CLEVELAND – Documenting the prevalence of axial spondyloarthritis (axSpA) among Black Americans has been difficult because of little published data, but new research suggests that when Black Americans do have the disease, it seems to be more severe.

Iman Abutineh, MD, of the University of Tennessee, Memphis, discussed her team’s work at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

A total of 244 patients with axSpA were identified, including 168 (69%) males, 78 (32%) Black patients, and 143 (59%) White patients.

Average age of onset for patients overall was 27.7 years, and age at diagnosis was 36.1 years with a 7-year delay in diagnosis. Sixty-six (27%) patients had nonradiographic axSpA, 83% were on tumor necrosis factor inhibitors, and 38% were prescribed glucocorticoids.

The researchers found several differences by race.

White patients were more likely to be HLA-B27 positive (77% vs. 59%; P = .010). White patients also had higher prevalence of psoriasis, coronary artery disease, and family history of SpA. White females had a higher prevalence of inflammatory bowel disease, fibromyalgia, depression, and lower grades of sacroiliitis.
 

Black patients had more hip involvement

A higher percentage of Black patients had elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and hip involvement. In comparing hip involvement, the researchers found that 39 (39%) White males had hip involvement as did 9 (21%) White females. In comparison, 22 (45%) Black men in the study and 14 (54%) Black women showed hip involvement (P = .035).

After adjustment for age, sex, HLA-B27, and insurance status, Black patients had higher grades of sacroiliitis with an odds ratio of 2.32 (95% confidence interval, 1.23-4.44). Black patients had a numerically longer delay in diagnosis, compared with Whites (7.93 vs. 6.64 years), but this did not achieve statistical significance (P = .454), the researchers wrote.
 

Study addresses racial disparities

“Traditionally we think of axial spondyloarthritis largely in Caucasian males who are HLA-B27 positive,” Dr. Abutineh said, “and we found that there is still a significant portion of patients who don’t meet the criteria that do have disease that is very significant.”

Although actual prevalence was not clear from this study, Dr. Abutineh said their data suggest a 3-to-1 ratio of White-to-Black patients with spondyloarthritis, “but of the Black patients who are diagnosed, their disease is almost always more severe. That points to why it’s important to have a high index of suspicion for this disease in that patient population because if you miss it, it could be detrimental to the patients.”

Swetha Alexander, MD, a rheumatology fellow at the University of Utah, Salt Lake City, who was not part of the study, said in an interview, “It is an excellent and timely study addressing the racial disparities and inequities surrounding axSpA diagnosis. It highlights the delay in diagnosis and increased burden of disease among Black Americans.”

She said the study may prompt a further look into barriers to care for Black Americans and their beliefs regarding seeking health care for their pain.
 

Higher rates of nonradiographic axSpA among Black patients

The rate of nonradiographic axSpA among Black Americans was more than twice that of their White counterparts, which, Dr. Alexander noted, could make it more difficult to diagnose axSpA in that population.

The odds ratio for Black patients having nonradiographic axSpA, compared with Whites, was 2.265 (95% CI, 1.082-4.999; P = .035), after adjustment for age, sex, and HLA-B27 status.

Adult patients with axSpA were identified from rheumatology clinics at four major hospital systems and one private clinic in Shelby County, Tenn., between 2011 and 2021. Patients met modified New York (mNY) or Assessment of Spondyloarthritis International Society (ASAS) criteria as assessed by reviewers.

The authors and Dr. Alexander reported no relevant financial relationships.

CLEVELAND – Documenting the prevalence of axial spondyloarthritis (axSpA) among Black Americans has been difficult because of little published data, but new research suggests that when Black Americans do have the disease, it seems to be more severe.

Iman Abutineh, MD, of the University of Tennessee, Memphis, discussed her team’s work at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

A total of 244 patients with axSpA were identified, including 168 (69%) males, 78 (32%) Black patients, and 143 (59%) White patients.

Average age of onset for patients overall was 27.7 years, and age at diagnosis was 36.1 years with a 7-year delay in diagnosis. Sixty-six (27%) patients had nonradiographic axSpA, 83% were on tumor necrosis factor inhibitors, and 38% were prescribed glucocorticoids.

The researchers found several differences by race.

White patients were more likely to be HLA-B27 positive (77% vs. 59%; P = .010). White patients also had higher prevalence of psoriasis, coronary artery disease, and family history of SpA. White females had a higher prevalence of inflammatory bowel disease, fibromyalgia, depression, and lower grades of sacroiliitis.
 

Black patients had more hip involvement

A higher percentage of Black patients had elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and hip involvement. In comparing hip involvement, the researchers found that 39 (39%) White males had hip involvement as did 9 (21%) White females. In comparison, 22 (45%) Black men in the study and 14 (54%) Black women showed hip involvement (P = .035).

After adjustment for age, sex, HLA-B27, and insurance status, Black patients had higher grades of sacroiliitis with an odds ratio of 2.32 (95% confidence interval, 1.23-4.44). Black patients had a numerically longer delay in diagnosis, compared with Whites (7.93 vs. 6.64 years), but this did not achieve statistical significance (P = .454), the researchers wrote.
 

Study addresses racial disparities

“Traditionally we think of axial spondyloarthritis largely in Caucasian males who are HLA-B27 positive,” Dr. Abutineh said, “and we found that there is still a significant portion of patients who don’t meet the criteria that do have disease that is very significant.”

Although actual prevalence was not clear from this study, Dr. Abutineh said their data suggest a 3-to-1 ratio of White-to-Black patients with spondyloarthritis, “but of the Black patients who are diagnosed, their disease is almost always more severe. That points to why it’s important to have a high index of suspicion for this disease in that patient population because if you miss it, it could be detrimental to the patients.”

Swetha Alexander, MD, a rheumatology fellow at the University of Utah, Salt Lake City, who was not part of the study, said in an interview, “It is an excellent and timely study addressing the racial disparities and inequities surrounding axSpA diagnosis. It highlights the delay in diagnosis and increased burden of disease among Black Americans.”

She said the study may prompt a further look into barriers to care for Black Americans and their beliefs regarding seeking health care for their pain.
 

Higher rates of nonradiographic axSpA among Black patients

The rate of nonradiographic axSpA among Black Americans was more than twice that of their White counterparts, which, Dr. Alexander noted, could make it more difficult to diagnose axSpA in that population.

The odds ratio for Black patients having nonradiographic axSpA, compared with Whites, was 2.265 (95% CI, 1.082-4.999; P = .035), after adjustment for age, sex, and HLA-B27 status.

Adult patients with axSpA were identified from rheumatology clinics at four major hospital systems and one private clinic in Shelby County, Tenn., between 2011 and 2021. Patients met modified New York (mNY) or Assessment of Spondyloarthritis International Society (ASAS) criteria as assessed by reviewers.

The authors and Dr. Alexander reported no relevant financial relationships.

CLEVELAND – Documenting the prevalence of axial spondyloarthritis (axSpA) among Black Americans has been difficult because of little published data, but new research suggests that when Black Americans do have the disease, it seems to be more severe.

Iman Abutineh, MD, of the University of Tennessee, Memphis, discussed her team’s work at the annual meeting of the Spondyloarthritis Research and Treatment Network (SPARTAN).

A total of 244 patients with axSpA were identified, including 168 (69%) males, 78 (32%) Black patients, and 143 (59%) White patients.

Average age of onset for patients overall was 27.7 years, and age at diagnosis was 36.1 years with a 7-year delay in diagnosis. Sixty-six (27%) patients had nonradiographic axSpA, 83% were on tumor necrosis factor inhibitors, and 38% were prescribed glucocorticoids.

The researchers found several differences by race.

White patients were more likely to be HLA-B27 positive (77% vs. 59%; P = .010). White patients also had higher prevalence of psoriasis, coronary artery disease, and family history of SpA. White females had a higher prevalence of inflammatory bowel disease, fibromyalgia, depression, and lower grades of sacroiliitis.
 

Black patients had more hip involvement

A higher percentage of Black patients had elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and hip involvement. In comparing hip involvement, the researchers found that 39 (39%) White males had hip involvement as did 9 (21%) White females. In comparison, 22 (45%) Black men in the study and 14 (54%) Black women showed hip involvement (P = .035).

After adjustment for age, sex, HLA-B27, and insurance status, Black patients had higher grades of sacroiliitis with an odds ratio of 2.32 (95% confidence interval, 1.23-4.44). Black patients had a numerically longer delay in diagnosis, compared with Whites (7.93 vs. 6.64 years), but this did not achieve statistical significance (P = .454), the researchers wrote.
 

Study addresses racial disparities

“Traditionally we think of axial spondyloarthritis largely in Caucasian males who are HLA-B27 positive,” Dr. Abutineh said, “and we found that there is still a significant portion of patients who don’t meet the criteria that do have disease that is very significant.”

Although actual prevalence was not clear from this study, Dr. Abutineh said their data suggest a 3-to-1 ratio of White-to-Black patients with spondyloarthritis, “but of the Black patients who are diagnosed, their disease is almost always more severe. That points to why it’s important to have a high index of suspicion for this disease in that patient population because if you miss it, it could be detrimental to the patients.”

Swetha Alexander, MD, a rheumatology fellow at the University of Utah, Salt Lake City, who was not part of the study, said in an interview, “It is an excellent and timely study addressing the racial disparities and inequities surrounding axSpA diagnosis. It highlights the delay in diagnosis and increased burden of disease among Black Americans.”

She said the study may prompt a further look into barriers to care for Black Americans and their beliefs regarding seeking health care for their pain.
 

Higher rates of nonradiographic axSpA among Black patients

The rate of nonradiographic axSpA among Black Americans was more than twice that of their White counterparts, which, Dr. Alexander noted, could make it more difficult to diagnose axSpA in that population.

