User login
FDA investigates issues with rivaroxaban trial
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. 
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.
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.
Gene therapy could treat aplastic anemia
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.
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.
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.
Agent can mobilize HSCs for transplant, study suggests
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.
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.
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.
Team develops hospital-based Zika test
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.
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.
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.
Financial toxicity is prevalent among patients with head and neck cancer
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.
AT THE MULTIDISCIPLINARY HEAD AND NECK CANCER SYMPOSIUM
Key clinical point: The majority of patients with head and neck cancer resort to steps such as tapping their savings to help pay for their care.
Major finding: Overall, 69% of patients used life-altering strategies to cope with costs, and those with a high level of social isolation were more likely to do so.
Data source: A prospective longitudinal cohort study of 73 patients with locally advanced head and neck cancer.
Disclosures: Ms. Kung disclosed that she had no relevant conflicts of interest.
VIDEO: MS stem cell therapy research progresses, including oligodendrocyte progenitor trial
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
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.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
EXPERT ANALYSIS FROM ACTRIMS FORUM 2016
Ocrelizumab subanalysis hints at better efficacy with active inflammatory lesions
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.
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.
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.
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.
AT ACTRIMS FORUM 2016
Key clinical point: Certain subgroups of patients may respond better to treatment
Major finding: Reduction in the risk of confirmed disability progression at 12 weeks 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).
Data source: The phase III, randomized, double-blind, placebo-controlled ORATORIO trial.
Disclosures: 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.
Long-term PPI use linked to increased risk of dementia
Long-term use of proton pump inhibitors was significantly associated with later diagnoses of dementia in adults aged 75 years and older in a prospective cohort study of more than 73,000 individuals. The findings were published online Feb. 15 in JAMA Neurology.
Overall, the risk of incident dementia was 44% higher among the 2,950 patients who received regular proton pump inhibitors, compared with 70,729 who didn’t receive PPIs (hazard ratio of 1.44), according to Willy Gomm, Ph.D., of the German Center for Neurodegenerative Diseases in Bonn, and his colleagues.
To assess the potential link between PPIs and dementia, the researchers reviewed data from a German insurance database during 2004-2011. The study population included 73,679 community-dwelling adults aged 75 years and older who were free of dementia at the start of the study (JAMA Neurol. 2016 Feb 15. doi: 10.1001/jamaneurol.2015.4791). The patients taking PPIs were slightly but significantly older than those not taking PPIs and had a higher proportion of women (P less than .001 for both). PPI users were also significantly more likely than nonusers to have a history of depression, stroke, coronary disease, and use of polypharmacy (P less than .001 for each).
The risk of incident dementia decreased with age, from 69% for patients aged 75-79 years to 49% among those 80-84-years and 32% among those aged 85 years and older.
In addition, the risk of dementia was not significantly different based on specific drug in a subgroup analysis of the three most often prescribed PPIs, omeprazole, pantoprazole, and esomeprazole, for which the hazard ratios were 1.51, 1.58, and 2.12, respectively.
“If PPIs have adverse effects, it is important to be aware of them,” Dr. Daniel E. Freedberg of Columbia University, New York, said in an interview. “When PPIs are indicated, the preponderance of data indicate that their benefits outweigh their potential risks,” he added. “Clinicians should reassure patients that this was a single study and that previous studies have reached different conclusions. Clinicians should focus on whether or not PPIs are indicated rather than on PPI side effects.”
Dr. Freedberg also noted several key limitations of the study.
“First, the authors were unable to adjust for crucial variables that might explain a noncausal link between PPIs and dementia. For example, lower socioeconomic status is an established predictor of dementia and may also be associated with PPI use. However, the authors could not capture socioeconomic status.
“Second, patients who use PPIs have more frequent and more intensive health care interactions than patients who do not use PPIs. These patients are thus also more likely to be diagnosed with dementia. This is another source for bias that the authors were not able to capture. Third, clinicians should be aware that this study was designed to compare extremes of PPI use,” Dr. Freedberg emphasized.
In addition, “In the primary analysis, patients were classified as exposed to PPIs only if they received at least one PPI prescription every 3 months for an 18-month period. Patients who used occasional PPIs were excluded from the study,” said Dr. Freedberg.
“The present study can only provide a statistical association between PPI use and risk of dementia,” the researchers noted. “The possible underlying causal biological mechanism has to be explored in future studies,” they wrote.
