Conference Coverage

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.

Measuring serum levels of neurofilament light chain (NfL) is an effective way of detecting disease activity and the need to optimize treatment in patients with multiple sclerosis (MS), independent of relapse and MRI activity, a new study has shown. 

The study found that current serum NfL levels predicted relapses, disability worsening, and MRI activity in the following year independent of standard metrics for treatment monitoring, such as relapse rate, disability worsening, and MRI findings. The biomarker also detected subclinical disease activity in patients with no evidence of disease activity (NEDA3), as measured by absence of previous relapses, worsening score on the Expanded Disability Status Scale (EDSS), or brain lesion formation on MRI. 

“Our data in this well-characterized large real-world cohort supports the value of serum NfL levels for treatment monitoring in MS clinical practice,” lead author Özgür Yaldizli, MD, concluded.

Dr. Yaldizli, who is a consultant neurologist at University Hospital Basel (Switzerland), presented the findings at the Joint European Committee for Treatment and Research in Multiple Sclerosis–Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2020, this year known as MSVirtual2020.

“This is the first study to compare NfL simultaneously with other markers of disease progression, such as MRI lesions and relapse rate in treated patients. We show that NfL gives a unique signal that is not captured by other markers,” Dr. Yaldizli said.

“This is likely the largest study of NfL in MS to date, with more than 7,000 samples from well-characterized MS patients followed longitudinally for more than 5 years of sampling and including high quality data on MRI and clinical examinations. It is the first time all these factors have been combined so that we can see how NfL compares with other markers of disease progression in predicting clinical events and monitoring treatment efficacy,” said senior author Jens Kuhle, MD, PhD, also from University Hospital Basel. 
 

Large normative database for reference

The researchers also reported a large normative database of NfL values with data from more than 8,000 healthy controls. “This is the largest normative database to date, that gives us reliable reference values for NfL across a range of ages and comorbidities,” Dr. Kuhle noted.

In his presentation, Dr. Yaldizli explained that NfL is a neuronal cytoskeletal protein released into the cerebrospinal fluid and blood following neuroaxonal injury. Although numerous studies have shown that serum NfL is associated with clinical and MRI disease activity and treatment response, it is not clear whether serum NfL under established disease-modifying therapy (DMT) can identify patients with suboptimal treatment response, compared with standard clinical and MRI activity measures.

This study addressed that question in the large real-world Swiss MS cohort.

The study involved 1,366 patients (88.8% with relapsing remitting MS [RRMS], 5.4% with secondary progressive MS, and 5.8% with primary progressive MS) receiving DMT for at least 3 months from seven MS centers. The median disease duration was 7.2 years. Serum NfL was measured every 6 or 12 months with NF-Light assay on the latest-generation HDX platform (blinded for clinical and MRI data). The median follow-up was 4.9 years. There was an average of five samples per patient, with a total of 7462 samples.

Results showed that NfL levels were higher in older patients (14.5% per 10 years), those with secondary progressive MS (12.4% vs. RRMS), those with primary progressive MS (14.4% vs. RRMS), and in those who had a relapse in the last 4 months (53.4%).

NfL levels were 13.4% lower in patients receiving oral DMT (vs. untreated patients) and 17.7% in patients receiving monoclonal antibodies (vs. untreated patients).

In the large cohort of healthy controls, NfL levels also increased with age, but levels in patients with MS were higher than in controls across the whole age spectrum.

To obtain a measure of deviation from normal, the authors converted NfL levels to z score, which express how much (in terms of number of standard deviations) a measurement differs from mean values found in healthy controls of the same age. Effects were more pronounced with use of z score derived from the normative database than with use of absolute NfL levels even after adjustment for age.

In the univariate analysis, serum NfL z score predicted relapse or EDSS worsening in the following year: The higher the z score, the higher the risk for relapse or EDSS worsening. Patients with an NfL z score greater than 1 had a 41% higher risk for relapse or EDSS worsening in the following year, compared with those whose z score was less than 1 (odds ratio, 1.41).

Patients with an NfL z score exceeding 1.5 had an 80% higher risk for relapse or EDSS worsening in the following year than did those whose score was below 1.5 (OR, 1.8).

Patients with an NfL z score greater than 2 had a 2.3 times higher risk for relapse or EDSS worsening in the following year versus those with a score below 2. (P < 0.001 for all comparisons.)

A screen for nervous system conditions?

Dr, Kuhle reported that NfL is being used on an individual basis in clinical practice at present – at certain MS centers. “One of the problems is not having reliable reference values, so this database of normative values will be very helpful in developing those,” he said. “We see an increase in NfL with age in healthy controls. In order to know what pathological levels are, we need to know what normal levels are in controls throughout the spectrum of ages and other comorbidities, which also play a role. If we normalize these, then we can work out the MS signal in a more efficient way.”

Dr. Kuhle believes that, in the future, NfL may be used to screen for nervous system disease. “NfL is a measure of neuronal health independent of MS. If we have increased levels, we should be worried.”

There is a “high level of energy in this field,” he added. “In future, it could be like having a cholesterol test at present – picking up that something is not right and indicating the need for more tests.”

Dr. Yaldizli suggested that NfL monitoring could also help to individualize and optimize use of MS treatments. “There is a huge unmet need in MS. While we have a plethora of treatment options, we are struggling to individualize and monitor treatments. If NfL levels increase, this is likely a strong indication to change treatment even if there are no other overt symptoms.”

Commenting on the current study, ACTRIMS president, Jeffrey Cohen, MD, Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic, called it “an important study.” 

“NfL clearly can detect disease activity and distinguish efficacy of DMT in groups of patients,” Dr. Cohen said.  

“This study shows that NfL can be used to monitor DMT efficacy in individual patients and can detect suboptimal treatment response in patients with NEDA (i.e., who appear stable by the measures we typically employ in practice),” he added.

Dr. Yaldizli sits on advisory boards for Sanofi Genzyme, Novartis, Biogen, and Novartis. Dr. Kuhle reported no relevant disclosures.

This article first appeared on Medscape.com.

Hematopoietic stem cell transplantation (HCT) is one of the most important treatment options for acute leukemias. However, posttransplant cancer recurrence remains a continuing issue. And while there are reasons to think that hypomethylating agents (HMAS) could be helpful as maintenance tools to prevent cancer recurrence after HCT in leukemia, a hematologist/oncologist told colleagues that the treatment isn’t yet ready for prime time.

“I don’t think you can prefer hypomethylating agents over anything right now. Unfortunately, there’s no data that we can hang our hat on that says they are of benefit in the posttransplant setting,” said Frederick Appelbaum, MD, executive vice president and deputy director of the Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

However, there’s still plenty of room for improvement for patients following HCT, he said, pointing to the findings of a 2020 study. The report, which he cowrote, found that 200-day mortality after HCT fell by a third from 2003-2007 to 2013-20017, but also noted that “relapse of cancer remains the largest obstacle to better survival outcomes.”

Dr. Appelbaum described the findings this way: “Without a doubt, the major limitation to transplants for hematologic malignancies today is disease recurrence,” he said. “In fact, if you look at patients after day 100, over 60% of the reason for failure is tumor regrowth. Thus, people are very anxious to look at any method that we can to prevent posttransplant relapse, including the use of hypomethylating agents.”

In regard to strategy, “we don’t have to get rid of every last leukemic cell. Just delaying recurrence might be enough,” he said. “If you can keep the patient from relapsing for the first 3 months, and then take the brakes off the immune suppression and allow immunity to regrow, that may be enough to allow increased numbers of patients to be cured of their disease.”
 

A potential role

Why might HMAS be a possible option after transplant? They do appear to play a role after chemotherapy, he said, pointing to four 2019 studies: One that examined decitabine and three that examined azacytidine: Here, here, and here.

“These four studies provide convincing evidence that hypomethylating-agent therapy after conventional chemotherapy may either prevent or delay relapse when given as maintenance,” Dr. Appelbaum said.

If HMAS work after standard chemotherapy, why might they fail to work after transplantation? “For one, by the time the disease has been able to go through chemotherapy and transplant, you’re left with highly resistant cells,” he said. “Therefore, hypomethylating agents may not be enough to get rid of the disease. Secondly, any of you who have tried to give a maintenance therapy after transplantation know how difficult it can be with CMV [cytomegalovirus] reactivation, count suppression with ganciclovir, graft-versus-host disease [GVHD] causing nausea and vomiting, diarrhea and renal dysfunction caused by calcineurin inhibitors. These are daily events during the first 3 months after transplantation, making drug administration difficult.”

In addition, he said, “even if you can give the drug, the clinical and disease variability may make it very difficult to detect an effect.”

In another study, researchers “did make a valiant attempt to study azacitidine in the posttransplant setting by randomizing 181 patients to either azacitidine or observation,” Dr. Appelbaum said. “Unfortunately, as they reported in 2018, they could not detect a difference in either disease-free or overall survival.”

The researchers reported that nearly 75% of patients in the azacitidine arm failed to complete the planned 12 cycles of treatment, he said. “The reasons for stopping the drug were pretty profound. Half of the patients stopped because they relapsed. Others had stopped because of grades three or four toxicity, death, or severe GVHD or significant infections. It is very difficult to give the drug.”

In the future, “if we truly want to optimize the benefit of using hypomethylating agents after transplantation, it’s going to be very important for us to understand how they work,” he said. “Understanding that would then help us to select which drug we should use, what the dosing and schedule might be, and also to select patients that might benefit from it. Unfortunately, right now, it’s pretty much of a black box. We don’t really understand the effects of hypomethylating agents in the posttransplant period.”

Still, he added, “without question, the results that we have seen with the use of hypomethylating agents after conventional chemotherapy – prolonging disease-free and, probably, overall survival – are going to provide a very, very strong stimulus to study hypomethylating agents after transplantation as well.”

