9% of new weekly reported cases,” Dr. Sisk and associates wrote.

Despite the increase, however, the proportion of pediatric COVID-19 cases is still well below children’s share of the overall population (22.6%). Also, “it is unclear how much of the increase in child cases is due to increased testing capacity, although CDC data from public and commercial laboratories show the share of all tests administered to children ages 0-17 has remained stable at 5%-7% since late April,” they said.

Data for the current report were drawn from 49 state health department websites (New York state does not report ages for COVID-19 cases), along with New York City, the District of Columbia, Puerto Rico, and Guam. Alabama changed its definition of a child case in August and was not included in the trend analysis (see graph), the investigators explained.

Those data show “substantial variation in case growth by region: in April, a preponderance of cases was in the Northeast. In June, cases surged in the South and West, followed by mid-July increases in the Midwest,” Dr. Sisk and associates said.

The increase among children in Midwest states is ongoing with the number of new cases reaching its highest level yet during the week ending Sept. 10, they reported.

[email protected]

SOURCE: Sisk B et al. Pediatrics. 2020 Sep 29. doi: 10.1542/peds.2020-027425.

The cumulative percentage of COVID-19 cases reported in children continues to climb, but “the history behind that cumulative number shows substantial change,” according to a new analysis of state health department data.

As of Sept. 10, the 549,432 cases in children represented 10.0% of all reported COVID-19 cases in the United States following a substantial rise over the course of the pandemic – the figure was 7.7% on July 16 and 3.2% on May 7, Blake Sisk, PhD, of the American Academy of Pediatrics and associates reported Sept. 29 in Pediatrics.

Unlike the cumulative number, the weekly proportion of cases in children fell early in the summer but then started climbing again in late July. “In the last 8 weeks, children represented between 12%-15.9% of new weekly reported cases,” Dr. Sisk and associates wrote.

Despite the increase, however, the proportion of pediatric COVID-19 cases is still well below children’s share of the overall population (22.6%). Also, “it is unclear how much of the increase in child cases is due to increased testing capacity, although CDC data from public and commercial laboratories show the share of all tests administered to children ages 0-17 has remained stable at 5%-7% since late April,” they said.

Data for the current report were drawn from 49 state health department websites (New York state does not report ages for COVID-19 cases), along with New York City, the District of Columbia, Puerto Rico, and Guam. Alabama changed its definition of a child case in August and was not included in the trend analysis (see graph), the investigators explained.

Those data show “substantial variation in case growth by region: in April, a preponderance of cases was in the Northeast. In June, cases surged in the South and West, followed by mid-July increases in the Midwest,” Dr. Sisk and associates said.

The increase among children in Midwest states is ongoing with the number of new cases reaching its highest level yet during the week ending Sept. 10, they reported.

[email protected]

SOURCE: Sisk B et al. Pediatrics. 2020 Sep 29. doi: 10.1542/peds.2020-027425.

Requests for self-managed abortion via a telemedicine service increased by 27% from March 20, 2020, to April 11, 2020, in the United States in the wake of widespread lockdowns and shelter-in-place directives because of the COVID-19 pandemic, based on data from a provider of such services.

nortonrsx/Getty Images

Access to abortion care is challenging in many areas under ordinary circumstances, but the disruption of the COVID-19 pandemic led to many states suspending or limiting in-clinic services, wrote Abigail R.A. Aiken, MD, PhD, of the University of Texas at Austin and colleagues.

“As a result, people may increasingly be seeking self-managed abortion outside the formal health care system,” they said.

In a research letter published in Obstetrics & Gynecology, the investigators reviewed request data from Aid Access, a telemedicine service that provides medication for abortion at up to 10 weeks’ gestation for users who complete an online consultation form. They also collected data on the implementation and scope of COVID-19–related abortion restrictions by state.

The analysis included all 49,935 requests made between January 1, 2019, and April 11, 2020.

Overall, the rate of requests for self-managed medical abortions increased significantly, by 27%, during the period from March 20, 2020, to April 11, 2020, which reflected the average period after clinic restrictions or closures at the state level. A total of 11 states showed individually significant increases in requests for self-managed medical abortions, with the highest of 94% in Texas and the lowest of 22% in Ohio. In these 11 states, the median time spent at home was 5% higher than in states without significant increases in requests for self-managed medical abortions during the same period. These states also had “particularly high COVID-19 rates or more severe COVID-19–related restrictions on in-clinic abortion access,” the researchers noted.

Patients want alternatives to in-person care

“Our results may reflect two distinct phenomena,” Dr. Aiken and associates wrote. “First, more people may be seeking abortion through all channels, whether due to COVID-19 risks during pregnancy, reduced access to prenatal care, or the pandemic-related economic downturn. Second, there may be shift in demand from in-clinic to self-managed abortion during the pandemic, possibly owing to fear of infection during in-person care or inability to get to a clinic because of childcare and transit disruptions,” they explained.

The study findings were limited by the inability to measure all options for women to achieve self-managed abortions and a lack of power to detect changes in states with low request numbers or where restrictions were implemented at later dates, the researchers noted. However, the results suggest that telemedicine services for medication abortion should be a policy priority because patients may continue to seek alternatives while in-clinic services remain restricted, they said.

In fact, “the World Health Organization recommends telemedicine and self-management abortion-care models during the pandemic, and the United Kingdom has temporarily implemented fully remote provision of abortion medications,” the researchers wrote. However, similar strategies in the United States “would depend on sustained changes to the U.S. Food and Drug Administration’s Risk Evaluation and Mitigation Strategy, which requires patients to collect mifepristone at a hospital or medical facility, as well as changes to state-specific laws that prohibit remote provider consultation,” Dr. Aiken and associates concluded.

Lift barriers to protect patients

“This important and timely article assesses the association between the disruptions of the coronavirus pandemic and online requests for telemedicine abortion,” Eve Espey, MD, of the University of New Mexico, Albuquerque, said in an interview.

“As background, state abortion restrictions have increased exponentially over the last decade, while research over the same time period has demonstrated the safety of telemedicine abortion – a form of self-managed abortion – with no in-person visit for appropriate candidates,” she said.

“Enter the coronavirus pandemic with safety concerns related to in-person medical visits and certain states leveraging the opportunity to enact even more stringent abortion restrictions. Unsurprisingly, the result, as documented in this excellent research report, is a significant increase in requests for telemedicine abortion in many states, particularly the most restrictive, from the single online service in the United States, Aid Access,” said Dr. Espey.

“Barriers to self-managed abortion include the [FDA] Risk Evaluation and Mitigation Strategy for mifepristone, a set of unnecessary restrictions requiring that providers meet certain qualifications and dispense the medication only in a clinic, office, or hospital,” she said. “The REMS precludes the use of telemedicine abortion; Aid Access and the FDA are in legal proceedings,” she noted.

“Most recently, the [American Civil Liberties Union] sued the FDA on behalf of a coalition of medical experts led by [American College of Obstetricians and Gynecologists] to suspend the REMS for mifepristone during the COVID public health emergency, to allow patients to receive the medications for early abortion without a visit to a health care provider,” Dr. Espey said. “Fortunately, a federal district court required the temporary suspension of the in-person dispensing restriction. Although this is a great step to improve abortion access during the pandemic, a permanent removal of the REMS would pave the way for ongoing safe, effective, and patient-centered early abortion care,” noted Dr. Espey, who was asked to comment on the research letter.

Dr. Aiken disclosed serving as a consultant for Agile Therapeutics, and a coauthor is the founder and director of Aid Access. Dr. Espey had no financial conflicts to disclose. She is a member of the Ob.Gyn. News Editorial Advisory Board.

SOURCE: Aiken ARA et al. Obstet Gynecol. 2020 Jul 21. doi: 10.1097/AOG.0000000000004081.

Requests for self-managed abortion via a telemedicine service increased by 27% from March 20, 2020, to April 11, 2020, in the United States in the wake of widespread lockdowns and shelter-in-place directives because of the COVID-19 pandemic, based on data from a provider of such services.

nortonrsx/Getty Images

Access to abortion care is challenging in many areas under ordinary circumstances, but the disruption of the COVID-19 pandemic led to many states suspending or limiting in-clinic services, wrote Abigail R.A. Aiken, MD, PhD, of the University of Texas at Austin and colleagues.

“As a result, people may increasingly be seeking self-managed abortion outside the formal health care system,” they said.

In a research letter published in Obstetrics & Gynecology, the investigators reviewed request data from Aid Access, a telemedicine service that provides medication for abortion at up to 10 weeks’ gestation for users who complete an online consultation form. They also collected data on the implementation and scope of COVID-19–related abortion restrictions by state.

The analysis included all 49,935 requests made between January 1, 2019, and April 11, 2020.

Overall, the rate of requests for self-managed medical abortions increased significantly, by 27%, during the period from March 20, 2020, to April 11, 2020, which reflected the average period after clinic restrictions or closures at the state level. A total of 11 states showed individually significant increases in requests for self-managed medical abortions, with the highest of 94% in Texas and the lowest of 22% in Ohio. In these 11 states, the median time spent at home was 5% higher than in states without significant increases in requests for self-managed medical abortions during the same period. These states also had “particularly high COVID-19 rates or more severe COVID-19–related restrictions on in-clinic abortion access,” the researchers noted.

Patients want alternatives to in-person care

“Our results may reflect two distinct phenomena,” Dr. Aiken and associates wrote. “First, more people may be seeking abortion through all channels, whether due to COVID-19 risks during pregnancy, reduced access to prenatal care, or the pandemic-related economic downturn. Second, there may be shift in demand from in-clinic to self-managed abortion during the pandemic, possibly owing to fear of infection during in-person care or inability to get to a clinic because of childcare and transit disruptions,” they explained.

The study findings were limited by the inability to measure all options for women to achieve self-managed abortions and a lack of power to detect changes in states with low request numbers or where restrictions were implemented at later dates, the researchers noted. However, the results suggest that telemedicine services for medication abortion should be a policy priority because patients may continue to seek alternatives while in-clinic services remain restricted, they said.