The researchers had no financial conflicts to disclose.
Challenging research lies ahead
The researchers have provided an important and interesting challenge to evaluate the possible association of the use of PPIs and the risk of dementia.
|
Dr. Lewis H. Kuller |
Further determinants of whether PPIs are causal for dementia requires validation in large cohorts and probably in well-designed case-control studies with good measures of long-term PPI use, covariates, and especially methods to measure incidence of dementia.
Dr. Lewis H. Kuller is affiliated with the department of epidemiology at the University of Pittsburgh. He made his remarks in an accompanying editorial and had no financial conflicts to disclose.
PPIs and dementia: More of much ado about nothing?
This study has attracted considerable media attention. Unfortunately, this was somewhat unbalanced. One TV news program stated that there was a “44% increased risk of dementia.” Many of our patients would not be able to interpret that appropriately – let alone weigh the potential risks and benefits of PPI treatment.
The 44% increase is derived from the hazard ratio of 1.44 that the investigators reported. However, to quote Dr. David A. Grimes and Dr. Kenneth F. Schulz, “Any claim coming from an observational study is most likely to be wrong. Of the reported associations that are correct, most are exaggerated” (Obstet Gynecol. 2012;120:920-7).
In the German study, the patients who had been taking PPIs were more likely to have prior diagnoses of depression, stroke, and ischemic heart disease than those not on PPIs. They were also much more likely to be on multiple other medicines. These patients may have been more likely to be given a PPI because of their comorbidity. There may, therefore, be an element of channeling bias or confounding by indication to explain the findings.
However, let us assume that there had been a stronger suggestion of a causal association between PPI use and the risk of developing dementia. It would be important to consider what its underlying biological rationale might be. The investigators state that PPI use “has been shown to be potentially involved in cognitive decline.” The evidence offered in support of this claim comes from a case-control study that did not evaluate cognitive function but reported an increased incidence of vitamin B12 deficiency among adults taking PPIs for 2 or more years [very small odds ratio of 1.65 (JAMA 2013;310:2435-42)]. Low B12 levels were linked to “cognitive deficit” in a population-based study from Norway (Psychosom Med. 2013;75:20-9). So, the proposed biological rationale for any association between PPI use and dementia is tenuous at best.
For PPIs, long-term or indefinite use is appropriate for indications such as erosive esophagitis, esophageal stricture, or the prevention of upper GI tract ulcers and ulcer bleeding in patients taking aspirin or NSAIDs. Patients with a valid indication for PPI treatment should continue to receive it for as long as clinically indicated – and at the lowest effective dose. It would be unfortunate if patients with indications for PPI treatment discontinued it on the basis of this study.
Dr. Colin W. Howden, AGAF, is Hyman Professor of Medicine, chief of the division of gastroenterology, University of Tennessee Health Science Center, Memphis. He is a consultant for Takeda, Otsuka, Ironwood, Allergan, Aralez, and Pfizer Consumer Health.
Challenging research lies ahead
The researchers have provided an important and interesting challenge to evaluate the possible association of the use of PPIs and the risk of dementia.
|
|
Dr. Lewis H. Kuller |
Further determinants of whether PPIs are causal for dementia requires validation in large cohorts and probably in well-designed case-control studies with good measures of long-term PPI use, covariates, and especially methods to measure incidence of dementia.
Dr. Lewis H. Kuller is affiliated with the department of epidemiology at the University of Pittsburgh. He made his remarks in an accompanying editorial and had no financial conflicts to disclose.
PPIs and dementia: More of much ado about nothing?
This study has attracted considerable media attention. Unfortunately, this was somewhat unbalanced. One TV news program stated that there was a “44% increased risk of dementia.” Many of our patients would not be able to interpret that appropriately – let alone weigh the potential risks and benefits of PPI treatment.
The 44% increase is derived from the hazard ratio of 1.44 that the investigators reported. However, to quote Dr. David A. Grimes and Dr. Kenneth F. Schulz, “Any claim coming from an observational study is most likely to be wrong. Of the reported associations that are correct, most are exaggerated” (Obstet Gynecol. 2012;120:920-7).
In the German study, the patients who had been taking PPIs were more likely to have prior diagnoses of depression, stroke, and ischemic heart disease than those not on PPIs. They were also much more likely to be on multiple other medicines. These patients may have been more likely to be given a PPI because of their comorbidity. There may, therefore, be an element of channeling bias or confounding by indication to explain the findings.
