BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.

Will Pass/MDedge News

This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.

“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”

To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.

Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).

While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.

“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.

Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.

“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”

In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.

“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”

The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.

SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.

BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.

Will Pass/MDedge News

This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.

“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”

To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.

Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).

While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.

“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.

Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.

“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”

In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.

“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”

The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.

SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.

BOSTON – For patients with hepatitis C virus infection who achieve sustained virologic response to interferon-free therapy, changes in hepatic venous pressure gradient (HVPG) predict clinical benefit, according to investigators.

Will Pass/MDedge News

This finding will allow investigators to use HVPG as a surrogate endpoint for etiologic therapies, which could accelerate future research, reported lead author Mattias Mandorfer, MD, PhD, of the Medical University of Vienna and colleagues.

“Sustained virologic response to interferon-free therapies ameliorates portal hypertension,” Dr. Mandorfer said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “[Previous research has shown that] nearly two-thirds of patients with pretreatment clinically significant portal hypertension had an HVPG decrease above or equal to 10%, which denotes a clinically meaningful change according to current recommendations. However, evidence is limited to studies evaluating the impact of HVPG response to nonselective beta-blockers, and nonselective beta-blockers have a completely different mode of action than etiological therapies. Accordingly, it is unclear whether a decrease in HVPG after the cure of hepatitis C translates into the same clinical benefit.”

To find out, the investigators enrolled 90 patients with hepatitis C virus who had an elevated HVPG of 6 mm Hg or higher prior to sustained virologic response. Before and after interferon-free therapy, patients underwent paired HVPG measurement. In addition, to evaluate noninvasive methods of HVPG assessment, transient elastography and von Willebrand factor to platelet count ratio testing were performed.

Analysis showed that HVPG measurements after, but not before, interferon-free therapy predicted liver decompensation. Specifically, HVPG was associated with an 18% increased risk of hepatic decompensation per mm Hg. After 3 years, 40.1% of patients with posttherapy HVPG measurements of 16 mm Hg or more developed hepatic decompensation, an event that occurred in none of the patients with a posttherapy HVPG of 9 mm Hg or less. Among patients who had a baseline HVPG of 10 mm Hg or more, which is considered a clinically significant level of portal hypertension, a decrease in HVPG of least 10% after therapy was associated with a similar level of protection against decompensation, compared with those who had no such decrease (2.5% vs. 31.8%).

While the two noninvasive methods (transient elastography and von Willebrand factor to platelet count ratio) were able to detect clinically significant portal hypertension (at least 10 mm Hg), they were not accurate enough to detect the protective 10% drop in HVPG.

“These results support the concept of applying HVPG as a surrogate endpoint for interventions that primarily aim at decreasing intrahepatic resistance (e.g., etiological therapies),” the investigators concluded in their abstract.

Jaime Bosch, MD, PhD, of the University of Barcelona provided some expert insight into the findings.

“The significance of the work is very important,” Dr. Bosch said in a public comment. “This provides, for the first time, firm evidence that HVPG can be taken as a surrogate endpoint ... for studies involving portal hypertension and cirrhosis in general.”

In an interview, Dr. Bosch elaborated on this statement. “The problem is, it takes a long time to get rid of cirrhosis [after sustained virologic response], and meanwhile, as long as portal hypertension remains, there is a risk for decompensation, so the patients cannot be said to be cured. They are cured of the infection, of the consequences of the infection, but it may take 10 years or more [to resolve cirrhosis], so the patient needs clinical surveillance and treatment after curing the cause of the disease.

“An academic consequence of these findings is that they’ve proved that decreasing HVPG by means of achieving sustained virologic response is followed by an improvement in prognosis. ... And when you can influence prognosis, and the influence in prognosis is reflected by a measurement independent from the way that we achieve this effect on the measurement, it means that this measurement is robust and now has to be used as a surrogate marker of resolution of cirrhosis.”

The study was funded by the Medical Scientific Fund of the city of Vienna. The investigators disclosed relationships with AbbVie, Bristol-Myers Squibb, Gilead, and others.

SOURCE: Mandorfer M et al. The Liver Meeting 2019, Abstract 146.

The Oncology Care Model is a value-based payment approach aimed at encouraging coordinated cancer care through targeted bonus payments to practices. The payment experiment was launched by the Centers for Medicare & Medicaid Services in 2016 and now includes 175 practices and 10 payers. It is set to end in 2021. As agency officials consider whether to continue the program, Stephen S. Grubbs, MD, vice president for clinical affairs at the American Society of Clinical Oncology, weighs in on the model’s track record and its future.

utah778/Thinkstock

Question: How would you rate the Oncology Care Model in helping to drive practice transformation?

Dr. Grubbs: Participants in the Oncology Care Model (OCM) have demonstrated improved care coordination, psychosocial support, use of risk assessment tools, and other strategies to lower costs and adverse events. Over the past 2 years, ASCO has accepted numerous posters, articles, and abstracts from OCM participants on their outstanding work to advance cancer care delivery.

Question: Should the model be extended beyond 2021?

Dr. Grubbs: Changes to the model are necessary prior to a significant extension or expansion. Some have suggested that CMS extend OCM for an additional year with current participants. This would give CMS time to consider input from all stakeholders on its eventual replacement.

Question: What additional resources or payments do oncology practices need to be more successful in meeting the goals of the Oncology Care Model?

Dr. Grubbs: OCM has shown that by providing oncologists with payment for care management – OCM participants receive $160 per patient, per month – the results are better care coordination and reduced hospital and emergency department visits. If CMS chooses to expand payments to all oncology providers, we could expect to see improved care for cancer patients.

Question: ASCO has advanced its own Patient-Centered Oncology Payment model. What are the main elements of this strategy and how does it differ from the Oncology Care Model?

Dr. Grubbs: The Patient-Centered Oncology Payment (PCOP) model is the result of input from a wide group of stakeholders, including providers, employers, and managed care organizations. In the coming months, ASCO will publish an updated copy of the PCOP model.

Our review of OCM is that the included prediction model and two-sided risk options place small, rural, and certain other practices at considerable peril because of imprecise and inconsistent cost predictions. PCOP takes a different approach. Rather than requiring that practices take on actuarial risk for total cost of care, PCOP includes a three-part performance methodology. Practices are measured on adherence to clinical treatment pathways; electronically capturable quality measures; and select, targeted cost-of-care measures. Practices that perform well in PCOP’s performance methodology receive increased incentive payments to fund further advancements in care.

Question: The PCOP model includes payments to oncology practices for participation in clinical trials. How might that drive a change in behavior in a typical practice?

Dr. Grubbs: Practices that enroll patients in clinical trials have the same or greater storage and handling requirements as those treated with standard treatments, yet forgo revenue associated with the Medicare Part B average sales price methodology. PCOP ensures that such practices are not disadvantaged for supporting clinical research.

Question: Are there other areas – such as tumor biomarker tests – in which a tailored payment approach would improve the quality of care?

Dr. Grubbs: Recent studies have shown that not all patients receive the appropriate genomic profiling and other tests necessary to ensure that they benefit from personalized therapies. Clinical treatment pathways have the ability to inform and measure diagnostic completeness to improve the quality of care.

Question: What are the barriers that are keeping oncology practices from participating in alternative payment models designed to improve care?

Dr. Grubbs: Some alternative payment models, such as OCM, place a high administrative burden on their participants. Manual reporting of measures and clinical data, complicated billing requirements, and lack of support from electronic health record vendors create barriers for expanded participation. Practices are also concerned about the financial risks placed upon participants; it is impractical to expect that physicians hire actuaries in order to participate in a Medicare program.

ASCO has offered support for OCM practices through its PracticeNET benchmarking program, but we have also proposed PCOP as an appropriate alternative, applicable to practices of all types and sizes.

Dr. Grubbs joined ASCO in 2015 as the vice president of the newly launched clinical affairs department. Before joining ASCO, Dr. Grubbs worked as a community oncologist and managing partner at Medical Oncology Hematology Consultants in Newark, Del. Dr. Grubbs is a volunteer and the principal investigator of the Delaware Christiana Care National Cancer Institute Community Oncology Research Program. Dr. Grubbs reported having no financial disclosures.

The Oncology Care Model is a value-based payment approach aimed at encouraging coordinated cancer care through targeted bonus payments to practices. The payment experiment was launched by the Centers for Medicare & Medicaid Services in 2016 and now includes 175 practices and 10 payers. It is set to end in 2021. As agency officials consider whether to continue the program, Stephen S. Grubbs, MD, vice president for clinical affairs at the American Society of Clinical Oncology, weighs in on the model’s track record and its future.

utah778/Thinkstock

Question: How would you rate the Oncology Care Model in helping to drive practice transformation?

Dr. Grubbs: Participants in the Oncology Care Model (OCM) have demonstrated improved care coordination, psychosocial support, use of risk assessment tools, and other strategies to lower costs and adverse events. Over the past 2 years, ASCO has accepted numerous posters, articles, and abstracts from OCM participants on their outstanding work to advance cancer care delivery.

Question: Should the model be extended beyond 2021?