Dr. Appelbaum reports no disclosures.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Hematopoietic stem cell transplantation (HCT) is one of the most important treatment options for acute leukemias. However, posttransplant cancer recurrence remains a continuing issue. And while there are reasons to think that hypomethylating agents (HMAS) could be helpful as maintenance tools to prevent cancer recurrence after HCT in leukemia, a hematologist/oncologist told colleagues that the treatment isn’t yet ready for prime time.

“I don’t think you can prefer hypomethylating agents over anything right now. Unfortunately, there’s no data that we can hang our hat on that says they are of benefit in the posttransplant setting,” said Frederick Appelbaum, MD, executive vice president and deputy director of the Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

However, there’s still plenty of room for improvement for patients following HCT, he said, pointing to the findings of a 2020 study. The report, which he cowrote, found that 200-day mortality after HCT fell by a third from 2003-2007 to 2013-20017, but also noted that “relapse of cancer remains the largest obstacle to better survival outcomes.”

Dr. Appelbaum described the findings this way: “Without a doubt, the major limitation to transplants for hematologic malignancies today is disease recurrence,” he said. “In fact, if you look at patients after day 100, over 60% of the reason for failure is tumor regrowth. Thus, people are very anxious to look at any method that we can to prevent posttransplant relapse, including the use of hypomethylating agents.”

In regard to strategy, “we don’t have to get rid of every last leukemic cell. Just delaying recurrence might be enough,” he said. “If you can keep the patient from relapsing for the first 3 months, and then take the brakes off the immune suppression and allow immunity to regrow, that may be enough to allow increased numbers of patients to be cured of their disease.”
 

A potential role

Why might HMAS be a possible option after transplant? They do appear to play a role after chemotherapy, he said, pointing to four 2019 studies: One that examined decitabine and three that examined azacytidine: Here, here, and here.

“These four studies provide convincing evidence that hypomethylating-agent therapy after conventional chemotherapy may either prevent or delay relapse when given as maintenance,” Dr. Appelbaum said.

If HMAS work after standard chemotherapy, why might they fail to work after transplantation? “For one, by the time the disease has been able to go through chemotherapy and transplant, you’re left with highly resistant cells,” he said. “Therefore, hypomethylating agents may not be enough to get rid of the disease. Secondly, any of you who have tried to give a maintenance therapy after transplantation know how difficult it can be with CMV [cytomegalovirus] reactivation, count suppression with ganciclovir, graft-versus-host disease [GVHD] causing nausea and vomiting, diarrhea and renal dysfunction caused by calcineurin inhibitors. These are daily events during the first 3 months after transplantation, making drug administration difficult.”

In addition, he said, “even if you can give the drug, the clinical and disease variability may make it very difficult to detect an effect.”

In another study, researchers “did make a valiant attempt to study azacitidine in the posttransplant setting by randomizing 181 patients to either azacitidine or observation,” Dr. Appelbaum said. “Unfortunately, as they reported in 2018, they could not detect a difference in either disease-free or overall survival.”

The researchers reported that nearly 75% of patients in the azacitidine arm failed to complete the planned 12 cycles of treatment, he said. “The reasons for stopping the drug were pretty profound. Half of the patients stopped because they relapsed. Others had stopped because of grades three or four toxicity, death, or severe GVHD or significant infections. It is very difficult to give the drug.”

In the future, “if we truly want to optimize the benefit of using hypomethylating agents after transplantation, it’s going to be very important for us to understand how they work,” he said. “Understanding that would then help us to select which drug we should use, what the dosing and schedule might be, and also to select patients that might benefit from it. Unfortunately, right now, it’s pretty much of a black box. We don’t really understand the effects of hypomethylating agents in the posttransplant period.”

Still, he added, “without question, the results that we have seen with the use of hypomethylating agents after conventional chemotherapy – prolonging disease-free and, probably, overall survival – are going to provide a very, very strong stimulus to study hypomethylating agents after transplantation as well.”

Dr. Appelbaum reports no disclosures.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

Hematopoietic stem cell transplantation (HCT) is one of the most important treatment options for acute leukemias. However, posttransplant cancer recurrence remains a continuing issue. And while there are reasons to think that hypomethylating agents (HMAS) could be helpful as maintenance tools to prevent cancer recurrence after HCT in leukemia, a hematologist/oncologist told colleagues that the treatment isn’t yet ready for prime time.

“I don’t think you can prefer hypomethylating agents over anything right now. Unfortunately, there’s no data that we can hang our hat on that says they are of benefit in the posttransplant setting,” said Frederick Appelbaum, MD, executive vice president and deputy director of the Fred Hutchinson Cancer Research Center, Seattle, in a presentation at the virtual Acute Leukemia Forum of Hemedicus.

However, there’s still plenty of room for improvement for patients following HCT, he said, pointing to the findings of a 2020 study. The report, which he cowrote, found that 200-day mortality after HCT fell by a third from 2003-2007 to 2013-20017, but also noted that “relapse of cancer remains the largest obstacle to better survival outcomes.”

Dr. Appelbaum described the findings this way: “Without a doubt, the major limitation to transplants for hematologic malignancies today is disease recurrence,” he said. “In fact, if you look at patients after day 100, over 60% of the reason for failure is tumor regrowth. Thus, people are very anxious to look at any method that we can to prevent posttransplant relapse, including the use of hypomethylating agents.”

In regard to strategy, “we don’t have to get rid of every last leukemic cell. Just delaying recurrence might be enough,” he said. “If you can keep the patient from relapsing for the first 3 months, and then take the brakes off the immune suppression and allow immunity to regrow, that may be enough to allow increased numbers of patients to be cured of their disease.”
 

A potential role

Why might HMAS be a possible option after transplant? They do appear to play a role after chemotherapy, he said, pointing to four 2019 studies: One that examined decitabine and three that examined azacytidine: Here, here, and here.

“These four studies provide convincing evidence that hypomethylating-agent therapy after conventional chemotherapy may either prevent or delay relapse when given as maintenance,” Dr. Appelbaum said.

If HMAS work after standard chemotherapy, why might they fail to work after transplantation? “For one, by the time the disease has been able to go through chemotherapy and transplant, you’re left with highly resistant cells,” he said. “Therefore, hypomethylating agents may not be enough to get rid of the disease. Secondly, any of you who have tried to give a maintenance therapy after transplantation know how difficult it can be with CMV [cytomegalovirus] reactivation, count suppression with ganciclovir, graft-versus-host disease [GVHD] causing nausea and vomiting, diarrhea and renal dysfunction caused by calcineurin inhibitors. These are daily events during the first 3 months after transplantation, making drug administration difficult.”

In addition, he said, “even if you can give the drug, the clinical and disease variability may make it very difficult to detect an effect.”

In another study, researchers “did make a valiant attempt to study azacitidine in the posttransplant setting by randomizing 181 patients to either azacitidine or observation,” Dr. Appelbaum said. “Unfortunately, as they reported in 2018, they could not detect a difference in either disease-free or overall survival.”

The researchers reported that nearly 75% of patients in the azacitidine arm failed to complete the planned 12 cycles of treatment, he said. “The reasons for stopping the drug were pretty profound. Half of the patients stopped because they relapsed. Others had stopped because of grades three or four toxicity, death, or severe GVHD or significant infections. It is very difficult to give the drug.”

In the future, “if we truly want to optimize the benefit of using hypomethylating agents after transplantation, it’s going to be very important for us to understand how they work,” he said. “Understanding that would then help us to select which drug we should use, what the dosing and schedule might be, and also to select patients that might benefit from it. Unfortunately, right now, it’s pretty much of a black box. We don’t really understand the effects of hypomethylating agents in the posttransplant period.”

Still, he added, “without question, the results that we have seen with the use of hypomethylating agents after conventional chemotherapy – prolonging disease-free and, probably, overall survival – are going to provide a very, very strong stimulus to study hypomethylating agents after transplantation as well.”

Dr. Appelbaum reports no disclosures.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

New CFTR [cystic fibrosis transmembrane conductance regulator] modulator therapies can offer life-altering benefits to some patients with cystic fibrosis, even those with advanced disease.

Triple combination therapy in cystic fibrosis patients with advanced lung disease appears to improve lung function, and may delay the need for lung transplantation, according to a multicenter analysis of patients taking elexacaftor, tezacaftor, and ivacaftor.

The study participants had a percent predicted forced expiratory volume in 1 second (ppFEV₁) of 40% or below, or other high-risk factors. Researchers compared them to control patients who were genetically ineligible for triple combination therapy.

Previous studies of such patients on individual drugs or previous combinations showed increases in lung function in patients with advanced disease, though the magnitude of improvement varied across regimens. “With this improvement, it’s unclear how CFTR modulators should affect lung transplant referral timing,” Brent Bermingham, MD, said during a presentation of the study at the virtual North American Cystic Fibrosis Conference.

“The rationale for our study was that despite patients with advanced lung disease being excluded from phase III trials (of elexacaftor, tezacaftor, and ivacaftor), they are receiving a therapy with an unknown clinical efficacy and safety profile,” said Dr. Bermingham, a pulmonary and critical care fellow at the Medical University of South Carolina, Charleston.

Lung transplant referral guidelines recommend that physicians initiate discussions about the potential benefit of lung transplant when FEV₁ drops below 50% of the predicted value. Patients should be referred for a transplant when the value is below 50% and rapidly declining (>20% decline in the past 12 months), when it drops below 40% with accompanying predictors of shortened survival, or when it drops below 30%. The guidelines were published before approval of triple combination therapy.

The researchers conducted an open-label retrospective analysis of 60 patients started on triple combination therapy between September 2019 and February 2020 at three centers in the Southeast. They compared percent predicted ppFEV₁ values prior to initiation of therapy to ppFEV₁ values obtained 2-12 weeks after the start of therapy. Patients on therapy were compared with 10 genetically ineligible controls. The two groups were generally similar aside from genetic status, though 100% of the therapy group had pancreatic insufficiency, compared with 90% of controls (P = .013).

