Jennifer Lubell

A new genetic mutation in schizophrenia that blocks neuron communication in the brain may lead to novel treatment strategies and improve understanding of the mechanics of this disease.

The discovery of this new gene, PCDHA3, could enhance the development of genetic-risk calculators “that may help us understand vulnerability to schizophrenia in high-risk individuals and identify individuals with schizophrenia who have a greater risk for poor outcomes,” said Todd Lencz, PhD, a professor at the Feinstein Institutes for Medical Research in New York, and lead author of this research. Dr. Lencz and associates reported on this new finding in the journal Neuron.

Schizophrenia affects 20 million people worldwide. Previous research has identified the important role genes play in the disease, but isolating individual genes to better understand schizophrenia has proven to be a challenge. This is a very heterogeneous disorder, with many hundreds if not thousands of genes involved, Dr. Lencz explained in an interview. “It is very different from single-gene disorders like Huntington disease, for example. For this reason, we need very large sample sizes to find any one gene that seems to be common to many cases in a sample.”
 

Study focused on homogeneous population

To enhance the power of finding rare variants in a heterogeneous disease with large numbers of genes, Dr. Lencz and colleagues chose a homogeneous “founder” population, a cohort of Ashkenazi Jews, to examine genomes from schizophrenia patients and controls. “As we have reported in prior work over the last decade, the 10 million or so Ashkenazi Jews living worldwide today all are descended from just a few hundred people who lived approximately 750 years ago, and moved into Central and Eastern Europe,” said Dr. Lencz. The study included 786 cases of schizophrenia and 463 controls from this Ashkenazi population. This is considered to be an extremely small sample for a genetic study. However, because this population evolved from a few hundred individuals to a massive explosion in a historically short period of time, it had enhanced statistical power, said Dr. Lencz.

“We showed that just a few thousand Ashkenazi Jewish cases would have the statistical power of a regular population that was 5-10 times larger, from a genetic discovery perspective,” he added.
 

Search for ultrarare variants

The investigators used whole-genome sequencing to conduct their analysis, using public databases to filter out any variants that had been previously observed in healthy individuals worldwide. “We were looking for ultrarare variants that might have a very powerful effect on the disease,” Dr. Lencz said. Such individual mutations are very rarely seen in the general population.

Because of the disease’s ultraheterogeneity, it’s extremely unusual to find a recurrent, ultrarare variant. “In some ways, the genetics of schizophrenia is so complex that every patient worldwide is unique in the genetics that led to his or her disorder.” The goal was to find individual mutations that might be observed multiple times across the schizophrenia group, Dr. Lencz said.
 

Rare gene found in five cases

Dr. Lencz and colleagues accomplished this with their unique Ashkenazi Jewish population. “We identified one particular mutation that was repeatedly observed in our cases that has not been observed in healthy individuals that we’re aware of,” he said. The PCDHA3 mutation was identified in 3 out of the 786 schizophrenia cases.

In another dataset, they examined from the Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium, they found it two additional times, bringing the total to five cases. SCHEMA is a large international consortium of genetics studies in schizophrenia that contains thousands of cases and controls, some of which are Ashkenazi Jewish cases.

“Importantly, the mutation was not observed in any controls, in either our Ashkenazi dataset, the SCHEMA dataset, or more than 100,000 other controls reported in several publicly available genetics databases,” Dr. Lencz said.
 

How the gene leads to schizophrenia

PCDHA3 derives from the protocadherin gene family, which generates a unique bar code that enables neurons to recognize and communicate with other neurons. This communication creates a scaffolding of sorts that enables normal brain function. Dr. Lencz and colleagues discovered that the PCDHA3 variant blocks this normal protocadherin function.

Among the 786 cases, the investigators found several other genes in the broad cadherin family that had implications in schizophrenia development.

Much of the genetics of schizophrenia in recent years has focused on the synapse as the point of abnormality underlying the disorder. “We think our paper demonstrates in multiple ways the synaptic scaffolding role the cadherins superfamily of genes play in schizophrenia pathophysiology. This is novel – it has never been described before,” said Dr. Lencz. The discovery of the PCDHA3 variant adds a level of detail and resolution to this process, pointing researchers toward a specific aspect of synaptic formation that may be aberrant. “So the hope is we’re not just learning about these five individuals and their synapses. This result is perhaps telling us to look very carefully at this aspect of synaptic formation.”
 

Implications for clinical practice

Dr. Lencz and colleagues plan to expand upon and enhance their existing Ashkenazi sample to take advantage of the founder effect in this population. “Of course, there are many large-scale efforts to recruit ethnically diverse patients with schizophrenia to study around the world. We encourage that. Our expectation is that the biology is not in any way unique to Ashkenazi individuals. This is just the approach we took to enhance our power,” he said.

The PCDHA3 discovery won’t have an immediate impact on clinical practice. In the longer term, “we are aware of certain pharmacologic approaches that might be able to manipulate the cadherins. That would be a worthy focus for future research,” Dr. Lencz said.

Additional studies will be critical to see how current medications in schizophrenia treatment could mitigate and improve any changes caused by this genetic mutation, noted Anthony T. Ng, MD, who was not involved with the study. More specifically, studies would help assess the impact of a schizophrenia patient with this mutation in areas of functioning, “so that psychosocial and rehabilitation treatment models of schizophrenia can provide more targeted treatment,” said Dr. Ng, medical director of community services and director of neuromodulation services at Northern Light Acadia Hospital in Bangor, Maine.

The work of Dr. Lencz and associates is significant in that “it started to identify a very specific genetic change that can help focus treatment of schizophrenia,” Dr. Ng said.

Neither Dr. Lencz nor his associates had any conflicts of interest. Dr. Ng had no disclosures.

A new genetic mutation in schizophrenia that blocks neuron communication in the brain may lead to novel treatment strategies and improve understanding of the mechanics of this disease.

The discovery of this new gene, PCDHA3, could enhance the development of genetic-risk calculators “that may help us understand vulnerability to schizophrenia in high-risk individuals and identify individuals with schizophrenia who have a greater risk for poor outcomes,” said Todd Lencz, PhD, a professor at the Feinstein Institutes for Medical Research in New York, and lead author of this research. Dr. Lencz and associates reported on this new finding in the journal Neuron.

Schizophrenia affects 20 million people worldwide. Previous research has identified the important role genes play in the disease, but isolating individual genes to better understand schizophrenia has proven to be a challenge. This is a very heterogeneous disorder, with many hundreds if not thousands of genes involved, Dr. Lencz explained in an interview. “It is very different from single-gene disorders like Huntington disease, for example. For this reason, we need very large sample sizes to find any one gene that seems to be common to many cases in a sample.”
 

Study focused on homogeneous population

To enhance the power of finding rare variants in a heterogeneous disease with large numbers of genes, Dr. Lencz and colleagues chose a homogeneous “founder” population, a cohort of Ashkenazi Jews, to examine genomes from schizophrenia patients and controls. “As we have reported in prior work over the last decade, the 10 million or so Ashkenazi Jews living worldwide today all are descended from just a few hundred people who lived approximately 750 years ago, and moved into Central and Eastern Europe,” said Dr. Lencz. The study included 786 cases of schizophrenia and 463 controls from this Ashkenazi population. This is considered to be an extremely small sample for a genetic study. However, because this population evolved from a few hundred individuals to a massive explosion in a historically short period of time, it had enhanced statistical power, said Dr. Lencz.

“We showed that just a few thousand Ashkenazi Jewish cases would have the statistical power of a regular population that was 5-10 times larger, from a genetic discovery perspective,” he added.
 

Search for ultrarare variants

The investigators used whole-genome sequencing to conduct their analysis, using public databases to filter out any variants that had been previously observed in healthy individuals worldwide. “We were looking for ultrarare variants that might have a very powerful effect on the disease,” Dr. Lencz said. Such individual mutations are very rarely seen in the general population.

Because of the disease’s ultraheterogeneity, it’s extremely unusual to find a recurrent, ultrarare variant. “In some ways, the genetics of schizophrenia is so complex that every patient worldwide is unique in the genetics that led to his or her disorder.” The goal was to find individual mutations that might be observed multiple times across the schizophrenia group, Dr. Lencz said.
 

Rare gene found in five cases

Dr. Lencz and colleagues accomplished this with their unique Ashkenazi Jewish population. “We identified one particular mutation that was repeatedly observed in our cases that has not been observed in healthy individuals that we’re aware of,” he said. The PCDHA3 mutation was identified in 3 out of the 786 schizophrenia cases.

In another dataset, they examined from the Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium, they found it two additional times, bringing the total to five cases. SCHEMA is a large international consortium of genetics studies in schizophrenia that contains thousands of cases and controls, some of which are Ashkenazi Jewish cases.

“Importantly, the mutation was not observed in any controls, in either our Ashkenazi dataset, the SCHEMA dataset, or more than 100,000 other controls reported in several publicly available genetics databases,” Dr. Lencz said.
 

How the gene leads to schizophrenia

PCDHA3 derives from the protocadherin gene family, which generates a unique bar code that enables neurons to recognize and communicate with other neurons. This communication creates a scaffolding of sorts that enables normal brain function. Dr. Lencz and colleagues discovered that the PCDHA3 variant blocks this normal protocadherin function.

Among the 786 cases, the investigators found several other genes in the broad cadherin family that had implications in schizophrenia development.

Much of the genetics of schizophrenia in recent years has focused on the synapse as the point of abnormality underlying the disorder. “We think our paper demonstrates in multiple ways the synaptic scaffolding role the cadherins superfamily of genes play in schizophrenia pathophysiology. This is novel – it has never been described before,” said Dr. Lencz. The discovery of the PCDHA3 variant adds a level of detail and resolution to this process, pointing researchers toward a specific aspect of synaptic formation that may be aberrant. “So the hope is we’re not just learning about these five individuals and their synapses. This result is perhaps telling us to look very carefully at this aspect of synaptic formation.”
 

Implications for clinical practice

Dr. Lencz and colleagues plan to expand upon and enhance their existing Ashkenazi sample to take advantage of the founder effect in this population. “Of course, there are many large-scale efforts to recruit ethnically diverse patients with schizophrenia to study around the world. We encourage that. Our expectation is that the biology is not in any way unique to Ashkenazi individuals. This is just the approach we took to enhance our power,” he said.

The PCDHA3 discovery won’t have an immediate impact on clinical practice. In the longer term, “we are aware of certain pharmacologic approaches that might be able to manipulate the cadherins. That would be a worthy focus for future research,” Dr. Lencz said.

Additional studies will be critical to see how current medications in schizophrenia treatment could mitigate and improve any changes caused by this genetic mutation, noted Anthony T. Ng, MD, who was not involved with the study. More specifically, studies would help assess the impact of a schizophrenia patient with this mutation in areas of functioning, “so that psychosocial and rehabilitation treatment models of schizophrenia can provide more targeted treatment,” said Dr. Ng, medical director of community services and director of neuromodulation services at Northern Light Acadia Hospital in Bangor, Maine.

The work of Dr. Lencz and associates is significant in that “it started to identify a very specific genetic change that can help focus treatment of schizophrenia,” Dr. Ng said.

Neither Dr. Lencz nor his associates had any conflicts of interest. Dr. Ng had no disclosures.

A new genetic mutation in schizophrenia that blocks neuron communication in the brain may lead to novel treatment strategies and improve understanding of the mechanics of this disease.

The discovery of this new gene, PCDHA3, could enhance the development of genetic-risk calculators “that may help us understand vulnerability to schizophrenia in high-risk individuals and identify individuals with schizophrenia who have a greater risk for poor outcomes,” said Todd Lencz, PhD, a professor at the Feinstein Institutes for Medical Research in New York, and lead author of this research. Dr. Lencz and associates reported on this new finding in the journal Neuron.

Schizophrenia affects 20 million people worldwide. Previous research has identified the important role genes play in the disease, but isolating individual genes to better understand schizophrenia has proven to be a challenge. This is a very heterogeneous disorder, with many hundreds if not thousands of genes involved, Dr. Lencz explained in an interview. “It is very different from single-gene disorders like Huntington disease, for example. For this reason, we need very large sample sizes to find any one gene that seems to be common to many cases in a sample.”
 

Study focused on homogeneous population

To enhance the power of finding rare variants in a heterogeneous disease with large numbers of genes, Dr. Lencz and colleagues chose a homogeneous “founder” population, a cohort of Ashkenazi Jews, to examine genomes from schizophrenia patients and controls. “As we have reported in prior work over the last decade, the 10 million or so Ashkenazi Jews living worldwide today all are descended from just a few hundred people who lived approximately 750 years ago, and moved into Central and Eastern Europe,” said Dr. Lencz. The study included 786 cases of schizophrenia and 463 controls from this Ashkenazi population. This is considered to be an extremely small sample for a genetic study. However, because this population evolved from a few hundred individuals to a massive explosion in a historically short period of time, it had enhanced statistical power, said Dr. Lencz.

“We showed that just a few thousand Ashkenazi Jewish cases would have the statistical power of a regular population that was 5-10 times larger, from a genetic discovery perspective,” he added.
 

Search for ultrarare variants

The investigators used whole-genome sequencing to conduct their analysis, using public databases to filter out any variants that had been previously observed in healthy individuals worldwide. “We were looking for ultrarare variants that might have a very powerful effect on the disease,” Dr. Lencz said. Such individual mutations are very rarely seen in the general population.

Because of the disease’s ultraheterogeneity, it’s extremely unusual to find a recurrent, ultrarare variant. “In some ways, the genetics of schizophrenia is so complex that every patient worldwide is unique in the genetics that led to his or her disorder.” The goal was to find individual mutations that might be observed multiple times across the schizophrenia group, Dr. Lencz said.
 

Rare gene found in five cases

Dr. Lencz and colleagues accomplished this with their unique Ashkenazi Jewish population. “We identified one particular mutation that was repeatedly observed in our cases that has not been observed in healthy individuals that we’re aware of,” he said. The PCDHA3 mutation was identified in 3 out of the 786 schizophrenia cases.

In another dataset, they examined from the Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) consortium, they found it two additional times, bringing the total to five cases. SCHEMA is a large international consortium of genetics studies in schizophrenia that contains thousands of cases and controls, some of which are Ashkenazi Jewish cases.

“Importantly, the mutation was not observed in any controls, in either our Ashkenazi dataset, the SCHEMA dataset, or more than 100,000 other controls reported in several publicly available genetics databases,” Dr. Lencz said.
 

How the gene leads to schizophrenia

PCDHA3 derives from the protocadherin gene family, which generates a unique bar code that enables neurons to recognize and communicate with other neurons. This communication creates a scaffolding of sorts that enables normal brain function. Dr. Lencz and colleagues discovered that the PCDHA3 variant blocks this normal protocadherin function.

Among the 786 cases, the investigators found several other genes in the broad cadherin family that had implications in schizophrenia development.

Much of the genetics of schizophrenia in recent years has focused on the synapse as the point of abnormality underlying the disorder. “We think our paper demonstrates in multiple ways the synaptic scaffolding role the cadherins superfamily of genes play in schizophrenia pathophysiology. This is novel – it has never been described before,” said Dr. Lencz. The discovery of the PCDHA3 variant adds a level of detail and resolution to this process, pointing researchers toward a specific aspect of synaptic formation that may be aberrant. “So the hope is we’re not just learning about these five individuals and their synapses. This result is perhaps telling us to look very carefully at this aspect of synaptic formation.”
 

Implications for clinical practice

Dr. Lencz and colleagues plan to expand upon and enhance their existing Ashkenazi sample to take advantage of the founder effect in this population. “Of course, there are many large-scale efforts to recruit ethnically diverse patients with schizophrenia to study around the world. We encourage that. Our expectation is that the biology is not in any way unique to Ashkenazi individuals. This is just the approach we took to enhance our power,” he said.

The PCDHA3 discovery won’t have an immediate impact on clinical practice. In the longer term, “we are aware of certain pharmacologic approaches that might be able to manipulate the cadherins. That would be a worthy focus for future research,” Dr. Lencz said.

Additional studies will be critical to see how current medications in schizophrenia treatment could mitigate and improve any changes caused by this genetic mutation, noted Anthony T. Ng, MD, who was not involved with the study. More specifically, studies would help assess the impact of a schizophrenia patient with this mutation in areas of functioning, “so that psychosocial and rehabilitation treatment models of schizophrenia can provide more targeted treatment,” said Dr. Ng, medical director of community services and director of neuromodulation services at Northern Light Acadia Hospital in Bangor, Maine.

The work of Dr. Lencz and associates is significant in that “it started to identify a very specific genetic change that can help focus treatment of schizophrenia,” Dr. Ng said.

Neither Dr. Lencz nor his associates had any conflicts of interest. Dr. Ng had no disclosures.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Broadening the diagnosis of gestational diabetes mellitus (GDM) with a one-step screening approach does not lead to significant differences in maternal or perinatal outcomes, compared with a two-step approach. Investigators reported these findings in the New England Journal of Medicine after testing the two screening methods in more than 23,000 pregnant women.

GDM affects 6%-25% of pregnant women, increasing the risk of neonatal death and stillborn births. It can also lead to serious complications such as fetal overgrowth. Clinical guidelines recommend GDM screening between 24 and 28 weeks’ gestation to improve outcomes in mothers and infants. However, the scientific community has struggled to reach a consensus on testing approach.

For decades, clinicians used a two-step screening approach: a nonfasting 1-hour glucose challenge test and a longer 3-hour fasting oral glucose tolerance test to diagnose GDM; roughly 20% who test positive on this glucose challenge test require the second step. Results of a large study led to new diagnostic criteria on a one-step 75-g oral glucose tolerance test. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study “found a linear relationship with hyperglycemia and outcomes – the higher the glucose, the worse the outcomes,” said Teresa Hillier, MD, MS, an endocrinologist and investigator with Kaiser Permanente Center for Health Research Northwest and CHR-Hawaii. The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) made a clinical recommendation on the one-step approach, now a common screening tool in the United States.
 

A focus on rare GDM outcomes

The IADPSG fasting one-step criteria typically identifies women with milder symptoms as having gestational diabetes, a factor expected to increase diagnosis rates by two- or threefold, said Dr. Hillier. “The unknown question was whether diagnosing and treating more women would be associated with any differences in any of the multiple GDM-associated outcomes for mother and baby.”

She and her colleagues conducted a large-scale randomized trial at two Kaiser sites to assess multiple maternal and perinatal outcomes including rare but important GDM-associated outcomes such as stillbirth and neonatal death between the two screening methods.

They randomized 23,792 pregnant women 1:1 to the one- or two-step gestational diabetes test at their first prenatal visit. Primary outcomes included diagnosis of gestational diabetes; large-for-gestational-age infants; primary cesarean section, and gestational hypertension or preeclampsia; and a composite perinatal outcome of any stillbirth, neonatal death, shoulder dystocia, bone fracture, or arm or hand nerve palsy related to birth injury.

Most participants (94%) completed screening, although there was lower adherence to screening in the one-step approach. The reasons for this aren’t entirely clear, said Dr. Hillier. Convenience may be a factor; patients have to fast for several hours to complete the one-step test, whereas the first test of the two-step screening approach can be done at any time of day, and most patients pass this test.

Corroborating HAPO’s results, twice as many women in the one-step group (16.5%) received a GDM diagnosis, compared with 8.5% in the two-step group (unadjusted relative risk, 1.94; 97.5% confidence interval, 1.79-2.11). However, for the other primary outcomes, investigators found no significant differences in incidences or unadjusted risks. Perinatal composite outcomes for the one- and two-step groups were 3.1% and 3.0%, respectively, and primary cesarean section outcomes were 24.0% and 24.6%.

In the one-step group, 8.9% experienced large-for-gestational-age infants outcomes, compared with 9.2% in the two-step group (RR, 0.95; 97.5% CI, 0.87-1.05). Among those diagnosed with gestational diabetes, similar percentages of women in the one- and two-step groups received insulin or hypoglycemic medication (42.6% and 45.6%, respectively).

Dr. Hillier and colleagues also reported comparable results among the two groups on safety outcomes and secondary outcomes such as macrosomia incidence, small-for-gestational-age infants, and factors such as neonatal hypoglycemia and respiratory distress.