In fact, “the World Health Organization recommends telemedicine and self-management abortion-care models during the pandemic, and the United Kingdom has temporarily implemented fully remote provision of abortion medications,” the researchers wrote. However, similar strategies in the United States “would depend on sustained changes to the U.S. Food and Drug Administration’s Risk Evaluation and Mitigation Strategy, which requires patients to collect mifepristone at a hospital or medical facility, as well as changes to state-specific laws that prohibit remote provider consultation,” Dr. Aiken and associates concluded.

Lift barriers to protect patients

“This important and timely article assesses the association between the disruptions of the coronavirus pandemic and online requests for telemedicine abortion,” Eve Espey, MD, of the University of New Mexico, Albuquerque, said in an interview.

“As background, state abortion restrictions have increased exponentially over the last decade, while research over the same time period has demonstrated the safety of telemedicine abortion – a form of self-managed abortion – with no in-person visit for appropriate candidates,” she said.

“Enter the coronavirus pandemic with safety concerns related to in-person medical visits and certain states leveraging the opportunity to enact even more stringent abortion restrictions. Unsurprisingly, the result, as documented in this excellent research report, is a significant increase in requests for telemedicine abortion in many states, particularly the most restrictive, from the single online service in the United States, Aid Access,” said Dr. Espey.

“Barriers to self-managed abortion include the [FDA] Risk Evaluation and Mitigation Strategy for mifepristone, a set of unnecessary restrictions requiring that providers meet certain qualifications and dispense the medication only in a clinic, office, or hospital,” she said. “The REMS precludes the use of telemedicine abortion; Aid Access and the FDA are in legal proceedings,” she noted.

“Most recently, the [American Civil Liberties Union] sued the FDA on behalf of a coalition of medical experts led by [American College of Obstetricians and Gynecologists] to suspend the REMS for mifepristone during the COVID public health emergency, to allow patients to receive the medications for early abortion without a visit to a health care provider,” Dr. Espey said. “Fortunately, a federal district court required the temporary suspension of the in-person dispensing restriction. Although this is a great step to improve abortion access during the pandemic, a permanent removal of the REMS would pave the way for ongoing safe, effective, and patient-centered early abortion care,” noted Dr. Espey, who was asked to comment on the research letter.

Dr. Aiken disclosed serving as a consultant for Agile Therapeutics, and a coauthor is the founder and director of Aid Access. Dr. Espey had no financial conflicts to disclose. She is a member of the Ob.Gyn. News Editorial Advisory Board.

SOURCE: Aiken ARA et al. Obstet Gynecol. 2020 Jul 21. doi: 10.1097/AOG.0000000000004081.

Requests for self-managed abortion via a telemedicine service increased by 27% from March 20, 2020, to April 11, 2020, in the United States in the wake of widespread lockdowns and shelter-in-place directives because of the COVID-19 pandemic, based on data from a provider of such services.

nortonrsx/Getty Images

Access to abortion care is challenging in many areas under ordinary circumstances, but the disruption of the COVID-19 pandemic led to many states suspending or limiting in-clinic services, wrote Abigail R.A. Aiken, MD, PhD, of the University of Texas at Austin and colleagues.

“As a result, people may increasingly be seeking self-managed abortion outside the formal health care system,” they said.

In a research letter published in Obstetrics & Gynecology, the investigators reviewed request data from Aid Access, a telemedicine service that provides medication for abortion at up to 10 weeks’ gestation for users who complete an online consultation form. They also collected data on the implementation and scope of COVID-19–related abortion restrictions by state.

The analysis included all 49,935 requests made between January 1, 2019, and April 11, 2020.

Overall, the rate of requests for self-managed medical abortions increased significantly, by 27%, during the period from March 20, 2020, to April 11, 2020, which reflected the average period after clinic restrictions or closures at the state level. A total of 11 states showed individually significant increases in requests for self-managed medical abortions, with the highest of 94% in Texas and the lowest of 22% in Ohio. In these 11 states, the median time spent at home was 5% higher than in states without significant increases in requests for self-managed medical abortions during the same period. These states also had “particularly high COVID-19 rates or more severe COVID-19–related restrictions on in-clinic abortion access,” the researchers noted.

Patients want alternatives to in-person care

“Our results may reflect two distinct phenomena,” Dr. Aiken and associates wrote. “First, more people may be seeking abortion through all channels, whether due to COVID-19 risks during pregnancy, reduced access to prenatal care, or the pandemic-related economic downturn. Second, there may be shift in demand from in-clinic to self-managed abortion during the pandemic, possibly owing to fear of infection during in-person care or inability to get to a clinic because of childcare and transit disruptions,” they explained.

The study findings were limited by the inability to measure all options for women to achieve self-managed abortions and a lack of power to detect changes in states with low request numbers or where restrictions were implemented at later dates, the researchers noted. However, the results suggest that telemedicine services for medication abortion should be a policy priority because patients may continue to seek alternatives while in-clinic services remain restricted, they said.

In fact, “the World Health Organization recommends telemedicine and self-management abortion-care models during the pandemic, and the United Kingdom has temporarily implemented fully remote provision of abortion medications,” the researchers wrote. However, similar strategies in the United States “would depend on sustained changes to the U.S. Food and Drug Administration’s Risk Evaluation and Mitigation Strategy, which requires patients to collect mifepristone at a hospital or medical facility, as well as changes to state-specific laws that prohibit remote provider consultation,” Dr. Aiken and associates concluded.

Lift barriers to protect patients

“This important and timely article assesses the association between the disruptions of the coronavirus pandemic and online requests for telemedicine abortion,” Eve Espey, MD, of the University of New Mexico, Albuquerque, said in an interview.

“As background, state abortion restrictions have increased exponentially over the last decade, while research over the same time period has demonstrated the safety of telemedicine abortion – a form of self-managed abortion – with no in-person visit for appropriate candidates,” she said.

“Enter the coronavirus pandemic with safety concerns related to in-person medical visits and certain states leveraging the opportunity to enact even more stringent abortion restrictions. Unsurprisingly, the result, as documented in this excellent research report, is a significant increase in requests for telemedicine abortion in many states, particularly the most restrictive, from the single online service in the United States, Aid Access,” said Dr. Espey.

“Barriers to self-managed abortion include the [FDA] Risk Evaluation and Mitigation Strategy for mifepristone, a set of unnecessary restrictions requiring that providers meet certain qualifications and dispense the medication only in a clinic, office, or hospital,” she said. “The REMS precludes the use of telemedicine abortion; Aid Access and the FDA are in legal proceedings,” she noted.

“Most recently, the [American Civil Liberties Union] sued the FDA on behalf of a coalition of medical experts led by [American College of Obstetricians and Gynecologists] to suspend the REMS for mifepristone during the COVID public health emergency, to allow patients to receive the medications for early abortion without a visit to a health care provider,” Dr. Espey said. “Fortunately, a federal district court required the temporary suspension of the in-person dispensing restriction. Although this is a great step to improve abortion access during the pandemic, a permanent removal of the REMS would pave the way for ongoing safe, effective, and patient-centered early abortion care,” noted Dr. Espey, who was asked to comment on the research letter.

Dr. Aiken disclosed serving as a consultant for Agile Therapeutics, and a coauthor is the founder and director of Aid Access. Dr. Espey had no financial conflicts to disclose. She is a member of the Ob.Gyn. News Editorial Advisory Board.

SOURCE: Aiken ARA et al. Obstet Gynecol. 2020 Jul 21. doi: 10.1097/AOG.0000000000004081.

Rural primary care doctors are facing a new set of obstacles to practicing in the COVID-19 pandemic. These include struggling with seeing patients virtually and treating patients who have politicized the virus. Additionally, the pandemic has exposed rural practices to greater financial difficulties.

Courtesy Dr. Jacqueline W. Fincher

Before the pandemic some rurally based primary care physicians were already working through big challenges, such as having few local medical colleagues to consult and working in small practices with lean budgets. In fact, data gathered by the National Rural Health Association showed that there are only 40 primary care physicians per 100,000 patients in rural regions, compared with 53 in urban areas – and the number of physicians overall is 13 per 10,000 in rural areas, compared with 31 in cities.

In the prepandemic world, for some doctors, the challenges were balanced by the benefits of practicing in these sparsely populated communities with scenic, low-traffic roads. Some perks of practicing in rural areas touted by doctors included having a fast commute, being able to swim in a lake near the office before work, having a low cost of living, and feeling like they are making a difference in their communities as they treat generations of the families they see around town.

But today, new hurdles to practicing medicine in rural America created by the COVID-19 pandemic have caused the hardships to feel heavier than the joys at times for some physicians interviewed by MDedge.

Many independent rural practices in need of assistance were not able to get much from the federal Provider Relief Funds, said John M. Westfall, MD, who is director of the Robert Graham Center for Policy Studies in Family Medicine and Primary Care, in an interview.

“Rural primary care doctors function independently or in smaller critical access hospitals and community health centers,” said Dr. Westfall, who previously practiced family medicine in a small town in Colorado. “Many of these have much less financial reserves so are at risk of cutbacks and closure.”

Jacqueline W. Fincher, MD, an internist based in a tiny Georgia community along the highway between Atlanta and Augusta, said her small practice works on really thin margins and doesn’t have much cushion. At the beginning of the pandemic, all visits were down, and her practice operated at a loss. To help, Dr. Fincher and her colleagues applied for funding from the Small Business Administration’s Paycheck Protection Program (PPP) through the CARES Act.

“COVID-19 has had a tremendous impact especially on primary care practices. We live and die by volume. … Our volume in mid-March to mid-May really dropped dramatically,” explained Dr. Fincher, who is also president of the American College of Physicians. “The PPP sustained us for 2 months, enabling us to pay our staff and to remain open and get us up and running on telehealth.”
 

Starting up telemedicine

Experiencing spotty or no access to broadband Internet is nothing new to rural physicians, but having this problem interfere with their ability to provide care to patients is.