Dr. Grubbs: Changes to the model are necessary prior to a significant extension or expansion. Some have suggested that CMS extend OCM for an additional year with current participants. This would give CMS time to consider input from all stakeholders on its eventual replacement.

Question: What additional resources or payments do oncology practices need to be more successful in meeting the goals of the Oncology Care Model?

Dr. Grubbs: OCM has shown that by providing oncologists with payment for care management – OCM participants receive $160 per patient, per month – the results are better care coordination and reduced hospital and emergency department visits. If CMS chooses to expand payments to all oncology providers, we could expect to see improved care for cancer patients.

Question: ASCO has advanced its own Patient-Centered Oncology Payment model. What are the main elements of this strategy and how does it differ from the Oncology Care Model?

Dr. Grubbs: The Patient-Centered Oncology Payment (PCOP) model is the result of input from a wide group of stakeholders, including providers, employers, and managed care organizations. In the coming months, ASCO will publish an updated copy of the PCOP model.

Our review of OCM is that the included prediction model and two-sided risk options place small, rural, and certain other practices at considerable peril because of imprecise and inconsistent cost predictions. PCOP takes a different approach. Rather than requiring that practices take on actuarial risk for total cost of care, PCOP includes a three-part performance methodology. Practices are measured on adherence to clinical treatment pathways; electronically capturable quality measures; and select, targeted cost-of-care measures. Practices that perform well in PCOP’s performance methodology receive increased incentive payments to fund further advancements in care.

Question: The PCOP model includes payments to oncology practices for participation in clinical trials. How might that drive a change in behavior in a typical practice?

Dr. Grubbs: Practices that enroll patients in clinical trials have the same or greater storage and handling requirements as those treated with standard treatments, yet forgo revenue associated with the Medicare Part B average sales price methodology. PCOP ensures that such practices are not disadvantaged for supporting clinical research.

Question: Are there other areas – such as tumor biomarker tests – in which a tailored payment approach would improve the quality of care?

Dr. Grubbs: Recent studies have shown that not all patients receive the appropriate genomic profiling and other tests necessary to ensure that they benefit from personalized therapies. Clinical treatment pathways have the ability to inform and measure diagnostic completeness to improve the quality of care.

Question: What are the barriers that are keeping oncology practices from participating in alternative payment models designed to improve care?

Dr. Grubbs: Some alternative payment models, such as OCM, place a high administrative burden on their participants. Manual reporting of measures and clinical data, complicated billing requirements, and lack of support from electronic health record vendors create barriers for expanded participation. Practices are also concerned about the financial risks placed upon participants; it is impractical to expect that physicians hire actuaries in order to participate in a Medicare program.

ASCO has offered support for OCM practices through its PracticeNET benchmarking program, but we have also proposed PCOP as an appropriate alternative, applicable to practices of all types and sizes.

Dr. Grubbs joined ASCO in 2015 as the vice president of the newly launched clinical affairs department. Before joining ASCO, Dr. Grubbs worked as a community oncologist and managing partner at Medical Oncology Hematology Consultants in Newark, Del. Dr. Grubbs is a volunteer and the principal investigator of the Delaware Christiana Care National Cancer Institute Community Oncology Research Program. Dr. Grubbs reported having no financial disclosures.

The Oncology Care Model is a value-based payment approach aimed at encouraging coordinated cancer care through targeted bonus payments to practices. The payment experiment was launched by the Centers for Medicare & Medicaid Services in 2016 and now includes 175 practices and 10 payers. It is set to end in 2021. As agency officials consider whether to continue the program, Stephen S. Grubbs, MD, vice president for clinical affairs at the American Society of Clinical Oncology, weighs in on the model’s track record and its future.

utah778/Thinkstock

Question: How would you rate the Oncology Care Model in helping to drive practice transformation?

Dr. Grubbs: Participants in the Oncology Care Model (OCM) have demonstrated improved care coordination, psychosocial support, use of risk assessment tools, and other strategies to lower costs and adverse events. Over the past 2 years, ASCO has accepted numerous posters, articles, and abstracts from OCM participants on their outstanding work to advance cancer care delivery.

Question: Should the model be extended beyond 2021?

Dr. Grubbs: Changes to the model are necessary prior to a significant extension or expansion. Some have suggested that CMS extend OCM for an additional year with current participants. This would give CMS time to consider input from all stakeholders on its eventual replacement.

Question: What additional resources or payments do oncology practices need to be more successful in meeting the goals of the Oncology Care Model?

Dr. Grubbs: OCM has shown that by providing oncologists with payment for care management – OCM participants receive $160 per patient, per month – the results are better care coordination and reduced hospital and emergency department visits. If CMS chooses to expand payments to all oncology providers, we could expect to see improved care for cancer patients.

Question: ASCO has advanced its own Patient-Centered Oncology Payment model. What are the main elements of this strategy and how does it differ from the Oncology Care Model?

Dr. Grubbs: The Patient-Centered Oncology Payment (PCOP) model is the result of input from a wide group of stakeholders, including providers, employers, and managed care organizations. In the coming months, ASCO will publish an updated copy of the PCOP model.

Our review of OCM is that the included prediction model and two-sided risk options place small, rural, and certain other practices at considerable peril because of imprecise and inconsistent cost predictions. PCOP takes a different approach. Rather than requiring that practices take on actuarial risk for total cost of care, PCOP includes a three-part performance methodology. Practices are measured on adherence to clinical treatment pathways; electronically capturable quality measures; and select, targeted cost-of-care measures. Practices that perform well in PCOP’s performance methodology receive increased incentive payments to fund further advancements in care.

Question: The PCOP model includes payments to oncology practices for participation in clinical trials. How might that drive a change in behavior in a typical practice?

Dr. Grubbs: Practices that enroll patients in clinical trials have the same or greater storage and handling requirements as those treated with standard treatments, yet forgo revenue associated with the Medicare Part B average sales price methodology. PCOP ensures that such practices are not disadvantaged for supporting clinical research.

Question: Are there other areas – such as tumor biomarker tests – in which a tailored payment approach would improve the quality of care?

Dr. Grubbs: Recent studies have shown that not all patients receive the appropriate genomic profiling and other tests necessary to ensure that they benefit from personalized therapies. Clinical treatment pathways have the ability to inform and measure diagnostic completeness to improve the quality of care.

Question: What are the barriers that are keeping oncology practices from participating in alternative payment models designed to improve care?

Dr. Grubbs: Some alternative payment models, such as OCM, place a high administrative burden on their participants. Manual reporting of measures and clinical data, complicated billing requirements, and lack of support from electronic health record vendors create barriers for expanded participation. Practices are also concerned about the financial risks placed upon participants; it is impractical to expect that physicians hire actuaries in order to participate in a Medicare program.

ASCO has offered support for OCM practices through its PracticeNET benchmarking program, but we have also proposed PCOP as an appropriate alternative, applicable to practices of all types and sizes.

Dr. Grubbs joined ASCO in 2015 as the vice president of the newly launched clinical affairs department. Before joining ASCO, Dr. Grubbs worked as a community oncologist and managing partner at Medical Oncology Hematology Consultants in Newark, Del. Dr. Grubbs is a volunteer and the principal investigator of the Delaware Christiana Care National Cancer Institute Community Oncology Research Program. Dr. Grubbs reported having no financial disclosures.

BOSTON – Children who have recurrence of primary sclerosing cholangitis after liver transplant tend to be younger and have more rapidly progressive disease, based on an international retrospective analysis.

Will Pass/MDedge News

Within 5 years of transplant, the probability of primary sclerosing cholangitis (PSC) recurrence in pediatric patients is 26%, reported lead author Mercedes Martinez, MD, of Columbia University, New York, and colleagues.

“The aim of our study was to identify risk factors for primary sclerosing cholangitis recurrence following transplant,” Dr. Martinez said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. This may be the largest pediatric study evaluating recurrent PSC to date, she added.

The investigators drew data from 35 centers around the world via the Pediatric PSC Consortium database. Recurrence was defined by cholestatic biochemistry with nonanastomotic biliary strictures and beading of bile ducts on cholangiography. Recurrences caused by hepatic artery thrombosis or chronic rejection were excluded, as were any cases that recurred within 6 months of transplant.

The final analysis included 149 patients with a median age at diagnosis and liver transplant of 12 years and 15.4 years, respectively. Of these, 31 patients had recurrence after a median of 3.3 years. A closer look at the data showed that recurrence was linked with younger median age at time of transplant (13.2 vs. 16.2 years). In cases of recurrence, PSC was generally more aggressive prior to transplant, with a shorter interval between diagnosis and transplant (1.6 vs. 4.1 years), higher total bilirubin (7.8 vs. 3.8 mg/dL), and higher ALT (118 vs. 62 U/L). Furthermore, almost half of the patients (45%) who had recurrence also had pretransplant autoimmune hepatitis overlap, compared with approximately one-quarter of the patients (27%) who did not have recurrence, although this trend was not statistically significant (P = .06).