“Although we did not find increased harms associated with the diagnosis and treatment of gestational diabetes in many more women with the one-step approach, some retrospective observational cohort studies have shown higher incidences of primary cesarean delivery and neonatal hypoglycemia with one-step screening after conversion from two-step protocols, with no substantive improvement in outcomes,” Dr. Hillier and colleagues noted.

The trial had several limitations. Adjustments made to address lower adherence to the one-step approach might not have accounted for all nonadherence differences. Another issue is the two sites didn’t use identical thresholds for the glucose challenge test in the two-step cohort. Demographically, the study lacked Black and American Indian representation.

“Moreover, the potential long-term benefits of increased diagnoses of gestational diabetes – such as the identification of more women at high risk for subsequent diabetes who might benefit from risk-reduction strategies – were not addressed by the trial,” Brian Casey, MD, wrote in a related editorial. Based on the study’s findings, “the perinatal benefits of the diagnosis of gestational diabetes with the use of the IADPSG single-step approach appear to be insufficient to justify the associated patient and health care costs of broadening the diagnosis” of GDM, added Dr. Casey, a professor with the department of obstetrics and gynecology at the University of Alabama at Birmingham.
 

U.S. doctors unlikely to change behaviors

Most U.S. physicians favor the two-step method. This has been a huge controversy worldwide, with other countries pushing the United States to use the one-step method, Vincenzo Berghella, MD, a professor with Thomas Jefferson University, Philadelphia, said in an interview. “I expect this study will increase the divide between the U.S. and the rest of the world,” since U.S. physicians will see no benefit to the one-step method, and continue to use the two-step method. 

It’s not surprising that GDM diagnosis incidence went up to 16.5% with the inclusion of the one-step test, compared with 8.5% with the two-step test, Dr. Berghella continued. What’s less clear, are the details of treatment among the 8% diagnosed to have GDM with the one-step test, but not the two-step test. 

These women were likely to have milder degrees of insulin resistance or GDM. Dr. Berghella, who has advocated in the past for the one-step approach, said it would be important to find out if these women, who test positive at the one-step test but would test negative at the two-step test, were treated properly with diet, exercise, and possibly insulin or other hypoglycemic agents for their mild degree of insulin resistance. The researchers concluded that expanding the definition of GDM through the one-step test didn’t make a difference. However, “it’s not just the test that will make the difference in maternal and baby outcomes, but the aggressive management of diabetes with diet, exercise, and medications as needed once that test comes back abnormal,” he said.

The randomized trial was a massive undertaking, said Dr. Hillier.

“We are still evaluating our future plans,” she added. Forthcoming subgroup analyses from the trial could further help inform clinical practice guidelines.

Dr. Hillier received a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development to support this study. The investigators reported no potential conflict of interest relevant to this article.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

Clinicians using systemic retinoids for treating ichthyosis and other disorders of cornification (DOC) in children and adolescents should aim for the lowest dose possible to balance therapeutic goals with acceptable toxicity levels, advised the authors of a new consensus statement.

In the statement, published in Pediatric Dermatology, they also addressed the effects of topical and systemic retinoid use on bone, eye, cardiovascular, and mental health, and the risks some retinoids pose to reproductive health.

Many patients with these chronic conditions, driven by multiple genetic mutations, respond to topical and/or systemic retinoids. However, to date, no specific guidance has addressed the safety, efficacy, or overall precautions for their use in the pediatric population, one of the statement authors, Moise L. Levy, MD, professor of pediatrics and medicine at the University of Texas at Austin, said in an interview.

Dr. Levy was one of the physicians on the multidisciplinary panel, The Pediatric Dermatology Research Alliance Use of Retinoids in Ichthyosis Work Group, formed to devise best practice recommendations on the use of retinoids in the management of ichthyoses and other cornification disorders in children and adolescents. The panel conducted an extensive evidence-based literature review and met in person to arrive at their conclusions. Representation from the Foundation for Ichthyosis and Related Skin Types (FIRST) was also key to this work. “Additionally, the teratogenic effects of retinoids prompted examination of gynecologic considerations and the role of the iPLEDGE program in the United States on patient access to isotretinoin,” the authors wrote.


 

Retinoid effects, dosing

“Both topical and systemic retinoids can improve scaling in patients with select forms of ichthyosis,” and some subtypes of disease respond better to treatment than others, they noted. Oral or topical retinoids are known to improve cases of congenital ichthyosiform erythroderma (select genotypes), Sjögren-Larsson syndrome, ichthyosis follicularis–alopecia-photophobia syndromes and keratitis-ichthyosis-deafness syndrome, erythrokeratodermia variabilis, harlequin ichthyosis, ichthyosis with confetti, and other subtypes.

Comparatively, they added, there are no data on the use of retinoids, or data showing no improvement with retinoids for several ichthyosis subtypes, including congenital hemidysplasia with ichthyosiform erythroderma and limb defects, CHIME syndrome, Conradi-Hünermann-Happle syndrome, ichthyosis-hypotrichosis syndrome, ichthyosis-hypotrichosis-sclerosing cholangitis, ichthyosis prematurity syndrome, MEDNIK syndrome, peeling skin disease, Refsum syndrome, and trichothiodystrophy though the response to such cases may vary.

Retinoids may worsen conditions that lead to peeling or skin fragility, atopic diathesis, or excessive desquamation, “and should be used with caution,” the authors advised.

Pediatric and adult patients with moderate to severe disease and significant functional or psychological impairment “should be offered the opportunity to make a benefit/risk assessment of treatment” with a systemic retinoid, they added, noting that topical retinoids have a lower risk profile and may be a better choice for milder disease.

Clinicians should aim for the lowest dose possible “that will achieve and maintain the desired therapeutic effect with acceptable mucocutaneous and systemic toxicities,” the panel recommended. Lower doses work especially well in patients with epidermolytic ichthyoses and erythrokeratodermia variabilis.

“Given the cutaneous and extracutaneous toxicities of oral retinoids, lower doses were found to achieve the most acceptable risk-benefit result. Few individuals now receive more than 1 mg/kg per day of isotretinoin or 0.5 mg/kg per day of acitretin,” according to the panel.

Dosing decisions call for a group conversation between physicians, patients and caregivers, addressing skin care, comfort and appearance issues, risk of adverse effects, and tolerance of the therapy.
 

Retinoid effects on organs

The impact of retinoids on the body varies by organ system, type of therapy and dosage. Dose and duration of therapy, for example, help determine the toxic effects of retinoids on bone. “Long-term use of systemic retinoids in ichthyosis/DOC is associated with skeletal concerns,” noted the authors, adding that clinicians should still consider this therapeutic approach if there is a strong clinical case for using it in a patient.

Children on long-term systemic therapy should undergo a series of tests and evaluations for bone monitoring, including an annual growth assessment. The group also recommended a baseline skeletal radiographic survey when children are on long-term systemic retinoid therapy, repeated after 3-5 years or when symptoms are present. Clinicians should also inquire about diet and discuss with patients factors that impact susceptibility to retinoid bone toxicity, such as genetic risk, diet and physical activity.

They also recommended monitoring patients taking systemic retinoids for psychiatric symptoms.

Adolescents of childbearing potential using systemic retinoids, who are sexually active, should receive counseling about contraceptive options, and should use two forms of contraception, including one highly effective method, the statement advises.

In the United States, all patients and prescribers of isotretinoin must comply with iPLEDGE guidelines; the statement addresses the issue that iPLEDGE was not designed for long-term use of isotretinoin in patients with ichthyosis, and “imposes a significant burden” in this group.

Other practice gaps and unmet needs in this area of study were discussed, calling for a closer examination of optimal timing of therapy initiation, and the adverse effects of long-term retinoid treatment. “The work, as a whole, is a starting point for these important management issues,” said Dr. Levy.

Unrestricted educational grants from Sun Pharmaceuticals and FIRST funded this effort. Dr. Levy’s disclosed serving on the advisory board and as a consultant for Cassiopea, Regeneron, and UCB, and an investigator for Fibrocell, Galderma, Janssen, and Pfizer. The other authors disclosed serving as investigators, advisers, consultants, and/or other relationships with various pharmaceutical companies.

COVID-19 is having a disproportionate impact on the lives of all women physicians, Linda Brubaker, MD, recently wrote in JAMA.

“Women physicians do not have trouble balancing competing demands any more than men physicians do. It is simply a more common expectation that women physicians will adjust their professional lives,” she observed.

The daily grind of caring for patients during a global pandemic is taking an emotional and mental toll on doctors as well as a physical one. “The recently publicized suicide of emergency physician Lorna Breen, MD, following her intense work during the pandemic in New York should cause every physician to reflect on their culture in medicine,” Dr. Brubaker wrote in the article. In an interview, she expounded on the current climate for women psychiatrists and physicians in general, offering some coping techniques.

Question: The pandemic has amplified disparities among men and women physicians. What may be the repercussions from this, not just for patient care, but for work-life balance among women physicians?

Answer: Focusing on women in academic roles, both research and clinical productivity have changed in the professional arena. Many women continue to bear a disproportionate share of family responsibilities and have reduced paid work to accommodate these needs. These changes can impact academic promotion and, therefore, subsequent academic opportunities for leadership. These gaps will add to the well-recognized gender wage gap. Women physicians are more likely to experience reduced wages associated with reduced professional activities. This reduces their annual earnings, which reduces their contributions to Social Security and other retirement programs. This can adversely impact their financial security later in life, at a time when women are already disadvantaged, compared with men.



Q: Are women psychiatrists facing additional burdens, given that many patients are suffering from anxiety and depression right now, and seeking out prescriptions?

A: We know that mental health concerns are on the rise. Although I cannot point to specific evidence, I wouldn’t be at all surprised to hear that psychiatrists are dealing with an increased professional load as a result. Similar to those on the more well-recognized “front lines” in the ED and critical care units, I consider my psychiatric colleagues to be on the front lines as well, as they are addressing this marked increase in care needs, for patients and for other members of the health care team.



Q: You mentioned the suicide of Dr. Breen. What might women psychiatrists take away from this incident?

A: Physicians are drawn to our vocation with a commitment to be of service to others. During such demanding times as these, the “safety” rails between service to others and self-care shift – clearly this can endanger individual doctors.



Q: What advice might you have for women in this profession? Any resources that could provide support?

A: My advice is to ensure your own well-being, knowing that this differs for each woman. Be realistic with your time and commitments, allowing time for restoration and rest. Sometimes I tell my peers to meditate or do some other form of contemplative practice. Exercise (preferably outdoors) and sleep, including preparing for good sleep, such as not reading emails or patient charts right up until sleep time, are all important. Most importantly, identify your support team and check in regularly with them. Never hesitate to reach out for help. People truly do care and want to help you.

COVID-19 is having a disproportionate impact on the lives of all women physicians, Linda Brubaker, MD, recently wrote in JAMA.

“Women physicians do not have trouble balancing competing demands any more than men physicians do. It is simply a more common expectation that women physicians will adjust their professional lives,” she observed.

The daily grind of caring for patients during a global pandemic is taking an emotional and mental toll on doctors as well as a physical one. “The recently publicized suicide of emergency physician Lorna Breen, MD, following her intense work during the pandemic in New York should cause every physician to reflect on their culture in medicine,” Dr. Brubaker wrote in the article. In an interview, she expounded on the current climate for women psychiatrists and physicians in general, offering some coping techniques.

Question: The pandemic has amplified disparities among men and women physicians. What may be the repercussions from this, not just for patient care, but for work-life balance among women physicians?

Answer: Focusing on women in academic roles, both research and clinical productivity have changed in the professional arena. Many women continue to bear a disproportionate share of family responsibilities and have reduced paid work to accommodate these needs. These changes can impact academic promotion and, therefore, subsequent academic opportunities for leadership. These gaps will add to the well-recognized gender wage gap. Women physicians are more likely to experience reduced wages associated with reduced professional activities. This reduces their annual earnings, which reduces their contributions to Social Security and other retirement programs. This can adversely impact their financial security later in life, at a time when women are already disadvantaged, compared with men.



Q: Are women psychiatrists facing additional burdens, given that many patients are suffering from anxiety and depression right now, and seeking out prescriptions?

A: We know that mental health concerns are on the rise. Although I cannot point to specific evidence, I wouldn’t be at all surprised to hear that psychiatrists are dealing with an increased professional load as a result. Similar to those on the more well-recognized “front lines” in the ED and critical care units, I consider my psychiatric colleagues to be on the front lines as well, as they are addressing this marked increase in care needs, for patients and for other members of the health care team.



Q: You mentioned the suicide of Dr. Breen. What might women psychiatrists take away from this incident?

A: Physicians are drawn to our vocation with a commitment to be of service to others. During such demanding times as these, the “safety” rails between service to others and self-care shift – clearly this can endanger individual doctors.



Q: What advice might you have for women in this profession? Any resources that could provide support?

A: My advice is to ensure your own well-being, knowing that this differs for each woman. Be realistic with your time and commitments, allowing time for restoration and rest. Sometimes I tell my peers to meditate or do some other form of contemplative practice. Exercise (preferably outdoors) and sleep, including preparing for good sleep, such as not reading emails or patient charts right up until sleep time, are all important. Most importantly, identify your support team and check in regularly with them. Never hesitate to reach out for help. People truly do care and want to help you.

COVID-19 is having a disproportionate impact on the lives of all women physicians, Linda Brubaker, MD, recently wrote in JAMA.

“Women physicians do not have trouble balancing competing demands any more than men physicians do. It is simply a more common expectation that women physicians will adjust their professional lives,” she observed.

The daily grind of caring for patients during a global pandemic is taking an emotional and mental toll on doctors as well as a physical one. “The recently publicized suicide of emergency physician Lorna Breen, MD, following her intense work during the pandemic in New York should cause every physician to reflect on their culture in medicine,” Dr. Brubaker wrote in the article. In an interview, she expounded on the current climate for women psychiatrists and physicians in general, offering some coping techniques.

Question: The pandemic has amplified disparities among men and women physicians. What may be the repercussions from this, not just for patient care, but for work-life balance among women physicians?

Answer: Focusing on women in academic roles, both research and clinical productivity have changed in the professional arena. Many women continue to bear a disproportionate share of family responsibilities and have reduced paid work to accommodate these needs. These changes can impact academic promotion and, therefore, subsequent academic opportunities for leadership. These gaps will add to the well-recognized gender wage gap. Women physicians are more likely to experience reduced wages associated with reduced professional activities. This reduces their annual earnings, which reduces their contributions to Social Security and other retirement programs. This can adversely impact their financial security later in life, at a time when women are already disadvantaged, compared with men.



Q: Are women psychiatrists facing additional burdens, given that many patients are suffering from anxiety and depression right now, and seeking out prescriptions?

A: We know that mental health concerns are on the rise. Although I cannot point to specific evidence, I wouldn’t be at all surprised to hear that psychiatrists are dealing with an increased professional load as a result. Similar to those on the more well-recognized “front lines” in the ED and critical care units, I consider my psychiatric colleagues to be on the front lines as well, as they are addressing this marked increase in care needs, for patients and for other members of the health care team.



Q: You mentioned the suicide of Dr. Breen. What might women psychiatrists take away from this incident?

A: Physicians are drawn to our vocation with a commitment to be of service to others. During such demanding times as these, the “safety” rails between service to others and self-care shift – clearly this can endanger individual doctors.



Q: What advice might you have for women in this profession? Any resources that could provide support?

A: My advice is to ensure your own well-being, knowing that this differs for each woman. Be realistic with your time and commitments, allowing time for restoration and rest. Sometimes I tell my peers to meditate or do some other form of contemplative practice. Exercise (preferably outdoors) and sleep, including preparing for good sleep, such as not reading emails or patient charts right up until sleep time, are all important. Most importantly, identify your support team and check in regularly with them. Never hesitate to reach out for help. People truly do care and want to help you.

Daily life is now a juggling act for Misty Richards, MD, MS. As the program director of a rigorous child psychiatry fellowship, a psychiatrist caring for women with perinatal psychiatric disorders, and the mother of three young children, Dr. Richards tries to view these tasks as an opportunity for growth. But some days it feels as if she’s navigating a storm in the middle of the ocean without a life jacket.

In the age of COVID, “the wave of demands has morphed into one giant tidal wave of desperate need,” Dr. Richards, of the department of psychiatry & biobehavioral sciences, University of California, Los Angeles, Semel Institute of Neuroscience & Human Behavior, said in an interview. “The painfully loud and clear message is that our patients need us, and our children – who have been stripped from healthy routines and peer interactions that nourish social-emotional development – rely on us. We cannot turn our backs for even a moment, or else they will suffer.”

Tasked with caring for a much sicker and distressed population, navigating home duties such as child care, online school, and taking care of certain family members, women psychiatrists are feeling the impact of COVID-19.

Many have seamlessly transferred their practices online, maintaining a lifeline with their patients through telehealth visits. Even with this convenience, the emotional labor of being a psychiatrist is still very stressful, Pooja Lakshmin, MD, of the department of psychiatry and behavioral sciences at George Washington University, Washington, said in an interview. Because the nature of work has changed, and many are doing things virtually at home, separating home from work life can be a challenge. “It’s harder to disconnect,” admitted Dr. Lakshmin. “Even my patients tell me that they have no time to themselves anymore.”

The pandemic demands that women in the profession “white-knuckle” their way to the finish line – a moving target that remains nowhere in sight, Dr. Richards said. “In this process, we are expected to fill the emotional cups of a broken nation, to provide answers that do not exist, and to do so with never-ending gratitude for a demanding system that has no ‘off’ switch,” she noted.
 

‘In two places at once’

COVID-19’s physical and emotional toll has swept across the various subspecialties of clinical psychiatry. As some navigate outpatient/telehealth work, inpatient psychiatrists directly interact with COVID patients.

“Our inpatient psychiatry unit regularly takes care of COVID patients, including perinatal patients who are COVID positive,” Samantha Meltzer-Brody, MD, MPH, distinguished professor and chair, University of North Carolina, Chapel Hill, department of psychiatry and director of medical school’s Center for Women’s Mood Disorders, said in an interview. A psychiatry consultation-liaison service also provides psychiatry care to medical and surgical patients, including medically ill COVID patients across the hospital.

“We are on the front lines in the sense that we are dealing with the trauma of the general population and having to be present for that emotional distress,” Dr. Meltzer-Brody said.

The struggle to balance rising caseloads and home responsibilities makes things difficult, she continued. “There’s a never-ending onslaught of patient referrals,” reflecting the anxiety and depression issues people are experiencing in the wake of a global pandemic, frenetic political situation in the United States, and job uncertainty.

Child care and elder care responsibilities affect both men and women, yet research shows that caregiving demands disproportionately affect women, observed Dr. Meltzer-Brody.

Overall, the stress of caregiving and parenting responsibilities for men and women has been markedly higher during the pandemic. Most clinical psychiatrists “have been extraordinarily busy for a very long time,” she added.

Tiffani L. Bell, MD, a psychiatrist in Winston-Salem, N.C., has seen an increase in anxiety and depression in people with no previous history of diagnosed mental illness. “The impact of the pandemic has truly been multifaceted. People are struggling with loss of jobs, loss of wages, and loss of loved ones, along with grieving the loss of the usual way of life,” she said in an interview.

Many of her colleagues report feeling overburdened at work with increased admissions and patient loads, decreased time to see each patient, and the feeling of “needing to be in two places at once.”

“As a female psychiatrist, I do believe that we can sometimes have an increased mental burden due to the emotional and physical burnout that can occur when our routines are shaken,” added Dr. Bell, who specializes in adult, child, and adolescent psychiatry, and obesity and lifestyle medicine. Even in the early months of the pandemic, Dr. Bell said she heard people joke that “they don’t know if they are working from home or living at work.”

Physicians aren’t the only ones who are overwhelmed. “We’re also hearing stories from our patients – those at risk for partner violence, dealing with kids out of school, working full time while providing support at home,” Ludmila De Faria, MD, chair of the American Psychiatric Association’s Committee on Women’s Mental Health, said in an interview.

