More than 170 physician groups are calling on the Centers for Medicare & Medicaid Services to withdraw a provision in the proposed 2019 physician fee schedule that would flatten evaluation and management payments.

TheaDesign/Thinkstock

The controversial proposal would set the payment rate for a level 1 evaluation and management (E/M) office visit for a new patient at $44, down from the $45 using the current methodology. Payment for levels 2-5 would be $135. Currently, payments for level 2 new patient visits are set at $76, level 3 at $110, level 4 at $167, and level 5 at $211.

For E/M office visits with established patients, the proposed rate would be $24 for level 1, up from the current payment of $22. Payment for levels 2-5 would be $93. Under the current methodology, payments for established patient level 2 visits are set at $45, level 3 at $74, level 4 at $109, and level 5 at $148.

In an Aug. 28 letter to the CMS, led by the American College of Rheumatology, physician groups applauded CMS recognition of the problems with the current E/M documentation guidelines and codes, but urged them to reconsider plans to “cut and consolidate evaluation and management services.” Doing so would “severely reduce Medicare patients’ access to care by cutting payments for complex office visits, adversely affecting the care and treatment of patients with complex conditions, and potentially exacerbate physician workforce shortages.”

A separate letter, led by the American Medical Association, made similar assertions that the current proposal has the potential to “hurt physicians and other health care professionals in specialties that treat the sickest patients, as well as those who provide comprehensive primary care, ultimately jeopardizing patients’ access to care.”

The American Gastroenterological Association sigend on to both letters.

AGA, along with the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy, sent out a member alert, asking their members to tell CMS not to move forward with the proposed change because all three societies believe that such a payment system undervalues care provided to their sickest and most vulnerable seniors and other Medicare beneficiaries.

Another concern related to the implementation of this proposal is the financial impact on physicians.

Implementation of the CMS proposal, as currently written, “would be amazingly expensive for private practice [doctors] and really for anyone else because we would have to change our EMRs,” Barbara Levy, MD, cochair of the CPT/RUC Work Group at the AMA.

“We would have to reprogram our billing software. All of that comes with a significant cost,” said Dr. Levy, who also serves as vice president of health policy at the American College of Obstetricians and Gynecologists.

Part of the selling point of the CMS proposal is the reduction in documentation that accompanies the E/M payment changes. The goal, according to the CMS, is to reduce time spent on paperwork and free up physicians to devote more time to patient care. But some physicians are skeptical it would work out that way.

"CMS has clearly heard from physicians about the need to reduce administrative burdens for physicians, and AGA appreciates that they're listening," said Peter S. Margolis, MD, AGAF, AGA Practice Councillor, University Gastroenterology, Providence, Rhode Island. "However, CMS' proposal drastically undervalues the care gastroenterologists and hepatologists provide to complex patients, including but not limited to those with inflammatory bowel disease, motility disorders, and chronic liver disease. Additionally, our experience shows that utilization management methods, such as prior authorization and step therapy appeals, are far more burdensome to physicians and physician practices than current E/M documentation requirements." 

Another element of the proposal that is raising concerns among physician groups is a proposed payment reduction when a visit involves more than one service. For example, when a single office visit includes both an E/M code and a procedure code, the proposal calls for the E/M code to be cut in half.

“From the patients’ perspective, the potential threat is that doctors could be incentivized to spend less time with patients or potentially bring patients back for subsequent visits to handle multiple problems,” Angus Worthing, MD, chair of the American College of Rheumatology’s Committee on Government Affairs, said in an interview.

Comments on the proposed update to the 2019 Medicare physician fee schedule are due Sept. 10.

gtwachtman@mdedge.com

More than 170 physician groups are calling on the Centers for Medicare & Medicaid Services to withdraw a provision in the proposed 2019 physician fee schedule that would flatten evaluation and management payments.

TheaDesign/Thinkstock

The controversial proposal would set the payment rate for a level 1 evaluation and management (E/M) office visit for a new patient at $44, down from the $45 using the current methodology. Payment for levels 2-5 would be $135. Currently, payments for level 2 new patient visits are set at $76, level 3 at $110, level 4 at $167, and level 5 at $211.

For E/M office visits with established patients, the proposed rate would be $24 for level 1, up from the current payment of $22. Payment for levels 2-5 would be $93. Under the current methodology, payments for established patient level 2 visits are set at $45, level 3 at $74, level 4 at $109, and level 5 at $148.

In an Aug. 28 letter to the CMS, led by the American College of Rheumatology, physician groups applauded CMS recognition of the problems with the current E/M documentation guidelines and codes, but urged them to reconsider plans to “cut and consolidate evaluation and management services.” Doing so would “severely reduce Medicare patients’ access to care by cutting payments for complex office visits, adversely affecting the care and treatment of patients with complex conditions, and potentially exacerbate physician workforce shortages.”

A separate letter, led by the American Medical Association, made similar assertions that the current proposal has the potential to “hurt physicians and other health care professionals in specialties that treat the sickest patients, as well as those who provide comprehensive primary care, ultimately jeopardizing patients’ access to care.”

The American Gastroenterological Association sigend on to both letters.

AGA, along with the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy, sent out a member alert, asking their members to tell CMS not to move forward with the proposed change because all three societies believe that such a payment system undervalues care provided to their sickest and most vulnerable seniors and other Medicare beneficiaries.

Another concern related to the implementation of this proposal is the financial impact on physicians.

Implementation of the CMS proposal, as currently written, “would be amazingly expensive for private practice [doctors] and really for anyone else because we would have to change our EMRs,” Barbara Levy, MD, cochair of the CPT/RUC Work Group at the AMA.

“We would have to reprogram our billing software. All of that comes with a significant cost,” said Dr. Levy, who also serves as vice president of health policy at the American College of Obstetricians and Gynecologists.

Part of the selling point of the CMS proposal is the reduction in documentation that accompanies the E/M payment changes. The goal, according to the CMS, is to reduce time spent on paperwork and free up physicians to devote more time to patient care. But some physicians are skeptical it would work out that way.

"CMS has clearly heard from physicians about the need to reduce administrative burdens for physicians, and AGA appreciates that they're listening," said Peter S. Margolis, MD, AGAF, AGA Practice Councillor, University Gastroenterology, Providence, Rhode Island. "However, CMS' proposal drastically undervalues the care gastroenterologists and hepatologists provide to complex patients, including but not limited to those with inflammatory bowel disease, motility disorders, and chronic liver disease. Additionally, our experience shows that utilization management methods, such as prior authorization and step therapy appeals, are far more burdensome to physicians and physician practices than current E/M documentation requirements." 

Another element of the proposal that is raising concerns among physician groups is a proposed payment reduction when a visit involves more than one service. For example, when a single office visit includes both an E/M code and a procedure code, the proposal calls for the E/M code to be cut in half.

“From the patients’ perspective, the potential threat is that doctors could be incentivized to spend less time with patients or potentially bring patients back for subsequent visits to handle multiple problems,” Angus Worthing, MD, chair of the American College of Rheumatology’s Committee on Government Affairs, said in an interview.

Comments on the proposed update to the 2019 Medicare physician fee schedule are due Sept. 10.

gtwachtman@mdedge.com

More than 170 physician groups are calling on the Centers for Medicare & Medicaid Services to withdraw a provision in the proposed 2019 physician fee schedule that would flatten evaluation and management payments.

TheaDesign/Thinkstock

The controversial proposal would set the payment rate for a level 1 evaluation and management (E/M) office visit for a new patient at $44, down from the $45 using the current methodology. Payment for levels 2-5 would be $135. Currently, payments for level 2 new patient visits are set at $76, level 3 at $110, level 4 at $167, and level 5 at $211.

For E/M office visits with established patients, the proposed rate would be $24 for level 1, up from the current payment of $22. Payment for levels 2-5 would be $93. Under the current methodology, payments for established patient level 2 visits are set at $45, level 3 at $74, level 4 at $109, and level 5 at $148.

In an Aug. 28 letter to the CMS, led by the American College of Rheumatology, physician groups applauded CMS recognition of the problems with the current E/M documentation guidelines and codes, but urged them to reconsider plans to “cut and consolidate evaluation and management services.” Doing so would “severely reduce Medicare patients’ access to care by cutting payments for complex office visits, adversely affecting the care and treatment of patients with complex conditions, and potentially exacerbate physician workforce shortages.”

A separate letter, led by the American Medical Association, made similar assertions that the current proposal has the potential to “hurt physicians and other health care professionals in specialties that treat the sickest patients, as well as those who provide comprehensive primary care, ultimately jeopardizing patients’ access to care.”