As much of the American health system rapidly embraced telehealth during the pandemic, obtaining access to high-speed Internet has been a major challenge for rural patients, noted Dr. Westfall.

“Some practices were able to quickly adopt some telehealth capacity with phone and video. Changes in payment for telehealth helped. But in some rural communities there was not adequate Internet bandwidth for quality video connections. And some patients did not have the means for high-speed video connections,” Dr. Westfall said.

Indeed, according to a 2019 Pew Research Center survey, 63% of rural Americans say they can access the Internet through a broadband connection at home, compared with 75% and 79% in suburban and urban areas, respectively.

G&P Productions

In the Appalachian town of Zanesville, Ohio, for example, family physician Shelly L. Dunmyer, MD, and her colleagues discovered that many patients don’t have Internet access at home. Dr. Fincher has to go to the office to conduct telehealth visits because her own Internet access at home is unpredictable. As for patients, it may take 15 minutes for them to work out technical glitches and find good Internet reception, said Dr. Fincher. For internist Y. Ki Shin, MD, who practices in the coastal town of Montesano in Washington state, about 25% of his practice’s telehealth visits must be conducted by phone because of limitations on video, such as lack of high-speed access.

But telephone visits are often insufficient replacements for appointments via video, according to several rural physicians interviewed for this piece.

“Telehealth can be frustrating at times due to connectivity issues which can be difficult at times in the rural areas,” said Dr. Fincher. “In order for telehealth to be reasonably helpful to patients and physicians to care for people with chronic problems, the patients must have things like blood pressure monitors, glucometers, and scales to address problems like hypertension, diabetes myelitis, and congestive heart failure.”

“If you have the audio and video and the data from these devices, you’re good. If you don’t have these data, and/or don’t have the video you just can’t provide good care,” she explained.

G&P Productions

Dr. Dunmyer and her colleagues at Medical Home Primary Care Center in Zanesville, Ohio, found a way to get around the problem of patients not being able to access Internet to participate in video visits from their homes. This involved having her patients drive into her practice’s parking lot to participate in modified telehealth visits. Staffers gave iPads to patients in their cars, and Dr. Dunmyer conducted visits from her office, about 50 yards away.

“We were even doing Medicare wellness visits: Instead of asking them to get up and move around the room, we would sit at the window and wave at them, ask them to get out, walk around the car. We were able to check mobility and all kinds of things that we’d normally do in the office,” Dr. Dunmyer explained in an interview.

The family physician noted that her practice is now conducting fewer parking lot visits since her office is allowing in-person appointments, but that they’re still an option for her patients.
 

Treating political adversaries

Some rural physicians have experienced strained relationships with patients for reasons other than technology – stark differences in opinion over the pandemic itself. Certain patients are following President Trump’s lead and questioning everything from the pandemic death toll to preventive measures recommended by scientists and medical experts, physicians interviewed by MDedge said.

Patients everywhere share these viewpoints, of course, but research and election results confirm that rural areas are more receptive to conservative viewpoints. In 2018, a Pew Research Center survey reported that rural and urban areas are “becoming more polarized politically,” and “rural areas tend to have a higher concentration of Republicans and Republican-leaning independents.” For example, 40% of rural respondents reported “very warm” or “somewhat warm” feelings toward Donald Trump, compared with just 19% in urban areas.

Dr. Shin has struggled to cope with patients who want to argue about pandemic safety precautions like wearing masks and seem to question whether systemic racism exists.

“We are seeing a lot more people who feel that this pandemic is not real, that it’s a political and not-true infection,” he said in an interview. “We’ve had patients who were angry at us because we made them wear masks, and some were demanding hydroxychloroquine and wanted to have an argument because we’re not going to prescribe it for them.”

In one situation, which he found especially disturbing, Dr. Shin had to leave the exam room because a patient wouldn’t stop challenging him regarding the pandemic. Things have gotten so bad that Dr. Shin has even questioned whether he wants to continue his long career in his small town because of local political attitudes such as opposition to mask-wearing and social distancing.

“Mr. Trump’s misinformation on this pandemic made my job much more difficult. As a minority, I feel less safe in my community than ever,” said Dr. Shin, who described himself as Asian American.

Despite these new stressors, Dr. Shin has experienced some joyful moments while practicing medicine in the pandemic.

Courtesy Dr. Clara Shin

He said a recent home visit to a patient who had been hospitalized for over 3 months and nearly died helped him put political disputes with his patients into perspective.

“He was discharged home but is bedbound. He had gangrene on his toes, and I could not fully examine him using video,” Dr. Shin recalled. “It was tricky to find the house, but a very large Trump sign was very helpful in locating it. It was a good visit: He was happy to see me, and I was happy to see that he was doing okay at home.”

“I need to remind myself that supporting Mr. Trump does not always mean that my patient supports Mr. Trump’s view on the pandemic and the race issues in our country,” Dr. Shin added.

The Washington-based internist said he also tells himself that, even if his patients refuse to follow his strong advice regarding pandemic precautions, it does not mean he has failed as a doctor.

“I need to continue to educate patients about the dangers of COVID infection but cannot be angry if they don’t choose to follow my recommendations,” he noted.

Dr. Fincher says her close connection with patients has allowed her to smooth over politically charged claims about the pandemic in the town of Thomson, Georgia, with a population 6,800.

“I have a sense that, even though we may differ in our understanding of some basic facts, they appreciate what I say since we have a long-term relationship built on trust,” she said. This kind of trust, Dr. Fincher suggested, may be more common than in urban areas where there’s a larger supply of physicians, and patients don’t see the same doctors for long periods of time.

“It’s more meaningful when it comes from me, rather than doctors who are [new to patients] every year when their employer changes their insurance,” she noted.

Rural primary care doctors are facing a new set of obstacles to practicing in the COVID-19 pandemic. These include struggling with seeing patients virtually and treating patients who have politicized the virus. Additionally, the pandemic has exposed rural practices to greater financial difficulties.

Courtesy Dr. Jacqueline W. Fincher

Before the pandemic some rurally based primary care physicians were already working through big challenges, such as having few local medical colleagues to consult and working in small practices with lean budgets. In fact, data gathered by the National Rural Health Association showed that there are only 40 primary care physicians per 100,000 patients in rural regions, compared with 53 in urban areas – and the number of physicians overall is 13 per 10,000 in rural areas, compared with 31 in cities.

In the prepandemic world, for some doctors, the challenges were balanced by the benefits of practicing in these sparsely populated communities with scenic, low-traffic roads. Some perks of practicing in rural areas touted by doctors included having a fast commute, being able to swim in a lake near the office before work, having a low cost of living, and feeling like they are making a difference in their communities as they treat generations of the families they see around town.

But today, new hurdles to practicing medicine in rural America created by the COVID-19 pandemic have caused the hardships to feel heavier than the joys at times for some physicians interviewed by MDedge.

Many independent rural practices in need of assistance were not able to get much from the federal Provider Relief Funds, said John M. Westfall, MD, who is director of the Robert Graham Center for Policy Studies in Family Medicine and Primary Care, in an interview.

“Rural primary care doctors function independently or in smaller critical access hospitals and community health centers,” said Dr. Westfall, who previously practiced family medicine in a small town in Colorado. “Many of these have much less financial reserves so are at risk of cutbacks and closure.”

Jacqueline W. Fincher, MD, an internist based in a tiny Georgia community along the highway between Atlanta and Augusta, said her small practice works on really thin margins and doesn’t have much cushion. At the beginning of the pandemic, all visits were down, and her practice operated at a loss. To help, Dr. Fincher and her colleagues applied for funding from the Small Business Administration’s Paycheck Protection Program (PPP) through the CARES Act.

“COVID-19 has had a tremendous impact especially on primary care practices. We live and die by volume. … Our volume in mid-March to mid-May really dropped dramatically,” explained Dr. Fincher, who is also president of the American College of Physicians. “The PPP sustained us for 2 months, enabling us to pay our staff and to remain open and get us up and running on telehealth.”
 

Starting up telemedicine

Experiencing spotty or no access to broadband Internet is nothing new to rural physicians, but having this problem interfere with their ability to provide care to patients is.

As much of the American health system rapidly embraced telehealth during the pandemic, obtaining access to high-speed Internet has been a major challenge for rural patients, noted Dr. Westfall.

“Some practices were able to quickly adopt some telehealth capacity with phone and video. Changes in payment for telehealth helped. But in some rural communities there was not adequate Internet bandwidth for quality video connections. And some patients did not have the means for high-speed video connections,” Dr. Westfall said.

Indeed, according to a 2019 Pew Research Center survey, 63% of rural Americans say they can access the Internet through a broadband connection at home, compared with 75% and 79% in suburban and urban areas, respectively.

G&P Productions

In the Appalachian town of Zanesville, Ohio, for example, family physician Shelly L. Dunmyer, MD, and her colleagues discovered that many patients don’t have Internet access at home. Dr. Fincher has to go to the office to conduct telehealth visits because her own Internet access at home is unpredictable. As for patients, it may take 15 minutes for them to work out technical glitches and find good Internet reception, said Dr. Fincher. For internist Y. Ki Shin, MD, who practices in the coastal town of Montesano in Washington state, about 25% of his practice’s telehealth visits must be conducted by phone because of limitations on video, such as lack of high-speed access.

But telephone visits are often insufficient replacements for appointments via video, according to several rural physicians interviewed for this piece.

“Telehealth can be frustrating at times due to connectivity issues which can be difficult at times in the rural areas,” said Dr. Fincher. “In order for telehealth to be reasonably helpful to patients and physicians to care for people with chronic problems, the patients must have things like blood pressure monitors, glucometers, and scales to address problems like hypertension, diabetes myelitis, and congestive heart failure.”

“If you have the audio and video and the data from these devices, you’re good. If you don’t have these data, and/or don’t have the video you just can’t provide good care,” she explained.

G&P Productions

Dr. Dunmyer and her colleagues at Medical Home Primary Care Center in Zanesville, Ohio, found a way to get around the problem of patients not being able to access Internet to participate in video visits from their homes. This involved having her patients drive into her practice’s parking lot to participate in modified telehealth visits. Staffers gave iPads to patients in their cars, and Dr. Dunmyer conducted visits from her office, about 50 yards away.

