Daria Pagliara, MD, PhD

STOCKHOLM—Researchers have identified a “highly effective” transplant strategy for pediatric patients with primary immunodeficiencies who lack a suitable HLA-compatible donor, according to a speaker at the 23rd Congress of the European Hematology Association (EHA).

The strategy involves α/β T-cell- and B-cell-depleted haploidentical hematopoietic stem cell transplant (haplo-HSCT) followed by infusion of the T-cell product BPX-501.

Children treated with this strategy in a phase 1/2 trial had disease-free and overall survival rates that compared favorably with rates observed in recipients of matched, unrelated transplants.

In addition, the incidence of severe acute and chronic graft-versus-host disease (GHVD) was low in this trial.

Daria Pagliara, MD, PhD, of Ospedale Pediatrico Bambino Gesu in Rome, Italy, presented these results at the recent EHA Congress as abstract S871.

The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity. Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

Dr Pagliara explained that T cells are collected from donors via non-mobilized apheresis, the cells are modified to create the BPX-501 product, and the product is infused in HSCT recipients at day 14 after transplant (+/- 4 days).

The patients do not receive GVHD prophylaxis after transplant but are given rimiducid if they develop GVHD that does not respond to standard therapy.

Patients and transplant characteristics

Dr Pagliara reported results with BPX-501 in 59 patients. They had a median age of 1.85 years (range, 0.21 to 17.55), and 57.6% were male.

Patients had severe combined immune deficiency (32%), Wiskott–Aldrich syndrome (15%), chronic granulomatous disease (12%), hemophagocytic lymphohistiocytosis (10%), combined immunodeficiency disease (7%), major histocompatibility complex class II deficiency (5%), and “other” immunodeficiencies (19%).

The patients received BPX-501 after an α/β T-cell-depleted, B-cell-depleted haplo-HSCT. Most patients had a parent donor (94.9%), and 5.1% had a sibling donor. The median donor age was 34 (range, 21-52).

About half of patients (49.2%) received treosulfan-based conditioning, 39% received busulfan-based conditioning, and 11.9% received other conditioning.

The median CD34 dose was 22.0 x 10⁶/kg, and the median α/β T-cell dose was 0.4 x 10⁵/kg.

The median time to BPX-501 infusion was 15 days (range, 11-56). The median time to discharge was 40 days (range, 18-204).

The median follow-up was 536 days (range, 32-1252).

Engraftment and survival

The median time to neutrophil engraftment was 16 days, and the median time to platelet engraftment was 11 days.

Three patients had primary graft failure (5.1%), but 1 of these patients was successfully re-transplanted from the same donor.

The cumulative incidence of transplant-related mortality was 8.7%.

There were 5 cases of transplant-related mortality, which were due to graft failure/disseminated fungal infection, cytomegalovirus (CMV) encephalitis, worsening juvenile dermatomyositis/macrophage activation syndrome, bronchopulmonary hemorrhage, and CMV/adenovirus.

“I would like to underline that 3 of these 5 patients died of infectious complications that were present before the transplant—1 fungal invasive infection, 1 encephalitis due to CMV reactivation, and 1 pulmonary infection due to the presence of adenovirus and cytomegalovirus,” Dr Pagliara said.

The rate of disease-free survival and overall survival were both 87.6%.

GVHD and adverse events

Dr Pagliara said there were low rates of acute GVHD in the first 100 days.

The rate of grade 2-4 acute GVHD was 8.9%, and the rate of grade 3-4 acute GVHD was 1.8%. There were 4 cases of grade 2 GVHD—three stage 3 skin and one stage 1 upper gastrointestinal. There was a single case of grade 3 GVHD—stage 3 liver.

Of the 19 patients who developed acute GVHD, 7 received at least 1 dose of rimiducid. These patients had visceral involvement or GVHD that was not responsive to standard care.

Four patients had a complete response to rimiducid, and 1 had a partial response. One patient did not respond, and 1 was not evaluable. The non-evaluable patient was on corticosteroids and cyclosporine with controlled GVHD but was unable to be weaned off corticosteroids. Rimiducid was given in an attempt to wean the patient off corticosteroids.

“Most importantly, only 1 patient out of 59 developed chronic GVHD, with only mild involvement of the skin,” Dr Pagliara said. This patient did not receive rimiducid.

Nine patients (15.2%) had at least 1 adverse event (AE).

AEs occurring after BPX-501 administration were grade 1 or 2 in nature. They included diarrhea, vomiting, pyrexia, CMV viremia, rhinovirus infection, hypokalemia, pruritus, and rash.

There were no severe AEs attributed to BPX-501.

Daria Pagliara, MD, PhD

STOCKHOLM—Researchers have identified a “highly effective” transplant strategy for pediatric patients with primary immunodeficiencies who lack a suitable HLA-compatible donor, according to a speaker at the 23rd Congress of the European Hematology Association (EHA).

The strategy involves α/β T-cell- and B-cell-depleted haploidentical hematopoietic stem cell transplant (haplo-HSCT) followed by infusion of the T-cell product BPX-501.

Children treated with this strategy in a phase 1/2 trial had disease-free and overall survival rates that compared favorably with rates observed in recipients of matched, unrelated transplants.

In addition, the incidence of severe acute and chronic graft-versus-host disease (GHVD) was low in this trial.

Daria Pagliara, MD, PhD, of Ospedale Pediatrico Bambino Gesu in Rome, Italy, presented these results at the recent EHA Congress as abstract S871.

The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity. Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

Dr Pagliara explained that T cells are collected from donors via non-mobilized apheresis, the cells are modified to create the BPX-501 product, and the product is infused in HSCT recipients at day 14 after transplant (+/- 4 days).

The patients do not receive GVHD prophylaxis after transplant but are given rimiducid if they develop GVHD that does not respond to standard therapy.

Patients and transplant characteristics

Dr Pagliara reported results with BPX-501 in 59 patients. They had a median age of 1.85 years (range, 0.21 to 17.55), and 57.6% were male.

Patients had severe combined immune deficiency (32%), Wiskott–Aldrich syndrome (15%), chronic granulomatous disease (12%), hemophagocytic lymphohistiocytosis (10%), combined immunodeficiency disease (7%), major histocompatibility complex class II deficiency (5%), and “other” immunodeficiencies (19%).

The patients received BPX-501 after an α/β T-cell-depleted, B-cell-depleted haplo-HSCT. Most patients had a parent donor (94.9%), and 5.1% had a sibling donor. The median donor age was 34 (range, 21-52).

About half of patients (49.2%) received treosulfan-based conditioning, 39% received busulfan-based conditioning, and 11.9% received other conditioning.

The median CD34 dose was 22.0 x 10⁶/kg, and the median α/β T-cell dose was 0.4 x 10⁵/kg.

The median time to BPX-501 infusion was 15 days (range, 11-56). The median time to discharge was 40 days (range, 18-204).

The median follow-up was 536 days (range, 32-1252).

Engraftment and survival

The median time to neutrophil engraftment was 16 days, and the median time to platelet engraftment was 11 days.

Three patients had primary graft failure (5.1%), but 1 of these patients was successfully re-transplanted from the same donor.

The cumulative incidence of transplant-related mortality was 8.7%.