However, let us assume that there had been a stronger suggestion of a causal association between PPI use and the risk of developing dementia. It would be important to consider what its underlying biological rationale might be. The investigators state that PPI use “has been shown to be potentially involved in cognitive decline.” The evidence offered in support of this claim comes from a case-control study that did not evaluate cognitive function but reported an increased incidence of vitamin B12 deficiency among adults taking PPIs for 2 or more years [very small odds ratio of 1.65 (JAMA 2013;310:2435-42)]. Low B12 levels were linked to “cognitive deficit” in a population-based study from Norway (Psychosom Med. 2013;75:20-9). So, the proposed biological rationale for any association between PPI use and dementia is tenuous at best.
For PPIs, long-term or indefinite use is appropriate for indications such as erosive esophagitis, esophageal stricture, or the prevention of upper GI tract ulcers and ulcer bleeding in patients taking aspirin or NSAIDs. Patients with a valid indication for PPI treatment should continue to receive it for as long as clinically indicated – and at the lowest effective dose. It would be unfortunate if patients with indications for PPI treatment discontinued it on the basis of this study.
Dr. Colin W. Howden, AGAF, is Hyman Professor of Medicine, chief of the division of gastroenterology, University of Tennessee Health Science Center, Memphis. He is a consultant for Takeda, Otsuka, Ironwood, Allergan, Aralez, and Pfizer Consumer Health.
Challenging research lies ahead
The researchers have provided an important and interesting challenge to evaluate the possible association of the use of PPIs and the risk of dementia.
|
|
Dr. Lewis H. Kuller |
Further determinants of whether PPIs are causal for dementia requires validation in large cohorts and probably in well-designed case-control studies with good measures of long-term PPI use, covariates, and especially methods to measure incidence of dementia.
Dr. Lewis H. Kuller is affiliated with the department of epidemiology at the University of Pittsburgh. He made his remarks in an accompanying editorial and had no financial conflicts to disclose.
PPIs and dementia: More of much ado about nothing?
This study has attracted considerable media attention. Unfortunately, this was somewhat unbalanced. One TV news program stated that there was a “44% increased risk of dementia.” Many of our patients would not be able to interpret that appropriately – let alone weigh the potential risks and benefits of PPI treatment.
The 44% increase is derived from the hazard ratio of 1.44 that the investigators reported. However, to quote Dr. David A. Grimes and Dr. Kenneth F. Schulz, “Any claim coming from an observational study is most likely to be wrong. Of the reported associations that are correct, most are exaggerated” (Obstet Gynecol. 2012;120:920-7).
In the German study, the patients who had been taking PPIs were more likely to have prior diagnoses of depression, stroke, and ischemic heart disease than those not on PPIs. They were also much more likely to be on multiple other medicines. These patients may have been more likely to be given a PPI because of their comorbidity. There may, therefore, be an element of channeling bias or confounding by indication to explain the findings.
However, let us assume that there had been a stronger suggestion of a causal association between PPI use and the risk of developing dementia. It would be important to consider what its underlying biological rationale might be. The investigators state that PPI use “has been shown to be potentially involved in cognitive decline.” The evidence offered in support of this claim comes from a case-control study that did not evaluate cognitive function but reported an increased incidence of vitamin B12 deficiency among adults taking PPIs for 2 or more years [very small odds ratio of 1.65 (JAMA 2013;310:2435-42)]. Low B12 levels were linked to “cognitive deficit” in a population-based study from Norway (Psychosom Med. 2013;75:20-9). So, the proposed biological rationale for any association between PPI use and dementia is tenuous at best.
For PPIs, long-term or indefinite use is appropriate for indications such as erosive esophagitis, esophageal stricture, or the prevention of upper GI tract ulcers and ulcer bleeding in patients taking aspirin or NSAIDs. Patients with a valid indication for PPI treatment should continue to receive it for as long as clinically indicated – and at the lowest effective dose. It would be unfortunate if patients with indications for PPI treatment discontinued it on the basis of this study.
Dr. Colin W. Howden, AGAF, is Hyman Professor of Medicine, chief of the division of gastroenterology, University of Tennessee Health Science Center, Memphis. He is a consultant for Takeda, Otsuka, Ironwood, Allergan, Aralez, and Pfizer Consumer Health.
