HT Staff

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The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

Photo from Business Wire

The US Food and Drug Administration (FDA) has approved brentuximab vedotin (ADCETRIS) in combination with chemotherapy for adults with previously untreated, stage III or IV classical Hodgkin lymphoma (cHL).

This is the fifth approved indication for BV in the US and the first regimen approved for frontline, stage III/IV cHL in the US in more than 40 years.

“The standard of care for treating newly diagnosed, advanced Hodgkin lymphoma has not changed in more than 4 decades,” said Joseph M. Connors, MD, of BC Cancer in Vancouver, British Columbia, Canada.

“For years, the physician community has been conducting clinical trials to identify improved regimens that are both less toxic and more effective—to no avail.”

The ECHELON-1 study changed that, according to Dr Connors.

“The ECHELON-1 study results demonstrated superior efficacy of the ADCETRIS plus chemotherapy regimen, when compared to the standard of care, while removing bleomycin—an agent that can cause unpredictable and sometimes fatal lung toxicity—completely from the regimen,” he said. “This represents a meaningful advance for this often younger patient population.”

In the phase 3 ECHELON-1 trial, researchers compared BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) to doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD).

In addition to supporting the new approval for BV in cHL, ECHELON-1 results also served to convert an accelerated approval of BV to standard approval. The drug now has standard FDA approval for the treatment of adults with systemic anaplastic large-cell lymphoma (ALCL) who have failed at least 1 prior multi-agent chemotherapy regimen.

BV also has standard FDA approval for:

• Adults with cHL who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or, in those who are not auto-HSCT candidates, have failed at least 2 prior multi-agent chemotherapy regimens
• Post-auto-HSCT consolidation in adults with cHL at high risk of relapse or progression
• Adults with primary cutaneous ALCL or CD30-expressing mycosis fungoides who have received prior systemic therapy.

ECHELON-1

Result from ECHELON-1 were presented at the 2017 ASH Annual Meeting and simultaneously published in NEJM.

In this trial, researchers compared A+AVD to ABVD as frontline treatment for 1334 patients with advanced cHL. The primary endpoint was modified progression-free survival (PFS), which was defined as time to progression, death, or evidence of non-complete response after completion of frontline therapy followed by subsequent anticancer therapy.

According to an independent review facility, A+AVD provided a significant improvement in modified PFS compared to ABVD. The hazard ratio was 0.77 (P=0.035), which corresponds to a 23% reduction in the risk of progression, death, or the need for additional anticancer therapy.

The 2-year modified PFS rate was 82.1% in the A+AVD arm and 77.2% in the ABVD arm.

There was no significant difference between the treatment arms when it came to response rates or overall survival.

The objective response rate was 86% in the A+AVD arm and 83% in the ABVD arm (P=0.12). The complete response rate was 73% and 70%, respectively (P=0.22).

The interim 2-year overall survival rate was 97% in the A+AVD arm and 95% in the ABVD arm (hazard ratio=0.72; P=0.19).

The overall incidence of adverse events (AEs) was 99% in the A+AVD arm and 98% in the ABVD arm. The incidence of grade 3 or higher AEs was 83% and 66%, respectively, and the incidence of serious AEs was 43% and 27%, respectively.

Neutropenia, febrile neutropenia, and peripheral neuropathy were more common with A+AVD, while pulmonary toxicity was more common with ABVD.

stem cell graft

LISBON—Phase 1 results suggest a programmed cellular therapy is safe for use in patients with hematologic malignancies.

The therapy, ProTmune, is being developed as a next-generation allogeneic graft intended to reduce the incidence and severity of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT).

Three of 7 patients who received ProTmune in this trial did develop acute GVHD, and 2 patients died.

However, the remaining 5 patients were still alive and disease-free at last follow-up.

There were no serious adverse events (AEs) attributed to ProTmune. The most common AEs were nausea, vomiting, and chest pain.

These results were presented at the 44th Annual Meeting of the EBMT (abstract A401*).

The trial, known as PROTECT, is sponsored by Fate Therapeutics, the company developing ProTmune.

