PENTAX, the manufacturer of the ED-3490TK video duodenoscope, has issued updated validated manual reprocessing instructions to replace those provided in the original device labeling in response to a Food and Drug Administration Safety Communication released last February concerning the design of endoscopic retrograde cholangiopancreatography (ERCP) duodenoscopes and the risk of multidrug-resistant bacterial infections.

The FDA has reviewed these updated reprocessing instructions and recommends that staff be trained to implement them as soon as possible. Several changes have been made to the protocol for precleaning, manual cleaning, and high-level disinfection that the FDA found to be adequate.

Olympus, the manufacturer of the TJF-Q180V duodenoscope has also issued updated manual reprocessing instructions.

In February 2015, the FDA first announced that the agency had received reports of multidrug-resistant bacterial infections in patients who had undergone ERCP with duodenoscopes that had been cleaned and disinfected properly (according to manufacturer instructions) and determined that the “complex design of ERCP endoscopes (also called duodenoscopes) may impede effective reprocessing.”

Since then, the FDA has been working with duodenoscope manufacturers to revise their manual reprocessing instructions to devise standard procedures to eliminate the risk of spreading infection between patients and better survey any contamination of the duodenoscopes.

The American Gastroenterological Association's Center for GI Innovation and Technology has been working closely with the FDA and device manufacturers to develop a path forward with zero device-associated infections.

Adverse events associated with duodenoscopes should be reported to the FDA’s MedWatch program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch.

PENTAX, the manufacturer of the ED-3490TK video duodenoscope, has issued updated validated manual reprocessing instructions to replace those provided in the original device labeling in response to a Food and Drug Administration Safety Communication released last February concerning the design of endoscopic retrograde cholangiopancreatography (ERCP) duodenoscopes and the risk of multidrug-resistant bacterial infections.

The FDA has reviewed these updated reprocessing instructions and recommends that staff be trained to implement them as soon as possible. Several changes have been made to the protocol for precleaning, manual cleaning, and high-level disinfection that the FDA found to be adequate.

Olympus, the manufacturer of the TJF-Q180V duodenoscope has also issued updated manual reprocessing instructions.

In February 2015, the FDA first announced that the agency had received reports of multidrug-resistant bacterial infections in patients who had undergone ERCP with duodenoscopes that had been cleaned and disinfected properly (according to manufacturer instructions) and determined that the “complex design of ERCP endoscopes (also called duodenoscopes) may impede effective reprocessing.”

Since then, the FDA has been working with duodenoscope manufacturers to revise their manual reprocessing instructions to devise standard procedures to eliminate the risk of spreading infection between patients and better survey any contamination of the duodenoscopes.

The American Gastroenterological Association's Center for GI Innovation and Technology has been working closely with the FDA and device manufacturers to develop a path forward with zero device-associated infections.

Adverse events associated with duodenoscopes should be reported to the FDA’s MedWatch program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch.

PENTAX, the manufacturer of the ED-3490TK video duodenoscope, has issued updated validated manual reprocessing instructions to replace those provided in the original device labeling in response to a Food and Drug Administration Safety Communication released last February concerning the design of endoscopic retrograde cholangiopancreatography (ERCP) duodenoscopes and the risk of multidrug-resistant bacterial infections.

The FDA has reviewed these updated reprocessing instructions and recommends that staff be trained to implement them as soon as possible. Several changes have been made to the protocol for precleaning, manual cleaning, and high-level disinfection that the FDA found to be adequate.

Olympus, the manufacturer of the TJF-Q180V duodenoscope has also issued updated manual reprocessing instructions.

In February 2015, the FDA first announced that the agency had received reports of multidrug-resistant bacterial infections in patients who had undergone ERCP with duodenoscopes that had been cleaned and disinfected properly (according to manufacturer instructions) and determined that the “complex design of ERCP endoscopes (also called duodenoscopes) may impede effective reprocessing.”

Since then, the FDA has been working with duodenoscope manufacturers to revise their manual reprocessing instructions to devise standard procedures to eliminate the risk of spreading infection between patients and better survey any contamination of the duodenoscopes.

The American Gastroenterological Association's Center for GI Innovation and Technology has been working closely with the FDA and device manufacturers to develop a path forward with zero device-associated infections.

Adverse events associated with duodenoscopes should be reported to the FDA’s MedWatch program at 800-332-1088 or www.accessdata.fda.gov/scripts/medwatch.

A study of closed malpractice claims involving more than 2,100 hospitalists shows that claims* arising from hospitalist care are more likely to have a higher injury severity than claims against other physician specialties. This latest analysis of allegations made by patients against hospitalists—and the factors that led to these claims—was produced by The Doctors Company, the nation’s largest physician-owned medical malpractice insurer.

The study also shows that the vast majority of claims against hospitalists were diagnosis related (36%), involved improper management of treatment (31%), or were the result of a medication-related error (11%).

The study is based on 464 claims against hospitalists that closed from 2007 to 2014. All claims were studied regardless of their ultimate outcome.

The research is unique compared with other studies of malpractice claims because it includes expert insights into the specific elements that led to the patient injury. Findings by expert physician reviewers were consistent with the patients’ allegations—that their problems arose from incorrect or delayed diagnoses. Reviewers noted that 35% of the cases resulted from an inadequate initial assessment, consequently decreasing the chance that the hospitalist would arrive at the correct diagnosis.

The study also includes 15 examples of malpractice cases, lists the conditions that were most commonly involved in incorrect or delayed diagnoses, and provides risk-mitigation strategies.

“We hope that the information presented in this study will prompt physicians to collaborate with hospital leadership to identify system weaknesses, thereby reducing the risk of harm to patients,” says study co-author David B. Troxel, MD, medical director of the The Doctors Company.

Copies of the full study will be available at The Doctors Company’s exhibit space at HM16 or at www.thedoctors.com/hospitaliststudy.

*A written notice, demand, lawsuit, arbitration proceeding, or screening panel in which a demand is made for money or a bill reduction and that alleges injury, disability, sickness, disease, or death of a patient arising from the physician’s rendering or failing to render professional services.

A study of closed malpractice claims involving more than 2,100 hospitalists shows that claims* arising from hospitalist care are more likely to have a higher injury severity than claims against other physician specialties. This latest analysis of allegations made by patients against hospitalists—and the factors that led to these claims—was produced by The Doctors Company, the nation’s largest physician-owned medical malpractice insurer.

The study also shows that the vast majority of claims against hospitalists were diagnosis related (36%), involved improper management of treatment (31%), or were the result of a medication-related error (11%).

The study is based on 464 claims against hospitalists that closed from 2007 to 2014. All claims were studied regardless of their ultimate outcome.

The research is unique compared with other studies of malpractice claims because it includes expert insights into the specific elements that led to the patient injury. Findings by expert physician reviewers were consistent with the patients’ allegations—that their problems arose from incorrect or delayed diagnoses. Reviewers noted that 35% of the cases resulted from an inadequate initial assessment, consequently decreasing the chance that the hospitalist would arrive at the correct diagnosis.

The study also includes 15 examples of malpractice cases, lists the conditions that were most commonly involved in incorrect or delayed diagnoses, and provides risk-mitigation strategies.

“We hope that the information presented in this study will prompt physicians to collaborate with hospital leadership to identify system weaknesses, thereby reducing the risk of harm to patients,” says study co-author David B. Troxel, MD, medical director of the The Doctors Company.

Copies of the full study will be available at The Doctors Company’s exhibit space at HM16 or at www.thedoctors.com/hospitaliststudy.

*A written notice, demand, lawsuit, arbitration proceeding, or screening panel in which a demand is made for money or a bill reduction and that alleges injury, disability, sickness, disease, or death of a patient arising from the physician’s rendering or failing to render professional services.

A study of closed malpractice claims involving more than 2,100 hospitalists shows that claims* arising from hospitalist care are more likely to have a higher injury severity than claims against other physician specialties. This latest analysis of allegations made by patients against hospitalists—and the factors that led to these claims—was produced by The Doctors Company, the nation’s largest physician-owned medical malpractice insurer.

The study also shows that the vast majority of claims against hospitalists were diagnosis related (36%), involved improper management of treatment (31%), or were the result of a medication-related error (11%).