The American Gastroenterological Association sigend on to both letters.

AGA, along with the American College of Gastroenterology and the American Society for Gastrointestinal Endoscopy, sent out a member alert, asking their members to tell CMS not to move forward with the proposed change because all three societies believe that such a payment system undervalues care provided to their sickest and most vulnerable seniors and other Medicare beneficiaries.

Another concern related to the implementation of this proposal is the financial impact on physicians.

Implementation of the CMS proposal, as currently written, “would be amazingly expensive for private practice [doctors] and really for anyone else because we would have to change our EMRs,” Barbara Levy, MD, cochair of the CPT/RUC Work Group at the AMA.

“We would have to reprogram our billing software. All of that comes with a significant cost,” said Dr. Levy, who also serves as vice president of health policy at the American College of Obstetricians and Gynecologists.

Part of the selling point of the CMS proposal is the reduction in documentation that accompanies the E/M payment changes. The goal, according to the CMS, is to reduce time spent on paperwork and free up physicians to devote more time to patient care. But some physicians are skeptical it would work out that way.

"CMS has clearly heard from physicians about the need to reduce administrative burdens for physicians, and AGA appreciates that they're listening," said Peter S. Margolis, MD, AGAF, AGA Practice Councillor, University Gastroenterology, Providence, Rhode Island. "However, CMS' proposal drastically undervalues the care gastroenterologists and hepatologists provide to complex patients, including but not limited to those with inflammatory bowel disease, motility disorders, and chronic liver disease. Additionally, our experience shows that utilization management methods, such as prior authorization and step therapy appeals, are far more burdensome to physicians and physician practices than current E/M documentation requirements." 

Another element of the proposal that is raising concerns among physician groups is a proposed payment reduction when a visit involves more than one service. For example, when a single office visit includes both an E/M code and a procedure code, the proposal calls for the E/M code to be cut in half.

“From the patients’ perspective, the potential threat is that doctors could be incentivized to spend less time with patients or potentially bring patients back for subsequent visits to handle multiple problems,” Angus Worthing, MD, chair of the American College of Rheumatology’s Committee on Government Affairs, said in an interview.

Comments on the proposed update to the 2019 Medicare physician fee schedule are due Sept. 10.

gtwachtman@mdedge.com

New research suggests that investigators involved in oncology trials sometimes fail to disclose payments from the pharmaceutical industry.

utah778/Thinkstock

Researchers looked at clinical trials associated with cancer drugs recently approved in the United States and assessed whether funding was properly disclosed when the trial results were published in scientific journals.

The data showed that roughly a third of investigators failed to completely disclose payments from trial sponsors.

“We know that pharmaceutical companies sponsor trials of their own drugs. That’s not a surprise,” Cole Wayant, a DO/PhD student at Oklahoma State University in Tulsa, said in a statement. “But what is a surprise, and what warrants concern, is that this funding is often not disclosed in the publication of clinical trials that form the basis of FDA [Food and Drug Administration] approvals and clinical practice guidelines.”

Mr. Wayant and his colleagues conducted this research and reported the findings in a research letter published in JAMA Oncology.

The researchers began by searching the FDA Hematology/Oncology Approvals & Safety Notifications website for oncology drugs approved from Jan. 1, 2016, to Aug. 31, 2017.

The team then identified the published trials supporting these drug approvals and searched the Open Payments Database for industry payment data for each U.S.-based oncologist involved in the trials. Finally, the researchers compared the Open Payments data to the disclosure statements from the publications.

There were 344 authors of clinical trials associated with oncology drugs approved during the period studied. Most authors (76.5%) received at least one industry payment, and the total amount they received exceeded $216 million.

Nearly a third of the authors (32%, n = 110) did not fully disclose payments from a trial sponsor.

In all, the authors received about $6.3 million in general payments, such as speaking fees, and $1.7 million of that was undisclosed.

They received more than $500,000 in research payments, such as fees for study coordination, and more than $200,000 of that was undisclosed.

The authors received close to $210 million in associated research payments, such as grants, and about $78 million of that was undisclosed.

Mr. Wayant and his colleagues said these results suggest financial relationships between the pharmaceutical industry and oncology trial investigators “may be common, expensive, and frequently undisclosed.”

However, the research also suggests that Open Payments data could be used to ensure complete disclosure of industry payments.

The researchers reported having no financial disclosures.

jensmith@mdedge.com

SOURCE: Wayant C et al. JAMA Oncol. 2018 Aug 30. doi: 10.1001/jamaoncol.2018.3738.

New research suggests that investigators involved in oncology trials sometimes fail to disclose payments from the pharmaceutical industry.

utah778/Thinkstock

Researchers looked at clinical trials associated with cancer drugs recently approved in the United States and assessed whether funding was properly disclosed when the trial results were published in scientific journals.

The data showed that roughly a third of investigators failed to completely disclose payments from trial sponsors.

“We know that pharmaceutical companies sponsor trials of their own drugs. That’s not a surprise,” Cole Wayant, a DO/PhD student at Oklahoma State University in Tulsa, said in a statement. “But what is a surprise, and what warrants concern, is that this funding is often not disclosed in the publication of clinical trials that form the basis of FDA [Food and Drug Administration] approvals and clinical practice guidelines.”

Mr. Wayant and his colleagues conducted this research and reported the findings in a research letter published in JAMA Oncology.

The researchers began by searching the FDA Hematology/Oncology Approvals & Safety Notifications website for oncology drugs approved from Jan. 1, 2016, to Aug. 31, 2017.

The team then identified the published trials supporting these drug approvals and searched the Open Payments Database for industry payment data for each U.S.-based oncologist involved in the trials. Finally, the researchers compared the Open Payments data to the disclosure statements from the publications.

There were 344 authors of clinical trials associated with oncology drugs approved during the period studied. Most authors (76.5%) received at least one industry payment, and the total amount they received exceeded $216 million.

Nearly a third of the authors (32%, n = 110) did not fully disclose payments from a trial sponsor.

In all, the authors received about $6.3 million in general payments, such as speaking fees, and $1.7 million of that was undisclosed.

They received more than $500,000 in research payments, such as fees for study coordination, and more than $200,000 of that was undisclosed.

The authors received close to $210 million in associated research payments, such as grants, and about $78 million of that was undisclosed.

Mr. Wayant and his colleagues said these results suggest financial relationships between the pharmaceutical industry and oncology trial investigators “may be common, expensive, and frequently undisclosed.”

However, the research also suggests that Open Payments data could be used to ensure complete disclosure of industry payments.

The researchers reported having no financial disclosures.

jensmith@mdedge.com

SOURCE: Wayant C et al. JAMA Oncol. 2018 Aug 30. doi: 10.1001/jamaoncol.2018.3738.

New research suggests that investigators involved in oncology trials sometimes fail to disclose payments from the pharmaceutical industry.

utah778/Thinkstock

Researchers looked at clinical trials associated with cancer drugs recently approved in the United States and assessed whether funding was properly disclosed when the trial results were published in scientific journals.

The data showed that roughly a third of investigators failed to completely disclose payments from trial sponsors.

“We know that pharmaceutical companies sponsor trials of their own drugs. That’s not a surprise,” Cole Wayant, a DO/PhD student at Oklahoma State University in Tulsa, said in a statement. “But what is a surprise, and what warrants concern, is that this funding is often not disclosed in the publication of clinical trials that form the basis of FDA [Food and Drug Administration] approvals and clinical practice guidelines.”

Mr. Wayant and his colleagues conducted this research and reported the findings in a research letter published in JAMA Oncology.

The researchers began by searching the FDA Hematology/Oncology Approvals & Safety Notifications website for oncology drugs approved from Jan. 1, 2016, to Aug. 31, 2017.

The team then identified the published trials supporting these drug approvals and searched the Open Payments Database for industry payment data for each U.S.-based oncologist involved in the trials. Finally, the researchers compared the Open Payments data to the disclosure statements from the publications.

There were 344 authors of clinical trials associated with oncology drugs approved during the period studied. Most authors (76.5%) received at least one industry payment, and the total amount they received exceeded $216 million.

Nearly a third of the authors (32%, n = 110) did not fully disclose payments from a trial sponsor.

In all, the authors received about $6.3 million in general payments, such as speaking fees, and $1.7 million of that was undisclosed.

They received more than $500,000 in research payments, such as fees for study coordination, and more than $200,000 of that was undisclosed.

