Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Women with type 2 diabetes who take metformin during pregnancy to control their blood glucose levels experience a range of benefits, including reduced weight gain, reduced insulin doses, and fewer large-for-gestational-age babies, suggest the results of a randomized controlled trial.

However, the drug was associated with an increased risk of small-for-gestational-age babies, which poses the question as to risk versus benefit of metformin on the health of offspring.

“Better understanding of the short- and long-term implications of these effects on infants will be important to properly advise patients with type 2 diabetes contemplating use of metformin during pregnancy,” said lead author Denice S. Feig, MD, Mount Sinai Hospital, Toronto.

The research was presented at the Diabetes UK Professional Conference: Online Series on Nov. 17 and recently published in The Lancet Diabetes & Endocrinology.

Summing up, Dr. Feig said that, on balance, she would be inclined to give metformin to most pregnant women with type 2 diabetes, perhaps with the exception of those who may have risk factors for small-for-gestational-age babies; for example, women who’ve had intrauterine growth restriction, who are smokers, and have significant renal disease, or have a lower body mass index.
 

Increased prevalence of type 2 diabetes in pregnancy

Dr. Feig said that across the developed world there have been huge increases in the prevalence of type 2 diabetes in pregnancy in recent years.

Insulin is the standard treatment for the management of type 2 diabetes in pregnancy, but these women have marked insulin resistance that worsens in pregnancy, which means their insulin requirements increase, leading to weight gain, painful injections, high cost, and noncompliance.

So despite treatment with insulin, these women continue to face increased rates of adverse maternal and fetal outcomes.

And although metformin is increasingly being used in women with type 2 diabetes during pregnancy, there is a scarcity of data on the benefits and harms of metformin use on pregnancy outcomes in these women.

The MiTy trial was therefore undertaken to determine whether metformin could improve outcomes.

The team recruited 502 women from 29 sites in Canada and Australia who had type 2 diabetes prior to pregnancy or were diagnosed during pregnancy, before 20 weeks’ gestation. The women were randomized to metformin 1 g twice daily or placebo, in addition to their usual insulin regimen, at between 6 and 28 weeks’ gestation.

Type 2 diabetes was diagnosed prior to pregnancy in 83% of women in the metformin group and in 90% of those assigned to placebo. The mean hemoglobin A1c level at randomization was 47 mmol/mol (6.5%) in both groups.

The average maternal age at baseline was approximately 35 years and mean gestational age at randomization was 16 weeks. Mean prepregnancy BMI was approximately 34 kg/m².

Of note, only 30% were of European ethnicity.
 

Less weight gain, lower A1c, less insulin needed with metformin

Dr. Feig reported that there was no significant difference between the treatment groups in terms of the proportion of women with the composite primary outcome of pregnancy loss, preterm birth, birth injury, respiratory distress, neonatal hypoglycemia, or admission to neonatal intensive care lasting more than 24 hours (P = 0.86).

However, women in the metformin group had significantly less overall weight gain during pregnancy than did those in the placebo group, at –1.8 kg (P < .0001).

They also had a significantly lower last A1c level in pregnancy, at 41 mmol/mol (5.9%) versus 43.2 mmol/mol (6.1%) in those given placebo (P = .015), and required fewer insulin doses, at 1.1 versus 1.5 units/kg/day (P < .0001), which translated to a reduction of almost 44 units/day.

Women given metformin were also less likely to require Cesarean section delivery, at 53.4% versus 62.7% in the placebo group (P = .03), although there was no difference between groups in terms of gestational hypertension or preeclampsia.

The most common adverse events were gastrointestinal complications, which occurred in 27.3% of women in the metformin group and 22.3% of those given placebo.

There were no significant differences between the metformin and placebo groups in rates of pregnancy loss (P = .81), preterm birth (P = .16), birth injury (P = .37), respiratory distress (P = .49), and congenital anomalies (P = .16).
 

Average birth weight lower with metformin

However, Dr. Feig showed that the average birth weight was lower for offspring of women given metformin than those assigned to placebo, at 3.2 kg (7.05 lb) versus 3.4 kg (7.4 lb) (P = .002).

Women given metformin were also less likely to have a baby with a birth weight of 4 kg (8.8 lb) or more, at 12.1% versus 19.2%, or a relative risk of 0.65 (P = .046), and a baby that was extremely large for gestational age, at 8.6% versus 14.8%, or a relative risk of 0.58 (P = .046).

But of concern, metformin was associated with an increased risk of small-for-gestational-age babies, at 12.9% versus 6.6% with placebo, or a relative risk of 1.96 (P = .03).

Dr. Feig suggested that this may be due to a direct effect of metformin “because as we know metformin inhibits the mTOR pathway,” which is a “primary nutrient sensor in the placenta” and could “attenuate nutrient flux and fetal growth.”

She said it is not clear whether the small-for-gestational-age babies were “healthy or unhealthy.”

To investigate further, the team has launched the MiTy Kids study, which will follow the offspring in the MiTy trial to determine whether metformin during pregnancy is associated with a reduction in adiposity and improvement in insulin resistance in the babies at 2 years of age.
 

Who should be given metformin?

During the discussion, Helen R. Murphy, MD, PhD, Norwich Medical School, University of East Anglia, England, asked whether Dr. Feig would recommend continuing metformin in pregnancy if it was started preconception for fertility issues rather than diabetes.

She replied: “If they don’t have diabetes and it’s simply for PCOS [polycystic ovary syndrome], then I have either stopped it as soon as they got pregnant or sometimes continued it through the first trimester, and then stopped.

“If the person has diabetes, however, I think given this work, for most people I would continue it,” she said.

The study was funded by the Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, and the University of Toronto. The authors have reported no relevant financial relationships.

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

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with a primary humoral immunodeficiency (PID) are 91% more likely to have a psychiatric disorder and 84% more likely to exhibit suicidal behavior, compared against those without the condition, new research shows.

Results showed that this association, which was stronger in women, could not be fully explained by comorbid autoimmune diseases or by familial confounding.

These findings have important clinical implications, study investigator Josef Isung, MD, PhD, Centre for Psychiatry Research, Karolinska Institute, Stockholm, Sweden, told Medscape Medical News.

Clinicians managing patients with PID “should be aware of this increased association with psychiatric disorders and perhaps screen for them,” said Isung.

The study was published in the November issue of JAMA Psychiatry.
 

Registry study

Mounting evidence suggests immune disruption plays a role in psychiatric disorders through a range of mechanisms, including altered neurodevelopment. However, little is known about the neuropsychiatric consequences resulting from the underproduction of homeostatic antibodies.

PIDs involve a deficiency in antibody production, mainly affecting immunoglobulin, “or the humoral aspect of the immune system,” said Isung. They’re associated with an increased risk for recurrent infections and of developing autoimmune diseases.

The immunodeficiency can be severe, even life threatening, but can also be relatively mild. One of the less severe PID types is selective IgA deficiency, which is linked to increased infections within the mucosa-associated lymphoid tissue (MALT), an important immune barrier.

Experts have long suspected that infections within the MALT are associated with certain forms of psychopathology in children, particularly obsessive-compulsive disorder and chronic tic disorders.

While patients with this selective IgA subtype may be at some increased risk for infection and autoimmune disease, their overall health otherwise is good, said Isung.

The prevalence of PIDs ranges from about 1:250 to 1:20,000, depending on the type of humoral immunodeficiency, although most would fall into the relatively rare category, he added.

Using several linked national Swedish registries, researchers identified individuals with any PID diagnosis affecting immunoglobulin levels, their full siblings, and those with a lifetime diagnosis of selective IgA deficiency. In addition, they collected data on autoimmune diseases.

The study outcome was a lifetime record of a psychiatric disorder, a suicide attempt, or death by suicide.
 

Strong link to autism

Researchers identified 8378 patients (59% women) with PID affecting immunoglobulin levels (median age at first diagnosis, 47.8 years). They compared this group with almost 14.3 million subjects without PID.

In those with PID, 27.6% had an autoimmune disease vs 6.8% of those without PID, a statistically significant difference (P < .001).

About 20.5% of those with PID and 10.7% of unexposed subjects had at least one diagnosis of a psychiatric disorder.

In a model adjusted for year of birth, sex, and history of autoimmune disease, subjects with PID had a 91% higher likelihood of any psychiatric disorder (adjusted odds ratio [AOR] 1.91; 95% CI, 1.81 - 2.01; P < .001) vs their counterparts without PID.

The AORs for individual psychiatric disorders ranged from 1.34 (95% CI, 1.17 - 1.54; P < .001) for schizophrenia and other psychotic disorders to 2.99 (95% CI, 2.42 - 3.70; P < .001) for autism spectrum disorders (ASDs)

It’s unclear why the association with PID was strongest for autism, “but being a neurodevelopmental disorder, maybe autism is logically more associated with this type of disruption,” said Isung.

Research suggests that immunologic disruption may play a role in ASD, either through altered maternal immune function in utero or through immune disruption after birth, the researchers note.

Compared to those without PID, individuals with it had a significantly increased likelihood of any suicidal behavior (AOR, 1.84; 95% CI, 1.66 - 2.04, P < .001) as well as individual outcomes of death by suicide and suicide attempts.

The association with psychiatric disorders and suicidal behavior was markedly stronger for exposure to both PID and autoimmune disease than for exposure to either of these alone, which suggest an additive effect for these immune-related conditions.
 

Sex differences

“It was unclear to us why women seemed particularly vulnerable,” said Isung. He noted that PIDs are generally about as common in women as in men, but women tend to have higher rates of psychiatric disorders.

The analysis of the sibling cohort also revealed an elevated risk for psychiatric disorders, including ASD and suicidal behavior, but to a lesser degree.

“From this we could infer that at least part of the associations would be genetic, but part would be related to the disruption in itself,” said Isung.

An analysis examining selective IgA subtype also revealed a link with psychiatric disorders and suicidal behavior, suggesting this link is not exclusive to severe PID cases.

“Our conclusion here was that it seems like PID itself, or the immune disruption in itself, could explain the association rather than the burden of illness,” said Isung.

However, he acknowledged that the long-term stress and mental health fallout of having a chronic illness like PID may also explain some of the increased risk for psychiatric disorders.

This study, he said, provides more evidence that immune disruptions affect neurodevelopment and the brain. However, he added, the underlying mechanism still isn’t fully understood.

The results highlight the need to raise awareness of the association between immunodeficiency and mental illness, including suicidality among clinicians, patients, and advocates.

These findings may also have implications in patients with other immune deficiencies, said Isung, noting, “it would be interesting to further explore associations with other immunocompromised populations.”
 

No surprises

Commenting on the findings for Medscape Medical News, Igor Galynker, MD, professor of psychiatry at Icahn School of Medicine at Mount Sinai, New York City, said the study was “very well-done” and used “reliable and well-controlled” databases.

However, he added, the results “are neither particularly dramatic nor conclusive” as it makes sense that medical illnesses like PID would “increase risk of psychopathology,” said Galynker.

PID patients are much more likely to have contact with clinicians and to receive a psychiatric diagnosis, he said.

“People with a chronic illness are more stressed and generally have high incidences of depression, anxiety, and suicidal behavior. In addition to that, they may be more likely to be diagnosed with those conditions because they see a clinician more frequently.”

However, that reasoning doesn’t apply to autism, which manifests in early childhood and so is unlikely to be the result of stress, said Galynker, which is why he believes the finding that ASD is the psychiatric outcome most strongly associated with PID is “the most convincing.”

Galynker wasn’t surprised that the association between PID and psychiatric illnesses, and suicidal behaviors, was stronger among women.

“Women attempt suicide four times more often than men to begin with, so you would expect this to be more pronounced” in those with PID.

The study was supported by grants from the Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute; Stockholm Care Services; the Soderstrom Konig Foundation; and the Fredrik & Ingrid Thurings Foundation. Isung and Galynker have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

People with chronic lung disease who need significant amounts of oxygen should be able to take it in liquid form when they are able to leave home, according to a new guideline from the American Thoracic Society.

“For those patients, often the other types of devices either can’t supply enough oxygen or are not portable enough,” said Anne Holland, PT, PhD, a professor of physiotherapy at Monash University and Alfred Hospital in Melbourne. “They’re heavy and cumbersome to use.”

Dr. Holland and colleagues also gave a more general recommendation to prescribe ambulatory oxygen – though not necessarily in liquid form – for adults with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) who have severe exertional room air hypoxemia.

They published the recommendations as part of the ATS’ first-ever guideline on home oxygen therapy for adults with chronic lung disease in the American Journal of Respiratory and Critical Care Medicine.

The ATS identified the need for an updated guideline because of new research, and because an online survey of almost 2,000 U.S. oxygen users showed they were having problems accessing and using oxygen.

For long-term oxygen therapy, the guideline reinforces what most practitioners are already doing, Dr. Holland said. It recommends that adults with COPD or ILD who have severe chronic resting room air hypoxemia receive oxygen therapy at least 15 hours per day.

On the other hand, in adults with COPD who have moderate chronic resting room-air hypoxemia, the guideline recommends against long-term oxygen therapy.

The recommendation to prescribe ambulatory oxygen for people with severe exertional room-air hypoxemia may have more effect on practice, Dr. Holland said. Laboratory-based tests have suggested oxygen can improve exercise capacity, but clinical trials used during daily life have had inconsistent results.

The evidence is particularly lacking for patients with ILD, Dr. Holland said in an interview. “It’s such an important part of practice to maintain oxygen therapy that it’s ethically very difficult to conduct such a trial. So, we did have to make use of indirect evidence from patients with COPD” for the guidelines.

The portable equipment comes with burdens, including managing its weight and bulk, social stigma, fear of cylinders running out, and equipment noise.

“We tried to clearly set out both the benefits and burdens of that therapy and made a conditional recommendation, and also a really strong call for shared decision-making with patients and health professionals,” Dr. Holland said.

In addition to looking at the evidence, the panel took into consideration the concerns identified by patients. This included the challenge of figuring out how to use the equipment. “All the oxygen equipment was ‘dumped’ on me,” wrote one oxygen user quoted in the guideline. “I knew nothing and was in a daze. I am sure that the delivery guy gave me some instructions when it was delivered but I retained nothing.”

For this reason, the guideline describes instruction and training on the use and maintenance of the equipment, including smoking cessation, fire prevention, and tripping hazards, as a “best practice.”

Nothing about the guideline is surprising, said MeiLan K. Han, MD, a spokesperson for the American Lung Association and professor of pulmonary and critical care medicine at the University of Michigan Health System in Ann Arbor. “I don’t think they’ve actually come to any new conclusion,” she said in an interview. “This is pretty much how I practice already.”

But the guideline could have an effect on policy, she said. The panel noted research showing that lower Medicare reimbursement to durable medical equipment companies since 2011 has forced many patients to switch from small, easily portable liquid oxygen to home-fill oxygen systems that include heavy cylinders.

“The impact of this decline in the availability and adequacy of portable oxygen devices in the United States has been profound,” Dr. Holland and colleagues wrote. “Supplemental oxygen users reported numerous problems, with the overarching theme being restricted mobility and isolation due to inadequate portable options.”

For this reason, the guideline recommends liquid oxygen for patients with chronic lung disease who are mobile outside of the home and require continuous oxygen flow rates of >3 L/min during exertion.

Many of Dr. Han’s patients have struggled with this problem, she said. “The clunkiest, most painful form of ‘ambulatory oxygen’ are these really large metal cylinders. They’re huge. And you have to carry them on a cart. It’s portable in theory only.”

Some of her patients have resorted to buying their own equipment on eBay, she said.

The authors report multiple disclosures including serving as advisory board members to foundations and pharmaceutical companies, and some are company employees or stockholders.

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

People with chronic lung disease who need significant amounts of oxygen should be able to take it in liquid form when they are able to leave home, according to a new guideline from the American Thoracic Society.

“For those patients, often the other types of devices either can’t supply enough oxygen or are not portable enough,” said Anne Holland, PT, PhD, a professor of physiotherapy at Monash University and Alfred Hospital in Melbourne. “They’re heavy and cumbersome to use.”

Dr. Holland and colleagues also gave a more general recommendation to prescribe ambulatory oxygen – though not necessarily in liquid form – for adults with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) who have severe exertional room air hypoxemia.

They published the recommendations as part of the ATS’ first-ever guideline on home oxygen therapy for adults with chronic lung disease in the American Journal of Respiratory and Critical Care Medicine.

The ATS identified the need for an updated guideline because of new research, and because an online survey of almost 2,000 U.S. oxygen users showed they were having problems accessing and using oxygen.

For long-term oxygen therapy, the guideline reinforces what most practitioners are already doing, Dr. Holland said. It recommends that adults with COPD or ILD who have severe chronic resting room air hypoxemia receive oxygen therapy at least 15 hours per day.

On the other hand, in adults with COPD who have moderate chronic resting room-air hypoxemia, the guideline recommends against long-term oxygen therapy.

The recommendation to prescribe ambulatory oxygen for people with severe exertional room-air hypoxemia may have more effect on practice, Dr. Holland said. Laboratory-based tests have suggested oxygen can improve exercise capacity, but clinical trials used during daily life have had inconsistent results.

The evidence is particularly lacking for patients with ILD, Dr. Holland said in an interview. “It’s such an important part of practice to maintain oxygen therapy that it’s ethically very difficult to conduct such a trial. So, we did have to make use of indirect evidence from patients with COPD” for the guidelines.

The portable equipment comes with burdens, including managing its weight and bulk, social stigma, fear of cylinders running out, and equipment noise.

“We tried to clearly set out both the benefits and burdens of that therapy and made a conditional recommendation, and also a really strong call for shared decision-making with patients and health professionals,” Dr. Holland said.

In addition to looking at the evidence, the panel took into consideration the concerns identified by patients. This included the challenge of figuring out how to use the equipment. “All the oxygen equipment was ‘dumped’ on me,” wrote one oxygen user quoted in the guideline. “I knew nothing and was in a daze. I am sure that the delivery guy gave me some instructions when it was delivered but I retained nothing.”

For this reason, the guideline describes instruction and training on the use and maintenance of the equipment, including smoking cessation, fire prevention, and tripping hazards, as a “best practice.”

Nothing about the guideline is surprising, said MeiLan K. Han, MD, a spokesperson for the American Lung Association and professor of pulmonary and critical care medicine at the University of Michigan Health System in Ann Arbor. “I don’t think they’ve actually come to any new conclusion,” she said in an interview. “This is pretty much how I practice already.”

But the guideline could have an effect on policy, she said. The panel noted research showing that lower Medicare reimbursement to durable medical equipment companies since 2011 has forced many patients to switch from small, easily portable liquid oxygen to home-fill oxygen systems that include heavy cylinders.

“The impact of this decline in the availability and adequacy of portable oxygen devices in the United States has been profound,” Dr. Holland and colleagues wrote. “Supplemental oxygen users reported numerous problems, with the overarching theme being restricted mobility and isolation due to inadequate portable options.”

For this reason, the guideline recommends liquid oxygen for patients with chronic lung disease who are mobile outside of the home and require continuous oxygen flow rates of >3 L/min during exertion.

Many of Dr. Han’s patients have struggled with this problem, she said. “The clunkiest, most painful form of ‘ambulatory oxygen’ are these really large metal cylinders. They’re huge. And you have to carry them on a cart. It’s portable in theory only.”

Some of her patients have resorted to buying their own equipment on eBay, she said.

The authors report multiple disclosures including serving as advisory board members to foundations and pharmaceutical companies, and some are company employees or stockholders.

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

People with chronic lung disease who need significant amounts of oxygen should be able to take it in liquid form when they are able to leave home, according to a new guideline from the American Thoracic Society.

“For those patients, often the other types of devices either can’t supply enough oxygen or are not portable enough,” said Anne Holland, PT, PhD, a professor of physiotherapy at Monash University and Alfred Hospital in Melbourne. “They’re heavy and cumbersome to use.”

Dr. Holland and colleagues also gave a more general recommendation to prescribe ambulatory oxygen – though not necessarily in liquid form – for adults with chronic obstructive pulmonary disease (COPD) or interstitial lung disease (ILD) who have severe exertional room air hypoxemia.

They published the recommendations as part of the ATS’ first-ever guideline on home oxygen therapy for adults with chronic lung disease in the American Journal of Respiratory and Critical Care Medicine.

The ATS identified the need for an updated guideline because of new research, and because an online survey of almost 2,000 U.S. oxygen users showed they were having problems accessing and using oxygen.

For long-term oxygen therapy, the guideline reinforces what most practitioners are already doing, Dr. Holland said. It recommends that adults with COPD or ILD who have severe chronic resting room air hypoxemia receive oxygen therapy at least 15 hours per day.

On the other hand, in adults with COPD who have moderate chronic resting room-air hypoxemia, the guideline recommends against long-term oxygen therapy.

The recommendation to prescribe ambulatory oxygen for people with severe exertional room-air hypoxemia may have more effect on practice, Dr. Holland said. Laboratory-based tests have suggested oxygen can improve exercise capacity, but clinical trials used during daily life have had inconsistent results.

The evidence is particularly lacking for patients with ILD, Dr. Holland said in an interview. “It’s such an important part of practice to maintain oxygen therapy that it’s ethically very difficult to conduct such a trial. So, we did have to make use of indirect evidence from patients with COPD” for the guidelines.

The portable equipment comes with burdens, including managing its weight and bulk, social stigma, fear of cylinders running out, and equipment noise.

“We tried to clearly set out both the benefits and burdens of that therapy and made a conditional recommendation, and also a really strong call for shared decision-making with patients and health professionals,” Dr. Holland said.

In addition to looking at the evidence, the panel took into consideration the concerns identified by patients. This included the challenge of figuring out how to use the equipment. “All the oxygen equipment was ‘dumped’ on me,” wrote one oxygen user quoted in the guideline. “I knew nothing and was in a daze. I am sure that the delivery guy gave me some instructions when it was delivered but I retained nothing.”

For this reason, the guideline describes instruction and training on the use and maintenance of the equipment, including smoking cessation, fire prevention, and tripping hazards, as a “best practice.”