There were 5 cases of transplant-related mortality, which were due to graft failure/disseminated fungal infection, cytomegalovirus (CMV) encephalitis, worsening juvenile dermatomyositis/macrophage activation syndrome, bronchopulmonary hemorrhage, and CMV/adenovirus.

“I would like to underline that 3 of these 5 patients died of infectious complications that were present before the transplant—1 fungal invasive infection, 1 encephalitis due to CMV reactivation, and 1 pulmonary infection due to the presence of adenovirus and cytomegalovirus,” Dr Pagliara said.

The rate of disease-free survival and overall survival were both 87.6%.

GVHD and adverse events

Dr Pagliara said there were low rates of acute GVHD in the first 100 days.

The rate of grade 2-4 acute GVHD was 8.9%, and the rate of grade 3-4 acute GVHD was 1.8%. There were 4 cases of grade 2 GVHD—three stage 3 skin and one stage 1 upper gastrointestinal. There was a single case of grade 3 GVHD—stage 3 liver.

Of the 19 patients who developed acute GVHD, 7 received at least 1 dose of rimiducid. These patients had visceral involvement or GVHD that was not responsive to standard care.

Four patients had a complete response to rimiducid, and 1 had a partial response. One patient did not respond, and 1 was not evaluable. The non-evaluable patient was on corticosteroids and cyclosporine with controlled GVHD but was unable to be weaned off corticosteroids. Rimiducid was given in an attempt to wean the patient off corticosteroids.

“Most importantly, only 1 patient out of 59 developed chronic GVHD, with only mild involvement of the skin,” Dr Pagliara said. This patient did not receive rimiducid.

Nine patients (15.2%) had at least 1 adverse event (AE).

AEs occurring after BPX-501 administration were grade 1 or 2 in nature. They included diarrhea, vomiting, pyrexia, CMV viremia, rhinovirus infection, hypokalemia, pruritus, and rash.

There were no severe AEs attributed to BPX-501.

Daria Pagliara, MD, PhD

STOCKHOLM—Researchers have identified a “highly effective” transplant strategy for pediatric patients with primary immunodeficiencies who lack a suitable HLA-compatible donor, according to a speaker at the 23rd Congress of the European Hematology Association (EHA).

The strategy involves α/β T-cell- and B-cell-depleted haploidentical hematopoietic stem cell transplant (haplo-HSCT) followed by infusion of the T-cell product BPX-501.

Children treated with this strategy in a phase 1/2 trial had disease-free and overall survival rates that compared favorably with rates observed in recipients of matched, unrelated transplants.

In addition, the incidence of severe acute and chronic graft-versus-host disease (GHVD) was low in this trial.

Daria Pagliara, MD, PhD, of Ospedale Pediatrico Bambino Gesu in Rome, Italy, presented these results at the recent EHA Congress as abstract S871.

The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity. Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

Dr Pagliara explained that T cells are collected from donors via non-mobilized apheresis, the cells are modified to create the BPX-501 product, and the product is infused in HSCT recipients at day 14 after transplant (+/- 4 days).

The patients do not receive GVHD prophylaxis after transplant but are given rimiducid if they develop GVHD that does not respond to standard therapy.

Patients and transplant characteristics

Dr Pagliara reported results with BPX-501 in 59 patients. They had a median age of 1.85 years (range, 0.21 to 17.55), and 57.6% were male.

Patients had severe combined immune deficiency (32%), Wiskott–Aldrich syndrome (15%), chronic granulomatous disease (12%), hemophagocytic lymphohistiocytosis (10%), combined immunodeficiency disease (7%), major histocompatibility complex class II deficiency (5%), and “other” immunodeficiencies (19%).

The patients received BPX-501 after an α/β T-cell-depleted, B-cell-depleted haplo-HSCT. Most patients had a parent donor (94.9%), and 5.1% had a sibling donor. The median donor age was 34 (range, 21-52).

About half of patients (49.2%) received treosulfan-based conditioning, 39% received busulfan-based conditioning, and 11.9% received other conditioning.

The median CD34 dose was 22.0 x 10⁶/kg, and the median α/β T-cell dose was 0.4 x 10⁵/kg.

The median time to BPX-501 infusion was 15 days (range, 11-56). The median time to discharge was 40 days (range, 18-204).

The median follow-up was 536 days (range, 32-1252).

Engraftment and survival

The median time to neutrophil engraftment was 16 days, and the median time to platelet engraftment was 11 days.

Three patients had primary graft failure (5.1%), but 1 of these patients was successfully re-transplanted from the same donor.

The cumulative incidence of transplant-related mortality was 8.7%.

There were 5 cases of transplant-related mortality, which were due to graft failure/disseminated fungal infection, cytomegalovirus (CMV) encephalitis, worsening juvenile dermatomyositis/macrophage activation syndrome, bronchopulmonary hemorrhage, and CMV/adenovirus.

“I would like to underline that 3 of these 5 patients died of infectious complications that were present before the transplant—1 fungal invasive infection, 1 encephalitis due to CMV reactivation, and 1 pulmonary infection due to the presence of adenovirus and cytomegalovirus,” Dr Pagliara said.

The rate of disease-free survival and overall survival were both 87.6%.

GVHD and adverse events

Dr Pagliara said there were low rates of acute GVHD in the first 100 days.

The rate of grade 2-4 acute GVHD was 8.9%, and the rate of grade 3-4 acute GVHD was 1.8%. There were 4 cases of grade 2 GVHD—three stage 3 skin and one stage 1 upper gastrointestinal. There was a single case of grade 3 GVHD—stage 3 liver.

Of the 19 patients who developed acute GVHD, 7 received at least 1 dose of rimiducid. These patients had visceral involvement or GVHD that was not responsive to standard care.

Four patients had a complete response to rimiducid, and 1 had a partial response. One patient did not respond, and 1 was not evaluable. The non-evaluable patient was on corticosteroids and cyclosporine with controlled GVHD but was unable to be weaned off corticosteroids. Rimiducid was given in an attempt to wean the patient off corticosteroids.

“Most importantly, only 1 patient out of 59 developed chronic GVHD, with only mild involvement of the skin,” Dr Pagliara said. This patient did not receive rimiducid.

Nine patients (15.2%) had at least 1 adverse event (AE).

AEs occurring after BPX-501 administration were grade 1 or 2 in nature. They included diarrhea, vomiting, pyrexia, CMV viremia, rhinovirus infection, hypokalemia, pruritus, and rash.

There were no severe AEs attributed to BPX-501.

Photo from UAB Hospital

Patients who receive red blood cell (RBC) transfusions before, during, or immediately after surgery may have an increased risk of venous thromboembolism (VTE), a new study suggests.

In this retrospective study, transfusion recipients had twice the risk of VTE as patients who did not receive RBC transfusions during the perioperative period.

Investigators say these findings require validation, but they suggest a need for physicians to consider non-transfusion alternatives to treat anemia in patients undergoing surgery.

“These findings reinforce the importance of following rigorous perioperative patient blood management practices for transfusions,” said Ruchika Goel, MD, of Weill Cornell Medicine in New York, New York.

Dr Goel and her colleagues reported their findings in JAMA Surgery.