The phase 1 portion of PROTECT enrolled 7 adults with hematologic malignancies—1 with myelodysplastic syndrome, 3 with acute lymphoblastic leukemia, and 3 with acute myeloid leukemia.

Patients were set to undergo matched, unrelated donor HSCT and received ProTmune as the graft. ProTmune is manufactured by modulating a mobilized peripheral blood graft with 2 small molecules, FT1050 and FT4145.

The patients ranged in age from 34 to 69, and most (n=5) were female. For conditioning, patients received fludarabine/busulfan (n=1), busulfan/cyclophosphamide (n=1), fludarabine/melphalan (n=3), or cyclophosphamide/total body irradiation (n=2).

Results

The data cut-off was February 26, 2018. The median time on study was 228 days (range, 151 to 353).

None of the patients had graft failure. The median time to neutrophil engraftment was 18 days (range, 14 to 22).

Three patients had acute GVHD at day 100 after HSCT. Two patients had grade 2 skin GVHD, and 1 had grade 3 GVHD in the skin and gut.

All 3 patients responded to steroid treatment. GVHD resolved in 5 days for the patient with grade 3 GVHD. For the grade 2 patients, GVHD resolved in 7 days and 8 days, respectively.

None of the patients relapsed, but 2 died—1 of pulmonary edema and 1 of atrial fibrillation.

AEs related to ProTmune included grade 1 vomiting (n=2), grade 2 nausea (n=2), and grade 2 chest pain (n=1).

Phase 2

The phase 2 portion of PROTECT is ongoing. This is a randomized, controlled, double-blinded trial designed to assess the safety and efficacy of ProTmune in up to 60 adults with hematologic malignancies undergoing matched, unrelated donor HSCT following myeloablative conditioning.

Patients are being randomized, in a 1:1 ratio, to receive either ProTmune or a conventional, mobilized peripheral blood cell graft from a matched, unrelated donor.

The primary efficacy endpoint is the cumulative incidence of grade 2-4 acute GVHD by day 100 post-HSCT. Rates of chronic GVHD, cancer relapse, disease-free survival, and overall survival are also being assessed.

*Some data in the abstract differ from the presentation.

stem cell graft

LISBON—Phase 1 results suggest a programmed cellular therapy is safe for use in patients with hematologic malignancies.

The therapy, ProTmune, is being developed as a next-generation allogeneic graft intended to reduce the incidence and severity of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT).

Three of 7 patients who received ProTmune in this trial did develop acute GVHD, and 2 patients died.

However, the remaining 5 patients were still alive and disease-free at last follow-up.

There were no serious adverse events (AEs) attributed to ProTmune. The most common AEs were nausea, vomiting, and chest pain.

These results were presented at the 44th Annual Meeting of the EBMT (abstract A401*).

The trial, known as PROTECT, is sponsored by Fate Therapeutics, the company developing ProTmune.

The phase 1 portion of PROTECT enrolled 7 adults with hematologic malignancies—1 with myelodysplastic syndrome, 3 with acute lymphoblastic leukemia, and 3 with acute myeloid leukemia.

Patients were set to undergo matched, unrelated donor HSCT and received ProTmune as the graft. ProTmune is manufactured by modulating a mobilized peripheral blood graft with 2 small molecules, FT1050 and FT4145.

The patients ranged in age from 34 to 69, and most (n=5) were female. For conditioning, patients received fludarabine/busulfan (n=1), busulfan/cyclophosphamide (n=1), fludarabine/melphalan (n=3), or cyclophosphamide/total body irradiation (n=2).

Results

The data cut-off was February 26, 2018. The median time on study was 228 days (range, 151 to 353).

None of the patients had graft failure. The median time to neutrophil engraftment was 18 days (range, 14 to 22).

Three patients had acute GVHD at day 100 after HSCT. Two patients had grade 2 skin GVHD, and 1 had grade 3 GVHD in the skin and gut.

All 3 patients responded to steroid treatment. GVHD resolved in 5 days for the patient with grade 3 GVHD. For the grade 2 patients, GVHD resolved in 7 days and 8 days, respectively.