Recurrent PSC was also associated with poorer outcomes; almost half of those with recurrence (48%) were relisted for liver transplant, developed portal hypertension, or died within 2 years of diagnosis. Mean rejection rates were higher in recurrent versus nonrecurrent cases (3 vs. 1); recurrent cases also had shorter time until rejection (3 vs. 6 months) and greater prevalence of rejection that was refractory to steroids (23% vs. 12%). Moreover, a significantly greater proportion of patients with recurrence had Epstein-Barr viremia (41% vs. 21%).

Dr. Martinez noted that ongoing therapy involving mammalian target of rapamycin inhibition was associated with lower rates of recurrence and suggested that this deserves further investigation; however, owing to small population size, she urged a cautious interpretation of this finding.

“We have to do prospective research,” Dr. Martinez said, emphasizing that tissue immunophenotyping was needed, as a better understanding of underlying immune processes and disease subtypes may open doors to more effective therapies.

The investigators disclosed relationships with Gilead, Merck, Novartis, and others.

SOURCE: Martinez M et al. The Liver Meeting 2019, Abstract 44.

BOSTON – Children who have recurrence of primary sclerosing cholangitis after liver transplant tend to be younger and have more rapidly progressive disease, based on an international retrospective analysis.

Will Pass/MDedge News

Within 5 years of transplant, the probability of primary sclerosing cholangitis (PSC) recurrence in pediatric patients is 26%, reported lead author Mercedes Martinez, MD, of Columbia University, New York, and colleagues.

“The aim of our study was to identify risk factors for primary sclerosing cholangitis recurrence following transplant,” Dr. Martinez said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. This may be the largest pediatric study evaluating recurrent PSC to date, she added.

The investigators drew data from 35 centers around the world via the Pediatric PSC Consortium database. Recurrence was defined by cholestatic biochemistry with nonanastomotic biliary strictures and beading of bile ducts on cholangiography. Recurrences caused by hepatic artery thrombosis or chronic rejection were excluded, as were any cases that recurred within 6 months of transplant.

The final analysis included 149 patients with a median age at diagnosis and liver transplant of 12 years and 15.4 years, respectively. Of these, 31 patients had recurrence after a median of 3.3 years. A closer look at the data showed that recurrence was linked with younger median age at time of transplant (13.2 vs. 16.2 years). In cases of recurrence, PSC was generally more aggressive prior to transplant, with a shorter interval between diagnosis and transplant (1.6 vs. 4.1 years), higher total bilirubin (7.8 vs. 3.8 mg/dL), and higher ALT (118 vs. 62 U/L). Furthermore, almost half of the patients (45%) who had recurrence also had pretransplant autoimmune hepatitis overlap, compared with approximately one-quarter of the patients (27%) who did not have recurrence, although this trend was not statistically significant (P = .06).

Recurrent PSC was also associated with poorer outcomes; almost half of those with recurrence (48%) were relisted for liver transplant, developed portal hypertension, or died within 2 years of diagnosis. Mean rejection rates were higher in recurrent versus nonrecurrent cases (3 vs. 1); recurrent cases also had shorter time until rejection (3 vs. 6 months) and greater prevalence of rejection that was refractory to steroids (23% vs. 12%). Moreover, a significantly greater proportion of patients with recurrence had Epstein-Barr viremia (41% vs. 21%).

Dr. Martinez noted that ongoing therapy involving mammalian target of rapamycin inhibition was associated with lower rates of recurrence and suggested that this deserves further investigation; however, owing to small population size, she urged a cautious interpretation of this finding.

“We have to do prospective research,” Dr. Martinez said, emphasizing that tissue immunophenotyping was needed, as a better understanding of underlying immune processes and disease subtypes may open doors to more effective therapies.

The investigators disclosed relationships with Gilead, Merck, Novartis, and others.

SOURCE: Martinez M et al. The Liver Meeting 2019, Abstract 44.

BOSTON – Children who have recurrence of primary sclerosing cholangitis after liver transplant tend to be younger and have more rapidly progressive disease, based on an international retrospective analysis.

Will Pass/MDedge News

Within 5 years of transplant, the probability of primary sclerosing cholangitis (PSC) recurrence in pediatric patients is 26%, reported lead author Mercedes Martinez, MD, of Columbia University, New York, and colleagues.

“The aim of our study was to identify risk factors for primary sclerosing cholangitis recurrence following transplant,” Dr. Martinez said during a presentation at the annual meeting of the American Association for the Study of Liver Diseases. This may be the largest pediatric study evaluating recurrent PSC to date, she added.

The investigators drew data from 35 centers around the world via the Pediatric PSC Consortium database. Recurrence was defined by cholestatic biochemistry with nonanastomotic biliary strictures and beading of bile ducts on cholangiography. Recurrences caused by hepatic artery thrombosis or chronic rejection were excluded, as were any cases that recurred within 6 months of transplant.

The final analysis included 149 patients with a median age at diagnosis and liver transplant of 12 years and 15.4 years, respectively. Of these, 31 patients had recurrence after a median of 3.3 years. A closer look at the data showed that recurrence was linked with younger median age at time of transplant (13.2 vs. 16.2 years). In cases of recurrence, PSC was generally more aggressive prior to transplant, with a shorter interval between diagnosis and transplant (1.6 vs. 4.1 years), higher total bilirubin (7.8 vs. 3.8 mg/dL), and higher ALT (118 vs. 62 U/L). Furthermore, almost half of the patients (45%) who had recurrence also had pretransplant autoimmune hepatitis overlap, compared with approximately one-quarter of the patients (27%) who did not have recurrence, although this trend was not statistically significant (P = .06).

Recurrent PSC was also associated with poorer outcomes; almost half of those with recurrence (48%) were relisted for liver transplant, developed portal hypertension, or died within 2 years of diagnosis. Mean rejection rates were higher in recurrent versus nonrecurrent cases (3 vs. 1); recurrent cases also had shorter time until rejection (3 vs. 6 months) and greater prevalence of rejection that was refractory to steroids (23% vs. 12%). Moreover, a significantly greater proportion of patients with recurrence had Epstein-Barr viremia (41% vs. 21%).

Dr. Martinez noted that ongoing therapy involving mammalian target of rapamycin inhibition was associated with lower rates of recurrence and suggested that this deserves further investigation; however, owing to small population size, she urged a cautious interpretation of this finding.

“We have to do prospective research,” Dr. Martinez said, emphasizing that tissue immunophenotyping was needed, as a better understanding of underlying immune processes and disease subtypes may open doors to more effective therapies.

The investigators disclosed relationships with Gilead, Merck, Novartis, and others.

SOURCE: Martinez M et al. The Liver Meeting 2019, Abstract 44.

NATIONAL HARBOR, MD. – If the United States does not step up and create a thriving biosimilars market soon, it risks destroying the market not only domestically but internationally as well.

Gregory Twachtman/MDedge News

This was the warning Gillian Woollett, senior vice president at Avalere, provided to attendees at the annual meeting of the Academy of Managed Care Pharmacy.

She prefaced her warning by quoting Alex Azar, secretary of Health & Human Services, who said that those “trying to hold back biosimilars are simply on the wrong side of history,” though Ms. Woollett said they “may be on the right side of the current economic model in the United States.”

And despite the probusiness, procompetition philosophy of current HHS leadership, there has been very little movement on creating a competitive market for biosimilars in the United States, evidenced by the very expensive regulatory requirements that biosimilar manufacturers need to meet in order to get products to market.

“It’s not that we won’t have competition in the U.S.,” she said. “I think we will. We do have that innovation. ... It’s just that biosimilars may not ultimately be part of that competition. And for that, we will pay a price, and I actually think the whole world will pay a price because if we are not providing the [return on investment], I am not sure the other markets can sustain it.”

One issue biosimilars have is the lack of recognition of the value that they bring.

“That biosimilars offer the same clinical outcomes at a lower price is yet to be a recognized value,” she said. “To me that’s a really surprising situation in the United States.”

Ms. Woollett disclosed no relevant conflicts of interest.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health care providers and patients about biosimilars and how they can be used for IBD patient care. Learn more at www.gastro.org/biosimilars.

[email protected]

NATIONAL HARBOR, MD. – If the United States does not step up and create a thriving biosimilars market soon, it risks destroying the market not only domestically but internationally as well.

Gregory Twachtman/MDedge News

This was the warning Gillian Woollett, senior vice president at Avalere, provided to attendees at the annual meeting of the Academy of Managed Care Pharmacy.

She prefaced her warning by quoting Alex Azar, secretary of Health & Human Services, who said that those “trying to hold back biosimilars are simply on the wrong side of history,” though Ms. Woollett said they “may be on the right side of the current economic model in the United States.”

And despite the probusiness, procompetition philosophy of current HHS leadership, there has been very little movement on creating a competitive market for biosimilars in the United States, evidenced by the very expensive regulatory requirements that biosimilar manufacturers need to meet in order to get products to market.

“It’s not that we won’t have competition in the U.S.,” she said. “I think we will. We do have that innovation. ... It’s just that biosimilars may not ultimately be part of that competition. And for that, we will pay a price, and I actually think the whole world will pay a price because if we are not providing the [return on investment], I am not sure the other markets can sustain it.”