The study is based on 464 claims against hospitalists that closed from 2007 to 2014. All claims were studied regardless of their ultimate outcome.

The research is unique compared with other studies of malpractice claims because it includes expert insights into the specific elements that led to the patient injury. Findings by expert physician reviewers were consistent with the patients’ allegations—that their problems arose from incorrect or delayed diagnoses. Reviewers noted that 35% of the cases resulted from an inadequate initial assessment, consequently decreasing the chance that the hospitalist would arrive at the correct diagnosis.

The study also includes 15 examples of malpractice cases, lists the conditions that were most commonly involved in incorrect or delayed diagnoses, and provides risk-mitigation strategies.

“We hope that the information presented in this study will prompt physicians to collaborate with hospital leadership to identify system weaknesses, thereby reducing the risk of harm to patients,” says study co-author David B. Troxel, MD, medical director of the The Doctors Company.

Copies of the full study will be available at The Doctors Company’s exhibit space at HM16 or at www.thedoctors.com/hospitaliststudy.

*A written notice, demand, lawsuit, arbitration proceeding, or screening panel in which a demand is made for money or a bill reduction and that alleges injury, disability, sickness, disease, or death of a patient arising from the physician’s rendering or failing to render professional services.

NEW YORK (Reuters) - The U.S. government on Friday proposed raising payments by 1.35 percent on average next year to the health insurers who offer Medicare Advantage health benefits to elderly and disabled Americans.

Payments to insurers will vary under the 2017 Medicare Advantage proposal, based on the region the plans are sold and on the size of bonus payments insurers can receive based on quality ratings, the government said.

Shares of health insurers rose in after-hours trade. Analysts said the proposal looked positive for insurers at first glance, but cautioned that they needed to parse it fully.

"Looks like the best case scenario has played itself out,"said Ipsita Smolinski of Capitol Street, a Washington D.C. research firm, who had anticipated about 1 percent increase in payments.

Insurers and lawmakers have pressured the government not to cut payments, saying any decrease would hurt older Americans by forcing insurers to cut benefits.

Insurer lobbyist America's Health Insurance Plans President Marilyn Tavenner said it was important that the final policy ensure the long-term stability of Medicare Advantage. She said in a statement that the group was looking closely at the proposal.

About 17 million Americans have healthcare coverage through Medicare Advantage, offered by insurers including UnitedHealth Group Inc, Aetna Inc, and Anthem Inc among others. Another more than 30 million people receive benefits through the government Medicare fee-for-service program.

Shares of Anthem Inc rose 1.4 percent in after-hours trading, while UnitedHealth Group gained 1.6 percent.

Some insurers may benefit more than others from the proposal to pay more to insurers who are managing plans for people who qualify for both Medicare and Medicaid for the poor, said Kim Monk, managing director of Capital Alpha Partners.

The 1.35 percent increase is based mostly on anticipated medical cost increases next year. The government expects a 3 percent payment growth rate, which is in line with estimates the government provided to insurers in December.

That 3 percent increase is then reduced to 1.35 percent due to lower payments to insurers for sicker-than-average customers and some medical coding changes, the U.S. Department of Health and Human Services Medicare agency said on Friday.

The 1.35 percent also takes into account an increase in how it pays insurers based on quality measures, called star ratings, it said.

The final rate for 2017 Medicare Advantage payments is based on this proposed figure and will be released in April.

NEW YORK (Reuters) - The U.S. government on Friday proposed raising payments by 1.35 percent on average next year to the health insurers who offer Medicare Advantage health benefits to elderly and disabled Americans.

Payments to insurers will vary under the 2017 Medicare Advantage proposal, based on the region the plans are sold and on the size of bonus payments insurers can receive based on quality ratings, the government said.

Shares of health insurers rose in after-hours trade. Analysts said the proposal looked positive for insurers at first glance, but cautioned that they needed to parse it fully.

"Looks like the best case scenario has played itself out,"said Ipsita Smolinski of Capitol Street, a Washington D.C. research firm, who had anticipated about 1 percent increase in payments.

Insurers and lawmakers have pressured the government not to cut payments, saying any decrease would hurt older Americans by forcing insurers to cut benefits.

Insurer lobbyist America's Health Insurance Plans President Marilyn Tavenner said it was important that the final policy ensure the long-term stability of Medicare Advantage. She said in a statement that the group was looking closely at the proposal.

About 17 million Americans have healthcare coverage through Medicare Advantage, offered by insurers including UnitedHealth Group Inc, Aetna Inc, and Anthem Inc among others. Another more than 30 million people receive benefits through the government Medicare fee-for-service program.

Shares of Anthem Inc rose 1.4 percent in after-hours trading, while UnitedHealth Group gained 1.6 percent.

Some insurers may benefit more than others from the proposal to pay more to insurers who are managing plans for people who qualify for both Medicare and Medicaid for the poor, said Kim Monk, managing director of Capital Alpha Partners.

The 1.35 percent increase is based mostly on anticipated medical cost increases next year. The government expects a 3 percent payment growth rate, which is in line with estimates the government provided to insurers in December.

That 3 percent increase is then reduced to 1.35 percent due to lower payments to insurers for sicker-than-average customers and some medical coding changes, the U.S. Department of Health and Human Services Medicare agency said on Friday.

The 1.35 percent also takes into account an increase in how it pays insurers based on quality measures, called star ratings, it said.

The final rate for 2017 Medicare Advantage payments is based on this proposed figure and will be released in April.

NEW YORK (Reuters) - The U.S. government on Friday proposed raising payments by 1.35 percent on average next year to the health insurers who offer Medicare Advantage health benefits to elderly and disabled Americans.

Payments to insurers will vary under the 2017 Medicare Advantage proposal, based on the region the plans are sold and on the size of bonus payments insurers can receive based on quality ratings, the government said.

Shares of health insurers rose in after-hours trade. Analysts said the proposal looked positive for insurers at first glance, but cautioned that they needed to parse it fully.

"Looks like the best case scenario has played itself out,"said Ipsita Smolinski of Capitol Street, a Washington D.C. research firm, who had anticipated about 1 percent increase in payments.

Insurers and lawmakers have pressured the government not to cut payments, saying any decrease would hurt older Americans by forcing insurers to cut benefits.

Insurer lobbyist America's Health Insurance Plans President Marilyn Tavenner said it was important that the final policy ensure the long-term stability of Medicare Advantage. She said in a statement that the group was looking closely at the proposal.

About 17 million Americans have healthcare coverage through Medicare Advantage, offered by insurers including UnitedHealth Group Inc, Aetna Inc, and Anthem Inc among others. Another more than 30 million people receive benefits through the government Medicare fee-for-service program.

Shares of Anthem Inc rose 1.4 percent in after-hours trading, while UnitedHealth Group gained 1.6 percent.

Some insurers may benefit more than others from the proposal to pay more to insurers who are managing plans for people who qualify for both Medicare and Medicaid for the poor, said Kim Monk, managing director of Capital Alpha Partners.

The 1.35 percent increase is based mostly on anticipated medical cost increases next year. The government expects a 3 percent payment growth rate, which is in line with estimates the government provided to insurers in December.

That 3 percent increase is then reduced to 1.35 percent due to lower payments to insurers for sicker-than-average customers and some medical coding changes, the U.S. Department of Health and Human Services Medicare agency said on Friday.

The 1.35 percent also takes into account an increase in how it pays insurers based on quality measures, called star ratings, it said.

The final rate for 2017 Medicare Advantage payments is based on this proposed figure and will be released in April.

Rivaroxaban (Xarelto)

The US Food and Drug Administration (FDA) is investigating issues surrounding a defect in the device that was used to test international normalized ratios (INRs) in the ROCKET AF trial.

ROCKET AF was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union.

According to a legal brief filed in federal court earlier this week, the FDA has asked rivaroxaban’s manufacturer, Johnson & Johnson, if there was evidence of the defect in the INR-measuring device while ROCKET AF was underway.

The trial was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.

Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

However, an article recently published in The BMJ questioned these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ INRs during the trial, was recalled in December 2014 after giving falsely low test results.