Nothing about the guideline is surprising, said MeiLan K. Han, MD, a spokesperson for the American Lung Association and professor of pulmonary and critical care medicine at the University of Michigan Health System in Ann Arbor. “I don’t think they’ve actually come to any new conclusion,” she said in an interview. “This is pretty much how I practice already.”

But the guideline could have an effect on policy, she said. The panel noted research showing that lower Medicare reimbursement to durable medical equipment companies since 2011 has forced many patients to switch from small, easily portable liquid oxygen to home-fill oxygen systems that include heavy cylinders.

“The impact of this decline in the availability and adequacy of portable oxygen devices in the United States has been profound,” Dr. Holland and colleagues wrote. “Supplemental oxygen users reported numerous problems, with the overarching theme being restricted mobility and isolation due to inadequate portable options.”

For this reason, the guideline recommends liquid oxygen for patients with chronic lung disease who are mobile outside of the home and require continuous oxygen flow rates of >3 L/min during exertion.

Many of Dr. Han’s patients have struggled with this problem, she said. “The clunkiest, most painful form of ‘ambulatory oxygen’ are these really large metal cylinders. They’re huge. And you have to carry them on a cart. It’s portable in theory only.”

Some of her patients have resorted to buying their own equipment on eBay, she said.

The authors report multiple disclosures including serving as advisory board members to foundations and pharmaceutical companies, and some are company employees or stockholders.

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

A neoadjuvant strategy combining two immunostimulatory agents with differing mechanisms of action is efficacious and safe in patients with high-risk, resectable melanoma, according to final results of the phase 2 Neo-C-Nivo trial.

The two agents are the PD-1 inhibitor nivolumab and CMP-001, an investigational Toll-like receptor 9 agonist that activates tumor-associated plasmacytoid dendritic cells.

CMP-001 and nivolumab produced a major pathologic response in 60% of patients, and these patients had a 1-year relapse-free survival rate of 89%. About 23% of patients had grade 3 treatment-related adverse events, and there were no grade 4-5 treatment-related events.

These data were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

“Stage III melanoma is a very, very high risk disease. Despite appropriate management, which involves surgical resection followed by adjuvant immunotherapy, a large number of patients still relapse,” noted study author Diwakar Davar, MD, of the University of Pittsburgh Hillman Cancer Center.

“Neoadjuvant immunotherapy in this setting enhances the systemic T-cell response to tumor antigens,” he explained. “As a result, there is greater detection and killing of micrometastatic disease. And, indeed, neoadjuvant immunotherapy with anti–[programmed death–1] monotherapy or with anti-PD1 and anti-CTLA4 combination therapy produces high response rates, although the combination therapy is associated with significant toxicity.”
 

Patients, treatment, and response

The Neo-C-Nivo trial enrolled 31 patients with resectable stage IIIB/C/D melanoma having clinically apparent lymph node disease.

The patients were treated with three cycles of nivolumab given every 2 weeks. They also received seven weekly injections of CMP-001 subcutaneously and then intratumorally. After surgical resection, the patients received more of the same immunotherapy.

At a median follow-up of 15 months, 60% of patients had a major pathologic response, 50% had a complete response, and 10% had a major response. Some 70% of patients (after additionally including partial responders) had any pathologic response.

“More than half of the patients that we treated had more than one injectable lesion,” Dr. Davar noted. “I want to emphasize that only one lesion was injected, so the results we got illustrate that the rest of the patients who had more than one injectable lesion had regression in their injected and uninjected lesions.”

Biomarker analyses showed that response was associated with evidence of immune activation, both in the tumor and in the blood. With immunotherapy, the density of CD8 tumor-infiltrating lymphocytes increased by a median of 10.3-fold in pathologic responders as compared with only 0.8-fold in nonresponders (P < .05). In addition, responders had evidence of activated CD8-positive T cells peripherally, as well as presence of plasmacytoid dendritic cells within the tumor microenvironment.
 

Survival and safety

Patients had better median relapse-free survival if they attained a major pathologic response (not reached in either group, P = .0106) or any pathologic response (not reached vs. 5 months, P = .0001).

The landmark 1-year relapse-free survival rate was 89% for major pathologic responders and 90% for all pathologic responders.

Overall, 22.6% of patients experienced grade 3 treatment-related adverse events, the majority of which did not require medical intervention and none of which delayed planned surgery. There were no grade 4-5 treatment-related adverse events.

Cytokine release syndrome was uncommon, seen in 16.1% of patients, possibly because the cohort received prophylaxis, Dr. Davar proposed.
 

Another treatment option?

“Intratumoral CMP-001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in patients with regionally advanced melanoma. Further study of this combination in high-risk resectable melanoma is planned,” Dr. Davar concluded.

“This combination achieved high response rates and certainly should be considered for a larger trial,” agreed session cochair Brian Gastman, MD, of the Cleveland (Ohio) Clinic.

However, long-term outcomes are pending, and it is not clear how efficacy of the studied combination will ultimately stack up against that of other treatment options, Dr. Gastman cautioned in an interview. “For example, it’s hard to tell if this will lead to better results versus, say, T-VEC [talimogene laherparepvec] with an anti-PD-1 agent,” he elaborated.

Nonetheless, “the implication of these findings is that there is another potential injectable option that can be combined with checkpoint inhibitors, and it may be useful for patients with refractory disease,” Dr. Gastman concluded.

The trial was funded by Checkmate Pharmaceuticals. Dr. Davar disclosed relationships with Checkmate Pharmaceuticals, Array Biopharma, Merck, Shionogi, Vedanta, Bristol-Myers Squibb, CellSight Technologies, GlaxoSmithKline/Tesaro, and Medpacto. Dr. Gastman disclosed no relevant conflicts of interest.

SOURCE: Davar D et al. SITC 2020, Abstract 303.

A neoadjuvant strategy combining two immunostimulatory agents with differing mechanisms of action is efficacious and safe in patients with high-risk, resectable melanoma, according to final results of the phase 2 Neo-C-Nivo trial.

The two agents are the PD-1 inhibitor nivolumab and CMP-001, an investigational Toll-like receptor 9 agonist that activates tumor-associated plasmacytoid dendritic cells.

CMP-001 and nivolumab produced a major pathologic response in 60% of patients, and these patients had a 1-year relapse-free survival rate of 89%. About 23% of patients had grade 3 treatment-related adverse events, and there were no grade 4-5 treatment-related events.

These data were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

“Stage III melanoma is a very, very high risk disease. Despite appropriate management, which involves surgical resection followed by adjuvant immunotherapy, a large number of patients still relapse,” noted study author Diwakar Davar, MD, of the University of Pittsburgh Hillman Cancer Center.

“Neoadjuvant immunotherapy in this setting enhances the systemic T-cell response to tumor antigens,” he explained. “As a result, there is greater detection and killing of micrometastatic disease. And, indeed, neoadjuvant immunotherapy with anti–[programmed death–1] monotherapy or with anti-PD1 and anti-CTLA4 combination therapy produces high response rates, although the combination therapy is associated with significant toxicity.”
 

Patients, treatment, and response

The Neo-C-Nivo trial enrolled 31 patients with resectable stage IIIB/C/D melanoma having clinically apparent lymph node disease.

The patients were treated with three cycles of nivolumab given every 2 weeks. They also received seven weekly injections of CMP-001 subcutaneously and then intratumorally. After surgical resection, the patients received more of the same immunotherapy.

At a median follow-up of 15 months, 60% of patients had a major pathologic response, 50% had a complete response, and 10% had a major response. Some 70% of patients (after additionally including partial responders) had any pathologic response.

“More than half of the patients that we treated had more than one injectable lesion,” Dr. Davar noted. “I want to emphasize that only one lesion was injected, so the results we got illustrate that the rest of the patients who had more than one injectable lesion had regression in their injected and uninjected lesions.”

Biomarker analyses showed that response was associated with evidence of immune activation, both in the tumor and in the blood. With immunotherapy, the density of CD8 tumor-infiltrating lymphocytes increased by a median of 10.3-fold in pathologic responders as compared with only 0.8-fold in nonresponders (P < .05). In addition, responders had evidence of activated CD8-positive T cells peripherally, as well as presence of plasmacytoid dendritic cells within the tumor microenvironment.
 

Survival and safety

Patients had better median relapse-free survival if they attained a major pathologic response (not reached in either group, P = .0106) or any pathologic response (not reached vs. 5 months, P = .0001).

The landmark 1-year relapse-free survival rate was 89% for major pathologic responders and 90% for all pathologic responders.

Overall, 22.6% of patients experienced grade 3 treatment-related adverse events, the majority of which did not require medical intervention and none of which delayed planned surgery. There were no grade 4-5 treatment-related adverse events.

Cytokine release syndrome was uncommon, seen in 16.1% of patients, possibly because the cohort received prophylaxis, Dr. Davar proposed.
 

Another treatment option?

“Intratumoral CMP-001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in patients with regionally advanced melanoma. Further study of this combination in high-risk resectable melanoma is planned,” Dr. Davar concluded.

“This combination achieved high response rates and certainly should be considered for a larger trial,” agreed session cochair Brian Gastman, MD, of the Cleveland (Ohio) Clinic.

However, long-term outcomes are pending, and it is not clear how efficacy of the studied combination will ultimately stack up against that of other treatment options, Dr. Gastman cautioned in an interview. “For example, it’s hard to tell if this will lead to better results versus, say, T-VEC [talimogene laherparepvec] with an anti-PD-1 agent,” he elaborated.

Nonetheless, “the implication of these findings is that there is another potential injectable option that can be combined with checkpoint inhibitors, and it may be useful for patients with refractory disease,” Dr. Gastman concluded.

The trial was funded by Checkmate Pharmaceuticals. Dr. Davar disclosed relationships with Checkmate Pharmaceuticals, Array Biopharma, Merck, Shionogi, Vedanta, Bristol-Myers Squibb, CellSight Technologies, GlaxoSmithKline/Tesaro, and Medpacto. Dr. Gastman disclosed no relevant conflicts of interest.

SOURCE: Davar D et al. SITC 2020, Abstract 303.

A neoadjuvant strategy combining two immunostimulatory agents with differing mechanisms of action is efficacious and safe in patients with high-risk, resectable melanoma, according to final results of the phase 2 Neo-C-Nivo trial.

The two agents are the PD-1 inhibitor nivolumab and CMP-001, an investigational Toll-like receptor 9 agonist that activates tumor-associated plasmacytoid dendritic cells.

CMP-001 and nivolumab produced a major pathologic response in 60% of patients, and these patients had a 1-year relapse-free survival rate of 89%. About 23% of patients had grade 3 treatment-related adverse events, and there were no grade 4-5 treatment-related events.

These data were reported at the Society for Immunotherapy of Cancer’s 35th Anniversary Annual Meeting.

“Stage III melanoma is a very, very high risk disease. Despite appropriate management, which involves surgical resection followed by adjuvant immunotherapy, a large number of patients still relapse,” noted study author Diwakar Davar, MD, of the University of Pittsburgh Hillman Cancer Center.

“Neoadjuvant immunotherapy in this setting enhances the systemic T-cell response to tumor antigens,” he explained. “As a result, there is greater detection and killing of micrometastatic disease. And, indeed, neoadjuvant immunotherapy with anti–[programmed death–1] monotherapy or with anti-PD1 and anti-CTLA4 combination therapy produces high response rates, although the combination therapy is associated with significant toxicity.”
 

Patients, treatment, and response

The Neo-C-Nivo trial enrolled 31 patients with resectable stage IIIB/C/D melanoma having clinically apparent lymph node disease.

The patients were treated with three cycles of nivolumab given every 2 weeks. They also received seven weekly injections of CMP-001 subcutaneously and then intratumorally. After surgical resection, the patients received more of the same immunotherapy.

At a median follow-up of 15 months, 60% of patients had a major pathologic response, 50% had a complete response, and 10% had a major response. Some 70% of patients (after additionally including partial responders) had any pathologic response.

“More than half of the patients that we treated had more than one injectable lesion,” Dr. Davar noted. “I want to emphasize that only one lesion was injected, so the results we got illustrate that the rest of the patients who had more than one injectable lesion had regression in their injected and uninjected lesions.”

Biomarker analyses showed that response was associated with evidence of immune activation, both in the tumor and in the blood. With immunotherapy, the density of CD8 tumor-infiltrating lymphocytes increased by a median of 10.3-fold in pathologic responders as compared with only 0.8-fold in nonresponders (P < .05). In addition, responders had evidence of activated CD8-positive T cells peripherally, as well as presence of plasmacytoid dendritic cells within the tumor microenvironment.
 

Survival and safety

Patients had better median relapse-free survival if they attained a major pathologic response (not reached in either group, P = .0106) or any pathologic response (not reached vs. 5 months, P = .0001).

The landmark 1-year relapse-free survival rate was 89% for major pathologic responders and 90% for all pathologic responders.

Overall, 22.6% of patients experienced grade 3 treatment-related adverse events, the majority of which did not require medical intervention and none of which delayed planned surgery. There were no grade 4-5 treatment-related adverse events.

Cytokine release syndrome was uncommon, seen in 16.1% of patients, possibly because the cohort received prophylaxis, Dr. Davar proposed.
 

Another treatment option?

“Intratumoral CMP-001 increases clinical efficacy of PD-1 blockade with minimal additional toxicity in patients with regionally advanced melanoma. Further study of this combination in high-risk resectable melanoma is planned,” Dr. Davar concluded.

“This combination achieved high response rates and certainly should be considered for a larger trial,” agreed session cochair Brian Gastman, MD, of the Cleveland (Ohio) Clinic.

However, long-term outcomes are pending, and it is not clear how efficacy of the studied combination will ultimately stack up against that of other treatment options, Dr. Gastman cautioned in an interview. “For example, it’s hard to tell if this will lead to better results versus, say, T-VEC [talimogene laherparepvec] with an anti-PD-1 agent,” he elaborated.

Nonetheless, “the implication of these findings is that there is another potential injectable option that can be combined with checkpoint inhibitors, and it may be useful for patients with refractory disease,” Dr. Gastman concluded.

The trial was funded by Checkmate Pharmaceuticals. Dr. Davar disclosed relationships with Checkmate Pharmaceuticals, Array Biopharma, Merck, Shionogi, Vedanta, Bristol-Myers Squibb, CellSight Technologies, GlaxoSmithKline/Tesaro, and Medpacto. Dr. Gastman disclosed no relevant conflicts of interest.

SOURCE: Davar D et al. SITC 2020, Abstract 303.

A small percentage of patients with cancer show exceptional responses to treatment and survive significantly longer than patients with clinically comparable tumors, despite having advanced disease.

An ongoing research project is studying why some patients have exceptional responses. The researchers have found particular molecular features in the tumors of about a quarter of these patients. In some cases, there are multiple rare genetic changes in the tumor genome. In other cases, the tumors are infiltrated with certain types of immune cells.

The findings were published online November 19 in Cancer Cell. They come from a genomic analysis of tumor biopsy specimens from 111 patients who were identified by the National Cancer Institute’s (NCI’s) Exceptional Responders Initiative, a national project launched in 2014.

An exceptional responder is defined as an individual who achieves a partial or complete response to a treatment that would be effective in fewer than 10% of similar patients. For exceptional response, the duration of response is at least three times longer than the usual median response time.

In this study of 111 such patients, about one quarter (24%, n = 26 patients) were found to have tumors in which there were molecular features that could potentially explain exceptional responses to treatment.

“We won’t be able to identify, in every patient, which particular drugs will be beneficial,” said Louis Staudt, MD, PhD, director of the NCI’s Center for Cancer Genomics, who co-led the study. “We are nowhere near that. But what it does say is that we have identified particular mutations, some of which we knew about in some types of cancer but can also occur less commonly in other cancer types.”

Staudt noted that these mutations can “illuminate” the path that the cancer will take — and potentially can be used to predict whether the cancer will be aggressive and will require treatment or could be managed with surveillance. This is why this research can be useful in the short term, he said.

“In the longer term, this is the kind of research that inspires future work,” he told Medscape Medical News. “That would encompass clinical trials involving drugs that target some of the pathways we found to be genetically inactivated in some of these responders.”

These results support the use of genetic testing in routine clinical care, he said.

Earlier this year, the NCI team published the results of a pilot study that affirmed the feasibility of this approach. Of the more than 100 cases that were analyzed, six were identified as involving potentially clinically actionable germline mutations.
 

‘Curiosity drove the research’

“We had these wonderful and gratifying experiences with our patients, so we were immediately curious how that happened, so it was pretty much that curiosity that drove a lot of this work,” said Staudt.

In the current study, Staudt and colleagues used multiple genomic methodologies to detect mutations, copy number changes, aberrant methylation, outlier gene expression, and the cellular makeup of the tumor microenvironment.

The hypothesized mechanisms for exceptional responses were broadly divided into the following four categories: DNA damage response (n = 15), intracellular signaling pathway (n = 9), prognostic genetics (n = 9), and immunologic engagement (n = 16). For many patients, two or more of these mechanisms were involved.

The authors note that the “predominance of plausible DNA damage response mechanisms parallels the frequent use of cytotoxic chemotherapy in routine cancer treatment reflected in this cohort.”

Twenty-six patients were identified as exceptional responders. Among these patients, a variety of cancer types was represented: brain (8); gastrointestinal tract (6); breast (4); cholangiocarcinoma (2); lung (2); pancreas, endometrium, ovarian, and bladder (1 each). Many of these patients (65%, n = 17) were treated with chemotherapy that included DNA-damaging agents. For more than half (54%, n = 14), targeted therapies were used, and some patients received both.

The authors highlight several patients as examples of exceptional responders:

• One patient with glioblastoma multiforme (GBM) was treated sequentially with surgery, localized carmustine, and radiotherapy. When the cancer recurred, temozolomide was administered. This induced a complete response that has lasted for more than a decade.
• A patient with metastatic colon adenocarcinoma has had an ongoing and nearly complete response that has lasted 45 months (last follow-up) after receiving temozolomide in combination with the investigational drug TRC102 (methoxyamine, under development by Tracon) in a phase 1 clinical trial. TRC102 is an inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics.
• A patient with metastatic, estrogen receptor–positive breast cancer received trastuzumab because of a high-level ERBB2 amplification, together with anastrozole. This resulted in an ongoing 2.4-year partial response.
• Although the patient was clinically HER2 positive, her tumor had exceedingly low expression of ERBB2 mRNA. Molecular profiling had classified the tumor as of the basal-like subtype rather than the HER2-enriched subtype. This meant that it was unlikely that trastuzumab contributed to the exceptional response, the authors note. Because the patient was estrogen-receptor positive, she received anastrozole, an inhibitor of aromatase (CYP19A), which converts testosterone into estradiol.
• A patient who had a gastrointestinal stromal tumor with a deletion of KIT exon 11 experienced relapse after an initial response to imatinib, which targets KIT and other tyrosine kinases, but then achieved a complete response with sunitinib. Gene expression profiling revealed high expression not only of KIT but also of genes encoding several tyrosine kinases that are targeted by sunitinib (KDR, FLT1, and FLT3). This may have accounted for the patient’s response.

Favorable genomic characteristics

The authors defined a “prognostic genetics” category of tumors, characterized by genetic lesions that are now known to be associated with a favorable prognosis but that were not addressed through routine care that these patients received when they were first diagnosed. Although the patients experienced relapse after first-line treatment, their exceptional survival after salvage therapy could be linked to favorable genomic characteristics.

For example, several of the patients with high-grade GBMs and astrocytomas had genetic lesions that are generally more common in low-grade glioma and that have been associated with an indolent clinical course following standard therapy.

The authors also assessed immune response. Examining immune cell infiltration in responder tumors in comparison with control cases, the team found that signatures of B cells and activated (CD56dim) natural killer cells were higher in exceptional-responder tumors.

In one patient with metastatic urothelial cancer who experienced disease progression after chemotherapy, radiotherapy, and surgery, treatment with nivolumab produced a complete response that lasted 7 months. Such an outcome occurs in only about 3% of bladder cancer patients. The tumor expressed high mRNA levels of PDCD1, which encodes the nivolumab target PD-1, and CD274, which encodes the PD-1 ligand PD-L1. There was also a high level of amplification of IFNG, which encodes interferon-gamma, a cytokine that has been linked to favorable response to immune checkpoint blockade.
 

Moving to precision medicine

“It is very valuable to be tested up front and again when the disease progresses, because there may have been some genetic changes, and this may change the treatment,” said co–lead author S. Percy Ivy, MD, of the NCI’s Division of Cancer Treatment and Diagnosis.

“The goal of this study was to understand what was unique about these patients and their genetic makeup that led them to be classified as exceptional responders, and hopefully we will be able to tease that out,” she added.

“As researchers, we have a lot to learn from these patients, and they have a lot to teach us,” she added. “In the future, they will help us as we move closer to the goal of delivering precision oncology to all of our patients. We’re not there yet, but every time we study more deeply and learn more, we are able to provide better care.”

To encourage participation in this effort by investigators around the world, the NCI team and their colleagues have made their molecular profiling results and clinical information publicly available in the NCI Genomic Data Commons.

The study was supported by the NCI’s Intramural Research Program, the National Institutes of Health, the Center for Cancer Research, and the NCI’s Center for Cancer Genomics. Staudt and Ivy have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A small percentage of patients with cancer show exceptional responses to treatment and survive significantly longer than patients with clinically comparable tumors, despite having advanced disease.

An ongoing research project is studying why some patients have exceptional responses. The researchers have found particular molecular features in the tumors of about a quarter of these patients. In some cases, there are multiple rare genetic changes in the tumor genome. In other cases, the tumors are infiltrated with certain types of immune cells.

The findings were published online November 19 in Cancer Cell. They come from a genomic analysis of tumor biopsy specimens from 111 patients who were identified by the National Cancer Institute’s (NCI’s) Exceptional Responders Initiative, a national project launched in 2014.

An exceptional responder is defined as an individual who achieves a partial or complete response to a treatment that would be effective in fewer than 10% of similar patients. For exceptional response, the duration of response is at least three times longer than the usual median response time.