American mothers in particular spend nearly twice as much time caring for their children and cooking than their spouses, said Dr. Bell, citing recent studies. “Even if one is not a mom, if you couple the increased housework at baseline with the added responsibilities of working as a front-line physician and/or working from home while managing a household, it can lead to increased stress for all involved.”
 

Women leaving the workforce

Nationally, a growing number of women are either reducing their hours or leaving the workforce in response to the pandemic. Fidelity Investments, which surveyed 1,902 U.S. adults in mid-2020 projected that 4 in 10 women were mulling such options. Among 951 women surveyed, 42% were considering stepping back from their jobs because of their children’s homeschooling needs, and 27% cited difficulties of balancing home and job responsibilities.

Interruptions caused by child care affect women more than men, according to a report from the Century Foundation and the Center for American Progress. “Study after study has shown that, in response to school, child care, and camp closings, as well as reduced hours and reduced class sizes, significantly more women than men have reduced their work hours, left work to care for children, and spent more time on education and household tasks,” the authors noted.

They estimated that the American economy could incur $64.5 billion per year in lost wages and economic activity from the fallout of these trends. In September 2020, four times as many women as men left the workforce, nearly 865,000 women in comparison to 216,000 men.

Many women psychiatrists have been forced to choose between their careers or child care duties – decisions they don’t want to make, but that may be necessary during these unprecedented circumstances. They may be reducing their work hours to assist at home. Others are leaving their jobs, “a terrible situation given the enormous mental health needs of the pandemic” and the fact that so many areas of the United States already suffer from a shortage of clinical psychiatrists, said Dr. Meltzer-Brody.

She has personally seen the effects of this in the large academic department she supervises. “I’m seeing women reducing their work hours or leave positions,” she continued. In addition to child care needs, these women are tending to aging parents affected by COVID-19 or other illnesses, or dealing with the fact that options for elder care aren’t available.

“I have multiple faculty contending with that situation,” added Dr. Meltzer-Brody. As a result, productivity is going down. “These women are trying to keep all of the balls in the air but find they can’t.”

Dr. Richards believes some changes are in order to take the disproportionate burden off of women in psychiatry, and the workforce as a whole. The health care system “places too much pressure on individuals to compensate for its deficiencies. Those individuals who often step up to the plate are women, and this is not their sole burden to carry.”

A move toward telehealth in clinical psychiatry has made it possible for patients and physicians to meet virtually in their respective homes and discuss treatment options. “Even while this is both a blessing and privilege, it comes with the unique challenges of having to manage Zoom calls, child care, meals, distance learning, cleaning, and work responsibilities, while previously there was a clearer delineation to the day for many,” Dr. Bell said.

Clinical psychiatrists educating the public about the mental stressors of COVID-19 face their own unique challenges.

Dr. Lakshmin, who makes appearances in various media and social media outlets, said this adds more pressure to the job. “One of the challenges for me is to figure out how much outward facing I do. That’s hard when you’re navigating working and living through a pandemic. This is something I do because I enjoy doing it. But it’s still a type of work. And it’s certainly increased because the media has been paying more attention to mental health” since the pandemic started, she added.
 

The dual stress of COVID and social justice

Some women psychiatrists of color are dealing with social justice issues on top of other COVID stressors, Dr. De Faria said. The focus on addressing institutionalized racism means that minority women are taking on extra work to advocate for their peers.

Michelle Jacobs-Elliott, MD, of the department of psychiatry and assistant dean of the Office of Diversity and Health Equity at the University of Florida, Gainesville, knows of such responsibilities. “I have been in many discussions either with my coworkers in my department or others who work for the University of Florida” on systemic racism, she said in an interview.

Dr. Jacobs-Elliott became a trainer for Bias Reduction in Internal Medicine, a workshop aimed at reducing bias, and prior to 2020 participated in a social justice summit at the University of Florida. “Talking with my medical as well as undergraduate students about their experiences both here in Gainesville and elsewhere, they are all feeling the hurt, disappointment, and disbelief that we are still fighting battles that our grandparents fought in health care, housing, and employment. This adds an extra layer of stress to everyone’s life.”

The tense social climate has made the apparent racial inequalities in COVID-19 deaths and severity of disease hard to ignore, Dr. Bell noted. “It is my sincere hope that the availability of COVID-19 vaccines will help decrease the number of people affected by this horrible disease. The added burden of racism on top of the stressors of this pandemic can feel insurmountable. I hope 2021 will provide a way forward for us all.”
 

Taking time for self-care

Amid the endless referrals and increasing demands at home, women psychiatrists often don’t have the time to do normal activities, Dr. Meltzer-Brody observed. Like most people, COVID restrictions prevent them from traveling or going to the gym or restaurants. Dr. De Faria has not been able to visit family in Latin America, a trip she used to make twice a year. “That was once my de-stress time. But now, I can’t connect with my roots. My father is elderly and very much at risk.”

This is the time to get creative and resourceful – to make time for self-care, several sources said.

“We need to realize that we cannot be all things to all people, at the same time,” noted Dr. Bell. It’s important to prioritize what’s most important – and keep assessing your priorities. There’s no shame in tending to your own needs. Dr. Bell recommended that women in her profession should pick 1 day a week, put it in their calendar, and stick to this goal of self-care.

“Even if it’s only 15 minutes, it is important to put time aside. Some quick, cheap ideas are to do a quick meditation session, read a chapter in a book, listen to an audiobook, journal, go for a walk and get fresh air. Eat a healthy meal. Even 10 minutes helps,” she urged.

COVID-19 has pushed society to find new ways to do things, Dr. Bell continued. Women psychiatrists, in assessing their work-life balance, may need to reassess their goals. Consider work schedules and see if there’s a place to scale back a task. Delegate tasks at home to family members, if necessary. Most importantly, exercise self-compassion, she stressed. “During this pandemic, I believe it is vital to keep our cups filled so we can pour into others.”

Dr. Lakshmin said she has benefited greatly from having a therapist during the pandemic. “It has been so instrumental in forcing me to take that time for myself, to give me a space to take care of me, and remember it’s okay to take care of me. It’s so important for us as psychiatrists to have that for ourselves. It’s not just for our patients – we need it, too.”

The APA has resources and numerous support groups that meet regularly to address and discuss the stressors of the pandemic. Its College Mental Health Caucus, for example, holds a monthly, hour-long Zoom meeting. Not surprisingly, women comprise the majority of attendees, Dr. De Faria said. “Most women in academic psychiatry are working from home and using telehealth, which isolates people a lot.” Maureen Sayres Van Niel, MD, who is head of the APA’s Women’s Caucus, sends out a regular newsletter that advises on self-care. Women psychiatrists should also contact their local psychiatric organizations to get support from their professional peers.

Sometimes it’s wise to leave work behind and engage with friends. Dr. De Faria regularly Zooms with a group of friends outside of her profession to de-stress and reconnect. “At least I can talk to them about things other than psychiatry.”

Mentally and physically exhausted, Dr. Jacobs-Elliott said she looks forward to the day when society can return to meeting with friends and family “without being afraid that we are an asymptomatic carrier who is infecting our loved ones.”

Daily life is now a juggling act for Misty Richards, MD, MS. As the program director of a rigorous child psychiatry fellowship, a psychiatrist caring for women with perinatal psychiatric disorders, and the mother of three young children, Dr. Richards tries to view these tasks as an opportunity for growth. But some days it feels as if she’s navigating a storm in the middle of the ocean without a life jacket.

In the age of COVID, “the wave of demands has morphed into one giant tidal wave of desperate need,” Dr. Richards, of the department of psychiatry & biobehavioral sciences, University of California, Los Angeles, Semel Institute of Neuroscience & Human Behavior, said in an interview. “The painfully loud and clear message is that our patients need us, and our children – who have been stripped from healthy routines and peer interactions that nourish social-emotional development – rely on us. We cannot turn our backs for even a moment, or else they will suffer.”

Tasked with caring for a much sicker and distressed population, navigating home duties such as child care, online school, and taking care of certain family members, women psychiatrists are feeling the impact of COVID-19.

Many have seamlessly transferred their practices online, maintaining a lifeline with their patients through telehealth visits. Even with this convenience, the emotional labor of being a psychiatrist is still very stressful, Pooja Lakshmin, MD, of the department of psychiatry and behavioral sciences at George Washington University, Washington, said in an interview. Because the nature of work has changed, and many are doing things virtually at home, separating home from work life can be a challenge. “It’s harder to disconnect,” admitted Dr. Lakshmin. “Even my patients tell me that they have no time to themselves anymore.”

The pandemic demands that women in the profession “white-knuckle” their way to the finish line – a moving target that remains nowhere in sight, Dr. Richards said. “In this process, we are expected to fill the emotional cups of a broken nation, to provide answers that do not exist, and to do so with never-ending gratitude for a demanding system that has no ‘off’ switch,” she noted.
 

‘In two places at once’

COVID-19’s physical and emotional toll has swept across the various subspecialties of clinical psychiatry. As some navigate outpatient/telehealth work, inpatient psychiatrists directly interact with COVID patients.

“Our inpatient psychiatry unit regularly takes care of COVID patients, including perinatal patients who are COVID positive,” Samantha Meltzer-Brody, MD, MPH, distinguished professor and chair, University of North Carolina, Chapel Hill, department of psychiatry and director of medical school’s Center for Women’s Mood Disorders, said in an interview. A psychiatry consultation-liaison service also provides psychiatry care to medical and surgical patients, including medically ill COVID patients across the hospital.

“We are on the front lines in the sense that we are dealing with the trauma of the general population and having to be present for that emotional distress,” Dr. Meltzer-Brody said.

The struggle to balance rising caseloads and home responsibilities makes things difficult, she continued. “There’s a never-ending onslaught of patient referrals,” reflecting the anxiety and depression issues people are experiencing in the wake of a global pandemic, frenetic political situation in the United States, and job uncertainty.

Child care and elder care responsibilities affect both men and women, yet research shows that caregiving demands disproportionately affect women, observed Dr. Meltzer-Brody.

Overall, the stress of caregiving and parenting responsibilities for men and women has been markedly higher during the pandemic. Most clinical psychiatrists “have been extraordinarily busy for a very long time,” she added.

Tiffani L. Bell, MD, a psychiatrist in Winston-Salem, N.C., has seen an increase in anxiety and depression in people with no previous history of diagnosed mental illness. “The impact of the pandemic has truly been multifaceted. People are struggling with loss of jobs, loss of wages, and loss of loved ones, along with grieving the loss of the usual way of life,” she said in an interview.

Many of her colleagues report feeling overburdened at work with increased admissions and patient loads, decreased time to see each patient, and the feeling of “needing to be in two places at once.”

“As a female psychiatrist, I do believe that we can sometimes have an increased mental burden due to the emotional and physical burnout that can occur when our routines are shaken,” added Dr. Bell, who specializes in adult, child, and adolescent psychiatry, and obesity and lifestyle medicine. Even in the early months of the pandemic, Dr. Bell said she heard people joke that “they don’t know if they are working from home or living at work.”

Physicians aren’t the only ones who are overwhelmed. “We’re also hearing stories from our patients – those at risk for partner violence, dealing with kids out of school, working full time while providing support at home,” Ludmila De Faria, MD, chair of the American Psychiatric Association’s Committee on Women’s Mental Health, said in an interview.

American mothers in particular spend nearly twice as much time caring for their children and cooking than their spouses, said Dr. Bell, citing recent studies. “Even if one is not a mom, if you couple the increased housework at baseline with the added responsibilities of working as a front-line physician and/or working from home while managing a household, it can lead to increased stress for all involved.”
 

Women leaving the workforce

Nationally, a growing number of women are either reducing their hours or leaving the workforce in response to the pandemic. Fidelity Investments, which surveyed 1,902 U.S. adults in mid-2020 projected that 4 in 10 women were mulling such options. Among 951 women surveyed, 42% were considering stepping back from their jobs because of their children’s homeschooling needs, and 27% cited difficulties of balancing home and job responsibilities.

Interruptions caused by child care affect women more than men, according to a report from the Century Foundation and the Center for American Progress. “Study after study has shown that, in response to school, child care, and camp closings, as well as reduced hours and reduced class sizes, significantly more women than men have reduced their work hours, left work to care for children, and spent more time on education and household tasks,” the authors noted.

They estimated that the American economy could incur $64.5 billion per year in lost wages and economic activity from the fallout of these trends. In September 2020, four times as many women as men left the workforce, nearly 865,000 women in comparison to 216,000 men.

Many women psychiatrists have been forced to choose between their careers or child care duties – decisions they don’t want to make, but that may be necessary during these unprecedented circumstances. They may be reducing their work hours to assist at home. Others are leaving their jobs, “a terrible situation given the enormous mental health needs of the pandemic” and the fact that so many areas of the United States already suffer from a shortage of clinical psychiatrists, said Dr. Meltzer-Brody.

She has personally seen the effects of this in the large academic department she supervises. “I’m seeing women reducing their work hours or leave positions,” she continued. In addition to child care needs, these women are tending to aging parents affected by COVID-19 or other illnesses, or dealing with the fact that options for elder care aren’t available.

“I have multiple faculty contending with that situation,” added Dr. Meltzer-Brody. As a result, productivity is going down. “These women are trying to keep all of the balls in the air but find they can’t.”

Dr. Richards believes some changes are in order to take the disproportionate burden off of women in psychiatry, and the workforce as a whole. The health care system “places too much pressure on individuals to compensate for its deficiencies. Those individuals who often step up to the plate are women, and this is not their sole burden to carry.”

A move toward telehealth in clinical psychiatry has made it possible for patients and physicians to meet virtually in their respective homes and discuss treatment options. “Even while this is both a blessing and privilege, it comes with the unique challenges of having to manage Zoom calls, child care, meals, distance learning, cleaning, and work responsibilities, while previously there was a clearer delineation to the day for many,” Dr. Bell said.

Clinical psychiatrists educating the public about the mental stressors of COVID-19 face their own unique challenges.

Dr. Lakshmin, who makes appearances in various media and social media outlets, said this adds more pressure to the job. “One of the challenges for me is to figure out how much outward facing I do. That’s hard when you’re navigating working and living through a pandemic. This is something I do because I enjoy doing it. But it’s still a type of work. And it’s certainly increased because the media has been paying more attention to mental health” since the pandemic started, she added.
 

The dual stress of COVID and social justice

Some women psychiatrists of color are dealing with social justice issues on top of other COVID stressors, Dr. De Faria said. The focus on addressing institutionalized racism means that minority women are taking on extra work to advocate for their peers.

Michelle Jacobs-Elliott, MD, of the department of psychiatry and assistant dean of the Office of Diversity and Health Equity at the University of Florida, Gainesville, knows of such responsibilities. “I have been in many discussions either with my coworkers in my department or others who work for the University of Florida” on systemic racism, she said in an interview.

Dr. Jacobs-Elliott became a trainer for Bias Reduction in Internal Medicine, a workshop aimed at reducing bias, and prior to 2020 participated in a social justice summit at the University of Florida. “Talking with my medical as well as undergraduate students about their experiences both here in Gainesville and elsewhere, they are all feeling the hurt, disappointment, and disbelief that we are still fighting battles that our grandparents fought in health care, housing, and employment. This adds an extra layer of stress to everyone’s life.”

The tense social climate has made the apparent racial inequalities in COVID-19 deaths and severity of disease hard to ignore, Dr. Bell noted. “It is my sincere hope that the availability of COVID-19 vaccines will help decrease the number of people affected by this horrible disease. The added burden of racism on top of the stressors of this pandemic can feel insurmountable. I hope 2021 will provide a way forward for us all.”
 

Taking time for self-care

Amid the endless referrals and increasing demands at home, women psychiatrists often don’t have the time to do normal activities, Dr. Meltzer-Brody observed. Like most people, COVID restrictions prevent them from traveling or going to the gym or restaurants. Dr. De Faria has not been able to visit family in Latin America, a trip she used to make twice a year. “That was once my de-stress time. But now, I can’t connect with my roots. My father is elderly and very much at risk.”

This is the time to get creative and resourceful – to make time for self-care, several sources said.

“We need to realize that we cannot be all things to all people, at the same time,” noted Dr. Bell. It’s important to prioritize what’s most important – and keep assessing your priorities. There’s no shame in tending to your own needs. Dr. Bell recommended that women in her profession should pick 1 day a week, put it in their calendar, and stick to this goal of self-care.

“Even if it’s only 15 minutes, it is important to put time aside. Some quick, cheap ideas are to do a quick meditation session, read a chapter in a book, listen to an audiobook, journal, go for a walk and get fresh air. Eat a healthy meal. Even 10 minutes helps,” she urged.

COVID-19 has pushed society to find new ways to do things, Dr. Bell continued. Women psychiatrists, in assessing their work-life balance, may need to reassess their goals. Consider work schedules and see if there’s a place to scale back a task. Delegate tasks at home to family members, if necessary. Most importantly, exercise self-compassion, she stressed. “During this pandemic, I believe it is vital to keep our cups filled so we can pour into others.”

Dr. Lakshmin said she has benefited greatly from having a therapist during the pandemic. “It has been so instrumental in forcing me to take that time for myself, to give me a space to take care of me, and remember it’s okay to take care of me. It’s so important for us as psychiatrists to have that for ourselves. It’s not just for our patients – we need it, too.”

The APA has resources and numerous support groups that meet regularly to address and discuss the stressors of the pandemic. Its College Mental Health Caucus, for example, holds a monthly, hour-long Zoom meeting. Not surprisingly, women comprise the majority of attendees, Dr. De Faria said. “Most women in academic psychiatry are working from home and using telehealth, which isolates people a lot.” Maureen Sayres Van Niel, MD, who is head of the APA’s Women’s Caucus, sends out a regular newsletter that advises on self-care. Women psychiatrists should also contact their local psychiatric organizations to get support from their professional peers.

Sometimes it’s wise to leave work behind and engage with friends. Dr. De Faria regularly Zooms with a group of friends outside of her profession to de-stress and reconnect. “At least I can talk to them about things other than psychiatry.”

Mentally and physically exhausted, Dr. Jacobs-Elliott said she looks forward to the day when society can return to meeting with friends and family “without being afraid that we are an asymptomatic carrier who is infecting our loved ones.”

Daily life is now a juggling act for Misty Richards, MD, MS. As the program director of a rigorous child psychiatry fellowship, a psychiatrist caring for women with perinatal psychiatric disorders, and the mother of three young children, Dr. Richards tries to view these tasks as an opportunity for growth. But some days it feels as if she’s navigating a storm in the middle of the ocean without a life jacket.

In the age of COVID, “the wave of demands has morphed into one giant tidal wave of desperate need,” Dr. Richards, of the department of psychiatry & biobehavioral sciences, University of California, Los Angeles, Semel Institute of Neuroscience & Human Behavior, said in an interview. “The painfully loud and clear message is that our patients need us, and our children – who have been stripped from healthy routines and peer interactions that nourish social-emotional development – rely on us. We cannot turn our backs for even a moment, or else they will suffer.”

Tasked with caring for a much sicker and distressed population, navigating home duties such as child care, online school, and taking care of certain family members, women psychiatrists are feeling the impact of COVID-19.

Many have seamlessly transferred their practices online, maintaining a lifeline with their patients through telehealth visits. Even with this convenience, the emotional labor of being a psychiatrist is still very stressful, Pooja Lakshmin, MD, of the department of psychiatry and behavioral sciences at George Washington University, Washington, said in an interview. Because the nature of work has changed, and many are doing things virtually at home, separating home from work life can be a challenge. “It’s harder to disconnect,” admitted Dr. Lakshmin. “Even my patients tell me that they have no time to themselves anymore.”

The pandemic demands that women in the profession “white-knuckle” their way to the finish line – a moving target that remains nowhere in sight, Dr. Richards said. “In this process, we are expected to fill the emotional cups of a broken nation, to provide answers that do not exist, and to do so with never-ending gratitude for a demanding system that has no ‘off’ switch,” she noted.
 

‘In two places at once’

COVID-19’s physical and emotional toll has swept across the various subspecialties of clinical psychiatry. As some navigate outpatient/telehealth work, inpatient psychiatrists directly interact with COVID patients.