The odds ratio for Black patients having nonradiographic axSpA, compared with Whites, was 2.265 (95% CI, 1.082-4.999; P = .035), after adjustment for age, sex, and HLA-B27 status.

Adult patients with axSpA were identified from rheumatology clinics at four major hospital systems and one private clinic in Shelby County, Tenn., between 2011 and 2021. Patients met modified New York (mNY) or Assessment of Spondyloarthritis International Society (ASAS) criteria as assessed by reviewers.

The authors and Dr. Alexander reported no relevant financial relationships.

A novel antibody, NI006 (Neurimmune), was safe for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in a phase 1 trial and appeared to reduce the amount of amyloid protein deposited in the heart, a new study suggests.

Currently, the only drug approved to treat ATTR is tafamidis, which improves survival and reduces hospitalizations, but does not reverse disease symptoms, the authors noted.

NI006 is a recombinant human anti-ATTR antibody given by infusion that was developed to trigger removal of ATTR by the body’s phagocytic immune cells.

Use of the drug was not associated with serious drug-related adverse events, though mild and moderate adverse events did occur.

Median N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin T levels also seemed to be reduced over the study period.

Given the success of the antibody in this initial 40-patient trial, a larger phase-3 placebo-controlled trial is planned and expected to launch in the second half of 2023, said lead author Pablo Garcia-Pavia, MD, of Hospital Universitario Puerta de Hierro and the Spanish National Cardiovascular Research Institute, Madrid.

However, “The design of appropriate phase-3 trials to demonstrate efficacy of drugs for ATTR-CM is becoming more complicated and challenging,” he said.

“Increased awareness of the disease and advances in cardiac imaging techniques have led to recognition of a larger number of patients with ATTR-CM who have a different clinical profile and a different prognosis than the patients who were diagnosed in previous years and were enrolled in the initial trials of stabilizers,” Dr. Garcia-Pavia added.

“Moreover, the availability of tafamidis, and hopefully soon other medications to treat ATTR-CM has complicated the design of new clinical trials because of the heterogenicity of treatments that patients might receive,” he said. “Therefore, it is critical to plan the design very well.”

Dr. Garcia-Pavia presented the findings on NI006 at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions. The study was published simultaneously in the New England Journal of Medicine.
 

No serious adverse events

For the phase-1, double-blind, multicenter study, the investigators randomly assigned (2:1 ratio) 40 patients (median age, 72 years; 98% men) with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive IV infusions of either NI006, at one of six doses ranging from 0.3 mg/kg to 60 mg/kg of body weight, or placebo every 4 weeks for 4 months.

After the four infusions, participants were enrolled in an open-label extension phase in which they received eight NI006 infusions with stepwise increases in the dose.

Participants had a confirmed diagnosis of ATTR-CM; left ventricular wall thickness of at least 14 mm; left ventricular ejection fraction of at least 40%; New York Heart Association class I, II, or III; estimated glomerular filtration rate of more than 30 mL/min per 1.73 m²; and an NT-proBNP level of 600 to 6,000 pg/mL.

Most (36) were receiving tafamidis, with a median treatment duration of 7 months; other ATTR-specific drugs were not permitted. Patients randomly assigned to receive NI006 seemed to have more advanced disease compared with those assigned to placebo.

Adherence to the trial protocol was high: Thirty-four patients received the four scheduled infusions during the ascending-dose phase, and 34 of 35 patients who completed this phase subsequently enrolled in the open-label extension.

No apparent drug-related serious adverse events were reported. However, during the ascending-dose phase, 38 patients had at least one adverse event, most of which were mild or moderate; of the 191 total events, 124 were grade 1 and 60 were grade 2 (most commonly heart failure and arrhythmias). Three patients had cytokine release syndrome; all three completed treatment through the extension phase.

Musculoskeletal events increased with ascending doses of NI006, which led two patients to withdraw from the trial.

At doses of at least 10 mg/kg, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac MRI, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over 12 months.

Because NI006 stimulates the patient’s own immune system to eliminate cardiac amyloid fibrils, one session chair at the meeting wondered whether NI006 represented the “rise of immunology in cardiology,” and whether biologics might follow.

Another questioned how removing amyloid might affect cardiac function. The echocardiographic findings gathered so far don’t indicate dysfunction, “but this is a small trial, and we need more data,” Dr. Garcia-Pavia said.
 

Tempered excitement

In a comment, Ronald Witteles, MD, professor of cardiovascular medicine, Stanford (Calif.) University, and founder/codirector of the Stanford Amyloid Center, said that “antibody-based amyloid removal strategies are not currently clinically available and represent a fundamentally different mechanism to treat the disease from what we currently have.

“While the data are encouraging and will generate excitement for later-phase studies, we’re talking about small numbers of patients and nothing definitive should be drawn from this data,” said Dr. Witteles, deputy editor of JACC: CardioOncology.

“The biggest caveat is that similar approaches of antibody removal of amyloid deposits for other forms of amyloidosis — most notably AL amyloidosis (amyloid light chain or primary amyloidosis) – have failed in late-phase trials. Although there is reason to believe that ATTR amyloidosis may be more amenable to improvements with amyloid fibril removal than AL amyloidosis, the unimpressive results in other forms of amyloidosis still do temper the excitement to a degree.”

Like Dr. Garcia-Pavia, Dr. Witteles said, “Ultimately, we are going to need to see a phase 3 clinical trial which shows that NI006 – on top of standard-of-care treatment – improves hard outcomes in the disease. As treatment options likely expand in the coming years, that is likely to be a harder and harder bar to reach.”

Furthermore, although the safety profile was favorable overall, it “wasn’t entirely clean,” given cytokine release syndrome in three patients, a lowering of platelet counts in a couple of patients, and musculoskeletal side effects that triggered two to withdraw from the study. “Unless that changes,” he said, “that will be a barrier for some patients.”

Overall, he noted, “With the vast majority of patients being able to be diagnosed noninvasively, and with treatment options now available, we have seen a true explosion in the number of patients being diagnosed.

“But we also know that the large majority ... are still not getting diagnosed or are having huge delays in diagnosis. As such, the biggest thing we can do for patients with the disease is to continue to educate people about it,” Dr. Witteles concluded.

The study was funded by Neurimmune. Dr. Garcia-Pavia disclosed ties to Alexion, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio, General Electric, Intellia, Ionis Pharmaceuticals, Neurimmune, Novo Nordisk, and Pfizer. Dr. Witteles reported ties to Alexion, Alnylam, AstraZeneca, BridgeBio, Intellia, Ionis, Janssen, Novo Nordisk, and Pfizer.

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

A novel antibody, NI006 (Neurimmune), was safe for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in a phase 1 trial and appeared to reduce the amount of amyloid protein deposited in the heart, a new study suggests.

Currently, the only drug approved to treat ATTR is tafamidis, which improves survival and reduces hospitalizations, but does not reverse disease symptoms, the authors noted.

NI006 is a recombinant human anti-ATTR antibody given by infusion that was developed to trigger removal of ATTR by the body’s phagocytic immune cells.

Use of the drug was not associated with serious drug-related adverse events, though mild and moderate adverse events did occur.

Median N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin T levels also seemed to be reduced over the study period.

Given the success of the antibody in this initial 40-patient trial, a larger phase-3 placebo-controlled trial is planned and expected to launch in the second half of 2023, said lead author Pablo Garcia-Pavia, MD, of Hospital Universitario Puerta de Hierro and the Spanish National Cardiovascular Research Institute, Madrid.

However, “The design of appropriate phase-3 trials to demonstrate efficacy of drugs for ATTR-CM is becoming more complicated and challenging,” he said.

“Increased awareness of the disease and advances in cardiac imaging techniques have led to recognition of a larger number of patients with ATTR-CM who have a different clinical profile and a different prognosis than the patients who were diagnosed in previous years and were enrolled in the initial trials of stabilizers,” Dr. Garcia-Pavia added.

“Moreover, the availability of tafamidis, and hopefully soon other medications to treat ATTR-CM has complicated the design of new clinical trials because of the heterogenicity of treatments that patients might receive,” he said. “Therefore, it is critical to plan the design very well.”

Dr. Garcia-Pavia presented the findings on NI006 at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions. The study was published simultaneously in the New England Journal of Medicine.
 

No serious adverse events

For the phase-1, double-blind, multicenter study, the investigators randomly assigned (2:1 ratio) 40 patients (median age, 72 years; 98% men) with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive IV infusions of either NI006, at one of six doses ranging from 0.3 mg/kg to 60 mg/kg of body weight, or placebo every 4 weeks for 4 months.

After the four infusions, participants were enrolled in an open-label extension phase in which they received eight NI006 infusions with stepwise increases in the dose.

Participants had a confirmed diagnosis of ATTR-CM; left ventricular wall thickness of at least 14 mm; left ventricular ejection fraction of at least 40%; New York Heart Association class I, II, or III; estimated glomerular filtration rate of more than 30 mL/min per 1.73 m²; and an NT-proBNP level of 600 to 6,000 pg/mL.

Most (36) were receiving tafamidis, with a median treatment duration of 7 months; other ATTR-specific drugs were not permitted. Patients randomly assigned to receive NI006 seemed to have more advanced disease compared with those assigned to placebo.

Adherence to the trial protocol was high: Thirty-four patients received the four scheduled infusions during the ascending-dose phase, and 34 of 35 patients who completed this phase subsequently enrolled in the open-label extension.

No apparent drug-related serious adverse events were reported. However, during the ascending-dose phase, 38 patients had at least one adverse event, most of which were mild or moderate; of the 191 total events, 124 were grade 1 and 60 were grade 2 (most commonly heart failure and arrhythmias). Three patients had cytokine release syndrome; all three completed treatment through the extension phase.