One issue biosimilars have is the lack of recognition of the value that they bring.

“That biosimilars offer the same clinical outcomes at a lower price is yet to be a recognized value,” she said. “To me that’s a really surprising situation in the United States.”

Ms. Woollett disclosed no relevant conflicts of interest.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health care providers and patients about biosimilars and how they can be used for IBD patient care. Learn more at www.gastro.org/biosimilars.

[email protected]

NATIONAL HARBOR, MD. – If the United States does not step up and create a thriving biosimilars market soon, it risks destroying the market not only domestically but internationally as well.

Gregory Twachtman/MDedge News

This was the warning Gillian Woollett, senior vice president at Avalere, provided to attendees at the annual meeting of the Academy of Managed Care Pharmacy.

She prefaced her warning by quoting Alex Azar, secretary of Health & Human Services, who said that those “trying to hold back biosimilars are simply on the wrong side of history,” though Ms. Woollett said they “may be on the right side of the current economic model in the United States.”

And despite the probusiness, procompetition philosophy of current HHS leadership, there has been very little movement on creating a competitive market for biosimilars in the United States, evidenced by the very expensive regulatory requirements that biosimilar manufacturers need to meet in order to get products to market.

“It’s not that we won’t have competition in the U.S.,” she said. “I think we will. We do have that innovation. ... It’s just that biosimilars may not ultimately be part of that competition. And for that, we will pay a price, and I actually think the whole world will pay a price because if we are not providing the [return on investment], I am not sure the other markets can sustain it.”

One issue biosimilars have is the lack of recognition of the value that they bring.

“That biosimilars offer the same clinical outcomes at a lower price is yet to be a recognized value,” she said. “To me that’s a really surprising situation in the United States.”

Ms. Woollett disclosed no relevant conflicts of interest.

To prepare for the entry of biosimilars to the market, AGA is taking the lead in educating health care providers and patients about biosimilars and how they can be used for IBD patient care. Learn more at www.gastro.org/biosimilars.

[email protected]

MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

MADRID – Oral apremilast’s beneficial effects on Behçet’s disease oral ulcer disease severity and patient quality of life were sustained through week 64 of the long-term extension phase of the pivotal RELIEF trial, Alfred Mahr, MD, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

“We now have strong evidence that apremilast is an effective and safe therapy to treat oral ulcers in patients with Behçet’s syndrome. I think this is a major advance in the field,” declared Dr. Mahr, a rheumatologist at St. Gallen (Switzerland) Cantonal Hospital.

Based largely upon the results of the 12-week, double-blind portion of the phase 3 RELIEF trial, the Food and Drug Administration approved apremilast (Otezla) for the treatment of oral ulcers in patients with Behçet’s disease in the summer of 2019.

The safety profile of the oral phosphodiesterase-4 inhibitor was as seen in other studies, including in patients with psoriatic arthritis, an FDA-approved indication for the drug since 2014. The main side effects in the long-term extension of RELIEF were diarrhea and nausea, typically mild or moderate in nature and roughly twice as frequent as in placebo-treated controls in the double-blind study phase.

“At the end of the day, at week 64, only 12% of patients treated with apremilast during the entire 64 weeks discontinued the drug due to a treatment-emergent adverse event, which I believe is a good indicator of the safety of this medication,” the rheumatologist said. “The overall feeling is that the benefit-to-risk ratio is very good and it’s a safe drug to prescribe.”

At the close of the initial 12-week, double-blind phase of RELIEF, 178 of the original 207 participants elected to enter the long-term extension, either staying on apremilast at 30 mg twice a day for an additional 52 weeks or switching to that regimen from placebo.

The focus of the long-term extension was on disease activity and quality of life outcomes. The results in patients who had switched from placebo to apremilast after 12 weeks proved to be reassuringly similar to outcomes in patients on the drug for the full duration. For example, the mean improvement on the patient-reported Behçet’s Syndrome Activity Scale was 18.6 points after 12 weeks of double-blind apremilast, 16.9 points after 64 weeks of continuous apremilast, and 16.8 points with 12 weeks of placebo followed by 52 weeks of active therapy.

After 12 weeks of double-blind apremilast, patients averaged a 3.4-point improvement on the Behçet’s Disease Quality of Life measure. After 64 weeks on the drug, the improvement over baseline was 3.6 points, while in the switch group it was 3.4 points. Similarly, on all three components of the SF-36 quality of life metric, the continuous apremilast group showed maintenance of effect from week 12 to week 64, while the placebo-to-apremilast group caught up. The same was true with regards to the Behçet’s Disease Current Activity Index, which encompasses measures of both the patient’s and clinician’s perception of disease activity.

At the outset of the RELIEF trial, participants averaged four oral ulcers. At week 64, the continuous apremilast group averaged 1.4 and the switch group 0.8, a nonsignificant difference.

Asked if apremilast had a favorable impact upon other manifestations of Behçet’s disease besides the oral ulcers, Dr. Mahr replied, “This is a very good question. People often wonder about it. We do, too. But this trial was not designed to capture less common manifestations of Behçet’s syndrome, such as genital ulcers. There have been some analyses done, but the number of patients who had genital ulcers at 12 weeks were very few. The same was true for eye manifestations. There was sort of a signal that it works, but we can’t prove it in a placebo-controlled trial.”

Dr. Mahr reported receiving research funding from and serving as a consultant to Celgene, the study sponsor.

[email protected]

ANSWER

The radiograph does not demonstrate any evidence of infiltrate or pleural effusion. However, of note is a rather large lytic lesion involving the posterior aspect of the right fourth rib. This finding is very concerning for either a primary bone neoplasm or (more likely) a metastatic one.

The patient denied any history of cancer. She was promptly referred to Hematology/Oncology for further evaluation and workup. At last update, she had undergone a bone marrow biopsy, with preliminary pathology results suggestive of a plasma cell neoplasm.

ANSWER

The radiograph does not demonstrate any evidence of infiltrate or pleural effusion. However, of note is a rather large lytic lesion involving the posterior aspect of the right fourth rib. This finding is very concerning for either a primary bone neoplasm or (more likely) a metastatic one.

The patient denied any history of cancer. She was promptly referred to Hematology/Oncology for further evaluation and workup. At last update, she had undergone a bone marrow biopsy, with preliminary pathology results suggestive of a plasma cell neoplasm.

ANSWER

The radiograph does not demonstrate any evidence of infiltrate or pleural effusion. However, of note is a rather large lytic lesion involving the posterior aspect of the right fourth rib. This finding is very concerning for either a primary bone neoplasm or (more likely) a metastatic one.

The patient denied any history of cancer. She was promptly referred to Hematology/Oncology for further evaluation and workup. At last update, she had undergone a bone marrow biopsy, with preliminary pathology results suggestive of a plasma cell neoplasm.

Cholinergic neurons in the nucleus basalis of Meynert appear more susceptible to neurofibrillary tangles and neuronal destruction in women, patients carrying the apolipoprotein E–epsilon 4 (APOE4) allele, and people with hippocampal-sparing Alzheimer’s disease, a subtype characterized by early onset and rapid cognitive decline.

Kheng guan Toh/Thinkstock

Those findings and others from a postmortem study published in JAMA Neurology also suggests that the nucleus basalis of Meynert (nbM) could be the first place that neuronal damage appears in Alzheimer’s disease (AD), according to first author Fadi S. Hanna Al-Shaikh and colleagues.

The study also confirmed the authors’ previous categorization of three AD subtypes: early-onset, rapidly declining hippocampal-sparing AD (HpSp), typical sporadic AD, and limbic predominant AD, a later-onset form with a slower rate of decline.

“We observed a wave of vulnerability in which the exacerbation of nbM neurofibrillary tangles [NFTs] in HpSp AD may leave the cortex more vulnerable to [tangle] accumulation, perhaps via a biologically accelerated process or through a mechanism of disinhibition,” wrote Mr. Al-Shaikh, of the Mayo Clinic, Jacksonville, Fla., and colleagues. “By contrast, the limbic predominant AD cases had an exacerbation of areas vulnerable early in the Braak-like pattern of NFT accumulation, perhaps via a biologically restrictive process that relatively confines pathology to limbic areas.”

The nbM is of interest to researchers because 90% of its neurons are cholinergic with cortical penetration. “Postmortem studies of AD and more recent neuroimaging studies provide evidence that involvement of the nucleus basalis of Meynert may be critical and early in the molecular cascade of events,” the authors said. “The accumulation of NFTs in the nbM may precede entorhinal cortex and locus coeruleus involvement, making the nbM potentially one of the earliest sites where NFT accumulation occurs.”

Previously, this team had identified three AD subtypes based on patterns of corticolimbic neurofibrillary tangling. In HpSp, the hippocampus is relatively spared, while the cortex has a greater number of tangles. In limbic predominant AD, the cortex is relatively spared, and the hippocampus is severely involved. Typical AD shows the expected patterns of hippocampal and cortical tangling.