“Our inpatient psychiatry unit regularly takes care of COVID patients, including perinatal patients who are COVID positive,” Samantha Meltzer-Brody, MD, MPH, distinguished professor and chair, University of North Carolina, Chapel Hill, department of psychiatry and director of medical school’s Center for Women’s Mood Disorders, said in an interview. A psychiatry consultation-liaison service also provides psychiatry care to medical and surgical patients, including medically ill COVID patients across the hospital.

“We are on the front lines in the sense that we are dealing with the trauma of the general population and having to be present for that emotional distress,” Dr. Meltzer-Brody said.

The struggle to balance rising caseloads and home responsibilities makes things difficult, she continued. “There’s a never-ending onslaught of patient referrals,” reflecting the anxiety and depression issues people are experiencing in the wake of a global pandemic, frenetic political situation in the United States, and job uncertainty.

Child care and elder care responsibilities affect both men and women, yet research shows that caregiving demands disproportionately affect women, observed Dr. Meltzer-Brody.

Overall, the stress of caregiving and parenting responsibilities for men and women has been markedly higher during the pandemic. Most clinical psychiatrists “have been extraordinarily busy for a very long time,” she added.

Tiffani L. Bell, MD, a psychiatrist in Winston-Salem, N.C., has seen an increase in anxiety and depression in people with no previous history of diagnosed mental illness. “The impact of the pandemic has truly been multifaceted. People are struggling with loss of jobs, loss of wages, and loss of loved ones, along with grieving the loss of the usual way of life,” she said in an interview.

Many of her colleagues report feeling overburdened at work with increased admissions and patient loads, decreased time to see each patient, and the feeling of “needing to be in two places at once.”

“As a female psychiatrist, I do believe that we can sometimes have an increased mental burden due to the emotional and physical burnout that can occur when our routines are shaken,” added Dr. Bell, who specializes in adult, child, and adolescent psychiatry, and obesity and lifestyle medicine. Even in the early months of the pandemic, Dr. Bell said she heard people joke that “they don’t know if they are working from home or living at work.”

Physicians aren’t the only ones who are overwhelmed. “We’re also hearing stories from our patients – those at risk for partner violence, dealing with kids out of school, working full time while providing support at home,” Ludmila De Faria, MD, chair of the American Psychiatric Association’s Committee on Women’s Mental Health, said in an interview.

American mothers in particular spend nearly twice as much time caring for their children and cooking than their spouses, said Dr. Bell, citing recent studies. “Even if one is not a mom, if you couple the increased housework at baseline with the added responsibilities of working as a front-line physician and/or working from home while managing a household, it can lead to increased stress for all involved.”
 

Women leaving the workforce

Nationally, a growing number of women are either reducing their hours or leaving the workforce in response to the pandemic. Fidelity Investments, which surveyed 1,902 U.S. adults in mid-2020 projected that 4 in 10 women were mulling such options. Among 951 women surveyed, 42% were considering stepping back from their jobs because of their children’s homeschooling needs, and 27% cited difficulties of balancing home and job responsibilities.

Interruptions caused by child care affect women more than men, according to a report from the Century Foundation and the Center for American Progress. “Study after study has shown that, in response to school, child care, and camp closings, as well as reduced hours and reduced class sizes, significantly more women than men have reduced their work hours, left work to care for children, and spent more time on education and household tasks,” the authors noted.

They estimated that the American economy could incur $64.5 billion per year in lost wages and economic activity from the fallout of these trends. In September 2020, four times as many women as men left the workforce, nearly 865,000 women in comparison to 216,000 men.

Many women psychiatrists have been forced to choose between their careers or child care duties – decisions they don’t want to make, but that may be necessary during these unprecedented circumstances. They may be reducing their work hours to assist at home. Others are leaving their jobs, “a terrible situation given the enormous mental health needs of the pandemic” and the fact that so many areas of the United States already suffer from a shortage of clinical psychiatrists, said Dr. Meltzer-Brody.

She has personally seen the effects of this in the large academic department she supervises. “I’m seeing women reducing their work hours or leave positions,” she continued. In addition to child care needs, these women are tending to aging parents affected by COVID-19 or other illnesses, or dealing with the fact that options for elder care aren’t available.

“I have multiple faculty contending with that situation,” added Dr. Meltzer-Brody. As a result, productivity is going down. “These women are trying to keep all of the balls in the air but find they can’t.”

Dr. Richards believes some changes are in order to take the disproportionate burden off of women in psychiatry, and the workforce as a whole. The health care system “places too much pressure on individuals to compensate for its deficiencies. Those individuals who often step up to the plate are women, and this is not their sole burden to carry.”

A move toward telehealth in clinical psychiatry has made it possible for patients and physicians to meet virtually in their respective homes and discuss treatment options. “Even while this is both a blessing and privilege, it comes with the unique challenges of having to manage Zoom calls, child care, meals, distance learning, cleaning, and work responsibilities, while previously there was a clearer delineation to the day for many,” Dr. Bell said.

Clinical psychiatrists educating the public about the mental stressors of COVID-19 face their own unique challenges.

Dr. Lakshmin, who makes appearances in various media and social media outlets, said this adds more pressure to the job. “One of the challenges for me is to figure out how much outward facing I do. That’s hard when you’re navigating working and living through a pandemic. This is something I do because I enjoy doing it. But it’s still a type of work. And it’s certainly increased because the media has been paying more attention to mental health” since the pandemic started, she added.
 

The dual stress of COVID and social justice

Some women psychiatrists of color are dealing with social justice issues on top of other COVID stressors, Dr. De Faria said. The focus on addressing institutionalized racism means that minority women are taking on extra work to advocate for their peers.

Michelle Jacobs-Elliott, MD, of the department of psychiatry and assistant dean of the Office of Diversity and Health Equity at the University of Florida, Gainesville, knows of such responsibilities. “I have been in many discussions either with my coworkers in my department or others who work for the University of Florida” on systemic racism, she said in an interview.

Dr. Jacobs-Elliott became a trainer for Bias Reduction in Internal Medicine, a workshop aimed at reducing bias, and prior to 2020 participated in a social justice summit at the University of Florida. “Talking with my medical as well as undergraduate students about their experiences both here in Gainesville and elsewhere, they are all feeling the hurt, disappointment, and disbelief that we are still fighting battles that our grandparents fought in health care, housing, and employment. This adds an extra layer of stress to everyone’s life.”

The tense social climate has made the apparent racial inequalities in COVID-19 deaths and severity of disease hard to ignore, Dr. Bell noted. “It is my sincere hope that the availability of COVID-19 vaccines will help decrease the number of people affected by this horrible disease. The added burden of racism on top of the stressors of this pandemic can feel insurmountable. I hope 2021 will provide a way forward for us all.”
 

Taking time for self-care

Amid the endless referrals and increasing demands at home, women psychiatrists often don’t have the time to do normal activities, Dr. Meltzer-Brody observed. Like most people, COVID restrictions prevent them from traveling or going to the gym or restaurants. Dr. De Faria has not been able to visit family in Latin America, a trip she used to make twice a year. “That was once my de-stress time. But now, I can’t connect with my roots. My father is elderly and very much at risk.”

This is the time to get creative and resourceful – to make time for self-care, several sources said.

“We need to realize that we cannot be all things to all people, at the same time,” noted Dr. Bell. It’s important to prioritize what’s most important – and keep assessing your priorities. There’s no shame in tending to your own needs. Dr. Bell recommended that women in her profession should pick 1 day a week, put it in their calendar, and stick to this goal of self-care.

“Even if it’s only 15 minutes, it is important to put time aside. Some quick, cheap ideas are to do a quick meditation session, read a chapter in a book, listen to an audiobook, journal, go for a walk and get fresh air. Eat a healthy meal. Even 10 minutes helps,” she urged.

COVID-19 has pushed society to find new ways to do things, Dr. Bell continued. Women psychiatrists, in assessing their work-life balance, may need to reassess their goals. Consider work schedules and see if there’s a place to scale back a task. Delegate tasks at home to family members, if necessary. Most importantly, exercise self-compassion, she stressed. “During this pandemic, I believe it is vital to keep our cups filled so we can pour into others.”

Dr. Lakshmin said she has benefited greatly from having a therapist during the pandemic. “It has been so instrumental in forcing me to take that time for myself, to give me a space to take care of me, and remember it’s okay to take care of me. It’s so important for us as psychiatrists to have that for ourselves. It’s not just for our patients – we need it, too.”

The APA has resources and numerous support groups that meet regularly to address and discuss the stressors of the pandemic. Its College Mental Health Caucus, for example, holds a monthly, hour-long Zoom meeting. Not surprisingly, women comprise the majority of attendees, Dr. De Faria said. “Most women in academic psychiatry are working from home and using telehealth, which isolates people a lot.” Maureen Sayres Van Niel, MD, who is head of the APA’s Women’s Caucus, sends out a regular newsletter that advises on self-care. Women psychiatrists should also contact their local psychiatric organizations to get support from their professional peers.

Sometimes it’s wise to leave work behind and engage with friends. Dr. De Faria regularly Zooms with a group of friends outside of her profession to de-stress and reconnect. “At least I can talk to them about things other than psychiatry.”

Mentally and physically exhausted, Dr. Jacobs-Elliott said she looks forward to the day when society can return to meeting with friends and family “without being afraid that we are an asymptomatic carrier who is infecting our loved ones.”

Oxidative stress may account for the “lipid paradox,” a higher incidence of heart disease burden found in nonobese rheumatoid arthritis (RA) patients with lower levels of low-density lipoprotein (LDL). George Karpouzas, MD, an investigator at the Lundquist Institute of Biomedical Innovation, St, Torrance, Calif., discussed this exploratory finding at the virtual annual meeting of the American College of Rheumatology.

A complex dynamic exists between traditional risk factors and cardiovascular (CV) events in RA patients, said Dr. Karpouzas, professor of medicine at the University of California, Los Angeles, and chief of the division of rheumatology, Harbor-UCLA Medical Center. “Lower lipid levels, specifically total cholesterol and to a lesser extent LDL, may be associated with higher risk,” he said. One recent study found that coronary artery calcium (CAC) scores were four times higher in RA patients with lower LDL concentrations (> 70 mg/dL) than those in control groups. “This was especially true in patients who were nonobese, non-Hispanic Whites and never smokers,” said Dr. Karpouzas. Other studies have reported this association between low LDL and increased CVD risk.

These paradoxes led to several questions: Does obesity modify the effect of LDL on cardiovascular disease (CVD) risk in RA and does it moderate the effect of LDL on coronary plaque burden and progression? Do LDL particle composition and oxidation variations underlie the paradoxical association of low LDL with higher coronary atherosclerosis burden in RA? To find answers, Dr. Karpouzas’ team in the Prospective Evaluation of Latent Coronary Atherosclerosis in Rheumatoid Arthritis (PROTECT-RA) trial studied a cohort of 150 established RA patients without symptoms or diagnosis of CV disease.

Dr. Karpouzas presented two oral abstracts that summarized this research during the ACR 2020 session, “RA, diagnosis, manifestations and outcomes: heart of the matter,” which was held virtually.
 

Higher plaque burden seen in nonobese patients

In one part of the study, patients underwent baseline cardiac coronary CT angiography (CTA) over 1 year (2010-2011). Investigators evaluated CAC scores, segment involvement scores (SIS), segment stenosis scores (SSS), and extensive and obstructive disease. Low LDL was defined as < 70 mg/dL, obesity as a waist to height ratio of > 0.58 squared.

Investigators in follow-up work (2017-2018) evaluated for plaque progression, prospectively recording all cardiovascular disease events such as cardiac death, myocardial infarction, unstable angina, stroke, and heart failure hospitalization. Multivariable models assessed the effects of LDL lower than 70 mg/dL, obesity, and their interaction, accounting for factors such as age, sex, statin use, diabetes and hypertension.
 

Four LDL obesity cohorts

Nonobese RA patients with low LDL exhibited the highest plaque burden. “Despite no differences in RA inflammation, patients in this group were more likely to exhibit high levels of LDL oxidation,” Dr. Karpouzas said in an interview. “Nonobese patients with low LDL more likely exhibited new coronary plaque formation as well as increased stenotic severity of prevalent plaque after adjustments for relevant covariates,” he added.

The study’s observational nature exposed it to biases and unmeasured confounding, Dr. Karpouzas emphasized. Because it took place in a single center, the results might not be generalizable to ethnically and racially diverse cohorts. Patients with calcifications, extensive or obstructive coronary plaque at baseline scan received more aggressive treatments, which could have slowed CVD event risk and plaque progression. Investigators cautioned that the results should be seen as “exploratory,” given that CVD event analysis wasn’t applied to the original study design.
 

The oxidation-LDL connection

Another arm of the study examined the oxidation association question. Investigators did a similar analysis of the same patients but also evaluated for cholesterol content, Lp(a) mass, OxLDL levels, IgG and IgM anti-OxLDL and apoB100 immune complexes and proinflammatory cytokines.

RA patients with LDL lower than 70 mg/dL had higher SSS and CAC scores and were more likely to have extensive or obstructive plaque. Statin-naive patients with lower LDL exhibited greater LDL oxidation than higher LDL groups. In addition, those with lower LDL had higher anti-OxLDL and apoB100 than patients with higher LDL.

“Oxidation makes the cholesterol more ‘sticky,’ allowing it to penetrate into the walls of the endothelium, and changes macrophages to foam cells. This malignant process is very powerful and can potentially increase atheroma burden,” study coauthor Matthew Budoff, MD, professor of medicine at UCLA and endowed chair of preventive cardiology at the Lundquist Institute, said in an interview.

Investigators also found an independent association between Lp(a) content and LDL oxidation. This association seemed strong in patients with lower LDL compared to higher LDL groups. In addition, “greater oxidation and immune recognition of oxLDL further associated with higher IL-6 elaboration which may in turn augment atherosclerosis burden in the low LDL group,” said Dr. Karpouzas.

The analysis did not explore alternate mechanisms such as increased cholesterol loading capacity, lower efflux capacity or increased hepatocyte uptake through LDL-R upregulation, a key limitation. Dr. Karpouzas also acknowledged that higher cumulative inflammatory burden incurred before evaluating low LDL patients at baseline may have led to greater coronary plaque burden.

Overall, the study shows that low LDL is not protective in this population, said Dr. Budoff. “Low LDL patients who have atherosclerosis should be treated with statins and other therapies to lower their CV risk.”
 

Larger studies to confirm associations

Attendees of the ACR 2020 session called for additional studies to confirm that LDL oxidation leads to increased coronary atherosclerotic burden in RA patients.

The study provides “mechanistic insight into this important problem for patients with RA,” noted Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine at Harvard Medical School and associate physician at Brigham and Women’s Hospital, Boston.

Some of the patients studied were on lipid-lowering drugs such as statins, though the statistical analysis adjusted for use of these medications, noted Dr. Sparks. “It is possible that excess systemic inflammation alone is responsible for changes in LDL oxidation that may ultimately lead to cardiovascular disease,” he offered.

Future mechanistic and interventional studies related specifically to LDL oxidation “should establish the importance of this pathway in the development of cardiovascular disease in patients with RA,” said Dr. Sparks.

Large studies of patients with different BMI and LDL values followed prospectively for CV events would be ideal, said Joel M. Kremer, MD, president of the Corrona Research Foundation and founder of Corrona, a biopharma data solutions firm. Investigators would need to follow patients for several years. And, such a venture might face some obstacles. “The practical impediments and cost would be substantial. Also, as LDL oxidation may be related to disease activity, there would be ethical and pragmatic issues associated with controlling disease activity in these patients. This would obscure these outcomes of interest,” said Dr. Kremer.

Dr. Karpouzas receives grant and research support from the American Heart Association and Pfizer-Aspire. Dr. Budoff receives grant support from General Electric.

[email protected]

SOURCE: Karpouzas G et al. ACR 2020. Abstract 0485 and Abstract 0486.

Oxidative stress may account for the “lipid paradox,” a higher incidence of heart disease burden found in nonobese rheumatoid arthritis (RA) patients with lower levels of low-density lipoprotein (LDL). George Karpouzas, MD, an investigator at the Lundquist Institute of Biomedical Innovation, St, Torrance, Calif., discussed this exploratory finding at the virtual annual meeting of the American College of Rheumatology.

A complex dynamic exists between traditional risk factors and cardiovascular (CV) events in RA patients, said Dr. Karpouzas, professor of medicine at the University of California, Los Angeles, and chief of the division of rheumatology, Harbor-UCLA Medical Center. “Lower lipid levels, specifically total cholesterol and to a lesser extent LDL, may be associated with higher risk,” he said. One recent study found that coronary artery calcium (CAC) scores were four times higher in RA patients with lower LDL concentrations (> 70 mg/dL) than those in control groups. “This was especially true in patients who were nonobese, non-Hispanic Whites and never smokers,” said Dr. Karpouzas. Other studies have reported this association between low LDL and increased CVD risk.

These paradoxes led to several questions: Does obesity modify the effect of LDL on cardiovascular disease (CVD) risk in RA and does it moderate the effect of LDL on coronary plaque burden and progression? Do LDL particle composition and oxidation variations underlie the paradoxical association of low LDL with higher coronary atherosclerosis burden in RA? To find answers, Dr. Karpouzas’ team in the Prospective Evaluation of Latent Coronary Atherosclerosis in Rheumatoid Arthritis (PROTECT-RA) trial studied a cohort of 150 established RA patients without symptoms or diagnosis of CV disease.

Dr. Karpouzas presented two oral abstracts that summarized this research during the ACR 2020 session, “RA, diagnosis, manifestations and outcomes: heart of the matter,” which was held virtually.
 

Higher plaque burden seen in nonobese patients

In one part of the study, patients underwent baseline cardiac coronary CT angiography (CTA) over 1 year (2010-2011). Investigators evaluated CAC scores, segment involvement scores (SIS), segment stenosis scores (SSS), and extensive and obstructive disease. Low LDL was defined as < 70 mg/dL, obesity as a waist to height ratio of > 0.58 squared.

Investigators in follow-up work (2017-2018) evaluated for plaque progression, prospectively recording all cardiovascular disease events such as cardiac death, myocardial infarction, unstable angina, stroke, and heart failure hospitalization. Multivariable models assessed the effects of LDL lower than 70 mg/dL, obesity, and their interaction, accounting for factors such as age, sex, statin use, diabetes and hypertension.
 

Four LDL obesity cohorts

Nonobese RA patients with low LDL exhibited the highest plaque burden. “Despite no differences in RA inflammation, patients in this group were more likely to exhibit high levels of LDL oxidation,” Dr. Karpouzas said in an interview. “Nonobese patients with low LDL more likely exhibited new coronary plaque formation as well as increased stenotic severity of prevalent plaque after adjustments for relevant covariates,” he added.

The study’s observational nature exposed it to biases and unmeasured confounding, Dr. Karpouzas emphasized. Because it took place in a single center, the results might not be generalizable to ethnically and racially diverse cohorts. Patients with calcifications, extensive or obstructive coronary plaque at baseline scan received more aggressive treatments, which could have slowed CVD event risk and plaque progression. Investigators cautioned that the results should be seen as “exploratory,” given that CVD event analysis wasn’t applied to the original study design.
 

The oxidation-LDL connection

Another arm of the study examined the oxidation association question. Investigators did a similar analysis of the same patients but also evaluated for cholesterol content, Lp(a) mass, OxLDL levels, IgG and IgM anti-OxLDL and apoB100 immune complexes and proinflammatory cytokines.

RA patients with LDL lower than 70 mg/dL had higher SSS and CAC scores and were more likely to have extensive or obstructive plaque. Statin-naive patients with lower LDL exhibited greater LDL oxidation than higher LDL groups. In addition, those with lower LDL had higher anti-OxLDL and apoB100 than patients with higher LDL.

“Oxidation makes the cholesterol more ‘sticky,’ allowing it to penetrate into the walls of the endothelium, and changes macrophages to foam cells. This malignant process is very powerful and can potentially increase atheroma burden,” study coauthor Matthew Budoff, MD, professor of medicine at UCLA and endowed chair of preventive cardiology at the Lundquist Institute, said in an interview.