The investigators analyzed data on 750,937 patients who underwent surgery in 2014. In all, 6.3% (n=47,410) of patients received at least one RBC transfusion.

Within 30 days of surgery, 0.8% (n=6309) of all patients had a VTE. This included 0.6% (n=4336) with deep vein thrombosis (DVT), 0.3% (n=2514) with pulmonary embolism (PE), and 0.1% (n=541) with DVT and PE.

Analyses showed that patients who received RBC transfusions were twice as likely to develop VTE as those who did not receive transfusions (adjusted odds ratio [aOR]=2.1). This was true for both DVT (aOR=2.2) and PE (aOR=1.9).

“We also saw this risk across different surgical disciplines, ranging from neurosurgery to cardiac surgery,” said study author Aaron Tobian, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

Furthermore, VTE risk increased with the number of RBC transfusions a patient received. The aORs were 2.1 for 1 transfusion, 3.1 for 2 transfusions, and 4.5 for 3 or more transfusions (compared to patients who did not receive any transfusions).

“This retrospective study demonstrates that there may be additional risks to blood transfusion that are not generally recognized in the community,” Dr Tobian said. “While additional research is needed to confirm these results, the findings reinforce the need to limit blood transfusions to only when necessary.”

Photo from UAB Hospital

Patients who receive red blood cell (RBC) transfusions before, during, or immediately after surgery may have an increased risk of venous thromboembolism (VTE), a new study suggests.

In this retrospective study, transfusion recipients had twice the risk of VTE as patients who did not receive RBC transfusions during the perioperative period.

Investigators say these findings require validation, but they suggest a need for physicians to consider non-transfusion alternatives to treat anemia in patients undergoing surgery.

“These findings reinforce the importance of following rigorous perioperative patient blood management practices for transfusions,” said Ruchika Goel, MD, of Weill Cornell Medicine in New York, New York.

Dr Goel and her colleagues reported their findings in JAMA Surgery.

The investigators analyzed data on 750,937 patients who underwent surgery in 2014. In all, 6.3% (n=47,410) of patients received at least one RBC transfusion.

Within 30 days of surgery, 0.8% (n=6309) of all patients had a VTE. This included 0.6% (n=4336) with deep vein thrombosis (DVT), 0.3% (n=2514) with pulmonary embolism (PE), and 0.1% (n=541) with DVT and PE.

Analyses showed that patients who received RBC transfusions were twice as likely to develop VTE as those who did not receive transfusions (adjusted odds ratio [aOR]=2.1). This was true for both DVT (aOR=2.2) and PE (aOR=1.9).

“We also saw this risk across different surgical disciplines, ranging from neurosurgery to cardiac surgery,” said study author Aaron Tobian, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

Furthermore, VTE risk increased with the number of RBC transfusions a patient received. The aORs were 2.1 for 1 transfusion, 3.1 for 2 transfusions, and 4.5 for 3 or more transfusions (compared to patients who did not receive any transfusions).

“This retrospective study demonstrates that there may be additional risks to blood transfusion that are not generally recognized in the community,” Dr Tobian said. “While additional research is needed to confirm these results, the findings reinforce the need to limit blood transfusions to only when necessary.”

Photo from UAB Hospital

Patients who receive red blood cell (RBC) transfusions before, during, or immediately after surgery may have an increased risk of venous thromboembolism (VTE), a new study suggests.

In this retrospective study, transfusion recipients had twice the risk of VTE as patients who did not receive RBC transfusions during the perioperative period.

Investigators say these findings require validation, but they suggest a need for physicians to consider non-transfusion alternatives to treat anemia in patients undergoing surgery.

“These findings reinforce the importance of following rigorous perioperative patient blood management practices for transfusions,” said Ruchika Goel, MD, of Weill Cornell Medicine in New York, New York.

Dr Goel and her colleagues reported their findings in JAMA Surgery.

The investigators analyzed data on 750,937 patients who underwent surgery in 2014. In all, 6.3% (n=47,410) of patients received at least one RBC transfusion.

Within 30 days of surgery, 0.8% (n=6309) of all patients had a VTE. This included 0.6% (n=4336) with deep vein thrombosis (DVT), 0.3% (n=2514) with pulmonary embolism (PE), and 0.1% (n=541) with DVT and PE.

Analyses showed that patients who received RBC transfusions were twice as likely to develop VTE as those who did not receive transfusions (adjusted odds ratio [aOR]=2.1). This was true for both DVT (aOR=2.2) and PE (aOR=1.9).

“We also saw this risk across different surgical disciplines, ranging from neurosurgery to cardiac surgery,” said study author Aaron Tobian, MD, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland.

Furthermore, VTE risk increased with the number of RBC transfusions a patient received. The aORs were 2.1 for 1 transfusion, 3.1 for 2 transfusions, and 4.5 for 3 or more transfusions (compared to patients who did not receive any transfusions).

“This retrospective study demonstrates that there may be additional risks to blood transfusion that are not generally recognized in the community,” Dr Tobian said. “While additional research is needed to confirm these results, the findings reinforce the need to limit blood transfusions to only when necessary.”

Red blood cells

Erytech Pharma said it plans to stop development of eryaspase for acute lymphoblastic leukemia (ALL).

This means withdrawal of the European marketing authorization application for eryaspase as a treatment for relapsed and refractory ALL.

However, Erytech will continue development of eryaspase as a treatment for certain solid tumor malignancies.

Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.

Erytech noted that eryaspase has produced favorable efficacy and safety results in ALL.

However, based on recent feedback from regulatory agencies in Europe and the US, the company believes significant additional investment would be required to seek regulatory approval of eryaspase for the treatment of ALL. Erytech also believes there would be a limited market opportunity for eryaspase in ALL.

Therefore, the company decided to cease further clinical development efforts in ALL. The resources that will become available as a result of this decision will be allocated to the development of eryaspase in solid tumors.

In 2017, Erytech announced results from a phase 2b clinical trial of eryaspase plus chemotherapy in patients with second-line metastatic pancreatic cancer. The company expects to begin enrollment in a phase 3 trial of this patient population in the third quarter of 2018.

In addition, Erytech is preparing for a pair of phase 2 proof-of-concept trials of eryaspase. One is in first-line pancreatic cancer, and the other is in metastatic triple-negative breast cancer. The company is also evaluating development options in additional solid tumor indications with high unmet medical need.

To ensure an adequate supply of eryaspase, Erytech is constructing a large-scale manufacturing facility in Princeton, New Jersey, and is expanding its manufacturing capacity in Lyon, France. The company expects both facilities to be operational for clinical production at the expanded capacity in the first quarter of 2019.

Red blood cells

Erytech Pharma said it plans to stop development of eryaspase for acute lymphoblastic leukemia (ALL).

This means withdrawal of the European marketing authorization application for eryaspase as a treatment for relapsed and refractory ALL.

However, Erytech will continue development of eryaspase as a treatment for certain solid tumor malignancies.

Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.

Erytech noted that eryaspase has produced favorable efficacy and safety results in ALL.

However, based on recent feedback from regulatory agencies in Europe and the US, the company believes significant additional investment would be required to seek regulatory approval of eryaspase for the treatment of ALL. Erytech also believes there would be a limited market opportunity for eryaspase in ALL.