Cases in this study came from the Florida Autopsied Multi-Ethnic (FLAME) cohort, comprising 1,361 brain tissue samples from confirmed AD cases and 103 nondemented controls. The investigators sought to understand the patterns of neuronal demise in the nbM, and any associations with clinical signs, demographics, and the recently described three subtypes.

In the cohort, AD subtypes included 175 with HpSp, 1,014 with typical AD, and 172 with limbic predominant AD. Patients with HpSp were the youngest, with a median disease onset age of 65 years, compared with 71 years in typical AD and 78 in limbic predominant. There were fewer women in the HpSp group (35%), compared with the typical AD group (54%) and the limbic group (70%). More patients with HpSp had atypical presentation (38%) in comparison with typical (11%) and limbic predominant AD (2%). But patients with HpSp were less likely to be APOE4 positive (46%), whereas those with limbic predominant AD were most likely to be APOE4 positive (72%).

Cognitively, HpSp patients declined more rapidly, losing a median of 4 points per year on the Mini Mental State Exam (MMSE), compared with 2 and 1 points in those with typical and limbic predominant AD. At death, the HpSp patients had a median MMSE score of 7, versus 13 in the typical AD group and 18 in the limbic group.

Patients with HpSp had the highest concentration of tangles and the lowest neuronal density in the nbM. Limbic predominant cases had the lowest tangle burden and the highest neuronal density. Typical AD cases lay between these extremes on both measures.

A multivariate regression analysis determined the overlap of neuronal findings and AD subtypes. A younger age at symptom onset was significantly associated with higher tangle counts in the nbM regions among patients with HpSp. In women with typical AD, there were 2.5 times more tangles than in men. APOE4 carriers had 1.3 times more tangles than did noncarriers.

There were also associations with cognition. “For every 10-point decrease in final MMSE of typical AD cases, the number of nbM NFTs was expected to increase by 1.8,” the authors wrote.

Although limbic predominant AD wasn’t associated with any clinical or demographic variables in this analysis, it was associated with neuronal changes in the nbM. “For every 10 years’ younger age at onset, the number of neurons was expected to be lower by 4.6 [per mm²]. … In addition, limbic predominant cases were observed to have 4.3 [per mm²] fewer neurons for every 10-point decrease in MMSE,” the authors said.

This study was supported by the National Institute on Aging, the Florida Department of Health, the Ed and Ethel Moore Alzheimer’s Disease Research Program, a Gerstner Family Career Development Award, and the Alzheimer’s Association. Two authors reported financial relationships with industry outside the submitted work.

[email protected]

SOURCE: Al Shaikh FSH et al. JAMA Neurol. 2019 Oct 28. doi: 10.1001/jamaneurol.2019.3606.

Cholinergic neurons in the nucleus basalis of Meynert appear more susceptible to neurofibrillary tangles and neuronal destruction in women, patients carrying the apolipoprotein E–epsilon 4 (APOE4) allele, and people with hippocampal-sparing Alzheimer’s disease, a subtype characterized by early onset and rapid cognitive decline.

Kheng guan Toh/Thinkstock

Those findings and others from a postmortem study published in JAMA Neurology also suggests that the nucleus basalis of Meynert (nbM) could be the first place that neuronal damage appears in Alzheimer’s disease (AD), according to first author Fadi S. Hanna Al-Shaikh and colleagues.

The study also confirmed the authors’ previous categorization of three AD subtypes: early-onset, rapidly declining hippocampal-sparing AD (HpSp), typical sporadic AD, and limbic predominant AD, a later-onset form with a slower rate of decline.

“We observed a wave of vulnerability in which the exacerbation of nbM neurofibrillary tangles [NFTs] in HpSp AD may leave the cortex more vulnerable to [tangle] accumulation, perhaps via a biologically accelerated process or through a mechanism of disinhibition,” wrote Mr. Al-Shaikh, of the Mayo Clinic, Jacksonville, Fla., and colleagues. “By contrast, the limbic predominant AD cases had an exacerbation of areas vulnerable early in the Braak-like pattern of NFT accumulation, perhaps via a biologically restrictive process that relatively confines pathology to limbic areas.”

The nbM is of interest to researchers because 90% of its neurons are cholinergic with cortical penetration. “Postmortem studies of AD and more recent neuroimaging studies provide evidence that involvement of the nucleus basalis of Meynert may be critical and early in the molecular cascade of events,” the authors said. “The accumulation of NFTs in the nbM may precede entorhinal cortex and locus coeruleus involvement, making the nbM potentially one of the earliest sites where NFT accumulation occurs.”

Previously, this team had identified three AD subtypes based on patterns of corticolimbic neurofibrillary tangling. In HpSp, the hippocampus is relatively spared, while the cortex has a greater number of tangles. In limbic predominant AD, the cortex is relatively spared, and the hippocampus is severely involved. Typical AD shows the expected patterns of hippocampal and cortical tangling.

Cases in this study came from the Florida Autopsied Multi-Ethnic (FLAME) cohort, comprising 1,361 brain tissue samples from confirmed AD cases and 103 nondemented controls. The investigators sought to understand the patterns of neuronal demise in the nbM, and any associations with clinical signs, demographics, and the recently described three subtypes.

In the cohort, AD subtypes included 175 with HpSp, 1,014 with typical AD, and 172 with limbic predominant AD. Patients with HpSp were the youngest, with a median disease onset age of 65 years, compared with 71 years in typical AD and 78 in limbic predominant. There were fewer women in the HpSp group (35%), compared with the typical AD group (54%) and the limbic group (70%). More patients with HpSp had atypical presentation (38%) in comparison with typical (11%) and limbic predominant AD (2%). But patients with HpSp were less likely to be APOE4 positive (46%), whereas those with limbic predominant AD were most likely to be APOE4 positive (72%).

Cognitively, HpSp patients declined more rapidly, losing a median of 4 points per year on the Mini Mental State Exam (MMSE), compared with 2 and 1 points in those with typical and limbic predominant AD. At death, the HpSp patients had a median MMSE score of 7, versus 13 in the typical AD group and 18 in the limbic group.

Patients with HpSp had the highest concentration of tangles and the lowest neuronal density in the nbM. Limbic predominant cases had the lowest tangle burden and the highest neuronal density. Typical AD cases lay between these extremes on both measures.

A multivariate regression analysis determined the overlap of neuronal findings and AD subtypes. A younger age at symptom onset was significantly associated with higher tangle counts in the nbM regions among patients with HpSp. In women with typical AD, there were 2.5 times more tangles than in men. APOE4 carriers had 1.3 times more tangles than did noncarriers.

There were also associations with cognition. “For every 10-point decrease in final MMSE of typical AD cases, the number of nbM NFTs was expected to increase by 1.8,” the authors wrote.

Although limbic predominant AD wasn’t associated with any clinical or demographic variables in this analysis, it was associated with neuronal changes in the nbM. “For every 10 years’ younger age at onset, the number of neurons was expected to be lower by 4.6 [per mm²]. … In addition, limbic predominant cases were observed to have 4.3 [per mm²] fewer neurons for every 10-point decrease in MMSE,” the authors said.

This study was supported by the National Institute on Aging, the Florida Department of Health, the Ed and Ethel Moore Alzheimer’s Disease Research Program, a Gerstner Family Career Development Award, and the Alzheimer’s Association. Two authors reported financial relationships with industry outside the submitted work.

[email protected]

SOURCE: Al Shaikh FSH et al. JAMA Neurol. 2019 Oct 28. doi: 10.1001/jamaneurol.2019.3606.

Cholinergic neurons in the nucleus basalis of Meynert appear more susceptible to neurofibrillary tangles and neuronal destruction in women, patients carrying the apolipoprotein E–epsilon 4 (APOE4) allele, and people with hippocampal-sparing Alzheimer’s disease, a subtype characterized by early onset and rapid cognitive decline.

Kheng guan Toh/Thinkstock

Those findings and others from a postmortem study published in JAMA Neurology also suggests that the nucleus basalis of Meynert (nbM) could be the first place that neuronal damage appears in Alzheimer’s disease (AD), according to first author Fadi S. Hanna Al-Shaikh and colleagues.

The study also confirmed the authors’ previous categorization of three AD subtypes: early-onset, rapidly declining hippocampal-sparing AD (HpSp), typical sporadic AD, and limbic predominant AD, a later-onset form with a slower rate of decline.

“We observed a wave of vulnerability in which the exacerbation of nbM neurofibrillary tangles [NFTs] in HpSp AD may leave the cortex more vulnerable to [tangle] accumulation, perhaps via a biologically accelerated process or through a mechanism of disinhibition,” wrote Mr. Al-Shaikh, of the Mayo Clinic, Jacksonville, Fla., and colleagues. “By contrast, the limbic predominant AD cases had an exacerbation of areas vulnerable early in the Braak-like pattern of NFT accumulation, perhaps via a biologically restrictive process that relatively confines pathology to limbic areas.”