Investigators also found an independent association between Lp(a) content and LDL oxidation. This association seemed strong in patients with lower LDL compared to higher LDL groups. In addition, “greater oxidation and immune recognition of oxLDL further associated with higher IL-6 elaboration which may in turn augment atherosclerosis burden in the low LDL group,” said Dr. Karpouzas.

The analysis did not explore alternate mechanisms such as increased cholesterol loading capacity, lower efflux capacity or increased hepatocyte uptake through LDL-R upregulation, a key limitation. Dr. Karpouzas also acknowledged that higher cumulative inflammatory burden incurred before evaluating low LDL patients at baseline may have led to greater coronary plaque burden.

Overall, the study shows that low LDL is not protective in this population, said Dr. Budoff. “Low LDL patients who have atherosclerosis should be treated with statins and other therapies to lower their CV risk.”
 

Larger studies to confirm associations

Attendees of the ACR 2020 session called for additional studies to confirm that LDL oxidation leads to increased coronary atherosclerotic burden in RA patients.

The study provides “mechanistic insight into this important problem for patients with RA,” noted Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine at Harvard Medical School and associate physician at Brigham and Women’s Hospital, Boston.

Some of the patients studied were on lipid-lowering drugs such as statins, though the statistical analysis adjusted for use of these medications, noted Dr. Sparks. “It is possible that excess systemic inflammation alone is responsible for changes in LDL oxidation that may ultimately lead to cardiovascular disease,” he offered.

Future mechanistic and interventional studies related specifically to LDL oxidation “should establish the importance of this pathway in the development of cardiovascular disease in patients with RA,” said Dr. Sparks.

Large studies of patients with different BMI and LDL values followed prospectively for CV events would be ideal, said Joel M. Kremer, MD, president of the Corrona Research Foundation and founder of Corrona, a biopharma data solutions firm. Investigators would need to follow patients for several years. And, such a venture might face some obstacles. “The practical impediments and cost would be substantial. Also, as LDL oxidation may be related to disease activity, there would be ethical and pragmatic issues associated with controlling disease activity in these patients. This would obscure these outcomes of interest,” said Dr. Kremer.

Dr. Karpouzas receives grant and research support from the American Heart Association and Pfizer-Aspire. Dr. Budoff receives grant support from General Electric.

[email protected]

SOURCE: Karpouzas G et al. ACR 2020. Abstract 0485 and Abstract 0486.

Oxidative stress may account for the “lipid paradox,” a higher incidence of heart disease burden found in nonobese rheumatoid arthritis (RA) patients with lower levels of low-density lipoprotein (LDL). George Karpouzas, MD, an investigator at the Lundquist Institute of Biomedical Innovation, St, Torrance, Calif., discussed this exploratory finding at the virtual annual meeting of the American College of Rheumatology.

A complex dynamic exists between traditional risk factors and cardiovascular (CV) events in RA patients, said Dr. Karpouzas, professor of medicine at the University of California, Los Angeles, and chief of the division of rheumatology, Harbor-UCLA Medical Center. “Lower lipid levels, specifically total cholesterol and to a lesser extent LDL, may be associated with higher risk,” he said. One recent study found that coronary artery calcium (CAC) scores were four times higher in RA patients with lower LDL concentrations (> 70 mg/dL) than those in control groups. “This was especially true in patients who were nonobese, non-Hispanic Whites and never smokers,” said Dr. Karpouzas. Other studies have reported this association between low LDL and increased CVD risk.

These paradoxes led to several questions: Does obesity modify the effect of LDL on cardiovascular disease (CVD) risk in RA and does it moderate the effect of LDL on coronary plaque burden and progression? Do LDL particle composition and oxidation variations underlie the paradoxical association of low LDL with higher coronary atherosclerosis burden in RA? To find answers, Dr. Karpouzas’ team in the Prospective Evaluation of Latent Coronary Atherosclerosis in Rheumatoid Arthritis (PROTECT-RA) trial studied a cohort of 150 established RA patients without symptoms or diagnosis of CV disease.

Dr. Karpouzas presented two oral abstracts that summarized this research during the ACR 2020 session, “RA, diagnosis, manifestations and outcomes: heart of the matter,” which was held virtually.
 

Higher plaque burden seen in nonobese patients

In one part of the study, patients underwent baseline cardiac coronary CT angiography (CTA) over 1 year (2010-2011). Investigators evaluated CAC scores, segment involvement scores (SIS), segment stenosis scores (SSS), and extensive and obstructive disease. Low LDL was defined as < 70 mg/dL, obesity as a waist to height ratio of > 0.58 squared.

Investigators in follow-up work (2017-2018) evaluated for plaque progression, prospectively recording all cardiovascular disease events such as cardiac death, myocardial infarction, unstable angina, stroke, and heart failure hospitalization. Multivariable models assessed the effects of LDL lower than 70 mg/dL, obesity, and their interaction, accounting for factors such as age, sex, statin use, diabetes and hypertension.
 

Four LDL obesity cohorts

Nonobese RA patients with low LDL exhibited the highest plaque burden. “Despite no differences in RA inflammation, patients in this group were more likely to exhibit high levels of LDL oxidation,” Dr. Karpouzas said in an interview. “Nonobese patients with low LDL more likely exhibited new coronary plaque formation as well as increased stenotic severity of prevalent plaque after adjustments for relevant covariates,” he added.

The study’s observational nature exposed it to biases and unmeasured confounding, Dr. Karpouzas emphasized. Because it took place in a single center, the results might not be generalizable to ethnically and racially diverse cohorts. Patients with calcifications, extensive or obstructive coronary plaque at baseline scan received more aggressive treatments, which could have slowed CVD event risk and plaque progression. Investigators cautioned that the results should be seen as “exploratory,” given that CVD event analysis wasn’t applied to the original study design.
 

The oxidation-LDL connection

Another arm of the study examined the oxidation association question. Investigators did a similar analysis of the same patients but also evaluated for cholesterol content, Lp(a) mass, OxLDL levels, IgG and IgM anti-OxLDL and apoB100 immune complexes and proinflammatory cytokines.

RA patients with LDL lower than 70 mg/dL had higher SSS and CAC scores and were more likely to have extensive or obstructive plaque. Statin-naive patients with lower LDL exhibited greater LDL oxidation than higher LDL groups. In addition, those with lower LDL had higher anti-OxLDL and apoB100 than patients with higher LDL.

“Oxidation makes the cholesterol more ‘sticky,’ allowing it to penetrate into the walls of the endothelium, and changes macrophages to foam cells. This malignant process is very powerful and can potentially increase atheroma burden,” study coauthor Matthew Budoff, MD, professor of medicine at UCLA and endowed chair of preventive cardiology at the Lundquist Institute, said in an interview.

Investigators also found an independent association between Lp(a) content and LDL oxidation. This association seemed strong in patients with lower LDL compared to higher LDL groups. In addition, “greater oxidation and immune recognition of oxLDL further associated with higher IL-6 elaboration which may in turn augment atherosclerosis burden in the low LDL group,” said Dr. Karpouzas.

The analysis did not explore alternate mechanisms such as increased cholesterol loading capacity, lower efflux capacity or increased hepatocyte uptake through LDL-R upregulation, a key limitation. Dr. Karpouzas also acknowledged that higher cumulative inflammatory burden incurred before evaluating low LDL patients at baseline may have led to greater coronary plaque burden.

Overall, the study shows that low LDL is not protective in this population, said Dr. Budoff. “Low LDL patients who have atherosclerosis should be treated with statins and other therapies to lower their CV risk.”
 

Larger studies to confirm associations

Attendees of the ACR 2020 session called for additional studies to confirm that LDL oxidation leads to increased coronary atherosclerotic burden in RA patients.

The study provides “mechanistic insight into this important problem for patients with RA,” noted Jeffrey A. Sparks, MD, MMSc, assistant professor of medicine at Harvard Medical School and associate physician at Brigham and Women’s Hospital, Boston.

Some of the patients studied were on lipid-lowering drugs such as statins, though the statistical analysis adjusted for use of these medications, noted Dr. Sparks. “It is possible that excess systemic inflammation alone is responsible for changes in LDL oxidation that may ultimately lead to cardiovascular disease,” he offered.

Future mechanistic and interventional studies related specifically to LDL oxidation “should establish the importance of this pathway in the development of cardiovascular disease in patients with RA,” said Dr. Sparks.

Large studies of patients with different BMI and LDL values followed prospectively for CV events would be ideal, said Joel M. Kremer, MD, president of the Corrona Research Foundation and founder of Corrona, a biopharma data solutions firm. Investigators would need to follow patients for several years. And, such a venture might face some obstacles. “The practical impediments and cost would be substantial. Also, as LDL oxidation may be related to disease activity, there would be ethical and pragmatic issues associated with controlling disease activity in these patients. This would obscure these outcomes of interest,” said Dr. Kremer.

Dr. Karpouzas receives grant and research support from the American Heart Association and Pfizer-Aspire. Dr. Budoff receives grant support from General Electric.

[email protected]

SOURCE: Karpouzas G et al. ACR 2020. Abstract 0485 and Abstract 0486.

New clinical practice guidelines on Lyme disease place a strong emphasis on antibody testing to assess for rheumatologic and neurologic syndromes. “Diagnostically, we recommend testing via antibodies, and an index of antibodies in cerebrospinal fluid [CSF] versus serum. Importantly, we recommend against using polymerase chain reaction [PCR] in CSF,” Jeffrey A. Rumbaugh, MD, PhD, a coauthor of the guidelines and a member of the American Academy of Neurology, said in an interview.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

The Infectious Diseases Society of America, AAN, and the American College of Rheumatology convened a multidisciplinary panel to develop the 43 recommendations, seeking input from 12 additional medical specialties, and patients. The panel conducted a systematic review of available evidence on preventing, diagnosing, and treating Lyme disease, using the Grading of Recommendations Assessment, Development and Evaluation model to evaluate clinical evidence and strength of recommendations. The guidelines were simultaneous published in Clinical Infectious Diseases, Neurology, Arthritis & Rheumatology, and Arthritis Care & Research.

This is the first time these organizations have collaborated on joint Lyme disease guidelines, which focus mainly on neurologic, cardiac, and rheumatologic manifestations.

“We are very excited to provide these updated guidelines to assist clinicians working in numerous medical specialties around the country, and even the world, as they care for patients suffering from Lyme disease,” Dr. Rumbaugh said.
 

When to use and not to use PCR

Guideline authors called for specific testing regimens depending on presentation of symptoms. Generally, they advised that individuals with a skin rash suggestive of early disease seek a clinical diagnosis instead of laboratory testing.

Recommendations on Lyme arthritis support previous IDSA guidelines published in 2006, Linda K. Bockenstedt, MD, professor of medicine at Yale University, New Haven, Conn., and a coauthor of the guidelines, said in an interview.

To evaluate for potential Lyme arthritis, clinicians should choose serum antibody testing over PCR or culture of blood or synovial fluid/tissue. However, if a doctor is assessing a seropositive patient for Lyme arthritis diagnosis but needs more information for treatment decisions, the authors recommended PCR applied to synovial fluid or tissue over Borrelia culture.

“Synovial fluid can be analyzed by PCR, but sensitivity is generally lower than serology,” Dr. Bockenstedt explained. Additionally, culture of joint fluid or synovial tissue for Lyme spirochetes has 0% sensitivity in multiple studies. “For these reasons, we recommend serum antibody testing over PCR of joint fluid or other methods for an initial diagnosis.”

Serum antibody testing over PCR or culture is also recommended for identifying Lyme neuroborreliosis in the peripheral nervous system (PNS) or CNS.

Despite the recent popularity of Lyme PCR testing in hospitals and labs, “with Lyme at least, antibodies are better in the CSF,” Dr. Rumbaugh said. Studies have shown that “most patients with even early neurologic Lyme disease are seropositive by conventional antibody testing at time of initial clinical presentation, and that intrathecal antibody production, as demonstrated by an elevated CSF:serum index, is highly specific for CNS involvement.”

If done correctly, antibody testing is both sensitive and specific for neurologic Lyme disease. “On the other hand, sensitivity of Lyme PCR performed on CSF has been only in the 5%-17% range in studies. Incidentally, Lyme PCR on blood is also not sensitive and therefore not recommended,” Dr. Rumbaugh said.

Guideline authors recommended testing in patients with the following conditions: acute neurologic disorders such as meningitis, painful radiculoneuritis, mononeuropathy multiplex; evidence of spinal cord or brain inflammation; and acute myocarditis/pericarditis of unknown cause in an appropriate epidemiologic setting.

They did not recommend testing in patients with typical amyotrophic lateral sclerosis; relapsing remitting multiple sclerosis; Parkinson’s disease, dementia, or cognitive decline; new-onset seizures; other neurologic syndromes or those lacking clinical or epidemiologic history that would support a diagnosis of Lyme disease; and patients with chronic cardiomyopathy of unknown cause.

The authors also called for judicious use of electrocardiogram to screen for Lyme carditis, recommending it only in patients signs or symptoms of this condition. However, patients at risk for or showing signs of severe cardiac complications of Lyme disease should be hospitalized and monitored via ECG.

Timelines for antibiotics

Most patients with Lyme disease should receive oral antibiotics, although duration times vary depending on the disease state. “We recommend that prophylactic antibiotic therapy be given to adults and children only within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk,” according to the guideline authors.

Specific antibiotic treatment regimens by condition are as follows: 10-14 days for early-stage disease, 14 days for Lyme carditis, 14-21 days for neurologic Lyme disease, and 28 days for late Lyme arthritis.

“Despite arthritis occurring late in the course of infection, treatment with a 28-day course of oral antibiotic is effective, although the rates of complete resolution of joint swelling can vary,” Dr. Bockenstedt said. Clinicians may consider a second 28-day course of oral antibiotics or a 2- to 4-week course of ceftriaxone in patients with persistent swelling, after an initial course of oral antibiotics.

Citing knowledge gaps, the authors made no recommendation on secondary antibiotic treatment for unresolved Lyme arthritis. Rheumatologists can play an important role in the care of this small subset of patients, Dr. Bockenstedt noted. “Studies of patients with ‘postantibiotic Lyme arthritis’ show that they can be treated successfully with intra-articular steroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, biologic response modifiers, and even synovectomy with successful outcomes.” Some of these therapies also work in cases where first courses of oral and intravenous antibiotics are unsuccessful.

“Antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included one course of IV therapy,” the authors clarified.

For patients with Lyme disease–associated meningitis, cranial neuropathy, radiculoneuropathy, or other PNS manifestations, the authors recommended intravenous ceftriaxone, cefotaxime, penicillin G, or oral doxycycline over other antimicrobials.

“For most neurologic presentations, oral doxycycline is just as effective as appropriate IV antibiotics,” Dr. Rumbaugh said. “The exception is the relatively rare situation where the patient is felt to have parenchymal involvement of brain or spinal cord, in which case the guidelines recommend IV antibiotics over oral antibiotics.” In the studies, there was no statistically significant difference between oral or intravenous regimens in response rate or risk of adverse effects.

Patients with nonspecific symptoms such as fatigue, pain, or cognitive impairment following treatment should not receive additional antibiotic therapy if there’s no evidence of treatment failure or infection. These two markers “would include objective signs of disease activity, such as arthritis, meningitis, or neuropathy,” the guideline authors wrote in comments accompanying the recommendation.

Clinicians caring for patients with symptomatic bradycardia caused by Lyme carditis should consider temporary pacing measures instead of a permanent pacemaker. For patients hospitalized with Lyme carditis, “we suggest initially using IV ceftriaxone over oral antibiotics until there is evidence of clinical improvement, then switching to oral antibiotics to complete treatment,” they advised. Outpatients with this condition should receive oral antibiotics instead of intravenous antibiotics.

Advice on antibodies testing ‘particularly cogent’

For individuals without expertise in these areas, the recommendations are clear and useful, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy), said in an interview.

“As a rheumatologist, I would have appreciated literature references for some of the recommendations but, nevertheless, find these useful. I applaud the care with which the evidence was gathered and the general formatting, which tried to review multiple possible scenarios surrounding Lyme arthritis,” said Dr. Furst, offering a third-party perspective.

The advice on using antibodies tests to make a diagnosis of Lyme arthritis “is particularly cogent and more useful than trying to culture these fastidious organisms,” he added.

The IDSA, AAN, and ACR provided support for the guideline. Dr. Bockenstedt reported receiving research funding from the National Institutes of Health and the Gordon and the Llura Gund Foundation and remuneration from L2 Diagnostics for investigator-initiated NIH-sponsored research. Dr. Rumbaugh had no conflicts of interest to disclose. Dr. Furst reported no conflicts of interest in commenting on these guidelines.

SOURCE: Rumbaugh JA et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1215.

New clinical practice guidelines on Lyme disease place a strong emphasis on antibody testing to assess for rheumatologic and neurologic syndromes. “Diagnostically, we recommend testing via antibodies, and an index of antibodies in cerebrospinal fluid [CSF] versus serum. Importantly, we recommend against using polymerase chain reaction [PCR] in CSF,” Jeffrey A. Rumbaugh, MD, PhD, a coauthor of the guidelines and a member of the American Academy of Neurology, said in an interview.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

The Infectious Diseases Society of America, AAN, and the American College of Rheumatology convened a multidisciplinary panel to develop the 43 recommendations, seeking input from 12 additional medical specialties, and patients. The panel conducted a systematic review of available evidence on preventing, diagnosing, and treating Lyme disease, using the Grading of Recommendations Assessment, Development and Evaluation model to evaluate clinical evidence and strength of recommendations. The guidelines were simultaneous published in Clinical Infectious Diseases, Neurology, Arthritis & Rheumatology, and Arthritis Care & Research.

This is the first time these organizations have collaborated on joint Lyme disease guidelines, which focus mainly on neurologic, cardiac, and rheumatologic manifestations.

“We are very excited to provide these updated guidelines to assist clinicians working in numerous medical specialties around the country, and even the world, as they care for patients suffering from Lyme disease,” Dr. Rumbaugh said.
 

When to use and not to use PCR

Guideline authors called for specific testing regimens depending on presentation of symptoms. Generally, they advised that individuals with a skin rash suggestive of early disease seek a clinical diagnosis instead of laboratory testing.

Recommendations on Lyme arthritis support previous IDSA guidelines published in 2006, Linda K. Bockenstedt, MD, professor of medicine at Yale University, New Haven, Conn., and a coauthor of the guidelines, said in an interview.

To evaluate for potential Lyme arthritis, clinicians should choose serum antibody testing over PCR or culture of blood or synovial fluid/tissue. However, if a doctor is assessing a seropositive patient for Lyme arthritis diagnosis but needs more information for treatment decisions, the authors recommended PCR applied to synovial fluid or tissue over Borrelia culture.

“Synovial fluid can be analyzed by PCR, but sensitivity is generally lower than serology,” Dr. Bockenstedt explained. Additionally, culture of joint fluid or synovial tissue for Lyme spirochetes has 0% sensitivity in multiple studies. “For these reasons, we recommend serum antibody testing over PCR of joint fluid or other methods for an initial diagnosis.”

Serum antibody testing over PCR or culture is also recommended for identifying Lyme neuroborreliosis in the peripheral nervous system (PNS) or CNS.

Despite the recent popularity of Lyme PCR testing in hospitals and labs, “with Lyme at least, antibodies are better in the CSF,” Dr. Rumbaugh said. Studies have shown that “most patients with even early neurologic Lyme disease are seropositive by conventional antibody testing at time of initial clinical presentation, and that intrathecal antibody production, as demonstrated by an elevated CSF:serum index, is highly specific for CNS involvement.”

If done correctly, antibody testing is both sensitive and specific for neurologic Lyme disease. “On the other hand, sensitivity of Lyme PCR performed on CSF has been only in the 5%-17% range in studies. Incidentally, Lyme PCR on blood is also not sensitive and therefore not recommended,” Dr. Rumbaugh said.

Guideline authors recommended testing in patients with the following conditions: acute neurologic disorders such as meningitis, painful radiculoneuritis, mononeuropathy multiplex; evidence of spinal cord or brain inflammation; and acute myocarditis/pericarditis of unknown cause in an appropriate epidemiologic setting.