Musculoskeletal events increased with ascending doses of NI006, which led two patients to withdraw from the trial.

At doses of at least 10 mg/kg, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac MRI, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over 12 months.

Because NI006 stimulates the patient’s own immune system to eliminate cardiac amyloid fibrils, one session chair at the meeting wondered whether NI006 represented the “rise of immunology in cardiology,” and whether biologics might follow.

Another questioned how removing amyloid might affect cardiac function. The echocardiographic findings gathered so far don’t indicate dysfunction, “but this is a small trial, and we need more data,” Dr. Garcia-Pavia said.
 

Tempered excitement

In a comment, Ronald Witteles, MD, professor of cardiovascular medicine, Stanford (Calif.) University, and founder/codirector of the Stanford Amyloid Center, said that “antibody-based amyloid removal strategies are not currently clinically available and represent a fundamentally different mechanism to treat the disease from what we currently have.

“While the data are encouraging and will generate excitement for later-phase studies, we’re talking about small numbers of patients and nothing definitive should be drawn from this data,” said Dr. Witteles, deputy editor of JACC: CardioOncology.

“The biggest caveat is that similar approaches of antibody removal of amyloid deposits for other forms of amyloidosis — most notably AL amyloidosis (amyloid light chain or primary amyloidosis) – have failed in late-phase trials. Although there is reason to believe that ATTR amyloidosis may be more amenable to improvements with amyloid fibril removal than AL amyloidosis, the unimpressive results in other forms of amyloidosis still do temper the excitement to a degree.”

Like Dr. Garcia-Pavia, Dr. Witteles said, “Ultimately, we are going to need to see a phase 3 clinical trial which shows that NI006 – on top of standard-of-care treatment – improves hard outcomes in the disease. As treatment options likely expand in the coming years, that is likely to be a harder and harder bar to reach.”

Furthermore, although the safety profile was favorable overall, it “wasn’t entirely clean,” given cytokine release syndrome in three patients, a lowering of platelet counts in a couple of patients, and musculoskeletal side effects that triggered two to withdraw from the study. “Unless that changes,” he said, “that will be a barrier for some patients.”

Overall, he noted, “With the vast majority of patients being able to be diagnosed noninvasively, and with treatment options now available, we have seen a true explosion in the number of patients being diagnosed.

“But we also know that the large majority ... are still not getting diagnosed or are having huge delays in diagnosis. As such, the biggest thing we can do for patients with the disease is to continue to educate people about it,” Dr. Witteles concluded.

The study was funded by Neurimmune. Dr. Garcia-Pavia disclosed ties to Alexion, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio, General Electric, Intellia, Ionis Pharmaceuticals, Neurimmune, Novo Nordisk, and Pfizer. Dr. Witteles reported ties to Alexion, Alnylam, AstraZeneca, BridgeBio, Intellia, Ionis, Janssen, Novo Nordisk, and Pfizer.

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

A novel antibody, NI006 (Neurimmune), was safe for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) in a phase 1 trial and appeared to reduce the amount of amyloid protein deposited in the heart, a new study suggests.

Currently, the only drug approved to treat ATTR is tafamidis, which improves survival and reduces hospitalizations, but does not reverse disease symptoms, the authors noted.

NI006 is a recombinant human anti-ATTR antibody given by infusion that was developed to trigger removal of ATTR by the body’s phagocytic immune cells.

Use of the drug was not associated with serious drug-related adverse events, though mild and moderate adverse events did occur.

Median N-terminal pro–B-type natriuretic peptide (NT-proBNP) and troponin T levels also seemed to be reduced over the study period.

Given the success of the antibody in this initial 40-patient trial, a larger phase-3 placebo-controlled trial is planned and expected to launch in the second half of 2023, said lead author Pablo Garcia-Pavia, MD, of Hospital Universitario Puerta de Hierro and the Spanish National Cardiovascular Research Institute, Madrid.

However, “The design of appropriate phase-3 trials to demonstrate efficacy of drugs for ATTR-CM is becoming more complicated and challenging,” he said.

“Increased awareness of the disease and advances in cardiac imaging techniques have led to recognition of a larger number of patients with ATTR-CM who have a different clinical profile and a different prognosis than the patients who were diagnosed in previous years and were enrolled in the initial trials of stabilizers,” Dr. Garcia-Pavia added.

“Moreover, the availability of tafamidis, and hopefully soon other medications to treat ATTR-CM has complicated the design of new clinical trials because of the heterogenicity of treatments that patients might receive,” he said. “Therefore, it is critical to plan the design very well.”

Dr. Garcia-Pavia presented the findings on NI006 at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions. The study was published simultaneously in the New England Journal of Medicine.
 

No serious adverse events

For the phase-1, double-blind, multicenter study, the investigators randomly assigned (2:1 ratio) 40 patients (median age, 72 years; 98% men) with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive IV infusions of either NI006, at one of six doses ranging from 0.3 mg/kg to 60 mg/kg of body weight, or placebo every 4 weeks for 4 months.

After the four infusions, participants were enrolled in an open-label extension phase in which they received eight NI006 infusions with stepwise increases in the dose.

Participants had a confirmed diagnosis of ATTR-CM; left ventricular wall thickness of at least 14 mm; left ventricular ejection fraction of at least 40%; New York Heart Association class I, II, or III; estimated glomerular filtration rate of more than 30 mL/min per 1.73 m²; and an NT-proBNP level of 600 to 6,000 pg/mL.

Most (36) were receiving tafamidis, with a median treatment duration of 7 months; other ATTR-specific drugs were not permitted. Patients randomly assigned to receive NI006 seemed to have more advanced disease compared with those assigned to placebo.

Adherence to the trial protocol was high: Thirty-four patients received the four scheduled infusions during the ascending-dose phase, and 34 of 35 patients who completed this phase subsequently enrolled in the open-label extension.

No apparent drug-related serious adverse events were reported. However, during the ascending-dose phase, 38 patients had at least one adverse event, most of which were mild or moderate; of the 191 total events, 124 were grade 1 and 60 were grade 2 (most commonly heart failure and arrhythmias). Three patients had cytokine release syndrome; all three completed treatment through the extension phase.

Musculoskeletal events increased with ascending doses of NI006, which led two patients to withdraw from the trial.

At doses of at least 10 mg/kg, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac MRI, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over 12 months.

Because NI006 stimulates the patient’s own immune system to eliminate cardiac amyloid fibrils, one session chair at the meeting wondered whether NI006 represented the “rise of immunology in cardiology,” and whether biologics might follow.

Another questioned how removing amyloid might affect cardiac function. The echocardiographic findings gathered so far don’t indicate dysfunction, “but this is a small trial, and we need more data,” Dr. Garcia-Pavia said.
 

Tempered excitement

In a comment, Ronald Witteles, MD, professor of cardiovascular medicine, Stanford (Calif.) University, and founder/codirector of the Stanford Amyloid Center, said that “antibody-based amyloid removal strategies are not currently clinically available and represent a fundamentally different mechanism to treat the disease from what we currently have.

“While the data are encouraging and will generate excitement for later-phase studies, we’re talking about small numbers of patients and nothing definitive should be drawn from this data,” said Dr. Witteles, deputy editor of JACC: CardioOncology.

“The biggest caveat is that similar approaches of antibody removal of amyloid deposits for other forms of amyloidosis — most notably AL amyloidosis (amyloid light chain or primary amyloidosis) – have failed in late-phase trials. Although there is reason to believe that ATTR amyloidosis may be more amenable to improvements with amyloid fibril removal than AL amyloidosis, the unimpressive results in other forms of amyloidosis still do temper the excitement to a degree.”

Like Dr. Garcia-Pavia, Dr. Witteles said, “Ultimately, we are going to need to see a phase 3 clinical trial which shows that NI006 – on top of standard-of-care treatment – improves hard outcomes in the disease. As treatment options likely expand in the coming years, that is likely to be a harder and harder bar to reach.”

Furthermore, although the safety profile was favorable overall, it “wasn’t entirely clean,” given cytokine release syndrome in three patients, a lowering of platelet counts in a couple of patients, and musculoskeletal side effects that triggered two to withdraw from the study. “Unless that changes,” he said, “that will be a barrier for some patients.”

Overall, he noted, “With the vast majority of patients being able to be diagnosed noninvasively, and with treatment options now available, we have seen a true explosion in the number of patients being diagnosed.

“But we also know that the large majority ... are still not getting diagnosed or are having huge delays in diagnosis. As such, the biggest thing we can do for patients with the disease is to continue to educate people about it,” Dr. Witteles concluded.

The study was funded by Neurimmune. Dr. Garcia-Pavia disclosed ties to Alexion, Alnylam Pharmaceuticals, AstraZeneca, Attralus, BridgeBio, General Electric, Intellia, Ionis Pharmaceuticals, Neurimmune, Novo Nordisk, and Pfizer. Dr. Witteles reported ties to Alexion, Alnylam, AstraZeneca, BridgeBio, Intellia, Ionis, Janssen, Novo Nordisk, and Pfizer.

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

The U.S. Food and Drug Administration on May 22 approved a new autoinjection option for adalimumab-adbm (Cyltezo), a biosimilar to AbbVie’s adalimumab (Humira), ahead of Cyltezo’s commercial launch on July 1, 2023.

Cyltezo was approved by the FDA in 2017 as a prefilled syringe and was the first biosimilar deemed to be interchangeable with Humira in 2021. It is indicated to treat multiple chronic inflammatory conditions, including rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and hidradenitis suppurativa. This new design, which features one-button, three-step activation, has been certified as an “Ease of Use” product by the Arthritis Foundation, Boehringer Ingelheim said in a press release. The 40-mg, prefilled Cyltezo Pen will be available in two-, four-, and six-pack options.