The therapeutic group experienced a 7.8% increase in ppFEV₁ after starting therapy (P < .001), compared with a 0.5% decrease in controls (P = .65). Before initiation of therapy, 33% of the therapy group met the criteria for initiating a transplant discussion, while 67% had been recommended for transplant. After therapy, 55% met the criteria for discussion, 33% were recommended for transplant, and 12% no longer met the criteria for discussion of transplantation. Fifty percent of controls were in discussion, and this dropped to 40%, while 50% were referred for transplantation, and this increased to 60%. On therapy, transplant referral candidates had an increase of forced vital capacity from 48.9 to 59.16 (P < .001).

Adverse events were rare, with only one discontinuation that occurred following a lung transplant and was not believed to be treatment related.

“Our study had a large number of patients taken from multiple centers, which suggests generalizabilty and real-world experience,” said Dr. Bermingham.

The results are encouraging, said Robert J. Giusti, MD, clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center.

“We’re all remarking how wonderful patients feel these days. It’s really a disease-altering treatment. But for the high-risk group, whose FEV₁ is less than 40%, those are the patients we’re more concerned about because we thought maybe they had too much lung disease, and that they wouldn’t benefit from triple combination. But they seem to be improving, so that’s very reassuring,” said Dr. Giusti, who was not involved in the study.

The study received funding from the Cystic Fibrosis Foundation and Dartmouth College. Dr. Bermingham and Dr. Giusti have no relevant financial disclosures.

SOURCE: Bermingham B et al. NACFC 2020, Abstract 645.

New CFTR [cystic fibrosis transmembrane conductance regulator] modulator therapies can offer life-altering benefits to some patients with cystic fibrosis, even those with advanced disease.

Triple combination therapy in cystic fibrosis patients with advanced lung disease appears to improve lung function, and may delay the need for lung transplantation, according to a multicenter analysis of patients taking elexacaftor, tezacaftor, and ivacaftor.

The study participants had a percent predicted forced expiratory volume in 1 second (ppFEV₁) of 40% or below, or other high-risk factors. Researchers compared them to control patients who were genetically ineligible for triple combination therapy.

Previous studies of such patients on individual drugs or previous combinations showed increases in lung function in patients with advanced disease, though the magnitude of improvement varied across regimens. “With this improvement, it’s unclear how CFTR modulators should affect lung transplant referral timing,” Brent Bermingham, MD, said during a presentation of the study at the virtual North American Cystic Fibrosis Conference.

“The rationale for our study was that despite patients with advanced lung disease being excluded from phase III trials (of elexacaftor, tezacaftor, and ivacaftor), they are receiving a therapy with an unknown clinical efficacy and safety profile,” said Dr. Bermingham, a pulmonary and critical care fellow at the Medical University of South Carolina, Charleston.

Lung transplant referral guidelines recommend that physicians initiate discussions about the potential benefit of lung transplant when FEV₁ drops below 50% of the predicted value. Patients should be referred for a transplant when the value is below 50% and rapidly declining (>20% decline in the past 12 months), when it drops below 40% with accompanying predictors of shortened survival, or when it drops below 30%. The guidelines were published before approval of triple combination therapy.

The researchers conducted an open-label retrospective analysis of 60 patients started on triple combination therapy between September 2019 and February 2020 at three centers in the Southeast. They compared percent predicted ppFEV₁ values prior to initiation of therapy to ppFEV₁ values obtained 2-12 weeks after the start of therapy. Patients on therapy were compared with 10 genetically ineligible controls. The two groups were generally similar aside from genetic status, though 100% of the therapy group had pancreatic insufficiency, compared with 90% of controls (P = .013).

The therapeutic group experienced a 7.8% increase in ppFEV₁ after starting therapy (P < .001), compared with a 0.5% decrease in controls (P = .65). Before initiation of therapy, 33% of the therapy group met the criteria for initiating a transplant discussion, while 67% had been recommended for transplant. After therapy, 55% met the criteria for discussion, 33% were recommended for transplant, and 12% no longer met the criteria for discussion of transplantation. Fifty percent of controls were in discussion, and this dropped to 40%, while 50% were referred for transplantation, and this increased to 60%. On therapy, transplant referral candidates had an increase of forced vital capacity from 48.9 to 59.16 (P < .001).

Adverse events were rare, with only one discontinuation that occurred following a lung transplant and was not believed to be treatment related.

“Our study had a large number of patients taken from multiple centers, which suggests generalizabilty and real-world experience,” said Dr. Bermingham.

The results are encouraging, said Robert J. Giusti, MD, clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center.

“We’re all remarking how wonderful patients feel these days. It’s really a disease-altering treatment. But for the high-risk group, whose FEV₁ is less than 40%, those are the patients we’re more concerned about because we thought maybe they had too much lung disease, and that they wouldn’t benefit from triple combination. But they seem to be improving, so that’s very reassuring,” said Dr. Giusti, who was not involved in the study.

The study received funding from the Cystic Fibrosis Foundation and Dartmouth College. Dr. Bermingham and Dr. Giusti have no relevant financial disclosures.

SOURCE: Bermingham B et al. NACFC 2020, Abstract 645.

New CFTR [cystic fibrosis transmembrane conductance regulator] modulator therapies can offer life-altering benefits to some patients with cystic fibrosis, even those with advanced disease.

Triple combination therapy in cystic fibrosis patients with advanced lung disease appears to improve lung function, and may delay the need for lung transplantation, according to a multicenter analysis of patients taking elexacaftor, tezacaftor, and ivacaftor.

The study participants had a percent predicted forced expiratory volume in 1 second (ppFEV₁) of 40% or below, or other high-risk factors. Researchers compared them to control patients who were genetically ineligible for triple combination therapy.

Previous studies of such patients on individual drugs or previous combinations showed increases in lung function in patients with advanced disease, though the magnitude of improvement varied across regimens. “With this improvement, it’s unclear how CFTR modulators should affect lung transplant referral timing,” Brent Bermingham, MD, said during a presentation of the study at the virtual North American Cystic Fibrosis Conference.

“The rationale for our study was that despite patients with advanced lung disease being excluded from phase III trials (of elexacaftor, tezacaftor, and ivacaftor), they are receiving a therapy with an unknown clinical efficacy and safety profile,” said Dr. Bermingham, a pulmonary and critical care fellow at the Medical University of South Carolina, Charleston.

Lung transplant referral guidelines recommend that physicians initiate discussions about the potential benefit of lung transplant when FEV₁ drops below 50% of the predicted value. Patients should be referred for a transplant when the value is below 50% and rapidly declining (>20% decline in the past 12 months), when it drops below 40% with accompanying predictors of shortened survival, or when it drops below 30%. The guidelines were published before approval of triple combination therapy.

The researchers conducted an open-label retrospective analysis of 60 patients started on triple combination therapy between September 2019 and February 2020 at three centers in the Southeast. They compared percent predicted ppFEV₁ values prior to initiation of therapy to ppFEV₁ values obtained 2-12 weeks after the start of therapy. Patients on therapy were compared with 10 genetically ineligible controls. The two groups were generally similar aside from genetic status, though 100% of the therapy group had pancreatic insufficiency, compared with 90% of controls (P = .013).

The therapeutic group experienced a 7.8% increase in ppFEV₁ after starting therapy (P < .001), compared with a 0.5% decrease in controls (P = .65). Before initiation of therapy, 33% of the therapy group met the criteria for initiating a transplant discussion, while 67% had been recommended for transplant. After therapy, 55% met the criteria for discussion, 33% were recommended for transplant, and 12% no longer met the criteria for discussion of transplantation. Fifty percent of controls were in discussion, and this dropped to 40%, while 50% were referred for transplantation, and this increased to 60%. On therapy, transplant referral candidates had an increase of forced vital capacity from 48.9 to 59.16 (P < .001).

Adverse events were rare, with only one discontinuation that occurred following a lung transplant and was not believed to be treatment related.

“Our study had a large number of patients taken from multiple centers, which suggests generalizabilty and real-world experience,” said Dr. Bermingham.

The results are encouraging, said Robert J. Giusti, MD, clinical professor of pediatrics at the New York University and director of the Pediatric Cystic Fibrosis Center.

“We’re all remarking how wonderful patients feel these days. It’s really a disease-altering treatment. But for the high-risk group, whose FEV₁ is less than 40%, those are the patients we’re more concerned about because we thought maybe they had too much lung disease, and that they wouldn’t benefit from triple combination. But they seem to be improving, so that’s very reassuring,” said Dr. Giusti, who was not involved in the study.

The study received funding from the Cystic Fibrosis Foundation and Dartmouth College. Dr. Bermingham and Dr. Giusti have no relevant financial disclosures.

SOURCE: Bermingham B et al. NACFC 2020, Abstract 645.

Most fecal immunochemical tests (FIT) in the hospital setting or the ED are performed for inappropriate indications, according to new data.

“This is the largest study that focuses exclusively on the use of FIT in the ED, inpatient wards, and in the ICU, and it shows significant misuse,” said investigator Umer Bhatti, MD, from Indiana University, Indianapolis.

The only “validated indication” for FIT is to screen for colorectal cancer. However, “99.5% of the FIT tests done in our study were for inappropriate indications,” he reported at the annual meeting of the American College of Gastroenterology, where the study was honored with an ACG Presidential Poster Award.

And the inappropriate use of FIT in these settings had no positive effect on clinical decision-making, he added.

For their study, Dr. Bhatti and colleagues looked at all instances of FIT use in their hospital’s electronic medical records from November 2017 to October 2019 to assess how often FIT was being used, the indications for which it was being used, and the impact of its use on clinical care.