They did not recommend testing in patients with typical amyotrophic lateral sclerosis; relapsing remitting multiple sclerosis; Parkinson’s disease, dementia, or cognitive decline; new-onset seizures; other neurologic syndromes or those lacking clinical or epidemiologic history that would support a diagnosis of Lyme disease; and patients with chronic cardiomyopathy of unknown cause.

The authors also called for judicious use of electrocardiogram to screen for Lyme carditis, recommending it only in patients signs or symptoms of this condition. However, patients at risk for or showing signs of severe cardiac complications of Lyme disease should be hospitalized and monitored via ECG.

Timelines for antibiotics

Most patients with Lyme disease should receive oral antibiotics, although duration times vary depending on the disease state. “We recommend that prophylactic antibiotic therapy be given to adults and children only within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk,” according to the guideline authors.

Specific antibiotic treatment regimens by condition are as follows: 10-14 days for early-stage disease, 14 days for Lyme carditis, 14-21 days for neurologic Lyme disease, and 28 days for late Lyme arthritis.

“Despite arthritis occurring late in the course of infection, treatment with a 28-day course of oral antibiotic is effective, although the rates of complete resolution of joint swelling can vary,” Dr. Bockenstedt said. Clinicians may consider a second 28-day course of oral antibiotics or a 2- to 4-week course of ceftriaxone in patients with persistent swelling, after an initial course of oral antibiotics.

Citing knowledge gaps, the authors made no recommendation on secondary antibiotic treatment for unresolved Lyme arthritis. Rheumatologists can play an important role in the care of this small subset of patients, Dr. Bockenstedt noted. “Studies of patients with ‘postantibiotic Lyme arthritis’ show that they can be treated successfully with intra-articular steroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, biologic response modifiers, and even synovectomy with successful outcomes.” Some of these therapies also work in cases where first courses of oral and intravenous antibiotics are unsuccessful.

“Antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included one course of IV therapy,” the authors clarified.

For patients with Lyme disease–associated meningitis, cranial neuropathy, radiculoneuropathy, or other PNS manifestations, the authors recommended intravenous ceftriaxone, cefotaxime, penicillin G, or oral doxycycline over other antimicrobials.

“For most neurologic presentations, oral doxycycline is just as effective as appropriate IV antibiotics,” Dr. Rumbaugh said. “The exception is the relatively rare situation where the patient is felt to have parenchymal involvement of brain or spinal cord, in which case the guidelines recommend IV antibiotics over oral antibiotics.” In the studies, there was no statistically significant difference between oral or intravenous regimens in response rate or risk of adverse effects.

Patients with nonspecific symptoms such as fatigue, pain, or cognitive impairment following treatment should not receive additional antibiotic therapy if there’s no evidence of treatment failure or infection. These two markers “would include objective signs of disease activity, such as arthritis, meningitis, or neuropathy,” the guideline authors wrote in comments accompanying the recommendation.

Clinicians caring for patients with symptomatic bradycardia caused by Lyme carditis should consider temporary pacing measures instead of a permanent pacemaker. For patients hospitalized with Lyme carditis, “we suggest initially using IV ceftriaxone over oral antibiotics until there is evidence of clinical improvement, then switching to oral antibiotics to complete treatment,” they advised. Outpatients with this condition should receive oral antibiotics instead of intravenous antibiotics.

Advice on antibodies testing ‘particularly cogent’

For individuals without expertise in these areas, the recommendations are clear and useful, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy), said in an interview.

“As a rheumatologist, I would have appreciated literature references for some of the recommendations but, nevertheless, find these useful. I applaud the care with which the evidence was gathered and the general formatting, which tried to review multiple possible scenarios surrounding Lyme arthritis,” said Dr. Furst, offering a third-party perspective.

The advice on using antibodies tests to make a diagnosis of Lyme arthritis “is particularly cogent and more useful than trying to culture these fastidious organisms,” he added.

The IDSA, AAN, and ACR provided support for the guideline. Dr. Bockenstedt reported receiving research funding from the National Institutes of Health and the Gordon and the Llura Gund Foundation and remuneration from L2 Diagnostics for investigator-initiated NIH-sponsored research. Dr. Rumbaugh had no conflicts of interest to disclose. Dr. Furst reported no conflicts of interest in commenting on these guidelines.

SOURCE: Rumbaugh JA et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1215.

New clinical practice guidelines on Lyme disease place a strong emphasis on antibody testing to assess for rheumatologic and neurologic syndromes. “Diagnostically, we recommend testing via antibodies, and an index of antibodies in cerebrospinal fluid [CSF] versus serum. Importantly, we recommend against using polymerase chain reaction [PCR] in CSF,” Jeffrey A. Rumbaugh, MD, PhD, a coauthor of the guidelines and a member of the American Academy of Neurology, said in an interview.

CDC/ Dr. Amanda Loftis, Dr. William Nicholson, Dr. Will Reeves, Dr. Chris Paddock

The Infectious Diseases Society of America, AAN, and the American College of Rheumatology convened a multidisciplinary panel to develop the 43 recommendations, seeking input from 12 additional medical specialties, and patients. The panel conducted a systematic review of available evidence on preventing, diagnosing, and treating Lyme disease, using the Grading of Recommendations Assessment, Development and Evaluation model to evaluate clinical evidence and strength of recommendations. The guidelines were simultaneous published in Clinical Infectious Diseases, Neurology, Arthritis & Rheumatology, and Arthritis Care & Research.

This is the first time these organizations have collaborated on joint Lyme disease guidelines, which focus mainly on neurologic, cardiac, and rheumatologic manifestations.

“We are very excited to provide these updated guidelines to assist clinicians working in numerous medical specialties around the country, and even the world, as they care for patients suffering from Lyme disease,” Dr. Rumbaugh said.
 

When to use and not to use PCR

Guideline authors called for specific testing regimens depending on presentation of symptoms. Generally, they advised that individuals with a skin rash suggestive of early disease seek a clinical diagnosis instead of laboratory testing.

Recommendations on Lyme arthritis support previous IDSA guidelines published in 2006, Linda K. Bockenstedt, MD, professor of medicine at Yale University, New Haven, Conn., and a coauthor of the guidelines, said in an interview.

To evaluate for potential Lyme arthritis, clinicians should choose serum antibody testing over PCR or culture of blood or synovial fluid/tissue. However, if a doctor is assessing a seropositive patient for Lyme arthritis diagnosis but needs more information for treatment decisions, the authors recommended PCR applied to synovial fluid or tissue over Borrelia culture.

“Synovial fluid can be analyzed by PCR, but sensitivity is generally lower than serology,” Dr. Bockenstedt explained. Additionally, culture of joint fluid or synovial tissue for Lyme spirochetes has 0% sensitivity in multiple studies. “For these reasons, we recommend serum antibody testing over PCR of joint fluid or other methods for an initial diagnosis.”

Serum antibody testing over PCR or culture is also recommended for identifying Lyme neuroborreliosis in the peripheral nervous system (PNS) or CNS.

Despite the recent popularity of Lyme PCR testing in hospitals and labs, “with Lyme at least, antibodies are better in the CSF,” Dr. Rumbaugh said. Studies have shown that “most patients with even early neurologic Lyme disease are seropositive by conventional antibody testing at time of initial clinical presentation, and that intrathecal antibody production, as demonstrated by an elevated CSF:serum index, is highly specific for CNS involvement.”

If done correctly, antibody testing is both sensitive and specific for neurologic Lyme disease. “On the other hand, sensitivity of Lyme PCR performed on CSF has been only in the 5%-17% range in studies. Incidentally, Lyme PCR on blood is also not sensitive and therefore not recommended,” Dr. Rumbaugh said.

Guideline authors recommended testing in patients with the following conditions: acute neurologic disorders such as meningitis, painful radiculoneuritis, mononeuropathy multiplex; evidence of spinal cord or brain inflammation; and acute myocarditis/pericarditis of unknown cause in an appropriate epidemiologic setting.

They did not recommend testing in patients with typical amyotrophic lateral sclerosis; relapsing remitting multiple sclerosis; Parkinson’s disease, dementia, or cognitive decline; new-onset seizures; other neurologic syndromes or those lacking clinical or epidemiologic history that would support a diagnosis of Lyme disease; and patients with chronic cardiomyopathy of unknown cause.

The authors also called for judicious use of electrocardiogram to screen for Lyme carditis, recommending it only in patients signs or symptoms of this condition. However, patients at risk for or showing signs of severe cardiac complications of Lyme disease should be hospitalized and monitored via ECG.

Timelines for antibiotics

Most patients with Lyme disease should receive oral antibiotics, although duration times vary depending on the disease state. “We recommend that prophylactic antibiotic therapy be given to adults and children only within 72 hours of removal of an identified high-risk tick bite, but not for bites that are equivocal risk or low risk,” according to the guideline authors.

Specific antibiotic treatment regimens by condition are as follows: 10-14 days for early-stage disease, 14 days for Lyme carditis, 14-21 days for neurologic Lyme disease, and 28 days for late Lyme arthritis.

“Despite arthritis occurring late in the course of infection, treatment with a 28-day course of oral antibiotic is effective, although the rates of complete resolution of joint swelling can vary,” Dr. Bockenstedt said. Clinicians may consider a second 28-day course of oral antibiotics or a 2- to 4-week course of ceftriaxone in patients with persistent swelling, after an initial course of oral antibiotics.

Citing knowledge gaps, the authors made no recommendation on secondary antibiotic treatment for unresolved Lyme arthritis. Rheumatologists can play an important role in the care of this small subset of patients, Dr. Bockenstedt noted. “Studies of patients with ‘postantibiotic Lyme arthritis’ show that they can be treated successfully with intra-articular steroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, biologic response modifiers, and even synovectomy with successful outcomes.” Some of these therapies also work in cases where first courses of oral and intravenous antibiotics are unsuccessful.

“Antibiotic therapy for longer than 8 weeks is not expected to provide additional benefit to patients with persistent arthritis if that treatment has included one course of IV therapy,” the authors clarified.

For patients with Lyme disease–associated meningitis, cranial neuropathy, radiculoneuropathy, or other PNS manifestations, the authors recommended intravenous ceftriaxone, cefotaxime, penicillin G, or oral doxycycline over other antimicrobials.

“For most neurologic presentations, oral doxycycline is just as effective as appropriate IV antibiotics,” Dr. Rumbaugh said. “The exception is the relatively rare situation where the patient is felt to have parenchymal involvement of brain or spinal cord, in which case the guidelines recommend IV antibiotics over oral antibiotics.” In the studies, there was no statistically significant difference between oral or intravenous regimens in response rate or risk of adverse effects.

Patients with nonspecific symptoms such as fatigue, pain, or cognitive impairment following treatment should not receive additional antibiotic therapy if there’s no evidence of treatment failure or infection. These two markers “would include objective signs of disease activity, such as arthritis, meningitis, or neuropathy,” the guideline authors wrote in comments accompanying the recommendation.

Clinicians caring for patients with symptomatic bradycardia caused by Lyme carditis should consider temporary pacing measures instead of a permanent pacemaker. For patients hospitalized with Lyme carditis, “we suggest initially using IV ceftriaxone over oral antibiotics until there is evidence of clinical improvement, then switching to oral antibiotics to complete treatment,” they advised. Outpatients with this condition should receive oral antibiotics instead of intravenous antibiotics.

Advice on antibodies testing ‘particularly cogent’

For individuals without expertise in these areas, the recommendations are clear and useful, Daniel E. Furst, MD, professor of medicine (emeritus) at the University of California, Los Angeles, adjunct professor at the University of Washington, Seattle, and research professor at the University of Florence (Italy), said in an interview.

“As a rheumatologist, I would have appreciated literature references for some of the recommendations but, nevertheless, find these useful. I applaud the care with which the evidence was gathered and the general formatting, which tried to review multiple possible scenarios surrounding Lyme arthritis,” said Dr. Furst, offering a third-party perspective.

The advice on using antibodies tests to make a diagnosis of Lyme arthritis “is particularly cogent and more useful than trying to culture these fastidious organisms,” he added.

The IDSA, AAN, and ACR provided support for the guideline. Dr. Bockenstedt reported receiving research funding from the National Institutes of Health and the Gordon and the Llura Gund Foundation and remuneration from L2 Diagnostics for investigator-initiated NIH-sponsored research. Dr. Rumbaugh had no conflicts of interest to disclose. Dr. Furst reported no conflicts of interest in commenting on these guidelines.

SOURCE: Rumbaugh JA et al. Clin Infect Dis. 2020 Nov 30. doi: 10.1093/cid/ciaa1215.

Once the fog lifts on a global pandemic that led to an explosion in telehealth visits in 2020, mental health experts expect virtual and in-person visits to merge to become a standard model of care in clinical psychiatry.

Hybrid care is the future, Peter Yellowlees, MBBS, MD, a professor of psychiatry and chief wellness officer at the University of California, Davis, said in an interview. “I’ve been working this way for several years – where all of my patients get to see me in person or online, or both.”

The model’s increasing popularity reflects a major shift toward virtual consults. Telemedicine offers safer, quicker, and less expensive alternatives, Steven Chan, MD, MBA, of Stanford (Calif.) University, said in an interview. “This continuity is essential to helping to reduce emergency room visits, reduce inpatient hospitalizations and readmissions, and improving adherence to treatment,” Dr. Chan said. State and federal regulators’ actions to lift certain licensing and prescribing restrictions and expand coverage made it easier for clinical psychiatrists to offer and get paid for these services.

The catch is that no one knows whether these easements will remain in place once COVID-19 recedes, ending the national public health emergency, Jay H. Shore, MD, MPH, chairperson of the American Psychiatric Association telepsychiatry committee, and professor and director of telemedicine programming at the University of Colorado at Denver, Aurora’s department of psychiatry, said in an interview. “These all temporarily changed during this time period, but we have no idea when they’re going to end or if they’re going to continue off of COVID. So now, there’s a lot of uncertainty.”

 

‘Suite of different technologies’

New freedoms to deliver telehealth care left some practices scrambling to adopt or refine technology. Once COVID-19 hit, “I can’t think of a psychiatrist or provider or institution that didn’t have to rapidly virtualize and do at least some video conferencing,” Dr. Shore said. This immediate shift signaled a key move toward hybrid patient-doctor relations. “It means you hold a relationship with your patients through multiple different mediums, email, portal, telephone, in person. It’s not just about in-person versus video, it’s about a suite of different technologies.”

Dr. Shore began practicing telehealth 20 years ago, long before the age of COVID. He’s since established rewarding relationships with patients he’s never met. “I’ve done everything from medical management to long-term psychotherapy, group psychotherapy, and I’ve been successful with different populations.”

Many nuances exist around matching the right patient with the right videoconferencing adaptation, Dr. Shore continued. However, “in general, the literature supports that you can get equal clinical outcomes with telehealth versus in-person treatment.”
 

‘I see their garden’

While some may eschew the idea of providing care over a virtual platform, other physicians see it as an insightful window into a person’s mental state. “I think some are actually quite surprised by how much good care you can give using video,” said Dr. Yellowlees. Unlike a phone conversation, video allows you to see a person’s home. “The beauty of a video is not just that you can see the person, you can also look around their home, and learn more about them.”

In his own visits, he asks patients to take him on a virtual “walk” through their house, provided there are no confidentiality issues.

“I get to meet their pets, the carers, the spouses; I get to see their garden. I get to see what their interests are from looking at the paintings on their walls. I learn more about my patients that way. If you use video to purely see people from the neck up, then that’s fine, but I think you can also use it to your advantage, seeing people at home.” He also encourages patients to do visits in their cars – as long as the windows are shut, they’re in a safe area, and most importantly, they’re not driving.

Nina Vasan, MD, MBA, who treats patients at Stanford and in a concierge private practice for executives, agrees that seeing patients in the home offers a more direct view of patients’ lives. “These little extra pieces of information are things that we didn’t get before COVID, when patients would come by themselves into the office week after week. I do feel like I know some patients much better by being able to see their surroundings and home interactions,” Dr. Vasan, founder and executive director of Brainstorm: The Stanford Lab for Mental Health Innovation and chair of the APA’s committee on innovation, said in an interview.

She uses Zoom for her sessions, and regularly texts with her concierge patients. In both clinics, where most visits have gone virtual, “the no-show rate is near zero. Before COVID, it was around 10%-20%.”

Safety is a key advantage of virtual visits, noted Dr. Shore. “It’s certainly better than some of the risks of seeing people in person.”
 

Lack of integration causes frustration

Some challenges exist around access and adaptation of virtual technology. The pandemic’s sudden onslaught left many clinicians scrambling to adjust to a virtual format without any training or tools to support them. “This has caused some stress,” Dr. Shore said.

Electronic health record systems may or may not integrate video visits, noted Dr. Chan. “For instance, I work at a health system where mental health questionnaires, imaging systems, notes, and video visit scheduling are housed in separate systems.”

Without a seamless national, integrated system in place, physicians are often left to couple different IT formats together. “There are some systems that work pretty well, and there are some that are really clunky where you’re forcing the two together, so that’s a challenge,” Dr. Shore said. Providers may be using one system for their office and another system to provide care. “They may be using different EHRs and different teleconferencing platforms. That adds complexity.” Video conferencing platforms aren’t as challenging to use as EHRs. However, if some people are self-taught, there’s no way of knowing if they’re using best practices, he added.

Many health systems do offer video built into EMRs. Companies such as Epic have provided integrations with Vidyo, Amwell, and other platforms, noted Dr. Chan.

An integrated platform is useful if done well – but isn’t necessarily essential, according to Dr. Yellowlees. In his own setup, he signs a laptop into an EMR and uses an iPad to communicate with patients via video on the iPad and all video on the phone.

“The big advantage of telemedicine is you can type your notes in a socially appropriate way while talking to the patient on video. I do that, and it saves me a considerable amount of time. I don’t have to spend time after a consultation typing up notes.”

Still, others may struggle with bandwidth or connectivity. “Perhaps there’s a problem with privacy or the types of patients you’re dealing with,” Dr. Shore said. Older patients in a nursing home, for example, may require a team of people that works onsite. Suddenly, their care has to transition to a virtual system. “You may need to figure how to put the right team together to do straightforward and individual interactions,” he said.

Virtual care also suffers from the “digital divide,” an issue that predates COVID-19, said Dr. Shore. Not all patients have access to bandwidth and the technology to see clinicians. Other lack expertise and comfort with using the technology, or can’t afford the equipment necessary to bring them online. The pandemic has highlighted all of these disparities, he emphasized.

Dr. Chan offered that the digital divide is part of a larger socioeconomic divide, where barriers to any care – including transportation for in-person care – exist.

Technology and access issues aside, insidious “Zoom fatigue” is affecting everyone right now. “That’s clearly real,” Dr. Shore said. “And it’s not just about videoconferencing; it’s about being in quarantine. We’re all in this virtual lockdown, where people are using the term ‘videoconferencing fatigue.’ It’s a complicated problem.”

To assist with telehealth implementation, the APA has issued practice guidance and a toolkit that includes an extensive set of educational materials, including 40 videos on various topics. It’s also hosted webinars on telehealth policies and written up standard operating procedures on this topic, Dr. Yellowlees said. “The most important thing is APA, like other organizations, is advocating to have the relaxation of regulations during COVID made permanent,” he said.

Reimbursement post pandemic

As virtual visits rose in 2020, so did billing for such services. According to America’s Health Insurance Plans, claims to private insurers exploded by more than 4,000% in 2020. AHIP last July reported that mental health conditions made up one-third or more than 33% of telehealth claims to private insurers during the pandemic. Dr. Yellowlees said the health insurers he’s dealt with “have been good about paying for telehealth visits during the COVID-declared emergency.”

Whether this coverage will continue once the public health emergency ends, is unclear, some contend. “My sense is that there will be a rollback of coverage, but it won’t be back to what we had prepandemic,” said Ateev Mehrotra, MD, MPH, who studies telemedicine trends, in an interview. Right now, there’s still a great deal of uncertainty about reimbursement, “and that’s what’s giving providers pause,” said Dr. Mehrotra, of the department of health care policy and medicine at Harvard Medical School and a hospitalist at Beth Israel Deaconess Medical Center, both in Boston.