Therefore, the company decided to cease further clinical development efforts in ALL. The resources that will become available as a result of this decision will be allocated to the development of eryaspase in solid tumors.

In 2017, Erytech announced results from a phase 2b clinical trial of eryaspase plus chemotherapy in patients with second-line metastatic pancreatic cancer. The company expects to begin enrollment in a phase 3 trial of this patient population in the third quarter of 2018.

In addition, Erytech is preparing for a pair of phase 2 proof-of-concept trials of eryaspase. One is in first-line pancreatic cancer, and the other is in metastatic triple-negative breast cancer. The company is also evaluating development options in additional solid tumor indications with high unmet medical need.

To ensure an adequate supply of eryaspase, Erytech is constructing a large-scale manufacturing facility in Princeton, New Jersey, and is expanding its manufacturing capacity in Lyon, France. The company expects both facilities to be operational for clinical production at the expanded capacity in the first quarter of 2019.

Red blood cells

Erytech Pharma said it plans to stop development of eryaspase for acute lymphoblastic leukemia (ALL).

This means withdrawal of the European marketing authorization application for eryaspase as a treatment for relapsed and refractory ALL.

However, Erytech will continue development of eryaspase as a treatment for certain solid tumor malignancies.

Eryaspase consists of L-asparaginase encapsulated inside donor-derived red blood cells. These enzyme-loaded red blood cells function as bioreactors to eliminate circulating asparagine and “starve” cancer cells, thereby inducing their death.

Erytech noted that eryaspase has produced favorable efficacy and safety results in ALL.

However, based on recent feedback from regulatory agencies in Europe and the US, the company believes significant additional investment would be required to seek regulatory approval of eryaspase for the treatment of ALL. Erytech also believes there would be a limited market opportunity for eryaspase in ALL.

Therefore, the company decided to cease further clinical development efforts in ALL. The resources that will become available as a result of this decision will be allocated to the development of eryaspase in solid tumors.

In 2017, Erytech announced results from a phase 2b clinical trial of eryaspase plus chemotherapy in patients with second-line metastatic pancreatic cancer. The company expects to begin enrollment in a phase 3 trial of this patient population in the third quarter of 2018.

In addition, Erytech is preparing for a pair of phase 2 proof-of-concept trials of eryaspase. One is in first-line pancreatic cancer, and the other is in metastatic triple-negative breast cancer. The company is also evaluating development options in additional solid tumor indications with high unmet medical need.

To ensure an adequate supply of eryaspase, Erytech is constructing a large-scale manufacturing facility in Princeton, New Jersey, and is expanding its manufacturing capacity in Lyon, France. The company expects both facilities to be operational for clinical production at the expanded capacity in the first quarter of 2019.

Hepatitis C virus infection often is associated with the accumulation of fat in hepatocytes, which shows a connection between the virus and the lipid metabolism of the liver, according to Sarah Hoffman, MD, of the Leibniz Institute for Experimental Virology, Hamburg, Germany, and her colleagues. “Our study provides a detailed analysis of the changes in the lipid composition in HCV-infected cells that revealed dependency on FA [fatty acid] elongation and desaturation for effective viral replication and virion production,” they reported.

Dr. Hoffman and her colleagues assessed lipid composition of infected cells in an in vitro study of cell lines, which were assessed 8-11 days post infection, according to the report published in BBA: Molecular and Cell Biology of Lipids. They determined the abundance of each major lipid class and compared the pattern of HCV-infected cells with that of controls.

The researchers found that HCV caused an accumulation of membrane phosopholipids but not neutral lipids and that cholesterol accumulated in the perinuclear region of HCV-infected cells. In addition, lipid species with longer fatty acyl chains were more abundant in HCV-infected cells and free polyunsaturated fatty acid (PUFA) levels were greatly increased.

In further confirmation of the critical role of lipid metabolism in HCV replication, they found that knockdown of fatty acid elongases and desaturases disrupted HCV replication, while overexpression of these enzymes showed a proviral effect.

“We identified several lipid-remodeling pathways that are required for distinct steps in viral infection. Future studies have to address the molecular function of longer fatty acyl chains in HCV RNA replication and why PUFAs are needed for HCV particle production,” the researchers concluded.

The authors reported government and institutional-only funding and no personal disclosures.

[email protected]

SOURCE: Hoffman S et al. Biochim Biophys Acta. 2018 Jun 6;1863(9):1041-56.

Hepatitis C virus infection often is associated with the accumulation of fat in hepatocytes, which shows a connection between the virus and the lipid metabolism of the liver, according to Sarah Hoffman, MD, of the Leibniz Institute for Experimental Virology, Hamburg, Germany, and her colleagues. “Our study provides a detailed analysis of the changes in the lipid composition in HCV-infected cells that revealed dependency on FA [fatty acid] elongation and desaturation for effective viral replication and virion production,” they reported.

Dr. Hoffman and her colleagues assessed lipid composition of infected cells in an in vitro study of cell lines, which were assessed 8-11 days post infection, according to the report published in BBA: Molecular and Cell Biology of Lipids. They determined the abundance of each major lipid class and compared the pattern of HCV-infected cells with that of controls.

The researchers found that HCV caused an accumulation of membrane phosopholipids but not neutral lipids and that cholesterol accumulated in the perinuclear region of HCV-infected cells. In addition, lipid species with longer fatty acyl chains were more abundant in HCV-infected cells and free polyunsaturated fatty acid (PUFA) levels were greatly increased.

In further confirmation of the critical role of lipid metabolism in HCV replication, they found that knockdown of fatty acid elongases and desaturases disrupted HCV replication, while overexpression of these enzymes showed a proviral effect.

“We identified several lipid-remodeling pathways that are required for distinct steps in viral infection. Future studies have to address the molecular function of longer fatty acyl chains in HCV RNA replication and why PUFAs are needed for HCV particle production,” the researchers concluded.

The authors reported government and institutional-only funding and no personal disclosures.

[email protected]

SOURCE: Hoffman S et al. Biochim Biophys Acta. 2018 Jun 6;1863(9):1041-56.

Hepatitis C virus infection often is associated with the accumulation of fat in hepatocytes, which shows a connection between the virus and the lipid metabolism of the liver, according to Sarah Hoffman, MD, of the Leibniz Institute for Experimental Virology, Hamburg, Germany, and her colleagues. “Our study provides a detailed analysis of the changes in the lipid composition in HCV-infected cells that revealed dependency on FA [fatty acid] elongation and desaturation for effective viral replication and virion production,” they reported.

Dr. Hoffman and her colleagues assessed lipid composition of infected cells in an in vitro study of cell lines, which were assessed 8-11 days post infection, according to the report published in BBA: Molecular and Cell Biology of Lipids. They determined the abundance of each major lipid class and compared the pattern of HCV-infected cells with that of controls.

The researchers found that HCV caused an accumulation of membrane phosopholipids but not neutral lipids and that cholesterol accumulated in the perinuclear region of HCV-infected cells. In addition, lipid species with longer fatty acyl chains were more abundant in HCV-infected cells and free polyunsaturated fatty acid (PUFA) levels were greatly increased.