They identified 550 patients, 48% of whom were women, who underwent at least one FIT test. Mean age of the study cohort was 54 years. Only three of the tests, or 0.5%, were performed to screen for colorectal cancer (95% confidence interval, 0.09%-1.52%).

Among the indications documented for FIT were anemia in 242 (44.0%) patients, suspected GI bleeding in 225 (40.9%), abdominal pain in 31 (5.6%), and change in bowel habits in 19 (3.5%).

The tests were performed most often in the ED (45.3%) and on the hospital floor (42.2%), but were also performed in the ICU (10.5%) and burn unit (2.0%).

Overall, 297 of the tests, or 54%, were negative, and 253, or 46%, were positive.

“GI consults were obtained in 46.2% of the FIT-positive group, compared with 13.1% of the FIT-negative patients” (odds ratio, 5.93; 95% CI, 3.88-9.04, P < .0001), Dr. Bhatti reported.

Among FIT-positive patients, those with overt bleeding were more likely to receive a GI consultation than those without (OR, 3.3; 95% CI, 1.9-5.5; P < .0001).

Of the 117 FIT-positive patients who underwent a GI consultation, upper endoscopy was a more common outcome than colonoscopy (51.3% vs. 23.1%; P < .0001). Of the 34 patients who underwent colonoscopy or sigmoidoscopy, one was diagnosed with colorectal cancer and one with advanced adenoma.

Overt GI bleeding was a better predictor of a GI consultation than a positive FIT result. In fact, use of FIT for patients with overt GI bleeding indicates a poor understanding of the test’s utility, the investigators reported.

“For patients with overt GI bleeding, having a positive FIT made no difference on how often a bleeding source was identified on endoscopy, suggesting that FIT should not be used to guide decisions about endoscopy or hospitalization,” Dr. Bhatti said.

In light of these findings, the team urges their peers to consider measures to reduce FIT tests for unnecessary indications.

“We feel that FIT is unfit for use in the inpatient and emergency settings, and measures should be taken to curb its use,” Dr. Bhatti concluded. “We presented our data to our hospital leadership and a decision was made to remove the FIT as an orderable test from the EMR.”

These results are “striking,” said Jennifer Christie, MD, from the University, Atlanta.

“We should be educating our ER providers and inpatient providers about the proper use of FIT,” she said in an interview. “Another option – and this has been done in many settings with the fecal occult blood test – is just take FIT off the units or out of the ER, so providers won’t be tempted to use it as an assessment of these patients. Because often times, as this study showed, it doesn’t really impact outcomes.”

In fact, unnecessary FI testing could put patients at risk for unnecessary procedures. “We also know that calling for an inpatient or ER consult from a gastroenterologist may increase both length of stay and costs,” she added.

Dr. Bhatti and Dr. Christie disclosed no relevant financial relationships.

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

Most fecal immunochemical tests (FIT) in the hospital setting or the ED are performed for inappropriate indications, according to new data.

“This is the largest study that focuses exclusively on the use of FIT in the ED, inpatient wards, and in the ICU, and it shows significant misuse,” said investigator Umer Bhatti, MD, from Indiana University, Indianapolis.

The only “validated indication” for FIT is to screen for colorectal cancer. However, “99.5% of the FIT tests done in our study were for inappropriate indications,” he reported at the annual meeting of the American College of Gastroenterology, where the study was honored with an ACG Presidential Poster Award.

And the inappropriate use of FIT in these settings had no positive effect on clinical decision-making, he added.

For their study, Dr. Bhatti and colleagues looked at all instances of FIT use in their hospital’s electronic medical records from November 2017 to October 2019 to assess how often FIT was being used, the indications for which it was being used, and the impact of its use on clinical care.

They identified 550 patients, 48% of whom were women, who underwent at least one FIT test. Mean age of the study cohort was 54 years. Only three of the tests, or 0.5%, were performed to screen for colorectal cancer (95% confidence interval, 0.09%-1.52%).

Among the indications documented for FIT were anemia in 242 (44.0%) patients, suspected GI bleeding in 225 (40.9%), abdominal pain in 31 (5.6%), and change in bowel habits in 19 (3.5%).

The tests were performed most often in the ED (45.3%) and on the hospital floor (42.2%), but were also performed in the ICU (10.5%) and burn unit (2.0%).

Overall, 297 of the tests, or 54%, were negative, and 253, or 46%, were positive.

“GI consults were obtained in 46.2% of the FIT-positive group, compared with 13.1% of the FIT-negative patients” (odds ratio, 5.93; 95% CI, 3.88-9.04, P < .0001), Dr. Bhatti reported.

Among FIT-positive patients, those with overt bleeding were more likely to receive a GI consultation than those without (OR, 3.3; 95% CI, 1.9-5.5; P < .0001).

Of the 117 FIT-positive patients who underwent a GI consultation, upper endoscopy was a more common outcome than colonoscopy (51.3% vs. 23.1%; P < .0001). Of the 34 patients who underwent colonoscopy or sigmoidoscopy, one was diagnosed with colorectal cancer and one with advanced adenoma.

Overt GI bleeding was a better predictor of a GI consultation than a positive FIT result. In fact, use of FIT for patients with overt GI bleeding indicates a poor understanding of the test’s utility, the investigators reported.

“For patients with overt GI bleeding, having a positive FIT made no difference on how often a bleeding source was identified on endoscopy, suggesting that FIT should not be used to guide decisions about endoscopy or hospitalization,” Dr. Bhatti said.

In light of these findings, the team urges their peers to consider measures to reduce FIT tests for unnecessary indications.

“We feel that FIT is unfit for use in the inpatient and emergency settings, and measures should be taken to curb its use,” Dr. Bhatti concluded. “We presented our data to our hospital leadership and a decision was made to remove the FIT as an orderable test from the EMR.”

These results are “striking,” said Jennifer Christie, MD, from the University, Atlanta.

“We should be educating our ER providers and inpatient providers about the proper use of FIT,” she said in an interview. “Another option – and this has been done in many settings with the fecal occult blood test – is just take FIT off the units or out of the ER, so providers won’t be tempted to use it as an assessment of these patients. Because often times, as this study showed, it doesn’t really impact outcomes.”

In fact, unnecessary FI testing could put patients at risk for unnecessary procedures. “We also know that calling for an inpatient or ER consult from a gastroenterologist may increase both length of stay and costs,” she added.

Dr. Bhatti and Dr. Christie disclosed no relevant financial relationships.

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

Most fecal immunochemical tests (FIT) in the hospital setting or the ED are performed for inappropriate indications, according to new data.

“This is the largest study that focuses exclusively on the use of FIT in the ED, inpatient wards, and in the ICU, and it shows significant misuse,” said investigator Umer Bhatti, MD, from Indiana University, Indianapolis.

The only “validated indication” for FIT is to screen for colorectal cancer. However, “99.5% of the FIT tests done in our study were for inappropriate indications,” he reported at the annual meeting of the American College of Gastroenterology, where the study was honored with an ACG Presidential Poster Award.

And the inappropriate use of FIT in these settings had no positive effect on clinical decision-making, he added.

For their study, Dr. Bhatti and colleagues looked at all instances of FIT use in their hospital’s electronic medical records from November 2017 to October 2019 to assess how often FIT was being used, the indications for which it was being used, and the impact of its use on clinical care.

They identified 550 patients, 48% of whom were women, who underwent at least one FIT test. Mean age of the study cohort was 54 years. Only three of the tests, or 0.5%, were performed to screen for colorectal cancer (95% confidence interval, 0.09%-1.52%).

Among the indications documented for FIT were anemia in 242 (44.0%) patients, suspected GI bleeding in 225 (40.9%), abdominal pain in 31 (5.6%), and change in bowel habits in 19 (3.5%).

The tests were performed most often in the ED (45.3%) and on the hospital floor (42.2%), but were also performed in the ICU (10.5%) and burn unit (2.0%).

Overall, 297 of the tests, or 54%, were negative, and 253, or 46%, were positive.

“GI consults were obtained in 46.2% of the FIT-positive group, compared with 13.1% of the FIT-negative patients” (odds ratio, 5.93; 95% CI, 3.88-9.04, P < .0001), Dr. Bhatti reported.

Among FIT-positive patients, those with overt bleeding were more likely to receive a GI consultation than those without (OR, 3.3; 95% CI, 1.9-5.5; P < .0001).

Of the 117 FIT-positive patients who underwent a GI consultation, upper endoscopy was a more common outcome than colonoscopy (51.3% vs. 23.1%; P < .0001). Of the 34 patients who underwent colonoscopy or sigmoidoscopy, one was diagnosed with colorectal cancer and one with advanced adenoma.

Overt GI bleeding was a better predictor of a GI consultation than a positive FIT result. In fact, use of FIT for patients with overt GI bleeding indicates a poor understanding of the test’s utility, the investigators reported.

“For patients with overt GI bleeding, having a positive FIT made no difference on how often a bleeding source was identified on endoscopy, suggesting that FIT should not be used to guide decisions about endoscopy or hospitalization,” Dr. Bhatti said.

In light of these findings, the team urges their peers to consider measures to reduce FIT tests for unnecessary indications.

“We feel that FIT is unfit for use in the inpatient and emergency settings, and measures should be taken to curb its use,” Dr. Bhatti concluded. “We presented our data to our hospital leadership and a decision was made to remove the FIT as an orderable test from the EMR.”

These results are “striking,” said Jennifer Christie, MD, from the University, Atlanta.

“We should be educating our ER providers and inpatient providers about the proper use of FIT,” she said in an interview. “Another option – and this has been done in many settings with the fecal occult blood test – is just take FIT off the units or out of the ER, so providers won’t be tempted to use it as an assessment of these patients. Because often times, as this study showed, it doesn’t really impact outcomes.”

In fact, unnecessary FI testing could put patients at risk for unnecessary procedures. “We also know that calling for an inpatient or ER consult from a gastroenterologist may increase both length of stay and costs,” she added.