The article suggested the system could have provided falsely low INR values in some patients in the warfarin arm. The lower values could have led investigators to give incorrect doses of warfarin, increasing the risk of bleeding for those patients and therefore giving a false impression of the comparative safety of rivaroxaban.

Two days after The BMJ article was published, the European Medicines Agency released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.

Researchers at the Duke Clinical Research Institute, which oversaw ROCKET AF, also assessed the impact of the INRatio defect. Their findings, published in NEJM, suggested the defect did not affect the trial’s outcome.

However, it appears the FDA still has some concerns. The agency has asked Johnson & Johnson whether there was evidence of the INRatio defect during ROCKET AF, according to a legal brief filed by lawyers representing individuals claiming injuries resulting from rivaroxaban.

The brief also cited internal emails that, according to the lawyers, showed some ROCKET AF investigators questioned the accuracy of the INRatio system during the trial. In fact, the lawyers said a special program was set up to investigate the malfunctions, but Johnson & Johnson never disclosed this information to the FDA.

Rivaroxaban (Xarelto)

The US Food and Drug Administration (FDA) is investigating issues surrounding a defect in the device that was used to test international normalized ratios (INRs) in the ROCKET AF trial.

ROCKET AF was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union.

According to a legal brief filed in federal court earlier this week, the FDA has asked rivaroxaban’s manufacturer, Johnson & Johnson, if there was evidence of the defect in the INR-measuring device while ROCKET AF was underway.

The trial was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.

Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

However, an article recently published in The BMJ questioned these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ INRs during the trial, was recalled in December 2014 after giving falsely low test results.

The article suggested the system could have provided falsely low INR values in some patients in the warfarin arm. The lower values could have led investigators to give incorrect doses of warfarin, increasing the risk of bleeding for those patients and therefore giving a false impression of the comparative safety of rivaroxaban.

Two days after The BMJ article was published, the European Medicines Agency released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.

Researchers at the Duke Clinical Research Institute, which oversaw ROCKET AF, also assessed the impact of the INRatio defect. Their findings, published in NEJM, suggested the defect did not affect the trial’s outcome.

However, it appears the FDA still has some concerns. The agency has asked Johnson & Johnson whether there was evidence of the INRatio defect during ROCKET AF, according to a legal brief filed by lawyers representing individuals claiming injuries resulting from rivaroxaban.

The brief also cited internal emails that, according to the lawyers, showed some ROCKET AF investigators questioned the accuracy of the INRatio system during the trial. In fact, the lawyers said a special program was set up to investigate the malfunctions, but Johnson & Johnson never disclosed this information to the FDA.

Rivaroxaban (Xarelto)

The US Food and Drug Administration (FDA) is investigating issues surrounding a defect in the device that was used to test international normalized ratios (INRs) in the ROCKET AF trial.

ROCKET AF was used to support approval for the direct oral anticoagulant rivaroxaban (Xarelto) in the US and European Union.

According to a legal brief filed in federal court earlier this week, the FDA has asked rivaroxaban’s manufacturer, Johnson & Johnson, if there was evidence of the defect in the INR-measuring device while ROCKET AF was underway.

The trial was a comparison of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation.

Results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

However, an article recently published in The BMJ questioned these results because the Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips), which was used to measure patients’ INRs during the trial, was recalled in December 2014 after giving falsely low test results.

The article suggested the system could have provided falsely low INR values in some patients in the warfarin arm. The lower values could have led investigators to give incorrect doses of warfarin, increasing the risk of bleeding for those patients and therefore giving a false impression of the comparative safety of rivaroxaban.

Two days after The BMJ article was published, the European Medicines Agency released a statement saying the defect with the INRatio system does not change the overall conclusions of ROCKET AF.

Researchers at the Duke Clinical Research Institute, which oversaw ROCKET AF, also assessed the impact of the INRatio defect. Their findings, published in NEJM, suggested the defect did not affect the trial’s outcome.

However, it appears the FDA still has some concerns. The agency has asked Johnson & Johnson whether there was evidence of the INRatio defect during ROCKET AF, according to a legal brief filed by lawyers representing individuals claiming injuries resulting from rivaroxaban.

The brief also cited internal emails that, according to the lawyers, showed some ROCKET AF investigators questioned the accuracy of the INRatio system during the trial. In fact, the lawyers said a special program was set up to investigate the malfunctions, but Johnson & Johnson never disclosed this information to the FDA.

Chromosomes in red
with telomeres in green
Image by Claus Azzalin

Researchers say they have found a new way to fight aplastic anemia—using a therapy designed to delay aging.

Four years ago, the group created telomerase gene therapy, an antiaging treatment based on repairing telomeres.

Now, they have found evidence to suggest this therapy can be effective against both acquired and inherited aplastic anemia.

The team reported preclinical results with the treatment in Blood.

In 2012, Maria A. Blasco, PhD, of Centro Nacional de Investigaciones Oncologicas in Madrid, Spain, and her colleagues described a strategy to repair telomeres.

They used adeno-associated virus (AAV9) vectors to deliver telomerase (Tert) gene therapy, which attenuated or reverted aging-associated telomere erosion in peripheral blood mononuclear cells.

For the current study, the researchers tested the therapy in a mouse model of acquired aplastic anemia and one of inherited aplastic anemia.

Acquired aplastic anemia

For the model of acquired aplastic anemia, the researchers depleted the TRF1 shelterin protein in the bone marrow. The team said this causes severe telomere uncapping and provokes a persistent DNA damage response at telomeres, which leads to fast clearance of hematopoietic stem and progenitor cells (HSPCs) deficient for Trf1.

The remaining HSPCs then undergo additional rounds of compensatory proliferation to regenerate the bone marrow, which leads to rapid telomere attrition. So this model recapitulates the compensatory hyperproliferation and short-telomere phenotype observed in acquired aplastic anemia.

The researchers induced Trf1 deletion with polyinosinic-polycytidylic acid injections given 3 times a week for 5 weeks. At that point, the mice began to show signs of aplastic anemia. A week after the last injection, the mice received either AAV9-Tert or AAV9-empty vectors.

Eighty-seven percent of the AAV9-Tert mice were still alive at 100 days, compared to 55% of mice in the empty vector group (P=0.0025).

In addition, 13% (4/31) of the mice treated with AAV9-Tert actually developed aplastic anemia, while 44% (16/36) of the control mice died showing “clear signs” of aplastic anemia (P=0.0006).

Finally, the researchers found that AAV9-Tert reversed telomere shortening in peripheral blood and bone marrow cells.

Inherited aplastic anemia

For the model of inherited aplastic anemia, the researchers transplanted irradiated wild-type mice with bone marrow from third-generation telomerase-deficient Tert knockout mice. These mice have short telomeres resulting from telomerase deficiency over 3 generations.

As with the previous model, these mice received AAV9-Tert or AAV9-empty vectors. The AAV9-Tert mice had a superior survival rate that nearly reached statistical significance (P=0.058).

The researchers also found that, compared to controls, AAV9-Tert-treated mice had significant increases in hemoglobin levels (P=0.003), erythrocyte counts (P=0.006), and platelet counts (P=0.035), as well as a trend toward an increase in leukocyte counts (P=0.09).

In addition, AAV9-Tert treatment led to a net increase in average telomere length of 5.18Kb, while control mice had a slight telomere shortening of 1.76Kb.

The researchers noted that there are types of aplastic anemia not associated with short telomeres. However, they believe these results provide proof of concept that gene therapy is a valid strategy for treating aplastic anemia.

Chromosomes in red
with telomeres in green
Image by Claus Azzalin

Researchers say they have found a new way to fight aplastic anemia—using a therapy designed to delay aging.

Four years ago, the group created telomerase gene therapy, an antiaging treatment based on repairing telomeres.

Now, they have found evidence to suggest this therapy can be effective against both acquired and inherited aplastic anemia.

The team reported preclinical results with the treatment in Blood.

In 2012, Maria A. Blasco, PhD, of Centro Nacional de Investigaciones Oncologicas in Madrid, Spain, and her colleagues described a strategy to repair telomeres.