“The FDA approval of the Cyltezo Pen is great news for patients living with chronic inflammatory diseases who may prefer administering the medication needed to manage their conditions via an autoinjector,” said Stephen Pagnotta, the executive director and biosimilar commercial lead at Boehringer Ingelheim in a statement; “we’re excited to be able to offer the Cyltezo Pen as an additional option to patients at Cyltezo’s launch on July 1.”

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

SAN FRANCISCO – Much of the information posted on TikTok about dissociative identity disorder (DID), a rare psychiatric disorder, is misleading and not useful, new research shows.

These findings, say investigators, underscore the need for mental health professionals to help counter the spread of false information by creating accurate content and posting it on the popular social media platform.

Isreal Bladimir Munoz

“Health care professionals need to make engaging content to post on social media platforms like YouTube and especially TikTok, to reach wider audiences and combat misinformation about DID,” study investigator Isreal Bladimir Munoz, a fourth-year medical student at University of Texas, Galveston, said in an interview.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Popularized by the media

A rare condition affecting less than 1% of the general population, DID involves two or more distinct personality states, along with changes in behavior and memory gaps.

The condition has been popularized in books and the media. Movies such as “Split,” “Psycho,” and “Fight Club” all feature characters with DID.

“These bring awareness about the condition, but also often sensationalize or stigmatize it and reinforce stereotypes,” said Mr. Munoz.

In recent years, social media has become an integral part of everyday life. An estimated 4.2 billion people actively frequent sites such as YouTube, TikTok, Twitter, and Meta.

Although social media allows for instant communication and the opportunity for self-expression, there are mounting concerns about the spread of misinformation and its potential impact on mental health and privacy, said Mr. Munoz.

To evaluate the quality and accuracy of information about DID on social media, investigators analyzed 60 YouTube and 97 TikTok videos on the condition.

To evaluate the reliability and the intent and reliability of videos, researchers used the modified DISCERN instrument and the Global Quality Scale, a five-point rating system.

Using these tools, the researchers determined whether the selected videos were useful, misleading, or neither. Mr. Munoz said videos were classified as useful if they contained accurate information about the condition and its pathogenesis, treatment, and management.

Researchers determined that for YouTube videos, 51.7% were useful, 6.6% were misleading, and 34.7% were neither. About 43.3% of these videos involved interviews, 21.7% were educational, 15% involved personal stories, 8.3% were films/TV programs, 5% were comedy skits, and 3.3% were another content type.

The highest quality YouTube videos were from educational organizations and health care professionals. The least accurate videos came from independent users and film/TV sources.

As for TikTok videos on DID, only 5.2% were useful, 10.3% were misleading, and 41.7% were neither.

The main sources for TikTok videos were independent organizations, whereas podcasts and film/TV were the least common sources.

The findings, said Mr. Munoz, underscore the need for medical professionals to develop high-quality content about DID and post it on TikTok to counter misinformation on social media.
 

Call to action

In a comment, Howard Y. Liu, MD, a child and adolescent psychiatrist and chair of the department of psychiatry, University of Nebraska, Omaha, described the study as “compelling.”

When it comes to public health messages, it’s important to know what social media people are using. Today’s parents are on Twitter and Facebook, whereas their children are more likely to be checking out YouTube and TikTok, said Dr. Liu, chair of the APA’s Council on Communications.

“TikTok is critical because that’s where all the youth eyeballs are,” he said.

The medical profession needs to engage with the platform to reach this next-generation audience and help stop the spread of misinformation about DID, said Dr. Liu. He noted that the APA is looking into undertaking such an initiative.

The study investigators report no relevant disclosures. Dr. Liu reports no relevant disclosures.

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

SAN FRANCISCO – Much of the information posted on TikTok about dissociative identity disorder (DID), a rare psychiatric disorder, is misleading and not useful, new research shows.

These findings, say investigators, underscore the need for mental health professionals to help counter the spread of false information by creating accurate content and posting it on the popular social media platform.

Isreal Bladimir Munoz

“Health care professionals need to make engaging content to post on social media platforms like YouTube and especially TikTok, to reach wider audiences and combat misinformation about DID,” study investigator Isreal Bladimir Munoz, a fourth-year medical student at University of Texas, Galveston, said in an interview.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Popularized by the media

A rare condition affecting less than 1% of the general population, DID involves two or more distinct personality states, along with changes in behavior and memory gaps.

The condition has been popularized in books and the media. Movies such as “Split,” “Psycho,” and “Fight Club” all feature characters with DID.

“These bring awareness about the condition, but also often sensationalize or stigmatize it and reinforce stereotypes,” said Mr. Munoz.

In recent years, social media has become an integral part of everyday life. An estimated 4.2 billion people actively frequent sites such as YouTube, TikTok, Twitter, and Meta.

Although social media allows for instant communication and the opportunity for self-expression, there are mounting concerns about the spread of misinformation and its potential impact on mental health and privacy, said Mr. Munoz.

To evaluate the quality and accuracy of information about DID on social media, investigators analyzed 60 YouTube and 97 TikTok videos on the condition.

To evaluate the reliability and the intent and reliability of videos, researchers used the modified DISCERN instrument and the Global Quality Scale, a five-point rating system.

Using these tools, the researchers determined whether the selected videos were useful, misleading, or neither. Mr. Munoz said videos were classified as useful if they contained accurate information about the condition and its pathogenesis, treatment, and management.

Researchers determined that for YouTube videos, 51.7% were useful, 6.6% were misleading, and 34.7% were neither. About 43.3% of these videos involved interviews, 21.7% were educational, 15% involved personal stories, 8.3% were films/TV programs, 5% were comedy skits, and 3.3% were another content type.

The highest quality YouTube videos were from educational organizations and health care professionals. The least accurate videos came from independent users and film/TV sources.

As for TikTok videos on DID, only 5.2% were useful, 10.3% were misleading, and 41.7% were neither.

The main sources for TikTok videos were independent organizations, whereas podcasts and film/TV were the least common sources.

The findings, said Mr. Munoz, underscore the need for medical professionals to develop high-quality content about DID and post it on TikTok to counter misinformation on social media.
 

Call to action

In a comment, Howard Y. Liu, MD, a child and adolescent psychiatrist and chair of the department of psychiatry, University of Nebraska, Omaha, described the study as “compelling.”

When it comes to public health messages, it’s important to know what social media people are using. Today’s parents are on Twitter and Facebook, whereas their children are more likely to be checking out YouTube and TikTok, said Dr. Liu, chair of the APA’s Council on Communications.

“TikTok is critical because that’s where all the youth eyeballs are,” he said.

The medical profession needs to engage with the platform to reach this next-generation audience and help stop the spread of misinformation about DID, said Dr. Liu. He noted that the APA is looking into undertaking such an initiative.

The study investigators report no relevant disclosures. Dr. Liu reports no relevant disclosures.

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

SAN FRANCISCO – Much of the information posted on TikTok about dissociative identity disorder (DID), a rare psychiatric disorder, is misleading and not useful, new research shows.

These findings, say investigators, underscore the need for mental health professionals to help counter the spread of false information by creating accurate content and posting it on the popular social media platform.

Isreal Bladimir Munoz

“Health care professionals need to make engaging content to post on social media platforms like YouTube and especially TikTok, to reach wider audiences and combat misinformation about DID,” study investigator Isreal Bladimir Munoz, a fourth-year medical student at University of Texas, Galveston, said in an interview.

The findings were presented at the annual meeting of the American Psychiatric Association.
 

Popularized by the media

A rare condition affecting less than 1% of the general population, DID involves two or more distinct personality states, along with changes in behavior and memory gaps.

The condition has been popularized in books and the media. Movies such as “Split,” “Psycho,” and “Fight Club” all feature characters with DID.

“These bring awareness about the condition, but also often sensationalize or stigmatize it and reinforce stereotypes,” said Mr. Munoz.

In recent years, social media has become an integral part of everyday life. An estimated 4.2 billion people actively frequent sites such as YouTube, TikTok, Twitter, and Meta.

Although social media allows for instant communication and the opportunity for self-expression, there are mounting concerns about the spread of misinformation and its potential impact on mental health and privacy, said Mr. Munoz.

To evaluate the quality and accuracy of information about DID on social media, investigators analyzed 60 YouTube and 97 TikTok videos on the condition.

To evaluate the reliability and the intent and reliability of videos, researchers used the modified DISCERN instrument and the Global Quality Scale, a five-point rating system.

Using these tools, the researchers determined whether the selected videos were useful, misleading, or neither. Mr. Munoz said videos were classified as useful if they contained accurate information about the condition and its pathogenesis, treatment, and management.

Researchers determined that for YouTube videos, 51.7% were useful, 6.6% were misleading, and 34.7% were neither. About 43.3% of these videos involved interviews, 21.7% were educational, 15% involved personal stories, 8.3% were films/TV programs, 5% were comedy skits, and 3.3% were another content type.

The highest quality YouTube videos were from educational organizations and health care professionals. The least accurate videos came from independent users and film/TV sources.

As for TikTok videos on DID, only 5.2% were useful, 10.3% were misleading, and 41.7% were neither.

The main sources for TikTok videos were independent organizations, whereas podcasts and film/TV were the least common sources.

The findings, said Mr. Munoz, underscore the need for medical professionals to develop high-quality content about DID and post it on TikTok to counter misinformation on social media.
 

Call to action

In a comment, Howard Y. Liu, MD, a child and adolescent psychiatrist and chair of the department of psychiatry, University of Nebraska, Omaha, described the study as “compelling.”

When it comes to public health messages, it’s important to know what social media people are using. Today’s parents are on Twitter and Facebook, whereas their children are more likely to be checking out YouTube and TikTok, said Dr. Liu, chair of the APA’s Council on Communications.