Dr. Bhatti and Dr. Christie disclosed no relevant financial relationships.

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

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

jremaly@mdedge.com

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

jremaly@mdedge.com

Wildfires burned millions of acres in California, Oregon, and Washington this year. Record numbers of tropical storms and hurricanes formed in the Atlantic. “Climate change is here. Disasters are here. They are going to be increasing, which is why we want to talk about this and talk about how pediatricians can help and respond to these events,” Scott Needle, MD, said at the annual meeting American Academy of Pediatrics, held virtually this year.

SounderBruce/flickr.com/CC BY-SA 2.0

“We have seen from past disasters that people look to us ... as a trusted source of information,” said Dr. Needle, chief medical officer of Elica Health Centers in Sacramento, California. “We can be a positive influence in terms of getting out proactive messaging and keeping people informed.”

The Federal Emergency Management Agency (FEMA) 2019 National Household Survey found that about half of households had an emergency plan. A theme across surveys is that, although households take some steps to get ready for disasters, the public generally “is not as prepared for these events as they really need to be,” Dr. Needle said.

The AAP, the Red Cross, and FEMA are among the organizations that offer planning guides, most of which emphasize three simple things: have a kit, have a plan, and be informed, he said.

To prepare for a disaster, parents might refill a child’s medications ahead of time if possible, Dr. Needle suggested. And during the COVID-19 pandemic, families should add masks, sanitizers, and wipes to their go-bags.

Physicians also can help families by asking how they are coping.
 

Wildfire smoke

“Smoke from wildfires can blanket large, large areas,” Mark Miller, MD, MPH, said during the presentation at the AAP meeting. “This year, we have seen wildfire smoke from the western states reach all the way to the East Coast. So this impacts your patients and your own families sometimes, regardless of wherever you live.”

Children may be more vulnerable to wildfire smoke because they often spend more time outdoors and tend to be more active. In addition, their ongoing development means exposure to air pollutants could have lifelong consequences, said Dr. Miller, who recently reviewed the effects of wildfire smoke on children.

“Children with asthma should have some information about wildfires built into their asthma management plan,” said Dr. Miller, who is affiliated with Western States Pediatric Environmental Health Specialty Unit (PEHSU) and University of California, San Francisco. Pollutants are associated with respiratory visits and admissions, asthma exacerbations, decreased lung function, and neurocognitive effects. They also may be carcinogenic.

A study in monkeys found that smoke exposure during California wildfires in 2008 was associated with immune dysregulation and compromised lung function in adolescence.

Another study of three cohorts of children in southern California found that air pollutant levels were associated with children’s lung function.

Organizations have provided resources on creating cleaner air spaces during wildfires, including guides to build DIY air filter fans. AirNow.gov provides air quality and fire maps that can inform decisions about school closures and outdoor activities. Communities should prioritize establishing schools as clean air shelters, Dr. Miller suggested.

Studies have found that respirators and medical masks may decrease children’s exposure to smoke. Children should not use face coverings, however, if they are younger than 2 years, if they are not able to remove the face covering on their own or tell an adult that they need help, or if they have difficulty breathing with a face covering. Younger children should be observed by an adult.

During the pandemic, families should be aware that some types of masks are sold only for health care use, many foreign respirators are counterfeit, and cloth masks used for COVID-19 are not suitable for reducing wildfire smoke exposure, Dr. Miller said.
 

Hazards may linger

Long-term mental health issues may be the disaster consequence that pediatricians encounter most often, Dr. Needle said.

Eighteen months after a major wildfire in Canada, more than one-third of middle and high school students in one community had probable posttraumatic stress disorder (that is, intrusive thoughts, avoidance, and increased arousal). In addition, 31% of students had probable depression. Rates were elevated relative to a control group of students in another community that was not affected by the fire.

Findings indicate that a patient’s degree of exposure to a disaster affects the likelihood of adverse outcomes. On the other hand, resiliency may help mitigate adverse effects. “The hope is that if we can find ways to encourage resiliency before or in the aftermath of an event, we may be able to, in a sense, reduce some of these mental health sequelae,” Dr. Needle said.

Posttraumatic reactions in kids are likely after a disaster. “They may not rise to the level of a diagnosable condition, but they are very common in kids,” he said. “It is important to at least be able to counsel parents to recognize some of the common reactions,” such as acting withdrawn or aggressive, somatic complaints, and having trouble sleeping.

The AAP has a policy statement that encourages talking to children about their concerns with honest and age-appropriate responses, he noted.

When returning to an area after a disaster, many hazards may remain, such as floodwaters, ash pits, mold, and carbon monoxide from generators. “Generally speaking, you don’t want to have kids return to these areas until it is safe,” Dr. Needle said.

Exacerbation of existing conditions – perhaps because of lost medications, smoke exposure, or stress – may be another common problem. Other problems after a disaster could include domestic violence (direct or witnessed) and substance abuse.

“We have a responsibility to take care of our own health as well,” Dr. Needle added. “You can’t take care of others if you’re not taking care of yourself. It’s not being selfish. As a matter of fact, it’s being prudent. It’s survival.”

Dr. Needle and Dr. Miller had no relevant financial disclosures. Dr. Miller’s presentation was supported by the AAP and funded in part by the Agency for Toxic Substances and Disease Registry. The U.S. Environmental Protection Agency (EPA) provides funding support for the Pediatric Environmental Health Specialty Unit.

jremaly@mdedge.com

When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.

“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”

Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.

Bipolar disorder with associated psychosis

In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.

“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”

Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.

Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”

In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.

Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.

In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
 

Bipolar disorder with anxiety

An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.

In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.

“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”

To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. Olanzapine can also be potentially used in cases where a patient has mania and anxiety to treat both conditions, he added.

Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
 

Bipolar disorder and ADHD

Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.

“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.

Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.

“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.

Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.

In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).

Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).

“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.

He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.

When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.

“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”

Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.

Bipolar disorder with associated psychosis

In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.

“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”

Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.

Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”

In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.

Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.

In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
 

Bipolar disorder with anxiety

An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.

In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.

“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”

To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. Olanzapine can also be potentially used in cases where a patient has mania and anxiety to treat both conditions, he added.

Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
 

Bipolar disorder and ADHD

Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.

“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.

Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.

“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.

Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.

In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).

Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).

“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.

He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.

When selecting pharmacotherapy for patients with bipolar disorder, clinical and prognostic correlates will ultimately influence what treatments make the most sense for a patient – but the process is a balancing act, according to Joseph F. Goldberg, MD.

“Everything we do in medicine in general, and psychiatry, and bipolar disorder in particular is a risk-benefit analysis,” Dr. Goldberg said at the virtual Psychopharmacology Update presented by Current Psychiatry and Global Academy for Medical Education. “Everything has its side effects. We’re always balancing risks and benefits.”

Patients with bipolar disorder often present with three common subtypes of the illness: Those who have associated psychosis, comorbid anxiety disorders, and comorbid ADHD. “These are three common presentations of the many, many kinds of presentations,” said Dr. Goldberg, clinical professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York.

Bipolar disorder with associated psychosis

In the case of bipolar I disorder, more than 50% of manic episodes have some element of psychosis, with as many as 10% of patients showing signs of delusions 2 years after an episode, Dr. Goldberg explained. In these patients, mania relapse is predicted by mood-incongruent psychosis – a condition usually associated with schizophrenia, he said.

“If [they] have unusual beliefs and ideas, and they’re not consistent with a particular mood state, we sometimes clinically think this sounds more like a primary psychotic process,” he said. “Maybe, but not necessarily. So just because the patient may say, ‘The FBI is after me,’ or, ‘My thoughts are being read over the Internet,’ and they don’t connect that with a grandiose theme, it doesn’t negate a diagnosis of bipolar disorder.”

Psychotic mania is also associated with comorbid anxiety disorder. About half of patients with bipolar I disorder will also experience impairments of attention, executive functioning, and verbal memory separately from ADHD. “The cognitive symptoms of bipolar disorder that are part of what’s inherited doesn’t seem to be the case, that there’s a clear greater degree of neuropsychological impairment in psychotic than nonpsychotic mania,” Dr. Goldberg said.

Lithium has a poor response in the presence of psychosis in patients with bipolar disorder but performs better when the patient receives it alongside an antipsychotic. “Lithium does have value in psychotic mania,” Dr. Goldberg said. “Psychosis would be a negative prognostic sign, and certainly an indication for including an antipsychotic.”

In contrast to lithium, divalproex has shown evidence in reducing manic and psychotic symptoms similarly to haloperidol. “Divalproex may reduce mania symptoms, whether or not it’s helping psychosis. You’d think you have to get both reduced at the same time, but actually can see that even if there’s baseline psychosis, that does not diminish the chance of seeing a reduction in core mania symptoms,” Dr. Goldberg said.

Carbamazepine may also be advantageous to use over lithium when patients present with delusions, and a combination of carbamazepine and lithium may be comparable to haloperidol in combination with lithium when treating psychotic mania. “What we do know is, at least in some studies, there may be some greater value in treating psychotic mania with carbamazepine as compared to lithium, particularly when there are delusions present, more so than hallucinations or formal thought disorder,” Dr. Goldberg said.

In patients with bipolar disorder and associated psychotic mania, clinicians should avoid dopamine agonists such as amphetamine and pramipexole, as well as ketamine. While some evidence has shown that second-generation antipsychotics work to treat bipolar depression, “there’s not really an evidence base to suggest that first-generation antipsychotics are protective against depression,” Dr. Goldberg said.
 

Bipolar disorder with anxiety

An association exists between comorbid anxiety disorders in patients with bipolar disorder and having a younger age of onset, in people who are less likely to recover from an initial mood episode, in people with poorer quality of life and role functioning, and in people who are less euthymic and more likely to attempt suicide, Dr. Goldberg said.