In this study of 111 such patients, about one quarter (24%, n = 26 patients) were found to have tumors in which there were molecular features that could potentially explain exceptional responses to treatment.

“We won’t be able to identify, in every patient, which particular drugs will be beneficial,” said Louis Staudt, MD, PhD, director of the NCI’s Center for Cancer Genomics, who co-led the study. “We are nowhere near that. But what it does say is that we have identified particular mutations, some of which we knew about in some types of cancer but can also occur less commonly in other cancer types.”

Staudt noted that these mutations can “illuminate” the path that the cancer will take — and potentially can be used to predict whether the cancer will be aggressive and will require treatment or could be managed with surveillance. This is why this research can be useful in the short term, he said.

“In the longer term, this is the kind of research that inspires future work,” he told Medscape Medical News. “That would encompass clinical trials involving drugs that target some of the pathways we found to be genetically inactivated in some of these responders.”

These results support the use of genetic testing in routine clinical care, he said.

Earlier this year, the NCI team published the results of a pilot study that affirmed the feasibility of this approach. Of the more than 100 cases that were analyzed, six were identified as involving potentially clinically actionable germline mutations.
 

‘Curiosity drove the research’

“We had these wonderful and gratifying experiences with our patients, so we were immediately curious how that happened, so it was pretty much that curiosity that drove a lot of this work,” said Staudt.

In the current study, Staudt and colleagues used multiple genomic methodologies to detect mutations, copy number changes, aberrant methylation, outlier gene expression, and the cellular makeup of the tumor microenvironment.

The hypothesized mechanisms for exceptional responses were broadly divided into the following four categories: DNA damage response (n = 15), intracellular signaling pathway (n = 9), prognostic genetics (n = 9), and immunologic engagement (n = 16). For many patients, two or more of these mechanisms were involved.

The authors note that the “predominance of plausible DNA damage response mechanisms parallels the frequent use of cytotoxic chemotherapy in routine cancer treatment reflected in this cohort.”

Twenty-six patients were identified as exceptional responders. Among these patients, a variety of cancer types was represented: brain (8); gastrointestinal tract (6); breast (4); cholangiocarcinoma (2); lung (2); pancreas, endometrium, ovarian, and bladder (1 each). Many of these patients (65%, n = 17) were treated with chemotherapy that included DNA-damaging agents. For more than half (54%, n = 14), targeted therapies were used, and some patients received both.

The authors highlight several patients as examples of exceptional responders:

• One patient with glioblastoma multiforme (GBM) was treated sequentially with surgery, localized carmustine, and radiotherapy. When the cancer recurred, temozolomide was administered. This induced a complete response that has lasted for more than a decade.
• A patient with metastatic colon adenocarcinoma has had an ongoing and nearly complete response that has lasted 45 months (last follow-up) after receiving temozolomide in combination with the investigational drug TRC102 (methoxyamine, under development by Tracon) in a phase 1 clinical trial. TRC102 is an inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics.
• A patient with metastatic, estrogen receptor–positive breast cancer received trastuzumab because of a high-level ERBB2 amplification, together with anastrozole. This resulted in an ongoing 2.4-year partial response.
• Although the patient was clinically HER2 positive, her tumor had exceedingly low expression of ERBB2 mRNA. Molecular profiling had classified the tumor as of the basal-like subtype rather than the HER2-enriched subtype. This meant that it was unlikely that trastuzumab contributed to the exceptional response, the authors note. Because the patient was estrogen-receptor positive, she received anastrozole, an inhibitor of aromatase (CYP19A), which converts testosterone into estradiol.
• A patient who had a gastrointestinal stromal tumor with a deletion of KIT exon 11 experienced relapse after an initial response to imatinib, which targets KIT and other tyrosine kinases, but then achieved a complete response with sunitinib. Gene expression profiling revealed high expression not only of KIT but also of genes encoding several tyrosine kinases that are targeted by sunitinib (KDR, FLT1, and FLT3). This may have accounted for the patient’s response.

Favorable genomic characteristics

The authors defined a “prognostic genetics” category of tumors, characterized by genetic lesions that are now known to be associated with a favorable prognosis but that were not addressed through routine care that these patients received when they were first diagnosed. Although the patients experienced relapse after first-line treatment, their exceptional survival after salvage therapy could be linked to favorable genomic characteristics.

For example, several of the patients with high-grade GBMs and astrocytomas had genetic lesions that are generally more common in low-grade glioma and that have been associated with an indolent clinical course following standard therapy.

The authors also assessed immune response. Examining immune cell infiltration in responder tumors in comparison with control cases, the team found that signatures of B cells and activated (CD56dim) natural killer cells were higher in exceptional-responder tumors.

In one patient with metastatic urothelial cancer who experienced disease progression after chemotherapy, radiotherapy, and surgery, treatment with nivolumab produced a complete response that lasted 7 months. Such an outcome occurs in only about 3% of bladder cancer patients. The tumor expressed high mRNA levels of PDCD1, which encodes the nivolumab target PD-1, and CD274, which encodes the PD-1 ligand PD-L1. There was also a high level of amplification of IFNG, which encodes interferon-gamma, a cytokine that has been linked to favorable response to immune checkpoint blockade.
 

Moving to precision medicine

“It is very valuable to be tested up front and again when the disease progresses, because there may have been some genetic changes, and this may change the treatment,” said co–lead author S. Percy Ivy, MD, of the NCI’s Division of Cancer Treatment and Diagnosis.

“The goal of this study was to understand what was unique about these patients and their genetic makeup that led them to be classified as exceptional responders, and hopefully we will be able to tease that out,” she added.

“As researchers, we have a lot to learn from these patients, and they have a lot to teach us,” she added. “In the future, they will help us as we move closer to the goal of delivering precision oncology to all of our patients. We’re not there yet, but every time we study more deeply and learn more, we are able to provide better care.”

To encourage participation in this effort by investigators around the world, the NCI team and their colleagues have made their molecular profiling results and clinical information publicly available in the NCI Genomic Data Commons.

The study was supported by the NCI’s Intramural Research Program, the National Institutes of Health, the Center for Cancer Research, and the NCI’s Center for Cancer Genomics. Staudt and Ivy have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

A small percentage of patients with cancer show exceptional responses to treatment and survive significantly longer than patients with clinically comparable tumors, despite having advanced disease.

An ongoing research project is studying why some patients have exceptional responses. The researchers have found particular molecular features in the tumors of about a quarter of these patients. In some cases, there are multiple rare genetic changes in the tumor genome. In other cases, the tumors are infiltrated with certain types of immune cells.

The findings were published online November 19 in Cancer Cell. They come from a genomic analysis of tumor biopsy specimens from 111 patients who were identified by the National Cancer Institute’s (NCI’s) Exceptional Responders Initiative, a national project launched in 2014.

An exceptional responder is defined as an individual who achieves a partial or complete response to a treatment that would be effective in fewer than 10% of similar patients. For exceptional response, the duration of response is at least three times longer than the usual median response time.

In this study of 111 such patients, about one quarter (24%, n = 26 patients) were found to have tumors in which there were molecular features that could potentially explain exceptional responses to treatment.

“We won’t be able to identify, in every patient, which particular drugs will be beneficial,” said Louis Staudt, MD, PhD, director of the NCI’s Center for Cancer Genomics, who co-led the study. “We are nowhere near that. But what it does say is that we have identified particular mutations, some of which we knew about in some types of cancer but can also occur less commonly in other cancer types.”

Staudt noted that these mutations can “illuminate” the path that the cancer will take — and potentially can be used to predict whether the cancer will be aggressive and will require treatment or could be managed with surveillance. This is why this research can be useful in the short term, he said.

“In the longer term, this is the kind of research that inspires future work,” he told Medscape Medical News. “That would encompass clinical trials involving drugs that target some of the pathways we found to be genetically inactivated in some of these responders.”

These results support the use of genetic testing in routine clinical care, he said.

Earlier this year, the NCI team published the results of a pilot study that affirmed the feasibility of this approach. Of the more than 100 cases that were analyzed, six were identified as involving potentially clinically actionable germline mutations.
 

‘Curiosity drove the research’

“We had these wonderful and gratifying experiences with our patients, so we were immediately curious how that happened, so it was pretty much that curiosity that drove a lot of this work,” said Staudt.

In the current study, Staudt and colleagues used multiple genomic methodologies to detect mutations, copy number changes, aberrant methylation, outlier gene expression, and the cellular makeup of the tumor microenvironment.

The hypothesized mechanisms for exceptional responses were broadly divided into the following four categories: DNA damage response (n = 15), intracellular signaling pathway (n = 9), prognostic genetics (n = 9), and immunologic engagement (n = 16). For many patients, two or more of these mechanisms were involved.

The authors note that the “predominance of plausible DNA damage response mechanisms parallels the frequent use of cytotoxic chemotherapy in routine cancer treatment reflected in this cohort.”

Twenty-six patients were identified as exceptional responders. Among these patients, a variety of cancer types was represented: brain (8); gastrointestinal tract (6); breast (4); cholangiocarcinoma (2); lung (2); pancreas, endometrium, ovarian, and bladder (1 each). Many of these patients (65%, n = 17) were treated with chemotherapy that included DNA-damaging agents. For more than half (54%, n = 14), targeted therapies were used, and some patients received both.

The authors highlight several patients as examples of exceptional responders:

• One patient with glioblastoma multiforme (GBM) was treated sequentially with surgery, localized carmustine, and radiotherapy. When the cancer recurred, temozolomide was administered. This induced a complete response that has lasted for more than a decade.
• A patient with metastatic colon adenocarcinoma has had an ongoing and nearly complete response that has lasted 45 months (last follow-up) after receiving temozolomide in combination with the investigational drug TRC102 (methoxyamine, under development by Tracon) in a phase 1 clinical trial. TRC102 is an inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics.
• A patient with metastatic, estrogen receptor–positive breast cancer received trastuzumab because of a high-level ERBB2 amplification, together with anastrozole. This resulted in an ongoing 2.4-year partial response.
• Although the patient was clinically HER2 positive, her tumor had exceedingly low expression of ERBB2 mRNA. Molecular profiling had classified the tumor as of the basal-like subtype rather than the HER2-enriched subtype. This meant that it was unlikely that trastuzumab contributed to the exceptional response, the authors note. Because the patient was estrogen-receptor positive, she received anastrozole, an inhibitor of aromatase (CYP19A), which converts testosterone into estradiol.
• A patient who had a gastrointestinal stromal tumor with a deletion of KIT exon 11 experienced relapse after an initial response to imatinib, which targets KIT and other tyrosine kinases, but then achieved a complete response with sunitinib. Gene expression profiling revealed high expression not only of KIT but also of genes encoding several tyrosine kinases that are targeted by sunitinib (KDR, FLT1, and FLT3). This may have accounted for the patient’s response.

Favorable genomic characteristics

The authors defined a “prognostic genetics” category of tumors, characterized by genetic lesions that are now known to be associated with a favorable prognosis but that were not addressed through routine care that these patients received when they were first diagnosed. Although the patients experienced relapse after first-line treatment, their exceptional survival after salvage therapy could be linked to favorable genomic characteristics.

For example, several of the patients with high-grade GBMs and astrocytomas had genetic lesions that are generally more common in low-grade glioma and that have been associated with an indolent clinical course following standard therapy.

The authors also assessed immune response. Examining immune cell infiltration in responder tumors in comparison with control cases, the team found that signatures of B cells and activated (CD56dim) natural killer cells were higher in exceptional-responder tumors.

In one patient with metastatic urothelial cancer who experienced disease progression after chemotherapy, radiotherapy, and surgery, treatment with nivolumab produced a complete response that lasted 7 months. Such an outcome occurs in only about 3% of bladder cancer patients. The tumor expressed high mRNA levels of PDCD1, which encodes the nivolumab target PD-1, and CD274, which encodes the PD-1 ligand PD-L1. There was also a high level of amplification of IFNG, which encodes interferon-gamma, a cytokine that has been linked to favorable response to immune checkpoint blockade.
 

Moving to precision medicine

“It is very valuable to be tested up front and again when the disease progresses, because there may have been some genetic changes, and this may change the treatment,” said co–lead author S. Percy Ivy, MD, of the NCI’s Division of Cancer Treatment and Diagnosis.

“The goal of this study was to understand what was unique about these patients and their genetic makeup that led them to be classified as exceptional responders, and hopefully we will be able to tease that out,” she added.

“As researchers, we have a lot to learn from these patients, and they have a lot to teach us,” she added. “In the future, they will help us as we move closer to the goal of delivering precision oncology to all of our patients. We’re not there yet, but every time we study more deeply and learn more, we are able to provide better care.”

To encourage participation in this effort by investigators around the world, the NCI team and their colleagues have made their molecular profiling results and clinical information publicly available in the NCI Genomic Data Commons.

The study was supported by the NCI’s Intramural Research Program, the National Institutes of Health, the Center for Cancer Research, and the NCI’s Center for Cancer Genomics. Staudt and Ivy have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Erin Shaughnessy, MD, assumed the role of director of pediatric hospital medicine at the University of Alabama at Birmingham and Children’s of Alabama, also in Birmingham, on Sept. 1. Dr. Shaughnessy has done research in improving outcomes in hospitalized children, as well as improving communication between physicians and pediatric patients’ families during care transitions.

Prior to joining UAB and Children’s of Alabama, Dr. Shaughnessy was division chief of hospital medicine at Phoenix (Ariz.) Children’s Hospital while also serving as an associate professor at the University of Arizona, Phoenix.
 

Chandra Lingisetty, MD, MBA, MHCM, was recently named chief administrative officer for Baptist Health Physician Partners, Arkansas. BHPP is Baptist Health’s clinically integrated network (CIN) with more than 1,600 providers across the state.

Baptist Health Arkansas is the state’s largest not for profit health system with 12 hospitals, hundreds of provider clinics, a nursing school, and a graduate medical education residency program. Prior to his promotion, he worked in Baptist Health System as a hospitalist for 10 years, served on the board of managers at BHPP, and strategized COVID-19 care management protocols and medical staff preparedness as part of surge planning and capacity expansion. In his new role, he is focused on leading the clinically integrated network toward value-based care. He is also the cofounder and inaugural president of the Arkansas state chapter of the Society of Hospital Medicine.
 

Grace Farris, MD, recently accepted a position with the division of hospital medicine at the Dell Medical School in Austin where she will be an assistant professor of internal medicine, as well as a working hospitalist.

Dr. Farris worked as chief of hospital medicine at Mount Sinai West Hospital in Manhattan from January 2017 until accepting her new position with Dell. In addition, she publishes a monthly comics column in the Annals of Internal Medicine.

Her visual storytelling through comics has appeared in several media outlets, and she has penned literal columns as well, including one recently in the New York Times about living apart from her children while treating COVID-19 patients in the emergency room.
 

Dell Medical School has also named a new division chief of hospital medicine. Read Pierce, MD, made the move to Texas from the University of Colorado at Denver, Aurora. Dr. Pierce will also serve as associate chair of faculty development of internal medicine at Dell. He is eager to build on his experience and passion for developing people, creating outstanding culture, and changing complex systems in innovative, sustainable ways.

Dr. Pierce worked at University of Colorado for the past 8 years, serving as the associate director of the school’s Institute for Healthcare Quality, Safety and Efficiency (IHQSE), a program he co-founded. Prior to that, Dr. Pierce was chief resident at the University of San Francisco medical school and later founded the hospital medicine center at the San Francisco VA Medical Center.
 

Gurinder Kaur, MD, was recently named medical director of the Health Hospitalist Program at St. Joseph’s Health Rome (N.Y.) Memorial Hospital. Dr. Kaur’s focus will be on improving infrastructure to allow for the highest quality of care possible. She will oversee the facility’s crew of eight hospitalists, who rotate to be available 24 hours per day.

Dr. Kaur comes to Rome from St. Joseph’s Health in Syracuse, N.Y., where she was chief resident and a member of the hospitalist team.
 

Colin McMahon, MD, was recently appointed chief of hospital medicine at Eastern Niagara Hospital in Lockport, N.Y., where he will oversee the hospitalist program. He comes to ENH after serving as medical director of hospital operations at Buffalo (N.Y.) General Medical Center.

Dr. McMahon has worked in medicine for a quarter of a century. He also is the president and founder of Dimensions of Internal Medicine and Pediatric Care, PC (DMP). Associates from DMP Medicine make up the hospitalist team at ENH.
 

Sam Antonios, MD, has been promoted to chief clinical officer of Ascension Kansas, the parent group of Ascension Via Christi Hospital in Wichita, where Dr. Antonios has served as chief medical officer for the past 4 years. Dr. Antonios has emerged as a leader within Ascension Kansas during the COVID-19 pandemic.

Prior to his appointment at Via Christi, he worked at that facility as a hospitalist and as medical director of information systems. Dr. Antonios is a board-certified internist.
 

Bret J. Rudy, MD, was named a Top 25 Healthcare Innovator by Modern Healthcare magazine. Dr. Rudy is chief of hospital operations and senior vice president at NYU Langone Hospital-Brooklyn in New York, and the magazine cited his efforts in elevating the quality, safety, and accountability of the facility, which merged with NYU Langone Health in 2016.

Dr. Rudy has established a 24-hour hospitalist service, added full-time emergency faculty, and reduced hospital wait times, among other patient-experience benchmarks, since his appointment at Langone-Brooklyn.

Dr. Rudy is a board-certified pediatrician who has served on the National Institutes of Health’s HIV research networks, including a spot on the White House Advisory Committee on Adolescents for the Office of National AIDS Policy.
 

Nasim Afsar, MD, MBA, SFHM, a past president of SHM, was recently named chief operating officer at UCI Health in Orange, Calif. Dr. Afsar served previously as chief ambulatory officer and chief medical officer for accountable care organizations at UCI Health.

Anthony J. Macchiavelli, MD, FHM, was recognized by Continental Who’s Who as a “Top Distinguished Hospitalist” with AtlantiCare Regional Medical Center, in Atlantic City, N.J. He has been with AtlantiCare for the past ten years, and currently serves as medical director for the PACE program, as well as medical director for the Anticoagulation Clinic.

Dr. Macchiavelli has been involved in the development of 3 different hospital medicine programs throughout his career and was the founder of the Associates in Hospital Medicine program at Methodist Division of Thomas Jefferson University Hospitals. He serves as a mentor for SHM’s VTE-FAST Program, and has served on the Standards Review Panel for the Joint Commission developing the National Patient Safety Goal for anticoagulation therapy.

Erin Shaughnessy, MD, assumed the role of director of pediatric hospital medicine at the University of Alabama at Birmingham and Children’s of Alabama, also in Birmingham, on Sept. 1. Dr. Shaughnessy has done research in improving outcomes in hospitalized children, as well as improving communication between physicians and pediatric patients’ families during care transitions.

Prior to joining UAB and Children’s of Alabama, Dr. Shaughnessy was division chief of hospital medicine at Phoenix (Ariz.) Children’s Hospital while also serving as an associate professor at the University of Arizona, Phoenix.
 

Chandra Lingisetty, MD, MBA, MHCM, was recently named chief administrative officer for Baptist Health Physician Partners, Arkansas. BHPP is Baptist Health’s clinically integrated network (CIN) with more than 1,600 providers across the state.

Baptist Health Arkansas is the state’s largest not for profit health system with 12 hospitals, hundreds of provider clinics, a nursing school, and a graduate medical education residency program. Prior to his promotion, he worked in Baptist Health System as a hospitalist for 10 years, served on the board of managers at BHPP, and strategized COVID-19 care management protocols and medical staff preparedness as part of surge planning and capacity expansion. In his new role, he is focused on leading the clinically integrated network toward value-based care. He is also the cofounder and inaugural president of the Arkansas state chapter of the Society of Hospital Medicine.
 

Grace Farris, MD, recently accepted a position with the division of hospital medicine at the Dell Medical School in Austin where she will be an assistant professor of internal medicine, as well as a working hospitalist.

Dr. Farris worked as chief of hospital medicine at Mount Sinai West Hospital in Manhattan from January 2017 until accepting her new position with Dell. In addition, she publishes a monthly comics column in the Annals of Internal Medicine.

Her visual storytelling through comics has appeared in several media outlets, and she has penned literal columns as well, including one recently in the New York Times about living apart from her children while treating COVID-19 patients in the emergency room.
 

Dell Medical School has also named a new division chief of hospital medicine. Read Pierce, MD, made the move to Texas from the University of Colorado at Denver, Aurora. Dr. Pierce will also serve as associate chair of faculty development of internal medicine at Dell. He is eager to build on his experience and passion for developing people, creating outstanding culture, and changing complex systems in innovative, sustainable ways.

Dr. Pierce worked at University of Colorado for the past 8 years, serving as the associate director of the school’s Institute for Healthcare Quality, Safety and Efficiency (IHQSE), a program he co-founded. Prior to that, Dr. Pierce was chief resident at the University of San Francisco medical school and later founded the hospital medicine center at the San Francisco VA Medical Center.
 

Gurinder Kaur, MD, was recently named medical director of the Health Hospitalist Program at St. Joseph’s Health Rome (N.Y.) Memorial Hospital. Dr. Kaur’s focus will be on improving infrastructure to allow for the highest quality of care possible. She will oversee the facility’s crew of eight hospitalists, who rotate to be available 24 hours per day.

Dr. Kaur comes to Rome from St. Joseph’s Health in Syracuse, N.Y., where she was chief resident and a member of the hospitalist team.
 

Colin McMahon, MD, was recently appointed chief of hospital medicine at Eastern Niagara Hospital in Lockport, N.Y., where he will oversee the hospitalist program. He comes to ENH after serving as medical director of hospital operations at Buffalo (N.Y.) General Medical Center.

Dr. McMahon has worked in medicine for a quarter of a century. He also is the president and founder of Dimensions of Internal Medicine and Pediatric Care, PC (DMP). Associates from DMP Medicine make up the hospitalist team at ENH.
 