They used adeno-associated virus (AAV9) vectors to deliver telomerase (Tert) gene therapy, which attenuated or reverted aging-associated telomere erosion in peripheral blood mononuclear cells.

For the current study, the researchers tested the therapy in a mouse model of acquired aplastic anemia and one of inherited aplastic anemia.

Acquired aplastic anemia

For the model of acquired aplastic anemia, the researchers depleted the TRF1 shelterin protein in the bone marrow. The team said this causes severe telomere uncapping and provokes a persistent DNA damage response at telomeres, which leads to fast clearance of hematopoietic stem and progenitor cells (HSPCs) deficient for Trf1.

The remaining HSPCs then undergo additional rounds of compensatory proliferation to regenerate the bone marrow, which leads to rapid telomere attrition. So this model recapitulates the compensatory hyperproliferation and short-telomere phenotype observed in acquired aplastic anemia.

The researchers induced Trf1 deletion with polyinosinic-polycytidylic acid injections given 3 times a week for 5 weeks. At that point, the mice began to show signs of aplastic anemia. A week after the last injection, the mice received either AAV9-Tert or AAV9-empty vectors.

Eighty-seven percent of the AAV9-Tert mice were still alive at 100 days, compared to 55% of mice in the empty vector group (P=0.0025).

In addition, 13% (4/31) of the mice treated with AAV9-Tert actually developed aplastic anemia, while 44% (16/36) of the control mice died showing “clear signs” of aplastic anemia (P=0.0006).

Finally, the researchers found that AAV9-Tert reversed telomere shortening in peripheral blood and bone marrow cells.

Inherited aplastic anemia

For the model of inherited aplastic anemia, the researchers transplanted irradiated wild-type mice with bone marrow from third-generation telomerase-deficient Tert knockout mice. These mice have short telomeres resulting from telomerase deficiency over 3 generations.

As with the previous model, these mice received AAV9-Tert or AAV9-empty vectors. The AAV9-Tert mice had a superior survival rate that nearly reached statistical significance (P=0.058).

The researchers also found that, compared to controls, AAV9-Tert-treated mice had significant increases in hemoglobin levels (P=0.003), erythrocyte counts (P=0.006), and platelet counts (P=0.035), as well as a trend toward an increase in leukocyte counts (P=0.09).

In addition, AAV9-Tert treatment led to a net increase in average telomere length of 5.18Kb, while control mice had a slight telomere shortening of 1.76Kb.

The researchers noted that there are types of aplastic anemia not associated with short telomeres. However, they believe these results provide proof of concept that gene therapy is a valid strategy for treating aplastic anemia.

Chromosomes in red
with telomeres in green
Image by Claus Azzalin

Researchers say they have found a new way to fight aplastic anemia—using a therapy designed to delay aging.

Four years ago, the group created telomerase gene therapy, an antiaging treatment based on repairing telomeres.

Now, they have found evidence to suggest this therapy can be effective against both acquired and inherited aplastic anemia.

The team reported preclinical results with the treatment in Blood.

In 2012, Maria A. Blasco, PhD, of Centro Nacional de Investigaciones Oncologicas in Madrid, Spain, and her colleagues described a strategy to repair telomeres.

They used adeno-associated virus (AAV9) vectors to deliver telomerase (Tert) gene therapy, which attenuated or reverted aging-associated telomere erosion in peripheral blood mononuclear cells.

For the current study, the researchers tested the therapy in a mouse model of acquired aplastic anemia and one of inherited aplastic anemia.

Acquired aplastic anemia

For the model of acquired aplastic anemia, the researchers depleted the TRF1 shelterin protein in the bone marrow. The team said this causes severe telomere uncapping and provokes a persistent DNA damage response at telomeres, which leads to fast clearance of hematopoietic stem and progenitor cells (HSPCs) deficient for Trf1.

The remaining HSPCs then undergo additional rounds of compensatory proliferation to regenerate the bone marrow, which leads to rapid telomere attrition. So this model recapitulates the compensatory hyperproliferation and short-telomere phenotype observed in acquired aplastic anemia.

The researchers induced Trf1 deletion with polyinosinic-polycytidylic acid injections given 3 times a week for 5 weeks. At that point, the mice began to show signs of aplastic anemia. A week after the last injection, the mice received either AAV9-Tert or AAV9-empty vectors.

Eighty-seven percent of the AAV9-Tert mice were still alive at 100 days, compared to 55% of mice in the empty vector group (P=0.0025).

In addition, 13% (4/31) of the mice treated with AAV9-Tert actually developed aplastic anemia, while 44% (16/36) of the control mice died showing “clear signs” of aplastic anemia (P=0.0006).

Finally, the researchers found that AAV9-Tert reversed telomere shortening in peripheral blood and bone marrow cells.

Inherited aplastic anemia

For the model of inherited aplastic anemia, the researchers transplanted irradiated wild-type mice with bone marrow from third-generation telomerase-deficient Tert knockout mice. These mice have short telomeres resulting from telomerase deficiency over 3 generations.

As with the previous model, these mice received AAV9-Tert or AAV9-empty vectors. The AAV9-Tert mice had a superior survival rate that nearly reached statistical significance (P=0.058).

The researchers also found that, compared to controls, AAV9-Tert-treated mice had significant increases in hemoglobin levels (P=0.003), erythrocyte counts (P=0.006), and platelet counts (P=0.035), as well as a trend toward an increase in leukocyte counts (P=0.09).

In addition, AAV9-Tert treatment led to a net increase in average telomere length of 5.18Kb, while control mice had a slight telomere shortening of 1.76Kb.

The researchers noted that there are types of aplastic anemia not associated with short telomeres. However, they believe these results provide proof of concept that gene therapy is a valid strategy for treating aplastic anemia.

Micrograph showing HSCs

in the bone marrow

HONOLULU—Early results from a pilot study suggest an investigational agent can effectively mobilize hematopoietic stem cells (HSCs) in healthy transplant donors.

The agent, CDX-301 (recombinant human Flt3 ligand), is a hematopoietic cytokine designed to expand dendritic cells and HSCs.

For the study, researchers tested CDX-301 in sibling-matched donors for hematopoietic stem cell transplant (HSCT) recipients with hematologic malignancies.

The team reported early results with 4 donor/recipient pairs at the 2016 BMT Tandem Meetings (abstract 479). The research was sponsored by Celldex Therapeutics, Inc., the company developing CDX-301.

Donor results

The donors received CDX-301 at 75 μg/kg/day for 5 days. Leukapheresis began on day 6 if the peripheral blood CD34+ count was 7/μL or greater. The goal CD34+ yield was at least 2x10⁶ per kilogram of recipient weight collected in 2 days of leukapheresis or less.

The donors could receive rescue plerixafor if the peripheral blood CD34+ count was less than 7/μL by day 8 or if the total CD34+ yield was less than 1x10⁶/kg after the second day of leukapheresis.

The researchers analyzed CDX-301-mobilized cells by flow cytometry and compared them to historical data for peripheral blood grafts mobilized by granulocyte colony-stimulating factor (G-CSF).

Compared to the G-CSF-mobilized grafts, CDX-301-mobilized grafts had an increase in CD127+ (IL-7R) naïve T cells, γδ T cells, natural killer cells, and B cells.

The CDX-301-mobilized grafts were more enriched with plasmacytoid dendritic cells. And dendritic cells from the CDX-301 grafts had a more mature phenotype, expressing CD80 and CD86.

“From these data and preclinical studies, CDX-301 appears to be an effective, targeted approach to mobilization comparable to G-CSF,” said Steven Devine, MD, of The Ohio State Comprehensive Cancer Center in Columbus.

“With a relatively short course of treatment, we are observing specificity for mobilized stem cells and a lack of toxicity, instead of broad cellular mobilization and side effects.”

CDX-301 related adverse events included dizziness (grade 2), back pain (grade 1), arthralgia (grade 1), injection site reaction (2 grade 1), dyspepsia (1 grade 1, 1 grade 2), and decreased platelet count (2 grade 1). There were no grade 3/4 adverse events.

Recipient results

Thus far, 4 recipients have undergone HSCT with CDX-301-mobilized grafts. Recipient 1 had acute myeloid leukemia, recipients 2 and 3 had mantle cell lymphoma, and recipient 4 had chronic myeloid leukemia.