The nbM is of interest to researchers because 90% of its neurons are cholinergic with cortical penetration. “Postmortem studies of AD and more recent neuroimaging studies provide evidence that involvement of the nucleus basalis of Meynert may be critical and early in the molecular cascade of events,” the authors said. “The accumulation of NFTs in the nbM may precede entorhinal cortex and locus coeruleus involvement, making the nbM potentially one of the earliest sites where NFT accumulation occurs.”

Previously, this team had identified three AD subtypes based on patterns of corticolimbic neurofibrillary tangling. In HpSp, the hippocampus is relatively spared, while the cortex has a greater number of tangles. In limbic predominant AD, the cortex is relatively spared, and the hippocampus is severely involved. Typical AD shows the expected patterns of hippocampal and cortical tangling.

Cases in this study came from the Florida Autopsied Multi-Ethnic (FLAME) cohort, comprising 1,361 brain tissue samples from confirmed AD cases and 103 nondemented controls. The investigators sought to understand the patterns of neuronal demise in the nbM, and any associations with clinical signs, demographics, and the recently described three subtypes.

In the cohort, AD subtypes included 175 with HpSp, 1,014 with typical AD, and 172 with limbic predominant AD. Patients with HpSp were the youngest, with a median disease onset age of 65 years, compared with 71 years in typical AD and 78 in limbic predominant. There were fewer women in the HpSp group (35%), compared with the typical AD group (54%) and the limbic group (70%). More patients with HpSp had atypical presentation (38%) in comparison with typical (11%) and limbic predominant AD (2%). But patients with HpSp were less likely to be APOE4 positive (46%), whereas those with limbic predominant AD were most likely to be APOE4 positive (72%).

Cognitively, HpSp patients declined more rapidly, losing a median of 4 points per year on the Mini Mental State Exam (MMSE), compared with 2 and 1 points in those with typical and limbic predominant AD. At death, the HpSp patients had a median MMSE score of 7, versus 13 in the typical AD group and 18 in the limbic group.

Patients with HpSp had the highest concentration of tangles and the lowest neuronal density in the nbM. Limbic predominant cases had the lowest tangle burden and the highest neuronal density. Typical AD cases lay between these extremes on both measures.

A multivariate regression analysis determined the overlap of neuronal findings and AD subtypes. A younger age at symptom onset was significantly associated with higher tangle counts in the nbM regions among patients with HpSp. In women with typical AD, there were 2.5 times more tangles than in men. APOE4 carriers had 1.3 times more tangles than did noncarriers.

There were also associations with cognition. “For every 10-point decrease in final MMSE of typical AD cases, the number of nbM NFTs was expected to increase by 1.8,” the authors wrote.

Although limbic predominant AD wasn’t associated with any clinical or demographic variables in this analysis, it was associated with neuronal changes in the nbM. “For every 10 years’ younger age at onset, the number of neurons was expected to be lower by 4.6 [per mm²]. … In addition, limbic predominant cases were observed to have 4.3 [per mm²] fewer neurons for every 10-point decrease in MMSE,” the authors said.

This study was supported by the National Institute on Aging, the Florida Department of Health, the Ed and Ethel Moore Alzheimer’s Disease Research Program, a Gerstner Family Career Development Award, and the Alzheimer’s Association. Two authors reported financial relationships with industry outside the submitted work.

[email protected]

SOURCE: Al Shaikh FSH et al. JAMA Neurol. 2019 Oct 28. doi: 10.1001/jamaneurol.2019.3606.

The proportion of family physicians providing inpatient care dropped 26% over a recent 5-year span, and by 2017, only one of four FPs was practicing hospital medicine, according to the American Academy of Family Physicians.

The share of family physicians who provided hospital care went from 34.1% in 2013 to 25.2% in 2017, for a relative decrease of 26% that left only a quarter of FPs seeing inpatients, based on data from the annual American Board of Family Medicine certification exam application questionnaire. For the 5-year period, 46,762 individuals were included in the study sample of FPs in direct patient care.

“As observed in other domains (prenatal care, home visits, nursing home care, and obstetric care), this study adds to the evidence demonstrating contracting scope of practice among FPs,” Anuradha Jetty, MPH, of the AAFP’s Robert Graham Center in Washington, D.C., and associates said in a recent Policy Brief published in the Journal of the American Board of Family Medicine.

Much of that contraction is occurring among new family physicians who can’t “find positions that allow them to use all their expertise,” the investigators said in a separate statement. The AAFP had previously reported that about 40% of family physicians had full hospital privileges in 2018, compared with 56% in 2012.

Many new FPs now work in large multispecialty practices or hospital systems, and “[some] of these employers dictate scope of practice, limiting family physicians to coordinating outpatient care and relying on subspecialists or hospitalists to provide inpatient care,” they noted.

[email protected]

The proportion of family physicians providing inpatient care dropped 26% over a recent 5-year span, and by 2017, only one of four FPs was practicing hospital medicine, according to the American Academy of Family Physicians.

The share of family physicians who provided hospital care went from 34.1% in 2013 to 25.2% in 2017, for a relative decrease of 26% that left only a quarter of FPs seeing inpatients, based on data from the annual American Board of Family Medicine certification exam application questionnaire. For the 5-year period, 46,762 individuals were included in the study sample of FPs in direct patient care.

“As observed in other domains (prenatal care, home visits, nursing home care, and obstetric care), this study adds to the evidence demonstrating contracting scope of practice among FPs,” Anuradha Jetty, MPH, of the AAFP’s Robert Graham Center in Washington, D.C., and associates said in a recent Policy Brief published in the Journal of the American Board of Family Medicine.

Much of that contraction is occurring among new family physicians who can’t “find positions that allow them to use all their expertise,” the investigators said in a separate statement. The AAFP had previously reported that about 40% of family physicians had full hospital privileges in 2018, compared with 56% in 2012.

Many new FPs now work in large multispecialty practices or hospital systems, and “[some] of these employers dictate scope of practice, limiting family physicians to coordinating outpatient care and relying on subspecialists or hospitalists to provide inpatient care,” they noted.

[email protected]

The proportion of family physicians providing inpatient care dropped 26% over a recent 5-year span, and by 2017, only one of four FPs was practicing hospital medicine, according to the American Academy of Family Physicians.

The share of family physicians who provided hospital care went from 34.1% in 2013 to 25.2% in 2017, for a relative decrease of 26% that left only a quarter of FPs seeing inpatients, based on data from the annual American Board of Family Medicine certification exam application questionnaire. For the 5-year period, 46,762 individuals were included in the study sample of FPs in direct patient care.

“As observed in other domains (prenatal care, home visits, nursing home care, and obstetric care), this study adds to the evidence demonstrating contracting scope of practice among FPs,” Anuradha Jetty, MPH, of the AAFP’s Robert Graham Center in Washington, D.C., and associates said in a recent Policy Brief published in the Journal of the American Board of Family Medicine.

Much of that contraction is occurring among new family physicians who can’t “find positions that allow them to use all their expertise,” the investigators said in a separate statement. The AAFP had previously reported that about 40% of family physicians had full hospital privileges in 2018, compared with 56% in 2012.

Many new FPs now work in large multispecialty practices or hospital systems, and “[some] of these employers dictate scope of practice, limiting family physicians to coordinating outpatient care and relying on subspecialists or hospitalists to provide inpatient care,” they noted.

[email protected]

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

CHICAGO – Is your practice ready for telemedicine – and should you dive in?

Once you and your practice managers work through regulatory, legal, and technical details, having a robust telemedicine practice can boost patient and clinician satisfaction – and the bottom line, said Theresa Lee, MD, a gastroenterologist in private practice in Lone Tree, Colorado, speaking at the 2019 AGA Partners in Value meeting.

Kari Oakes/MDedge News

The general field of telehealth – in which images might be shared or patients might message their care team for medication refills – is a broad term, said Dr. Lee. She explained that telemedicine is narrowly defined for Medicare and Medicaid reimbursement purposes as “two-way, real-time interactive communication between the patient and the physician or practitioner at [a] distant site ... that includes, at a minimum, audio and video equipment.” This is the video visit that many people think of when they imagine telemedicine, she said.

There’s increasing acceptance of telehealth services, said Dr. Lee, with a recent online poll showing that two-thirds of those surveyed would be willing to use telehealth; this would translate to about 24 million Americans who would be potential telehealth patients. And a 2019 survey of internal medicine physicians showed that more than half are working in practices in which telehealth is used in some capacity. Both patients and clinicians can benefit in a telehealth relationship, said Dr. Lee. The lack of physical travel and the potential for access after normal clinic hours can be a real boon for patients; “So how does this help us? How does it improve practice and make our lives easier?” she asked. Telehealth services can lead to improved efficiency, patient satisfaction and retention, and the ability to stand out in a market, especially if a practice can initiate telehealth services now, during the rapid growth and adoption phase for this newer technology.

“You want to make sure you really understand what some of the legal issues are surrounding telehealth and telemedicine,” said Dr. Lee, to ensure compliance with state and federal laws. There can be barriers to practicing across state lines; some states require an initial in-person visit, or the signing of a consent form, before initiating telemedicine; others may limit controlled substance prescribing via telemedicine.