Sam Antonios, MD, has been promoted to chief clinical officer of Ascension Kansas, the parent group of Ascension Via Christi Hospital in Wichita, where Dr. Antonios has served as chief medical officer for the past 4 years. Dr. Antonios has emerged as a leader within Ascension Kansas during the COVID-19 pandemic.

Prior to his appointment at Via Christi, he worked at that facility as a hospitalist and as medical director of information systems. Dr. Antonios is a board-certified internist.
 

Bret J. Rudy, MD, was named a Top 25 Healthcare Innovator by Modern Healthcare magazine. Dr. Rudy is chief of hospital operations and senior vice president at NYU Langone Hospital-Brooklyn in New York, and the magazine cited his efforts in elevating the quality, safety, and accountability of the facility, which merged with NYU Langone Health in 2016.

Dr. Rudy has established a 24-hour hospitalist service, added full-time emergency faculty, and reduced hospital wait times, among other patient-experience benchmarks, since his appointment at Langone-Brooklyn.

Dr. Rudy is a board-certified pediatrician who has served on the National Institutes of Health’s HIV research networks, including a spot on the White House Advisory Committee on Adolescents for the Office of National AIDS Policy.
 

Nasim Afsar, MD, MBA, SFHM, a past president of SHM, was recently named chief operating officer at UCI Health in Orange, Calif. Dr. Afsar served previously as chief ambulatory officer and chief medical officer for accountable care organizations at UCI Health.

Anthony J. Macchiavelli, MD, FHM, was recognized by Continental Who’s Who as a “Top Distinguished Hospitalist” with AtlantiCare Regional Medical Center, in Atlantic City, N.J. He has been with AtlantiCare for the past ten years, and currently serves as medical director for the PACE program, as well as medical director for the Anticoagulation Clinic.

Dr. Macchiavelli has been involved in the development of 3 different hospital medicine programs throughout his career and was the founder of the Associates in Hospital Medicine program at Methodist Division of Thomas Jefferson University Hospitals. He serves as a mentor for SHM’s VTE-FAST Program, and has served on the Standards Review Panel for the Joint Commission developing the National Patient Safety Goal for anticoagulation therapy.

Erin Shaughnessy, MD, assumed the role of director of pediatric hospital medicine at the University of Alabama at Birmingham and Children’s of Alabama, also in Birmingham, on Sept. 1. Dr. Shaughnessy has done research in improving outcomes in hospitalized children, as well as improving communication between physicians and pediatric patients’ families during care transitions.

Prior to joining UAB and Children’s of Alabama, Dr. Shaughnessy was division chief of hospital medicine at Phoenix (Ariz.) Children’s Hospital while also serving as an associate professor at the University of Arizona, Phoenix.
 

Chandra Lingisetty, MD, MBA, MHCM, was recently named chief administrative officer for Baptist Health Physician Partners, Arkansas. BHPP is Baptist Health’s clinically integrated network (CIN) with more than 1,600 providers across the state.

Baptist Health Arkansas is the state’s largest not for profit health system with 12 hospitals, hundreds of provider clinics, a nursing school, and a graduate medical education residency program. Prior to his promotion, he worked in Baptist Health System as a hospitalist for 10 years, served on the board of managers at BHPP, and strategized COVID-19 care management protocols and medical staff preparedness as part of surge planning and capacity expansion. In his new role, he is focused on leading the clinically integrated network toward value-based care. He is also the cofounder and inaugural president of the Arkansas state chapter of the Society of Hospital Medicine.
 

Grace Farris, MD, recently accepted a position with the division of hospital medicine at the Dell Medical School in Austin where she will be an assistant professor of internal medicine, as well as a working hospitalist.

Dr. Farris worked as chief of hospital medicine at Mount Sinai West Hospital in Manhattan from January 2017 until accepting her new position with Dell. In addition, she publishes a monthly comics column in the Annals of Internal Medicine.

Her visual storytelling through comics has appeared in several media outlets, and she has penned literal columns as well, including one recently in the New York Times about living apart from her children while treating COVID-19 patients in the emergency room.
 

Dell Medical School has also named a new division chief of hospital medicine. Read Pierce, MD, made the move to Texas from the University of Colorado at Denver, Aurora. Dr. Pierce will also serve as associate chair of faculty development of internal medicine at Dell. He is eager to build on his experience and passion for developing people, creating outstanding culture, and changing complex systems in innovative, sustainable ways.

Dr. Pierce worked at University of Colorado for the past 8 years, serving as the associate director of the school’s Institute for Healthcare Quality, Safety and Efficiency (IHQSE), a program he co-founded. Prior to that, Dr. Pierce was chief resident at the University of San Francisco medical school and later founded the hospital medicine center at the San Francisco VA Medical Center.
 

Gurinder Kaur, MD, was recently named medical director of the Health Hospitalist Program at St. Joseph’s Health Rome (N.Y.) Memorial Hospital. Dr. Kaur’s focus will be on improving infrastructure to allow for the highest quality of care possible. She will oversee the facility’s crew of eight hospitalists, who rotate to be available 24 hours per day.

Dr. Kaur comes to Rome from St. Joseph’s Health in Syracuse, N.Y., where she was chief resident and a member of the hospitalist team.
 

Colin McMahon, MD, was recently appointed chief of hospital medicine at Eastern Niagara Hospital in Lockport, N.Y., where he will oversee the hospitalist program. He comes to ENH after serving as medical director of hospital operations at Buffalo (N.Y.) General Medical Center.

Dr. McMahon has worked in medicine for a quarter of a century. He also is the president and founder of Dimensions of Internal Medicine and Pediatric Care, PC (DMP). Associates from DMP Medicine make up the hospitalist team at ENH.
 

Sam Antonios, MD, has been promoted to chief clinical officer of Ascension Kansas, the parent group of Ascension Via Christi Hospital in Wichita, where Dr. Antonios has served as chief medical officer for the past 4 years. Dr. Antonios has emerged as a leader within Ascension Kansas during the COVID-19 pandemic.

Prior to his appointment at Via Christi, he worked at that facility as a hospitalist and as medical director of information systems. Dr. Antonios is a board-certified internist.
 

Bret J. Rudy, MD, was named a Top 25 Healthcare Innovator by Modern Healthcare magazine. Dr. Rudy is chief of hospital operations and senior vice president at NYU Langone Hospital-Brooklyn in New York, and the magazine cited his efforts in elevating the quality, safety, and accountability of the facility, which merged with NYU Langone Health in 2016.

Dr. Rudy has established a 24-hour hospitalist service, added full-time emergency faculty, and reduced hospital wait times, among other patient-experience benchmarks, since his appointment at Langone-Brooklyn.

Dr. Rudy is a board-certified pediatrician who has served on the National Institutes of Health’s HIV research networks, including a spot on the White House Advisory Committee on Adolescents for the Office of National AIDS Policy.
 

Nasim Afsar, MD, MBA, SFHM, a past president of SHM, was recently named chief operating officer at UCI Health in Orange, Calif. Dr. Afsar served previously as chief ambulatory officer and chief medical officer for accountable care organizations at UCI Health.

Anthony J. Macchiavelli, MD, FHM, was recognized by Continental Who’s Who as a “Top Distinguished Hospitalist” with AtlantiCare Regional Medical Center, in Atlantic City, N.J. He has been with AtlantiCare for the past ten years, and currently serves as medical director for the PACE program, as well as medical director for the Anticoagulation Clinic.

Dr. Macchiavelli has been involved in the development of 3 different hospital medicine programs throughout his career and was the founder of the Associates in Hospital Medicine program at Methodist Division of Thomas Jefferson University Hospitals. He serves as a mentor for SHM’s VTE-FAST Program, and has served on the Standards Review Panel for the Joint Commission developing the National Patient Safety Goal for anticoagulation therapy.

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

In a single-center retrospective analysis of 102 patients with psoriasis induced by tumor necrosis factor (TNF) inhibitors, most cases improved or resolved with use of topical medications or with discontinuation of the inciting TNF inhibitor, with or without other interventions. All patients were treated and diagnosed by dermatologists.

While TNF inhibitors have revolutionized management of numerous debilitating chronic inflammatory diseases, they are associated with mild and potentially serious adverse reactions, including de novo psoriasiform eruptions, noted Sean E. Mazloom, MD, and colleagues, at the Cleveland Clinic, Cleveland, Ohio, in the Journal of the American Academy of Dermatology. Despite the fact that it has been more than 15 years since the first reports of TNF inhibitor-induced psoriasis, optimal treatment strategies still remain poorly understood.
 

IBD and RA most common

Dr. Mazloom and colleagues identified 102 patients (median onset, 41 years; 72.5% female) with TNF inhibitor-induced psoriasis seen at a single tertiary care institution (the Cleveland Clinic) over a 10-year period. The authors proposed a treatment algorithm based on their findings.

Inciting TNF inhibitors were prescribed most commonly for inflammatory bowel disease (IBD) (52%) and rheumatoid arthritis (RA) (24.5%). The most common inciting TNF inhibitor was infliximab (52%). TNF inhibitor-induced psoriasis improved or resolved with topical medications alone in 63.5% of patients, and cyclosporine and methotrexate (10 mg weekly) were often effective (cyclosporine in five of five patients; methotrexate in 7 of 13) if topicals failed.

Noting that the success with topicals in this cohort exceeded that of earlier reports, the authors suggested that more accurate diagnoses and optimal strategies attributable to the involvement of dermatologists may be explanatory.

In 67% of refractory cases, discontinuation of the inciting TNF inhibitor with or without other interventions improved or resolved TNF inhibitor-induced psoriasis. With switching of TNF inhibitors, persistence or worsening of TNF inhibitor-induced psoriasis was reported in 16 of 25 patients (64%).

Algorithm aims at balancing control

The treatment algorithm proposed by Dr. Mazloom and colleagues aims at balancing control of the primary disease with minimization of skin symptom discomfort and continuation of the inciting TNF inhibitor if possible. Only with cyclosporine or methotrexate failure amid severe symptoms and less-than-optimal primary disease control should TNF inhibitors be discontinued and biologics and/or small-molecule inhibitors with alternative mechanisms of action be introduced. Transitioning to other TNF inhibitors may be tried before alternative strategies when the underlying disease is well-controlled but TNF inhibitor-induced psoriasis remains severe.

“Most dermatologists who see TNF-induced psoriasis often are likely already using strategies like the one proposed in the algorithm,” commented senior author Anthony Fernandez, MD, PhD, of the Cleveland (Ohio) Clinic, in an interview. “The concern is over those who may not see TNF inhibitor-induced psoriasis very often, and who may, as a knee-jerk response to TNF-induced psoriasis, stop the inciting medication. When strong side effects occur in IBD and RA, it’s critical to know how well the TNF inhibitor is controlling the underlying disease because lack of control can lead to permanent damage.”

Risk to benefit ratio favors retaining TNF inhibitors

The dermatologist’s goal, if the TNF inhibitor is working well, should be to exhaust all reasonable options to control the psoriasiform eruption and keep the patient on the TNF inhibitor rather than turn to potentially less effective alternatives, Dr. Fernandez added. “The risk:benefit ratio still usually favors adding more immune therapies to treat these reactions in order to enable patients to stay” on their TNF inhibitors.

Study authors disclosed no direct funding for the study. Dr Fernandez, the senior author, receives research funding from Pfizer, Mallinckrodt, and Novartis, consults for AbbVie and Celgene, and is a speaker for AbbVie and Mallinckrodt.

SOURCE: Mazloom SE et al. J Am Acad Dermatol. 2020 Dec;83(6):1590-8.

Doctors commonly perform pelvic examinations approximately 6 weeks following hysterectomy to assess the integrity of the vaginal cuff. But this practice may not be necessary if patients do not have symptoms, a study suggests.

“The 6-week posthysterectomy pelvic examination in asymptomatic women may not be necessary, as it neither detected cuff dehiscence nor negated future risk for dehiscence,” Ritchie Mae Delara, MD, said at the meeting sponsored by AAGL, held virtually this year.

Dr. Delara, of the Mayo Clinic in Phoenix, and colleagues conducted a retrospective cohort study of data from more than 2,000 patients to assess the utility of the 6-week posthysterectomy pelvic examination in detecting cuff dehiscence in asymptomatic women.
 

An unpredictable complication

Vaginal cuff dehiscence is a rare complication of hysterectomy that can occur days or decades after surgery, which makes “identifying an optimal time for cuff evaluation difficult,” Dr. Delara said. “Currently there is neither evidence demonstrating benefit of routine posthysterectomy examination in detecting vaginal cuff dehiscence, nor data demonstrating the best time to perform posthysterectomy examination.”

For their study, which was also published in the Journal of Minimally Invasive Gynecology, the researchers examined data from 2,051 women who underwent hysterectomy at a single institution during a 6-year period. Patients received at least one postoperative evaluation within 90 days of surgery. Examination of the vaginal cuff routinely was performed approximately 6 weeks after hysterectomy. Patients’ posthysterectomy symptoms and pelvic examination findings were recorded.

About 80% of patients were asymptomatic at the 6-week visit.

Asymptomatic patients were more likely to have normal pelvic examination findings, compared with patients with posthysterectomy symptoms (86.4% vs. 54.3%).

In all, 13 patients experienced complete cuff dehiscence. All of them had an intact vaginal cuff at their 6-week examination. Three had symptoms at that time, including vaginal bleeding in one patient and pelvic pain in two patients.

One patient experienced a complete cuff dehiscence that was provoked by intercourse prior to her examination. The patient subsequently developed two additional episodes of dehiscence provoked by intercourse.

Dehiscence may present differently after benign and oncologic hysterectomies, the study indicated.

Eight patients who experienced complete cuff dehiscence after benign hysterectomy had symptoms such as pelvic pain and vaginal bleeding at the time of presentation for dehiscence, which mainly occurred after intercourse.

Five patients who experienced dehiscence after oncologic hysterectomy were more likely to present without symptoms or provocation.

The median time to dehiscence after benign hysterectomy was about 19 weeks, whereas the median time to dehiscence after oncologic hysterectomy was about 81 weeks.

Surgeons should educate patients about symptoms of dehiscence and the potential for events such as coitus to provoke its occurrence, and patients should promptly seek evaluation if symptoms occur, Dr. Delara said.

Patients with risk factors such as malignancy may benefit from continued routine evaluation, she added.

Timely research

The findings may be especially relevant during the COVID-19 pandemic, when states have issued shelter-in-place orders and doctors have increased their use of telemedicine to reduce in-person visits, Dr. Delara noted.

In that sense, the study is “extremely timely” and may inform and support practice changes, commented Emad Mikhail, MD, in a discussion following the research presentation.

Whether the results generalize to other centers, including smaller centers that perform fewer surgeries, is unclear, said Dr. Mikhail, of the University of South Florida, Tampa.

“It takes vision and critical thinking to challenge these traditional practices,” he said. “I applaud Dr. Delara for challenging one of these.”

Dr. Delara and Dr. Mikhail had no relevant disclosures.

[email protected]

SOURCE: Delara RMM et al. J Minim Invasive Gynecol. 2020 Nov 1. doi: 10.1016/j.jmig.2020.08.306.

Doctors commonly perform pelvic examinations approximately 6 weeks following hysterectomy to assess the integrity of the vaginal cuff. But this practice may not be necessary if patients do not have symptoms, a study suggests.

“The 6-week posthysterectomy pelvic examination in asymptomatic women may not be necessary, as it neither detected cuff dehiscence nor negated future risk for dehiscence,” Ritchie Mae Delara, MD, said at the meeting sponsored by AAGL, held virtually this year.

Dr. Delara, of the Mayo Clinic in Phoenix, and colleagues conducted a retrospective cohort study of data from more than 2,000 patients to assess the utility of the 6-week posthysterectomy pelvic examination in detecting cuff dehiscence in asymptomatic women.
 

An unpredictable complication

Vaginal cuff dehiscence is a rare complication of hysterectomy that can occur days or decades after surgery, which makes “identifying an optimal time for cuff evaluation difficult,” Dr. Delara said. “Currently there is neither evidence demonstrating benefit of routine posthysterectomy examination in detecting vaginal cuff dehiscence, nor data demonstrating the best time to perform posthysterectomy examination.”

For their study, which was also published in the Journal of Minimally Invasive Gynecology, the researchers examined data from 2,051 women who underwent hysterectomy at a single institution during a 6-year period. Patients received at least one postoperative evaluation within 90 days of surgery. Examination of the vaginal cuff routinely was performed approximately 6 weeks after hysterectomy. Patients’ posthysterectomy symptoms and pelvic examination findings were recorded.

About 80% of patients were asymptomatic at the 6-week visit.

Asymptomatic patients were more likely to have normal pelvic examination findings, compared with patients with posthysterectomy symptoms (86.4% vs. 54.3%).

In all, 13 patients experienced complete cuff dehiscence. All of them had an intact vaginal cuff at their 6-week examination. Three had symptoms at that time, including vaginal bleeding in one patient and pelvic pain in two patients.

One patient experienced a complete cuff dehiscence that was provoked by intercourse prior to her examination. The patient subsequently developed two additional episodes of dehiscence provoked by intercourse.

Dehiscence may present differently after benign and oncologic hysterectomies, the study indicated.

Eight patients who experienced complete cuff dehiscence after benign hysterectomy had symptoms such as pelvic pain and vaginal bleeding at the time of presentation for dehiscence, which mainly occurred after intercourse.

Five patients who experienced dehiscence after oncologic hysterectomy were more likely to present without symptoms or provocation.

The median time to dehiscence after benign hysterectomy was about 19 weeks, whereas the median time to dehiscence after oncologic hysterectomy was about 81 weeks.

Surgeons should educate patients about symptoms of dehiscence and the potential for events such as coitus to provoke its occurrence, and patients should promptly seek evaluation if symptoms occur, Dr. Delara said.

Patients with risk factors such as malignancy may benefit from continued routine evaluation, she added.

Timely research

The findings may be especially relevant during the COVID-19 pandemic, when states have issued shelter-in-place orders and doctors have increased their use of telemedicine to reduce in-person visits, Dr. Delara noted.

In that sense, the study is “extremely timely” and may inform and support practice changes, commented Emad Mikhail, MD, in a discussion following the research presentation.

Whether the results generalize to other centers, including smaller centers that perform fewer surgeries, is unclear, said Dr. Mikhail, of the University of South Florida, Tampa.

“It takes vision and critical thinking to challenge these traditional practices,” he said. “I applaud Dr. Delara for challenging one of these.”

Dr. Delara and Dr. Mikhail had no relevant disclosures.

[email protected]

SOURCE: Delara RMM et al. J Minim Invasive Gynecol. 2020 Nov 1. doi: 10.1016/j.jmig.2020.08.306.

Doctors commonly perform pelvic examinations approximately 6 weeks following hysterectomy to assess the integrity of the vaginal cuff. But this practice may not be necessary if patients do not have symptoms, a study suggests.

“The 6-week posthysterectomy pelvic examination in asymptomatic women may not be necessary, as it neither detected cuff dehiscence nor negated future risk for dehiscence,” Ritchie Mae Delara, MD, said at the meeting sponsored by AAGL, held virtually this year.

Dr. Delara, of the Mayo Clinic in Phoenix, and colleagues conducted a retrospective cohort study of data from more than 2,000 patients to assess the utility of the 6-week posthysterectomy pelvic examination in detecting cuff dehiscence in asymptomatic women.
 

An unpredictable complication

Vaginal cuff dehiscence is a rare complication of hysterectomy that can occur days or decades after surgery, which makes “identifying an optimal time for cuff evaluation difficult,” Dr. Delara said. “Currently there is neither evidence demonstrating benefit of routine posthysterectomy examination in detecting vaginal cuff dehiscence, nor data demonstrating the best time to perform posthysterectomy examination.”

For their study, which was also published in the Journal of Minimally Invasive Gynecology, the researchers examined data from 2,051 women who underwent hysterectomy at a single institution during a 6-year period. Patients received at least one postoperative evaluation within 90 days of surgery. Examination of the vaginal cuff routinely was performed approximately 6 weeks after hysterectomy. Patients’ posthysterectomy symptoms and pelvic examination findings were recorded.

About 80% of patients were asymptomatic at the 6-week visit.

Asymptomatic patients were more likely to have normal pelvic examination findings, compared with patients with posthysterectomy symptoms (86.4% vs. 54.3%).

In all, 13 patients experienced complete cuff dehiscence. All of them had an intact vaginal cuff at their 6-week examination. Three had symptoms at that time, including vaginal bleeding in one patient and pelvic pain in two patients.

One patient experienced a complete cuff dehiscence that was provoked by intercourse prior to her examination. The patient subsequently developed two additional episodes of dehiscence provoked by intercourse.

Dehiscence may present differently after benign and oncologic hysterectomies, the study indicated.

Eight patients who experienced complete cuff dehiscence after benign hysterectomy had symptoms such as pelvic pain and vaginal bleeding at the time of presentation for dehiscence, which mainly occurred after intercourse.

Five patients who experienced dehiscence after oncologic hysterectomy were more likely to present without symptoms or provocation.

The median time to dehiscence after benign hysterectomy was about 19 weeks, whereas the median time to dehiscence after oncologic hysterectomy was about 81 weeks.

Surgeons should educate patients about symptoms of dehiscence and the potential for events such as coitus to provoke its occurrence, and patients should promptly seek evaluation if symptoms occur, Dr. Delara said.

Patients with risk factors such as malignancy may benefit from continued routine evaluation, she added.

Timely research

The findings may be especially relevant during the COVID-19 pandemic, when states have issued shelter-in-place orders and doctors have increased their use of telemedicine to reduce in-person visits, Dr. Delara noted.

In that sense, the study is “extremely timely” and may inform and support practice changes, commented Emad Mikhail, MD, in a discussion following the research presentation.

Whether the results generalize to other centers, including smaller centers that perform fewer surgeries, is unclear, said Dr. Mikhail, of the University of South Florida, Tampa.

“It takes vision and critical thinking to challenge these traditional practices,” he said. “I applaud Dr. Delara for challenging one of these.”