“We were even doing Medicare wellness visits: Instead of asking them to get up and move around the room, we would sit at the window and wave at them, ask them to get out, walk around the car. We were able to check mobility and all kinds of things that we’d normally do in the office,” Dr. Dunmyer explained in an interview.

The family physician noted that her practice is now conducting fewer parking lot visits since her office is allowing in-person appointments, but that they’re still an option for her patients.
 

Treating political adversaries

Some rural physicians have experienced strained relationships with patients for reasons other than technology – stark differences in opinion over the pandemic itself. Certain patients are following President Trump’s lead and questioning everything from the pandemic death toll to preventive measures recommended by scientists and medical experts, physicians interviewed by MDedge said.

Patients everywhere share these viewpoints, of course, but research and election results confirm that rural areas are more receptive to conservative viewpoints. In 2018, a Pew Research Center survey reported that rural and urban areas are “becoming more polarized politically,” and “rural areas tend to have a higher concentration of Republicans and Republican-leaning independents.” For example, 40% of rural respondents reported “very warm” or “somewhat warm” feelings toward Donald Trump, compared with just 19% in urban areas.

Dr. Shin has struggled to cope with patients who want to argue about pandemic safety precautions like wearing masks and seem to question whether systemic racism exists.

“We are seeing a lot more people who feel that this pandemic is not real, that it’s a political and not-true infection,” he said in an interview. “We’ve had patients who were angry at us because we made them wear masks, and some were demanding hydroxychloroquine and wanted to have an argument because we’re not going to prescribe it for them.”

In one situation, which he found especially disturbing, Dr. Shin had to leave the exam room because a patient wouldn’t stop challenging him regarding the pandemic. Things have gotten so bad that Dr. Shin has even questioned whether he wants to continue his long career in his small town because of local political attitudes such as opposition to mask-wearing and social distancing.

“Mr. Trump’s misinformation on this pandemic made my job much more difficult. As a minority, I feel less safe in my community than ever,” said Dr. Shin, who described himself as Asian American.

Despite these new stressors, Dr. Shin has experienced some joyful moments while practicing medicine in the pandemic.

Courtesy Dr. Clara Shin

He said a recent home visit to a patient who had been hospitalized for over 3 months and nearly died helped him put political disputes with his patients into perspective.

“He was discharged home but is bedbound. He had gangrene on his toes, and I could not fully examine him using video,” Dr. Shin recalled. “It was tricky to find the house, but a very large Trump sign was very helpful in locating it. It was a good visit: He was happy to see me, and I was happy to see that he was doing okay at home.”

“I need to remind myself that supporting Mr. Trump does not always mean that my patient supports Mr. Trump’s view on the pandemic and the race issues in our country,” Dr. Shin added.

The Washington-based internist said he also tells himself that, even if his patients refuse to follow his strong advice regarding pandemic precautions, it does not mean he has failed as a doctor.

“I need to continue to educate patients about the dangers of COVID infection but cannot be angry if they don’t choose to follow my recommendations,” he noted.

Dr. Fincher says her close connection with patients has allowed her to smooth over politically charged claims about the pandemic in the town of Thomson, Georgia, with a population 6,800.

“I have a sense that, even though we may differ in our understanding of some basic facts, they appreciate what I say since we have a long-term relationship built on trust,” she said. This kind of trust, Dr. Fincher suggested, may be more common than in urban areas where there’s a larger supply of physicians, and patients don’t see the same doctors for long periods of time.

“It’s more meaningful when it comes from me, rather than doctors who are [new to patients] every year when their employer changes their insurance,” she noted.

Rural primary care doctors are facing a new set of obstacles to practicing in the COVID-19 pandemic. These include struggling with seeing patients virtually and treating patients who have politicized the virus. Additionally, the pandemic has exposed rural practices to greater financial difficulties.

Courtesy Dr. Jacqueline W. Fincher

Before the pandemic some rurally based primary care physicians were already working through big challenges, such as having few local medical colleagues to consult and working in small practices with lean budgets. In fact, data gathered by the National Rural Health Association showed that there are only 40 primary care physicians per 100,000 patients in rural regions, compared with 53 in urban areas – and the number of physicians overall is 13 per 10,000 in rural areas, compared with 31 in cities.

In the prepandemic world, for some doctors, the challenges were balanced by the benefits of practicing in these sparsely populated communities with scenic, low-traffic roads. Some perks of practicing in rural areas touted by doctors included having a fast commute, being able to swim in a lake near the office before work, having a low cost of living, and feeling like they are making a difference in their communities as they treat generations of the families they see around town.

But today, new hurdles to practicing medicine in rural America created by the COVID-19 pandemic have caused the hardships to feel heavier than the joys at times for some physicians interviewed by MDedge.

Many independent rural practices in need of assistance were not able to get much from the federal Provider Relief Funds, said John M. Westfall, MD, who is director of the Robert Graham Center for Policy Studies in Family Medicine and Primary Care, in an interview.

“Rural primary care doctors function independently or in smaller critical access hospitals and community health centers,” said Dr. Westfall, who previously practiced family medicine in a small town in Colorado. “Many of these have much less financial reserves so are at risk of cutbacks and closure.”

Jacqueline W. Fincher, MD, an internist based in a tiny Georgia community along the highway between Atlanta and Augusta, said her small practice works on really thin margins and doesn’t have much cushion. At the beginning of the pandemic, all visits were down, and her practice operated at a loss. To help, Dr. Fincher and her colleagues applied for funding from the Small Business Administration’s Paycheck Protection Program (PPP) through the CARES Act.

“COVID-19 has had a tremendous impact especially on primary care practices. We live and die by volume. … Our volume in mid-March to mid-May really dropped dramatically,” explained Dr. Fincher, who is also president of the American College of Physicians. “The PPP sustained us for 2 months, enabling us to pay our staff and to remain open and get us up and running on telehealth.”
 

Starting up telemedicine

Experiencing spotty or no access to broadband Internet is nothing new to rural physicians, but having this problem interfere with their ability to provide care to patients is.

As much of the American health system rapidly embraced telehealth during the pandemic, obtaining access to high-speed Internet has been a major challenge for rural patients, noted Dr. Westfall.

“Some practices were able to quickly adopt some telehealth capacity with phone and video. Changes in payment for telehealth helped. But in some rural communities there was not adequate Internet bandwidth for quality video connections. And some patients did not have the means for high-speed video connections,” Dr. Westfall said.

Indeed, according to a 2019 Pew Research Center survey, 63% of rural Americans say they can access the Internet through a broadband connection at home, compared with 75% and 79% in suburban and urban areas, respectively.

G&P Productions

In the Appalachian town of Zanesville, Ohio, for example, family physician Shelly L. Dunmyer, MD, and her colleagues discovered that many patients don’t have Internet access at home. Dr. Fincher has to go to the office to conduct telehealth visits because her own Internet access at home is unpredictable. As for patients, it may take 15 minutes for them to work out technical glitches and find good Internet reception, said Dr. Fincher. For internist Y. Ki Shin, MD, who practices in the coastal town of Montesano in Washington state, about 25% of his practice’s telehealth visits must be conducted by phone because of limitations on video, such as lack of high-speed access.

But telephone visits are often insufficient replacements for appointments via video, according to several rural physicians interviewed for this piece.

“Telehealth can be frustrating at times due to connectivity issues which can be difficult at times in the rural areas,” said Dr. Fincher. “In order for telehealth to be reasonably helpful to patients and physicians to care for people with chronic problems, the patients must have things like blood pressure monitors, glucometers, and scales to address problems like hypertension, diabetes myelitis, and congestive heart failure.”

“If you have the audio and video and the data from these devices, you’re good. If you don’t have these data, and/or don’t have the video you just can’t provide good care,” she explained.

G&P Productions

Dr. Dunmyer and her colleagues at Medical Home Primary Care Center in Zanesville, Ohio, found a way to get around the problem of patients not being able to access Internet to participate in video visits from their homes. This involved having her patients drive into her practice’s parking lot to participate in modified telehealth visits. Staffers gave iPads to patients in their cars, and Dr. Dunmyer conducted visits from her office, about 50 yards away.

“We were even doing Medicare wellness visits: Instead of asking them to get up and move around the room, we would sit at the window and wave at them, ask them to get out, walk around the car. We were able to check mobility and all kinds of things that we’d normally do in the office,” Dr. Dunmyer explained in an interview.

The family physician noted that her practice is now conducting fewer parking lot visits since her office is allowing in-person appointments, but that they’re still an option for her patients.
 

Treating political adversaries

Some rural physicians have experienced strained relationships with patients for reasons other than technology – stark differences in opinion over the pandemic itself. Certain patients are following President Trump’s lead and questioning everything from the pandemic death toll to preventive measures recommended by scientists and medical experts, physicians interviewed by MDedge said.

Patients everywhere share these viewpoints, of course, but research and election results confirm that rural areas are more receptive to conservative viewpoints. In 2018, a Pew Research Center survey reported that rural and urban areas are “becoming more polarized politically,” and “rural areas tend to have a higher concentration of Republicans and Republican-leaning independents.” For example, 40% of rural respondents reported “very warm” or “somewhat warm” feelings toward Donald Trump, compared with just 19% in urban areas.

Dr. Shin has struggled to cope with patients who want to argue about pandemic safety precautions like wearing masks and seem to question whether systemic racism exists.

“We are seeing a lot more people who feel that this pandemic is not real, that it’s a political and not-true infection,” he said in an interview. “We’ve had patients who were angry at us because we made them wear masks, and some were demanding hydroxychloroquine and wanted to have an argument because we’re not going to prescribe it for them.”

In one situation, which he found especially disturbing, Dr. Shin had to leave the exam room because a patient wouldn’t stop challenging him regarding the pandemic. Things have gotten so bad that Dr. Shin has even questioned whether he wants to continue his long career in his small town because of local political attitudes such as opposition to mask-wearing and social distancing.