And the mode of communication matters, said Dr. Lee: “Why can’t we just use Facetime to call our patients? The first thing to think about is privacy, and unauthorized access to data,” so it’s critical to do your research and use fully HIPAA-compliant communications technology.

Technology – and pricing plans – can vary widely, she added. “There’s some benefit to including technology that integrates with other clinical programs;” the platform Dr. Lee’s group chose communicates with their EHR for such functions as scheduling.

Pricing models can vary; a common scheme charges a per-user monthly fee, though blanket-fee plans also exist. Some telemedicine platforms use a hybrid pricing model that charges a flat fee up to a certain number of users and then adds a per-user fee after that.

Best practices to manage liability include continuing to maintain high standards of compliance after attorney consultation and notifying your practice’s malpractice insurance carrier, said Dr. Lee.

Reimbursement is on the upswing, as insurers see the benefits of telemedicine, and employers see their patients needing less time off work for appointments, and there are fewer emergency department visits for after-hours problems. Medicaid reimbursement is fairly straightforward, but Medicare is more restrictive and requires the beneficiary to be in a rural originating site.

Coding for a telemedicine visit is strictly based on face-to-face time spent in video conference, said Dr. Lee, at levels on par with time-based coding for office visits. “But you’re not including that time you spend doing chart review and not including the time you spend coordinating care.”

Dr. Lee’s own experience with telemedicine began in late 2016, when the 22-physician general gastroenterology group looked into it as a way to increase growth.

During the first half of the next year, the gastroenterology group’s administrative leaders and an engaged physician proponent vetted a number of telemedicine companies, and the group tried the leading candidates’ technologies.

By mid-2017, the comprehensive gastroenterology group, which also employs six advanced-practice clinicians, was piloting video visits with a group of four physicians. “One of those physicians was actually one of my partners who had sustained an Achilles tendon injury, so wasn’t really coming to the office post surgery. He was starting to use this at home, to do video visits, and everything went pretty smoothly with that,” said Dr. Lee.

When this trial was successful, the group went all in, with on-boarding of clinicians accomplished by the end of the year, site visits and 1:1 training provided by the telemedicine platform providers.

The practice is seeing video visits continue to grow in popularity, among both patients and clinicians, said Dr. Lee. She shared some tips and lessons learned from her practice.

There’s currently no formal protocol that selects patients for participation in the telemedicine program at Dr. Lee’s clinic. Providers may offer video visits to patients, and triage nurses also can suggest that patients ask their provider about them; flyers in waiting rooms and exam rooms encourage patients to ask about the possibility.

The practice maintains a telehealth committee that includes the practice’s president and administrator, about three core physicians who are strong telehealth champions, and additional physicians who are high telehealth users. The committee also folds in the office and information technology managers to make sure issues of workflow, billing, and technology are addressed.

Some practical considerations can pose challenges to a successful telemedicine program, said Dr. Lee. Connectivity problems on the patient end are fairly frequent, and no-shows also can be a problem. On the clinic side, not all clinicians have embraced video visits. For these low users, telemedicine may not represent a good value proposition. However, she said, they are seeing more and more clinicians come on board with video visits as word gets out of the generally positive experiences others are having.

Dr. Lee suggested several ways to up telemedicine utilization and make it work within your practice. “Identify which patient would benefit most,” she said – this might be patients with inflammatory bowel disease who mostly need medication management, or patients with limited mobility or who live far away. Staff can also help a patient get a same-day visit by scheduling a video visit with an available clinician. By mentioning video visits as an option for uncomplicated issues or a way to get a rapid read on a new concern, clinicians can get patients thinking about telemedicine as an appealing option.

In some clinics, exam room space can limit clinician productivity, and scheduling a block of video visits when space is tight can be a great solution. Clinicians can optimize their schedules if they incorporate video visits, said Dr. Lee, citing the example of a physician assistant in her practice who stacks video visits in the evening hours, so she’s able to be with her preschool-aged children during the day. After-hours video visits have been popular among patients too, said Dr. Lee, so the scheduling flexibility may help with both patient and provider retention, and be a practice differentiator.

“There’s great potential for value through improved patient satisfaction, provider efficiency, improved health care outcomes, and cost efficiency,” she said.

Dr. Lee reported that she had no relevant disclosures.

AGA has partnered with SupportedPatientTM, a HIPAA-secure telemedicine platform. It allows you to expand your practice and connect your patients with additional specialists. Learn more at https://www.gastro.org/practice-guidance/practice-updates/supportedpatient .

[email protected]

NATIONAL HARBOR, MD. – New research has shown increased immune infiltration in patients with TP53-mutated acute myeloid leukemia (AML).

Jennifer Smith/MDedge News

Patients with TP53-mutated AML had higher levels of T-cell infiltration, immune checkpoint molecules, and interferon (IFN)–gamma signaling than patients with wild-type TP53.

These findings may indicate that patients with TP53-mutated AML will respond to T-cell targeting immunotherapies, but more investigation is needed, according to Sergio Rutella, MD, PhD, of Nottingham (England) Trent University.

Dr. Rutella described the findings at the annual meeting of the Society for Immunotherapy of Cancer.

He and his colleagues recently identified subgroups of AML, called “immune infiltrated” and “immune depleted,” that can predict chemotherapy resistance and response to flotetuzumab (ASH 2019, Abstract 460). However, the team has not determined the genetic drivers of immune infiltration in AML.*

With the current study, Dr. Rutella and his colleagues wanted to determine if TP53 mutations are associated with the AML immune milieu and see if TP53-mutated patients might benefit from immunotherapy.

Discovery cohort

The researchers first analyzed 147 patients with non-promyelocytic AML from the Cancer Genome Atlas. In total, 9% of these patients (n = 13) had TP53-mutated AML. The researchers assessed how 45 immune gene and biological activity signatures correlated with prognostic molecular lesions (TP53 mutations, FLT3-ITD, etc.) and clinical outcomes in this cohort.

The data showed that immune subtypes were associated with overall survival (OS). The median OS was 11.8 months in patients with immune-infiltrated AML, 16.4 months in patients with intermediate AML, and 25.8 months in patients with immune-depleted AML.

The inflammatory chemokine score (P = .011), IDO1 score (P = .027), IFN-gamma score (P = .036), and B7H3 score (P = .045) were all significantly associated with OS. In fact, these factors were all better predictors of OS than cytogenetic risk score (P = .049).

The IFN-gamma score, inflammatory chemokine score, and lymphoid score were all significantly higher in TP53-mutated patients than in patients with RUNX1 mutations, NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .05).

Likewise, the tumor inflammation signature score was significantly higher among TP53-mutated patients than among patients with NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .01).

Validation cohort and bone marrow samples

The researchers also looked at data from a validation cohort, which consisted of 140 patients with non-promyelocytic AML in the Beat AML Master Trial. Twelve percent of these patients (n = 17) had TP53 mutations.

Data in this cohort showed that CD3G messenger RNA (mRNA) was significantly higher in TP53-mutated AML than in TP53-wild-type AML (P = .04). The same was true for CD8A mRNA (P = .0002) and GZMB mRNA (P = .0005).

Likewise, IFN-gamma mRNA (P = .0052), IFIT2 mRNA (P = .0064), and IFIT3 mRNA (P = .003) were all significantly higher in patients with TP53-mutated AML.

Lastly, the researchers analyzed gene expression profiles of bone marrow samples from patients with AML, 36 with mutated TP53 and 24 with wild-type TP53.

The team found that IFN-gamma–induced genes (IFNG and IRF1), markers of T-cell infiltration (CD8A and CD3G) and senescence (EOMES, KLRD1, and HRAS), immune checkpoint molecules (IDO1, LAG3, PDL1, and VISTA), effector function molecules (GZMB, GZMK, and GZMM), and proinflammatory cytokines (IL17A and TNF) were all significantly overexpressed in TP53-mutated AML.

Among the top overexpressed genes in TP53-mutated AML were genes associated with IFN signaling and inflammation pathways – IL-33, IL-6, IFN-gamma, OASL, RIPK2, TNFAIP3, CSF1, and PTGER4. The IL-17 and TNF signaling pathways were the most enriched pathways in TP53-mutated AML.

“Our analysis of primary bone marrow samples showed that TP53-mutated samples are enriched in IL-17, TNF, and IFN signaling molecules, and show higher levels of T-cell infiltrations and immune checkpoints relative to their wild-type counterparts,” Dr. Rutella said.

“The in silico analysis indicated that TP53-mutated cases will show higher levels of T-cell infiltration, immune checkpoints, and IFN-gamma signaling, compared with AML subgroups without risk-defining molecular lesions,” he added. “This is speculative. Whether TP53-mutated AML can be amenable to respond to T-cell targeting immunotherapies is still to be determined.”

Dr. Rutella reported research support from NanoString Technologies, MacroGenics, and Kura Oncology.

[email protected]

SOURCE: Rutella S et al. SITC 2019. Abstract O3.

*This article was updated on 11/19/2019.

NATIONAL HARBOR, MD. – New research has shown increased immune infiltration in patients with TP53-mutated acute myeloid leukemia (AML).