The authors received close to $210 million in associated research payments, such as grants, and about $78 million of that was undisclosed.

Mr. Wayant and his colleagues said these results suggest financial relationships between the pharmaceutical industry and oncology trial investigators “may be common, expensive, and frequently undisclosed.”

However, the research also suggests that Open Payments data could be used to ensure complete disclosure of industry payments.

The researchers reported having no financial disclosures.

jensmith@mdedge.com

SOURCE: Wayant C et al. JAMA Oncol. 2018 Aug 30. doi: 10.1001/jamaoncol.2018.3738.

Background: Septic shock is a serious and common health problem, associated with a more than 50% mortality rate. It is characterized by a dysregulated patient response to infection, resulting in life-threatening circulatory, cellular, and metabolic abnormalities. The benefit of corticosteroid use in septic shock is still controversial.

Dr. Salih is a hospitalist and instructor in the division of hospital medicine at the University of Kentucky, Lexington.
 

Background: Septic shock is a serious and common health problem, associated with a more than 50% mortality rate. It is characterized by a dysregulated patient response to infection, resulting in life-threatening circulatory, cellular, and metabolic abnormalities. The benefit of corticosteroid use in septic shock is still controversial.

Dr. Salih is a hospitalist and instructor in the division of hospital medicine at the University of Kentucky, Lexington.
 

Background: Septic shock is a serious and common health problem, associated with a more than 50% mortality rate. It is characterized by a dysregulated patient response to infection, resulting in life-threatening circulatory, cellular, and metabolic abnormalities. The benefit of corticosteroid use in septic shock is still controversial.

Dr. Salih is a hospitalist and instructor in the division of hospital medicine at the University of Kentucky, Lexington.
 

Click here to view the articles published in September 2018.

Click here to view the articles published in September 2018.

Click here to view the articles published in September 2018.

An escalating methotrexate strategy provided superior survival outcomes compared with high-dose methotrexate in a chemotherapy regimen for children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), results of a large, randomized trial show.

There were also fewer relapses reported for escalating versus high-dose methotrexate in the study, which evaluated the effects of these two intensification strategies in patients receiving an augmented Berlin-Frankfurt-Muenster (ABFM) chemotherapy regimen.

These findings come from a report in the Journal of Clinical Oncology on the Children’s Oncology Group (COG) AALL0434 trial, which to the knowledge of the investigators is the largest T-ALL study ever conducted.

The improved survival outcomes in AALL0434 are the “opposite effect” of what was observed in a parallel trial, AALL0232, showing that high-dose methotrexate was superior to the escalating strategy in B-cell acute lymphoblastic leukemia (B-ALL), the authors reported.

The parallel trial design was in fact used because of the known differences between T-ALL and B-ALL in sensitivity to methotrexate and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Cancer and Blood Disorders Program, Minneapolis, and his coauthors.

“Although treatment intensification has improved survival for children with ALL, the best timing and sequence of key therapeutic interventions, such as asparaginase and methotrexate, which seem to be particularly important for T-ALL, remain unclear,” Dr. Winter and his colleagues said.

In the AALL0434 study, a total of 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia were randomized to postinduction therapy that included either the so-called Capizzi-style escalating intravenous methotrexate or high-dose methotrexate.

The escalating intravenous regimen was superior to high-dose methotrexate, according to investigators. Respectively, the 5-year rate of disease-free survival was 91.5% versus 85.3% (P = .005) and the 5-year rate of overall survival was 93.7% versus 89.4% (P = .036).

Relapses were observed in 32 patients receiving the escalating regimen, versus 59 for patients receiving high-dose methotrexate.

By contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose methotrexate had superior 5-year event-free survival and overall survival, leading Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different methotrexate schedules, due to differences in doses of pegaspargase, 6-MP, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated methotrexate had two additional doses of pegaspargase. As a result, enhanced asparagine depletion in that arm may have also prevented relapse events, the investigators said.

Differences in adherence could also have played a role, as the cost and time burden of the escalated approach are “substantially less” than the high-dose approach, they added.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved disease-free survival, including a 91% 4-year disease-free survival rate for patients receiving both nelarabine and escalating-dose methotrexate.

The study was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. Study coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

hematologynews@mdedge.com

SOURCE: Winter SS et al. J Clin Oncol. 2018 Aug 23: doi: 10.1200/JCO.2018.77.7250.

An escalating methotrexate strategy provided superior survival outcomes compared with high-dose methotrexate in a chemotherapy regimen for children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), results of a large, randomized trial show.

There were also fewer relapses reported for escalating versus high-dose methotrexate in the study, which evaluated the effects of these two intensification strategies in patients receiving an augmented Berlin-Frankfurt-Muenster (ABFM) chemotherapy regimen.

These findings come from a report in the Journal of Clinical Oncology on the Children’s Oncology Group (COG) AALL0434 trial, which to the knowledge of the investigators is the largest T-ALL study ever conducted.

The improved survival outcomes in AALL0434 are the “opposite effect” of what was observed in a parallel trial, AALL0232, showing that high-dose methotrexate was superior to the escalating strategy in B-cell acute lymphoblastic leukemia (B-ALL), the authors reported.

The parallel trial design was in fact used because of the known differences between T-ALL and B-ALL in sensitivity to methotrexate and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Cancer and Blood Disorders Program, Minneapolis, and his coauthors.

“Although treatment intensification has improved survival for children with ALL, the best timing and sequence of key therapeutic interventions, such as asparaginase and methotrexate, which seem to be particularly important for T-ALL, remain unclear,” Dr. Winter and his colleagues said.

In the AALL0434 study, a total of 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia were randomized to postinduction therapy that included either the so-called Capizzi-style escalating intravenous methotrexate or high-dose methotrexate.

The escalating intravenous regimen was superior to high-dose methotrexate, according to investigators. Respectively, the 5-year rate of disease-free survival was 91.5% versus 85.3% (P = .005) and the 5-year rate of overall survival was 93.7% versus 89.4% (P = .036).

Relapses were observed in 32 patients receiving the escalating regimen, versus 59 for patients receiving high-dose methotrexate.

By contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose methotrexate had superior 5-year event-free survival and overall survival, leading Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different methotrexate schedules, due to differences in doses of pegaspargase, 6-MP, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated methotrexate had two additional doses of pegaspargase. As a result, enhanced asparagine depletion in that arm may have also prevented relapse events, the investigators said.

Differences in adherence could also have played a role, as the cost and time burden of the escalated approach are “substantially less” than the high-dose approach, they added.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved disease-free survival, including a 91% 4-year disease-free survival rate for patients receiving both nelarabine and escalating-dose methotrexate.

The study was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. Study coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

hematologynews@mdedge.com

SOURCE: Winter SS et al. J Clin Oncol. 2018 Aug 23: doi: 10.1200/JCO.2018.77.7250.

An escalating methotrexate strategy provided superior survival outcomes compared with high-dose methotrexate in a chemotherapy regimen for children and young adults with T-cell acute lymphoblastic leukemia (T-ALL), results of a large, randomized trial show.

There were also fewer relapses reported for escalating versus high-dose methotrexate in the study, which evaluated the effects of these two intensification strategies in patients receiving an augmented Berlin-Frankfurt-Muenster (ABFM) chemotherapy regimen.

These findings come from a report in the Journal of Clinical Oncology on the Children’s Oncology Group (COG) AALL0434 trial, which to the knowledge of the investigators is the largest T-ALL study ever conducted.

The improved survival outcomes in AALL0434 are the “opposite effect” of what was observed in a parallel trial, AALL0232, showing that high-dose methotrexate was superior to the escalating strategy in B-cell acute lymphoblastic leukemia (B-ALL), the authors reported.

The parallel trial design was in fact used because of the known differences between T-ALL and B-ALL in sensitivity to methotrexate and pegaspargase, according to investigator Stuart S. Winter, MD, of Children’s Minnesota Cancer and Blood Disorders Program, Minneapolis, and his coauthors.

“Although treatment intensification has improved survival for children with ALL, the best timing and sequence of key therapeutic interventions, such as asparaginase and methotrexate, which seem to be particularly important for T-ALL, remain unclear,” Dr. Winter and his colleagues said.

In the AALL0434 study, a total of 1,031 T-ALL patients between 1 and 31 years of age without CNS3 disease or testicular leukemia were randomized to postinduction therapy that included either the so-called Capizzi-style escalating intravenous methotrexate or high-dose methotrexate.