“Mr. Trump’s misinformation on this pandemic made my job much more difficult. As a minority, I feel less safe in my community than ever,” said Dr. Shin, who described himself as Asian American.

Despite these new stressors, Dr. Shin has experienced some joyful moments while practicing medicine in the pandemic.

Courtesy Dr. Clara Shin

He said a recent home visit to a patient who had been hospitalized for over 3 months and nearly died helped him put political disputes with his patients into perspective.

“He was discharged home but is bedbound. He had gangrene on his toes, and I could not fully examine him using video,” Dr. Shin recalled. “It was tricky to find the house, but a very large Trump sign was very helpful in locating it. It was a good visit: He was happy to see me, and I was happy to see that he was doing okay at home.”

“I need to remind myself that supporting Mr. Trump does not always mean that my patient supports Mr. Trump’s view on the pandemic and the race issues in our country,” Dr. Shin added.

The Washington-based internist said he also tells himself that, even if his patients refuse to follow his strong advice regarding pandemic precautions, it does not mean he has failed as a doctor.

“I need to continue to educate patients about the dangers of COVID infection but cannot be angry if they don’t choose to follow my recommendations,” he noted.

Dr. Fincher says her close connection with patients has allowed her to smooth over politically charged claims about the pandemic in the town of Thomson, Georgia, with a population 6,800.

“I have a sense that, even though we may differ in our understanding of some basic facts, they appreciate what I say since we have a long-term relationship built on trust,” she said. This kind of trust, Dr. Fincher suggested, may be more common than in urban areas where there’s a larger supply of physicians, and patients don’t see the same doctors for long periods of time.

“It’s more meaningful when it comes from me, rather than doctors who are [new to patients] every year when their employer changes their insurance,” she noted.

The Diagnosis: Onychodystrophy Secondary to Polydactyly

Radiographs of the feet demonstrated an accessory distal phalanx of the left great toe with a similar smaller accessory distal phalanx on the right great toe (Figure). The patient was referred to orthopedic surgery, and surgical intervention was recommended for only the left great toe given recurrent skin inflammation and nail complications. An excision of the left great toe polydactyly was performed. The patient healed well without complications.

Many clinically heterogeneous phenotypes exist for polydactyly and syndactyly, which both are common entities with incidences of 1 in 700 to 1000 births and 1 in 2000 to 3000 births, respectively.¹ Both polydactyly and syndactyly can be an isolated variant in newborns or present with multiple concurrent malformations as part of a genetic syndrome, with more than 300 syndromic anomalies described. The genetic basis of these conditions is equally diverse, with homeobox genes, hedgehog pathways, fibroblast growth factors, and boneand cartilage-derived morphogenetic proteins implicated in their development.¹

The differential diagnosis for our patient included congenital malalignment of the great toenails, nail-patella syndrome, onychodystrophy secondary to polydactyly, and congenital hypertrophy of the lateral nail fold. Given the strong family history, polydactyly was suspected.

Congenital malalignment of the great toenails results in lateral deviation of the nail plates.² It is an underdiagnosed condition with different etiologies hypothesized, such as genetic factors with possible autosomal-dominant transmission and extrinsic factors.³ One proposed mechanism of pathogenesis is desynchronization during growth of the nail and distal phalanx of the hallux, leading to larger nail plates that grow laterally.⁴ Typical features associated with this disease are nail discoloration, nail plate thickening, and transversal grooves or ridges, none of which were seen in our patient.²

Children with nail-patella syndrome have dysplastic nails and associated bony abnormalities, such as absent patellae.⁵ This syndrome results from an autosomaldominant mutation in the LIM homeobox transcription factor 1-beta gene, LMX1B, which is responsible for dorsal-ventral patterning of the limb, as well as patterning of the nails, patellae and long bones, and even the kidney tubule.⁶ As such, patients with nail-patella syndrome have associated renal abnormalities. The findings in our patient were limited to the feet, making an underlying syndrome unlikely to be the cause.

First described in 1968 by Meadow,⁷ fetal hydantoin syndrome is a well-documented sequela in women taking phenytoin throughout pregnancy. Multiple malformations are possible, including cardiac defects, cleft lip/palate, digit and nail hypoplasia, abnormal facial features, mental disability, and growth abnormalities.⁸ The teratogenicity behind phenytoin results from reactive oxygen species that alter embryonic DNA, proteins, and lipids.⁹ The mother of this child was not on any seizure prophylaxis, eliminating it from the differential.

Congenital hypertrophy of the lateral nail fold is a defect of the soft tissue of the hallux leading to hypertrophy of the nail fold, commonly presenting with inflammation and pain¹⁰ possibly due to dyssynchronous growth between the soft tissue and nail plate.¹¹ With this defect, a lip covering the nail plate is common, which was not seen in our patient.

As demonstrated in our patient, family history can help guide the diagnosis. Seven of 9 nonsyndromic forms of syndactyly are inherited in an autosomal-dominant fashion and range from mild presentations, as in our patient, to more severe deformations with underlying bone fusion and functional impairment.¹² Polydactyly also often is expressed in an autosomal-dominant pattern, with up to 30% of patients having a positive family history. Polydactyly traditionally is classified by the location of the supernumerary digit as preaxial (radial), central, or postaxial (ulnar), and many further morphologic variations exist within these groups. Overall, preaxial polydactyly is relatively rare and represents 15% of polydactylies, with central and postaxial comprising the other 6% and 79%, respectively.¹³ Delineation of the underlying anatomy may reveal ray duplications (digit and corresponding metacarpal or metatarsal bone), metatarsal variants, and duplicated phalanges that may be hypoplastic or deformed. Patients may report difficulty finding comfortable footwear, cosmetic concerns, and nail-related complications. Although not always required, surgical intervention may provide definitive treatment but can leave residual deformities in the surrounding altered anatomy; thus, orthopedic or plastic surgery consultations are critical in appropriately counseling patients.

The Diagnosis: Onychodystrophy Secondary to Polydactyly

Radiographs of the feet demonstrated an accessory distal phalanx of the left great toe with a similar smaller accessory distal phalanx on the right great toe (Figure). The patient was referred to orthopedic surgery, and surgical intervention was recommended for only the left great toe given recurrent skin inflammation and nail complications. An excision of the left great toe polydactyly was performed. The patient healed well without complications.

Many clinically heterogeneous phenotypes exist for polydactyly and syndactyly, which both are common entities with incidences of 1 in 700 to 1000 births and 1 in 2000 to 3000 births, respectively.¹ Both polydactyly and syndactyly can be an isolated variant in newborns or present with multiple concurrent malformations as part of a genetic syndrome, with more than 300 syndromic anomalies described. The genetic basis of these conditions is equally diverse, with homeobox genes, hedgehog pathways, fibroblast growth factors, and boneand cartilage-derived morphogenetic proteins implicated in their development.¹

The differential diagnosis for our patient included congenital malalignment of the great toenails, nail-patella syndrome, onychodystrophy secondary to polydactyly, and congenital hypertrophy of the lateral nail fold. Given the strong family history, polydactyly was suspected.

Congenital malalignment of the great toenails results in lateral deviation of the nail plates.² It is an underdiagnosed condition with different etiologies hypothesized, such as genetic factors with possible autosomal-dominant transmission and extrinsic factors.³ One proposed mechanism of pathogenesis is desynchronization during growth of the nail and distal phalanx of the hallux, leading to larger nail plates that grow laterally.⁴ Typical features associated with this disease are nail discoloration, nail plate thickening, and transversal grooves or ridges, none of which were seen in our patient.²

Children with nail-patella syndrome have dysplastic nails and associated bony abnormalities, such as absent patellae.⁵ This syndrome results from an autosomaldominant mutation in the LIM homeobox transcription factor 1-beta gene, LMX1B, which is responsible for dorsal-ventral patterning of the limb, as well as patterning of the nails, patellae and long bones, and even the kidney tubule.⁶ As such, patients with nail-patella syndrome have associated renal abnormalities. The findings in our patient were limited to the feet, making an underlying syndrome unlikely to be the cause.

First described in 1968 by Meadow,⁷ fetal hydantoin syndrome is a well-documented sequela in women taking phenytoin throughout pregnancy. Multiple malformations are possible, including cardiac defects, cleft lip/palate, digit and nail hypoplasia, abnormal facial features, mental disability, and growth abnormalities.⁸ The teratogenicity behind phenytoin results from reactive oxygen species that alter embryonic DNA, proteins, and lipids.⁹ The mother of this child was not on any seizure prophylaxis, eliminating it from the differential.

Congenital hypertrophy of the lateral nail fold is a defect of the soft tissue of the hallux leading to hypertrophy of the nail fold, commonly presenting with inflammation and pain¹⁰ possibly due to dyssynchronous growth between the soft tissue and nail plate.¹¹ With this defect, a lip covering the nail plate is common, which was not seen in our patient.

As demonstrated in our patient, family history can help guide the diagnosis. Seven of 9 nonsyndromic forms of syndactyly are inherited in an autosomal-dominant fashion and range from mild presentations, as in our patient, to more severe deformations with underlying bone fusion and functional impairment.¹² Polydactyly also often is expressed in an autosomal-dominant pattern, with up to 30% of patients having a positive family history. Polydactyly traditionally is classified by the location of the supernumerary digit as preaxial (radial), central, or postaxial (ulnar), and many further morphologic variations exist within these groups. Overall, preaxial polydactyly is relatively rare and represents 15% of polydactylies, with central and postaxial comprising the other 6% and 79%, respectively.¹³ Delineation of the underlying anatomy may reveal ray duplications (digit and corresponding metacarpal or metatarsal bone), metatarsal variants, and duplicated phalanges that may be hypoplastic or deformed. Patients may report difficulty finding comfortable footwear, cosmetic concerns, and nail-related complications. Although not always required, surgical intervention may provide definitive treatment but can leave residual deformities in the surrounding altered anatomy; thus, orthopedic or plastic surgery consultations are critical in appropriately counseling patients.