“TikTok is critical because that’s where all the youth eyeballs are,” he said.

The medical profession needs to engage with the platform to reach this next-generation audience and help stop the spread of misinformation about DID, said Dr. Liu. He noted that the APA is looking into undertaking such an initiative.

The study investigators report no relevant disclosures. Dr. Liu reports no relevant disclosures.

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

“Artificial intelligence (AI) in healthcare refers to the use of machine learning (ML), deep learning, natural language processing, and computer vision to process and analyze large amounts of health care data.”

The preceding line is a direct quote from ChatGPT when prompted with the question “What is AI in health care?” (OpenAI, 2022). AI has rapidly infiltrated our lives. From using facial recognition software to unlock our cellphones to scrolling through targeted media suggested by streaming services, our daily existence is interwoven with algorithms. With the recent introduction of GPT-3 (the model that powers ChatGPT) in late 2022 and its even more capable successor, GPT-4, in March 2023, AI will continue to dominate our everyday environment in even more complex and meaningful ways.

CHEST

For sleep medicine, the initial applications of AI in this field have been innovative and promising. To date, AI has been leveraged to explore sleep staging, respiratory event scoring, characterization of insomnia, prediction of circadian timing from gene expression, endotyping, and phenotyping of obstructive sleep apnea (OSA) (Bandyopadhyay A, et al. Sleep Breath. 2023;27[1]:39). Pépin and colleagues (JAMA Netw Open. 2020;3[1]:e1919657) combined ML with mandibular movement to diagnose OSA with a reasonable agreement to polysomnography as a novel home-based alternative for diagnosis. AI has also been used to predict adherence to positive airway pressure (PAP) therapy in OSA (Scioscia G, et al. Inform Health Soc Care. 2022;47[3]:274) and as a digital intervention tool accessed via a smartphone app for people with insomnia (Philip P, et al, J Med Internet Res. 2020;22[12]:e24268). The data-rich field of sleep medicine is primed for further advancements through AI, albeit with a few hurdles and regulations to overcome before becoming mainstream.
 

Future promise

Sleep medicine is uniquely positioned to develop robust AI algorithms because of its vast data trove. Using AI, scientists can efficiently analyze the raw data from polysomnography, consumer sleep technology (CST), and nightly remote monitoring (from PAP devices) to substantially improve comprehension and management of sleep disorders.

AI can redefine OSA through analysis of the big data available, rather than solely relying on the apnea-hypopnea index. In addition, novel variables such as facial structure; snoring index; temperature trends; and sleep environment, position, and timing using a camera-based contactless technology may be incorporated to enhance the diagnostic accuracy for OSA or better describe sleep quality. AI algorithms can also be embedded into the electronic health record (EHR) to facilitate screening for sleep disorders using patient characteristics, thus accelerating the recognition and evaluation of possible sleep disorders.

CHEST

New ways of collecting data may deliver deeper insights into sleep health, as well. CST such as wearables, nearables, and phone applications are improving with each iteration, resulting in more data about sleep for millions of people over thousands of nights.

AI can help achieve precision medicine by integrating multimodal data to establish endotypes and phenotypes of various sleep disorders. Delineating endotypes and phenotypes allows for personalized treatment recommendations, which may improve patient adherence and health outcomes.

Treatment personalization can also be achieved through AI by predicting compliance to various therapies and responses, as well as by discovering alternative forms of delivery to accomplish desired health outcomes. For example, to predict PAP compliance, we can record a patient encounter and use natural language processing to analyze their opinion of their treatment, extracting relevant keywords and combining such processing with other available data, such as environmental factors, sleep schedule, medical history, and other information extracted from the EHR. As another example, AI can determine the optimal time for cancer therapy by predicting a patient’s circadian timing (Hesse J, et al. Cancers (Basel). 2020;12[11]:3103). Circadian timing of drug delivery may be relevant in other specialties including cardiovascular disease, endocrine disorders, and psychiatric conditions due to its associations with sleep. Integration of the various “-omics” (eg, proteomics, genomics, and transcriptomics) with physiologic, behavioral, and environmental data can offer opportunities for drug discovery and possible prediction of sleep disorders and sleep-related morbidity. Although generative pretrained transformers are currently used to predict text (ie, ChatGPT), it is theoretically possible to also apply this technique to identify patients at risk for future sleep disorders from an earlier age.
 

Challenges to an AI renaissance

Despite making strides in numerous specialties such as radiology, ophthalmology, pathology, oncology, and dermatology, AI has not yet gained mainstream usage. Why isn’t AI as ubiquitous and heavily entrenched in health care as it is in other industries? According to the National Academy of Medicine’s AI in Healthcare: The Hope, The Hype, The Promise, The Peril, there are several realities to address before we fully embrace the AI revolution (Matheny M, et al. 2019).

First, AI algorithms should be trained on quality data that are representative of the population. Interoperability between health care systems and standardization across platforms is required to access large volumes of quality data. The current framework for data gathering is limited due to regulations, patient privacy concerns, and organizational preferences. The challenges to data acquisition and standardization of information will continue to snarl progress unless there are legislative remedies.

Furthermore, datasets should be diverse enough to avoid introducing bias into the AI algorithm. If the dataset is limited and health inequities (eg, societal bias and social determinants of health) are excluded from the training set, then the outcome will perpetuate further explicit and implicit biases.

The Food and Drug Administration (FDA) reviews and authorizes AI/ML-enabled devices. Its current regulatory structure treats AI as a static process and does not allow for exercise of its intrinsic ability to continuously learn from additional data, thereby preventing it from becoming more accurate and evolving with the population over time. A more flexible approach is needed.

Lastly, recent advanced AI algorithms including deep learning and neural network methodology function like a “black box.” The models are not explainable or transparent. Without clear comprehension of its methods, acceptance in clinical practice will be guarded and further risk of inherent biases may ensue.
 

A path forward

But these challenges, like any, can be overcome. Research in the area of differential privacy and the adoption of recent data-sharing standards (eg, HL7 FHIR) can facilitate access to training data (Saripalle R, et al. J Biomed Inform. 2019;94:103188). Regulators are also open to incorporating feedback from the AI research community and industry in favor of innovation in this frenetic domain. The FDA developed the AI/ML Software as a Medical Device Action Plan in response to stakeholder feedback for oversight (FDA, 2021). Specifically, the “Good Machine Learning Practice” will be developed to describe AI/ML best practices (eg, data management, training, interpretability, evaluation, and documentation) to guide product development and standardization.

Sleep medicine has significantly progressed over the last several decades. Rather than maintain the status quo, AI can help fill the existing knowledge gaps, augment clinical practice, and streamline operations by analyzing and processing data at a volume and efficiency beyond human capacity. Fallibility is inevitable in machines and humans; however, like humans, machines can improve with continued training and exposure.

We asked ChatGPT about the future of AI in sleep medicine. It states that AI could have a “significant impact” on sleep disorders diagnosis, treatment, prevention, and sleep tracking and monitoring. Only time will tell if its claims are accurate.

Dr. Tan is Clinical Associate Professor with the Division of Sleep Medicine at the Stanford University School of Medicine. Dr. Bhargava is Clinical Professor with the Division of Pediatric Pulmonary, Asthma, and Sleep Medicine at the Stanford University School of Medicine.

“Artificial intelligence (AI) in healthcare refers to the use of machine learning (ML), deep learning, natural language processing, and computer vision to process and analyze large amounts of health care data.”

The preceding line is a direct quote from ChatGPT when prompted with the question “What is AI in health care?” (OpenAI, 2022). AI has rapidly infiltrated our lives. From using facial recognition software to unlock our cellphones to scrolling through targeted media suggested by streaming services, our daily existence is interwoven with algorithms. With the recent introduction of GPT-3 (the model that powers ChatGPT) in late 2022 and its even more capable successor, GPT-4, in March 2023, AI will continue to dominate our everyday environment in even more complex and meaningful ways.

CHEST

For sleep medicine, the initial applications of AI in this field have been innovative and promising. To date, AI has been leveraged to explore sleep staging, respiratory event scoring, characterization of insomnia, prediction of circadian timing from gene expression, endotyping, and phenotyping of obstructive sleep apnea (OSA) (Bandyopadhyay A, et al. Sleep Breath. 2023;27[1]:39). Pépin and colleagues (JAMA Netw Open. 2020;3[1]:e1919657) combined ML with mandibular movement to diagnose OSA with a reasonable agreement to polysomnography as a novel home-based alternative for diagnosis. AI has also been used to predict adherence to positive airway pressure (PAP) therapy in OSA (Scioscia G, et al. Inform Health Soc Care. 2022;47[3]:274) and as a digital intervention tool accessed via a smartphone app for people with insomnia (Philip P, et al, J Med Internet Res. 2020;22[12]:e24268). The data-rich field of sleep medicine is primed for further advancements through AI, albeit with a few hurdles and regulations to overcome before becoming mainstream.
 

Future promise

Sleep medicine is uniquely positioned to develop robust AI algorithms because of its vast data trove. Using AI, scientists can efficiently analyze the raw data from polysomnography, consumer sleep technology (CST), and nightly remote monitoring (from PAP devices) to substantially improve comprehension and management of sleep disorders.

AI can redefine OSA through analysis of the big data available, rather than solely relying on the apnea-hypopnea index. In addition, novel variables such as facial structure; snoring index; temperature trends; and sleep environment, position, and timing using a camera-based contactless technology may be incorporated to enhance the diagnostic accuracy for OSA or better describe sleep quality. AI algorithms can also be embedded into the electronic health record (EHR) to facilitate screening for sleep disorders using patient characteristics, thus accelerating the recognition and evaluation of possible sleep disorders.

CHEST

New ways of collecting data may deliver deeper insights into sleep health, as well. CST such as wearables, nearables, and phone applications are improving with each iteration, resulting in more data about sleep for millions of people over thousands of nights.