The escalating intravenous regimen was superior to high-dose methotrexate, according to investigators. Respectively, the 5-year rate of disease-free survival was 91.5% versus 85.3% (P = .005) and the 5-year rate of overall survival was 93.7% versus 89.4% (P = .036).

Relapses were observed in 32 patients receiving the escalating regimen, versus 59 for patients receiving high-dose methotrexate.

By contrast, the parallel AALL0232 study of B-ALL patients showed that high-dose methotrexate had superior 5-year event-free survival and overall survival, leading Dr. Winter and his colleagues to speculate on how the findings could be reconciled.

Neither trial was a strict comparison of two different methotrexate schedules, due to differences in doses of pegaspargase, 6-MP, and vincristine between arms, as well as differences in the timing of cranial radiation therapy.

Of note, patients randomized to escalated methotrexate had two additional doses of pegaspargase. As a result, enhanced asparagine depletion in that arm may have also prevented relapse events, the investigators said.

Differences in adherence could also have played a role, as the cost and time burden of the escalated approach are “substantially less” than the high-dose approach, they added.

The AALL0434 trial also included a second randomization to an addition of five, 6-day cycles of nelarabine versus no nelarabine. Results of that randomization, reported earlier this year, showed that nelarabine improved disease-free survival, including a 91% 4-year disease-free survival rate for patients receiving both nelarabine and escalating-dose methotrexate.

The study was supported by grants from the National Institutes of Health and by St. Baldrick’s Foundation. Dr. Winter reported relationships with Amgen and Jazz Pharmaceuticals. Study coauthors reported relationships with Novo Nordisk, Tandem, Pfizer, Novartis, and TypeZero Technologies, among others.

hematologynews@mdedge.com

SOURCE: Winter SS et al. J Clin Oncol. 2018 Aug 23: doi: 10.1200/JCO.2018.77.7250.

Adults with obstructive sleep apnea are approximately twice as likely as are those without it to develop gout, according to data from a large, retrospective study with a median 5-year follow-up.

copyright designer491/Thinkstock

Data from previous studies have shown an increased risk in developing gout within the first year of an obstructive sleep apnea (OSA) diagnosis, wrote Milica Blagojevic-Bucknall, PhD, of Keele (England) University, and her colleagues.

In a study published in Arthritis & Rheumatology, the researchers compared 15,879 patients with OSA and 63,296 without.

Overall, 4.9% of OSA patients and 2.6% non‐OSA controls developed gout over a median follow‐up period of 5.8 years. The incidence rate for gout per 1,000 person‐years was 7.83 among patients with OSA and 4.03 for controls (adjusted hazard ratio, 1.42). The greatest risk for gout in the OSA patients occurred approximately 1-2 years after their diagnosis.

The researchers also found significant associations between body mass index and gout risk in sleep apnea across all BMI categories, but the strongest association occurred in the normal BMI group (HR 2.02) at 2-5 years after the index date of OSA.

“The novelty of this study lies in assessing both the short- and long-term association of OSA with incident gout in a large primary care-based population,” the researchers said. They proposed that the most likely explanation for the events was that “intermittent hypoxia increases nucleotide turnover which enhances endogenous uric acid production.”

The study findings were limited by several factors including potential misclassification of OSA and the impact of confounding variables such as genetics and diet, they noted.

However, the results support the association between sleep apnea and gout, but also serve to highlight that clinicians should “consider the possibility of gout in patients with sleep apnea regardless of obesity,” the researchers wrote.

The National Institute for Health Research funded the study. The authors have no conflicts of interest to declare.

SOURCE: Blagojevic-Bucknall M et al. Arthritis Rheumatol. 2018 Aug 30. doi: 10.1002/art.40662.

Adults with obstructive sleep apnea are approximately twice as likely as are those without it to develop gout, according to data from a large, retrospective study with a median 5-year follow-up.

copyright designer491/Thinkstock

Data from previous studies have shown an increased risk in developing gout within the first year of an obstructive sleep apnea (OSA) diagnosis, wrote Milica Blagojevic-Bucknall, PhD, of Keele (England) University, and her colleagues.

In a study published in Arthritis & Rheumatology, the researchers compared 15,879 patients with OSA and 63,296 without.

Overall, 4.9% of OSA patients and 2.6% non‐OSA controls developed gout over a median follow‐up period of 5.8 years. The incidence rate for gout per 1,000 person‐years was 7.83 among patients with OSA and 4.03 for controls (adjusted hazard ratio, 1.42). The greatest risk for gout in the OSA patients occurred approximately 1-2 years after their diagnosis.

The researchers also found significant associations between body mass index and gout risk in sleep apnea across all BMI categories, but the strongest association occurred in the normal BMI group (HR 2.02) at 2-5 years after the index date of OSA.

“The novelty of this study lies in assessing both the short- and long-term association of OSA with incident gout in a large primary care-based population,” the researchers said. They proposed that the most likely explanation for the events was that “intermittent hypoxia increases nucleotide turnover which enhances endogenous uric acid production.”

The study findings were limited by several factors including potential misclassification of OSA and the impact of confounding variables such as genetics and diet, they noted.

However, the results support the association between sleep apnea and gout, but also serve to highlight that clinicians should “consider the possibility of gout in patients with sleep apnea regardless of obesity,” the researchers wrote.

The National Institute for Health Research funded the study. The authors have no conflicts of interest to declare.

SOURCE: Blagojevic-Bucknall M et al. Arthritis Rheumatol. 2018 Aug 30. doi: 10.1002/art.40662.

Adults with obstructive sleep apnea are approximately twice as likely as are those without it to develop gout, according to data from a large, retrospective study with a median 5-year follow-up.

copyright designer491/Thinkstock

Data from previous studies have shown an increased risk in developing gout within the first year of an obstructive sleep apnea (OSA) diagnosis, wrote Milica Blagojevic-Bucknall, PhD, of Keele (England) University, and her colleagues.

In a study published in Arthritis & Rheumatology, the researchers compared 15,879 patients with OSA and 63,296 without.

Overall, 4.9% of OSA patients and 2.6% non‐OSA controls developed gout over a median follow‐up period of 5.8 years. The incidence rate for gout per 1,000 person‐years was 7.83 among patients with OSA and 4.03 for controls (adjusted hazard ratio, 1.42). The greatest risk for gout in the OSA patients occurred approximately 1-2 years after their diagnosis.

The researchers also found significant associations between body mass index and gout risk in sleep apnea across all BMI categories, but the strongest association occurred in the normal BMI group (HR 2.02) at 2-5 years after the index date of OSA.

“The novelty of this study lies in assessing both the short- and long-term association of OSA with incident gout in a large primary care-based population,” the researchers said. They proposed that the most likely explanation for the events was that “intermittent hypoxia increases nucleotide turnover which enhances endogenous uric acid production.”

The study findings were limited by several factors including potential misclassification of OSA and the impact of confounding variables such as genetics and diet, they noted.

However, the results support the association between sleep apnea and gout, but also serve to highlight that clinicians should “consider the possibility of gout in patients with sleep apnea regardless of obesity,” the researchers wrote.

The National Institute for Health Research funded the study. The authors have no conflicts of interest to declare.

SOURCE: Blagojevic-Bucknall M et al. Arthritis Rheumatol. 2018 Aug 30. doi: 10.1002/art.40662.

The European Commission has granted marketing authorization for caplacizumab (Cablivi), a humanized bivalent nanobody that inhibits the interaction between von Willebrand factor and platelets.

Caplacizumab is now approved to treat adults with acquired thrombotic thrombocytopenic purpura (aTTP) in all member countries of the European Union as well as Norway, Iceland, and Liechtenstein.

The drug has been accepted for priority review in the United States and the Food and Drug Administration is expected to make a decision by Feb. 6, 2019.

The European Commission’s approval of caplacizumab is supported by data from the phase 2 TITAN study and the phase 3 HERCULES study.

The TITAN trial included 75 aTTP patients who were randomized to caplacizumab (n = 36) or placebo (n = 39), with all patients receiving the current standard of care – daily plasma exchange and immunosuppressive therapy (N Engl J Med. 2016;374:511-22).

Patients in the caplacizumab arm had a 39% reduction in the median time to response, compared with patients in the placebo arm (P = .005).

The rate of adverse events (AEs) thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of AEs that were possibly related was 54% and 8%, respectively. The rate of serious AEs was 37% and 32%, respectively.

There were no deaths in the caplacizumab arm and two in the placebo arm. One death was attributable to severe, refractory TTP, and the other was attributable to cerebral hemorrhage.Results from the HERCULES trial were presented at the 2017 annual meeting of the American Society of Hematology.