The Diagnosis: Onychodystrophy Secondary to Polydactyly

Radiographs of the feet demonstrated an accessory distal phalanx of the left great toe with a similar smaller accessory distal phalanx on the right great toe (Figure). The patient was referred to orthopedic surgery, and surgical intervention was recommended for only the left great toe given recurrent skin inflammation and nail complications. An excision of the left great toe polydactyly was performed. The patient healed well without complications.

Many clinically heterogeneous phenotypes exist for polydactyly and syndactyly, which both are common entities with incidences of 1 in 700 to 1000 births and 1 in 2000 to 3000 births, respectively.¹ Both polydactyly and syndactyly can be an isolated variant in newborns or present with multiple concurrent malformations as part of a genetic syndrome, with more than 300 syndromic anomalies described. The genetic basis of these conditions is equally diverse, with homeobox genes, hedgehog pathways, fibroblast growth factors, and boneand cartilage-derived morphogenetic proteins implicated in their development.¹

The differential diagnosis for our patient included congenital malalignment of the great toenails, nail-patella syndrome, onychodystrophy secondary to polydactyly, and congenital hypertrophy of the lateral nail fold. Given the strong family history, polydactyly was suspected.

Congenital malalignment of the great toenails results in lateral deviation of the nail plates.² It is an underdiagnosed condition with different etiologies hypothesized, such as genetic factors with possible autosomal-dominant transmission and extrinsic factors.³ One proposed mechanism of pathogenesis is desynchronization during growth of the nail and distal phalanx of the hallux, leading to larger nail plates that grow laterally.⁴ Typical features associated with this disease are nail discoloration, nail plate thickening, and transversal grooves or ridges, none of which were seen in our patient.²

Children with nail-patella syndrome have dysplastic nails and associated bony abnormalities, such as absent patellae.⁵ This syndrome results from an autosomaldominant mutation in the LIM homeobox transcription factor 1-beta gene, LMX1B, which is responsible for dorsal-ventral patterning of the limb, as well as patterning of the nails, patellae and long bones, and even the kidney tubule.⁶ As such, patients with nail-patella syndrome have associated renal abnormalities. The findings in our patient were limited to the feet, making an underlying syndrome unlikely to be the cause.

First described in 1968 by Meadow,⁷ fetal hydantoin syndrome is a well-documented sequela in women taking phenytoin throughout pregnancy. Multiple malformations are possible, including cardiac defects, cleft lip/palate, digit and nail hypoplasia, abnormal facial features, mental disability, and growth abnormalities.⁸ The teratogenicity behind phenytoin results from reactive oxygen species that alter embryonic DNA, proteins, and lipids.⁹ The mother of this child was not on any seizure prophylaxis, eliminating it from the differential.

Congenital hypertrophy of the lateral nail fold is a defect of the soft tissue of the hallux leading to hypertrophy of the nail fold, commonly presenting with inflammation and pain¹⁰ possibly due to dyssynchronous growth between the soft tissue and nail plate.¹¹ With this defect, a lip covering the nail plate is common, which was not seen in our patient.

As demonstrated in our patient, family history can help guide the diagnosis. Seven of 9 nonsyndromic forms of syndactyly are inherited in an autosomal-dominant fashion and range from mild presentations, as in our patient, to more severe deformations with underlying bone fusion and functional impairment.¹² Polydactyly also often is expressed in an autosomal-dominant pattern, with up to 30% of patients having a positive family history. Polydactyly traditionally is classified by the location of the supernumerary digit as preaxial (radial), central, or postaxial (ulnar), and many further morphologic variations exist within these groups. Overall, preaxial polydactyly is relatively rare and represents 15% of polydactylies, with central and postaxial comprising the other 6% and 79%, respectively.¹³ Delineation of the underlying anatomy may reveal ray duplications (digit and corresponding metacarpal or metatarsal bone), metatarsal variants, and duplicated phalanges that may be hypoplastic or deformed. Patients may report difficulty finding comfortable footwear, cosmetic concerns, and nail-related complications. Although not always required, surgical intervention may provide definitive treatment but can leave residual deformities in the surrounding altered anatomy; thus, orthopedic or plastic surgery consultations are critical in appropriately counseling patients.

Guidance on the initiation and use of urate-lowering therapies was among the strong recommendations in the updated gout guideline recently issued by the American College of Rheumatology, said Brian F. Mandell, MD, PhD, in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

The 2020 American College of Rheumatology Guideline for the Management of Gout is “intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient,” said Dr. Mandell, chair of academic medicine at the Cleveland Clinic in Ohio and cochair of the conference. However, “there was a hope that, with additional evidence since the previous guideline issued in 2012, the recommendations are more firmly based and will improve care,” he said.

Of 42 recommendations, 16 were strong, and these included guidance on several points: when to initiate urate-lowering therapy and using a treat-to-target strategy for lowering serum uric acid to less than 6 mg/dL; prophylaxis against attacks; the use of allopurinol as the first-choice drug and how to avoid hypersensitivity reactions; the use of pegloticase (Krystexxa); and treating flares.

Hyperuricemia does not automatically equal gout, Dr. Mandell said. A 2018 published analysis of data from several large cohorts including 18,889 adults who were gout-free at baseline showed that serum uric acid levels could not accurately predict an initial gout attack. Therefore, the guideline conditionally recommends against initiating any pharmacologic urate-lowering therapy in patients with asymptomatic hyperuricemia. The guideline authors intentionally did not include the presence of comorbidities or deposits of uric acid in making their recommendation. But when advising an individual patient, these factors plus the patient’s age and family history should be considered, he said. “Individualize the decision to use ULT [urate-lowering therapy] to prevent possible future flares,” he advised, with consideration of age, the effects of the flare on the patient’s life, and challenges in treating flares.

For patients who are being treated with urate-lowering therapy, a published study indicated that if treatment is discontinued, “gout attacks will recur, depending on the new serum urate level,” Dr. Mandell said. “Maintenance of low SUA [serum uric acid] must be lifelong to stop attacks,” he emphasized, noting that this is counter to a management guideline published by the American College of Physicians in 2017.

“For patients starting any ULT, we strongly recommend allopurinol over all other urate-lowering therapies as the preferred first-line agent for all patients, including those with CKD [chronic kidney disease] stage 3 or higher,” according to the new guideline, which also recommends starting at a low dose followed by dose titration to target versus starting at a higher dose.

Two reasons in support of a slow up-titration of urate-lowering therapy are a lower frequency of mobilization flares and a possibly lower chance of allopurinol hypersensitivity reactions, Dr. Mandell said.

Although the guideline recommends allopurinol over probenecid, “probenecid works well as monotherapy and effectively as add-on therapy to a xanthine oxidase inhibitor, and it is cheap,” Dr. Mandell said.

Allopurinol can be associated with life-threatening hypersensitivity reactions, but most of these have been associated with a higher-than-recommended starting dose, according to the literature, he noted. The new guideline suggests checking for the HLA-B*5801 haplotype in high-risk demographic groups, and if it is present, to use an alternative to allopurinol if possible

The updated guideline also carries a strong recommendation for the use of pegloticase for patients with frequent gout flares and nonresolving subcutaneous tophi, but it strongly recommends against switching to pegloticase for patients with infrequent gout flares and no tophi.

However, Dr. Mandell said that he will consider off-label treatment of gout with pegloticase “in patients where a shorter time to response really matters,” which is consistent with his belief that, within these treatment principles, the management of gout must be individualized to the specific patient.

For treating acute gout flares, the guideline recommendations strongly supports the use of oral colchicine, NSAIDs, or glucocorticoids as an appropriate first-line therapy, based on patient factors and preferences, instead of using interleukin-1 inhibitors or adrenocorticotropic hormone. However, the interleukin-1 inhibitor anakinra has shown relatively rapid and successful response in treating patients hospitalized with acute gout, Dr. Mandell said. No large, randomized, trials have been conducted, but he cited his experience at the Cleveland Clinic in Ohio, where anakinra is the most common treatment for acute gout on inpatient consults, and he cited a representative small study of 26 patients in which 73% showed “significant response” within 5 days of treatment, which meant that they were able to move and bear weight without pain. In addition, a more recent study of 100 hospitalized patients in the Journal of Rheumatology, found that 75% showed a rapid response to anakinra and improvement or resolution of flares within 4 days, Dr. Mandell said.

Dr. Mandell disclosed relationships with companies including Horizon, Ardea/AstraZeneca/Ironwood, and Takeda. He served as coauthor on the 2012 American College of Rheumatology gout guideline.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Guidance on the initiation and use of urate-lowering therapies was among the strong recommendations in the updated gout guideline recently issued by the American College of Rheumatology, said Brian F. Mandell, MD, PhD, in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

The 2020 American College of Rheumatology Guideline for the Management of Gout is “intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient,” said Dr. Mandell, chair of academic medicine at the Cleveland Clinic in Ohio and cochair of the conference. However, “there was a hope that, with additional evidence since the previous guideline issued in 2012, the recommendations are more firmly based and will improve care,” he said.

Of 42 recommendations, 16 were strong, and these included guidance on several points: when to initiate urate-lowering therapy and using a treat-to-target strategy for lowering serum uric acid to less than 6 mg/dL; prophylaxis against attacks; the use of allopurinol as the first-choice drug and how to avoid hypersensitivity reactions; the use of pegloticase (Krystexxa); and treating flares.

Hyperuricemia does not automatically equal gout, Dr. Mandell said. A 2018 published analysis of data from several large cohorts including 18,889 adults who were gout-free at baseline showed that serum uric acid levels could not accurately predict an initial gout attack. Therefore, the guideline conditionally recommends against initiating any pharmacologic urate-lowering therapy in patients with asymptomatic hyperuricemia. The guideline authors intentionally did not include the presence of comorbidities or deposits of uric acid in making their recommendation. But when advising an individual patient, these factors plus the patient’s age and family history should be considered, he said. “Individualize the decision to use ULT [urate-lowering therapy] to prevent possible future flares,” he advised, with consideration of age, the effects of the flare on the patient’s life, and challenges in treating flares.