Recipients 1 through 3 received myeloablative conditioning, while recipient 4 received reduced-intensity conditioning. All patients received standard graft-vs-host disease (GVHD) prophylaxis (tacrolimus and methotrexate).

Recipient 4 has not yet engrafted. The other 3 had both neutrophil engraftment (day 17, 18, and 19) and platelet engraftment (day 14, 25, and 40).

There have been no infectious complications, and recipients 1 and 3 have not developed GVHD.

Recipient 2 developed steroid-responsive, grade 2, upper gastrointestinal GVHD on day 18, followed by grade 1 skin GVHD on day 50 that progressed to stage 3. Overall, the patient had grade 2 GVHD on day 64. The patient’s lymphoma has also progressed.

The researchers said these results suggest CDX-301 is well tolerated and can mobilize CD34+ cells when given as a single agent. They said recipients experienced successful engraftment in an expected time frame.

And the additional naïve T cells and plasmacytoid dendritic cells in CDX-301-mobilized grafts (compared to G-CSF-mobilized grafts) may provide better outcomes in HSCT recipients.

Now, the researchers plan to explore CDX-301 in combination with plerixafor. Additional donor/patient pairs are being accrued to a second study cohort.

Micrograph showing HSCs

in the bone marrow

HONOLULU—Early results from a pilot study suggest an investigational agent can effectively mobilize hematopoietic stem cells (HSCs) in healthy transplant donors.

The agent, CDX-301 (recombinant human Flt3 ligand), is a hematopoietic cytokine designed to expand dendritic cells and HSCs.

For the study, researchers tested CDX-301 in sibling-matched donors for hematopoietic stem cell transplant (HSCT) recipients with hematologic malignancies.

The team reported early results with 4 donor/recipient pairs at the 2016 BMT Tandem Meetings (abstract 479). The research was sponsored by Celldex Therapeutics, Inc., the company developing CDX-301.

Donor results

The donors received CDX-301 at 75 μg/kg/day for 5 days. Leukapheresis began on day 6 if the peripheral blood CD34+ count was 7/μL or greater. The goal CD34+ yield was at least 2x10⁶ per kilogram of recipient weight collected in 2 days of leukapheresis or less.

The donors could receive rescue plerixafor if the peripheral blood CD34+ count was less than 7/μL by day 8 or if the total CD34+ yield was less than 1x10⁶/kg after the second day of leukapheresis.

The researchers analyzed CDX-301-mobilized cells by flow cytometry and compared them to historical data for peripheral blood grafts mobilized by granulocyte colony-stimulating factor (G-CSF).

Compared to the G-CSF-mobilized grafts, CDX-301-mobilized grafts had an increase in CD127+ (IL-7R) naïve T cells, γδ T cells, natural killer cells, and B cells.

The CDX-301-mobilized grafts were more enriched with plasmacytoid dendritic cells. And dendritic cells from the CDX-301 grafts had a more mature phenotype, expressing CD80 and CD86.

“From these data and preclinical studies, CDX-301 appears to be an effective, targeted approach to mobilization comparable to G-CSF,” said Steven Devine, MD, of The Ohio State Comprehensive Cancer Center in Columbus.

“With a relatively short course of treatment, we are observing specificity for mobilized stem cells and a lack of toxicity, instead of broad cellular mobilization and side effects.”

CDX-301 related adverse events included dizziness (grade 2), back pain (grade 1), arthralgia (grade 1), injection site reaction (2 grade 1), dyspepsia (1 grade 1, 1 grade 2), and decreased platelet count (2 grade 1). There were no grade 3/4 adverse events.

Recipient results

Thus far, 4 recipients have undergone HSCT with CDX-301-mobilized grafts. Recipient 1 had acute myeloid leukemia, recipients 2 and 3 had mantle cell lymphoma, and recipient 4 had chronic myeloid leukemia.

Recipients 1 through 3 received myeloablative conditioning, while recipient 4 received reduced-intensity conditioning. All patients received standard graft-vs-host disease (GVHD) prophylaxis (tacrolimus and methotrexate).

Recipient 4 has not yet engrafted. The other 3 had both neutrophil engraftment (day 17, 18, and 19) and platelet engraftment (day 14, 25, and 40).

There have been no infectious complications, and recipients 1 and 3 have not developed GVHD.

Recipient 2 developed steroid-responsive, grade 2, upper gastrointestinal GVHD on day 18, followed by grade 1 skin GVHD on day 50 that progressed to stage 3. Overall, the patient had grade 2 GVHD on day 64. The patient’s lymphoma has also progressed.

The researchers said these results suggest CDX-301 is well tolerated and can mobilize CD34+ cells when given as a single agent. They said recipients experienced successful engraftment in an expected time frame.

And the additional naïve T cells and plasmacytoid dendritic cells in CDX-301-mobilized grafts (compared to G-CSF-mobilized grafts) may provide better outcomes in HSCT recipients.

Now, the researchers plan to explore CDX-301 in combination with plerixafor. Additional donor/patient pairs are being accrued to a second study cohort.

Micrograph showing HSCs

in the bone marrow

HONOLULU—Early results from a pilot study suggest an investigational agent can effectively mobilize hematopoietic stem cells (HSCs) in healthy transplant donors.

The agent, CDX-301 (recombinant human Flt3 ligand), is a hematopoietic cytokine designed to expand dendritic cells and HSCs.

For the study, researchers tested CDX-301 in sibling-matched donors for hematopoietic stem cell transplant (HSCT) recipients with hematologic malignancies.

The team reported early results with 4 donor/recipient pairs at the 2016 BMT Tandem Meetings (abstract 479). The research was sponsored by Celldex Therapeutics, Inc., the company developing CDX-301.

Donor results

The donors received CDX-301 at 75 μg/kg/day for 5 days. Leukapheresis began on day 6 if the peripheral blood CD34+ count was 7/μL or greater. The goal CD34+ yield was at least 2x10⁶ per kilogram of recipient weight collected in 2 days of leukapheresis or less.

The donors could receive rescue plerixafor if the peripheral blood CD34+ count was less than 7/μL by day 8 or if the total CD34+ yield was less than 1x10⁶/kg after the second day of leukapheresis.

The researchers analyzed CDX-301-mobilized cells by flow cytometry and compared them to historical data for peripheral blood grafts mobilized by granulocyte colony-stimulating factor (G-CSF).

Compared to the G-CSF-mobilized grafts, CDX-301-mobilized grafts had an increase in CD127+ (IL-7R) naïve T cells, γδ T cells, natural killer cells, and B cells.

The CDX-301-mobilized grafts were more enriched with plasmacytoid dendritic cells. And dendritic cells from the CDX-301 grafts had a more mature phenotype, expressing CD80 and CD86.

“From these data and preclinical studies, CDX-301 appears to be an effective, targeted approach to mobilization comparable to G-CSF,” said Steven Devine, MD, of The Ohio State Comprehensive Cancer Center in Columbus.

“With a relatively short course of treatment, we are observing specificity for mobilized stem cells and a lack of toxicity, instead of broad cellular mobilization and side effects.”

CDX-301 related adverse events included dizziness (grade 2), back pain (grade 1), arthralgia (grade 1), injection site reaction (2 grade 1), dyspepsia (1 grade 1, 1 grade 2), and decreased platelet count (2 grade 1). There were no grade 3/4 adverse events.

Recipient results

Thus far, 4 recipients have undergone HSCT with CDX-301-mobilized grafts. Recipient 1 had acute myeloid leukemia, recipients 2 and 3 had mantle cell lymphoma, and recipient 4 had chronic myeloid leukemia.

Recipients 1 through 3 received myeloablative conditioning, while recipient 4 received reduced-intensity conditioning. All patients received standard graft-vs-host disease (GVHD) prophylaxis (tacrolimus and methotrexate).

Recipient 4 has not yet engrafted. The other 3 had both neutrophil engraftment (day 17, 18, and 19) and platelet engraftment (day 14, 25, and 40).

There have been no infectious complications, and recipients 1 and 3 have not developed GVHD.