In further confirmation of the critical role of lipid metabolism in HCV replication, they found that knockdown of fatty acid elongases and desaturases disrupted HCV replication, while overexpression of these enzymes showed a proviral effect.

“We identified several lipid-remodeling pathways that are required for distinct steps in viral infection. Future studies have to address the molecular function of longer fatty acyl chains in HCV RNA replication and why PUFAs are needed for HCV particle production,” the researchers concluded.

The authors reported government and institutional-only funding and no personal disclosures.

[email protected]

SOURCE: Hoffman S et al. Biochim Biophys Acta. 2018 Jun 6;1863(9):1041-56.

BALTIMORE – Continuous positive airway pressure (CPAP) may supersede supplemental oxygen and patient education for improving one key marker of cardiac electrophysiological autonomic function during sleep, but supplemental oxygen may have the upper hand in improving a second key electrophysiological biomarker, according to results of a multicenter, randomized clinical trial presented at the annual meeting of the Associated Professional Sleep Societies.

“Based on these findings, it appears that there are opposing alterations in both frequency and time domain in heart rate variability indices in the CPAP versus oxygen groups,” said Jenie George, MD, of the Cleveland Clinic.

The study evaluated 3-month outcomes of frequency-based heart rate variability (HRV) indices obtained with ECG from sleep studies in 203 patients with obstructive sleep apnea and increased cardiovascular risk in the Heart Biomarker Elevation in Apnea Treatment (HeartBEAT) trial. The interventions were either CPAP, supplemental oxygen, or healthy lifestyle education. Dr. George noted that HRV is a noninvasive tool to evaluate autonomic function by quantifying changes in intervals between sinus beats during sleep.

On the high-frequency power index, patients on CPAP had a 9% reduction versus a 19% increase for those on supplemental oxygen, Dr. George said. However for the low frequency to high frequency ratio, the CPAP group had a 4% increase, whereas the oxygen group had a 34% reduction.

The increase of low frequency to high frequency ratio in the CPAP group is a reflection of sympathovagal balance – the ratio between low-frequency and high-frequency powers – while the changes in high-frequency power in the CPAP patients reflect changes in sinoatrial node electrophysiological function, Dr. George said.

Strengths of the study were its use of data from a large clinical trial, careful preprocessing of ECG data, and consideration of the influence of oxygen in sleep apnea and of confounding influences, such as medications. Limitations of the study, Dr. George noted, include the absence of sleep-wake data and acknowledgment that HRV measures are accepted surrogates of autonomic imbalance but that they are not direct measures.

The next steps for the current research, Dr. George said, include an analysis of how respiratory events influence HRV indices in CPAP and supplemental oxygen. Future trials should be designed to examine how the two interventions affect direct measures of autonomic function and consider a longer follow-up duration, she said.

Dr. George had no financial relationships to disclose. The trial received support from the National Heart, Lung, and Blood Institute and the National Center for Research Resources.

SOURCE: George J et al. Sleep 2018, Abstract 0444.

BALTIMORE – Continuous positive airway pressure (CPAP) may supersede supplemental oxygen and patient education for improving one key marker of cardiac electrophysiological autonomic function during sleep, but supplemental oxygen may have the upper hand in improving a second key electrophysiological biomarker, according to results of a multicenter, randomized clinical trial presented at the annual meeting of the Associated Professional Sleep Societies.

“Based on these findings, it appears that there are opposing alterations in both frequency and time domain in heart rate variability indices in the CPAP versus oxygen groups,” said Jenie George, MD, of the Cleveland Clinic.

The study evaluated 3-month outcomes of frequency-based heart rate variability (HRV) indices obtained with ECG from sleep studies in 203 patients with obstructive sleep apnea and increased cardiovascular risk in the Heart Biomarker Elevation in Apnea Treatment (HeartBEAT) trial. The interventions were either CPAP, supplemental oxygen, or healthy lifestyle education. Dr. George noted that HRV is a noninvasive tool to evaluate autonomic function by quantifying changes in intervals between sinus beats during sleep.

On the high-frequency power index, patients on CPAP had a 9% reduction versus a 19% increase for those on supplemental oxygen, Dr. George said. However for the low frequency to high frequency ratio, the CPAP group had a 4% increase, whereas the oxygen group had a 34% reduction.

The increase of low frequency to high frequency ratio in the CPAP group is a reflection of sympathovagal balance – the ratio between low-frequency and high-frequency powers – while the changes in high-frequency power in the CPAP patients reflect changes in sinoatrial node electrophysiological function, Dr. George said.

Strengths of the study were its use of data from a large clinical trial, careful preprocessing of ECG data, and consideration of the influence of oxygen in sleep apnea and of confounding influences, such as medications. Limitations of the study, Dr. George noted, include the absence of sleep-wake data and acknowledgment that HRV measures are accepted surrogates of autonomic imbalance but that they are not direct measures.

The next steps for the current research, Dr. George said, include an analysis of how respiratory events influence HRV indices in CPAP and supplemental oxygen. Future trials should be designed to examine how the two interventions affect direct measures of autonomic function and consider a longer follow-up duration, she said.

Dr. George had no financial relationships to disclose. The trial received support from the National Heart, Lung, and Blood Institute and the National Center for Research Resources.

SOURCE: George J et al. Sleep 2018, Abstract 0444.

BALTIMORE – Continuous positive airway pressure (CPAP) may supersede supplemental oxygen and patient education for improving one key marker of cardiac electrophysiological autonomic function during sleep, but supplemental oxygen may have the upper hand in improving a second key electrophysiological biomarker, according to results of a multicenter, randomized clinical trial presented at the annual meeting of the Associated Professional Sleep Societies.

“Based on these findings, it appears that there are opposing alterations in both frequency and time domain in heart rate variability indices in the CPAP versus oxygen groups,” said Jenie George, MD, of the Cleveland Clinic.

The study evaluated 3-month outcomes of frequency-based heart rate variability (HRV) indices obtained with ECG from sleep studies in 203 patients with obstructive sleep apnea and increased cardiovascular risk in the Heart Biomarker Elevation in Apnea Treatment (HeartBEAT) trial. The interventions were either CPAP, supplemental oxygen, or healthy lifestyle education. Dr. George noted that HRV is a noninvasive tool to evaluate autonomic function by quantifying changes in intervals between sinus beats during sleep.

On the high-frequency power index, patients on CPAP had a 9% reduction versus a 19% increase for those on supplemental oxygen, Dr. George said. However for the low frequency to high frequency ratio, the CPAP group had a 4% increase, whereas the oxygen group had a 34% reduction.

The increase of low frequency to high frequency ratio in the CPAP group is a reflection of sympathovagal balance – the ratio between low-frequency and high-frequency powers – while the changes in high-frequency power in the CPAP patients reflect changes in sinoatrial node electrophysiological function, Dr. George said.

Strengths of the study were its use of data from a large clinical trial, careful preprocessing of ECG data, and consideration of the influence of oxygen in sleep apnea and of confounding influences, such as medications. Limitations of the study, Dr. George noted, include the absence of sleep-wake data and acknowledgment that HRV measures are accepted surrogates of autonomic imbalance but that they are not direct measures.