For patients who are being treated with urate-lowering therapy, a published study indicated that if treatment is discontinued, “gout attacks will recur, depending on the new serum urate level,” Dr. Mandell said. “Maintenance of low SUA [serum uric acid] must be lifelong to stop attacks,” he emphasized, noting that this is counter to a management guideline published by the American College of Physicians in 2017.

“For patients starting any ULT, we strongly recommend allopurinol over all other urate-lowering therapies as the preferred first-line agent for all patients, including those with CKD [chronic kidney disease] stage 3 or higher,” according to the new guideline, which also recommends starting at a low dose followed by dose titration to target versus starting at a higher dose.

Two reasons in support of a slow up-titration of urate-lowering therapy are a lower frequency of mobilization flares and a possibly lower chance of allopurinol hypersensitivity reactions, Dr. Mandell said.

Although the guideline recommends allopurinol over probenecid, “probenecid works well as monotherapy and effectively as add-on therapy to a xanthine oxidase inhibitor, and it is cheap,” Dr. Mandell said.

Allopurinol can be associated with life-threatening hypersensitivity reactions, but most of these have been associated with a higher-than-recommended starting dose, according to the literature, he noted. The new guideline suggests checking for the HLA-B*5801 haplotype in high-risk demographic groups, and if it is present, to use an alternative to allopurinol if possible

The updated guideline also carries a strong recommendation for the use of pegloticase for patients with frequent gout flares and nonresolving subcutaneous tophi, but it strongly recommends against switching to pegloticase for patients with infrequent gout flares and no tophi.

However, Dr. Mandell said that he will consider off-label treatment of gout with pegloticase “in patients where a shorter time to response really matters,” which is consistent with his belief that, within these treatment principles, the management of gout must be individualized to the specific patient.

For treating acute gout flares, the guideline recommendations strongly supports the use of oral colchicine, NSAIDs, or glucocorticoids as an appropriate first-line therapy, based on patient factors and preferences, instead of using interleukin-1 inhibitors or adrenocorticotropic hormone. However, the interleukin-1 inhibitor anakinra has shown relatively rapid and successful response in treating patients hospitalized with acute gout, Dr. Mandell said. No large, randomized, trials have been conducted, but he cited his experience at the Cleveland Clinic in Ohio, where anakinra is the most common treatment for acute gout on inpatient consults, and he cited a representative small study of 26 patients in which 73% showed “significant response” within 5 days of treatment, which meant that they were able to move and bear weight without pain. In addition, a more recent study of 100 hospitalized patients in the Journal of Rheumatology, found that 75% showed a rapid response to anakinra and improvement or resolution of flares within 4 days, Dr. Mandell said.

Dr. Mandell disclosed relationships with companies including Horizon, Ardea/AstraZeneca/Ironwood, and Takeda. He served as coauthor on the 2012 American College of Rheumatology gout guideline.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Guidance on the initiation and use of urate-lowering therapies was among the strong recommendations in the updated gout guideline recently issued by the American College of Rheumatology, said Brian F. Mandell, MD, PhD, in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

The 2020 American College of Rheumatology Guideline for the Management of Gout is “intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient,” said Dr. Mandell, chair of academic medicine at the Cleveland Clinic in Ohio and cochair of the conference. However, “there was a hope that, with additional evidence since the previous guideline issued in 2012, the recommendations are more firmly based and will improve care,” he said.

Of 42 recommendations, 16 were strong, and these included guidance on several points: when to initiate urate-lowering therapy and using a treat-to-target strategy for lowering serum uric acid to less than 6 mg/dL; prophylaxis against attacks; the use of allopurinol as the first-choice drug and how to avoid hypersensitivity reactions; the use of pegloticase (Krystexxa); and treating flares.

Hyperuricemia does not automatically equal gout, Dr. Mandell said. A 2018 published analysis of data from several large cohorts including 18,889 adults who were gout-free at baseline showed that serum uric acid levels could not accurately predict an initial gout attack. Therefore, the guideline conditionally recommends against initiating any pharmacologic urate-lowering therapy in patients with asymptomatic hyperuricemia. The guideline authors intentionally did not include the presence of comorbidities or deposits of uric acid in making their recommendation. But when advising an individual patient, these factors plus the patient’s age and family history should be considered, he said. “Individualize the decision to use ULT [urate-lowering therapy] to prevent possible future flares,” he advised, with consideration of age, the effects of the flare on the patient’s life, and challenges in treating flares.

For patients who are being treated with urate-lowering therapy, a published study indicated that if treatment is discontinued, “gout attacks will recur, depending on the new serum urate level,” Dr. Mandell said. “Maintenance of low SUA [serum uric acid] must be lifelong to stop attacks,” he emphasized, noting that this is counter to a management guideline published by the American College of Physicians in 2017.

“For patients starting any ULT, we strongly recommend allopurinol over all other urate-lowering therapies as the preferred first-line agent for all patients, including those with CKD [chronic kidney disease] stage 3 or higher,” according to the new guideline, which also recommends starting at a low dose followed by dose titration to target versus starting at a higher dose.

Two reasons in support of a slow up-titration of urate-lowering therapy are a lower frequency of mobilization flares and a possibly lower chance of allopurinol hypersensitivity reactions, Dr. Mandell said.

Although the guideline recommends allopurinol over probenecid, “probenecid works well as monotherapy and effectively as add-on therapy to a xanthine oxidase inhibitor, and it is cheap,” Dr. Mandell said.

Allopurinol can be associated with life-threatening hypersensitivity reactions, but most of these have been associated with a higher-than-recommended starting dose, according to the literature, he noted. The new guideline suggests checking for the HLA-B*5801 haplotype in high-risk demographic groups, and if it is present, to use an alternative to allopurinol if possible

The updated guideline also carries a strong recommendation for the use of pegloticase for patients with frequent gout flares and nonresolving subcutaneous tophi, but it strongly recommends against switching to pegloticase for patients with infrequent gout flares and no tophi.

However, Dr. Mandell said that he will consider off-label treatment of gout with pegloticase “in patients where a shorter time to response really matters,” which is consistent with his belief that, within these treatment principles, the management of gout must be individualized to the specific patient.

For treating acute gout flares, the guideline recommendations strongly supports the use of oral colchicine, NSAIDs, or glucocorticoids as an appropriate first-line therapy, based on patient factors and preferences, instead of using interleukin-1 inhibitors or adrenocorticotropic hormone. However, the interleukin-1 inhibitor anakinra has shown relatively rapid and successful response in treating patients hospitalized with acute gout, Dr. Mandell said. No large, randomized, trials have been conducted, but he cited his experience at the Cleveland Clinic in Ohio, where anakinra is the most common treatment for acute gout on inpatient consults, and he cited a representative small study of 26 patients in which 73% showed “significant response” within 5 days of treatment, which meant that they were able to move and bear weight without pain. In addition, a more recent study of 100 hospitalized patients in the Journal of Rheumatology, found that 75% showed a rapid response to anakinra and improvement or resolution of flares within 4 days, Dr. Mandell said.

Dr. Mandell disclosed relationships with companies including Horizon, Ardea/AstraZeneca/Ironwood, and Takeda. He served as coauthor on the 2012 American College of Rheumatology gout guideline.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Patients with type 2 or type 1 diabetes who stay in a blood glucose range of 70-180 mg/dL at least 70% of the time have the lowest rates of major adverse coronary events, severe hypoglycemic episodes, and microvascular events, according to a post hoc analysis of data collected from 5,774 patients with type 2 diabetes.

Data collected by the DEVOTE trial showed that every additional 10% of the time that a patient with type 2 diabetes (T2D) spent in their target range for blood glucose linked with a significant 6% reduced rate for developing a major adverse cardiovascular event (MACE), Richard M. Bergenstal, MD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

For every 10% increase in time in range (TIR), patients showed an average 10% drop in their incidence of severe hypoglycemic episodes.
 

Increasing evidence from post hoc analyses

These findings confirmed a prior post hoc analysis of data collected in the DCCT trial (NCT00360815), which were published in the New England Journal of Medicine, although those results showed significant relationships between increased TIR and decreased rates of retinopathy and microalbuminuria. For every 10% drop in TIR, retinopathy rose by 64% and microalbuminuria increased by 40%, according to a post hoc analysis of the DCCT data that Dr. Bergenstal helped run and was published in Diabetes Care.

“It’s becoming clear that time in range is an important metric for diabetes management, and our new findings and those previously reported with the DCCT data make it look like time in range is becoming a good marker for clinical outcomes as well,” said Dr. Bergenstal, an endocrinologist at the Park Nicollet Clinic in Minneapolis.

“It’s a new concept, getting time-in-range data,” said Dr. Bergenstal, who was a coauthor of recommendations from Diabetes Care that were made in 2019 by an expert panel organized by the Advanced Technologies & Treatments for Diabetes Congress. “We think this will be a good marker to keep glycemia in a safe range, and the results look positive.” Patients who stay in the blood glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) at least 70% of the time generally have an hemoglobin A_1c of about 7%, which is what makes it a good target for patients and clinicians to focus on. Patients with a 50% TIR rate generally have an HbA_1c of about 8%.

But a TIR assessment can be more informative than HbA_1c, said the 2019 recommendations document. It called TIR assessments “appropriate and useful as clinical targets and outcome measurements that complement A1c for a wide range of people with diabetes.”
 

Data mining from DEVOTE

The analysis run by Dr. Bergenstal and his associates used data from 5,774 of the 7,637 patients enrolled in the DEVOTE trial, for whom adequate longitudinal blood glucose data were available to derive and track TIR. DEVOTE had the primary aim of comparing two different types of insulin in patients with T2D, according to its explanation in the New England Journal of Medicine. The DEVOTE patients did not undergo routine continuous blood glucose monitoring, so derivation of TIR was the only option with the dataset, Dr. Bergenstal said. “We’re trying to get continuous blood monitoring into T2D trials,” he said.