Recipient 2 developed steroid-responsive, grade 2, upper gastrointestinal GVHD on day 18, followed by grade 1 skin GVHD on day 50 that progressed to stage 3. Overall, the patient had grade 2 GVHD on day 64. The patient’s lymphoma has also progressed.

The researchers said these results suggest CDX-301 is well tolerated and can mobilize CD34+ cells when given as a single agent. They said recipients experienced successful engraftment in an expected time frame.

And the additional naïve T cells and plasmacytoid dendritic cells in CDX-301-mobilized grafts (compared to G-CSF-mobilized grafts) may provide better outcomes in HSCT recipients.

Now, the researchers plan to explore CDX-301 in combination with plerixafor. Additional donor/patient pairs are being accrued to a second study cohort.

Blood sample collection

Photo by Juan D. Alfonso

Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.

Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.

The test can be performed on blood, amniotic fluid, urine, or spinal fluid.

The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.

Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.

Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.

The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.

“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.

“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”

The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area.

Blood sample collection

Photo by Juan D. Alfonso

Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.

Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.

The test can be performed on blood, amniotic fluid, urine, or spinal fluid.

The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.

Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.

Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.

The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.

“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.

“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”

The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area.

Blood sample collection

Photo by Juan D. Alfonso

Two institutions in Houston, Texas, have developed the US’s first hospital-based, rapid diagnostic test for the Zika virus.

Pathologists and clinical laboratory scientists at Texas Children’s Hospital and Houston Methodist Hospital developed the test, which is customized to each hospital’s diagnostic laboratory and can provide results within several hours.

The test can be performed on blood, amniotic fluid, urine, or spinal fluid.

The test identifies virus-specific RNA sequences to detect Zika virus. It can distinguish Zika infection from dengue, West Nile, or chikungunya infections.

Right now, only registered patients at Texas Children’s or Houston Methodist Hospital can receive the test, but the labs will consider referral testing from other hospitals and clinics in the future.

Initially, the test will be offered to patients with a positive travel history and symptoms consistent with acute Zika virus infection (eg, rash, arthralgia, or fever) or asymptomatic pregnant women with a positive travel history to any of the Zika-affected countries.

The goal of hospital-based testing for Zika virus is to prevent the delays that may occur with testing conducted in local and state public health laboratories and the Centers for Disease Control and Prevention.

“Hospital-based testing that is state-of-the-art enables our physicians and patients to get very rapid diagnostic answers,” said James M. Musser, MD, PhD, of Houston Methodist Hospital.

“If tests need to be repeated or if our treating doctors need to talk with our pathologists, we have the resources near patient care settings.”

The collaboration between Texas Children’s and Houston Methodist Hospital was sponsored by the L.E. and Virginia Simmons Collaborative in Virus Detection and Surveillance. This program was designed to facilitate rapid development of tests for virus detection in a large metropolitan area.

SCOTTSDALE, ARIZ. – Costs of care are a major burden in patients undergoing treatment for head and neck cancer, especially those who are socially isolated, finds a study reported at the Multidisciplinary Head and Neck Cancer Symposium.

More than two-thirds of the 73 patients with locally advanced disease had adopted life-altering strategies, such as tapping their savings or using credit to help pay for treatment, according to data presented in a poster session and related press briefing.

Patients who had a high perceived level of social isolation were more than 10 times as likely to have taken such actions than counterparts who had a medium or low level of isolation.

“Based on our study, a majority of patients rely on lifestyle-altering, cost-coping strategies to manage the financial side effects of head and neck cancer care. Financial side effects should be considered a morbidity of head and neck cancer,” commented lead author Sunny Kung, a second-year medical student at the University of Chicago and lead author on the study. “A lack of social support, coupled with increased loneliness is a risk factor for suboptimal medication adherence, missed appointments, and longer length of hospital stay.”

“Our study demonstrates that it is important for physicians to assess risk factors such as financial burden, loneliness, and [lack of] social support in order to provide optimal care for our patients,” she added. “Additional studies should be done to identify patient-specific interventions in order to help these patients optimize their care.”

Press briefing moderator Dr. Randall J. Kimple of the University of Wisconsin–Madison, noted, “One of the questions that our patients often ask and one of the things that we often spend time talking to our patients about is how long can they continue working after treatment. Was your dataset able to provide any insight into that?”

“Our study confirms that many of our patients are actually unable to continue working,” Ms. Kung replied. “I think head and neck cancer has some of the highest rates of disability of all the cancers – it’s something above 50% or 60%. I’m not sure about the exact number, but it’s quite high.”

In the study, the investigators followed patients starting treatment at the University of Chicago, surveying them monthly for 6 months about out-of-pocket costs, coping strategies, medication compliance, health care use, and perceived social isolation (loneliness and lack of social support).

During that 6-month period, 69% of patients overall used one or more lifestyle-altering strategies to cope with the costs of treatment. Specifically, 62% used part or all of their savings, 42% borrowed money or used credit, 25% sold possessions or property, and 23% had family members work more hours.

“We only assessed whether or not they used their savings, not how much of their savings they used,” Ms. Kung noted. “So this is a limitation of our study.”

The patients’ mean total monthly out-of-pocket costs totaled to $1,589. This was mainly driven by direct medical costs such as deductibles and hospital bills ($1,286), but insurance premiums also contributed ($303). Median values were lower but still substantial.

In multivariate analyses that controlled for potential confounders including factors such as marital status, patients were significantly and markedly more likely to resort to cost-coping strategies if they had Medicaid as compared with private insurance (odds ratio, 42.3). The likelihood rose with each $1,000 increment in total out-of-pocket costs (OR, 1.07) and fell with each $10,000 increment in wealth status (OR, 0.95). Patients who had a high perceived level of social isolation before starting treatment were also dramatically more likely to use these strategies (OR, 11.5).

Furthermore, on average, patients with a high level of social isolation skipped medication on more days (21.4 vs. 5.5; P = .03) and missed more appointments (7 vs. 3; P = .008).

“I believe it’s important for physicians to start screening patients – just as we do for depression – and identifying patients who have high perceived social isolation so that we can intervene earlier on, before they experience these negative financial side effects of their care,” concluded Ms. Kung.

SCOTTSDALE, ARIZ. – Costs of care are a major burden in patients undergoing treatment for head and neck cancer, especially those who are socially isolated, finds a study reported at the Multidisciplinary Head and Neck Cancer Symposium.

More than two-thirds of the 73 patients with locally advanced disease had adopted life-altering strategies, such as tapping their savings or using credit to help pay for treatment, according to data presented in a poster session and related press briefing.

Patients who had a high perceived level of social isolation were more than 10 times as likely to have taken such actions than counterparts who had a medium or low level of isolation.

“Based on our study, a majority of patients rely on lifestyle-altering, cost-coping strategies to manage the financial side effects of head and neck cancer care. Financial side effects should be considered a morbidity of head and neck cancer,” commented lead author Sunny Kung, a second-year medical student at the University of Chicago and lead author on the study. “A lack of social support, coupled with increased loneliness is a risk factor for suboptimal medication adherence, missed appointments, and longer length of hospital stay.”

“Our study demonstrates that it is important for physicians to assess risk factors such as financial burden, loneliness, and [lack of] social support in order to provide optimal care for our patients,” she added. “Additional studies should be done to identify patient-specific interventions in order to help these patients optimize their care.”

Press briefing moderator Dr. Randall J. Kimple of the University of Wisconsin–Madison, noted, “One of the questions that our patients often ask and one of the things that we often spend time talking to our patients about is how long can they continue working after treatment. Was your dataset able to provide any insight into that?”

“Our study confirms that many of our patients are actually unable to continue working,” Ms. Kung replied. “I think head and neck cancer has some of the highest rates of disability of all the cancers – it’s something above 50% or 60%. I’m not sure about the exact number, but it’s quite high.”

In the study, the investigators followed patients starting treatment at the University of Chicago, surveying them monthly for 6 months about out-of-pocket costs, coping strategies, medication compliance, health care use, and perceived social isolation (loneliness and lack of social support).

During that 6-month period, 69% of patients overall used one or more lifestyle-altering strategies to cope with the costs of treatment. Specifically, 62% used part or all of their savings, 42% borrowed money or used credit, 25% sold possessions or property, and 23% had family members work more hours.