AI can help achieve precision medicine by integrating multimodal data to establish endotypes and phenotypes of various sleep disorders. Delineating endotypes and phenotypes allows for personalized treatment recommendations, which may improve patient adherence and health outcomes.

Treatment personalization can also be achieved through AI by predicting compliance to various therapies and responses, as well as by discovering alternative forms of delivery to accomplish desired health outcomes. For example, to predict PAP compliance, we can record a patient encounter and use natural language processing to analyze their opinion of their treatment, extracting relevant keywords and combining such processing with other available data, such as environmental factors, sleep schedule, medical history, and other information extracted from the EHR. As another example, AI can determine the optimal time for cancer therapy by predicting a patient’s circadian timing (Hesse J, et al. Cancers (Basel). 2020;12[11]:3103). Circadian timing of drug delivery may be relevant in other specialties including cardiovascular disease, endocrine disorders, and psychiatric conditions due to its associations with sleep. Integration of the various “-omics” (eg, proteomics, genomics, and transcriptomics) with physiologic, behavioral, and environmental data can offer opportunities for drug discovery and possible prediction of sleep disorders and sleep-related morbidity. Although generative pretrained transformers are currently used to predict text (ie, ChatGPT), it is theoretically possible to also apply this technique to identify patients at risk for future sleep disorders from an earlier age.
 

Challenges to an AI renaissance

Despite making strides in numerous specialties such as radiology, ophthalmology, pathology, oncology, and dermatology, AI has not yet gained mainstream usage. Why isn’t AI as ubiquitous and heavily entrenched in health care as it is in other industries? According to the National Academy of Medicine’s AI in Healthcare: The Hope, The Hype, The Promise, The Peril, there are several realities to address before we fully embrace the AI revolution (Matheny M, et al. 2019).

First, AI algorithms should be trained on quality data that are representative of the population. Interoperability between health care systems and standardization across platforms is required to access large volumes of quality data. The current framework for data gathering is limited due to regulations, patient privacy concerns, and organizational preferences. The challenges to data acquisition and standardization of information will continue to snarl progress unless there are legislative remedies.

Furthermore, datasets should be diverse enough to avoid introducing bias into the AI algorithm. If the dataset is limited and health inequities (eg, societal bias and social determinants of health) are excluded from the training set, then the outcome will perpetuate further explicit and implicit biases.

The Food and Drug Administration (FDA) reviews and authorizes AI/ML-enabled devices. Its current regulatory structure treats AI as a static process and does not allow for exercise of its intrinsic ability to continuously learn from additional data, thereby preventing it from becoming more accurate and evolving with the population over time. A more flexible approach is needed.

Lastly, recent advanced AI algorithms including deep learning and neural network methodology function like a “black box.” The models are not explainable or transparent. Without clear comprehension of its methods, acceptance in clinical practice will be guarded and further risk of inherent biases may ensue.
 

A path forward

But these challenges, like any, can be overcome. Research in the area of differential privacy and the adoption of recent data-sharing standards (eg, HL7 FHIR) can facilitate access to training data (Saripalle R, et al. J Biomed Inform. 2019;94:103188). Regulators are also open to incorporating feedback from the AI research community and industry in favor of innovation in this frenetic domain. The FDA developed the AI/ML Software as a Medical Device Action Plan in response to stakeholder feedback for oversight (FDA, 2021). Specifically, the “Good Machine Learning Practice” will be developed to describe AI/ML best practices (eg, data management, training, interpretability, evaluation, and documentation) to guide product development and standardization.

Sleep medicine has significantly progressed over the last several decades. Rather than maintain the status quo, AI can help fill the existing knowledge gaps, augment clinical practice, and streamline operations by analyzing and processing data at a volume and efficiency beyond human capacity. Fallibility is inevitable in machines and humans; however, like humans, machines can improve with continued training and exposure.

We asked ChatGPT about the future of AI in sleep medicine. It states that AI could have a “significant impact” on sleep disorders diagnosis, treatment, prevention, and sleep tracking and monitoring. Only time will tell if its claims are accurate.

Dr. Tan is Clinical Associate Professor with the Division of Sleep Medicine at the Stanford University School of Medicine. Dr. Bhargava is Clinical Professor with the Division of Pediatric Pulmonary, Asthma, and Sleep Medicine at the Stanford University School of Medicine.

“Artificial intelligence (AI) in healthcare refers to the use of machine learning (ML), deep learning, natural language processing, and computer vision to process and analyze large amounts of health care data.”

The preceding line is a direct quote from ChatGPT when prompted with the question “What is AI in health care?” (OpenAI, 2022). AI has rapidly infiltrated our lives. From using facial recognition software to unlock our cellphones to scrolling through targeted media suggested by streaming services, our daily existence is interwoven with algorithms. With the recent introduction of GPT-3 (the model that powers ChatGPT) in late 2022 and its even more capable successor, GPT-4, in March 2023, AI will continue to dominate our everyday environment in even more complex and meaningful ways.

CHEST

For sleep medicine, the initial applications of AI in this field have been innovative and promising. To date, AI has been leveraged to explore sleep staging, respiratory event scoring, characterization of insomnia, prediction of circadian timing from gene expression, endotyping, and phenotyping of obstructive sleep apnea (OSA) (Bandyopadhyay A, et al. Sleep Breath. 2023;27[1]:39). Pépin and colleagues (JAMA Netw Open. 2020;3[1]:e1919657) combined ML with mandibular movement to diagnose OSA with a reasonable agreement to polysomnography as a novel home-based alternative for diagnosis. AI has also been used to predict adherence to positive airway pressure (PAP) therapy in OSA (Scioscia G, et al. Inform Health Soc Care. 2022;47[3]:274) and as a digital intervention tool accessed via a smartphone app for people with insomnia (Philip P, et al, J Med Internet Res. 2020;22[12]:e24268). The data-rich field of sleep medicine is primed for further advancements through AI, albeit with a few hurdles and regulations to overcome before becoming mainstream.
 

Future promise

Sleep medicine is uniquely positioned to develop robust AI algorithms because of its vast data trove. Using AI, scientists can efficiently analyze the raw data from polysomnography, consumer sleep technology (CST), and nightly remote monitoring (from PAP devices) to substantially improve comprehension and management of sleep disorders.

AI can redefine OSA through analysis of the big data available, rather than solely relying on the apnea-hypopnea index. In addition, novel variables such as facial structure; snoring index; temperature trends; and sleep environment, position, and timing using a camera-based contactless technology may be incorporated to enhance the diagnostic accuracy for OSA or better describe sleep quality. AI algorithms can also be embedded into the electronic health record (EHR) to facilitate screening for sleep disorders using patient characteristics, thus accelerating the recognition and evaluation of possible sleep disorders.

CHEST

New ways of collecting data may deliver deeper insights into sleep health, as well. CST such as wearables, nearables, and phone applications are improving with each iteration, resulting in more data about sleep for millions of people over thousands of nights.

AI can help achieve precision medicine by integrating multimodal data to establish endotypes and phenotypes of various sleep disorders. Delineating endotypes and phenotypes allows for personalized treatment recommendations, which may improve patient adherence and health outcomes.

Treatment personalization can also be achieved through AI by predicting compliance to various therapies and responses, as well as by discovering alternative forms of delivery to accomplish desired health outcomes. For example, to predict PAP compliance, we can record a patient encounter and use natural language processing to analyze their opinion of their treatment, extracting relevant keywords and combining such processing with other available data, such as environmental factors, sleep schedule, medical history, and other information extracted from the EHR. As another example, AI can determine the optimal time for cancer therapy by predicting a patient’s circadian timing (Hesse J, et al. Cancers (Basel). 2020;12[11]:3103). Circadian timing of drug delivery may be relevant in other specialties including cardiovascular disease, endocrine disorders, and psychiatric conditions due to its associations with sleep. Integration of the various “-omics” (eg, proteomics, genomics, and transcriptomics) with physiologic, behavioral, and environmental data can offer opportunities for drug discovery and possible prediction of sleep disorders and sleep-related morbidity. Although generative pretrained transformers are currently used to predict text (ie, ChatGPT), it is theoretically possible to also apply this technique to identify patients at risk for future sleep disorders from an earlier age.
 

Challenges to an AI renaissance

Despite making strides in numerous specialties such as radiology, ophthalmology, pathology, oncology, and dermatology, AI has not yet gained mainstream usage. Why isn’t AI as ubiquitous and heavily entrenched in health care as it is in other industries? According to the National Academy of Medicine’s AI in Healthcare: The Hope, The Hype, The Promise, The Peril, there are several realities to address before we fully embrace the AI revolution (Matheny M, et al. 2019).

First, AI algorithms should be trained on quality data that are representative of the population. Interoperability between health care systems and standardization across platforms is required to access large volumes of quality data. The current framework for data gathering is limited due to regulations, patient privacy concerns, and organizational preferences. The challenges to data acquisition and standardization of information will continue to snarl progress unless there are legislative remedies.

Furthermore, datasets should be diverse enough to avoid introducing bias into the AI algorithm. If the dataset is limited and health inequities (eg, societal bias and social determinants of health) are excluded from the training set, then the outcome will perpetuate further explicit and implicit biases.

The Food and Drug Administration (FDA) reviews and authorizes AI/ML-enabled devices. Its current regulatory structure treats AI as a static process and does not allow for exercise of its intrinsic ability to continuously learn from additional data, thereby preventing it from becoming more accurate and evolving with the population over time. A more flexible approach is needed.

Lastly, recent advanced AI algorithms including deep learning and neural network methodology function like a “black box.” The models are not explainable or transparent. Without clear comprehension of its methods, acceptance in clinical practice will be guarded and further risk of inherent biases may ensue.
 