Dr. Delara and Dr. Mikhail had no relevant disclosures.

[email protected]

SOURCE: Delara RMM et al. J Minim Invasive Gynecol. 2020 Nov 1. doi: 10.1016/j.jmig.2020.08.306.

From the Senior Health Program, Providence Health & Services, Oregon, Portland, OR.

Abstract

Background: Approximately 51 million adults in the United States are 65 years of age or older, yet few geriatric-trained primary care providers (PCP) serve this population. The Age-Friendly Health System framework, consisting of evidence-based 4M care (Mobility, Medication, Mentation, and what Matters), encourages all PCPs to assess mobility in older adults.

Objective: To improve PCP knowledge, confidence, and clinical practice in assessing and managing fall risk.

Methods: A 1-week educational session focusing on mobility (part of a 4-week Geriatric Mini-Fellowship) for 6 selected PCPs from a large health care system was conducted to increase knowledge and ability to address fall risk in older adults. The week included learning and practicing a Fall Risk Management Plan (FRMP) algorithm, including planning for their own practice changes. Pre- and post-test surveys assessed changes in knowledge and confidence. Patient data were compared 12 months before and after training to evaluate PCP adoption of FRMP components.

Results: The training increased provider knowledge and confidence. The trained PCPs were 1.7 times more likely to screen for fall risk; 3.6 times more likely to discuss fall risk; and 5.8 times more likely to assess orthostatic blood pressure in their 65+ patients after the mini-fellowship. In high-risk patients, they were 4.1 times more likely to discuss fall risk and 6.3 times more likely to assess orthostatic blood pressure than their nontrained peers. Changes in physical therapy referral rates were not observed.

Conclusions: In-depth, skills-based geriatric educational sessions improved PCPs’ knowledge and confidence and also improved their fall risk management practices for their older patients.

Keywords: geriatrics; guidelines; Age-Friendly Health System; 4M; workforce training; practice change; fellowship.

The US population is aging rapidly. People aged 85 years and older are the largest-growing segment of the US population, and this segment is expected to increase by 123% by 2040.¹ Caregiving needs increase with age as older adults develop more chronic conditions, such as hypertension, heart disease, arthritis, and dementia. However, even with increasing morbidity and dependence, a majority of older adults still live in the community rather than in institutional settings.² These older adults seek medical care more frequently than younger people, with about 22% of patients 75 years and older having 10 or more health care visits in the previous 12 months. By 2040, nearly a quarter of the US population is expected to be 65 or older, with many of these older adults seeking regular primary care from providers who do not have formal training in the care of a population with multiple complex, chronic health conditions and increased caregiving needs.¹

Despite this growing demand for health care professionals trained in the care of older adults, access to these types of clinicians is limited. In 2018, there were roughly 7000 certified geriatricians, with only 3600 of them practicing full-time.^3,4 Similarly, of 290,000 certified nurse practitioners (NPs), about 9% of them have geriatric certification.⁵ Geriatricians, medical doctors trained in the care of older adults, and geriatric-trained NPs are part of a cadre of a geriatric-trained workforce that provides unique expertise in caring for older adults with chronic and advanced illness. They know how to manage multiple, complex geriatric syndromes like falls, dementia, and polypharmacy; understand and maximize team-based care; and focus on caring for an older person with a goal-centered versus a disease-centered approach.⁶

Broadly, geriatric care includes a spectrum of adults, from those who are aging healthfully to those who are the frailest. Research has suggested that approximately 30% of older adults need care by a geriatric-trained clinician, with the oldest and frailest patients needing more clinician time for assessment and treatment, care coordination, and coaching of caregivers.⁷ With this assumption in mind, it is projected that by 2025, there will be a national shortage of 26,980 geriatricians, with the western United States disproportionately affected by this shortage.⁴Rather than lamenting this shortage, Tinetti recommends a new path forward: “Our mission should not be to train enough geriatricians to provide direct care, but rather to ensure that every clinician caring for older adults is competent in geriatric principles and practices.”⁸ Sometimes called ”geriatricizing,” the idea is to use existing geriatric providers as a small elite training force to infuse geriatric principles and skills across their colleagues in primary care and other disciplines.^8,9 Efforts of the American Geriatrics Society (AGS), with support from the John A. Hartford Foundation (JAHF), have been successful in developing geriatric training across multiple specialties, including surgery, orthopedics, and emergency medicine (www.americangeriatrics.org/programs/geriatrics-specialists-initiative).

The Age-Friendly Health System and 4M Model

To help augment this idea of equipping health care systems and their clinicians with more readily available geriatric knowledge, skills, and tools, the JAHF, along with the Institute for Healthcare Improvement (IHI), created the Age-Friendly Health System (AFHS) paradigm in 2015.¹⁰ Using the 4M model, the AFHS initiative established a set of evidence-based geriatric priorities and interventions meant to improve the care of older adults, reduce harm and duplication, and provide a framework for engaging leadership, clinical teams, and operational systems across inpatient and ambulatory settings.¹¹ Mobility, including fall risk screening and intervention, is 1 of the 4M foundational elements of the Age-Friendly model. In addition to Mobility, the 4M model also includes 3 other key geriatric domains: Mentation (dementia, depression, and delirium), Medication (high-risk medications, polypharmacy, and deprescribing), and What Matters (goals of care conversations and understanding quality of life for older patients).¹¹ The 4M initiative encourages adoption of a geriatric lens that looks across chronic conditions and accounts for the interplay among geriatric syndromes, such as falls, cognitive impairment, and frailty, in order to provide care better tailored to what the patient needs and desires.¹² IHI and JAHF have targeted the adoption of the 4M model by 20% of US health care systems by 2020.¹¹

Mini-Fellowship and Mobility Week

To bolster geriatric skills among community-based primary care providers (PCPs), we initiated a Geriatric Mini-Fellowship, a 4-week condensed curriculum taught over 6 months. Each week focuses on 1 of the age-friendly 4Ms, with the goal of increasing the knowledge, self-efficacy, skills, and competencies of the participating PCPs (called “fellow” hereafter) and at the same time, equipping each to become a champion of geriatric practice. This article focuses on the Mobility week, the second week of the mini-fellowship, and the effect of the week on the fellows’ practice changes.

To construct the Mobility week’s curriculum with a focus on the ambulatory setting, we relied upon national evidence-based work in fall risk management. The Centers for Disease Control and Prevention (CDC) has made fall risk screening and management in primary care a high priority. Using the clinical practice guidelines for managing fall risk developed by the American and British Geriatrics Societies (AGS/BGS), the CDC developed the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) toolkit.¹³ Foundational to the toolkit is the validated 12-item Stay Independent falls screening questionnaire (STEADI questionnaire).¹⁴ Patients who score 4 or higher (out of a total score of 14) on the questionnaire are considered at increased risk of falling. The CDC has developed a clinical algorithm that guides clinical teams through screening and assessment to help identify appropriate interventions to target specific risk factors. Research has clearly established that a multifactorial approach to fall risk intervention can be successful in reducing fall risk by as much as 25%.^15-17

The significant morbidity and mortality caused by falls make training nongeriatrician clinicians on how to better address fall risk imperative. More than 25% of older adults fall each year.¹⁸ These falls contribute to rising rates of fall-related deaths,¹⁹ emergency department (ED) visits,²⁰ and hospital readmissions.²¹ Initiatives like the AFHS focus on mobility and the CDC’s development of supporting clinical materials²² aim to improve primary care adoption of fall risk screening and intervention practices.^23,24 The epidemic of falls must compel all PCPs, not just those practicing geriatrics, to make discussing and addressing fall risk and falls a priority.

Methods

Setting

This project took place as part of a regional primary care effort in Oregon. Providence Health & Services-Oregon is part of a multi-state integrated health care system in the western United States whose PCPs serve more than 80,000 patients aged 65 years and older per year; these patients comprise 38% of the system’s office visits each year. Regionally, there are 47 family and internal medicine clinics employing roughly 290 providers (physicians, NPs, and physician assistants). The organization has only 4 PCPs trained in geriatrics and does not offer any geriatric clinical consultation services. Six PCPs from different clinics, representing both rural and urban settings, are chosen to participate in the geriatric mini-fellowship each year.

This project was conducted as a quality improvement initiative within the organization and did not constitute human subjects research. It was not conducted under the oversight of the Institutional Review Board.

Intervention

The mini-fellowship was taught in 4 1-week blocks between April and October 2018, with a curriculum designed to be interactive and practical. The faculty was intentionally interdisciplinary to teach and model team-based practice. Each week participants were excused from their clinical practice. Approximately 160 hours of continuing medical education credits were awarded for the full mini-fellowship. As part of each weekly session, a performance improvement project (PIP) focused on that week’s topic (1 of the 4Ms) was developed by the fellow and their team members to incorporate the mini-fellowship learnings into their clinic workflows. Fellows also had 2 hours per week of dedicated administration time for a year, outside the fellowship, to work on their PIP and 4M practice changes within their clinic.

Provider Education

The week for mobility training comprised 4 daylong sessions. The first 2 days were spent learning about the epidemiology of falls; risk factors for falling; how to conduct a thorough history and assessment of fall risk; and how to create a prioritized Fall Risk Management Plan (FRMP) to decrease a patient’s individual fall risk through tailored interventions. The FRMP was adapted from the CDC STEADI toolkit.¹³ Core faculty were 2 geriatric-trained providers (NP and physician) and a physical therapist (PT) specializing in fall prevention.

On the third day, fellows took part in a simulated fall risk clinic, in which older adults volunteered to be patient partners, providing an opportunity to apply learnings from days 1 and 2. The clinic included the fellow observing a PT complete a mobility assessment and a pharmacist conduct a high-risk medication review. The fellow synthesized the findings of the mobility assessment and medication review, as well as their own history and assessment, to create a summary of fall risk recommendations to discuss with their volunteer patient partner. The fellows were observed and evaluated in their skills by their patient partner, course faculty, and another fellow. The patient partners, and their assigned fellow, also participated in a 45-minute fall risk presentation, led by a nurse.

On the fourth day, the fellows were joined by select clinic partners, including nurses, pharmacists, and/or medical assistants. The session included discussions among each fellow’s clinical team regarding the current state of fall risk efforts at their clinic, an analysis of barriers, and identification of opportunities to improve workflows and screening rates. Each fellow took with them an action plan tailored to their clinic to improve fall risk management practices, starting with the fellow’s own practice.

Fall Risk Management Plan

The educational sessions introduced the fellows to the FRMP. The FRMP, adapted from the STEADI toolkit, includes a process for fall risk screening (Figure 1) and stratifying a patient’s risk based on their STEADI score in order to promote 3 priority assessments (gait evaluation with PT referral if appropriate; orthostatic blood pressure; and high-risk medication review; Figure 2). Initial actions based on these priority assessments were followed over time, with additional fall risk interventions added as clinically indicated.²⁵ The FRMP is intended to be used during routine office visits, Medicare annual wellness visits, or office visits focused on fall risk or related medical disorders (ie, fall risk visits.)

Providers and their teams were encouraged to spread out fall-related conversations with their patients over multiple visits, since many patients have multiple fall risk factors at play, in addition to other chronic medical issues, and since many interventions often require behavior changes on the part of the patient. Providers also had access to fall-related electronic health record (EHR) templates as well as a comprehensive, internal fall risk management website that included assessment tools, evidence-based resources, and patient handouts.

Assessment and Measurements

We assessed provider knowledge and comfort in their fall risk evaluation and management skills before and after the educational intervention using an 11-item multiple-choice questionnaire and a 4-item confidence questionnaire. The confidence questions used a 7-point Likert scale, with 0 indicating “no confidence” and 7 indicating ”lots of confidence.” The questions were administered via a paper survey. Qualitative comments were derived from evaluations completed at the end of the week.

The fellows’ practice of fall risk screening and management was studied from May 2018, at the completion of Mobility week, to May 2019 for the post-intervention period. A 1-year timeframe before May 2018 was used as the pre-intervention period. Eligible visit types, during which we assumed fall risk was discussed, were any office visits for patients 65+ completed by the patients’ PCPs that used fall risk as a reason for the visit or had a fall-related diagnosis code. Fall risk visits performed by other clinic providers were not counted.

Of those patients who had fall risk screenings completed and were determined to be high risk (STEADI score ≥ 4), data were analyzed to determine whether these patients had any fall-related follow-up visits to their PCP within 60 days of the STEADI screening. For these high-risk patients, data were studied to understand whether orthostatic blood pressure measurements were performed (as documented in a flowsheet) and whether a PT referral was placed. These data were compared with those from providers who practiced in clinics within the same system but who did not participate in the mini-fellowship. Data were obtained from the organization’s EHR. Additional data were measured to evaluate patterns of deprescribing of select high-risk medications, but these data are not included in this analysis.

Analysis

A paired-samples t test was used to measure changes in provider confidence levels. Data were aggregated across fellows, resulting in a mean. A chi-square test of independence was performed to examine the relationship between rates of FRMP adoption by select provider groups. Analysis included a pre- and post-intervention assessment of the fellows’ adoption of FRMP practices, as well as a comparison between the fellows’ practice patterns and those of a control group of PCPs in the organization’s other clinics who did not participate in the mini-fellowship (nontrained control group). Excluded from the control group were providers from the same clinic as the fellows; providers in clinics with a geriatric-trained provider on staff; and clinics outside of the Portland metro and Medford service areas. We used an alpha level of 0.05 for all statistical tests.

Data from 5 providers were included in the analysis of the FRMP adoption. The sixth provider changed practice settings from the clinic to the ED after completing the fellowship; her patient data were not included in the FRMP part of the analysis. EHR data included data on all visits of patients 65+, as well as data for just those 65+ patients who had been identified as being at high risk to fall based on a STEADI score of 4 or higher.

Results

Provider Questionnaire

All 6 providers responded to the pre-intervention and post-intervention tests. For the knowledge questions, fellows, as a composite, correctly answered 57% of the questions before the intervention and 79% after the intervention. Provider confidence level in delivering fall risk care was measured prior to the training (mean, 4.12 [SD, 0.62]) and at the end of the training (mean, 6.47 [SD, 0.45]), demonstrating a significant increase in confidence (t (5) = –10.46, P < 0.001).

Qualitative Comments

Providers also had the opportunity to provide comments on their experience during the Mobility week and at the end of 1 year. In general, the simulated interdisciplinary fall risk clinic was highly rated (“the highlight of the week”) as a practical strategy to embed learning principles. One fellow commented, “Putting the learning into practice helps solidify it in my brain.” Fellows also appreciated the opportunity to learn and meet with their clinic colleagues to begin work on a fall-risk focused PIP and to “have a framework for what to do for people who screen positive [for fall risk].”

FRMP Adoption

A comparison of the care the fellows provided to their patients 65+ in the 12 months pre- and post-training shows the fellows demonstrated significant changes in practice patterns. The fellows were 1.7 times more likely to screen for fall risk; 3.6 times more likely to discuss fall risk; and 5.8 times more likely to check orthostatic blood pressure than prior to the mini-fellowship (Table 1).

The control providers also demonstrated significant increases in fall risk screening and discussion of fall risk between the pre- and post-intervention periods; however, the relative risk (RR) was between 1.10 and 1.13 for this group. For the control group, checking orthostatic blood pressure did not significantly change. In the 12 months after training (Table 2), the fellows were 4.2 times more likely to discuss fall risk and almost 5 times more likely to check orthostatic blood pressure than their nontrained peers for all of their patients 65+, regardless of their risk to fall.

As shown in Table 3, for those patients determined to be at high risk of falling (STEADI score ≥ 4), fellows showed statistically significant increases in fall risk visits (RR, 3.02) and assessment of orthostatic blood pressure (RR, 10.68) before and after the mini-fellowship. The control providers did not show any changes in practice patterns between the pre- and post-period among patients at high risk to fall.

Neither the fellows nor the control group showed changes in patterns of referral to PT. In comparing the 2 groups in the 12 months after training (Table 4), for their patients at risk of falling, the fellows were 4 times more likely to complete fall risk visits and over 6 times more likely to assess orthostatic blood pressure than their nontrained peers. Subgroup analysis of the 75+ population revealed similar trends and significance, but these results are not included here.

Discussion

This study aimed to improve not only providers’ knowledge and confidence in caring for older adults at increased risk to fall, but also their clinical practice in assessing and managing fall risk. In addition to improved knowledge and confidence, we found that the fellows increased their discussion of fall risk (through fall risk visits) and their assessment of orthostatic blood pressure for all of their patients, not just for those identified at increased risk to fall. This improvement held true for the fellows themselves before and after the intervention, but also as compared to their nontrained peers. These practice improvements for all of their 65+ patients, not just those identified as being at high risk to fall, are especially important, since studies indicate that early screening and intervention can help identify people at risk and prevent future falls.¹⁵

We were surprised that there were no significant differences in PT referrals made by the trained fellows, but this finding may have been confounded by the fact that the data included all PT referrals, regardless of diagnosis, not just those referrals that were fall-related. Furthermore, our baseline PT referral rates, at 39% for the intervention group and 42% for the control group, are higher than national data when looking at rehabilitation use by older adults.²⁶

In comparison to a study evaluating the occurrence of fall risk–related clinical practice in primary care before any fall-related educational intervention, orthostatics were checked less frequently in our study (10% versus 30%) and there were fewer PT referrals (42%–44% versus 53%).²⁷ However, the Phelan study took place in patients who had actually had a fall, rather than just having a higher risk for a fall, and was based on detailed chart review. Other studies^23,24 found higher rates of fall risk interventions, but did not break out PT referrals specifically.

In terms of the educational intervention itself, most studies of geriatric education interventions have measured changes in knowledge, confidence, or self-efficacy as they relate to geriatric competence,^28-30 and do not measure practice change as an outcome outside of intent to change or self-reported practice change.^31,32 In general, practice change or longer-term health care–related outcomes have not been studied. Additionally, a range of dosages of educational interventions has been studied, from 1-hour lunchtime presentations^23,32 to half-day²⁹ or several half-day workshops,²⁸ up to 160 hours over 10 months³⁰ or 5 weekends over 6 months.³¹ The duration of our entire intervention at 160 hours over 6 months would be considered on the upper end of dosing relative to these studies, with our Mobility week intervention comprising 32 hours during 1 week. In the Warshaw study, despite 107 1-hour sessions being taught to over 60 physicians in 16 practices over 4 years, only 2 practices ultimately initiated any practice change projects.³² We believe that only curricula that embed practice change skills and opportunities, at a significant enough dose, can actually impact practice change in a sustainable manner.

Knowledge and skill acquisition among individual providers does not take place to a sufficient degree in the current health care arena, which is focused on productivity and short visit times. Consistent with other studies, we included interdisciplinary members of the primary care team for part of the mini-fellowship, although other studies used models that train across disciplines for the entirety of the learning experience.^28-30,33 Our educational model was strengthened by including other professionals to provide some of the education and model the ideal geriatric team, including PT, occupational therapy, and pharmacy, for the week on mobility.

Most studies exploring interventions through geriatric educational initiatives are conducted within academic institutions, with a primary focus on physician faculty and, by extension, their teaching of residents and others.^34,35 We believe our integrated model, which is steeped in community-based primary care practices like Lam’s,³¹ offers the greatest outreach to large community-based care systems and their patients. Training providers to work with their teams to change their own practices first gives skills and expertise that help further establish them as geriatric champions within their practices, laying the groundwork for more widespread practice change at their clinics.

Limitations

In addition to the limitations described above relating to the capture of PT referrals, other limitations included the relatively short time period for follow-up data as well as the small size of the intervention group. However, we found value in the instructional depth that the small group size allowed.

While the nontrained providers did show some improvement during the same period, we believe the relative risk was not clinically significant. We suspect that the larger health system efforts to standardize screening of patients 65+ across all clinics as a core quality metric confounded these results. The data analysis also included only fall-related patient visits that occurred with a provider who was that patient’s PCP, which could have missed visits done by other PCP colleagues, RNs, or pharmacists in the same clinic, thus undercounting the true number of fall-related visits. Furthermore, counting of fall-related interventions relied upon providers documenting consistently in the EHR, which could also lead to under-represention of fall risk clinical efforts.

The data presented, while encouraging, do not reflect clinic-wide practice change patterns and are considered only proximate outcomes rather than more long-term or cost-related outcomes, as would be captured by fall-related utilization measures like emergency room visits and hospitalizations. We expect to evaluate the broader impact and these value-based outcomes in the future. All providers and teams were from the same health care system, which may not allow our results to transfer to other organizations or regions of clinical practice.

Summary

This study demonstrates that an intensive mini-fellowship model of geriatrics training improved both knowledge and confidence in the realm of fall risk assessment and intervention among PCPs who had not been formally trained in geriatrics. More importantly, the training improved the fall-related care of their patients at increased risk to fall, but also of all of their older patients, with improvements in care measured up to a year after the mini-fellowship. Although this article only describes the work done as part of the Mobility aim of the 4M AFHS model, we believe the entire mini-fellowship curriculum offers the opportunity to “geriatricize” clinicians and their teams in learning geriatric principles and skills that they can translate into their practice in a sustainable way, as Tinetti encourages.⁸ Future study to evaluate other process outcomes more precisely, such as PT, as well as cost- and value-based outcomes, and the influence of trained providers on their clinic partners, will further establish the value proposition of targeted, disseminated, intensive geriatrics training of primary care clinicians as a strategy of age-friendly health systems as they work to improve the care of their older adults.

Acknowledgment: We are grateful for the dedication and hard work of the 2018 Geriatric Mini-Fellowship fellows at Providence Health & Services-Oregon who made this article possible. Thanks to Drs. Stephanie Cha, Emily Puukka-Clark, Laurie Dutkiewicz, Cara Ellis, Deb Frost, Jordan Roth, and Subhechchha Shah for promoting the AFHS work within their Providence Medical Group clinics and to PMG leadership and the fellows’ clinical teams for supporting the fellows, the AFHS work, and their older patients.