In addition, some patients may demonstrate symptoms of anxiety that aren’t part of the DSM-5 criteria for an anxiety disorder. Dr. Goldberg said he asks his patients to specify what they mean when they say they feel anxious.

“I always ask patients to tell me in very basic terms what [they] mean by anxiety. If they say, ‘I just I can’t sit still; I’m very fidgety,’ maybe that’s akathisia,” he said. “Or maybe if they say they’re very anxious, what they mean is they have so much energy they can’t contain it. This is mania or hypomania that they’re misconstruing as anxiety. We have to be very diligent and vigilant in clarifying the language here.”

To treat comorbid anxiety in patients with bipolar disorder, consider adjunctive olanzapine or lamotrigine, as both have evidence of anxiolytic efficacy. “Olanzapine does count as an antianxiety agent. Would you use it just as an antianxiety agent? Probably not in and of itself, but there’s other compelling reasons to use it,” he said. Before assuming you need to add another medication to address anxiety in a patient, “step back and think perhaps their anxiety symptoms will in themselves remit with olanzapine,” he said. Olanzapine can also be potentially used in cases where a patient has mania and anxiety to treat both conditions, he added.

Divalproex is another option for patients that has anxiolytic efficacy. “In the context of bipolar depression, divalproex does have antianxiety properties,” Dr. Goldberg said. Other anxiolytic options include lurasidone, cariprazine, quetiapine, and combination olanzapine–fluoxetine.
 

Bipolar disorder and ADHD

Among patients with bipolar disorder and comorbid adult ADHD, cognitive dysfunction inherent to bipolar disorder may be difficult to distinguish from signs of ADHD, Dr. Goldberg explained, with about 20% of people with bipolar I disorder and about 30% of people with bipolar II disorder have deficits of attentional processing, verbal memory, and executive functioning.

“Some researchers are very intrigued by the notion that cognitive problems and attentional problems aren’t necessarily a sign of [ADHD] comorbidities. They might be, but they may just be part of the endophenotype or the non-overt, genetically driven phenomenology that makes bipolar disorder so heterogeneous,” he said.

Patients with bipolar disorder and comorbid ADHD are more likely to have mania than depression, the condition is more common in men, and these patients are more likely to have substance use problems, increased risk of suicide attempts, problems in school, lower socioeconomic status, greater unemployment history, higher divorce rates, and low family history of bipolar disorder. Clinicians should check a patient’s history if they suspect comorbid adult ADHD in their patients with bipolar disorder, as there is a good chance evidence of ADHD will be present around the time of adolescence.

“You don’t wake up with [ADHD] at age 40, at least that’s not the prevailing perspective,” Dr. Goldberg said.

Focus on the ADHD symptoms that do not overlap with bipolar disorder, such as nondiscrete, chronic symptoms; lack of psychosis and suicidality; no evidence of grandiose beliefs; lack of hypersexuality; and depression that is not prominent. “You really need to go back in time and get some clarity as to the longitudinal course. If this was present earlier on and it persists into adulthood and it’s not better accounted for by either what we think of as the cognitive pervasive problems that emerge in bipolar disorder, or in relatives as a collaborator for attentional problems and bipolar disorder, we can then contemplate [whether] there’s a plausible basis for using a stimulant or [other ADHD] treatment,” he said.

In patients who are found to have adult comorbid ADHD and are nonmanic and nonpsychotic, stimulants do have an effect. Studies suggest that amphetamines such as adjunctive lisdexamfetamine added to a mood stabilizer show an improvement in ADHD symptoms after 4 weeks (Hum Psychopharmacol. 2013; 28[5]:421-7).

Adjunctive methylphenidate added to a mood stabilizer has also shown evidence of not causing treatment-emergent mania. “If you’re going to use methylphenidate, make sure it’s in the context of an antimanic mood stabilizer,” Dr. Goldberg said. In one study, methylphenidate without a mood stabilizer caused an increase in manic episodes within 3 months (Am J Psychiatry. 2017 Apr 1;174:341-8).

“All may pose safe and effective evidence-based, albeit provisional, but evidence-based options to consider in targeting the attentional symptoms in patients with bipolar disorder,” Dr. Goldberg said.

He reported that he has been a consultant for BioXcel Therapeutics, Medscape/WebMD, Otsuka, and Sage Therapeutics. In addition, Dr. Goldberg is on the speakers bureau for Allergan, Neurocrine, Otsuka, and Sunovion; and receives royalties from American Psychiatric Publishing. Global Academy and this news organization are owned by the same parent company.

Cirrhosis may increase the risk of complications from endoscopic retrograde cholangiopancreatography (ERCP), according to a retrospective study involving almost 700 patients.

The study also showed that Child-Pugh class was a better predictor of risk than Model for End-Stage Liver Disease (MELD) score, reported lead author Michelle Bernshteyn, MD, a third-year internal medicine resident at State University of New York, Syracuse , and colleagues.

“There remains a scarcity in the literature regarding complications and adverse effects after ERCP in cirrhotic patients, particularly those incorporating Child-Pugh class and MELD score or type of intervention as predictors,” Dr. Bernshteyn said during a virtual presentation at the American College of Gastroenterology annual meeting. “Furthermore, literature review demonstrates inconsistency among results.”

To gain clarity, Dr. Bernshteyn and colleagues reviewed electronic medical records from 692 patients who underwent ERCP, of whom 174 had cirrhosis and 518 did not. For all patients, the investigators analyzed demographics, comorbidities, indications for ERCP, type of sedation, type of intervention, and complications within a 30-day period. Complications included bleeding, pancreatitis, cholangitis, perforation, mortality caused by ERCP, and mortality from other causes. Patients with cirrhosis were further analyzed based on etiology of cirrhosis, Child-Pugh class, and MELD score.

The analysis revealed that complications were significantly more common in patients with cirrhosis than in those without cirrhosis (21.30% vs. 13.51%; P = .015). No specific complications were significantly more common in patients with cirrhosis than in those without cirrhosis.

In patients with cirrhosis, 41.18% of Child-Pugh class C patients had complications, compared with 15.15% of class B patients and 19.30% of class A patients (P = .010). In contrast, MELD scores were not significantly associated with adverse events.

Further analysis showed that, in patients without cirrhosis, diagnostic-only ERCP and underlying chronic obstructive pulmonary disease were associated with high rates of complications (P = .039 and P = .003, respectively). In patients with cirrhosis, underlying chronic obstructive pulmonary disease and hypertension predicted adverse events (P = .009 and P = .003, respectively).

“The results of our study reaffirm that liver cirrhosis has an impact on the occurrence of complications during ERCP,” Dr. Bernshteyn said. “Child-Pugh class seems to be more reliable as compared to MELD score in predicting complications of ERCP in cirrhosis patients,” she added. “However, we are also aware that Child-Pugh and MELD scores are complementary to each other while evaluating outcomes of any surgery in patients with cirrhosis.”

In 2017, Udayakumar Navaneethan, MD, a gastroenterologist at AdventHealth Orlando’s Center for Interventional Endoscopy, and an assistant professor at the University of Central Florida, Orlando, and colleagues published a national database study concerning the safety of ERCP in patients with liver cirrhosis.

“[The present] study is important as it highlights the fact that ERCP is associated with significant complications in cirrhotic patients compared to those without cirrhosis,” Dr. Navaneethan said when asked to comment. “Also, Child-Pugh score appeared to be more reliable than MELD score in predicting complications of ERCP in cirrhotic patients.”

He went on to explain relevance for practicing clinicians. “The clinical implications of the study are that a detailed risk-benefit discussion needs to be done with patients with liver cirrhosis, particularly with advanced liver disease Child-Pugh class C, irrespective of the etiology,” Dr. Navaneethan said. “ERCP should be performed when there is clear evidence that the benefits outweigh the risks.” The investigators and Dr. Navaneethan reported no conflicts of interest.

SOURCE: Bernshteyn M et al. ACG 2020, Abstract S0982.

Cirrhosis may increase the risk of complications from endoscopic retrograde cholangiopancreatography (ERCP), according to a retrospective study involving almost 700 patients.

The study also showed that Child-Pugh class was a better predictor of risk than Model for End-Stage Liver Disease (MELD) score, reported lead author Michelle Bernshteyn, MD, a third-year internal medicine resident at State University of New York, Syracuse , and colleagues.

“There remains a scarcity in the literature regarding complications and adverse effects after ERCP in cirrhotic patients, particularly those incorporating Child-Pugh class and MELD score or type of intervention as predictors,” Dr. Bernshteyn said during a virtual presentation at the American College of Gastroenterology annual meeting. “Furthermore, literature review demonstrates inconsistency among results.”

To gain clarity, Dr. Bernshteyn and colleagues reviewed electronic medical records from 692 patients who underwent ERCP, of whom 174 had cirrhosis and 518 did not. For all patients, the investigators analyzed demographics, comorbidities, indications for ERCP, type of sedation, type of intervention, and complications within a 30-day period. Complications included bleeding, pancreatitis, cholangitis, perforation, mortality caused by ERCP, and mortality from other causes. Patients with cirrhosis were further analyzed based on etiology of cirrhosis, Child-Pugh class, and MELD score.

The analysis revealed that complications were significantly more common in patients with cirrhosis than in those without cirrhosis (21.30% vs. 13.51%; P = .015). No specific complications were significantly more common in patients with cirrhosis than in those without cirrhosis.

In patients with cirrhosis, 41.18% of Child-Pugh class C patients had complications, compared with 15.15% of class B patients and 19.30% of class A patients (P = .010). In contrast, MELD scores were not significantly associated with adverse events.

Further analysis showed that, in patients without cirrhosis, diagnostic-only ERCP and underlying chronic obstructive pulmonary disease were associated with high rates of complications (P = .039 and P = .003, respectively). In patients with cirrhosis, underlying chronic obstructive pulmonary disease and hypertension predicted adverse events (P = .009 and P = .003, respectively).