The next steps for the current research, Dr. George said, include an analysis of how respiratory events influence HRV indices in CPAP and supplemental oxygen. Future trials should be designed to examine how the two interventions affect direct measures of autonomic function and consider a longer follow-up duration, she said.

Dr. George had no financial relationships to disclose. The trial received support from the National Heart, Lung, and Blood Institute and the National Center for Research Resources.

SOURCE: George J et al. Sleep 2018, Abstract 0444.

Clinical question: Does prompting hospitalists during interdisciplinary rounds to discontinue lab orders on patients nearing discharge result in a decrease in lab testing?

Background: The Society of Hospital Medicine, as part of the Choosing Wisely campaign, has recommended against “repetitive complete blood count and chemistry testing in the face of clinical and lab stability.” Repeated phlebotomy has been shown to increase iatrogenic anemia and patient discomfort. While past interventions have been effective in decreasing lab testing, this study focused on identifying and intervening on patients who were clinically stable and nearing discharge.

Study design: Prospective, observational study.

Setting: Tertiary care teaching hospital in New York.

Synopsis: As part of structured, bedside, interdisciplinary rounds, over the course of a year, this study incorporated an inquiry to identify patients who were likely to be discharged in the next 24-48 hours; the unit medical director or nurse manager then prompted staff to discontinue labs for these patients when appropriate. This was supplemented by education of clinicians and regular review of lab utilization data with hospitalists.

The percentage of patients with labs ordered in the 24 hours prior to discharge decreased from 50.1% in the preintervention period to 34.5% in the postintervention period (P = .004). The number of labs ordered per patient-day dropped from 1.96 to 1.83 (P = .01).

Bottom line: An intervention with prompting during structured interdisciplinary rounds decreased the frequency of labs ordered for patients nearing hospital discharge.

Citation: Tsega S et al. Bedside assessment of the necessity of daily lab testing for patients nearing discharge. J Hosp Med. 2018 Jan 1;13(1):38-40.
 

Dr. Huang is associate chief of the division of hospital medicine at UC San Diego Health and an associate professor of medicine at the University of California, San Diego.

Clinical question: Does prompting hospitalists during interdisciplinary rounds to discontinue lab orders on patients nearing discharge result in a decrease in lab testing?

Background: The Society of Hospital Medicine, as part of the Choosing Wisely campaign, has recommended against “repetitive complete blood count and chemistry testing in the face of clinical and lab stability.” Repeated phlebotomy has been shown to increase iatrogenic anemia and patient discomfort. While past interventions have been effective in decreasing lab testing, this study focused on identifying and intervening on patients who were clinically stable and nearing discharge.

Study design: Prospective, observational study.

Setting: Tertiary care teaching hospital in New York.

Synopsis: As part of structured, bedside, interdisciplinary rounds, over the course of a year, this study incorporated an inquiry to identify patients who were likely to be discharged in the next 24-48 hours; the unit medical director or nurse manager then prompted staff to discontinue labs for these patients when appropriate. This was supplemented by education of clinicians and regular review of lab utilization data with hospitalists.

The percentage of patients with labs ordered in the 24 hours prior to discharge decreased from 50.1% in the preintervention period to 34.5% in the postintervention period (P = .004). The number of labs ordered per patient-day dropped from 1.96 to 1.83 (P = .01).

Bottom line: An intervention with prompting during structured interdisciplinary rounds decreased the frequency of labs ordered for patients nearing hospital discharge.

Citation: Tsega S et al. Bedside assessment of the necessity of daily lab testing for patients nearing discharge. J Hosp Med. 2018 Jan 1;13(1):38-40.
 

Dr. Huang is associate chief of the division of hospital medicine at UC San Diego Health and an associate professor of medicine at the University of California, San Diego.

Clinical question: Does prompting hospitalists during interdisciplinary rounds to discontinue lab orders on patients nearing discharge result in a decrease in lab testing?

Background: The Society of Hospital Medicine, as part of the Choosing Wisely campaign, has recommended against “repetitive complete blood count and chemistry testing in the face of clinical and lab stability.” Repeated phlebotomy has been shown to increase iatrogenic anemia and patient discomfort. While past interventions have been effective in decreasing lab testing, this study focused on identifying and intervening on patients who were clinically stable and nearing discharge.

Study design: Prospective, observational study.

Setting: Tertiary care teaching hospital in New York.

Synopsis: As part of structured, bedside, interdisciplinary rounds, over the course of a year, this study incorporated an inquiry to identify patients who were likely to be discharged in the next 24-48 hours; the unit medical director or nurse manager then prompted staff to discontinue labs for these patients when appropriate. This was supplemented by education of clinicians and regular review of lab utilization data with hospitalists.

The percentage of patients with labs ordered in the 24 hours prior to discharge decreased from 50.1% in the preintervention period to 34.5% in the postintervention period (P = .004). The number of labs ordered per patient-day dropped from 1.96 to 1.83 (P = .01).

Bottom line: An intervention with prompting during structured interdisciplinary rounds decreased the frequency of labs ordered for patients nearing hospital discharge.

Citation: Tsega S et al. Bedside assessment of the necessity of daily lab testing for patients nearing discharge. J Hosp Med. 2018 Jan 1;13(1):38-40.
 

Dr. Huang is associate chief of the division of hospital medicine at UC San Diego Health and an associate professor of medicine at the University of California, San Diego.

Citation: Middleton P, Shepherd E, Crowther CA. Induction of labour for improving birth outcomes for women at or beyond term. Cochrane Database Syst Rev. 2018;5:CD004945.

Citation: Middleton P, Shepherd E, Crowther CA. Induction of labour for improving birth outcomes for women at or beyond term. Cochrane Database Syst Rev. 2018;5:CD004945.

Citation: Middleton P, Shepherd E, Crowther CA. Induction of labour for improving birth outcomes for women at or beyond term. Cochrane Database Syst Rev. 2018;5:CD004945.

Ozenoxacin (Xepi cream), a potent novel topical antibacterial agent, is effective and well tolerated for treatment of impetigo in patients aged 2 months and older, according to results of a phase 3 randomized, double-blind, vehicle-controlled clinical trial.

A 1% cream formulation of ozenoxacin had a clinical and microbiologic response that was rapid and superior to placebo, investigators reported in this second phase 3 pivotal study, which demonstrated the efficacy of ozenoxacin cream in impetigo patients.

SOURCE: Rosen T et al. JAMA Dermatol. 2018 Jun 13. doi: 10.1001/jamadermatol.2018.1103.

Ozenoxacin (Xepi cream), a potent novel topical antibacterial agent, is effective and well tolerated for treatment of impetigo in patients aged 2 months and older, according to results of a phase 3 randomized, double-blind, vehicle-controlled clinical trial.

A 1% cream formulation of ozenoxacin had a clinical and microbiologic response that was rapid and superior to placebo, investigators reported in this second phase 3 pivotal study, which demonstrated the efficacy of ozenoxacin cream in impetigo patients.

SOURCE: Rosen T et al. JAMA Dermatol. 2018 Jun 13. doi: 10.1001/jamadermatol.2018.1103.