Corresponding author: Colleen M. Casey, PhD, ANP-BC, Providence Health & Services, Senior Health Program, 4400 NE Halsey, 5th Floor, Portland, OR 97213; [email protected].

Financial disclosures: None.

From the Senior Health Program, Providence Health & Services, Oregon, Portland, OR.

Abstract

Background: Approximately 51 million adults in the United States are 65 years of age or older, yet few geriatric-trained primary care providers (PCP) serve this population. The Age-Friendly Health System framework, consisting of evidence-based 4M care (Mobility, Medication, Mentation, and what Matters), encourages all PCPs to assess mobility in older adults.

Objective: To improve PCP knowledge, confidence, and clinical practice in assessing and managing fall risk.

Methods: A 1-week educational session focusing on mobility (part of a 4-week Geriatric Mini-Fellowship) for 6 selected PCPs from a large health care system was conducted to increase knowledge and ability to address fall risk in older adults. The week included learning and practicing a Fall Risk Management Plan (FRMP) algorithm, including planning for their own practice changes. Pre- and post-test surveys assessed changes in knowledge and confidence. Patient data were compared 12 months before and after training to evaluate PCP adoption of FRMP components.

Results: The training increased provider knowledge and confidence. The trained PCPs were 1.7 times more likely to screen for fall risk; 3.6 times more likely to discuss fall risk; and 5.8 times more likely to assess orthostatic blood pressure in their 65+ patients after the mini-fellowship. In high-risk patients, they were 4.1 times more likely to discuss fall risk and 6.3 times more likely to assess orthostatic blood pressure than their nontrained peers. Changes in physical therapy referral rates were not observed.

Conclusions: In-depth, skills-based geriatric educational sessions improved PCPs’ knowledge and confidence and also improved their fall risk management practices for their older patients.

Keywords: geriatrics; guidelines; Age-Friendly Health System; 4M; workforce training; practice change; fellowship.

The US population is aging rapidly. People aged 85 years and older are the largest-growing segment of the US population, and this segment is expected to increase by 123% by 2040.¹ Caregiving needs increase with age as older adults develop more chronic conditions, such as hypertension, heart disease, arthritis, and dementia. However, even with increasing morbidity and dependence, a majority of older adults still live in the community rather than in institutional settings.² These older adults seek medical care more frequently than younger people, with about 22% of patients 75 years and older having 10 or more health care visits in the previous 12 months. By 2040, nearly a quarter of the US population is expected to be 65 or older, with many of these older adults seeking regular primary care from providers who do not have formal training in the care of a population with multiple complex, chronic health conditions and increased caregiving needs.¹

Despite this growing demand for health care professionals trained in the care of older adults, access to these types of clinicians is limited. In 2018, there were roughly 7000 certified geriatricians, with only 3600 of them practicing full-time.^3,4 Similarly, of 290,000 certified nurse practitioners (NPs), about 9% of them have geriatric certification.⁵ Geriatricians, medical doctors trained in the care of older adults, and geriatric-trained NPs are part of a cadre of a geriatric-trained workforce that provides unique expertise in caring for older adults with chronic and advanced illness. They know how to manage multiple, complex geriatric syndromes like falls, dementia, and polypharmacy; understand and maximize team-based care; and focus on caring for an older person with a goal-centered versus a disease-centered approach.⁶

Broadly, geriatric care includes a spectrum of adults, from those who are aging healthfully to those who are the frailest. Research has suggested that approximately 30% of older adults need care by a geriatric-trained clinician, with the oldest and frailest patients needing more clinician time for assessment and treatment, care coordination, and coaching of caregivers.⁷ With this assumption in mind, it is projected that by 2025, there will be a national shortage of 26,980 geriatricians, with the western United States disproportionately affected by this shortage.⁴Rather than lamenting this shortage, Tinetti recommends a new path forward: “Our mission should not be to train enough geriatricians to provide direct care, but rather to ensure that every clinician caring for older adults is competent in geriatric principles and practices.”⁸ Sometimes called ”geriatricizing,” the idea is to use existing geriatric providers as a small elite training force to infuse geriatric principles and skills across their colleagues in primary care and other disciplines.^8,9 Efforts of the American Geriatrics Society (AGS), with support from the John A. Hartford Foundation (JAHF), have been successful in developing geriatric training across multiple specialties, including surgery, orthopedics, and emergency medicine (www.americangeriatrics.org/programs/geriatrics-specialists-initiative).

The Age-Friendly Health System and 4M Model

To help augment this idea of equipping health care systems and their clinicians with more readily available geriatric knowledge, skills, and tools, the JAHF, along with the Institute for Healthcare Improvement (IHI), created the Age-Friendly Health System (AFHS) paradigm in 2015.¹⁰ Using the 4M model, the AFHS initiative established a set of evidence-based geriatric priorities and interventions meant to improve the care of older adults, reduce harm and duplication, and provide a framework for engaging leadership, clinical teams, and operational systems across inpatient and ambulatory settings.¹¹ Mobility, including fall risk screening and intervention, is 1 of the 4M foundational elements of the Age-Friendly model. In addition to Mobility, the 4M model also includes 3 other key geriatric domains: Mentation (dementia, depression, and delirium), Medication (high-risk medications, polypharmacy, and deprescribing), and What Matters (goals of care conversations and understanding quality of life for older patients).¹¹ The 4M initiative encourages adoption of a geriatric lens that looks across chronic conditions and accounts for the interplay among geriatric syndromes, such as falls, cognitive impairment, and frailty, in order to provide care better tailored to what the patient needs and desires.¹² IHI and JAHF have targeted the adoption of the 4M model by 20% of US health care systems by 2020.¹¹

Mini-Fellowship and Mobility Week

To bolster geriatric skills among community-based primary care providers (PCPs), we initiated a Geriatric Mini-Fellowship, a 4-week condensed curriculum taught over 6 months. Each week focuses on 1 of the age-friendly 4Ms, with the goal of increasing the knowledge, self-efficacy, skills, and competencies of the participating PCPs (called “fellow” hereafter) and at the same time, equipping each to become a champion of geriatric practice. This article focuses on the Mobility week, the second week of the mini-fellowship, and the effect of the week on the fellows’ practice changes.

To construct the Mobility week’s curriculum with a focus on the ambulatory setting, we relied upon national evidence-based work in fall risk management. The Centers for Disease Control and Prevention (CDC) has made fall risk screening and management in primary care a high priority. Using the clinical practice guidelines for managing fall risk developed by the American and British Geriatrics Societies (AGS/BGS), the CDC developed the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) toolkit.¹³ Foundational to the toolkit is the validated 12-item Stay Independent falls screening questionnaire (STEADI questionnaire).¹⁴ Patients who score 4 or higher (out of a total score of 14) on the questionnaire are considered at increased risk of falling. The CDC has developed a clinical algorithm that guides clinical teams through screening and assessment to help identify appropriate interventions to target specific risk factors. Research has clearly established that a multifactorial approach to fall risk intervention can be successful in reducing fall risk by as much as 25%.^15-17

The significant morbidity and mortality caused by falls make training nongeriatrician clinicians on how to better address fall risk imperative. More than 25% of older adults fall each year.¹⁸ These falls contribute to rising rates of fall-related deaths,¹⁹ emergency department (ED) visits,²⁰ and hospital readmissions.²¹ Initiatives like the AFHS focus on mobility and the CDC’s development of supporting clinical materials²² aim to improve primary care adoption of fall risk screening and intervention practices.^23,24 The epidemic of falls must compel all PCPs, not just those practicing geriatrics, to make discussing and addressing fall risk and falls a priority.

Methods

Setting

This project took place as part of a regional primary care effort in Oregon. Providence Health & Services-Oregon is part of a multi-state integrated health care system in the western United States whose PCPs serve more than 80,000 patients aged 65 years and older per year; these patients comprise 38% of the system’s office visits each year. Regionally, there are 47 family and internal medicine clinics employing roughly 290 providers (physicians, NPs, and physician assistants). The organization has only 4 PCPs trained in geriatrics and does not offer any geriatric clinical consultation services. Six PCPs from different clinics, representing both rural and urban settings, are chosen to participate in the geriatric mini-fellowship each year.

This project was conducted as a quality improvement initiative within the organization and did not constitute human subjects research. It was not conducted under the oversight of the Institutional Review Board.

Intervention

The mini-fellowship was taught in 4 1-week blocks between April and October 2018, with a curriculum designed to be interactive and practical. The faculty was intentionally interdisciplinary to teach and model team-based practice. Each week participants were excused from their clinical practice. Approximately 160 hours of continuing medical education credits were awarded for the full mini-fellowship. As part of each weekly session, a performance improvement project (PIP) focused on that week’s topic (1 of the 4Ms) was developed by the fellow and their team members to incorporate the mini-fellowship learnings into their clinic workflows. Fellows also had 2 hours per week of dedicated administration time for a year, outside the fellowship, to work on their PIP and 4M practice changes within their clinic.

Provider Education

The week for mobility training comprised 4 daylong sessions. The first 2 days were spent learning about the epidemiology of falls; risk factors for falling; how to conduct a thorough history and assessment of fall risk; and how to create a prioritized Fall Risk Management Plan (FRMP) to decrease a patient’s individual fall risk through tailored interventions. The FRMP was adapted from the CDC STEADI toolkit.¹³ Core faculty were 2 geriatric-trained providers (NP and physician) and a physical therapist (PT) specializing in fall prevention.

On the third day, fellows took part in a simulated fall risk clinic, in which older adults volunteered to be patient partners, providing an opportunity to apply learnings from days 1 and 2. The clinic included the fellow observing a PT complete a mobility assessment and a pharmacist conduct a high-risk medication review. The fellow synthesized the findings of the mobility assessment and medication review, as well as their own history and assessment, to create a summary of fall risk recommendations to discuss with their volunteer patient partner. The fellows were observed and evaluated in their skills by their patient partner, course faculty, and another fellow. The patient partners, and their assigned fellow, also participated in a 45-minute fall risk presentation, led by a nurse.

On the fourth day, the fellows were joined by select clinic partners, including nurses, pharmacists, and/or medical assistants. The session included discussions among each fellow’s clinical team regarding the current state of fall risk efforts at their clinic, an analysis of barriers, and identification of opportunities to improve workflows and screening rates. Each fellow took with them an action plan tailored to their clinic to improve fall risk management practices, starting with the fellow’s own practice.

Fall Risk Management Plan

The educational sessions introduced the fellows to the FRMP. The FRMP, adapted from the STEADI toolkit, includes a process for fall risk screening (Figure 1) and stratifying a patient’s risk based on their STEADI score in order to promote 3 priority assessments (gait evaluation with PT referral if appropriate; orthostatic blood pressure; and high-risk medication review; Figure 2). Initial actions based on these priority assessments were followed over time, with additional fall risk interventions added as clinically indicated.²⁵ The FRMP is intended to be used during routine office visits, Medicare annual wellness visits, or office visits focused on fall risk or related medical disorders (ie, fall risk visits.)

Providers and their teams were encouraged to spread out fall-related conversations with their patients over multiple visits, since many patients have multiple fall risk factors at play, in addition to other chronic medical issues, and since many interventions often require behavior changes on the part of the patient. Providers also had access to fall-related electronic health record (EHR) templates as well as a comprehensive, internal fall risk management website that included assessment tools, evidence-based resources, and patient handouts.

Assessment and Measurements

We assessed provider knowledge and comfort in their fall risk evaluation and management skills before and after the educational intervention using an 11-item multiple-choice questionnaire and a 4-item confidence questionnaire. The confidence questions used a 7-point Likert scale, with 0 indicating “no confidence” and 7 indicating ”lots of confidence.” The questions were administered via a paper survey. Qualitative comments were derived from evaluations completed at the end of the week.

The fellows’ practice of fall risk screening and management was studied from May 2018, at the completion of Mobility week, to May 2019 for the post-intervention period. A 1-year timeframe before May 2018 was used as the pre-intervention period. Eligible visit types, during which we assumed fall risk was discussed, were any office visits for patients 65+ completed by the patients’ PCPs that used fall risk as a reason for the visit or had a fall-related diagnosis code. Fall risk visits performed by other clinic providers were not counted.

Of those patients who had fall risk screenings completed and were determined to be high risk (STEADI score ≥ 4), data were analyzed to determine whether these patients had any fall-related follow-up visits to their PCP within 60 days of the STEADI screening. For these high-risk patients, data were studied to understand whether orthostatic blood pressure measurements were performed (as documented in a flowsheet) and whether a PT referral was placed. These data were compared with those from providers who practiced in clinics within the same system but who did not participate in the mini-fellowship. Data were obtained from the organization’s EHR. Additional data were measured to evaluate patterns of deprescribing of select high-risk medications, but these data are not included in this analysis.

Analysis

A paired-samples t test was used to measure changes in provider confidence levels. Data were aggregated across fellows, resulting in a mean. A chi-square test of independence was performed to examine the relationship between rates of FRMP adoption by select provider groups. Analysis included a pre- and post-intervention assessment of the fellows’ adoption of FRMP practices, as well as a comparison between the fellows’ practice patterns and those of a control group of PCPs in the organization’s other clinics who did not participate in the mini-fellowship (nontrained control group). Excluded from the control group were providers from the same clinic as the fellows; providers in clinics with a geriatric-trained provider on staff; and clinics outside of the Portland metro and Medford service areas. We used an alpha level of 0.05 for all statistical tests.

Data from 5 providers were included in the analysis of the FRMP adoption. The sixth provider changed practice settings from the clinic to the ED after completing the fellowship; her patient data were not included in the FRMP part of the analysis. EHR data included data on all visits of patients 65+, as well as data for just those 65+ patients who had been identified as being at high risk to fall based on a STEADI score of 4 or higher.

Results

Provider Questionnaire

All 6 providers responded to the pre-intervention and post-intervention tests. For the knowledge questions, fellows, as a composite, correctly answered 57% of the questions before the intervention and 79% after the intervention. Provider confidence level in delivering fall risk care was measured prior to the training (mean, 4.12 [SD, 0.62]) and at the end of the training (mean, 6.47 [SD, 0.45]), demonstrating a significant increase in confidence (t (5) = –10.46, P < 0.001).

Qualitative Comments

Providers also had the opportunity to provide comments on their experience during the Mobility week and at the end of 1 year. In general, the simulated interdisciplinary fall risk clinic was highly rated (“the highlight of the week”) as a practical strategy to embed learning principles. One fellow commented, “Putting the learning into practice helps solidify it in my brain.” Fellows also appreciated the opportunity to learn and meet with their clinic colleagues to begin work on a fall-risk focused PIP and to “have a framework for what to do for people who screen positive [for fall risk].”

FRMP Adoption

A comparison of the care the fellows provided to their patients 65+ in the 12 months pre- and post-training shows the fellows demonstrated significant changes in practice patterns. The fellows were 1.7 times more likely to screen for fall risk; 3.6 times more likely to discuss fall risk; and 5.8 times more likely to check orthostatic blood pressure than prior to the mini-fellowship (Table 1).

The control providers also demonstrated significant increases in fall risk screening and discussion of fall risk between the pre- and post-intervention periods; however, the relative risk (RR) was between 1.10 and 1.13 for this group. For the control group, checking orthostatic blood pressure did not significantly change. In the 12 months after training (Table 2), the fellows were 4.2 times more likely to discuss fall risk and almost 5 times more likely to check orthostatic blood pressure than their nontrained peers for all of their patients 65+, regardless of their risk to fall.

As shown in Table 3, for those patients determined to be at high risk of falling (STEADI score ≥ 4), fellows showed statistically significant increases in fall risk visits (RR, 3.02) and assessment of orthostatic blood pressure (RR, 10.68) before and after the mini-fellowship. The control providers did not show any changes in practice patterns between the pre- and post-period among patients at high risk to fall.

Neither the fellows nor the control group showed changes in patterns of referral to PT. In comparing the 2 groups in the 12 months after training (Table 4), for their patients at risk of falling, the fellows were 4 times more likely to complete fall risk visits and over 6 times more likely to assess orthostatic blood pressure than their nontrained peers. Subgroup analysis of the 75+ population revealed similar trends and significance, but these results are not included here.

Discussion

This study aimed to improve not only providers’ knowledge and confidence in caring for older adults at increased risk to fall, but also their clinical practice in assessing and managing fall risk. In addition to improved knowledge and confidence, we found that the fellows increased their discussion of fall risk (through fall risk visits) and their assessment of orthostatic blood pressure for all of their patients, not just for those identified at increased risk to fall. This improvement held true for the fellows themselves before and after the intervention, but also as compared to their nontrained peers. These practice improvements for all of their 65+ patients, not just those identified as being at high risk to fall, are especially important, since studies indicate that early screening and intervention can help identify people at risk and prevent future falls.¹⁵

We were surprised that there were no significant differences in PT referrals made by the trained fellows, but this finding may have been confounded by the fact that the data included all PT referrals, regardless of diagnosis, not just those referrals that were fall-related. Furthermore, our baseline PT referral rates, at 39% for the intervention group and 42% for the control group, are higher than national data when looking at rehabilitation use by older adults.²⁶

In comparison to a study evaluating the occurrence of fall risk–related clinical practice in primary care before any fall-related educational intervention, orthostatics were checked less frequently in our study (10% versus 30%) and there were fewer PT referrals (42%–44% versus 53%).²⁷ However, the Phelan study took place in patients who had actually had a fall, rather than just having a higher risk for a fall, and was based on detailed chart review. Other studies^23,24 found higher rates of fall risk interventions, but did not break out PT referrals specifically.

In terms of the educational intervention itself, most studies of geriatric education interventions have measured changes in knowledge, confidence, or self-efficacy as they relate to geriatric competence,^28-30 and do not measure practice change as an outcome outside of intent to change or self-reported practice change.^31,32 In general, practice change or longer-term health care–related outcomes have not been studied. Additionally, a range of dosages of educational interventions has been studied, from 1-hour lunchtime presentations^23,32 to half-day²⁹ or several half-day workshops,²⁸ up to 160 hours over 10 months³⁰ or 5 weekends over 6 months.³¹ The duration of our entire intervention at 160 hours over 6 months would be considered on the upper end of dosing relative to these studies, with our Mobility week intervention comprising 32 hours during 1 week. In the Warshaw study, despite 107 1-hour sessions being taught to over 60 physicians in 16 practices over 4 years, only 2 practices ultimately initiated any practice change projects.³² We believe that only curricula that embed practice change skills and opportunities, at a significant enough dose, can actually impact practice change in a sustainable manner.

Knowledge and skill acquisition among individual providers does not take place to a sufficient degree in the current health care arena, which is focused on productivity and short visit times. Consistent with other studies, we included interdisciplinary members of the primary care team for part of the mini-fellowship, although other studies used models that train across disciplines for the entirety of the learning experience.^28-30,33 Our educational model was strengthened by including other professionals to provide some of the education and model the ideal geriatric team, including PT, occupational therapy, and pharmacy, for the week on mobility.

Most studies exploring interventions through geriatric educational initiatives are conducted within academic institutions, with a primary focus on physician faculty and, by extension, their teaching of residents and others.^34,35 We believe our integrated model, which is steeped in community-based primary care practices like Lam’s,³¹ offers the greatest outreach to large community-based care systems and their patients. Training providers to work with their teams to change their own practices first gives skills and expertise that help further establish them as geriatric champions within their practices, laying the groundwork for more widespread practice change at their clinics.

Limitations

In addition to the limitations described above relating to the capture of PT referrals, other limitations included the relatively short time period for follow-up data as well as the small size of the intervention group. However, we found value in the instructional depth that the small group size allowed.

While the nontrained providers did show some improvement during the same period, we believe the relative risk was not clinically significant. We suspect that the larger health system efforts to standardize screening of patients 65+ across all clinics as a core quality metric confounded these results. The data analysis also included only fall-related patient visits that occurred with a provider who was that patient’s PCP, which could have missed visits done by other PCP colleagues, RNs, or pharmacists in the same clinic, thus undercounting the true number of fall-related visits. Furthermore, counting of fall-related interventions relied upon providers documenting consistently in the EHR, which could also lead to under-represention of fall risk clinical efforts.

The data presented, while encouraging, do not reflect clinic-wide practice change patterns and are considered only proximate outcomes rather than more long-term or cost-related outcomes, as would be captured by fall-related utilization measures like emergency room visits and hospitalizations. We expect to evaluate the broader impact and these value-based outcomes in the future. All providers and teams were from the same health care system, which may not allow our results to transfer to other organizations or regions of clinical practice.

Summary

This study demonstrates that an intensive mini-fellowship model of geriatrics training improved both knowledge and confidence in the realm of fall risk assessment and intervention among PCPs who had not been formally trained in geriatrics. More importantly, the training improved the fall-related care of their patients at increased risk to fall, but also of all of their older patients, with improvements in care measured up to a year after the mini-fellowship. Although this article only describes the work done as part of the Mobility aim of the 4M AFHS model, we believe the entire mini-fellowship curriculum offers the opportunity to “geriatricize” clinicians and their teams in learning geriatric principles and skills that they can translate into their practice in a sustainable way, as Tinetti encourages.⁸ Future study to evaluate other process outcomes more precisely, such as PT, as well as cost- and value-based outcomes, and the influence of trained providers on their clinic partners, will further establish the value proposition of targeted, disseminated, intensive geriatrics training of primary care clinicians as a strategy of age-friendly health systems as they work to improve the care of their older adults.

Acknowledgment: We are grateful for the dedication and hard work of the 2018 Geriatric Mini-Fellowship fellows at Providence Health & Services-Oregon who made this article possible. Thanks to Drs. Stephanie Cha, Emily Puukka-Clark, Laurie Dutkiewicz, Cara Ellis, Deb Frost, Jordan Roth, and Subhechchha Shah for promoting the AFHS work within their Providence Medical Group clinics and to PMG leadership and the fellows’ clinical teams for supporting the fellows, the AFHS work, and their older patients.

Corresponding author: Colleen M. Casey, PhD, ANP-BC, Providence Health & Services, Senior Health Program, 4400 NE Halsey, 5th Floor, Portland, OR 97213; [email protected].