“We only assessed whether or not they used their savings, not how much of their savings they used,” Ms. Kung noted. “So this is a limitation of our study.”

The patients’ mean total monthly out-of-pocket costs totaled to $1,589. This was mainly driven by direct medical costs such as deductibles and hospital bills ($1,286), but insurance premiums also contributed ($303). Median values were lower but still substantial.

In multivariate analyses that controlled for potential confounders including factors such as marital status, patients were significantly and markedly more likely to resort to cost-coping strategies if they had Medicaid as compared with private insurance (odds ratio, 42.3). The likelihood rose with each $1,000 increment in total out-of-pocket costs (OR, 1.07) and fell with each $10,000 increment in wealth status (OR, 0.95). Patients who had a high perceived level of social isolation before starting treatment were also dramatically more likely to use these strategies (OR, 11.5).

Furthermore, on average, patients with a high level of social isolation skipped medication on more days (21.4 vs. 5.5; P = .03) and missed more appointments (7 vs. 3; P = .008).

“I believe it’s important for physicians to start screening patients – just as we do for depression – and identifying patients who have high perceived social isolation so that we can intervene earlier on, before they experience these negative financial side effects of their care,” concluded Ms. Kung.

SCOTTSDALE, ARIZ. – Costs of care are a major burden in patients undergoing treatment for head and neck cancer, especially those who are socially isolated, finds a study reported at the Multidisciplinary Head and Neck Cancer Symposium.

More than two-thirds of the 73 patients with locally advanced disease had adopted life-altering strategies, such as tapping their savings or using credit to help pay for treatment, according to data presented in a poster session and related press briefing.

Patients who had a high perceived level of social isolation were more than 10 times as likely to have taken such actions than counterparts who had a medium or low level of isolation.

“Based on our study, a majority of patients rely on lifestyle-altering, cost-coping strategies to manage the financial side effects of head and neck cancer care. Financial side effects should be considered a morbidity of head and neck cancer,” commented lead author Sunny Kung, a second-year medical student at the University of Chicago and lead author on the study. “A lack of social support, coupled with increased loneliness is a risk factor for suboptimal medication adherence, missed appointments, and longer length of hospital stay.”

“Our study demonstrates that it is important for physicians to assess risk factors such as financial burden, loneliness, and [lack of] social support in order to provide optimal care for our patients,” she added. “Additional studies should be done to identify patient-specific interventions in order to help these patients optimize their care.”

Press briefing moderator Dr. Randall J. Kimple of the University of Wisconsin–Madison, noted, “One of the questions that our patients often ask and one of the things that we often spend time talking to our patients about is how long can they continue working after treatment. Was your dataset able to provide any insight into that?”

“Our study confirms that many of our patients are actually unable to continue working,” Ms. Kung replied. “I think head and neck cancer has some of the highest rates of disability of all the cancers – it’s something above 50% or 60%. I’m not sure about the exact number, but it’s quite high.”

In the study, the investigators followed patients starting treatment at the University of Chicago, surveying them monthly for 6 months about out-of-pocket costs, coping strategies, medication compliance, health care use, and perceived social isolation (loneliness and lack of social support).

During that 6-month period, 69% of patients overall used one or more lifestyle-altering strategies to cope with the costs of treatment. Specifically, 62% used part or all of their savings, 42% borrowed money or used credit, 25% sold possessions or property, and 23% had family members work more hours.

“We only assessed whether or not they used their savings, not how much of their savings they used,” Ms. Kung noted. “So this is a limitation of our study.”

The patients’ mean total monthly out-of-pocket costs totaled to $1,589. This was mainly driven by direct medical costs such as deductibles and hospital bills ($1,286), but insurance premiums also contributed ($303). Median values were lower but still substantial.

In multivariate analyses that controlled for potential confounders including factors such as marital status, patients were significantly and markedly more likely to resort to cost-coping strategies if they had Medicaid as compared with private insurance (odds ratio, 42.3). The likelihood rose with each $1,000 increment in total out-of-pocket costs (OR, 1.07) and fell with each $10,000 increment in wealth status (OR, 0.95). Patients who had a high perceived level of social isolation before starting treatment were also dramatically more likely to use these strategies (OR, 11.5).

Furthermore, on average, patients with a high level of social isolation skipped medication on more days (21.4 vs. 5.5; P = .03) and missed more appointments (7 vs. 3; P = .008).

“I believe it’s important for physicians to start screening patients – just as we do for depression – and identifying patients who have high perceived social isolation so that we can intervene earlier on, before they experience these negative financial side effects of their care,” concluded Ms. Kung.

NEW ORLEANS – Stem cell therapy for progressive multiple sclerosis is an intriguing and controversial topic, and the state of the related science was addressed during a session on “the treatment pipeline” at a meeting sponsored by the Americas Committee for Treatment and Research in Multiple Sclerosis.

In a video interview at the meeting, session chair Dr. Mark Freedman of the University of Ottawa (Ont.) discussed the status of autologous hematopoietic stem cell transplantation; how mesenchymal stem cells are thought to be a potential source for immune system repair; and the intriguing potential for remyelinating therapy with human oligodendrocyte progenitor cells. Research is in the “very preliminary stage” on human oligodendrocyte progenitor cells, but “enticing news” of a safety trial set to begin in North America was presented during the session, he said.

NEW ORLEANS – Stem cell therapy for progressive multiple sclerosis is an intriguing and controversial topic, and the state of the related science was addressed during a session on “the treatment pipeline” at a meeting sponsored by the Americas Committee for Treatment and Research in Multiple Sclerosis.

In a video interview at the meeting, session chair Dr. Mark Freedman of the University of Ottawa (Ont.) discussed the status of autologous hematopoietic stem cell transplantation; how mesenchymal stem cells are thought to be a potential source for immune system repair; and the intriguing potential for remyelinating therapy with human oligodendrocyte progenitor cells. Research is in the “very preliminary stage” on human oligodendrocyte progenitor cells, but “enticing news” of a safety trial set to begin in North America was presented during the session, he said.

NEW ORLEANS – Stem cell therapy for progressive multiple sclerosis is an intriguing and controversial topic, and the state of the related science was addressed during a session on “the treatment pipeline” at a meeting sponsored by the Americas Committee for Treatment and Research in Multiple Sclerosis.

In a video interview at the meeting, session chair Dr. Mark Freedman of the University of Ottawa (Ont.) discussed the status of autologous hematopoietic stem cell transplantation; how mesenchymal stem cells are thought to be a potential source for immune system repair; and the intriguing potential for remyelinating therapy with human oligodendrocyte progenitor cells. Research is in the “very preliminary stage” on human oligodendrocyte progenitor cells, but “enticing news” of a safety trial set to begin in North America was presented during the session, he said.

NEW ORLEANS – The greatest effect of the investigational, B-cell–targeting humanized monoclonal antibody ocrelizumab in treating primary progressive multiple sclerosis (PPMS) may be in patients with T1 gadolinium-positive (Gd+) lesions at baseline, which are indicative of an ongoing or recent MS relapse, according to a subgroup analysis of the randomized, double-blind, placebo-controlled ORATORIO trial.

The analysis hinted at the possibility that ocrelizumab may reduce the risk of confirmed disability progression (CDP) at 12 weeks or 24 weeks to a slightly higher degree among PPMS patients with T1 Gd+ lesions than in those without such lesions, although the differences did not reach statistical significance. The findings await further study because ORATORIO was not powered to demonstrate efficacy differences between the subgroups, Dr. Jerry Wolinsky of the University of Texas Health Science Center at Houston noted in a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Brian Hoyle/Frontline Medical News

In ORATORIO, ocrelizumab (600 mg intravenous infused every 6 months as two 300-mg infusions given 2 weeks apart) was compared with placebo in 732 people with PPMS in a 120-week blinded treatment. The number of patients with T1 Gd+ lesions at baseline was similar in the placebo arm (60/244, 24.7%) and the ocrelizumab arm (133/488, 27.5%). T1 Gd-negative (Gd-) lesions, which are likely older and indicative of the absence of a relapse, were identified in 183 and 350 of the patients in the placebo and ocrelizumab arms, respectively.