A path forward

But these challenges, like any, can be overcome. Research in the area of differential privacy and the adoption of recent data-sharing standards (eg, HL7 FHIR) can facilitate access to training data (Saripalle R, et al. J Biomed Inform. 2019;94:103188). Regulators are also open to incorporating feedback from the AI research community and industry in favor of innovation in this frenetic domain. The FDA developed the AI/ML Software as a Medical Device Action Plan in response to stakeholder feedback for oversight (FDA, 2021). Specifically, the “Good Machine Learning Practice” will be developed to describe AI/ML best practices (eg, data management, training, interpretability, evaluation, and documentation) to guide product development and standardization.

Sleep medicine has significantly progressed over the last several decades. Rather than maintain the status quo, AI can help fill the existing knowledge gaps, augment clinical practice, and streamline operations by analyzing and processing data at a volume and efficiency beyond human capacity. Fallibility is inevitable in machines and humans; however, like humans, machines can improve with continued training and exposure.

We asked ChatGPT about the future of AI in sleep medicine. It states that AI could have a “significant impact” on sleep disorders diagnosis, treatment, prevention, and sleep tracking and monitoring. Only time will tell if its claims are accurate.

Dr. Tan is Clinical Associate Professor with the Division of Sleep Medicine at the Stanford University School of Medicine. Dr. Bhargava is Clinical Professor with the Division of Pediatric Pulmonary, Asthma, and Sleep Medicine at the Stanford University School of Medicine.

SAN FRANCISCO – Young people who commit suicide using a gun are often introduced to guns through family traditions and use the family gun to commit suicide, according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.

Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.

Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.

The study was presented at the American Psychiatric Association annual meeting. 

The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.

“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
 

Grim statistics

Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.

Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.

Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.

“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.

Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.

To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.

Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.

In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.

Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.

In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.

Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.

Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.

Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
 

‘Courageous study’

Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.

“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said. 

“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”

Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”

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

SAN FRANCISCO – Young people who commit suicide using a gun are often introduced to guns through family traditions and use the family gun to commit suicide, according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.

Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.

Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.

The study was presented at the American Psychiatric Association annual meeting. 

The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.

“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
 

Grim statistics

Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.

Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.

Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.

“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.

Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.

To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.

Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.

In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.

Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.

In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.

Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.

Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.

Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
 

‘Courageous study’

Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.

“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said. 

“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”

Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”

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

SAN FRANCISCO – Young people who commit suicide using a gun are often introduced to guns through family traditions and use the family gun to commit suicide, according to results of a novel “psychological autopsy study” of loved ones of youth who died by gun-related suicide.

Yet, families don’t always recognize the danger firearms pose to a young person with suicide risk factors, even when there is a young person in the house with a mental health condition, the data show.

Perhaps most importantly, many parents indicated that they would have removed firearms from the home if it had been suggested by their health care professionals.

The study was presented at the American Psychiatric Association annual meeting. 

The message is very clear: Clinicians need to ask about guns and gun safety with patients and families, said study investigator Paul Nestadt, MD, of Johns Hopkins Bloomberg School of Public Health in Baltimore.

“It’s never illegal to ask about gun access and it’s medically relevant. Just do it,” he said during a briefing with reporters.
 

Grim statistics

Suicide rates have been climbing in the United States for the majority of the past 20 years. Suicide is the second most common cause of death among youth.

Dr. Nestadt noted that overall about 8% of suicide attempts result in death, but when an attempt involves a firearm the percentage jumps astronomically to 90%.

Research has shown that for every 10% increase in household firearms in a given community there is a 27% increase in youth suicide deaths.

“In the world of public health and mental health, we think about having access to firearms as an important risk factor for completed suicide. But in the United States, guns have become an important part of how many Americans see themselves,” Dr. Nestadt told reporters.

Research has shown that half of gun owners say owning a gun is central to their identity and three quarters say it’s essential to their freedom, he noted.

To explore these attitudes further, Dr. Nestadt and colleagues did 11 “psychological autopsy interviews” with the loved ones of nine young people aged 17-21 who died by gun-related suicide. They interviewed six mothers, three fathers, one sibling, and one close friend.

Most of the families had some level of “familial engagement” with firearms, Dr. Nestadt reported.

In more than two-thirds of the families, the youth used a family-owned firearm to commit suicide.

Notably, more than three-quarters of the youth had received mental health care before taking their lives, with many receiving care in the weeks prior to their suicide; 44% had made a prior suicide attempt.

In many cases, parents shared that they had not considered their family-owned firearms to be sources of danger and indicated that had their clinicians expressed concern about the gun in the home, they may have acted to reduce the risk by removing it.

Several also shared that they would have considered using Maryland’s Extreme Risk Protective Order Law if it had existed at the time and they had been made aware of it.

Extreme risk protection order (ERPO) laws, or “red flag laws,” prohibit individuals at risk for harming themselves or others from purchasing or owning a firearm.

Dr. Nestadt said youth suicide interventions “must acknowledge culturally embedded roots of identity formation while rescripting firearms from expressions of family cohesion to instruments that may undermine that cohesion.”
 

‘Courageous study’

Dr. Nestadt noted that while this study was challenging on many fronts, it took no convincing to get these grieving families to participate.

“They wanted to talk to us, especially because they were hopeful that our work could help prevent future suicides, but also they wanted to talk about their loved ones,” he said. 

“When you lose someone to cancer, people give you hugs and flowers. When you lose someone to suicide, people don’t discuss it. Suicide has a stigma to it.”

Briefing moderator Howard Liu, MD, MBA, chair of the department of psychiatry, University of Nebraska Medical Center, Omaha, praised the study team for a “courageous study that really required a tremendous amount of vulnerability from the research team and clearly from the survivors as well.”

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

Twice-daily esmolol hydrochloride gel (Galnobax, NovaLead) appears to significantly improve closure of diabetic foot ulcers, particularly in patients with risk factors for impeded wound healing, say Indian researchers.
 

Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.

As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.

The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.

The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m² and in those who weighed more than 80 kg (176 lb).

“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.

Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”

However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).

He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”

In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”

And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.

She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”

The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.

“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.

The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.

Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.

Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.

The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.

Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.

The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.

Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.

In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm² and the average ulcer duration was 49.8 weeks.

The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.

Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).

The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.

In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).

Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).

Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.

The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.

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

Twice-daily esmolol hydrochloride gel (Galnobax, NovaLead) appears to significantly improve closure of diabetic foot ulcers, particularly in patients with risk factors for impeded wound healing, say Indian researchers.
 

Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.

As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.

The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.

The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m² and in those who weighed more than 80 kg (176 lb).

“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.

Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”

However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).

He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”

In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”

And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.

She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”

The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.

“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.

The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.

Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.

Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.

The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.

Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.

The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.

Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.

In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm² and the average ulcer duration was 49.8 weeks.

The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.

Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).

The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.

In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).

Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).

Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.

The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.

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

Twice-daily esmolol hydrochloride gel (Galnobax, NovaLead) appears to significantly improve closure of diabetic foot ulcers, particularly in patients with risk factors for impeded wound healing, say Indian researchers.
 

Esmolol is a short-acting beta-adrenergic receptor blocker that is currently approved by the Food and Drug Administration for cardiac indications such as short-term use for supraventricular tachycardia.

As a gel, esmolol hydrochloride is administered topically to stimulate wound healing via mechanisms such as the migration of keratinocytes, fibroblasts, and endothelial cells into wound tissue.

The current trial enrolled patients with type 1 or 2 diabetes, finding that, among 140 assessed, target ulcer closure within 12 weeks was more than twice as likely in those assigned esmolol gel plus standard of care than those given standard of care alone.

The impact of adding esmolol gel to standard of care was even greater in patients with a body mass index (BMI) over 25 kg/m² and in those who weighed more than 80 kg (176 lb).

“The use of esmolol in the treatment of diabetic foot ulcers in addition to standard of care may be an important addition to the endeavor of healing diabetic foot ulcers,” wrote Ashu Rastogi, MD, DM, department of endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India, and colleagues, in their article recently published in JAMA Network Open.

Dr. Rastogi first presented the findings at the 2022 annual meeting of the European Association for the Study of Diabetes. The results were well received, with one clinician describing them as “astounding.”

However, Andrew Boulton, MD, PhD, said in an interview that, although the final published data are “interesting,” they “need further confirmation” because “there are one or two unusual features” about the study. Dr. Boulton is a professor of medicine, division of diabetes, endocrinology & gastroenterology, at the University of Manchester (England).

He highlighted that the study was of “basically neuropathic ulcers, many of which were plantar and should be able to heal without any specific additional therapy.”

In addition, the inclusion criteria state that the ulcers could be below the malleoli or 5 cm above them, which Dr. Boulton explained is “very unusual and would therefore include some atypical and not truly diabetic ‘foot’ ulcers.”

And Frances Game, MBBCh, department of diabetes and endocrinology, University Hospitals of Derby (England) and Burton NHS Foundation Trust, added that there are questions about the study methodology.

She said in an interview that although it is a “fascinating study,” the main comparison group did not receive vehicle, or placebo, gel in addition to standard of care. “How were they blinded [to treatment]?”

The “biggest problem” with the study, however, is that the primary outcome was reported as a per-protocol endpoint, not as a standard intention-to-treat analysis, which allowed the researchers to exclude patients whose ulcers increased in size by over 30% on two consecutive visits.

“That kind of makes [esmolol gel] look better than it is because they’ve taken out the ones who got worse,” Dr. Game noted. However, the findings, while not conclusive, do warrant further study of esmolol gel.

The authors noted that diabetic foot ulcers are a severe complication of diabetes, with a prevalence of 1.3%-12.0% across various countries, And the complication contributes to patient morbidity and mortality, with a 5-year mortality that is substantially higher than that of many cancers.