Financial disclosures: None.

From the Senior Health Program, Providence Health & Services, Oregon, Portland, OR.

Abstract

Background: Approximately 51 million adults in the United States are 65 years of age or older, yet few geriatric-trained primary care providers (PCP) serve this population. The Age-Friendly Health System framework, consisting of evidence-based 4M care (Mobility, Medication, Mentation, and what Matters), encourages all PCPs to assess mobility in older adults.

Objective: To improve PCP knowledge, confidence, and clinical practice in assessing and managing fall risk.

Methods: A 1-week educational session focusing on mobility (part of a 4-week Geriatric Mini-Fellowship) for 6 selected PCPs from a large health care system was conducted to increase knowledge and ability to address fall risk in older adults. The week included learning and practicing a Fall Risk Management Plan (FRMP) algorithm, including planning for their own practice changes. Pre- and post-test surveys assessed changes in knowledge and confidence. Patient data were compared 12 months before and after training to evaluate PCP adoption of FRMP components.

Results: The training increased provider knowledge and confidence. The trained PCPs were 1.7 times more likely to screen for fall risk; 3.6 times more likely to discuss fall risk; and 5.8 times more likely to assess orthostatic blood pressure in their 65+ patients after the mini-fellowship. In high-risk patients, they were 4.1 times more likely to discuss fall risk and 6.3 times more likely to assess orthostatic blood pressure than their nontrained peers. Changes in physical therapy referral rates were not observed.

Conclusions: In-depth, skills-based geriatric educational sessions improved PCPs’ knowledge and confidence and also improved their fall risk management practices for their older patients.

Keywords: geriatrics; guidelines; Age-Friendly Health System; 4M; workforce training; practice change; fellowship.

The US population is aging rapidly. People aged 85 years and older are the largest-growing segment of the US population, and this segment is expected to increase by 123% by 2040.¹ Caregiving needs increase with age as older adults develop more chronic conditions, such as hypertension, heart disease, arthritis, and dementia. However, even with increasing morbidity and dependence, a majority of older adults still live in the community rather than in institutional settings.² These older adults seek medical care more frequently than younger people, with about 22% of patients 75 years and older having 10 or more health care visits in the previous 12 months. By 2040, nearly a quarter of the US population is expected to be 65 or older, with many of these older adults seeking regular primary care from providers who do not have formal training in the care of a population with multiple complex, chronic health conditions and increased caregiving needs.¹

Despite this growing demand for health care professionals trained in the care of older adults, access to these types of clinicians is limited. In 2018, there were roughly 7000 certified geriatricians, with only 3600 of them practicing full-time.^3,4 Similarly, of 290,000 certified nurse practitioners (NPs), about 9% of them have geriatric certification.⁵ Geriatricians, medical doctors trained in the care of older adults, and geriatric-trained NPs are part of a cadre of a geriatric-trained workforce that provides unique expertise in caring for older adults with chronic and advanced illness. They know how to manage multiple, complex geriatric syndromes like falls, dementia, and polypharmacy; understand and maximize team-based care; and focus on caring for an older person with a goal-centered versus a disease-centered approach.⁶

Broadly, geriatric care includes a spectrum of adults, from those who are aging healthfully to those who are the frailest. Research has suggested that approximately 30% of older adults need care by a geriatric-trained clinician, with the oldest and frailest patients needing more clinician time for assessment and treatment, care coordination, and coaching of caregivers.⁷ With this assumption in mind, it is projected that by 2025, there will be a national shortage of 26,980 geriatricians, with the western United States disproportionately affected by this shortage.⁴Rather than lamenting this shortage, Tinetti recommends a new path forward: “Our mission should not be to train enough geriatricians to provide direct care, but rather to ensure that every clinician caring for older adults is competent in geriatric principles and practices.”⁸ Sometimes called ”geriatricizing,” the idea is to use existing geriatric providers as a small elite training force to infuse geriatric principles and skills across their colleagues in primary care and other disciplines.^8,9 Efforts of the American Geriatrics Society (AGS), with support from the John A. Hartford Foundation (JAHF), have been successful in developing geriatric training across multiple specialties, including surgery, orthopedics, and emergency medicine (www.americangeriatrics.org/programs/geriatrics-specialists-initiative).

The Age-Friendly Health System and 4M Model

To help augment this idea of equipping health care systems and their clinicians with more readily available geriatric knowledge, skills, and tools, the JAHF, along with the Institute for Healthcare Improvement (IHI), created the Age-Friendly Health System (AFHS) paradigm in 2015.¹⁰ Using the 4M model, the AFHS initiative established a set of evidence-based geriatric priorities and interventions meant to improve the care of older adults, reduce harm and duplication, and provide a framework for engaging leadership, clinical teams, and operational systems across inpatient and ambulatory settings.¹¹ Mobility, including fall risk screening and intervention, is 1 of the 4M foundational elements of the Age-Friendly model. In addition to Mobility, the 4M model also includes 3 other key geriatric domains: Mentation (dementia, depression, and delirium), Medication (high-risk medications, polypharmacy, and deprescribing), and What Matters (goals of care conversations and understanding quality of life for older patients).¹¹ The 4M initiative encourages adoption of a geriatric lens that looks across chronic conditions and accounts for the interplay among geriatric syndromes, such as falls, cognitive impairment, and frailty, in order to provide care better tailored to what the patient needs and desires.¹² IHI and JAHF have targeted the adoption of the 4M model by 20% of US health care systems by 2020.¹¹

Mini-Fellowship and Mobility Week

To bolster geriatric skills among community-based primary care providers (PCPs), we initiated a Geriatric Mini-Fellowship, a 4-week condensed curriculum taught over 6 months. Each week focuses on 1 of the age-friendly 4Ms, with the goal of increasing the knowledge, self-efficacy, skills, and competencies of the participating PCPs (called “fellow” hereafter) and at the same time, equipping each to become a champion of geriatric practice. This article focuses on the Mobility week, the second week of the mini-fellowship, and the effect of the week on the fellows’ practice changes.

To construct the Mobility week’s curriculum with a focus on the ambulatory setting, we relied upon national evidence-based work in fall risk management. The Centers for Disease Control and Prevention (CDC) has made fall risk screening and management in primary care a high priority. Using the clinical practice guidelines for managing fall risk developed by the American and British Geriatrics Societies (AGS/BGS), the CDC developed the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) toolkit.¹³ Foundational to the toolkit is the validated 12-item Stay Independent falls screening questionnaire (STEADI questionnaire).¹⁴ Patients who score 4 or higher (out of a total score of 14) on the questionnaire are considered at increased risk of falling. The CDC has developed a clinical algorithm that guides clinical teams through screening and assessment to help identify appropriate interventions to target specific risk factors. Research has clearly established that a multifactorial approach to fall risk intervention can be successful in reducing fall risk by as much as 25%.^15-17

The significant morbidity and mortality caused by falls make training nongeriatrician clinicians on how to better address fall risk imperative. More than 25% of older adults fall each year.¹⁸ These falls contribute to rising rates of fall-related deaths,¹⁹ emergency department (ED) visits,²⁰ and hospital readmissions.²¹ Initiatives like the AFHS focus on mobility and the CDC’s development of supporting clinical materials²² aim to improve primary care adoption of fall risk screening and intervention practices.^23,24 The epidemic of falls must compel all PCPs, not just those practicing geriatrics, to make discussing and addressing fall risk and falls a priority.

Methods

Setting

This project took place as part of a regional primary care effort in Oregon. Providence Health & Services-Oregon is part of a multi-state integrated health care system in the western United States whose PCPs serve more than 80,000 patients aged 65 years and older per year; these patients comprise 38% of the system’s office visits each year. Regionally, there are 47 family and internal medicine clinics employing roughly 290 providers (physicians, NPs, and physician assistants). The organization has only 4 PCPs trained in geriatrics and does not offer any geriatric clinical consultation services. Six PCPs from different clinics, representing both rural and urban settings, are chosen to participate in the geriatric mini-fellowship each year.

This project was conducted as a quality improvement initiative within the organization and did not constitute human subjects research. It was not conducted under the oversight of the Institutional Review Board.

Intervention

The mini-fellowship was taught in 4 1-week blocks between April and October 2018, with a curriculum designed to be interactive and practical. The faculty was intentionally interdisciplinary to teach and model team-based practice. Each week participants were excused from their clinical practice. Approximately 160 hours of continuing medical education credits were awarded for the full mini-fellowship. As part of each weekly session, a performance improvement project (PIP) focused on that week’s topic (1 of the 4Ms) was developed by the fellow and their team members to incorporate the mini-fellowship learnings into their clinic workflows. Fellows also had 2 hours per week of dedicated administration time for a year, outside the fellowship, to work on their PIP and 4M practice changes within their clinic.

Provider Education

The week for mobility training comprised 4 daylong sessions. The first 2 days were spent learning about the epidemiology of falls; risk factors for falling; how to conduct a thorough history and assessment of fall risk; and how to create a prioritized Fall Risk Management Plan (FRMP) to decrease a patient’s individual fall risk through tailored interventions. The FRMP was adapted from the CDC STEADI toolkit.¹³ Core faculty were 2 geriatric-trained providers (NP and physician) and a physical therapist (PT) specializing in fall prevention.

On the third day, fellows took part in a simulated fall risk clinic, in which older adults volunteered to be patient partners, providing an opportunity to apply learnings from days 1 and 2. The clinic included the fellow observing a PT complete a mobility assessment and a pharmacist conduct a high-risk medication review. The fellow synthesized the findings of the mobility assessment and medication review, as well as their own history and assessment, to create a summary of fall risk recommendations to discuss with their volunteer patient partner. The fellows were observed and evaluated in their skills by their patient partner, course faculty, and another fellow. The patient partners, and their assigned fellow, also participated in a 45-minute fall risk presentation, led by a nurse.

On the fourth day, the fellows were joined by select clinic partners, including nurses, pharmacists, and/or medical assistants. The session included discussions among each fellow’s clinical team regarding the current state of fall risk efforts at their clinic, an analysis of barriers, and identification of opportunities to improve workflows and screening rates. Each fellow took with them an action plan tailored to their clinic to improve fall risk management practices, starting with the fellow’s own practice.

Fall Risk Management Plan

The educational sessions introduced the fellows to the FRMP. The FRMP, adapted from the STEADI toolkit, includes a process for fall risk screening (Figure 1) and stratifying a patient’s risk based on their STEADI score in order to promote 3 priority assessments (gait evaluation with PT referral if appropriate; orthostatic blood pressure; and high-risk medication review; Figure 2). Initial actions based on these priority assessments were followed over time, with additional fall risk interventions added as clinically indicated.²⁵ The FRMP is intended to be used during routine office visits, Medicare annual wellness visits, or office visits focused on fall risk or related medical disorders (ie, fall risk visits.)

Providers and their teams were encouraged to spread out fall-related conversations with their patients over multiple visits, since many patients have multiple fall risk factors at play, in addition to other chronic medical issues, and since many interventions often require behavior changes on the part of the patient. Providers also had access to fall-related electronic health record (EHR) templates as well as a comprehensive, internal fall risk management website that included assessment tools, evidence-based resources, and patient handouts.

Assessment and Measurements

We assessed provider knowledge and comfort in their fall risk evaluation and management skills before and after the educational intervention using an 11-item multiple-choice questionnaire and a 4-item confidence questionnaire. The confidence questions used a 7-point Likert scale, with 0 indicating “no confidence” and 7 indicating ”lots of confidence.” The questions were administered via a paper survey. Qualitative comments were derived from evaluations completed at the end of the week.

The fellows’ practice of fall risk screening and management was studied from May 2018, at the completion of Mobility week, to May 2019 for the post-intervention period. A 1-year timeframe before May 2018 was used as the pre-intervention period. Eligible visit types, during which we assumed fall risk was discussed, were any office visits for patients 65+ completed by the patients’ PCPs that used fall risk as a reason for the visit or had a fall-related diagnosis code. Fall risk visits performed by other clinic providers were not counted.

Of those patients who had fall risk screenings completed and were determined to be high risk (STEADI score ≥ 4), data were analyzed to determine whether these patients had any fall-related follow-up visits to their PCP within 60 days of the STEADI screening. For these high-risk patients, data were studied to understand whether orthostatic blood pressure measurements were performed (as documented in a flowsheet) and whether a PT referral was placed. These data were compared with those from providers who practiced in clinics within the same system but who did not participate in the mini-fellowship. Data were obtained from the organization’s EHR. Additional data were measured to evaluate patterns of deprescribing of select high-risk medications, but these data are not included in this analysis.

Analysis

A paired-samples t test was used to measure changes in provider confidence levels. Data were aggregated across fellows, resulting in a mean. A chi-square test of independence was performed to examine the relationship between rates of FRMP adoption by select provider groups. Analysis included a pre- and post-intervention assessment of the fellows’ adoption of FRMP practices, as well as a comparison between the fellows’ practice patterns and those of a control group of PCPs in the organization’s other clinics who did not participate in the mini-fellowship (nontrained control group). Excluded from the control group were providers from the same clinic as the fellows; providers in clinics with a geriatric-trained provider on staff; and clinics outside of the Portland metro and Medford service areas. We used an alpha level of 0.05 for all statistical tests.

Data from 5 providers were included in the analysis of the FRMP adoption. The sixth provider changed practice settings from the clinic to the ED after completing the fellowship; her patient data were not included in the FRMP part of the analysis. EHR data included data on all visits of patients 65+, as well as data for just those 65+ patients who had been identified as being at high risk to fall based on a STEADI score of 4 or higher.

Results

Provider Questionnaire

All 6 providers responded to the pre-intervention and post-intervention tests. For the knowledge questions, fellows, as a composite, correctly answered 57% of the questions before the intervention and 79% after the intervention. Provider confidence level in delivering fall risk care was measured prior to the training (mean, 4.12 [SD, 0.62]) and at the end of the training (mean, 6.47 [SD, 0.45]), demonstrating a significant increase in confidence (t (5) = –10.46, P < 0.001).

Qualitative Comments

Providers also had the opportunity to provide comments on their experience during the Mobility week and at the end of 1 year. In general, the simulated interdisciplinary fall risk clinic was highly rated (“the highlight of the week”) as a practical strategy to embed learning principles. One fellow commented, “Putting the learning into practice helps solidify it in my brain.” Fellows also appreciated the opportunity to learn and meet with their clinic colleagues to begin work on a fall-risk focused PIP and to “have a framework for what to do for people who screen positive [for fall risk].”

FRMP Adoption

A comparison of the care the fellows provided to their patients 65+ in the 12 months pre- and post-training shows the fellows demonstrated significant changes in practice patterns. The fellows were 1.7 times more likely to screen for fall risk; 3.6 times more likely to discuss fall risk; and 5.8 times more likely to check orthostatic blood pressure than prior to the mini-fellowship (Table 1).

The control providers also demonstrated significant increases in fall risk screening and discussion of fall risk between the pre- and post-intervention periods; however, the relative risk (RR) was between 1.10 and 1.13 for this group. For the control group, checking orthostatic blood pressure did not significantly change. In the 12 months after training (Table 2), the fellows were 4.2 times more likely to discuss fall risk and almost 5 times more likely to check orthostatic blood pressure than their nontrained peers for all of their patients 65+, regardless of their risk to fall.

As shown in Table 3, for those patients determined to be at high risk of falling (STEADI score ≥ 4), fellows showed statistically significant increases in fall risk visits (RR, 3.02) and assessment of orthostatic blood pressure (RR, 10.68) before and after the mini-fellowship. The control providers did not show any changes in practice patterns between the pre- and post-period among patients at high risk to fall.

Neither the fellows nor the control group showed changes in patterns of referral to PT. In comparing the 2 groups in the 12 months after training (Table 4), for their patients at risk of falling, the fellows were 4 times more likely to complete fall risk visits and over 6 times more likely to assess orthostatic blood pressure than their nontrained peers. Subgroup analysis of the 75+ population revealed similar trends and significance, but these results are not included here.

Discussion

This study aimed to improve not only providers’ knowledge and confidence in caring for older adults at increased risk to fall, but also their clinical practice in assessing and managing fall risk. In addition to improved knowledge and confidence, we found that the fellows increased their discussion of fall risk (through fall risk visits) and their assessment of orthostatic blood pressure for all of their patients, not just for those identified at increased risk to fall. This improvement held true for the fellows themselves before and after the intervention, but also as compared to their nontrained peers. These practice improvements for all of their 65+ patients, not just those identified as being at high risk to fall, are especially important, since studies indicate that early screening and intervention can help identify people at risk and prevent future falls.¹⁵

We were surprised that there were no significant differences in PT referrals made by the trained fellows, but this finding may have been confounded by the fact that the data included all PT referrals, regardless of diagnosis, not just those referrals that were fall-related. Furthermore, our baseline PT referral rates, at 39% for the intervention group and 42% for the control group, are higher than national data when looking at rehabilitation use by older adults.²⁶

In comparison to a study evaluating the occurrence of fall risk–related clinical practice in primary care before any fall-related educational intervention, orthostatics were checked less frequently in our study (10% versus 30%) and there were fewer PT referrals (42%–44% versus 53%).²⁷ However, the Phelan study took place in patients who had actually had a fall, rather than just having a higher risk for a fall, and was based on detailed chart review. Other studies^23,24 found higher rates of fall risk interventions, but did not break out PT referrals specifically.

In terms of the educational intervention itself, most studies of geriatric education interventions have measured changes in knowledge, confidence, or self-efficacy as they relate to geriatric competence,^28-30 and do not measure practice change as an outcome outside of intent to change or self-reported practice change.^31,32 In general, practice change or longer-term health care–related outcomes have not been studied. Additionally, a range of dosages of educational interventions has been studied, from 1-hour lunchtime presentations^23,32 to half-day²⁹ or several half-day workshops,²⁸ up to 160 hours over 10 months³⁰ or 5 weekends over 6 months.³¹ The duration of our entire intervention at 160 hours over 6 months would be considered on the upper end of dosing relative to these studies, with our Mobility week intervention comprising 32 hours during 1 week. In the Warshaw study, despite 107 1-hour sessions being taught to over 60 physicians in 16 practices over 4 years, only 2 practices ultimately initiated any practice change projects.³² We believe that only curricula that embed practice change skills and opportunities, at a significant enough dose, can actually impact practice change in a sustainable manner.

Knowledge and skill acquisition among individual providers does not take place to a sufficient degree in the current health care arena, which is focused on productivity and short visit times. Consistent with other studies, we included interdisciplinary members of the primary care team for part of the mini-fellowship, although other studies used models that train across disciplines for the entirety of the learning experience.^28-30,33 Our educational model was strengthened by including other professionals to provide some of the education and model the ideal geriatric team, including PT, occupational therapy, and pharmacy, for the week on mobility.

Most studies exploring interventions through geriatric educational initiatives are conducted within academic institutions, with a primary focus on physician faculty and, by extension, their teaching of residents and others.^34,35 We believe our integrated model, which is steeped in community-based primary care practices like Lam’s,³¹ offers the greatest outreach to large community-based care systems and their patients. Training providers to work with their teams to change their own practices first gives skills and expertise that help further establish them as geriatric champions within their practices, laying the groundwork for more widespread practice change at their clinics.

Limitations

In addition to the limitations described above relating to the capture of PT referrals, other limitations included the relatively short time period for follow-up data as well as the small size of the intervention group. However, we found value in the instructional depth that the small group size allowed.

While the nontrained providers did show some improvement during the same period, we believe the relative risk was not clinically significant. We suspect that the larger health system efforts to standardize screening of patients 65+ across all clinics as a core quality metric confounded these results. The data analysis also included only fall-related patient visits that occurred with a provider who was that patient’s PCP, which could have missed visits done by other PCP colleagues, RNs, or pharmacists in the same clinic, thus undercounting the true number of fall-related visits. Furthermore, counting of fall-related interventions relied upon providers documenting consistently in the EHR, which could also lead to under-represention of fall risk clinical efforts.

The data presented, while encouraging, do not reflect clinic-wide practice change patterns and are considered only proximate outcomes rather than more long-term or cost-related outcomes, as would be captured by fall-related utilization measures like emergency room visits and hospitalizations. We expect to evaluate the broader impact and these value-based outcomes in the future. All providers and teams were from the same health care system, which may not allow our results to transfer to other organizations or regions of clinical practice.

Summary

This study demonstrates that an intensive mini-fellowship model of geriatrics training improved both knowledge and confidence in the realm of fall risk assessment and intervention among PCPs who had not been formally trained in geriatrics. More importantly, the training improved the fall-related care of their patients at increased risk to fall, but also of all of their older patients, with improvements in care measured up to a year after the mini-fellowship. Although this article only describes the work done as part of the Mobility aim of the 4M AFHS model, we believe the entire mini-fellowship curriculum offers the opportunity to “geriatricize” clinicians and their teams in learning geriatric principles and skills that they can translate into their practice in a sustainable way, as Tinetti encourages.⁸ Future study to evaluate other process outcomes more precisely, such as PT, as well as cost- and value-based outcomes, and the influence of trained providers on their clinic partners, will further establish the value proposition of targeted, disseminated, intensive geriatrics training of primary care clinicians as a strategy of age-friendly health systems as they work to improve the care of their older adults.

Acknowledgment: We are grateful for the dedication and hard work of the 2018 Geriatric Mini-Fellowship fellows at Providence Health & Services-Oregon who made this article possible. Thanks to Drs. Stephanie Cha, Emily Puukka-Clark, Laurie Dutkiewicz, Cara Ellis, Deb Frost, Jordan Roth, and Subhechchha Shah for promoting the AFHS work within their Providence Medical Group clinics and to PMG leadership and the fellows’ clinical teams for supporting the fellows, the AFHS work, and their older patients.

Corresponding author: Colleen M. Casey, PhD, ANP-BC, Providence Health & Services, Senior Health Program, 4400 NE Halsey, 5th Floor, Portland, OR 97213; [email protected].

Financial disclosures: None.