Long-term use of proton pump inhibitors was significantly associated with later diagnoses of dementia in adults aged 75 years and older in a prospective cohort study of more than 73,000 individuals. The findings were published online Feb. 15 in JAMA Neurology.
Overall, the risk of incident dementia was 44% higher among the 2,950 patients who received regular proton pump inhibitors, compared with 70,729 who didn’t receive PPIs (hazard ratio of 1.44), according to Willy Gomm, Ph.D., of the German Center for Neurodegenerative Diseases in Bonn, and his colleagues.
To assess the potential link between PPIs and dementia, the researchers reviewed data from a German insurance database during 2004-2011. The study population included 73,679 community-dwelling adults aged 75 years and older who were free of dementia at the start of the study (JAMA Neurol. 2016 Feb 15. doi: 10.1001/jamaneurol.2015.4791). The patients taking PPIs were slightly but significantly older than those not taking PPIs and had a higher proportion of women (P less than .001 for both). PPI users were also significantly more likely than nonusers to have a history of depression, stroke, coronary disease, and use of polypharmacy (P less than .001 for each).
The risk of incident dementia decreased with age, from 69% for patients aged 75-79 years to 49% among those 80-84-years and 32% among those aged 85 years and older.
In addition, the risk of dementia was not significantly different based on specific drug in a subgroup analysis of the three most often prescribed PPIs, omeprazole, pantoprazole, and esomeprazole, for which the hazard ratios were 1.51, 1.58, and 2.12, respectively.
“If PPIs have adverse effects, it is important to be aware of them,” Dr. Daniel E. Freedberg of Columbia University, New York, said in an interview. “When PPIs are indicated, the preponderance of data indicate that their benefits outweigh their potential risks,” he added. “Clinicians should reassure patients that this was a single study and that previous studies have reached different conclusions. Clinicians should focus on whether or not PPIs are indicated rather than on PPI side effects.”
Dr. Freedberg also noted several key limitations of the study.
“First, the authors were unable to adjust for crucial variables that might explain a noncausal link between PPIs and dementia. For example, lower socioeconomic status is an established predictor of dementia and may also be associated with PPI use. However, the authors could not capture socioeconomic status.
“Second, patients who use PPIs have more frequent and more intensive health care interactions than patients who do not use PPIs. These patients are thus also more likely to be diagnosed with dementia. This is another source for bias that the authors were not able to capture. Third, clinicians should be aware that this study was designed to compare extremes of PPI use,” Dr. Freedberg emphasized.
In addition, “In the primary analysis, patients were classified as exposed to PPIs only if they received at least one PPI prescription every 3 months for an 18-month period. Patients who used occasional PPIs were excluded from the study,” said Dr. Freedberg.
“The present study can only provide a statistical association between PPI use and risk of dementia,” the researchers noted. “The possible underlying causal biological mechanism has to be explored in future studies,” they wrote.
The researchers had no financial conflicts to disclose.
Long-term use of proton pump inhibitors was significantly associated with later diagnoses of dementia in adults aged 75 years and older in a prospective cohort study of more than 73,000 individuals. The findings were published online Feb. 15 in JAMA Neurology.
Overall, the risk of incident dementia was 44% higher among the 2,950 patients who received regular proton pump inhibitors, compared with 70,729 who didn’t receive PPIs (hazard ratio of 1.44), according to Willy Gomm, Ph.D., of the German Center for Neurodegenerative Diseases in Bonn, and his colleagues.
To assess the potential link between PPIs and dementia, the researchers reviewed data from a German insurance database during 2004-2011. The study population included 73,679 community-dwelling adults aged 75 years and older who were free of dementia at the start of the study (JAMA Neurol. 2016 Feb 15. doi: 10.1001/jamaneurol.2015.4791). The patients taking PPIs were slightly but significantly older than those not taking PPIs and had a higher proportion of women (P less than .001 for both). PPI users were also significantly more likely than nonusers to have a history of depression, stroke, coronary disease, and use of polypharmacy (P less than .001 for each).
The risk of incident dementia decreased with age, from 69% for patients aged 75-79 years to 49% among those 80-84-years and 32% among those aged 85 years and older.
In addition, the risk of dementia was not significantly different based on specific drug in a subgroup analysis of the three most often prescribed PPIs, omeprazole, pantoprazole, and esomeprazole, for which the hazard ratios were 1.51, 1.58, and 2.12, respectively.