“The results of our study reaffirm that liver cirrhosis has an impact on the occurrence of complications during ERCP,” Dr. Bernshteyn said. “Child-Pugh class seems to be more reliable as compared to MELD score in predicting complications of ERCP in cirrhosis patients,” she added. “However, we are also aware that Child-Pugh and MELD scores are complementary to each other while evaluating outcomes of any surgery in patients with cirrhosis.”

In 2017, Udayakumar Navaneethan, MD, a gastroenterologist at AdventHealth Orlando’s Center for Interventional Endoscopy, and an assistant professor at the University of Central Florida, Orlando, and colleagues published a national database study concerning the safety of ERCP in patients with liver cirrhosis.

“[The present] study is important as it highlights the fact that ERCP is associated with significant complications in cirrhotic patients compared to those without cirrhosis,” Dr. Navaneethan said when asked to comment. “Also, Child-Pugh score appeared to be more reliable than MELD score in predicting complications of ERCP in cirrhotic patients.”

He went on to explain relevance for practicing clinicians. “The clinical implications of the study are that a detailed risk-benefit discussion needs to be done with patients with liver cirrhosis, particularly with advanced liver disease Child-Pugh class C, irrespective of the etiology,” Dr. Navaneethan said. “ERCP should be performed when there is clear evidence that the benefits outweigh the risks.” The investigators and Dr. Navaneethan reported no conflicts of interest.

SOURCE: Bernshteyn M et al. ACG 2020, Abstract S0982.

Cirrhosis may increase the risk of complications from endoscopic retrograde cholangiopancreatography (ERCP), according to a retrospective study involving almost 700 patients.

The study also showed that Child-Pugh class was a better predictor of risk than Model for End-Stage Liver Disease (MELD) score, reported lead author Michelle Bernshteyn, MD, a third-year internal medicine resident at State University of New York, Syracuse , and colleagues.

“There remains a scarcity in the literature regarding complications and adverse effects after ERCP in cirrhotic patients, particularly those incorporating Child-Pugh class and MELD score or type of intervention as predictors,” Dr. Bernshteyn said during a virtual presentation at the American College of Gastroenterology annual meeting. “Furthermore, literature review demonstrates inconsistency among results.”

To gain clarity, Dr. Bernshteyn and colleagues reviewed electronic medical records from 692 patients who underwent ERCP, of whom 174 had cirrhosis and 518 did not. For all patients, the investigators analyzed demographics, comorbidities, indications for ERCP, type of sedation, type of intervention, and complications within a 30-day period. Complications included bleeding, pancreatitis, cholangitis, perforation, mortality caused by ERCP, and mortality from other causes. Patients with cirrhosis were further analyzed based on etiology of cirrhosis, Child-Pugh class, and MELD score.

The analysis revealed that complications were significantly more common in patients with cirrhosis than in those without cirrhosis (21.30% vs. 13.51%; P = .015). No specific complications were significantly more common in patients with cirrhosis than in those without cirrhosis.

In patients with cirrhosis, 41.18% of Child-Pugh class C patients had complications, compared with 15.15% of class B patients and 19.30% of class A patients (P = .010). In contrast, MELD scores were not significantly associated with adverse events.

Further analysis showed that, in patients without cirrhosis, diagnostic-only ERCP and underlying chronic obstructive pulmonary disease were associated with high rates of complications (P = .039 and P = .003, respectively). In patients with cirrhosis, underlying chronic obstructive pulmonary disease and hypertension predicted adverse events (P = .009 and P = .003, respectively).

“The results of our study reaffirm that liver cirrhosis has an impact on the occurrence of complications during ERCP,” Dr. Bernshteyn said. “Child-Pugh class seems to be more reliable as compared to MELD score in predicting complications of ERCP in cirrhosis patients,” she added. “However, we are also aware that Child-Pugh and MELD scores are complementary to each other while evaluating outcomes of any surgery in patients with cirrhosis.”

In 2017, Udayakumar Navaneethan, MD, a gastroenterologist at AdventHealth Orlando’s Center for Interventional Endoscopy, and an assistant professor at the University of Central Florida, Orlando, and colleagues published a national database study concerning the safety of ERCP in patients with liver cirrhosis.

“[The present] study is important as it highlights the fact that ERCP is associated with significant complications in cirrhotic patients compared to those without cirrhosis,” Dr. Navaneethan said when asked to comment. “Also, Child-Pugh score appeared to be more reliable than MELD score in predicting complications of ERCP in cirrhotic patients.”

He went on to explain relevance for practicing clinicians. “The clinical implications of the study are that a detailed risk-benefit discussion needs to be done with patients with liver cirrhosis, particularly with advanced liver disease Child-Pugh class C, irrespective of the etiology,” Dr. Navaneethan said. “ERCP should be performed when there is clear evidence that the benefits outweigh the risks.” The investigators and Dr. Navaneethan reported no conflicts of interest.

SOURCE: Bernshteyn M et al. ACG 2020, Abstract S0982.

A short course of radiation therapy followed by neoadjuvant chemotherapy resulted in a clinical complete response (CR) in almost half of 90 patients with locally advanced rectal cancer, allowing the majority of responders to skip surgical resection, a retrospective study indicates.

Specifically, at a median follow-up of 16.6 months for living patients, the initial clinical CR rate was 48% overall.

“While we do not have enough follow-up yet to know the late side-effect profile of this regimen, our preliminary results are promising,” Re-I Chin, MD, of Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News in an email.

The study was presented at the virtual 2020 meeting of the American Society of Radiation Oncology (ASTRO).

“Certainly, longer follow-up will be needed in this study, but none of the observed patients to date has experienced an unsalvageable failure,” said meeting discussant Amol Narang, MD, of Johns Hopkins University, Baltimore, Maryland.

He reminded conference attendees that, despite good evidence supporting equivalency in oncologic outcomes between short-course radiation and long-course chemoradiation, the former is “highly underutilized in the US” with a mere 1% usage rate between 2004 and 2014.

The current study’s short-course treatment approach was compared in this setting to long-course chemoradiation and adjuvant chemotherapy in the RAPIDO trial reported at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), Narang pointed out.

Short-course patients had a higher rate of pathological complete response (pCR) and a lower rate of treatment failure compared with patients who received long-course chemoradiation and adjuvant chemotherapy; both patient groups underwent total mesorectal excision — which is different from the current analysis. The RAPIDO investigators concluded that the approach featuring the short course “can be considered as a new standard of care.”

Narang said the data collectively “begs the question as to whether the superiority of long-course chemoradiation should really have to be demonstrated to justify its use.”

But Chin highlighted toxicity issues. “Historically, there have been concerns regarding toxicity with short-course radiation therapy since it requires larger doses of radiation given over a shorter period of time,” Chin explained. “But [the short course] is particularly convenient for patients since it saves them more than a month of daily trips to the radiation oncology department.”
 

Seven local failures

The single-center study involved patients with newly diagnosed, nonmetastatic rectal adenocarcinoma treated with short-course radiation therapy followed by chemotherapy in 2018 and 2019. Nearly all (96%) had locally advanced disease, with either a T3/T4 tumor or node-positive disease. Median tumor size was 4.6 cm.

“Many of the patients in the study had low lying tumors,” Chin reported, with a median distance from the anal verge of 7 cm.

Radiation therapy was delivered in 25 Gy given in five fractions over 5 consecutive days, with the option to boost the dose to 30 Gy or 35 Gy in five fractions if extra-mesorectal lymph nodes were involved. Conventional 3D or intensity-modulated radiation was used and all patients completed treatment.

The median interval between diagnosis of rectal cancer and initiation of radiation therapy was 1.4 months, while the median interval between completion of radiation to initiation of chemotherapy was 2.7 weeks.

The most common chemotherapy regimen was FOLFOX – consisting of leucovorin, fluorouracil (5-FU), and oxaliplatin – or modified FOLFOX. For patients who received six or more cycles of chemotherapy, the median time spent on treatment was 3.9 months.

For those who completed at least six cycles of chemotherapy, the overall clinical CR was 51%, and, for patients with locally advanced disease, the clinical CR rate was 49%. Five of the 43 patients who achieved an initial clinical CR still underwent surgical resection because of patient or physician preference. Among this small group of patients, 4 of the 5 achieved a pCR, and the remaining patient achieved a pathological partial response (pPR).

A total of 42 patients (47% of the group) achieved a partial response following the radiation plus chemotherapy paradigm, and one patient had progressive disease. All underwent surgical resection. One patient did not complete chemotherapy and did not get surgery and subsequently died.

This left 38 patients to be managed nonoperatively. In this nonoperative cohort, 79% of patients continued to have a clinical CR at the end of follow-up. Of the 7 patients with local failure, 6 were salvaged by surgery, one was salvaged by chemotherapy, and all 7 treatment failures had no evidence of disease at last follow-up.

Of the small group of 5 patients who achieved an initial clinical CR following short-course radiation therapy and neoadjuvant chemotherapy, there were no further events in this group, whereas, for patients who achieved only an initial partial response or who had progressive disease, 72% remained event-free.

Approximately half of those who achieved a clinical CR to the treatment regimen had no late gastrointestinal toxicities, and no grade 3 or 4 toxicities were observed. “Surgical resection of tumors — even without a permanent stoma — can result in significantly decreased bowel function, so our goal is to treat patients without surgery and maintain good bowel function,” Chin noted.

“For rectal cancer, both short-course radiation therapy and nonoperative management are emerging treatment paradigms that may be more cost-effective and convenient compared to long-course chemoradiation followed by surgery, [especially since] the COVID-19 pandemic...has spurred changes in clinical practices in radiation oncology,” she said.

Chin has disclosed no relevant financial relationships. Narang reports receiving research support from Boston Scientific.
 

This article first appeared on Medscape.com.