Time to onset of 12-week confirmed disability progression (CDP) was delayed in a quarter of the overall population (hazard ratio, 0.76; 95% confidence interval, 0.59-0.98). Risk reduction was greater in the presence of T1 Gd+ lesions at baseline (HR, 0.65; 95% CI, 0.40-1.06), compared with patients harboring T1 Gd- lesions at baseline (HR, 0.84; 95% CI, 0.62-1.13). A similar pattern was evident for time to onset of 24-week CDP.

The changes in timed 25-foot walk from baseline to week 20, and in brain T2 hyperintense lesion volume from baseline to week 120 were significantly reduced overall by treatment. Reductions in walk time and lesion volume were apparent in the T1 Gd+ and Gd- lesion subgroups, with similar percentage change. In the overall study, ocrelizumab significantly slowed decline in brain volume from weeks 24 to 120, and slowed declines were also evident in the T1 Gd+ and Gd- lesion subgroups, compared with placebo.

The findings warrant further studies powered to assess the apparent treatment benefit in patients with Gd+ lesions – who are likely relapsing – at baseline. If the findings hold, stratifying patients prior to treatment based on MRI of T1 Gd+ lesions could help to guide ocrelizumab treatment.

Gadolinium normally cannot pass from the bloodstream into the brain or spinal cord because of the presence of the blood-brain barrier. Active inflammation in the brain or spinal cord during a MS relapse disrupts the barrier. Gadolinium enters the brain or spinal cord and permeates into MS lesions, which appear bright on MRI. 

The study was funded by Hoffmann-La Roche/Genentech. Dr. Wolinsky disclosed receiving consulting fees; compensation for service on steering committees or data monitoring boards; and/or research support from many companies that market MS drugs, including Hoffmann-La Roche/Genentech.

NEW ORLEANS – The greatest effect of the investigational, B-cell–targeting humanized monoclonal antibody ocrelizumab in treating primary progressive multiple sclerosis (PPMS) may be in patients with T1 gadolinium-positive (Gd+) lesions at baseline, which are indicative of an ongoing or recent MS relapse, according to a subgroup analysis of the randomized, double-blind, placebo-controlled ORATORIO trial.

The analysis hinted at the possibility that ocrelizumab may reduce the risk of confirmed disability progression (CDP) at 12 weeks or 24 weeks to a slightly higher degree among PPMS patients with T1 Gd+ lesions than in those without such lesions, although the differences did not reach statistical significance. The findings await further study because ORATORIO was not powered to demonstrate efficacy differences between the subgroups, Dr. Jerry Wolinsky of the University of Texas Health Science Center at Houston noted in a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Brian Hoyle/Frontline Medical News

In ORATORIO, ocrelizumab (600 mg intravenous infused every 6 months as two 300-mg infusions given 2 weeks apart) was compared with placebo in 732 people with PPMS in a 120-week blinded treatment. The number of patients with T1 Gd+ lesions at baseline was similar in the placebo arm (60/244, 24.7%) and the ocrelizumab arm (133/488, 27.5%). T1 Gd-negative (Gd-) lesions, which are likely older and indicative of the absence of a relapse, were identified in 183 and 350 of the patients in the placebo and ocrelizumab arms, respectively.

Time to onset of 12-week confirmed disability progression (CDP) was delayed in a quarter of the overall population (hazard ratio, 0.76; 95% confidence interval, 0.59-0.98). Risk reduction was greater in the presence of T1 Gd+ lesions at baseline (HR, 0.65; 95% CI, 0.40-1.06), compared with patients harboring T1 Gd- lesions at baseline (HR, 0.84; 95% CI, 0.62-1.13). A similar pattern was evident for time to onset of 24-week CDP.

The changes in timed 25-foot walk from baseline to week 20, and in brain T2 hyperintense lesion volume from baseline to week 120 were significantly reduced overall by treatment. Reductions in walk time and lesion volume were apparent in the T1 Gd+ and Gd- lesion subgroups, with similar percentage change. In the overall study, ocrelizumab significantly slowed decline in brain volume from weeks 24 to 120, and slowed declines were also evident in the T1 Gd+ and Gd- lesion subgroups, compared with placebo.

The findings warrant further studies powered to assess the apparent treatment benefit in patients with Gd+ lesions – who are likely relapsing – at baseline. If the findings hold, stratifying patients prior to treatment based on MRI of T1 Gd+ lesions could help to guide ocrelizumab treatment.

Gadolinium normally cannot pass from the bloodstream into the brain or spinal cord because of the presence of the blood-brain barrier. Active inflammation in the brain or spinal cord during a MS relapse disrupts the barrier. Gadolinium enters the brain or spinal cord and permeates into MS lesions, which appear bright on MRI. 

The study was funded by Hoffmann-La Roche/Genentech. Dr. Wolinsky disclosed receiving consulting fees; compensation for service on steering committees or data monitoring boards; and/or research support from many companies that market MS drugs, including Hoffmann-La Roche/Genentech.

NEW ORLEANS – The greatest effect of the investigational, B-cell–targeting humanized monoclonal antibody ocrelizumab in treating primary progressive multiple sclerosis (PPMS) may be in patients with T1 gadolinium-positive (Gd+) lesions at baseline, which are indicative of an ongoing or recent MS relapse, according to a subgroup analysis of the randomized, double-blind, placebo-controlled ORATORIO trial.

The analysis hinted at the possibility that ocrelizumab may reduce the risk of confirmed disability progression (CDP) at 12 weeks or 24 weeks to a slightly higher degree among PPMS patients with T1 Gd+ lesions than in those without such lesions, although the differences did not reach statistical significance. The findings await further study because ORATORIO was not powered to demonstrate efficacy differences between the subgroups, Dr. Jerry Wolinsky of the University of Texas Health Science Center at Houston noted in a presentation at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Brian Hoyle/Frontline Medical News

In ORATORIO, ocrelizumab (600 mg intravenous infused every 6 months as two 300-mg infusions given 2 weeks apart) was compared with placebo in 732 people with PPMS in a 120-week blinded treatment. The number of patients with T1 Gd+ lesions at baseline was similar in the placebo arm (60/244, 24.7%) and the ocrelizumab arm (133/488, 27.5%). T1 Gd-negative (Gd-) lesions, which are likely older and indicative of the absence of a relapse, were identified in 183 and 350 of the patients in the placebo and ocrelizumab arms, respectively.

Time to onset of 12-week confirmed disability progression (CDP) was delayed in a quarter of the overall population (hazard ratio, 0.76; 95% confidence interval, 0.59-0.98). Risk reduction was greater in the presence of T1 Gd+ lesions at baseline (HR, 0.65; 95% CI, 0.40-1.06), compared with patients harboring T1 Gd- lesions at baseline (HR, 0.84; 95% CI, 0.62-1.13). A similar pattern was evident for time to onset of 24-week CDP.

The changes in timed 25-foot walk from baseline to week 20, and in brain T2 hyperintense lesion volume from baseline to week 120 were significantly reduced overall by treatment. Reductions in walk time and lesion volume were apparent in the T1 Gd+ and Gd- lesion subgroups, with similar percentage change. In the overall study, ocrelizumab significantly slowed decline in brain volume from weeks 24 to 120, and slowed declines were also evident in the T1 Gd+ and Gd- lesion subgroups, compared with placebo.

The findings warrant further studies powered to assess the apparent treatment benefit in patients with Gd+ lesions – who are likely relapsing – at baseline. If the findings hold, stratifying patients prior to treatment based on MRI of T1 Gd+ lesions could help to guide ocrelizumab treatment.

Gadolinium normally cannot pass from the bloodstream into the brain or spinal cord because of the presence of the blood-brain barrier. Active inflammation in the brain or spinal cord during a MS relapse disrupts the barrier. Gadolinium enters the brain or spinal cord and permeates into MS lesions, which appear bright on MRI. 

The study was funded by Hoffmann-La Roche/Genentech. Dr. Wolinsky disclosed receiving consulting fees; compensation for service on steering committees or data monitoring boards; and/or research support from many companies that market MS drugs, including Hoffmann-La Roche/Genentech.