“Defund the police”: It’s a slogan, or perhaps a battle cry, that has emerged from the Black Lives Matter movement as a response to race-related police brutality and concerns that people of color are profiled, targeted, arrested, charged, manhandled, and killed by law enforcement in a disproportionate and unjust manner. It crosses into our realm as psychiatrists as mental health emergency calls are handled by the police and not by mental health professionals. The result is sometimes tragic: As many as half of police shootings involve people with psychiatric disorders, and the hope is that many of the police shootings could be avoided if crises were handed by mental health clinicians instead of, or in cooperation with, the police.

At best, police officers receive a week of specialized, crisis intervention training about how to approach those with psychiatric disorders; most officers receive no training. This leaves psychiatry as the only field where medical crises are routinely handled by the police – it is demeaning and embarrassing for some of our patients and dangerous for others. The reality remains, however, that there are times when psychiatric disorders result in violent behavior, and patients being taken for involuntary treatment often resist transport, so either way there is risk, both to the patient and to anyone who responds to a call for assistance.

Early this month, the office of New York City Mayor Bill de Blasio announced that a major change would be made in how mental health calls to 911 are handled in two “high-need” areas. The mayor’s website states:

“Beginning in February 2021, new Mental Health Teams will use their physical and mental health expertise, and experience in crisis response to de-escalate emergency situations, will help reduce the number of times police will need to respond to 911 mental health calls in these precincts. These teams will have the expertise to respond to a range of behavioral health problems, such as suicide attempts, substance misuse, and serious mental illness, as well as physical health problems, which can be exacerbated by or mask mental health problems. NYC Health + Hospitals will train and provide ongoing technical assistance and support. In selecting team members for this program, FDNY will prioritize professionals with significant experience with mental health crises.”

The press release goes on to say that, in situations where there is a weapon or reason to believe there is a risk of violence, the police will be dispatched along with the new mental health team.

“This is the first time in our history that health professionals will be the default responders to mental health emergencies,” New York City First Lady Chirlane McCray said as she announced the new program. “Treating mental health crises as mental health challenges and not public safety ones is the modern and more appropriate approach.”

New York City is not the first city to employ this model. In the United States, the CAHOOTS (Crisis Assistance Helping Out on the Streets) program in Eugene, Ore., has been run by the White Bird Clinic since 1989 as part of a community policing initiative. Last year, the team responded to 24,000 calls and police backup was required on only 150 of those responses. The CAHOOTS website states:

“The CAHOOTS model has been in the spotlight recently as our nation struggles to reimagine public safety. The program mobilizes two-person teams consisting of a medic (a nurse, paramedic, or EMT) and a crisis worker who has substantial training and experience in the mental health field. The CAHOOTS teams deal with a wide range of mental health-related crises, including conflict resolution, welfare checks, substance abuse, suicide threats, and more, relying on trauma-informed de-escalation and harm reduction techniques. CAHOOTS staff are not law enforcement officers and do not carry weapons; their training and experience are the tools they use to ensure a non-violent resolution of crisis situations. They also handle non-emergent medical issues, avoiding costly ambulance transport and emergency room treatment.”

Other cities in the United States are also looking at implementing programs where mental health teams, and not the police, respond to emergency calls. Last year, Oakland, Calif.’s city council invested $40,000 in research to assess how they could best implement a program like the one in Eugene. They hope to begin the Mobile Assistance Community Responders of Oakland (MACROS) next year. Sigal Samuel writes in a Vox article, “The goal is to launch the pilot next year with funding from the city budget, and although supporters are not yet sure what its size and duration will be, they’re hopeful it’ll make a big difference to Oakland’s overpoliced community of people without homes. They were among those who first called for a non-policing approach.”

The model is not unique to the United States. In 2005, Stockholm started a program with a psychiatric ambulance – equipped with comfortable seating rather than a stretcher – to respond to mental health emergencies. The ambulance responds to 130 calls a month. It is staffed with a driver and two psychiatric nurses, and for half of the calls, the police also come. While the Swedish program was not about removing resources from the police, it has relieved the police of the responsibility for many psychiatric emergencies.

The New York City program will be modeled after the CAHOOTS initiative in Eugene. It differs from the mobile crisis response services in many other cities because CAHOOTS is hooked directly into the 911 emergency services system. Its website notes that the program has saved money:

“The cost savings are considerable. The CAHOOTS program budget is about $2.1 million annually, while the combined annual budgets for the Eugene and Springfield police departments are $90 million. In 2017, the CAHOOTS teams answered 17% of the Eugene Police Department’s overall call volume. The program saves the city of Eugene an estimated $8.5 million in public safety spending annually.”

Some worry there is an unpredictable aspect to calls for psychiatric emergencies, and the potential for mental health professions to be injured or killed. Annette Hanson, MD, a forensic psychiatrist at University of Maryland, Baltimore, voiced her concerns, “While multidisciplinary teams are useful, there have been rare cases of violence against responding mental health providers. People with serious mental illness are rarely violent but their dangerousness is unpredictable and cannot be predicted by case screening.”

Daniel Felts is a mental health crisis counselor who has worked at CAHOOTS for the past 4* years. He has responded to about 8,000 calls, and called for police backup only three times to request an immediate "Code 3 cover" when someone's safety has been in danger. Mr. Felts calls the police about once a month for concerns that do not require an immediate response for safety.* “Over the last 4 years, I am only aware of three instances when a team member’s safety was compromised because of a client’s violent behavior. No employee has been seriously physically harmed. In 30 years, with hundreds of thousands (millions?) of calls responded to, no CAHOOTS worker has ever been killed, shot, or stabbed in the line of duty,” Mr. Felts noted.

Emergency calls are screened. “It is not uncommon for CAHOOTS to be dispatched to ‘stage’ for calls involving active disputes or acutely suicidal individuals where means are present. “Staging” entails us parking roughly a mile away while police make first contact and advise whether it is safe for CAHOOTS to engage.”

Mr. Felts went on to discuss the program’s relationship with the community. “I believe that one of the biggest things that keeps us safe is the community’s knowledge and understanding of our service and how we operate. Having operated in Eugene for 30 years, our service is well understood to be one that does not kill, harm, or violate personal boundaries or liberties.”

Would a program like the ones in Stockholm or in Eugene work in other places? Eugene is a city with a population of 172,000 with a low crime rate. Whether a program implemented in one city can be mimicked in another very different city is not clear.

Paul Appelbaum, MD, a forensic psychiatrist at Columbia University, New York, is optimistic about New York City’s forthcoming program.

“The proposed pilot project in NYC is a real step forward. Work that we’ve done looking at fatal encounters involving the police found that roughly 25% of all deaths at the hands of the police are of people with mental illness. In many of those cases, police were initially called to bring people who were clearly troubled for psychiatric evaluation, but as the situation escalated, the police turned to their weapons to control it, which led to a fatal outcome. Taking police out of the picture whenever possible in favor of trained mental health personnel is clearly a better approach. It will be important for the city to collect good outcome data to enable independent evaluation of the pilot project – not something that political entities are inclined toward, but a critical element in assessing the effectiveness of this approach.”

There are questions that remain about the new program. Mayor de Blasio’s office has not released information about which areas of the city are being chosen for the new program, how much the program will cost, or what the funding source will be. If it can be implemented safely and effectively, it has the potential to provide more sensitive care to patients in crisis, and to save lives.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2018). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore.

*Correction, 11/27/2020: An earlier version of this article misstated the number of years Daniel Felts has worked at CAHOOTS.

“Defund the police”: It’s a slogan, or perhaps a battle cry, that has emerged from the Black Lives Matter movement as a response to race-related police brutality and concerns that people of color are profiled, targeted, arrested, charged, manhandled, and killed by law enforcement in a disproportionate and unjust manner. It crosses into our realm as psychiatrists as mental health emergency calls are handled by the police and not by mental health professionals. The result is sometimes tragic: As many as half of police shootings involve people with psychiatric disorders, and the hope is that many of the police shootings could be avoided if crises were handed by mental health clinicians instead of, or in cooperation with, the police.

At best, police officers receive a week of specialized, crisis intervention training about how to approach those with psychiatric disorders; most officers receive no training. This leaves psychiatry as the only field where medical crises are routinely handled by the police – it is demeaning and embarrassing for some of our patients and dangerous for others. The reality remains, however, that there are times when psychiatric disorders result in violent behavior, and patients being taken for involuntary treatment often resist transport, so either way there is risk, both to the patient and to anyone who responds to a call for assistance.

Early this month, the office of New York City Mayor Bill de Blasio announced that a major change would be made in how mental health calls to 911 are handled in two “high-need” areas. The mayor’s website states:

“Beginning in February 2021, new Mental Health Teams will use their physical and mental health expertise, and experience in crisis response to de-escalate emergency situations, will help reduce the number of times police will need to respond to 911 mental health calls in these precincts. These teams will have the expertise to respond to a range of behavioral health problems, such as suicide attempts, substance misuse, and serious mental illness, as well as physical health problems, which can be exacerbated by or mask mental health problems. NYC Health + Hospitals will train and provide ongoing technical assistance and support. In selecting team members for this program, FDNY will prioritize professionals with significant experience with mental health crises.”

The press release goes on to say that, in situations where there is a weapon or reason to believe there is a risk of violence, the police will be dispatched along with the new mental health team.

“This is the first time in our history that health professionals will be the default responders to mental health emergencies,” New York City First Lady Chirlane McCray said as she announced the new program. “Treating mental health crises as mental health challenges and not public safety ones is the modern and more appropriate approach.”

New York City is not the first city to employ this model. In the United States, the CAHOOTS (Crisis Assistance Helping Out on the Streets) program in Eugene, Ore., has been run by the White Bird Clinic since 1989 as part of a community policing initiative. Last year, the team responded to 24,000 calls and police backup was required on only 150 of those responses. The CAHOOTS website states:

“The CAHOOTS model has been in the spotlight recently as our nation struggles to reimagine public safety. The program mobilizes two-person teams consisting of a medic (a nurse, paramedic, or EMT) and a crisis worker who has substantial training and experience in the mental health field. The CAHOOTS teams deal with a wide range of mental health-related crises, including conflict resolution, welfare checks, substance abuse, suicide threats, and more, relying on trauma-informed de-escalation and harm reduction techniques. CAHOOTS staff are not law enforcement officers and do not carry weapons; their training and experience are the tools they use to ensure a non-violent resolution of crisis situations. They also handle non-emergent medical issues, avoiding costly ambulance transport and emergency room treatment.”

Other cities in the United States are also looking at implementing programs where mental health teams, and not the police, respond to emergency calls. Last year, Oakland, Calif.’s city council invested $40,000 in research to assess how they could best implement a program like the one in Eugene. They hope to begin the Mobile Assistance Community Responders of Oakland (MACROS) next year. Sigal Samuel writes in a Vox article, “The goal is to launch the pilot next year with funding from the city budget, and although supporters are not yet sure what its size and duration will be, they’re hopeful it’ll make a big difference to Oakland’s overpoliced community of people without homes. They were among those who first called for a non-policing approach.”

The model is not unique to the United States. In 2005, Stockholm started a program with a psychiatric ambulance – equipped with comfortable seating rather than a stretcher – to respond to mental health emergencies. The ambulance responds to 130 calls a month. It is staffed with a driver and two psychiatric nurses, and for half of the calls, the police also come. While the Swedish program was not about removing resources from the police, it has relieved the police of the responsibility for many psychiatric emergencies.

The New York City program will be modeled after the CAHOOTS initiative in Eugene. It differs from the mobile crisis response services in many other cities because CAHOOTS is hooked directly into the 911 emergency services system. Its website notes that the program has saved money:

“The cost savings are considerable. The CAHOOTS program budget is about $2.1 million annually, while the combined annual budgets for the Eugene and Springfield police departments are $90 million. In 2017, the CAHOOTS teams answered 17% of the Eugene Police Department’s overall call volume. The program saves the city of Eugene an estimated $8.5 million in public safety spending annually.”

Some worry there is an unpredictable aspect to calls for psychiatric emergencies, and the potential for mental health professions to be injured or killed. Annette Hanson, MD, a forensic psychiatrist at University of Maryland, Baltimore, voiced her concerns, “While multidisciplinary teams are useful, there have been rare cases of violence against responding mental health providers. People with serious mental illness are rarely violent but their dangerousness is unpredictable and cannot be predicted by case screening.”

Daniel Felts is a mental health crisis counselor who has worked at CAHOOTS for the past 4* years. He has responded to about 8,000 calls, and called for police backup only three times to request an immediate "Code 3 cover" when someone's safety has been in danger. Mr. Felts calls the police about once a month for concerns that do not require an immediate response for safety.* “Over the last 4 years, I am only aware of three instances when a team member’s safety was compromised because of a client’s violent behavior. No employee has been seriously physically harmed. In 30 years, with hundreds of thousands (millions?) of calls responded to, no CAHOOTS worker has ever been killed, shot, or stabbed in the line of duty,” Mr. Felts noted.

Emergency calls are screened. “It is not uncommon for CAHOOTS to be dispatched to ‘stage’ for calls involving active disputes or acutely suicidal individuals where means are present. “Staging” entails us parking roughly a mile away while police make first contact and advise whether it is safe for CAHOOTS to engage.”

Mr. Felts went on to discuss the program’s relationship with the community. “I believe that one of the biggest things that keeps us safe is the community’s knowledge and understanding of our service and how we operate. Having operated in Eugene for 30 years, our service is well understood to be one that does not kill, harm, or violate personal boundaries or liberties.”

Would a program like the ones in Stockholm or in Eugene work in other places? Eugene is a city with a population of 172,000 with a low crime rate. Whether a program implemented in one city can be mimicked in another very different city is not clear.

Paul Appelbaum, MD, a forensic psychiatrist at Columbia University, New York, is optimistic about New York City’s forthcoming program.

“The proposed pilot project in NYC is a real step forward. Work that we’ve done looking at fatal encounters involving the police found that roughly 25% of all deaths at the hands of the police are of people with mental illness. In many of those cases, police were initially called to bring people who were clearly troubled for psychiatric evaluation, but as the situation escalated, the police turned to their weapons to control it, which led to a fatal outcome. Taking police out of the picture whenever possible in favor of trained mental health personnel is clearly a better approach. It will be important for the city to collect good outcome data to enable independent evaluation of the pilot project – not something that political entities are inclined toward, but a critical element in assessing the effectiveness of this approach.”

There are questions that remain about the new program. Mayor de Blasio’s office has not released information about which areas of the city are being chosen for the new program, how much the program will cost, or what the funding source will be. If it can be implemented safely and effectively, it has the potential to provide more sensitive care to patients in crisis, and to save lives.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2018). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore.

*Correction, 11/27/2020: An earlier version of this article misstated the number of years Daniel Felts has worked at CAHOOTS.

“Defund the police”: It’s a slogan, or perhaps a battle cry, that has emerged from the Black Lives Matter movement as a response to race-related police brutality and concerns that people of color are profiled, targeted, arrested, charged, manhandled, and killed by law enforcement in a disproportionate and unjust manner. It crosses into our realm as psychiatrists as mental health emergency calls are handled by the police and not by mental health professionals. The result is sometimes tragic: As many as half of police shootings involve people with psychiatric disorders, and the hope is that many of the police shootings could be avoided if crises were handed by mental health clinicians instead of, or in cooperation with, the police.

At best, police officers receive a week of specialized, crisis intervention training about how to approach those with psychiatric disorders; most officers receive no training. This leaves psychiatry as the only field where medical crises are routinely handled by the police – it is demeaning and embarrassing for some of our patients and dangerous for others. The reality remains, however, that there are times when psychiatric disorders result in violent behavior, and patients being taken for involuntary treatment often resist transport, so either way there is risk, both to the patient and to anyone who responds to a call for assistance.

Early this month, the office of New York City Mayor Bill de Blasio announced that a major change would be made in how mental health calls to 911 are handled in two “high-need” areas. The mayor’s website states:

“Beginning in February 2021, new Mental Health Teams will use their physical and mental health expertise, and experience in crisis response to de-escalate emergency situations, will help reduce the number of times police will need to respond to 911 mental health calls in these precincts. These teams will have the expertise to respond to a range of behavioral health problems, such as suicide attempts, substance misuse, and serious mental illness, as well as physical health problems, which can be exacerbated by or mask mental health problems. NYC Health + Hospitals will train and provide ongoing technical assistance and support. In selecting team members for this program, FDNY will prioritize professionals with significant experience with mental health crises.”

The press release goes on to say that, in situations where there is a weapon or reason to believe there is a risk of violence, the police will be dispatched along with the new mental health team.

“This is the first time in our history that health professionals will be the default responders to mental health emergencies,” New York City First Lady Chirlane McCray said as she announced the new program. “Treating mental health crises as mental health challenges and not public safety ones is the modern and more appropriate approach.”

New York City is not the first city to employ this model. In the United States, the CAHOOTS (Crisis Assistance Helping Out on the Streets) program in Eugene, Ore., has been run by the White Bird Clinic since 1989 as part of a community policing initiative. Last year, the team responded to 24,000 calls and police backup was required on only 150 of those responses. The CAHOOTS website states:

“The CAHOOTS model has been in the spotlight recently as our nation struggles to reimagine public safety. The program mobilizes two-person teams consisting of a medic (a nurse, paramedic, or EMT) and a crisis worker who has substantial training and experience in the mental health field. The CAHOOTS teams deal with a wide range of mental health-related crises, including conflict resolution, welfare checks, substance abuse, suicide threats, and more, relying on trauma-informed de-escalation and harm reduction techniques. CAHOOTS staff are not law enforcement officers and do not carry weapons; their training and experience are the tools they use to ensure a non-violent resolution of crisis situations. They also handle non-emergent medical issues, avoiding costly ambulance transport and emergency room treatment.”

Other cities in the United States are also looking at implementing programs where mental health teams, and not the police, respond to emergency calls. Last year, Oakland, Calif.’s city council invested $40,000 in research to assess how they could best implement a program like the one in Eugene. They hope to begin the Mobile Assistance Community Responders of Oakland (MACROS) next year. Sigal Samuel writes in a Vox article, “The goal is to launch the pilot next year with funding from the city budget, and although supporters are not yet sure what its size and duration will be, they’re hopeful it’ll make a big difference to Oakland’s overpoliced community of people without homes. They were among those who first called for a non-policing approach.”

The model is not unique to the United States. In 2005, Stockholm started a program with a psychiatric ambulance – equipped with comfortable seating rather than a stretcher – to respond to mental health emergencies. The ambulance responds to 130 calls a month. It is staffed with a driver and two psychiatric nurses, and for half of the calls, the police also come. While the Swedish program was not about removing resources from the police, it has relieved the police of the responsibility for many psychiatric emergencies.

The New York City program will be modeled after the CAHOOTS initiative in Eugene. It differs from the mobile crisis response services in many other cities because CAHOOTS is hooked directly into the 911 emergency services system. Its website notes that the program has saved money:

“The cost savings are considerable. The CAHOOTS program budget is about $2.1 million annually, while the combined annual budgets for the Eugene and Springfield police departments are $90 million. In 2017, the CAHOOTS teams answered 17% of the Eugene Police Department’s overall call volume. The program saves the city of Eugene an estimated $8.5 million in public safety spending annually.”

Some worry there is an unpredictable aspect to calls for psychiatric emergencies, and the potential for mental health professions to be injured or killed. Annette Hanson, MD, a forensic psychiatrist at University of Maryland, Baltimore, voiced her concerns, “While multidisciplinary teams are useful, there have been rare cases of violence against responding mental health providers. People with serious mental illness are rarely violent but their dangerousness is unpredictable and cannot be predicted by case screening.”

Daniel Felts is a mental health crisis counselor who has worked at CAHOOTS for the past 4* years. He has responded to about 8,000 calls, and called for police backup only three times to request an immediate "Code 3 cover" when someone's safety has been in danger. Mr. Felts calls the police about once a month for concerns that do not require an immediate response for safety.* “Over the last 4 years, I am only aware of three instances when a team member’s safety was compromised because of a client’s violent behavior. No employee has been seriously physically harmed. In 30 years, with hundreds of thousands (millions?) of calls responded to, no CAHOOTS worker has ever been killed, shot, or stabbed in the line of duty,” Mr. Felts noted.

Emergency calls are screened. “It is not uncommon for CAHOOTS to be dispatched to ‘stage’ for calls involving active disputes or acutely suicidal individuals where means are present. “Staging” entails us parking roughly a mile away while police make first contact and advise whether it is safe for CAHOOTS to engage.”

Mr. Felts went on to discuss the program’s relationship with the community. “I believe that one of the biggest things that keeps us safe is the community’s knowledge and understanding of our service and how we operate. Having operated in Eugene for 30 years, our service is well understood to be one that does not kill, harm, or violate personal boundaries or liberties.”

Would a program like the ones in Stockholm or in Eugene work in other places? Eugene is a city with a population of 172,000 with a low crime rate. Whether a program implemented in one city can be mimicked in another very different city is not clear.

Paul Appelbaum, MD, a forensic psychiatrist at Columbia University, New York, is optimistic about New York City’s forthcoming program.

“The proposed pilot project in NYC is a real step forward. Work that we’ve done looking at fatal encounters involving the police found that roughly 25% of all deaths at the hands of the police are of people with mental illness. In many of those cases, police were initially called to bring people who were clearly troubled for psychiatric evaluation, but as the situation escalated, the police turned to their weapons to control it, which led to a fatal outcome. Taking police out of the picture whenever possible in favor of trained mental health personnel is clearly a better approach. It will be important for the city to collect good outcome data to enable independent evaluation of the pilot project – not something that political entities are inclined toward, but a critical element in assessing the effectiveness of this approach.”

There are questions that remain about the new program. Mayor de Blasio’s office has not released information about which areas of the city are being chosen for the new program, how much the program will cost, or what the funding source will be. If it can be implemented safely and effectively, it has the potential to provide more sensitive care to patients in crisis, and to save lives.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2018). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, both in Baltimore.

*Correction, 11/27/2020: An earlier version of this article misstated the number of years Daniel Felts has worked at CAHOOTS.