AHIP will continue to support federal and state policies to further promote telehealth access during the public health emergency, spokesman David Allen said in a statement. “Insurance providers have independently shifted their policies to increase access to care and services, ranging from acute care needs and triage services to chronic disease management and behavioral health. We are still awaiting information on what changes will remain in place beyond the public health emergency,” he said.

Even before COVID-19, Mr. Allen noted, nearly all large employers (96%) offered access to telehealth services as a covered benefit in 2019. In May, the Kaiser Family Foundation reported that many insurers were reducing or lifting cost sharing for telehealth for limited time periods.

Some of the larger payers said they’re continuing benefits, although it’s not clear how long some benefits will remain in place.

UnitedHealthcare offers no-cost coverage for COVID-19 testing–related telehealth visits, but that benefit is set to expire once the public health emergency presumably ends on Jan. 20, 2021. Through Dec. 31, 2020, the payer said it would offer coverage with no cost sharing for telehealth visits related to COVID-19 treatment and expanded access to telehealth visits not related to COVID-19 through its network. Similarly, Anthem is waiving cost sharing for COVID-19 treatments via telehealth or in-person visits, and for telehealth visits not related to COVID-19 for Medicare members through the end of the year.

Anthem will continue to cover telehealth and encourage members and clinicians to use telehealth for behavioral health, a spokesperson said. Anthem also has a telehealth provider, LiveHealth Online, “another safe and effective way for members to see a doctor to receive health guidance from their home via mobile device or a computer with a webcam,” said the spokesperson.

Dr. Vasan hopes that insurers will increase coverage for telehealth and at the same rate as in-person visits, especially for mental health. “I have not felt that the quality of the clinic has decreased, and in fact, in some ways it’s gotten better, and insurance coverage should reflect this.”
 

Outlook for the hybrid model

As long as there’s COVID-19, psychiatry practices must remain virtual, at least for now, Dr. Shore said. “We will emerge from this pandemic, I suspect in bits and starts.” When that happens, practices will need to have a transition plan in place. “Once we get away from COVID, I don’t think our mental health will ever be the same again. We’ll have much more virtual technology along the lines of a hybrid model, where we’ll see patients in person, but we’ll use more technology to work with patients, but it will be more of a blend.” Practices will also have to address the regulatory, reimbursement, and prescribing conditions the new world offers.

Some practices are already discovering the benefits of relying less on a brick-and-mortar office.

Dr. Chan said his colleagues are finding that they no longer have to deal with the expense and upkeep of renting and furnishing office space. “Many are taking their practice virtual-only because the monthly recurring costs are so cheap, and they can see patients in distant, underserved communities.” In-person visits are now inconvenient and risky, he continued. They require expensive personal protective equipment and cleaning protocols. “Plus, there’s the risk that services must shut down when stay-at-home orders return or when a staff member gets infected.”

Physicians prescribing certain controlled substances will likely continue to use office space, once the public health emergency expires and face-to-face visits resume. “In such cases, they can rent office space part-time,” Dr. Chan added.

Dr. Vasan, also of the department of psychiatry at Stanford and chief medical officer of Real, hopes that such a model prevails. “I do miss seeing patients in person and think a hybrid will be a good balance.”

Most patients want it, as do the influx of Generation Z physicians coming into the profession, Dr. Yellowlees noted. These are young, technologically savvy doctors who grew up in the age of the Internet. “I think the silver lining of COVID is it led telemedicine past the tipping point, where both patients and providers are learning that it’s an appropriate way to get care, as long as you’re careful, use professional guidelines – and don’t drop your standards of care.”

Dr. Yellowlees and Dr. Shore are coauthors of Telepsychiatry and Health Technologies: A Guide for Mental Health Professionals (Washington: American Psychiatric Association Publishing, 2018), and receive royalties from the book. Dr. Shore also reported working with AccessCare and receiving royalties from Springer Press. Dr. Chan reported consulting for Orbit Health. Dr. Vasan reported no conflicts of interest. Dr. Mehrotra has received research funding from several U.S. agencies, including the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

Once the fog lifts on a global pandemic that led to an explosion in telehealth visits in 2020, mental health experts expect virtual and in-person visits to merge to become a standard model of care in clinical psychiatry.

Hybrid care is the future, Peter Yellowlees, MBBS, MD, a professor of psychiatry and chief wellness officer at the University of California, Davis, said in an interview. “I’ve been working this way for several years – where all of my patients get to see me in person or online, or both.”

The model’s increasing popularity reflects a major shift toward virtual consults. Telemedicine offers safer, quicker, and less expensive alternatives, Steven Chan, MD, MBA, of Stanford (Calif.) University, said in an interview. “This continuity is essential to helping to reduce emergency room visits, reduce inpatient hospitalizations and readmissions, and improving adherence to treatment,” Dr. Chan said. State and federal regulators’ actions to lift certain licensing and prescribing restrictions and expand coverage made it easier for clinical psychiatrists to offer and get paid for these services.

The catch is that no one knows whether these easements will remain in place once COVID-19 recedes, ending the national public health emergency, Jay H. Shore, MD, MPH, chairperson of the American Psychiatric Association telepsychiatry committee, and professor and director of telemedicine programming at the University of Colorado at Denver, Aurora’s department of psychiatry, said in an interview. “These all temporarily changed during this time period, but we have no idea when they’re going to end or if they’re going to continue off of COVID. So now, there’s a lot of uncertainty.”

 

‘Suite of different technologies’

New freedoms to deliver telehealth care left some practices scrambling to adopt or refine technology. Once COVID-19 hit, “I can’t think of a psychiatrist or provider or institution that didn’t have to rapidly virtualize and do at least some video conferencing,” Dr. Shore said. This immediate shift signaled a key move toward hybrid patient-doctor relations. “It means you hold a relationship with your patients through multiple different mediums, email, portal, telephone, in person. It’s not just about in-person versus video, it’s about a suite of different technologies.”

Dr. Shore began practicing telehealth 20 years ago, long before the age of COVID. He’s since established rewarding relationships with patients he’s never met. “I’ve done everything from medical management to long-term psychotherapy, group psychotherapy, and I’ve been successful with different populations.”

Many nuances exist around matching the right patient with the right videoconferencing adaptation, Dr. Shore continued. However, “in general, the literature supports that you can get equal clinical outcomes with telehealth versus in-person treatment.”
 

‘I see their garden’

While some may eschew the idea of providing care over a virtual platform, other physicians see it as an insightful window into a person’s mental state. “I think some are actually quite surprised by how much good care you can give using video,” said Dr. Yellowlees. Unlike a phone conversation, video allows you to see a person’s home. “The beauty of a video is not just that you can see the person, you can also look around their home, and learn more about them.”

In his own visits, he asks patients to take him on a virtual “walk” through their house, provided there are no confidentiality issues.

“I get to meet their pets, the carers, the spouses; I get to see their garden. I get to see what their interests are from looking at the paintings on their walls. I learn more about my patients that way. If you use video to purely see people from the neck up, then that’s fine, but I think you can also use it to your advantage, seeing people at home.” He also encourages patients to do visits in their cars – as long as the windows are shut, they’re in a safe area, and most importantly, they’re not driving.

Nina Vasan, MD, MBA, who treats patients at Stanford and in a concierge private practice for executives, agrees that seeing patients in the home offers a more direct view of patients’ lives. “These little extra pieces of information are things that we didn’t get before COVID, when patients would come by themselves into the office week after week. I do feel like I know some patients much better by being able to see their surroundings and home interactions,” Dr. Vasan, founder and executive director of Brainstorm: The Stanford Lab for Mental Health Innovation and chair of the APA’s committee on innovation, said in an interview.

She uses Zoom for her sessions, and regularly texts with her concierge patients. In both clinics, where most visits have gone virtual, “the no-show rate is near zero. Before COVID, it was around 10%-20%.”

Safety is a key advantage of virtual visits, noted Dr. Shore. “It’s certainly better than some of the risks of seeing people in person.”
 

Lack of integration causes frustration

Some challenges exist around access and adaptation of virtual technology. The pandemic’s sudden onslaught left many clinicians scrambling to adjust to a virtual format without any training or tools to support them. “This has caused some stress,” Dr. Shore said.

Electronic health record systems may or may not integrate video visits, noted Dr. Chan. “For instance, I work at a health system where mental health questionnaires, imaging systems, notes, and video visit scheduling are housed in separate systems.”

Without a seamless national, integrated system in place, physicians are often left to couple different IT formats together. “There are some systems that work pretty well, and there are some that are really clunky where you’re forcing the two together, so that’s a challenge,” Dr. Shore said. Providers may be using one system for their office and another system to provide care. “They may be using different EHRs and different teleconferencing platforms. That adds complexity.” Video conferencing platforms aren’t as challenging to use as EHRs. However, if some people are self-taught, there’s no way of knowing if they’re using best practices, he added.

Many health systems do offer video built into EMRs. Companies such as Epic have provided integrations with Vidyo, Amwell, and other platforms, noted Dr. Chan.

An integrated platform is useful if done well – but isn’t necessarily essential, according to Dr. Yellowlees. In his own setup, he signs a laptop into an EMR and uses an iPad to communicate with patients via video on the iPad and all video on the phone.

“The big advantage of telemedicine is you can type your notes in a socially appropriate way while talking to the patient on video. I do that, and it saves me a considerable amount of time. I don’t have to spend time after a consultation typing up notes.”

Still, others may struggle with bandwidth or connectivity. “Perhaps there’s a problem with privacy or the types of patients you’re dealing with,” Dr. Shore said. Older patients in a nursing home, for example, may require a team of people that works onsite. Suddenly, their care has to transition to a virtual system. “You may need to figure how to put the right team together to do straightforward and individual interactions,” he said.

Virtual care also suffers from the “digital divide,” an issue that predates COVID-19, said Dr. Shore. Not all patients have access to bandwidth and the technology to see clinicians. Other lack expertise and comfort with using the technology, or can’t afford the equipment necessary to bring them online. The pandemic has highlighted all of these disparities, he emphasized.

Dr. Chan offered that the digital divide is part of a larger socioeconomic divide, where barriers to any care – including transportation for in-person care – exist.

Technology and access issues aside, insidious “Zoom fatigue” is affecting everyone right now. “That’s clearly real,” Dr. Shore said. “And it’s not just about videoconferencing; it’s about being in quarantine. We’re all in this virtual lockdown, where people are using the term ‘videoconferencing fatigue.’ It’s a complicated problem.”

To assist with telehealth implementation, the APA has issued practice guidance and a toolkit that includes an extensive set of educational materials, including 40 videos on various topics. It’s also hosted webinars on telehealth policies and written up standard operating procedures on this topic, Dr. Yellowlees said. “The most important thing is APA, like other organizations, is advocating to have the relaxation of regulations during COVID made permanent,” he said.

Reimbursement post pandemic

As virtual visits rose in 2020, so did billing for such services. According to America’s Health Insurance Plans, claims to private insurers exploded by more than 4,000% in 2020. AHIP last July reported that mental health conditions made up one-third or more than 33% of telehealth claims to private insurers during the pandemic. Dr. Yellowlees said the health insurers he’s dealt with “have been good about paying for telehealth visits during the COVID-declared emergency.”

Whether this coverage will continue once the public health emergency ends, is unclear, some contend. “My sense is that there will be a rollback of coverage, but it won’t be back to what we had prepandemic,” said Ateev Mehrotra, MD, MPH, who studies telemedicine trends, in an interview. Right now, there’s still a great deal of uncertainty about reimbursement, “and that’s what’s giving providers pause,” said Dr. Mehrotra, of the department of health care policy and medicine at Harvard Medical School and a hospitalist at Beth Israel Deaconess Medical Center, both in Boston.

AHIP will continue to support federal and state policies to further promote telehealth access during the public health emergency, spokesman David Allen said in a statement. “Insurance providers have independently shifted their policies to increase access to care and services, ranging from acute care needs and triage services to chronic disease management and behavioral health. We are still awaiting information on what changes will remain in place beyond the public health emergency,” he said.

Even before COVID-19, Mr. Allen noted, nearly all large employers (96%) offered access to telehealth services as a covered benefit in 2019. In May, the Kaiser Family Foundation reported that many insurers were reducing or lifting cost sharing for telehealth for limited time periods.

Some of the larger payers said they’re continuing benefits, although it’s not clear how long some benefits will remain in place.

UnitedHealthcare offers no-cost coverage for COVID-19 testing–related telehealth visits, but that benefit is set to expire once the public health emergency presumably ends on Jan. 20, 2021. Through Dec. 31, 2020, the payer said it would offer coverage with no cost sharing for telehealth visits related to COVID-19 treatment and expanded access to telehealth visits not related to COVID-19 through its network. Similarly, Anthem is waiving cost sharing for COVID-19 treatments via telehealth or in-person visits, and for telehealth visits not related to COVID-19 for Medicare members through the end of the year.

Anthem will continue to cover telehealth and encourage members and clinicians to use telehealth for behavioral health, a spokesperson said. Anthem also has a telehealth provider, LiveHealth Online, “another safe and effective way for members to see a doctor to receive health guidance from their home via mobile device or a computer with a webcam,” said the spokesperson.

Dr. Vasan hopes that insurers will increase coverage for telehealth and at the same rate as in-person visits, especially for mental health. “I have not felt that the quality of the clinic has decreased, and in fact, in some ways it’s gotten better, and insurance coverage should reflect this.”
 

Outlook for the hybrid model

As long as there’s COVID-19, psychiatry practices must remain virtual, at least for now, Dr. Shore said. “We will emerge from this pandemic, I suspect in bits and starts.” When that happens, practices will need to have a transition plan in place. “Once we get away from COVID, I don’t think our mental health will ever be the same again. We’ll have much more virtual technology along the lines of a hybrid model, where we’ll see patients in person, but we’ll use more technology to work with patients, but it will be more of a blend.” Practices will also have to address the regulatory, reimbursement, and prescribing conditions the new world offers.

Some practices are already discovering the benefits of relying less on a brick-and-mortar office.

Dr. Chan said his colleagues are finding that they no longer have to deal with the expense and upkeep of renting and furnishing office space. “Many are taking their practice virtual-only because the monthly recurring costs are so cheap, and they can see patients in distant, underserved communities.” In-person visits are now inconvenient and risky, he continued. They require expensive personal protective equipment and cleaning protocols. “Plus, there’s the risk that services must shut down when stay-at-home orders return or when a staff member gets infected.”

Physicians prescribing certain controlled substances will likely continue to use office space, once the public health emergency expires and face-to-face visits resume. “In such cases, they can rent office space part-time,” Dr. Chan added.

Dr. Vasan, also of the department of psychiatry at Stanford and chief medical officer of Real, hopes that such a model prevails. “I do miss seeing patients in person and think a hybrid will be a good balance.”

Most patients want it, as do the influx of Generation Z physicians coming into the profession, Dr. Yellowlees noted. These are young, technologically savvy doctors who grew up in the age of the Internet. “I think the silver lining of COVID is it led telemedicine past the tipping point, where both patients and providers are learning that it’s an appropriate way to get care, as long as you’re careful, use professional guidelines – and don’t drop your standards of care.”

Dr. Yellowlees and Dr. Shore are coauthors of Telepsychiatry and Health Technologies: A Guide for Mental Health Professionals (Washington: American Psychiatric Association Publishing, 2018), and receive royalties from the book. Dr. Shore also reported working with AccessCare and receiving royalties from Springer Press. Dr. Chan reported consulting for Orbit Health. Dr. Vasan reported no conflicts of interest. Dr. Mehrotra has received research funding from several U.S. agencies, including the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

Once the fog lifts on a global pandemic that led to an explosion in telehealth visits in 2020, mental health experts expect virtual and in-person visits to merge to become a standard model of care in clinical psychiatry.

Hybrid care is the future, Peter Yellowlees, MBBS, MD, a professor of psychiatry and chief wellness officer at the University of California, Davis, said in an interview. “I’ve been working this way for several years – where all of my patients get to see me in person or online, or both.”

The model’s increasing popularity reflects a major shift toward virtual consults. Telemedicine offers safer, quicker, and less expensive alternatives, Steven Chan, MD, MBA, of Stanford (Calif.) University, said in an interview. “This continuity is essential to helping to reduce emergency room visits, reduce inpatient hospitalizations and readmissions, and improving adherence to treatment,” Dr. Chan said. State and federal regulators’ actions to lift certain licensing and prescribing restrictions and expand coverage made it easier for clinical psychiatrists to offer and get paid for these services.

The catch is that no one knows whether these easements will remain in place once COVID-19 recedes, ending the national public health emergency, Jay H. Shore, MD, MPH, chairperson of the American Psychiatric Association telepsychiatry committee, and professor and director of telemedicine programming at the University of Colorado at Denver, Aurora’s department of psychiatry, said in an interview. “These all temporarily changed during this time period, but we have no idea when they’re going to end or if they’re going to continue off of COVID. So now, there’s a lot of uncertainty.”

 

‘Suite of different technologies’

New freedoms to deliver telehealth care left some practices scrambling to adopt or refine technology. Once COVID-19 hit, “I can’t think of a psychiatrist or provider or institution that didn’t have to rapidly virtualize and do at least some video conferencing,” Dr. Shore said. This immediate shift signaled a key move toward hybrid patient-doctor relations. “It means you hold a relationship with your patients through multiple different mediums, email, portal, telephone, in person. It’s not just about in-person versus video, it’s about a suite of different technologies.”

Dr. Shore began practicing telehealth 20 years ago, long before the age of COVID. He’s since established rewarding relationships with patients he’s never met. “I’ve done everything from medical management to long-term psychotherapy, group psychotherapy, and I’ve been successful with different populations.”

Many nuances exist around matching the right patient with the right videoconferencing adaptation, Dr. Shore continued. However, “in general, the literature supports that you can get equal clinical outcomes with telehealth versus in-person treatment.”
 

‘I see their garden’

While some may eschew the idea of providing care over a virtual platform, other physicians see it as an insightful window into a person’s mental state. “I think some are actually quite surprised by how much good care you can give using video,” said Dr. Yellowlees. Unlike a phone conversation, video allows you to see a person’s home. “The beauty of a video is not just that you can see the person, you can also look around their home, and learn more about them.”

In his own visits, he asks patients to take him on a virtual “walk” through their house, provided there are no confidentiality issues.

“I get to meet their pets, the carers, the spouses; I get to see their garden. I get to see what their interests are from looking at the paintings on their walls. I learn more about my patients that way. If you use video to purely see people from the neck up, then that’s fine, but I think you can also use it to your advantage, seeing people at home.” He also encourages patients to do visits in their cars – as long as the windows are shut, they’re in a safe area, and most importantly, they’re not driving.

Nina Vasan, MD, MBA, who treats patients at Stanford and in a concierge private practice for executives, agrees that seeing patients in the home offers a more direct view of patients’ lives. “These little extra pieces of information are things that we didn’t get before COVID, when patients would come by themselves into the office week after week. I do feel like I know some patients much better by being able to see their surroundings and home interactions,” Dr. Vasan, founder and executive director of Brainstorm: The Stanford Lab for Mental Health Innovation and chair of the APA’s committee on innovation, said in an interview.

She uses Zoom for her sessions, and regularly texts with her concierge patients. In both clinics, where most visits have gone virtual, “the no-show rate is near zero. Before COVID, it was around 10%-20%.”

Safety is a key advantage of virtual visits, noted Dr. Shore. “It’s certainly better than some of the risks of seeing people in person.”
 

Lack of integration causes frustration

Some challenges exist around access and adaptation of virtual technology. The pandemic’s sudden onslaught left many clinicians scrambling to adjust to a virtual format without any training or tools to support them. “This has caused some stress,” Dr. Shore said.

Electronic health record systems may or may not integrate video visits, noted Dr. Chan. “For instance, I work at a health system where mental health questionnaires, imaging systems, notes, and video visit scheduling are housed in separate systems.”