Moreover, “even with the best therapy,” such as advanced moist wound therapy, bioengineered tissue or skin substitutes, peptides, growth factors, electric stimulation, and negative-pressure wound therapy, just 30% of wounds linked to diabetes heal and recurrence is as high as 70%.

Against this backdrop, topical esmolol 14% gel was shown in a phase 1/2 study to be associated with ulcer area reduction and earlier wound closure versus standard of care plus a control vehicle gel.

The current phase 3, randomized, controlled trial involved individuals aged 18-75 years with type 1 or type 2 diabetes and noninfected diabetic foot ulcers classified as grade 1A and 1C on the University of Texas Wound Classification System, which had been open for at least 6 weeks and had an area of 2-25 cm2.

Patients from 27 tertiary care centers across India were enrolled in 2018-2020. They were randomized in a 3:3:1 ratio to one of three groups: esmolol 14% gel plus standard of care, standard of care only, or vehicle plus standard of care.

The study lasted 25 weeks and included a 1-week screening phase, during which all patients received standard of care, a 12-week treatment phase, and a 12-week follow-up phase. The latter included a closure confirmation period of 4 weeks and an observation period of 8 weeks.

Patients were assessed once a week during the treatment phase, and then at weeks 14, 16, 20, and 24.

In all, 176 patients were enrolled. Participants were a mean age of 56.4 years and 69.3% were men. Average hemoglobin A1c was 8.6%. Mean diabetic foot ulcer area was 4.7 cm² and the average ulcer duration was 49.8 weeks.

The primary outcome was the proportion of patients who achieved target ulcer closure during the 12-week treatment phase and was assessed in 140 patients.

Overall, 60.3% of patients treated with esmolol gel plus standard of care achieved target ulcer closure versus 41.7% of those in the standard of care alone group (odds ratio, 2.13; P = .03).

The secondary outcome was the proportion of patients with target ulcer closure by the study end and was assessed in 120 patients.

In total, 77.2% of patients in the esmolol gel plus standard of care group met the secondary endpoint, compared with 55.6% of those receiving standard of care alone (OR, 1.72; P = .01).

Further analysis suggested the benefit seen with esmolol gel plus standard of care was greater in patients with a weight greater than 80 kg versus standard of care alone (OR, 4.04; P = .04), and in those with a BMI greater than 25 (OR, 2.72; P = .03).

Treatment-emergent adverse events were reported by 33 (18.8%) participants, with 12 events deemed serious. “However, none of the serious adverse events were considered as drug-related by the investigators,” concluded the researchers.

The study was partly funded by NovaLead Pharma and the Biotechnology Industry Research Assistance Council, New Delhi, set up by the Department of Biotechnology, Government of India. Dr. Rastogi reported no relevant financial relationships.

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

SAN FRANCISCO – Although less likely than White patients to get a psychiatric diagnosis, Black patients were more likely to be physically restrained at three North Carolina emergency departments – especially when they were brought in by police, a new study finds.

In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.

The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”

According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.

Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.

For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.

Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).

The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.

Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.

Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.

What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”

Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”

No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.

SAN FRANCISCO – Although less likely than White patients to get a psychiatric diagnosis, Black patients were more likely to be physically restrained at three North Carolina emergency departments – especially when they were brought in by police, a new study finds.

In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.

The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”

According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.

Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.

For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.

Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).

The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.

Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.

Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.

What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”

Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”

No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.

SAN FRANCISCO – Although less likely than White patients to get a psychiatric diagnosis, Black patients were more likely to be physically restrained at three North Carolina emergency departments – especially when they were brought in by police, a new study finds.

In contrast, Hispanic/Latino patients were less likely to be restrained than both Black and White patients, researchers reported in a poster presented at the annual meeting of the American Psychiatric Association. The study authors also found that clinicians rarely turned to restraints, using them in just 2,712 of 882,390 ED visits (0.3%) over a 7-year period.

The study doesn’t examine why the disparities exist. But lead author Erika Chang-Sing, a medical student at Yale University, New Haven, Conn., said in an interview that it’s clear that racial bias is the cause of the differences in restraint rates among White, Black, and Hispanics/Latino patients. “We think that there are multiple contributing factors to the higher rates of restraint for Black patients brought to the hospital by police, and all of them are rooted in systemic racism,” she said, adding that “the lower odds of restraint in the Hispanic or Latino group are also rooted in systemic racism and inequity.”

According to Ms. Chang-Sing, researchers launched the study to gain insight into the use of the restraints in the Southeast and to see what’s happening in light of the recent publicizing of killings of Black people by police. Being taken to the hospital by police “might contribute both to the individual patient’s behavior and the health care provider’s assessment of risk in determining whether or not to apply restraints,” she said.

Other research has linked ethnicity to higher rates of restraint use. For example, a 2021 study of 32,054 cases of patients under mandatory psychiatric hold in 11 Massachusetts emergency rooms found that Black (adjusted odds ratio, 1.22) and Hispanic (aOR, 1.45) patients were more likely to be restrained than White patients.

For the new study, researchers retrospectively tracked 885,102 emergency room visits at three North Carolina emergency departments from 2015 to 2022, including 9,130 who were brought in by police and 2,712 who were physically restrained because of the perceived risk of violence. “Providers use restraints, or straps, to secure the patient’s wrists and ankles to the bed,” Ms. Chang-Sing said.

Among all patients, 52.5% were Black, but 66% of those who were restrained were Black. The numbers for White patients were 35.7% and 23.9%, respectively, and 5.7% and 3.2% for Hispanics/Latino patients. Black patients were less likely than White patients to get a psychiatric primary emergency department diagnosis (aOR, 0.67), but those in that category were more likely than their White counterparts to be restrained (aOR, 1.36).

The higher risk of restraint use in Black patients overall disappeared when researchers adjusted their statistics to account for the effects of sex, age, and type of insurance (aOR, 0.86). Ms. Chang-Sing said the study team is reanalyzing the data since they think insurance may not be a confounder.

Why might Hispanic/Latino ethnicity be protective against restraint use? “This may be due to language barriers, fear of law enforcement, and avoidance of the hospital in the first place,” Ms. Chang-Sing said.

Emergency physician Wendy Macias-Konstantopoulos, MD, MPH, MBA, of Harvard Medical School and Massachusetts General Hospital, both in Boston, coauthored the 2021 study on police restraints. In an interview, she said the new findings add to previous research by providing data about the role played by the police who bring patients to the ED. She added that there is no evidence that certain populations simply need more restraints.

What can be done to reduce disparities in restraint use? Mental health teams can make a difference by responding to mental health emergencies, Ms. Chang-Sing said. “These providers can be instrumental in communicating to patients that the intention is to care for them, not to punish them.”

Another strategy is to increase the number of clinics and crisis response centers, she said. Hospital-based crisis response teams can also be helpful, she said. “Because these teams are focused only on behavioral emergencies, they can be more thoughtful in avoiding the use of restraints.”

No study funding was reported. The study authors and Dr. Macias-Konstantopoulos have no disclosures.

The U.S. Food and Drug Administration has approved avapritinib (AYVAKIT, Blueprint Medicines) for the treatment of adults with indolent systemic mastocytosis. The new approval, which expands use of the drug to patients with indolent systemic mastocytosis, represents the “first and only approved medicine” to treat this disease, according to the company press statement.

Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.

The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.

The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.

The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).

Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.

“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.

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

Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.

The U.S. Food and Drug Administration has approved avapritinib (AYVAKIT, Blueprint Medicines) for the treatment of adults with indolent systemic mastocytosis. The new approval, which expands use of the drug to patients with indolent systemic mastocytosis, represents the “first and only approved medicine” to treat this disease, according to the company press statement.

Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.

The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.

The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.

The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).

Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.

“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.

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

Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.

The U.S. Food and Drug Administration has approved avapritinib (AYVAKIT, Blueprint Medicines) for the treatment of adults with indolent systemic mastocytosis. The new approval, which expands use of the drug to patients with indolent systemic mastocytosis, represents the “first and only approved medicine” to treat this disease, according to the company press statement.

Avapritinib, a selective KIT mutation-targeted tyrosine kinase inhibitor, was approved in 2021 to treat advanced systemic mastocytosis, a rare and potentially fatal hematologic disorder. Nonadvanced forms include indolent or smoldering disease; advanced disease can progress to leukemia. The expanded approval now covers patients with indolent disease, which represents the majority of patients with systemic mastocytosis.

The drug is also approved for adults with unresectable or metastatic GIST that harbors a platelet-derived growth factor receptor alpha exon 18 mutation.

The approval is based on data from the phase 2 PIONEER trial. In the trial, 222 patients with moderate to severe indolent, systemic mastocytosis* were randomly assigned in a 2:1 ratio to receive either avapritinib 25 mg once daily plus best supportive care or placebo plus best supportive care.

The findings, published in February, revealed that patients who received avapritinib experienced significantly greater improvements in total symptom scores at 24 weeks (–15.6 vs. –9.2 for control patients). Significantly more patients in the avapritinib arm achieved greater than or equal to 50% reductions in serum tryptase (54% vs. 0%), bone marrow mast cell aggregates (53% vs. 23%), and KIT D816V variant allele fraction (68% vs. 6%).

Most adverse reactions were mild to moderate in severity and included eye edema, dizziness, peripheral edema, and flushing. Fewer than 1% of patients discontinued treatment because of serious adverse reactions.

“People with indolent systemic mastocytosis are significantly impacted by their disease symptoms, and many individuals self-isolate at home to protect against unpredictable external triggers,” Judith Kain Emmel, board chair of the Mast Cell Disease Society, said in the company press release. “Today’s approval is a historic moment for the [systemic mastocytosis] community and offers new hope for patients and their families.

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

Correction, 5/23/23: An earlier version of this article mischaracterized these patients' conditions. They had moderate to severe indolent, systemic mastocytosis.