The study enrolled patients with an acute episode of aTTP. They were randomized to receive caplacizumab (n = 72) or placebo (n = 73) in addition to standard care – plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization). There was a significant reduction in time to platelet count response in the caplacizumab arm, compared with the placebo arm. The platelet normalization rate ratio was 1.55 (P less than .01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12.7% (n = 9) in the caplacizumab arm and 49.3% (n = 36) in the placebo arm (P less than .0001).

The incidence of aTTP-related death was 0% (n = 0) in the caplacizumab arm and 4.1% (n = 3) in the placebo arm. The incidence of aTTP recurrence was 4.2% (n = 3) in the caplacizumab arm and 38.4% in the placebo arm (n = 28), and the incidence of at least one major thromboembolic event was 8.5% (n = 6) and 8.2% (n = 6), respectively.

jensmith@mdedge.com

The European Commission has granted marketing authorization for caplacizumab (Cablivi), a humanized bivalent nanobody that inhibits the interaction between von Willebrand factor and platelets.

Caplacizumab is now approved to treat adults with acquired thrombotic thrombocytopenic purpura (aTTP) in all member countries of the European Union as well as Norway, Iceland, and Liechtenstein.

The drug has been accepted for priority review in the United States and the Food and Drug Administration is expected to make a decision by Feb. 6, 2019.

The European Commission’s approval of caplacizumab is supported by data from the phase 2 TITAN study and the phase 3 HERCULES study.

The TITAN trial included 75 aTTP patients who were randomized to caplacizumab (n = 36) or placebo (n = 39), with all patients receiving the current standard of care – daily plasma exchange and immunosuppressive therapy (N Engl J Med. 2016;374:511-22).

Patients in the caplacizumab arm had a 39% reduction in the median time to response, compared with patients in the placebo arm (P = .005).

The rate of adverse events (AEs) thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of AEs that were possibly related was 54% and 8%, respectively. The rate of serious AEs was 37% and 32%, respectively.

There were no deaths in the caplacizumab arm and two in the placebo arm. One death was attributable to severe, refractory TTP, and the other was attributable to cerebral hemorrhage.Results from the HERCULES trial were presented at the 2017 annual meeting of the American Society of Hematology.

The study enrolled patients with an acute episode of aTTP. They were randomized to receive caplacizumab (n = 72) or placebo (n = 73) in addition to standard care – plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization). There was a significant reduction in time to platelet count response in the caplacizumab arm, compared with the placebo arm. The platelet normalization rate ratio was 1.55 (P less than .01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12.7% (n = 9) in the caplacizumab arm and 49.3% (n = 36) in the placebo arm (P less than .0001).

The incidence of aTTP-related death was 0% (n = 0) in the caplacizumab arm and 4.1% (n = 3) in the placebo arm. The incidence of aTTP recurrence was 4.2% (n = 3) in the caplacizumab arm and 38.4% in the placebo arm (n = 28), and the incidence of at least one major thromboembolic event was 8.5% (n = 6) and 8.2% (n = 6), respectively.

jensmith@mdedge.com

The European Commission has granted marketing authorization for caplacizumab (Cablivi), a humanized bivalent nanobody that inhibits the interaction between von Willebrand factor and platelets.

Caplacizumab is now approved to treat adults with acquired thrombotic thrombocytopenic purpura (aTTP) in all member countries of the European Union as well as Norway, Iceland, and Liechtenstein.

The drug has been accepted for priority review in the United States and the Food and Drug Administration is expected to make a decision by Feb. 6, 2019.

The European Commission’s approval of caplacizumab is supported by data from the phase 2 TITAN study and the phase 3 HERCULES study.

The TITAN trial included 75 aTTP patients who were randomized to caplacizumab (n = 36) or placebo (n = 39), with all patients receiving the current standard of care – daily plasma exchange and immunosuppressive therapy (N Engl J Med. 2016;374:511-22).

Patients in the caplacizumab arm had a 39% reduction in the median time to response, compared with patients in the placebo arm (P = .005).

The rate of adverse events (AEs) thought to be related to the study drug was 17% in the caplacizumab arm and 11% in the placebo arm. The rate of AEs that were possibly related was 54% and 8%, respectively. The rate of serious AEs was 37% and 32%, respectively.

There were no deaths in the caplacizumab arm and two in the placebo arm. One death was attributable to severe, refractory TTP, and the other was attributable to cerebral hemorrhage.Results from the HERCULES trial were presented at the 2017 annual meeting of the American Society of Hematology.

The study enrolled patients with an acute episode of aTTP. They were randomized to receive caplacizumab (n = 72) or placebo (n = 73) in addition to standard care – plasma exchange and immunosuppression.

The study’s primary endpoint was the time to platelet count response (normalization). There was a significant reduction in time to platelet count response in the caplacizumab arm, compared with the placebo arm. The platelet normalization rate ratio was 1.55 (P less than .01).

A secondary endpoint was the combination of aTTP-related death, aTTP recurrence, and at least one major thromboembolic event during study treatment. The incidence of this combined endpoint was 12.7% (n = 9) in the caplacizumab arm and 49.3% (n = 36) in the placebo arm (P less than .0001).

The incidence of aTTP-related death was 0% (n = 0) in the caplacizumab arm and 4.1% (n = 3) in the placebo arm. The incidence of aTTP recurrence was 4.2% (n = 3) in the caplacizumab arm and 38.4% in the placebo arm (n = 28), and the incidence of at least one major thromboembolic event was 8.5% (n = 6) and 8.2% (n = 6), respectively.

jensmith@mdedge.com

Peroral endoscopic myotomy (POEM) is safe and effective for several nonachalasia esophageal motility disorders, according to a retrospective study.

The procedure was clinically successful and relieved chest pain in most patients, reported Mouen A. Khashab, MD, director of therapeutic endoscopy at Johns Hopkins Hospital in Baltimore.

POEM was introduced in 2008 as a less invasive alternative to laparoscopic Heller myotomy. During the procedure, submucosal tunneling is performed through the lower esophageal sphincter to the gastric cardia, thereby weakening the lower esophageal sphincter to allow passage of food.

POEM is clinically successful in 80%-90% of patients with achalasia. Although the procedure is regarded as safe and effective for achalasia, it has not been thoroughly researched for treatment of other esophageal motility disorders, including junction outflow obstruction (EGJOO), jackhammer esophagus (JE), or esophagogastric distal esophageal spasm (DES). EGJOO is similar to achalasia, but with peristalsis and a mean integrated relaxation pressure (IRP) greater than 15 mm Hg. Both JE and DES are spastic esophageal disorders. Patients with JE exhibit extreme esophageal hypercontractility, whereas patients with DES have a normal mean IRP and at least 20% premature contractions.

“The role POEM plays in management of these disorders is not clear, mainly due to scarcity of studies on this topic,” the authors wrote in Endoscopy International Open. “A previous multicenter study investigated the role of POEM in 73 patients with spastic esophageal disorders. However, the vast majority of patients (n = 54) in that study had type III (spastic) achalasia.” Since therapies such as botulinum toxin injections and calcium channel blockers are ineffective for many patients with nonachalasia esophageal motility disorders, “POEM is potentially an ideal treatment.”

The international, multicenter study involved 11 treatment centers and 50 patients. Patients with JE (n = 18), EGJOO (n = 15), and DES (n = 17) were included, each diagnosed according to the Chicago classification of esophageal motility disorders. Patients with type III achalasia were excluded.

Outcomes included technical success (completion of myotomy) and clinical success (Eckardt score at least 3 and symptom improvement). Prior to the procedure, the mean Eckardt score was 6.9 and chest pain was reported by almost three-quarters of the patients (72%).

Technical success was achieved in all patients. Myotomy thickness varied between cases; approximately half had a selective inner circular myotomy (48%), slightly less had a full-thickness myotomy (44%), and several were undefined (8%). Mean esophageal myotomy length was 12.5 cm and mean gastric myotomy length was 2.5 cm. Mean procedure time was approximately 90 minutes. Median duration of hospital stay was 2 days.

Nine adverse events (AEs) occurred in 8 patients, including submucosal hematoma, aspiration pneumonia, inadvertent mucosotomy, postprocedure pain, esophageal leak, bleed, and symptomatic capno-thorax/peritoneum.

“Although AEs occurred in 18% of patients,” the authors noted, “55.6% were rated as mild and 44.4% as moderate with no severe events. Most AEs can be managed intraprocedurally.”