“If PPIs have adverse effects, it is important to be aware of them,” Dr. Daniel E. Freedberg of Columbia University, New York, said in an interview. “When PPIs are indicated, the preponderance of data indicate that their benefits outweigh their potential risks,” he added. “Clinicians should reassure patients that this was a single study and that previous studies have reached different conclusions. Clinicians should focus on whether or not PPIs are indicated rather than on PPI side effects.”
Dr. Freedberg also noted several key limitations of the study.
“First, the authors were unable to adjust for crucial variables that might explain a noncausal link between PPIs and dementia. For example, lower socioeconomic status is an established predictor of dementia and may also be associated with PPI use. However, the authors could not capture socioeconomic status.
“Second, patients who use PPIs have more frequent and more intensive health care interactions than patients who do not use PPIs. These patients are thus also more likely to be diagnosed with dementia. This is another source for bias that the authors were not able to capture. Third, clinicians should be aware that this study was designed to compare extremes of PPI use,” Dr. Freedberg emphasized.
In addition, “In the primary analysis, patients were classified as exposed to PPIs only if they received at least one PPI prescription every 3 months for an 18-month period. Patients who used occasional PPIs were excluded from the study,” said Dr. Freedberg.
“The present study can only provide a statistical association between PPI use and risk of dementia,” the researchers noted. “The possible underlying causal biological mechanism has to be explored in future studies,” they wrote.
The researchers had no financial conflicts to disclose.
FROM JAMA NEUROLOGY
Key clinical point: Proton pump inhibitors may add to the risk of dementia in older adults.
Major finding: The risk of incident dementia was 44% higher in adults who used PPIs long term, compared with those who did not.
Data source: The prospective cohort study included 73,679 adults aged 75 years and older.
Disclosures: The researchers had no financial conflicts to disclose.
ACA accelerated hospital readmission reduction efforts
Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.
The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).
Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.
The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.
The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.
Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.
“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.
Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.
The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.
The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.
Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.
The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).
Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.
The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.
The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.
Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.
“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.
Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.
The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.
The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.
Hospital readmissions have declined in recent years for three conditions targeted under the Affordable Care Act, with smaller declines for other conditions, according to new research.
The study, published online Feb. 24 in the New England Journal of Medicine, found that 30-day readmission rates declined quickly after the passage of the ACA in 2010 and then slowed at the end of 2012. The researchers also analyzed trends in the use of observation units during the same period and concluded that the drop in readmissions was not being masked by a similar uptick in patients being seen under observation status (N Engl J Med. 2016 Feb 24. doi: 10.1056/NEJMsa1513024).
Under the ACA’s Hospital Readmissions Reduction Program, hospitals are financially penalized if they have higher-than-expected readmission rates for acute myocardial infarction, heart failure, and pneumonia.
The researchers, led by Rachael B. Zuckerman, M.P.H., of the Department of Health & Human Services, examined Medicare data from 3,387 hospitals from October 2007 through May 2015. Overall readmissions for acute myocardial infarction, heart failure, and pneumonia – the three conditions targeted in the readmissions reduction program – dropped from 21.5% to 17.8% during this time period. Readmissions for nontargeted conditions also dropped from 15.3% to 13.1%.
The researchers reported that readmissions for the targeted conditions were already declining before the ACA implementation (slope of monthly rate, –0.017), accelerating between April 2010 and October 2010 (–0.103), then leveling off through 2015 (–0.05). A similar pattern was seen with readmissions for conditions not targeted under the health law, though the declines were less pronounced.
Observation rates for the targeted conditions increased from 2.6% to 4.7% during the study period, while rates for nontargeted conditions rose from 2.5% to 4.2%. The researchers did not observe any significant associations increases in observation-unit stays – which were steady throughout the study period – and the implementation of the ACA.
“It seems likely that the upward trend in observation-service use may be attributable to factors that are largely unrelated to the Hospital Readmissions Reduction Program, such as confusion over whether an inpatient stay would be deemed inappropriate by Medicare recovery audit contractors,” the researchers wrote.
Though the observational design of the study could not confirm a causal link between the ACA penalties and the drop in readmissions, the findings suggest that the declines are not solely a response to the ACA.
The health law likely “catalyzed behavioral change by many hospitals” that was already underway, possibly because of broader concern about readmissions and to earlier Medicare initiatives designed to reduce them. Also, the investigators noted, hospitals may have been helped by other government efforts on the readmission front, including the dissemination of best practices by the Centers for Medicare & Medicaid Services.