Jennifer Smith/MDedge News

Patients with TP53-mutated AML had higher levels of T-cell infiltration, immune checkpoint molecules, and interferon (IFN)–gamma signaling than patients with wild-type TP53.

These findings may indicate that patients with TP53-mutated AML will respond to T-cell targeting immunotherapies, but more investigation is needed, according to Sergio Rutella, MD, PhD, of Nottingham (England) Trent University.

Dr. Rutella described the findings at the annual meeting of the Society for Immunotherapy of Cancer.

He and his colleagues recently identified subgroups of AML, called “immune infiltrated” and “immune depleted,” that can predict chemotherapy resistance and response to flotetuzumab (ASH 2019, Abstract 460). However, the team has not determined the genetic drivers of immune infiltration in AML.*

With the current study, Dr. Rutella and his colleagues wanted to determine if TP53 mutations are associated with the AML immune milieu and see if TP53-mutated patients might benefit from immunotherapy.

Discovery cohort

The researchers first analyzed 147 patients with non-promyelocytic AML from the Cancer Genome Atlas. In total, 9% of these patients (n = 13) had TP53-mutated AML. The researchers assessed how 45 immune gene and biological activity signatures correlated with prognostic molecular lesions (TP53 mutations, FLT3-ITD, etc.) and clinical outcomes in this cohort.

The data showed that immune subtypes were associated with overall survival (OS). The median OS was 11.8 months in patients with immune-infiltrated AML, 16.4 months in patients with intermediate AML, and 25.8 months in patients with immune-depleted AML.

The inflammatory chemokine score (P = .011), IDO1 score (P = .027), IFN-gamma score (P = .036), and B7H3 score (P = .045) were all significantly associated with OS. In fact, these factors were all better predictors of OS than cytogenetic risk score (P = .049).

The IFN-gamma score, inflammatory chemokine score, and lymphoid score were all significantly higher in TP53-mutated patients than in patients with RUNX1 mutations, NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .05).

Likewise, the tumor inflammation signature score was significantly higher among TP53-mutated patients than among patients with NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .01).

Validation cohort and bone marrow samples

The researchers also looked at data from a validation cohort, which consisted of 140 patients with non-promyelocytic AML in the Beat AML Master Trial. Twelve percent of these patients (n = 17) had TP53 mutations.

Data in this cohort showed that CD3G messenger RNA (mRNA) was significantly higher in TP53-mutated AML than in TP53-wild-type AML (P = .04). The same was true for CD8A mRNA (P = .0002) and GZMB mRNA (P = .0005).

Likewise, IFN-gamma mRNA (P = .0052), IFIT2 mRNA (P = .0064), and IFIT3 mRNA (P = .003) were all significantly higher in patients with TP53-mutated AML.

Lastly, the researchers analyzed gene expression profiles of bone marrow samples from patients with AML, 36 with mutated TP53 and 24 with wild-type TP53.

The team found that IFN-gamma–induced genes (IFNG and IRF1), markers of T-cell infiltration (CD8A and CD3G) and senescence (EOMES, KLRD1, and HRAS), immune checkpoint molecules (IDO1, LAG3, PDL1, and VISTA), effector function molecules (GZMB, GZMK, and GZMM), and proinflammatory cytokines (IL17A and TNF) were all significantly overexpressed in TP53-mutated AML.

Among the top overexpressed genes in TP53-mutated AML were genes associated with IFN signaling and inflammation pathways – IL-33, IL-6, IFN-gamma, OASL, RIPK2, TNFAIP3, CSF1, and PTGER4. The IL-17 and TNF signaling pathways were the most enriched pathways in TP53-mutated AML.

“Our analysis of primary bone marrow samples showed that TP53-mutated samples are enriched in IL-17, TNF, and IFN signaling molecules, and show higher levels of T-cell infiltrations and immune checkpoints relative to their wild-type counterparts,” Dr. Rutella said.

“The in silico analysis indicated that TP53-mutated cases will show higher levels of T-cell infiltration, immune checkpoints, and IFN-gamma signaling, compared with AML subgroups without risk-defining molecular lesions,” he added. “This is speculative. Whether TP53-mutated AML can be amenable to respond to T-cell targeting immunotherapies is still to be determined.”

Dr. Rutella reported research support from NanoString Technologies, MacroGenics, and Kura Oncology.

[email protected]

SOURCE: Rutella S et al. SITC 2019. Abstract O3.

*This article was updated on 11/19/2019.

NATIONAL HARBOR, MD. – New research has shown increased immune infiltration in patients with TP53-mutated acute myeloid leukemia (AML).

Jennifer Smith/MDedge News

Patients with TP53-mutated AML had higher levels of T-cell infiltration, immune checkpoint molecules, and interferon (IFN)–gamma signaling than patients with wild-type TP53.

These findings may indicate that patients with TP53-mutated AML will respond to T-cell targeting immunotherapies, but more investigation is needed, according to Sergio Rutella, MD, PhD, of Nottingham (England) Trent University.

Dr. Rutella described the findings at the annual meeting of the Society for Immunotherapy of Cancer.

He and his colleagues recently identified subgroups of AML, called “immune infiltrated” and “immune depleted,” that can predict chemotherapy resistance and response to flotetuzumab (ASH 2019, Abstract 460). However, the team has not determined the genetic drivers of immune infiltration in AML.*

With the current study, Dr. Rutella and his colleagues wanted to determine if TP53 mutations are associated with the AML immune milieu and see if TP53-mutated patients might benefit from immunotherapy.

Discovery cohort

The researchers first analyzed 147 patients with non-promyelocytic AML from the Cancer Genome Atlas. In total, 9% of these patients (n = 13) had TP53-mutated AML. The researchers assessed how 45 immune gene and biological activity signatures correlated with prognostic molecular lesions (TP53 mutations, FLT3-ITD, etc.) and clinical outcomes in this cohort.

The data showed that immune subtypes were associated with overall survival (OS). The median OS was 11.8 months in patients with immune-infiltrated AML, 16.4 months in patients with intermediate AML, and 25.8 months in patients with immune-depleted AML.

The inflammatory chemokine score (P = .011), IDO1 score (P = .027), IFN-gamma score (P = .036), and B7H3 score (P = .045) were all significantly associated with OS. In fact, these factors were all better predictors of OS than cytogenetic risk score (P = .049).

The IFN-gamma score, inflammatory chemokine score, and lymphoid score were all significantly higher in TP53-mutated patients than in patients with RUNX1 mutations, NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .05).

Likewise, the tumor inflammation signature score was significantly higher among TP53-mutated patients than among patients with NPM1 mutations, FLT3-ITD (with or without NPM1 mutations), and TET2/DNMT3A/ASXL1 mutations (P values ranging from less than .0001 to .01).

Validation cohort and bone marrow samples

The researchers also looked at data from a validation cohort, which consisted of 140 patients with non-promyelocytic AML in the Beat AML Master Trial. Twelve percent of these patients (n = 17) had TP53 mutations.

Data in this cohort showed that CD3G messenger RNA (mRNA) was significantly higher in TP53-mutated AML than in TP53-wild-type AML (P = .04). The same was true for CD8A mRNA (P = .0002) and GZMB mRNA (P = .0005).

Likewise, IFN-gamma mRNA (P = .0052), IFIT2 mRNA (P = .0064), and IFIT3 mRNA (P = .003) were all significantly higher in patients with TP53-mutated AML.

Lastly, the researchers analyzed gene expression profiles of bone marrow samples from patients with AML, 36 with mutated TP53 and 24 with wild-type TP53.

The team found that IFN-gamma–induced genes (IFNG and IRF1), markers of T-cell infiltration (CD8A and CD3G) and senescence (EOMES, KLRD1, and HRAS), immune checkpoint molecules (IDO1, LAG3, PDL1, and VISTA), effector function molecules (GZMB, GZMK, and GZMM), and proinflammatory cytokines (IL17A and TNF) were all significantly overexpressed in TP53-mutated AML.

Among the top overexpressed genes in TP53-mutated AML were genes associated with IFN signaling and inflammation pathways – IL-33, IL-6, IFN-gamma, OASL, RIPK2, TNFAIP3, CSF1, and PTGER4. The IL-17 and TNF signaling pathways were the most enriched pathways in TP53-mutated AML.

“Our analysis of primary bone marrow samples showed that TP53-mutated samples are enriched in IL-17, TNF, and IFN signaling molecules, and show higher levels of T-cell infiltrations and immune checkpoints relative to their wild-type counterparts,” Dr. Rutella said.

“The in silico analysis indicated that TP53-mutated cases will show higher levels of T-cell infiltration, immune checkpoints, and IFN-gamma signaling, compared with AML subgroups without risk-defining molecular lesions,” he added. “This is speculative. Whether TP53-mutated AML can be amenable to respond to T-cell targeting immunotherapies is still to be determined.”

Dr. Rutella reported research support from NanoString Technologies, MacroGenics, and Kura Oncology.

[email protected]

SOURCE: Rutella S et al. SITC 2019. Abstract O3.

*This article was updated on 11/19/2019.