The post hoc analysis showed that, during the study’s follow-up of just under 2 years, patients who maintained a derived TIR of 70%-100% had about a 6% MACE rate, which peaked at nearly twice that in patients whose TIR was 30% or less. The analysis showed a roughly positive linear relationship between TIR and MACE rates across the range of TIR values. In an adjusted analysis, patients with at least a 70% TIR had a significant 31% lower rate of MACE events, compared with patients whose TIR was 50% or less.

A second analysis that looked for the association between TIR and incidence of hypoglycemic episodes showed a somewhat similar positive relationship, with incidence rates of severe hypoglycemia episodes of about 4%-5% among patients with a TIR of 70% or greater, and a rate of about 7% in patients with a TIR of 30% or less, spiking to 14% among patients with a TIR of 10% or less. In an adjusted analysis, patients with a TIR of at least 70% had a significant 46% lower rate of severe hypoglycemic events, compared with patients whose TIR was 50% or less. This finding belies a common misconception that the tighter glycemic control that produces a higher TIR will lead to increased episodes of severe hypoglycemia, Dr. Bergenstal noted.

He also reported less extensive data on microvascular events. In an adjusted analysis, patients with a TIR of at least 70% had a significant 40% cut in these events compared with patients with 50% or less TIR.

DEVOTE was funded by Novo Nordisk. Dr. Bergenstal has had financial relationships with Novo Nordisk and several other companies.

[email protected]

SOURCE: Bergenstal R et al. EASD 2020, abstract 159.

Patients with type 2 or type 1 diabetes who stay in a blood glucose range of 70-180 mg/dL at least 70% of the time have the lowest rates of major adverse coronary events, severe hypoglycemic episodes, and microvascular events, according to a post hoc analysis of data collected from 5,774 patients with type 2 diabetes.

Data collected by the DEVOTE trial showed that every additional 10% of the time that a patient with type 2 diabetes (T2D) spent in their target range for blood glucose linked with a significant 6% reduced rate for developing a major adverse cardiovascular event (MACE), Richard M. Bergenstal, MD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

For every 10% increase in time in range (TIR), patients showed an average 10% drop in their incidence of severe hypoglycemic episodes.
 

Increasing evidence from post hoc analyses

These findings confirmed a prior post hoc analysis of data collected in the DCCT trial (NCT00360815), which were published in the New England Journal of Medicine, although those results showed significant relationships between increased TIR and decreased rates of retinopathy and microalbuminuria. For every 10% drop in TIR, retinopathy rose by 64% and microalbuminuria increased by 40%, according to a post hoc analysis of the DCCT data that Dr. Bergenstal helped run and was published in Diabetes Care.

“It’s becoming clear that time in range is an important metric for diabetes management, and our new findings and those previously reported with the DCCT data make it look like time in range is becoming a good marker for clinical outcomes as well,” said Dr. Bergenstal, an endocrinologist at the Park Nicollet Clinic in Minneapolis.

“It’s a new concept, getting time-in-range data,” said Dr. Bergenstal, who was a coauthor of recommendations from Diabetes Care that were made in 2019 by an expert panel organized by the Advanced Technologies & Treatments for Diabetes Congress. “We think this will be a good marker to keep glycemia in a safe range, and the results look positive.” Patients who stay in the blood glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) at least 70% of the time generally have an hemoglobin A_1c of about 7%, which is what makes it a good target for patients and clinicians to focus on. Patients with a 50% TIR rate generally have an HbA_1c of about 8%.

But a TIR assessment can be more informative than HbA_1c, said the 2019 recommendations document. It called TIR assessments “appropriate and useful as clinical targets and outcome measurements that complement A1c for a wide range of people with diabetes.”
 

Data mining from DEVOTE

The analysis run by Dr. Bergenstal and his associates used data from 5,774 of the 7,637 patients enrolled in the DEVOTE trial, for whom adequate longitudinal blood glucose data were available to derive and track TIR. DEVOTE had the primary aim of comparing two different types of insulin in patients with T2D, according to its explanation in the New England Journal of Medicine. The DEVOTE patients did not undergo routine continuous blood glucose monitoring, so derivation of TIR was the only option with the dataset, Dr. Bergenstal said. “We’re trying to get continuous blood monitoring into T2D trials,” he said.

The post hoc analysis showed that, during the study’s follow-up of just under 2 years, patients who maintained a derived TIR of 70%-100% had about a 6% MACE rate, which peaked at nearly twice that in patients whose TIR was 30% or less. The analysis showed a roughly positive linear relationship between TIR and MACE rates across the range of TIR values. In an adjusted analysis, patients with at least a 70% TIR had a significant 31% lower rate of MACE events, compared with patients whose TIR was 50% or less.

A second analysis that looked for the association between TIR and incidence of hypoglycemic episodes showed a somewhat similar positive relationship, with incidence rates of severe hypoglycemia episodes of about 4%-5% among patients with a TIR of 70% or greater, and a rate of about 7% in patients with a TIR of 30% or less, spiking to 14% among patients with a TIR of 10% or less. In an adjusted analysis, patients with a TIR of at least 70% had a significant 46% lower rate of severe hypoglycemic events, compared with patients whose TIR was 50% or less. This finding belies a common misconception that the tighter glycemic control that produces a higher TIR will lead to increased episodes of severe hypoglycemia, Dr. Bergenstal noted.

He also reported less extensive data on microvascular events. In an adjusted analysis, patients with a TIR of at least 70% had a significant 40% cut in these events compared with patients with 50% or less TIR.

DEVOTE was funded by Novo Nordisk. Dr. Bergenstal has had financial relationships with Novo Nordisk and several other companies.

[email protected]

SOURCE: Bergenstal R et al. EASD 2020, abstract 159.

Patients with type 2 or type 1 diabetes who stay in a blood glucose range of 70-180 mg/dL at least 70% of the time have the lowest rates of major adverse coronary events, severe hypoglycemic episodes, and microvascular events, according to a post hoc analysis of data collected from 5,774 patients with type 2 diabetes.

Data collected by the DEVOTE trial showed that every additional 10% of the time that a patient with type 2 diabetes (T2D) spent in their target range for blood glucose linked with a significant 6% reduced rate for developing a major adverse cardiovascular event (MACE), Richard M. Bergenstal, MD, said at the virtual annual meeting of the European Association for the Study of Diabetes.

For every 10% increase in time in range (TIR), patients showed an average 10% drop in their incidence of severe hypoglycemic episodes.
 

Increasing evidence from post hoc analyses

These findings confirmed a prior post hoc analysis of data collected in the DCCT trial (NCT00360815), which were published in the New England Journal of Medicine, although those results showed significant relationships between increased TIR and decreased rates of retinopathy and microalbuminuria. For every 10% drop in TIR, retinopathy rose by 64% and microalbuminuria increased by 40%, according to a post hoc analysis of the DCCT data that Dr. Bergenstal helped run and was published in Diabetes Care.

“It’s becoming clear that time in range is an important metric for diabetes management, and our new findings and those previously reported with the DCCT data make it look like time in range is becoming a good marker for clinical outcomes as well,” said Dr. Bergenstal, an endocrinologist at the Park Nicollet Clinic in Minneapolis.

“It’s a new concept, getting time-in-range data,” said Dr. Bergenstal, who was a coauthor of recommendations from Diabetes Care that were made in 2019 by an expert panel organized by the Advanced Technologies & Treatments for Diabetes Congress. “We think this will be a good marker to keep glycemia in a safe range, and the results look positive.” Patients who stay in the blood glucose range of 70-180 mg/dL (3.9-10.0 mmol/L) at least 70% of the time generally have an hemoglobin A_1c of about 7%, which is what makes it a good target for patients and clinicians to focus on. Patients with a 50% TIR rate generally have an HbA_1c of about 8%.

But a TIR assessment can be more informative than HbA_1c, said the 2019 recommendations document. It called TIR assessments “appropriate and useful as clinical targets and outcome measurements that complement A1c for a wide range of people with diabetes.”
 

Data mining from DEVOTE

The analysis run by Dr. Bergenstal and his associates used data from 5,774 of the 7,637 patients enrolled in the DEVOTE trial, for whom adequate longitudinal blood glucose data were available to derive and track TIR. DEVOTE had the primary aim of comparing two different types of insulin in patients with T2D, according to its explanation in the New England Journal of Medicine. The DEVOTE patients did not undergo routine continuous blood glucose monitoring, so derivation of TIR was the only option with the dataset, Dr. Bergenstal said. “We’re trying to get continuous blood monitoring into T2D trials,” he said.

The post hoc analysis showed that, during the study’s follow-up of just under 2 years, patients who maintained a derived TIR of 70%-100% had about a 6% MACE rate, which peaked at nearly twice that in patients whose TIR was 30% or less. The analysis showed a roughly positive linear relationship between TIR and MACE rates across the range of TIR values. In an adjusted analysis, patients with at least a 70% TIR had a significant 31% lower rate of MACE events, compared with patients whose TIR was 50% or less.

A second analysis that looked for the association between TIR and incidence of hypoglycemic episodes showed a somewhat similar positive relationship, with incidence rates of severe hypoglycemia episodes of about 4%-5% among patients with a TIR of 70% or greater, and a rate of about 7% in patients with a TIR of 30% or less, spiking to 14% among patients with a TIR of 10% or less. In an adjusted analysis, patients with a TIR of at least 70% had a significant 46% lower rate of severe hypoglycemic events, compared with patients whose TIR was 50% or less. This finding belies a common misconception that the tighter glycemic control that produces a higher TIR will lead to increased episodes of severe hypoglycemia, Dr. Bergenstal noted.

He also reported less extensive data on microvascular events. In an adjusted analysis, patients with a TIR of at least 70% had a significant 40% cut in these events compared with patients with 50% or less TIR.

DEVOTE was funded by Novo Nordisk. Dr. Bergenstal has had financial relationships with Novo Nordisk and several other companies.

[email protected]

SOURCE: Bergenstal R et al. EASD 2020, abstract 159.