A short course of radiation therapy followed by neoadjuvant chemotherapy resulted in a clinical complete response (CR) in almost half of 90 patients with locally advanced rectal cancer, allowing the majority of responders to skip surgical resection, a retrospective study indicates.

Specifically, at a median follow-up of 16.6 months for living patients, the initial clinical CR rate was 48% overall.

“While we do not have enough follow-up yet to know the late side-effect profile of this regimen, our preliminary results are promising,” Re-I Chin, MD, of Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News in an email.

The study was presented at the virtual 2020 meeting of the American Society of Radiation Oncology (ASTRO).

“Certainly, longer follow-up will be needed in this study, but none of the observed patients to date has experienced an unsalvageable failure,” said meeting discussant Amol Narang, MD, of Johns Hopkins University, Baltimore, Maryland.

He reminded conference attendees that, despite good evidence supporting equivalency in oncologic outcomes between short-course radiation and long-course chemoradiation, the former is “highly underutilized in the US” with a mere 1% usage rate between 2004 and 2014.

The current study’s short-course treatment approach was compared in this setting to long-course chemoradiation and adjuvant chemotherapy in the RAPIDO trial reported at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), Narang pointed out.

Short-course patients had a higher rate of pathological complete response (pCR) and a lower rate of treatment failure compared with patients who received long-course chemoradiation and adjuvant chemotherapy; both patient groups underwent total mesorectal excision — which is different from the current analysis. The RAPIDO investigators concluded that the approach featuring the short course “can be considered as a new standard of care.”

Narang said the data collectively “begs the question as to whether the superiority of long-course chemoradiation should really have to be demonstrated to justify its use.”

But Chin highlighted toxicity issues. “Historically, there have been concerns regarding toxicity with short-course radiation therapy since it requires larger doses of radiation given over a shorter period of time,” Chin explained. “But [the short course] is particularly convenient for patients since it saves them more than a month of daily trips to the radiation oncology department.”
 

Seven local failures

The single-center study involved patients with newly diagnosed, nonmetastatic rectal adenocarcinoma treated with short-course radiation therapy followed by chemotherapy in 2018 and 2019. Nearly all (96%) had locally advanced disease, with either a T3/T4 tumor or node-positive disease. Median tumor size was 4.6 cm.

“Many of the patients in the study had low lying tumors,” Chin reported, with a median distance from the anal verge of 7 cm.

Radiation therapy was delivered in 25 Gy given in five fractions over 5 consecutive days, with the option to boost the dose to 30 Gy or 35 Gy in five fractions if extra-mesorectal lymph nodes were involved. Conventional 3D or intensity-modulated radiation was used and all patients completed treatment.

The median interval between diagnosis of rectal cancer and initiation of radiation therapy was 1.4 months, while the median interval between completion of radiation to initiation of chemotherapy was 2.7 weeks.

The most common chemotherapy regimen was FOLFOX – consisting of leucovorin, fluorouracil (5-FU), and oxaliplatin – or modified FOLFOX. For patients who received six or more cycles of chemotherapy, the median time spent on treatment was 3.9 months.

For those who completed at least six cycles of chemotherapy, the overall clinical CR was 51%, and, for patients with locally advanced disease, the clinical CR rate was 49%. Five of the 43 patients who achieved an initial clinical CR still underwent surgical resection because of patient or physician preference. Among this small group of patients, 4 of the 5 achieved a pCR, and the remaining patient achieved a pathological partial response (pPR).

A total of 42 patients (47% of the group) achieved a partial response following the radiation plus chemotherapy paradigm, and one patient had progressive disease. All underwent surgical resection. One patient did not complete chemotherapy and did not get surgery and subsequently died.

This left 38 patients to be managed nonoperatively. In this nonoperative cohort, 79% of patients continued to have a clinical CR at the end of follow-up. Of the 7 patients with local failure, 6 were salvaged by surgery, one was salvaged by chemotherapy, and all 7 treatment failures had no evidence of disease at last follow-up.

Of the small group of 5 patients who achieved an initial clinical CR following short-course radiation therapy and neoadjuvant chemotherapy, there were no further events in this group, whereas, for patients who achieved only an initial partial response or who had progressive disease, 72% remained event-free.

Approximately half of those who achieved a clinical CR to the treatment regimen had no late gastrointestinal toxicities, and no grade 3 or 4 toxicities were observed. “Surgical resection of tumors — even without a permanent stoma — can result in significantly decreased bowel function, so our goal is to treat patients without surgery and maintain good bowel function,” Chin noted.

“For rectal cancer, both short-course radiation therapy and nonoperative management are emerging treatment paradigms that may be more cost-effective and convenient compared to long-course chemoradiation followed by surgery, [especially since] the COVID-19 pandemic...has spurred changes in clinical practices in radiation oncology,” she said.

Chin has disclosed no relevant financial relationships. Narang reports receiving research support from Boston Scientific.
 

This article first appeared on Medscape.com.

A short course of radiation therapy followed by neoadjuvant chemotherapy resulted in a clinical complete response (CR) in almost half of 90 patients with locally advanced rectal cancer, allowing the majority of responders to skip surgical resection, a retrospective study indicates.

Specifically, at a median follow-up of 16.6 months for living patients, the initial clinical CR rate was 48% overall.

“While we do not have enough follow-up yet to know the late side-effect profile of this regimen, our preliminary results are promising,” Re-I Chin, MD, of Washington University School of Medicine, St. Louis, Missouri, told Medscape Medical News in an email.

The study was presented at the virtual 2020 meeting of the American Society of Radiation Oncology (ASTRO).

“Certainly, longer follow-up will be needed in this study, but none of the observed patients to date has experienced an unsalvageable failure,” said meeting discussant Amol Narang, MD, of Johns Hopkins University, Baltimore, Maryland.

He reminded conference attendees that, despite good evidence supporting equivalency in oncologic outcomes between short-course radiation and long-course chemoradiation, the former is “highly underutilized in the US” with a mere 1% usage rate between 2004 and 2014.

The current study’s short-course treatment approach was compared in this setting to long-course chemoradiation and adjuvant chemotherapy in the RAPIDO trial reported at the 2020 annual meeting of the American Society of Clinical Oncology (ASCO), Narang pointed out.

Short-course patients had a higher rate of pathological complete response (pCR) and a lower rate of treatment failure compared with patients who received long-course chemoradiation and adjuvant chemotherapy; both patient groups underwent total mesorectal excision — which is different from the current analysis. The RAPIDO investigators concluded that the approach featuring the short course “can be considered as a new standard of care.”

Narang said the data collectively “begs the question as to whether the superiority of long-course chemoradiation should really have to be demonstrated to justify its use.”

But Chin highlighted toxicity issues. “Historically, there have been concerns regarding toxicity with short-course radiation therapy since it requires larger doses of radiation given over a shorter period of time,” Chin explained. “But [the short course] is particularly convenient for patients since it saves them more than a month of daily trips to the radiation oncology department.”
 

Seven local failures

The single-center study involved patients with newly diagnosed, nonmetastatic rectal adenocarcinoma treated with short-course radiation therapy followed by chemotherapy in 2018 and 2019. Nearly all (96%) had locally advanced disease, with either a T3/T4 tumor or node-positive disease. Median tumor size was 4.6 cm.

“Many of the patients in the study had low lying tumors,” Chin reported, with a median distance from the anal verge of 7 cm.

Radiation therapy was delivered in 25 Gy given in five fractions over 5 consecutive days, with the option to boost the dose to 30 Gy or 35 Gy in five fractions if extra-mesorectal lymph nodes were involved. Conventional 3D or intensity-modulated radiation was used and all patients completed treatment.

The median interval between diagnosis of rectal cancer and initiation of radiation therapy was 1.4 months, while the median interval between completion of radiation to initiation of chemotherapy was 2.7 weeks.

The most common chemotherapy regimen was FOLFOX – consisting of leucovorin, fluorouracil (5-FU), and oxaliplatin – or modified FOLFOX. For patients who received six or more cycles of chemotherapy, the median time spent on treatment was 3.9 months.

For those who completed at least six cycles of chemotherapy, the overall clinical CR was 51%, and, for patients with locally advanced disease, the clinical CR rate was 49%. Five of the 43 patients who achieved an initial clinical CR still underwent surgical resection because of patient or physician preference. Among this small group of patients, 4 of the 5 achieved a pCR, and the remaining patient achieved a pathological partial response (pPR).

A total of 42 patients (47% of the group) achieved a partial response following the radiation plus chemotherapy paradigm, and one patient had progressive disease. All underwent surgical resection. One patient did not complete chemotherapy and did not get surgery and subsequently died.

This left 38 patients to be managed nonoperatively. In this nonoperative cohort, 79% of patients continued to have a clinical CR at the end of follow-up. Of the 7 patients with local failure, 6 were salvaged by surgery, one was salvaged by chemotherapy, and all 7 treatment failures had no evidence of disease at last follow-up.

Of the small group of 5 patients who achieved an initial clinical CR following short-course radiation therapy and neoadjuvant chemotherapy, there were no further events in this group, whereas, for patients who achieved only an initial partial response or who had progressive disease, 72% remained event-free.

Approximately half of those who achieved a clinical CR to the treatment regimen had no late gastrointestinal toxicities, and no grade 3 or 4 toxicities were observed. “Surgical resection of tumors — even without a permanent stoma — can result in significantly decreased bowel function, so our goal is to treat patients without surgery and maintain good bowel function,” Chin noted.

“For rectal cancer, both short-course radiation therapy and nonoperative management are emerging treatment paradigms that may be more cost-effective and convenient compared to long-course chemoradiation followed by surgery, [especially since] the COVID-19 pandemic...has spurred changes in clinical practices in radiation oncology,” she said.

Chin has disclosed no relevant financial relationships. Narang reports receiving research support from Boston Scientific.
 

This article first appeared on Medscape.com.