Median follow-up time was approximately 8 months, during which 42 patients (87.5%) achieved clinical success, with many dramatically improved; over half of the patients (52%) had Eckardt scores of 0 or 1. From the group of patients who had chest pain prior to the procedure, 87% had resolution of chest pain. Although reflux developed in almost a quarter of the patients (22.2%), this was successfully managed with proton pump inhibitors in all instances. Most patients (82.9%) who underwent postoperative manometry had resolution of preoperative abnormalities.

Subgroup analysis was also performed. Clinical success was achieved in 94.1% of patients with DES, 93.3% of patients with EGJOO, and 75.0% with JE. Collectively, the spastic disorders (DES/JE) had a lower numerical response than EGJOO. However, the authors noted that “the difference was not statistically significant (P = .41), likely a type II error due to the relatively small number of included patients.” In all subgroups, postprocedural mean Eckardt scores decreased to less than 2. Patients with EGJOO were most likely to achieve Eckardt scores of 0 or 1. AEs were similar between subgroups.

“Remarkably, chest pain improved in more than 85% of patients,” the authors wrote. “Chest pain is frequently the major presenting symptom in these disorders and is difficult to treat.”

“It is important to mention that a long esophageal myotomy is essential to ensure that proximal esophageal spasms are effectively covered and treated,” the authors wrote. “Mean length of esophageal myotomy in patients with DES and JE in the current study was about 14 cm, which is more than twice the length of a typical endoscopic or surgical myotomy performed in achalasia patients.”

Even with the need for an extended myotomy, “results from the current study along with published data suggest POEM as an effective technique” for nonachalasia esophageal motility disorders, the authors concluded.

Since retrospective studies are inherently limited by design, the authors encouraged randomized trials to clarify the primary role of POEM in the management of nonachalasia esophageal motility disorders.

The authors reported compensation from Olympus, Boston Scientific, and Cook Medical.

SOURCE: Khashab MA et al. Endosc Int Open. 2018 Aug 10. doi: 10.1055/a-0625-6288.

Peroral endoscopic myotomy (POEM) is safe and effective for several nonachalasia esophageal motility disorders, according to a retrospective study.

The procedure was clinically successful and relieved chest pain in most patients, reported Mouen A. Khashab, MD, director of therapeutic endoscopy at Johns Hopkins Hospital in Baltimore.

POEM was introduced in 2008 as a less invasive alternative to laparoscopic Heller myotomy. During the procedure, submucosal tunneling is performed through the lower esophageal sphincter to the gastric cardia, thereby weakening the lower esophageal sphincter to allow passage of food.

POEM is clinically successful in 80%-90% of patients with achalasia. Although the procedure is regarded as safe and effective for achalasia, it has not been thoroughly researched for treatment of other esophageal motility disorders, including junction outflow obstruction (EGJOO), jackhammer esophagus (JE), or esophagogastric distal esophageal spasm (DES). EGJOO is similar to achalasia, but with peristalsis and a mean integrated relaxation pressure (IRP) greater than 15 mm Hg. Both JE and DES are spastic esophageal disorders. Patients with JE exhibit extreme esophageal hypercontractility, whereas patients with DES have a normal mean IRP and at least 20% premature contractions.

“The role POEM plays in management of these disorders is not clear, mainly due to scarcity of studies on this topic,” the authors wrote in Endoscopy International Open. “A previous multicenter study investigated the role of POEM in 73 patients with spastic esophageal disorders. However, the vast majority of patients (n = 54) in that study had type III (spastic) achalasia.” Since therapies such as botulinum toxin injections and calcium channel blockers are ineffective for many patients with nonachalasia esophageal motility disorders, “POEM is potentially an ideal treatment.”

The international, multicenter study involved 11 treatment centers and 50 patients. Patients with JE (n = 18), EGJOO (n = 15), and DES (n = 17) were included, each diagnosed according to the Chicago classification of esophageal motility disorders. Patients with type III achalasia were excluded.

Outcomes included technical success (completion of myotomy) and clinical success (Eckardt score at least 3 and symptom improvement). Prior to the procedure, the mean Eckardt score was 6.9 and chest pain was reported by almost three-quarters of the patients (72%).

Technical success was achieved in all patients. Myotomy thickness varied between cases; approximately half had a selective inner circular myotomy (48%), slightly less had a full-thickness myotomy (44%), and several were undefined (8%). Mean esophageal myotomy length was 12.5 cm and mean gastric myotomy length was 2.5 cm. Mean procedure time was approximately 90 minutes. Median duration of hospital stay was 2 days.

Nine adverse events (AEs) occurred in 8 patients, including submucosal hematoma, aspiration pneumonia, inadvertent mucosotomy, postprocedure pain, esophageal leak, bleed, and symptomatic capno-thorax/peritoneum.

“Although AEs occurred in 18% of patients,” the authors noted, “55.6% were rated as mild and 44.4% as moderate with no severe events. Most AEs can be managed intraprocedurally.”

Median follow-up time was approximately 8 months, during which 42 patients (87.5%) achieved clinical success, with many dramatically improved; over half of the patients (52%) had Eckardt scores of 0 or 1. From the group of patients who had chest pain prior to the procedure, 87% had resolution of chest pain. Although reflux developed in almost a quarter of the patients (22.2%), this was successfully managed with proton pump inhibitors in all instances. Most patients (82.9%) who underwent postoperative manometry had resolution of preoperative abnormalities.

Subgroup analysis was also performed. Clinical success was achieved in 94.1% of patients with DES, 93.3% of patients with EGJOO, and 75.0% with JE. Collectively, the spastic disorders (DES/JE) had a lower numerical response than EGJOO. However, the authors noted that “the difference was not statistically significant (P = .41), likely a type II error due to the relatively small number of included patients.” In all subgroups, postprocedural mean Eckardt scores decreased to less than 2. Patients with EGJOO were most likely to achieve Eckardt scores of 0 or 1. AEs were similar between subgroups.

“Remarkably, chest pain improved in more than 85% of patients,” the authors wrote. “Chest pain is frequently the major presenting symptom in these disorders and is difficult to treat.”

“It is important to mention that a long esophageal myotomy is essential to ensure that proximal esophageal spasms are effectively covered and treated,” the authors wrote. “Mean length of esophageal myotomy in patients with DES and JE in the current study was about 14 cm, which is more than twice the length of a typical endoscopic or surgical myotomy performed in achalasia patients.”

Even with the need for an extended myotomy, “results from the current study along with published data suggest POEM as an effective technique” for nonachalasia esophageal motility disorders, the authors concluded.

Since retrospective studies are inherently limited by design, the authors encouraged randomized trials to clarify the primary role of POEM in the management of nonachalasia esophageal motility disorders.

The authors reported compensation from Olympus, Boston Scientific, and Cook Medical.

SOURCE: Khashab MA et al. Endosc Int Open. 2018 Aug 10. doi: 10.1055/a-0625-6288.

Peroral endoscopic myotomy (POEM) is safe and effective for several nonachalasia esophageal motility disorders, according to a retrospective study.

The procedure was clinically successful and relieved chest pain in most patients, reported Mouen A. Khashab, MD, director of therapeutic endoscopy at Johns Hopkins Hospital in Baltimore.

POEM was introduced in 2008 as a less invasive alternative to laparoscopic Heller myotomy. During the procedure, submucosal tunneling is performed through the lower esophageal sphincter to the gastric cardia, thereby weakening the lower esophageal sphincter to allow passage of food.

POEM is clinically successful in 80%-90% of patients with achalasia. Although the procedure is regarded as safe and effective for achalasia, it has not been thoroughly researched for treatment of other esophageal motility disorders, including junction outflow obstruction (EGJOO), jackhammer esophagus (JE), or esophagogastric distal esophageal spasm (DES). EGJOO is similar to achalasia, but with peristalsis and a mean integrated relaxation pressure (IRP) greater than 15 mm Hg. Both JE and DES are spastic esophageal disorders. Patients with JE exhibit extreme esophageal hypercontractility, whereas patients with DES have a normal mean IRP and at least 20% premature contractions.

“The role POEM plays in management of these disorders is not clear, mainly due to scarcity of studies on this topic,” the authors wrote in Endoscopy International Open. “A previous multicenter study investigated the role of POEM in 73 patients with spastic esophageal disorders. However, the vast majority of patients (n = 54) in that study had type III (spastic) achalasia.” Since therapies such as botulinum toxin injections and calcium channel blockers are ineffective for many patients with nonachalasia esophageal motility disorders, “POEM is potentially an ideal treatment.”