The study was funded by HHS and the researchers were agency employees. They reported having no other financial disclosures.
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Hospital readmission rates declined following ACA enactment in 2010, but increased use of observation units did not account for the change.
Major finding: During 2007-2015, 30-day hospital readmissions for three targeted conditions dropped from 21.5% to 17.8%.
Data source: An interrupted time-series analysis of readmission and observation unit stay data of elderly Medicare beneficiaries from nearly 3,400 hospitals from 2007-2015.
Disclosures: The Health and Human Services department funded the study and the researchers were agency employees. They reported having no other financial disclosures.
Marijuana tourists also visiting Colorado EDs
Out-of-state residents appear to be driving the recent increases in marijuana-related emergency department visits in Colorado, Dr. Howard S. Kim and his associates reported online Feb. 24 in the New England Journal of Medicine.
Using statewide data from the Colorado Hospital Association, they found that ED visits related to cannabis by out-of-state residents rose from 78 per 10,000 ED visits in 2012 to 163 per 10,000 in 2014, an increase of 109%. For Colorado residents, cannabis-related ED admissions over that same time period went up 44% – from 70 per 10,000 to 101, said Dr. Kim of Northwestern University, Chicago, and his associates (N Engl J Med. 2016 Feb 24;374[8]:797-8. doi:10.1056/NEJMc1515009).
The investigators also looked at a single urban academic hospital in Aurora, Colo., and found that cannabis-related ED visits there for out-of-state residents went from 85 per 10,000 visits in 2013 to 168 per 10,000 in 2014, compared with respective rates of 106 and 112 for Colorado residents.
“The flattening of the rates of ED visits possibly related to cannabis use among Colorado residents in an urban hospital may represent a learning curve during the period when marijuana was potentially available to Colorado residents for medical use (medical marijuana period) but was largely inaccessible to out-of-state residents,” they suggested.
Out-of-state residents appear to be driving the recent increases in marijuana-related emergency department visits in Colorado, Dr. Howard S. Kim and his associates reported online Feb. 24 in the New England Journal of Medicine.
Using statewide data from the Colorado Hospital Association, they found that ED visits related to cannabis by out-of-state residents rose from 78 per 10,000 ED visits in 2012 to 163 per 10,000 in 2014, an increase of 109%. For Colorado residents, cannabis-related ED admissions over that same time period went up 44% – from 70 per 10,000 to 101, said Dr. Kim of Northwestern University, Chicago, and his associates (N Engl J Med. 2016 Feb 24;374[8]:797-8. doi:10.1056/NEJMc1515009).
The investigators also looked at a single urban academic hospital in Aurora, Colo., and found that cannabis-related ED visits there for out-of-state residents went from 85 per 10,000 visits in 2013 to 168 per 10,000 in 2014, compared with respective rates of 106 and 112 for Colorado residents.
“The flattening of the rates of ED visits possibly related to cannabis use among Colorado residents in an urban hospital may represent a learning curve during the period when marijuana was potentially available to Colorado residents for medical use (medical marijuana period) but was largely inaccessible to out-of-state residents,” they suggested.
Out-of-state residents appear to be driving the recent increases in marijuana-related emergency department visits in Colorado, Dr. Howard S. Kim and his associates reported online Feb. 24 in the New England Journal of Medicine.
Using statewide data from the Colorado Hospital Association, they found that ED visits related to cannabis by out-of-state residents rose from 78 per 10,000 ED visits in 2012 to 163 per 10,000 in 2014, an increase of 109%. For Colorado residents, cannabis-related ED admissions over that same time period went up 44% – from 70 per 10,000 to 101, said Dr. Kim of Northwestern University, Chicago, and his associates (N Engl J Med. 2016 Feb 24;374[8]:797-8. doi:10.1056/NEJMc1515009).
The investigators also looked at a single urban academic hospital in Aurora, Colo., and found that cannabis-related ED visits there for out-of-state residents went from 85 per 10,000 visits in 2013 to 168 per 10,000 in 2014, compared with respective rates of 106 and 112 for Colorado residents.
“The flattening of the rates of ED visits possibly related to cannabis use among Colorado residents in an urban hospital may represent a learning curve during the period when marijuana was potentially available to Colorado residents for medical use (medical marijuana period) but was largely inaccessible to out-of-state residents,” they suggested.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