Without a seamless national, integrated system in place, physicians are often left to couple different IT formats together. “There are some systems that work pretty well, and there are some that are really clunky where you’re forcing the two together, so that’s a challenge,” Dr. Shore said. Providers may be using one system for their office and another system to provide care. “They may be using different EHRs and different teleconferencing platforms. That adds complexity.” Video conferencing platforms aren’t as challenging to use as EHRs. However, if some people are self-taught, there’s no way of knowing if they’re using best practices, he added.

Many health systems do offer video built into EMRs. Companies such as Epic have provided integrations with Vidyo, Amwell, and other platforms, noted Dr. Chan.

An integrated platform is useful if done well – but isn’t necessarily essential, according to Dr. Yellowlees. In his own setup, he signs a laptop into an EMR and uses an iPad to communicate with patients via video on the iPad and all video on the phone.

“The big advantage of telemedicine is you can type your notes in a socially appropriate way while talking to the patient on video. I do that, and it saves me a considerable amount of time. I don’t have to spend time after a consultation typing up notes.”

Still, others may struggle with bandwidth or connectivity. “Perhaps there’s a problem with privacy or the types of patients you’re dealing with,” Dr. Shore said. Older patients in a nursing home, for example, may require a team of people that works onsite. Suddenly, their care has to transition to a virtual system. “You may need to figure how to put the right team together to do straightforward and individual interactions,” he said.

Virtual care also suffers from the “digital divide,” an issue that predates COVID-19, said Dr. Shore. Not all patients have access to bandwidth and the technology to see clinicians. Other lack expertise and comfort with using the technology, or can’t afford the equipment necessary to bring them online. The pandemic has highlighted all of these disparities, he emphasized.

Dr. Chan offered that the digital divide is part of a larger socioeconomic divide, where barriers to any care – including transportation for in-person care – exist.

Technology and access issues aside, insidious “Zoom fatigue” is affecting everyone right now. “That’s clearly real,” Dr. Shore said. “And it’s not just about videoconferencing; it’s about being in quarantine. We’re all in this virtual lockdown, where people are using the term ‘videoconferencing fatigue.’ It’s a complicated problem.”

To assist with telehealth implementation, the APA has issued practice guidance and a toolkit that includes an extensive set of educational materials, including 40 videos on various topics. It’s also hosted webinars on telehealth policies and written up standard operating procedures on this topic, Dr. Yellowlees said. “The most important thing is APA, like other organizations, is advocating to have the relaxation of regulations during COVID made permanent,” he said.

Reimbursement post pandemic

As virtual visits rose in 2020, so did billing for such services. According to America’s Health Insurance Plans, claims to private insurers exploded by more than 4,000% in 2020. AHIP last July reported that mental health conditions made up one-third or more than 33% of telehealth claims to private insurers during the pandemic. Dr. Yellowlees said the health insurers he’s dealt with “have been good about paying for telehealth visits during the COVID-declared emergency.”

Whether this coverage will continue once the public health emergency ends, is unclear, some contend. “My sense is that there will be a rollback of coverage, but it won’t be back to what we had prepandemic,” said Ateev Mehrotra, MD, MPH, who studies telemedicine trends, in an interview. Right now, there’s still a great deal of uncertainty about reimbursement, “and that’s what’s giving providers pause,” said Dr. Mehrotra, of the department of health care policy and medicine at Harvard Medical School and a hospitalist at Beth Israel Deaconess Medical Center, both in Boston.

AHIP will continue to support federal and state policies to further promote telehealth access during the public health emergency, spokesman David Allen said in a statement. “Insurance providers have independently shifted their policies to increase access to care and services, ranging from acute care needs and triage services to chronic disease management and behavioral health. We are still awaiting information on what changes will remain in place beyond the public health emergency,” he said.

Even before COVID-19, Mr. Allen noted, nearly all large employers (96%) offered access to telehealth services as a covered benefit in 2019. In May, the Kaiser Family Foundation reported that many insurers were reducing or lifting cost sharing for telehealth for limited time periods.

Some of the larger payers said they’re continuing benefits, although it’s not clear how long some benefits will remain in place.

UnitedHealthcare offers no-cost coverage for COVID-19 testing–related telehealth visits, but that benefit is set to expire once the public health emergency presumably ends on Jan. 20, 2021. Through Dec. 31, 2020, the payer said it would offer coverage with no cost sharing for telehealth visits related to COVID-19 treatment and expanded access to telehealth visits not related to COVID-19 through its network. Similarly, Anthem is waiving cost sharing for COVID-19 treatments via telehealth or in-person visits, and for telehealth visits not related to COVID-19 for Medicare members through the end of the year.

Anthem will continue to cover telehealth and encourage members and clinicians to use telehealth for behavioral health, a spokesperson said. Anthem also has a telehealth provider, LiveHealth Online, “another safe and effective way for members to see a doctor to receive health guidance from their home via mobile device or a computer with a webcam,” said the spokesperson.

Dr. Vasan hopes that insurers will increase coverage for telehealth and at the same rate as in-person visits, especially for mental health. “I have not felt that the quality of the clinic has decreased, and in fact, in some ways it’s gotten better, and insurance coverage should reflect this.”
 

Outlook for the hybrid model

As long as there’s COVID-19, psychiatry practices must remain virtual, at least for now, Dr. Shore said. “We will emerge from this pandemic, I suspect in bits and starts.” When that happens, practices will need to have a transition plan in place. “Once we get away from COVID, I don’t think our mental health will ever be the same again. We’ll have much more virtual technology along the lines of a hybrid model, where we’ll see patients in person, but we’ll use more technology to work with patients, but it will be more of a blend.” Practices will also have to address the regulatory, reimbursement, and prescribing conditions the new world offers.

Some practices are already discovering the benefits of relying less on a brick-and-mortar office.

Dr. Chan said his colleagues are finding that they no longer have to deal with the expense and upkeep of renting and furnishing office space. “Many are taking their practice virtual-only because the monthly recurring costs are so cheap, and they can see patients in distant, underserved communities.” In-person visits are now inconvenient and risky, he continued. They require expensive personal protective equipment and cleaning protocols. “Plus, there’s the risk that services must shut down when stay-at-home orders return or when a staff member gets infected.”

Physicians prescribing certain controlled substances will likely continue to use office space, once the public health emergency expires and face-to-face visits resume. “In such cases, they can rent office space part-time,” Dr. Chan added.

Dr. Vasan, also of the department of psychiatry at Stanford and chief medical officer of Real, hopes that such a model prevails. “I do miss seeing patients in person and think a hybrid will be a good balance.”

Most patients want it, as do the influx of Generation Z physicians coming into the profession, Dr. Yellowlees noted. These are young, technologically savvy doctors who grew up in the age of the Internet. “I think the silver lining of COVID is it led telemedicine past the tipping point, where both patients and providers are learning that it’s an appropriate way to get care, as long as you’re careful, use professional guidelines – and don’t drop your standards of care.”

Dr. Yellowlees and Dr. Shore are coauthors of Telepsychiatry and Health Technologies: A Guide for Mental Health Professionals (Washington: American Psychiatric Association Publishing, 2018), and receive royalties from the book. Dr. Shore also reported working with AccessCare and receiving royalties from Springer Press. Dr. Chan reported consulting for Orbit Health. Dr. Vasan reported no conflicts of interest. Dr. Mehrotra has received research funding from several U.S. agencies, including the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

Lawmakers, physicians, and advocates alike have hailed a relaxation of telehealth rules under the COVID-19 emergency declaration, and they’d like things to stay this way.

Regulators previously restricted telemedicine use “by insisting that you could only see patients in the state you’re licensed in, by not reimbursing as widely for telehealth, and by not allowing us to prescribe controlled substances. They also didn’t allow us to see patients on the phone. So, there’s very good reasons to keep those regulations permanently relaxed,” said Peter Yellowlees, MBBS, MD, a professor of psychiatry and chief wellness officer at the University of California, Davis.

In his view, changes should take place in four key areas:

• Licensing. “Traditionally, state medical boards have been very insistent that clinical psychiatrists license in the state the patient resides in. This means physicians must have licenses in many different states. It’s very restrictive, because physicians can’t follow patients from one state to another. Under COVID, we can do this, but physicians want these licensing changes to be made permanent.”
• Reimbursement. “In the past, federal regulators have only allowed reimbursement for telemedicine in very specific, defined rural areas and specified clinical environments. This rule has since been relaxed, allowing us to see patients anywhere, especially in their homes. This is another area that should become permanent. Payers should continue to pay telehealth services on par with in-person visits.”
• Telephony. “Psychiatrists and other physicians haven’t been traditionally paid for telephone visits. But there’s no doubt that telephone follow-up visits can be very beneficial, so while I wouldn’t personally see a new patient on the phone, I now follow up with them on the phone once I have gotten to know them, and this works well.”
• Prescribing. The Ryan Haight Online Pharmacy Consumer Protection Act of 2008 was introduced to stop overseas pharmacies prescribing narcotics. “It was very successful, but as a side effect, it stopped most physicians from prescribing controlled substances on video. With COVID, we can now do this. For psychiatry, this is very important because it means we can use video to treat people for addictions with medications like buprenorphine and [prescribe] stimulants for children with ADHD. The U.S. Drug Enforcement Administration should finalize regulations for the Ryan Haight Act to allow for the prescribing of controlled substances via telehealth without a prior in-person exam.”

The American Psychiatric Association has called for an extension of the telehealth waiver authority under COVID-19 beyond the emergency declaration to study its impact. It will continue to advocate to allow for telephone-only telehealth to be reimbursed at the same rate as live audio-video, said a spokesperson. “We also will continue to advocate for the removal of geographic and originating site restrictions in Medicare, which prevent Medicare patients from being seen in the home,” with some exceptions, the spokesperson said.

The APA has also issued guidance to practitioners seeking clarity on telehealth coverage and COVID-19.

Lawmakers, physicians, and advocates alike have hailed a relaxation of telehealth rules under the COVID-19 emergency declaration, and they’d like things to stay this way.

Regulators previously restricted telemedicine use “by insisting that you could only see patients in the state you’re licensed in, by not reimbursing as widely for telehealth, and by not allowing us to prescribe controlled substances. They also didn’t allow us to see patients on the phone. So, there’s very good reasons to keep those regulations permanently relaxed,” said Peter Yellowlees, MBBS, MD, a professor of psychiatry and chief wellness officer at the University of California, Davis.

In his view, changes should take place in four key areas:

• Licensing. “Traditionally, state medical boards have been very insistent that clinical psychiatrists license in the state the patient resides in. This means physicians must have licenses in many different states. It’s very restrictive, because physicians can’t follow patients from one state to another. Under COVID, we can do this, but physicians want these licensing changes to be made permanent.”
• Reimbursement. “In the past, federal regulators have only allowed reimbursement for telemedicine in very specific, defined rural areas and specified clinical environments. This rule has since been relaxed, allowing us to see patients anywhere, especially in their homes. This is another area that should become permanent. Payers should continue to pay telehealth services on par with in-person visits.”
• Telephony. “Psychiatrists and other physicians haven’t been traditionally paid for telephone visits. But there’s no doubt that telephone follow-up visits can be very beneficial, so while I wouldn’t personally see a new patient on the phone, I now follow up with them on the phone once I have gotten to know them, and this works well.”
• Prescribing. The Ryan Haight Online Pharmacy Consumer Protection Act of 2008 was introduced to stop overseas pharmacies prescribing narcotics. “It was very successful, but as a side effect, it stopped most physicians from prescribing controlled substances on video. With COVID, we can now do this. For psychiatry, this is very important because it means we can use video to treat people for addictions with medications like buprenorphine and [prescribe] stimulants for children with ADHD. The U.S. Drug Enforcement Administration should finalize regulations for the Ryan Haight Act to allow for the prescribing of controlled substances via telehealth without a prior in-person exam.”

The American Psychiatric Association has called for an extension of the telehealth waiver authority under COVID-19 beyond the emergency declaration to study its impact. It will continue to advocate to allow for telephone-only telehealth to be reimbursed at the same rate as live audio-video, said a spokesperson. “We also will continue to advocate for the removal of geographic and originating site restrictions in Medicare, which prevent Medicare patients from being seen in the home,” with some exceptions, the spokesperson said.

The APA has also issued guidance to practitioners seeking clarity on telehealth coverage and COVID-19.

Lawmakers, physicians, and advocates alike have hailed a relaxation of telehealth rules under the COVID-19 emergency declaration, and they’d like things to stay this way.

Regulators previously restricted telemedicine use “by insisting that you could only see patients in the state you’re licensed in, by not reimbursing as widely for telehealth, and by not allowing us to prescribe controlled substances. They also didn’t allow us to see patients on the phone. So, there’s very good reasons to keep those regulations permanently relaxed,” said Peter Yellowlees, MBBS, MD, a professor of psychiatry and chief wellness officer at the University of California, Davis.

In his view, changes should take place in four key areas:

• Licensing. “Traditionally, state medical boards have been very insistent that clinical psychiatrists license in the state the patient resides in. This means physicians must have licenses in many different states. It’s very restrictive, because physicians can’t follow patients from one state to another. Under COVID, we can do this, but physicians want these licensing changes to be made permanent.”
• Reimbursement. “In the past, federal regulators have only allowed reimbursement for telemedicine in very specific, defined rural areas and specified clinical environments. This rule has since been relaxed, allowing us to see patients anywhere, especially in their homes. This is another area that should become permanent. Payers should continue to pay telehealth services on par with in-person visits.”
• Telephony. “Psychiatrists and other physicians haven’t been traditionally paid for telephone visits. But there’s no doubt that telephone follow-up visits can be very beneficial, so while I wouldn’t personally see a new patient on the phone, I now follow up with them on the phone once I have gotten to know them, and this works well.”
• Prescribing. The Ryan Haight Online Pharmacy Consumer Protection Act of 2008 was introduced to stop overseas pharmacies prescribing narcotics. “It was very successful, but as a side effect, it stopped most physicians from prescribing controlled substances on video. With COVID, we can now do this. For psychiatry, this is very important because it means we can use video to treat people for addictions with medications like buprenorphine and [prescribe] stimulants for children with ADHD. The U.S. Drug Enforcement Administration should finalize regulations for the Ryan Haight Act to allow for the prescribing of controlled substances via telehealth without a prior in-person exam.”

The American Psychiatric Association has called for an extension of the telehealth waiver authority under COVID-19 beyond the emergency declaration to study its impact. It will continue to advocate to allow for telephone-only telehealth to be reimbursed at the same rate as live audio-video, said a spokesperson. “We also will continue to advocate for the removal of geographic and originating site restrictions in Medicare, which prevent Medicare patients from being seen in the home,” with some exceptions, the spokesperson said.

The APA has also issued guidance to practitioners seeking clarity on telehealth coverage and COVID-19.

This year saw an unprecedented rise in medical consults over virtual platforms, as the COVID-19 pandemic raged on in the United States and worldwide.

Statistics from major health care groups and payers underscore this effect. Polling 1,004 U.S. adults this fall, the American Psychiatric Association found that 31% had used telehealth services – with 72% reporting they had ventured into this mode of care over the last 6 months.

The Coronavirus Aid, Relief, and Economic Security Act, or CARES Act, was a major catalyst, waiving geographic and Medicare telehealth payment restrictions for mental health services during certain emergency periods. Medicare beneficiaries gained access to telehealth services – they could start seeing doctors via videoconferencing in their homes, regardless of location. The Centers for Medicare and Medicaid Services began paying doctors for telehealth services at the same rate as in-office visits for all diagnoses and issued a toolkit to promote adoption of telehealth coverage policies among state Medicaid agencies.

Most states responded, expanding telehealth in Medicaid programs and relaxing restrictions on provider licensing, online prescribing, and patient consent for telehealth, the Kaiser Family Foundation reported in May. Other federal agencies took actions during the public health emergency. The Drug Enforcement Administration allowed for the prescribing of controlled substances through telemedicine, and the U.S. Department of Health & Human Services’s Office for Civil Rights agreed not to impose penalties for noncompliance of HIPAA during video conferencing, provided that physicians were acting in the best interests of the patient.

“The benefits we’re seeing on both sides – for patients and for doctors – around convenience and access are wonderful,” Nina Vasan, MD, MBA, founder and executive director of Brainstorm: The Stanford Lab for Mental Health Innovation and chair of APA’s Committee on Innovation, said in an interview. Before COVID began, only a handful of clinicians were seeing patients via televideo at Stanford, said Dr. Vasan. “Now, almost everyone is. The forced uptake and change of behavior was something we’ve needed for years, and now that it has happened, I don’t see it going away.”

This year saw an unprecedented rise in medical consults over virtual platforms, as the COVID-19 pandemic raged on in the United States and worldwide.

Statistics from major health care groups and payers underscore this effect. Polling 1,004 U.S. adults this fall, the American Psychiatric Association found that 31% had used telehealth services – with 72% reporting they had ventured into this mode of care over the last 6 months.

The Coronavirus Aid, Relief, and Economic Security Act, or CARES Act, was a major catalyst, waiving geographic and Medicare telehealth payment restrictions for mental health services during certain emergency periods. Medicare beneficiaries gained access to telehealth services – they could start seeing doctors via videoconferencing in their homes, regardless of location. The Centers for Medicare and Medicaid Services began paying doctors for telehealth services at the same rate as in-office visits for all diagnoses and issued a toolkit to promote adoption of telehealth coverage policies among state Medicaid agencies.

Most states responded, expanding telehealth in Medicaid programs and relaxing restrictions on provider licensing, online prescribing, and patient consent for telehealth, the Kaiser Family Foundation reported in May. Other federal agencies took actions during the public health emergency. The Drug Enforcement Administration allowed for the prescribing of controlled substances through telemedicine, and the U.S. Department of Health & Human Services’s Office for Civil Rights agreed not to impose penalties for noncompliance of HIPAA during video conferencing, provided that physicians were acting in the best interests of the patient.

“The benefits we’re seeing on both sides – for patients and for doctors – around convenience and access are wonderful,” Nina Vasan, MD, MBA, founder and executive director of Brainstorm: The Stanford Lab for Mental Health Innovation and chair of APA’s Committee on Innovation, said in an interview. Before COVID began, only a handful of clinicians were seeing patients via televideo at Stanford, said Dr. Vasan. “Now, almost everyone is. The forced uptake and change of behavior was something we’ve needed for years, and now that it has happened, I don’t see it going away.”

This year saw an unprecedented rise in medical consults over virtual platforms, as the COVID-19 pandemic raged on in the United States and worldwide.

Statistics from major health care groups and payers underscore this effect. Polling 1,004 U.S. adults this fall, the American Psychiatric Association found that 31% had used telehealth services – with 72% reporting they had ventured into this mode of care over the last 6 months.

The Coronavirus Aid, Relief, and Economic Security Act, or CARES Act, was a major catalyst, waiving geographic and Medicare telehealth payment restrictions for mental health services during certain emergency periods. Medicare beneficiaries gained access to telehealth services – they could start seeing doctors via videoconferencing in their homes, regardless of location. The Centers for Medicare and Medicaid Services began paying doctors for telehealth services at the same rate as in-office visits for all diagnoses and issued a toolkit to promote adoption of telehealth coverage policies among state Medicaid agencies.

Most states responded, expanding telehealth in Medicaid programs and relaxing restrictions on provider licensing, online prescribing, and patient consent for telehealth, the Kaiser Family Foundation reported in May. Other federal agencies took actions during the public health emergency. The Drug Enforcement Administration allowed for the prescribing of controlled substances through telemedicine, and the U.S. Department of Health & Human Services’s Office for Civil Rights agreed not to impose penalties for noncompliance of HIPAA during video conferencing, provided that physicians were acting in the best interests of the patient.

“The benefits we’re seeing on both sides – for patients and for doctors – around convenience and access are wonderful,” Nina Vasan, MD, MBA, founder and executive director of Brainstorm: The Stanford Lab for Mental Health Innovation and chair of APA’s Committee on Innovation, said in an interview. Before COVID began, only a handful of clinicians were seeing patients via televideo at Stanford, said Dr. Vasan. “Now, almost everyone is. The forced uptake and change of behavior was something we’ve needed for years, and now that it has happened, I don’t see it going away.”