The international, multicenter study involved 11 treatment centers and 50 patients. Patients with JE (n = 18), EGJOO (n = 15), and DES (n = 17) were included, each diagnosed according to the Chicago classification of esophageal motility disorders. Patients with type III achalasia were excluded.

Outcomes included technical success (completion of myotomy) and clinical success (Eckardt score at least 3 and symptom improvement). Prior to the procedure, the mean Eckardt score was 6.9 and chest pain was reported by almost three-quarters of the patients (72%).

Technical success was achieved in all patients. Myotomy thickness varied between cases; approximately half had a selective inner circular myotomy (48%), slightly less had a full-thickness myotomy (44%), and several were undefined (8%). Mean esophageal myotomy length was 12.5 cm and mean gastric myotomy length was 2.5 cm. Mean procedure time was approximately 90 minutes. Median duration of hospital stay was 2 days.

Nine adverse events (AEs) occurred in 8 patients, including submucosal hematoma, aspiration pneumonia, inadvertent mucosotomy, postprocedure pain, esophageal leak, bleed, and symptomatic capno-thorax/peritoneum.

“Although AEs occurred in 18% of patients,” the authors noted, “55.6% were rated as mild and 44.4% as moderate with no severe events. Most AEs can be managed intraprocedurally.”

Median follow-up time was approximately 8 months, during which 42 patients (87.5%) achieved clinical success, with many dramatically improved; over half of the patients (52%) had Eckardt scores of 0 or 1. From the group of patients who had chest pain prior to the procedure, 87% had resolution of chest pain. Although reflux developed in almost a quarter of the patients (22.2%), this was successfully managed with proton pump inhibitors in all instances. Most patients (82.9%) who underwent postoperative manometry had resolution of preoperative abnormalities.

Subgroup analysis was also performed. Clinical success was achieved in 94.1% of patients with DES, 93.3% of patients with EGJOO, and 75.0% with JE. Collectively, the spastic disorders (DES/JE) had a lower numerical response than EGJOO. However, the authors noted that “the difference was not statistically significant (P = .41), likely a type II error due to the relatively small number of included patients.” In all subgroups, postprocedural mean Eckardt scores decreased to less than 2. Patients with EGJOO were most likely to achieve Eckardt scores of 0 or 1. AEs were similar between subgroups.

“Remarkably, chest pain improved in more than 85% of patients,” the authors wrote. “Chest pain is frequently the major presenting symptom in these disorders and is difficult to treat.”

“It is important to mention that a long esophageal myotomy is essential to ensure that proximal esophageal spasms are effectively covered and treated,” the authors wrote. “Mean length of esophageal myotomy in patients with DES and JE in the current study was about 14 cm, which is more than twice the length of a typical endoscopic or surgical myotomy performed in achalasia patients.”

Even with the need for an extended myotomy, “results from the current study along with published data suggest POEM as an effective technique” for nonachalasia esophageal motility disorders, the authors concluded.

Since retrospective studies are inherently limited by design, the authors encouraged randomized trials to clarify the primary role of POEM in the management of nonachalasia esophageal motility disorders.

The authors reported compensation from Olympus, Boston Scientific, and Cook Medical.

SOURCE: Khashab MA et al. Endosc Int Open. 2018 Aug 10. doi: 10.1055/a-0625-6288.

When clinicians find out that one of their patients died of an overdose of a controlled substance, they are more likely to reduce the number and dose of opioid drugs they prescribe, according to a study funded in part by the National Institute on Aging.

Between July 1, 2015 and June 30, 2016, San Diego County in California reported 222 deaths for which Schedule II, III, or IV drugs were the primary or contributing cause. Of these, 170 deaths were listed in the Controlled Substance Utilization Review and Evaluation System (CURES) database.

In the study of 861 prescribing clinicians, 388 received a notification letter from the chief deputy medical examiner of San Diego County; 438 did not receive a letter. The letter identified the deceased patient by name, address, and age. It also outlined the annual number and types of prescription drug deaths seen by the medical examiner, discussed how to access the state’s prescription drug monitoring program, and reviewed safe prescribing strategies.

Physicians who received the letter wrote 9.7% fewer opioid prescriptions in the 3 months following the intervention.

"Behavioral ‘nudges’ like these letters could be a tool to help curb the opioid epidemic," said NIA Director Richard J. Hodes, MD. "This finding could be very useful in the effort to reduce inappropriate prescribing of opioids without severely restricting availability of legally prescribed opioids for patients who should be getting them."

When clinicians find out that one of their patients died of an overdose of a controlled substance, they are more likely to reduce the number and dose of opioid drugs they prescribe, according to a study funded in part by the National Institute on Aging.

Between July 1, 2015 and June 30, 2016, San Diego County in California reported 222 deaths for which Schedule II, III, or IV drugs were the primary or contributing cause. Of these, 170 deaths were listed in the Controlled Substance Utilization Review and Evaluation System (CURES) database.

In the study of 861 prescribing clinicians, 388 received a notification letter from the chief deputy medical examiner of San Diego County; 438 did not receive a letter. The letter identified the deceased patient by name, address, and age. It also outlined the annual number and types of prescription drug deaths seen by the medical examiner, discussed how to access the state’s prescription drug monitoring program, and reviewed safe prescribing strategies.

Physicians who received the letter wrote 9.7% fewer opioid prescriptions in the 3 months following the intervention.

"Behavioral ‘nudges’ like these letters could be a tool to help curb the opioid epidemic," said NIA Director Richard J. Hodes, MD. "This finding could be very useful in the effort to reduce inappropriate prescribing of opioids without severely restricting availability of legally prescribed opioids for patients who should be getting them."

When clinicians find out that one of their patients died of an overdose of a controlled substance, they are more likely to reduce the number and dose of opioid drugs they prescribe, according to a study funded in part by the National Institute on Aging.

Between July 1, 2015 and June 30, 2016, San Diego County in California reported 222 deaths for which Schedule II, III, or IV drugs were the primary or contributing cause. Of these, 170 deaths were listed in the Controlled Substance Utilization Review and Evaluation System (CURES) database.

In the study of 861 prescribing clinicians, 388 received a notification letter from the chief deputy medical examiner of San Diego County; 438 did not receive a letter. The letter identified the deceased patient by name, address, and age. It also outlined the annual number and types of prescription drug deaths seen by the medical examiner, discussed how to access the state’s prescription drug monitoring program, and reviewed safe prescribing strategies.

Physicians who received the letter wrote 9.7% fewer opioid prescriptions in the 3 months following the intervention.

"Behavioral ‘nudges’ like these letters could be a tool to help curb the opioid epidemic," said NIA Director Richard J. Hodes, MD. "This finding could be very useful in the effort to reduce inappropriate prescribing of opioids without severely restricting availability of legally prescribed opioids for patients who should be getting them."

ORLANDO – When investigators at Washington University, St. Louis, gave 42 patients with type 1 diabetes mellitus a dose of the sulfonylurea glipizide (Glucotrol), a curious thing happened.

C-peptide levels rose in 13 patients (31%), which means they secreted their own insulin.

The finding was unexpected; people with type 1 diabetes mellitus (T1DM) aren’t supposed to be able to produce endogenous insulin because they don’t have beta cells. They shouldn’t have had any response to glipizide, a beta-cell stimulator.

It wasn’t that the 13 subjects were in the honeymoon phase of T1DM, meaning that they still had a few beta cells left. Like the other patients, their glucose levels rose when they were given dextrose, but their C-peptide levels did not. Also, all patients, including the 13 who secreted insulin, had been diagnosed with T1DM for a mean of 6 years and were insulin dependent. They ranged in age up to 33 years, and their hemoglobin A1c was about 8.6%.

In short, the 13 patients didn’t have classic type 1 diabetes. They had something wrong with their beta cells, explained Colin G. Nichols, PhD, a professor of cell biology and physiology at Washington University.

They likely had monogenetic diabetes, a genetic mutation that caused potassium channels in their beta cells to be permanently hyperpolarized. Blocking the channels with a sulfonylurea allowed the cells to depolarize and secrete insulin.

Monogenetic diabetes is a known but underrecognized entity. If it’s not picked up in infancy, most patients are misdiagnosed with classic T1DM and inappropriately treated with insulin. If they finally try a sulfonylurea, “they don’t need insulin injections anymore. This has been a very magical story for this group of patients,” Dr. Nichols said at the annual scientific sessions of the American Diabetes Association.

All they need is a sulfonylurea pill once a day.