Ozenoxacin (Xepi cream), a potent novel topical antibacterial agent, is effective and well tolerated for treatment of impetigo in patients aged 2 months and older, according to results of a phase 3 randomized, double-blind, vehicle-controlled clinical trial.

A 1% cream formulation of ozenoxacin had a clinical and microbiologic response that was rapid and superior to placebo, investigators reported in this second phase 3 pivotal study, which demonstrated the efficacy of ozenoxacin cream in impetigo patients.

SOURCE: Rosen T et al. JAMA Dermatol. 2018 Jun 13. doi: 10.1001/jamadermatol.2018.1103.

There is a cigarette smoking epidemic embedded within the hepatitis C virus epidemic in the United States, according to the results of an analysis of data between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES).

©siwaporn999/Thinkstock

Smoking and hepatitis C information were available for 90.1% of the NHANES adult population. Of the 39,472 individuals evaluated, 1.3% were hepatitis C+ and 22.3% were current smokers. Hepatitis C+ individuals were almost three times as likely to be smokers as were those who were hepatitis C– (62.4% vs. 22.9%, respectively), according to the report, published in The American Journal of Medicine (Am J Med. 2018 Jun;131[6]:699-75).

Ryung S. Kim, PhD, of Albert Einstein College of Medicine, New York, and his colleagues also found that hepatitis C+ smokers were more likely to be older, male, black, less educated, poor, and uninsured compared with their hepatitis C– smoking counterparts. They also were more likely to use drugs, including heroin, and to be depressed.

Multivariate analysis showed a significant association of both hepatitis C infection and smoking with current depression and hypertension, Dr. Kim and his colleagues wrote.

“It is public health folly to spend tens of millions of dollars annually” on treatment of hepatitis C patients, “and ignore the lethal addiction affecting more than 60% of them. As we enter a new era of hepatitis C treatment, it is a public health imperative to research, develop, and implement tobacco treatments for the hepatitis C+ community,” Dr. Kim and his colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Kim RS et al. Am J Med. 2018Jun;131[6]:669-75).

There is a cigarette smoking epidemic embedded within the hepatitis C virus epidemic in the United States, according to the results of an analysis of data between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES).

©siwaporn999/Thinkstock

Smoking and hepatitis C information were available for 90.1% of the NHANES adult population. Of the 39,472 individuals evaluated, 1.3% were hepatitis C+ and 22.3% were current smokers. Hepatitis C+ individuals were almost three times as likely to be smokers as were those who were hepatitis C– (62.4% vs. 22.9%, respectively), according to the report, published in The American Journal of Medicine (Am J Med. 2018 Jun;131[6]:699-75).

Ryung S. Kim, PhD, of Albert Einstein College of Medicine, New York, and his colleagues also found that hepatitis C+ smokers were more likely to be older, male, black, less educated, poor, and uninsured compared with their hepatitis C– smoking counterparts. They also were more likely to use drugs, including heroin, and to be depressed.

Multivariate analysis showed a significant association of both hepatitis C infection and smoking with current depression and hypertension, Dr. Kim and his colleagues wrote.

“It is public health folly to spend tens of millions of dollars annually” on treatment of hepatitis C patients, “and ignore the lethal addiction affecting more than 60% of them. As we enter a new era of hepatitis C treatment, it is a public health imperative to research, develop, and implement tobacco treatments for the hepatitis C+ community,” Dr. Kim and his colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Kim RS et al. Am J Med. 2018Jun;131[6]:669-75).

There is a cigarette smoking epidemic embedded within the hepatitis C virus epidemic in the United States, according to the results of an analysis of data between 1999 and 2014 from the National Health and Nutrition Examination Survey (NHANES).

©siwaporn999/Thinkstock

Smoking and hepatitis C information were available for 90.1% of the NHANES adult population. Of the 39,472 individuals evaluated, 1.3% were hepatitis C+ and 22.3% were current smokers. Hepatitis C+ individuals were almost three times as likely to be smokers as were those who were hepatitis C– (62.4% vs. 22.9%, respectively), according to the report, published in The American Journal of Medicine (Am J Med. 2018 Jun;131[6]:699-75).

Ryung S. Kim, PhD, of Albert Einstein College of Medicine, New York, and his colleagues also found that hepatitis C+ smokers were more likely to be older, male, black, less educated, poor, and uninsured compared with their hepatitis C– smoking counterparts. They also were more likely to use drugs, including heroin, and to be depressed.

Multivariate analysis showed a significant association of both hepatitis C infection and smoking with current depression and hypertension, Dr. Kim and his colleagues wrote.

“It is public health folly to spend tens of millions of dollars annually” on treatment of hepatitis C patients, “and ignore the lethal addiction affecting more than 60% of them. As we enter a new era of hepatitis C treatment, it is a public health imperative to research, develop, and implement tobacco treatments for the hepatitis C+ community,” Dr. Kim and his colleagues concluded.

The authors reported that they had no conflicts of interest.

[email protected]

SOURCE: Kim RS et al. Am J Med. 2018Jun;131[6]:669-75).

Since 2000, Medicare beneficiaries have become less likely to die in hospitals, and more likely to die in their homes or in community health care facilities.

A review of Medicare records also determined that there was a decline in health care transitions in the final 3 days of life for these patients, Joan M. Teno, MD, and her colleagues wrote in JAMA.

It is not possible to identify a specific reason for the shift, wrote Dr. Teno, professor of medicine at the Oregon Health & Science University, Portland. Between the study years of 2000 and 2015, there were several large efforts to improve care at the end of life.

“Since 2009, programs ranging from ensuring informed patient decision making to enhanced care coordination have had the goal of improving care at the end of life. Specific interventions have included promoting conversations about the goals of care, continued growth of hospice services and palliative care, and the debate and passage of the Affordable Care Act … It is difficult to disentangle efforts such as public education, promotion of advance directives through the Patient Self- Determination Act, increased access to hospice and palliative care services, financial incentives of payment policies, and other secular changes.”

The study mined data from the Centers for Medicare & Medicaid Services, and examined end-of-life outcomes among two Medicare groups: Medicare fee-for-service recipients (1,361,870) during 2009-2015, and Medicare Advantage recipients (871,845), comparing 2011 and 2015. The mean age of both cohorts was 82 years.

Outcomes included site of death and “potentially burdensome transitions,” during the last days of life. These were defined as three or more hospitalizations in the previous 3 months, or two or more hospitalizations for pneumonia, urinary tract infection, dehydration, or sepsis during the last 120 days of life. Prolonged mechanical ventilation also was deemed potentially burdensome.

Among fee-for-service recipients, deaths in acute care hospitals declined from 32.6% to19.8%. Deaths in nursing homes remained steady, at 27.2% and 24.9%. Many of these deaths (42.9%) were preceded by a stay in an ICU. There was a transient increase in end-of-life ICU use, around 2009, but by 2015, the percentage was down to 29%, compared with 65.2% in 2000.

Transitions between a nursing home and hospital in the last 90 days of life were 0.49/person in 2000 and 0.33/person in 2015. Hospitalizations for infection or dehydration fell from 14.6% to12.2%. Hospitalization with prolonged ventilation fell from 3.1% to 2.5%.