Monogenetic patients are missed because there are no easy, widely-available screening tests for the condition. Genetic testing works, but it’s expensive and often not done. Dr. Nichols and his team hope their dextrose-sulfonylurea challenge will solve the problem.

They are currently working to recruit more subjects and perform confirmatory genetic testing. They want to know how much insulin secretion is possible for their glipizide responders and how long their responses last. If funding comes through, they hope to do a screening and treatment trial in patients with T1DM.

The promise is that the dextrose-sulfonylurea challenge will shorten the time to a correct diagnosis and proper treatment, and save people from decades of insulin shots. It might also pick up nongenetic, metabolic causes of beta-cell potassium channel dysfunction that would respond to sulfonylureas. The challenge could even be used to prescreen for genetic testing, to increase its yield and shift the cost-benefit ratio more into the black.

As for the specifics of the study, the 42 patients were given an intravenous dextrose bolus of 0.5 g/kg, followed 20 minutes later by a single dose of glipizide, 0.3 mg/kg. Blood glucose and C-peptide were measured at baseline and at regular intervals during the 4-hour challenge. The challenge was safe; there were no serious side effects.

Among the 13 responders – meaning flat insulin secretion with dextrose but insulin secretion with glipizide – the peak change in C-peptide was around 0.41 ng/mL ± 0.45 an hour or so after the glipizide dose, and was maintained for about an hour from a baseline of about 0.6 ng/mL.

To make sure that the responders didn’t have just a delayed insulin response to dextrose, they were given another dextrose challenge 6 months later, without the glipizide. Again, their C-peptide levels were flat.

The investigators had no disclosures to report, and there was no industry funding.

aotto@mdedge.com

SOURCE: Nichols CG et al. ADA 2018, Abstract 310-LB.

ORLANDO – When investigators at Washington University, St. Louis, gave 42 patients with type 1 diabetes mellitus a dose of the sulfonylurea glipizide (Glucotrol), a curious thing happened.

C-peptide levels rose in 13 patients (31%), which means they secreted their own insulin.

The finding was unexpected; people with type 1 diabetes mellitus (T1DM) aren’t supposed to be able to produce endogenous insulin because they don’t have beta cells. They shouldn’t have had any response to glipizide, a beta-cell stimulator.

It wasn’t that the 13 subjects were in the honeymoon phase of T1DM, meaning that they still had a few beta cells left. Like the other patients, their glucose levels rose when they were given dextrose, but their C-peptide levels did not. Also, all patients, including the 13 who secreted insulin, had been diagnosed with T1DM for a mean of 6 years and were insulin dependent. They ranged in age up to 33 years, and their hemoglobin A1c was about 8.6%.

In short, the 13 patients didn’t have classic type 1 diabetes. They had something wrong with their beta cells, explained Colin G. Nichols, PhD, a professor of cell biology and physiology at Washington University.

They likely had monogenetic diabetes, a genetic mutation that caused potassium channels in their beta cells to be permanently hyperpolarized. Blocking the channels with a sulfonylurea allowed the cells to depolarize and secrete insulin.

Monogenetic diabetes is a known but underrecognized entity. If it’s not picked up in infancy, most patients are misdiagnosed with classic T1DM and inappropriately treated with insulin. If they finally try a sulfonylurea, “they don’t need insulin injections anymore. This has been a very magical story for this group of patients,” Dr. Nichols said at the annual scientific sessions of the American Diabetes Association.

All they need is a sulfonylurea pill once a day.

Monogenetic patients are missed because there are no easy, widely-available screening tests for the condition. Genetic testing works, but it’s expensive and often not done. Dr. Nichols and his team hope their dextrose-sulfonylurea challenge will solve the problem.

They are currently working to recruit more subjects and perform confirmatory genetic testing. They want to know how much insulin secretion is possible for their glipizide responders and how long their responses last. If funding comes through, they hope to do a screening and treatment trial in patients with T1DM.

The promise is that the dextrose-sulfonylurea challenge will shorten the time to a correct diagnosis and proper treatment, and save people from decades of insulin shots. It might also pick up nongenetic, metabolic causes of beta-cell potassium channel dysfunction that would respond to sulfonylureas. The challenge could even be used to prescreen for genetic testing, to increase its yield and shift the cost-benefit ratio more into the black.

As for the specifics of the study, the 42 patients were given an intravenous dextrose bolus of 0.5 g/kg, followed 20 minutes later by a single dose of glipizide, 0.3 mg/kg. Blood glucose and C-peptide were measured at baseline and at regular intervals during the 4-hour challenge. The challenge was safe; there were no serious side effects.

Among the 13 responders – meaning flat insulin secretion with dextrose but insulin secretion with glipizide – the peak change in C-peptide was around 0.41 ng/mL ± 0.45 an hour or so after the glipizide dose, and was maintained for about an hour from a baseline of about 0.6 ng/mL.

To make sure that the responders didn’t have just a delayed insulin response to dextrose, they were given another dextrose challenge 6 months later, without the glipizide. Again, their C-peptide levels were flat.

The investigators had no disclosures to report, and there was no industry funding.

aotto@mdedge.com

SOURCE: Nichols CG et al. ADA 2018, Abstract 310-LB.

ORLANDO – When investigators at Washington University, St. Louis, gave 42 patients with type 1 diabetes mellitus a dose of the sulfonylurea glipizide (Glucotrol), a curious thing happened.

C-peptide levels rose in 13 patients (31%), which means they secreted their own insulin.

The finding was unexpected; people with type 1 diabetes mellitus (T1DM) aren’t supposed to be able to produce endogenous insulin because they don’t have beta cells. They shouldn’t have had any response to glipizide, a beta-cell stimulator.

It wasn’t that the 13 subjects were in the honeymoon phase of T1DM, meaning that they still had a few beta cells left. Like the other patients, their glucose levels rose when they were given dextrose, but their C-peptide levels did not. Also, all patients, including the 13 who secreted insulin, had been diagnosed with T1DM for a mean of 6 years and were insulin dependent. They ranged in age up to 33 years, and their hemoglobin A1c was about 8.6%.

In short, the 13 patients didn’t have classic type 1 diabetes. They had something wrong with their beta cells, explained Colin G. Nichols, PhD, a professor of cell biology and physiology at Washington University.

They likely had monogenetic diabetes, a genetic mutation that caused potassium channels in their beta cells to be permanently hyperpolarized. Blocking the channels with a sulfonylurea allowed the cells to depolarize and secrete insulin.

Monogenetic diabetes is a known but underrecognized entity. If it’s not picked up in infancy, most patients are misdiagnosed with classic T1DM and inappropriately treated with insulin. If they finally try a sulfonylurea, “they don’t need insulin injections anymore. This has been a very magical story for this group of patients,” Dr. Nichols said at the annual scientific sessions of the American Diabetes Association.

All they need is a sulfonylurea pill once a day.

Monogenetic patients are missed because there are no easy, widely-available screening tests for the condition. Genetic testing works, but it’s expensive and often not done. Dr. Nichols and his team hope their dextrose-sulfonylurea challenge will solve the problem.

They are currently working to recruit more subjects and perform confirmatory genetic testing. They want to know how much insulin secretion is possible for their glipizide responders and how long their responses last. If funding comes through, they hope to do a screening and treatment trial in patients with T1DM.

The promise is that the dextrose-sulfonylurea challenge will shorten the time to a correct diagnosis and proper treatment, and save people from decades of insulin shots. It might also pick up nongenetic, metabolic causes of beta-cell potassium channel dysfunction that would respond to sulfonylureas. The challenge could even be used to prescreen for genetic testing, to increase its yield and shift the cost-benefit ratio more into the black.

As for the specifics of the study, the 42 patients were given an intravenous dextrose bolus of 0.5 g/kg, followed 20 minutes later by a single dose of glipizide, 0.3 mg/kg. Blood glucose and C-peptide were measured at baseline and at regular intervals during the 4-hour challenge. The challenge was safe; there were no serious side effects.

Among the 13 responders – meaning flat insulin secretion with dextrose but insulin secretion with glipizide – the peak change in C-peptide was around 0.41 ng/mL ± 0.45 an hour or so after the glipizide dose, and was maintained for about an hour from a baseline of about 0.6 ng/mL.

To make sure that the responders didn’t have just a delayed insulin response to dextrose, they were given another dextrose challenge 6 months later, without the glipizide. Again, their C-peptide levels were flat.

The investigators had no disclosures to report, and there was no industry funding.

aotto@mdedge.com

SOURCE: Nichols CG et al. ADA 2018, Abstract 310-LB.