Dying in hospice care increased from 21.6% to 50.4%, and people were taking advantage of hospice services longer: the proportion using short-term services (3 days or less) fell from 9.8% to 7.7%.

Among Medicare Advantage recipients, the numbers were somewhat different. More than 50% of recipients entered hospice care in both 2011 and 2015; in both years, 8% had services for more than 3 days. About 27% had ICU care in the last days of life, in both years. Compared to fee-for-service recipients, fewer Medicare Advantage patients were in nursing homes at the time of death, and that number declined from 2011 to 2015 (37.7% to 33.2%).

In each year, about 10% of these patients had a hospitalization for dehydration or infection, and 3% had a stay requiring prolonged mechanical ventilation in each year. The mean number of health care transitions remained steady, at 0.23 and 0.21 per person each year.

Dr. Teno had no financial disclosures.

[email protected]

SOURCE: Teno JM et al. JAMA. 2018 Jun 25. doi: 10.1001/jama.2018.8981.

Since 2000, Medicare beneficiaries have become less likely to die in hospitals, and more likely to die in their homes or in community health care facilities.

A review of Medicare records also determined that there was a decline in health care transitions in the final 3 days of life for these patients, Joan M. Teno, MD, and her colleagues wrote in JAMA.

It is not possible to identify a specific reason for the shift, wrote Dr. Teno, professor of medicine at the Oregon Health & Science University, Portland. Between the study years of 2000 and 2015, there were several large efforts to improve care at the end of life.

“Since 2009, programs ranging from ensuring informed patient decision making to enhanced care coordination have had the goal of improving care at the end of life. Specific interventions have included promoting conversations about the goals of care, continued growth of hospice services and palliative care, and the debate and passage of the Affordable Care Act … It is difficult to disentangle efforts such as public education, promotion of advance directives through the Patient Self- Determination Act, increased access to hospice and palliative care services, financial incentives of payment policies, and other secular changes.”

The study mined data from the Centers for Medicare & Medicaid Services, and examined end-of-life outcomes among two Medicare groups: Medicare fee-for-service recipients (1,361,870) during 2009-2015, and Medicare Advantage recipients (871,845), comparing 2011 and 2015. The mean age of both cohorts was 82 years.

Outcomes included site of death and “potentially burdensome transitions,” during the last days of life. These were defined as three or more hospitalizations in the previous 3 months, or two or more hospitalizations for pneumonia, urinary tract infection, dehydration, or sepsis during the last 120 days of life. Prolonged mechanical ventilation also was deemed potentially burdensome.

Among fee-for-service recipients, deaths in acute care hospitals declined from 32.6% to19.8%. Deaths in nursing homes remained steady, at 27.2% and 24.9%. Many of these deaths (42.9%) were preceded by a stay in an ICU. There was a transient increase in end-of-life ICU use, around 2009, but by 2015, the percentage was down to 29%, compared with 65.2% in 2000.

Transitions between a nursing home and hospital in the last 90 days of life were 0.49/person in 2000 and 0.33/person in 2015. Hospitalizations for infection or dehydration fell from 14.6% to12.2%. Hospitalization with prolonged ventilation fell from 3.1% to 2.5%.

Dying in hospice care increased from 21.6% to 50.4%, and people were taking advantage of hospice services longer: the proportion using short-term services (3 days or less) fell from 9.8% to 7.7%.

Among Medicare Advantage recipients, the numbers were somewhat different. More than 50% of recipients entered hospice care in both 2011 and 2015; in both years, 8% had services for more than 3 days. About 27% had ICU care in the last days of life, in both years. Compared to fee-for-service recipients, fewer Medicare Advantage patients were in nursing homes at the time of death, and that number declined from 2011 to 2015 (37.7% to 33.2%).

In each year, about 10% of these patients had a hospitalization for dehydration or infection, and 3% had a stay requiring prolonged mechanical ventilation in each year. The mean number of health care transitions remained steady, at 0.23 and 0.21 per person each year.

Dr. Teno had no financial disclosures.

[email protected]

SOURCE: Teno JM et al. JAMA. 2018 Jun 25. doi: 10.1001/jama.2018.8981.

Since 2000, Medicare beneficiaries have become less likely to die in hospitals, and more likely to die in their homes or in community health care facilities.

A review of Medicare records also determined that there was a decline in health care transitions in the final 3 days of life for these patients, Joan M. Teno, MD, and her colleagues wrote in JAMA.

It is not possible to identify a specific reason for the shift, wrote Dr. Teno, professor of medicine at the Oregon Health & Science University, Portland. Between the study years of 2000 and 2015, there were several large efforts to improve care at the end of life.

“Since 2009, programs ranging from ensuring informed patient decision making to enhanced care coordination have had the goal of improving care at the end of life. Specific interventions have included promoting conversations about the goals of care, continued growth of hospice services and palliative care, and the debate and passage of the Affordable Care Act … It is difficult to disentangle efforts such as public education, promotion of advance directives through the Patient Self- Determination Act, increased access to hospice and palliative care services, financial incentives of payment policies, and other secular changes.”

The study mined data from the Centers for Medicare & Medicaid Services, and examined end-of-life outcomes among two Medicare groups: Medicare fee-for-service recipients (1,361,870) during 2009-2015, and Medicare Advantage recipients (871,845), comparing 2011 and 2015. The mean age of both cohorts was 82 years.

Outcomes included site of death and “potentially burdensome transitions,” during the last days of life. These were defined as three or more hospitalizations in the previous 3 months, or two or more hospitalizations for pneumonia, urinary tract infection, dehydration, or sepsis during the last 120 days of life. Prolonged mechanical ventilation also was deemed potentially burdensome.

Among fee-for-service recipients, deaths in acute care hospitals declined from 32.6% to19.8%. Deaths in nursing homes remained steady, at 27.2% and 24.9%. Many of these deaths (42.9%) were preceded by a stay in an ICU. There was a transient increase in end-of-life ICU use, around 2009, but by 2015, the percentage was down to 29%, compared with 65.2% in 2000.

Transitions between a nursing home and hospital in the last 90 days of life were 0.49/person in 2000 and 0.33/person in 2015. Hospitalizations for infection or dehydration fell from 14.6% to12.2%. Hospitalization with prolonged ventilation fell from 3.1% to 2.5%.

Dying in hospice care increased from 21.6% to 50.4%, and people were taking advantage of hospice services longer: the proportion using short-term services (3 days or less) fell from 9.8% to 7.7%.

Among Medicare Advantage recipients, the numbers were somewhat different. More than 50% of recipients entered hospice care in both 2011 and 2015; in both years, 8% had services for more than 3 days. About 27% had ICU care in the last days of life, in both years. Compared to fee-for-service recipients, fewer Medicare Advantage patients were in nursing homes at the time of death, and that number declined from 2011 to 2015 (37.7% to 33.2%).

In each year, about 10% of these patients had a hospitalization for dehydration or infection, and 3% had a stay requiring prolonged mechanical ventilation in each year. The mean number of health care transitions remained steady, at 0.23 and 0.21 per person each year.

Dr. Teno had no financial disclosures.

[email protected]

SOURCE: Teno JM et al. JAMA. 2018 Jun 25. doi: 10.1001/jama.2018.8981.