None of the patients relapsed, but 2 died—1 of pulmonary edema and 1 of atrial fibrillation.

AEs related to ProTmune included grade 1 vomiting (n=2), grade 2 nausea (n=2), and grade 2 chest pain (n=1).

Phase 2

The phase 2 portion of PROTECT is ongoing. This is a randomized, controlled, double-blinded trial designed to assess the safety and efficacy of ProTmune in up to 60 adults with hematologic malignancies undergoing matched, unrelated donor HSCT following myeloablative conditioning.

Patients are being randomized, in a 1:1 ratio, to receive either ProTmune or a conventional, mobilized peripheral blood cell graft from a matched, unrelated donor.

The primary efficacy endpoint is the cumulative incidence of grade 2-4 acute GVHD by day 100 post-HSCT. Rates of chronic GVHD, cancer relapse, disease-free survival, and overall survival are also being assessed.

*Some data in the abstract differ from the presentation.

stem cell graft

LISBON—Phase 1 results suggest a programmed cellular therapy is safe for use in patients with hematologic malignancies.

The therapy, ProTmune, is being developed as a next-generation allogeneic graft intended to reduce the incidence and severity of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplant (HSCT).

Three of 7 patients who received ProTmune in this trial did develop acute GVHD, and 2 patients died.

However, the remaining 5 patients were still alive and disease-free at last follow-up.

There were no serious adverse events (AEs) attributed to ProTmune. The most common AEs were nausea, vomiting, and chest pain.

These results were presented at the 44th Annual Meeting of the EBMT (abstract A401*).

The trial, known as PROTECT, is sponsored by Fate Therapeutics, the company developing ProTmune.

The phase 1 portion of PROTECT enrolled 7 adults with hematologic malignancies—1 with myelodysplastic syndrome, 3 with acute lymphoblastic leukemia, and 3 with acute myeloid leukemia.

Patients were set to undergo matched, unrelated donor HSCT and received ProTmune as the graft. ProTmune is manufactured by modulating a mobilized peripheral blood graft with 2 small molecules, FT1050 and FT4145.

The patients ranged in age from 34 to 69, and most (n=5) were female. For conditioning, patients received fludarabine/busulfan (n=1), busulfan/cyclophosphamide (n=1), fludarabine/melphalan (n=3), or cyclophosphamide/total body irradiation (n=2).

Results

The data cut-off was February 26, 2018. The median time on study was 228 days (range, 151 to 353).

None of the patients had graft failure. The median time to neutrophil engraftment was 18 days (range, 14 to 22).

Three patients had acute GVHD at day 100 after HSCT. Two patients had grade 2 skin GVHD, and 1 had grade 3 GVHD in the skin and gut.

All 3 patients responded to steroid treatment. GVHD resolved in 5 days for the patient with grade 3 GVHD. For the grade 2 patients, GVHD resolved in 7 days and 8 days, respectively.

None of the patients relapsed, but 2 died—1 of pulmonary edema and 1 of atrial fibrillation.

AEs related to ProTmune included grade 1 vomiting (n=2), grade 2 nausea (n=2), and grade 2 chest pain (n=1).

Phase 2

The phase 2 portion of PROTECT is ongoing. This is a randomized, controlled, double-blinded trial designed to assess the safety and efficacy of ProTmune in up to 60 adults with hematologic malignancies undergoing matched, unrelated donor HSCT following myeloablative conditioning.

Patients are being randomized, in a 1:1 ratio, to receive either ProTmune or a conventional, mobilized peripheral blood cell graft from a matched, unrelated donor.

The primary efficacy endpoint is the cumulative incidence of grade 2-4 acute GVHD by day 100 post-HSCT. Rates of chronic GVHD, cancer relapse, disease-free survival, and overall survival are also being assessed.

*Some data in the abstract differ from the presentation.

Photo by Nina Matthews

Pregnant women with severe anemia are twice as likely as those without it to die during or shortly after pregnancy, according to research published in The Lancet Global Health.

Previous studies suggested anemia was strongly associated with death, but this was due to other clinical reasons.

For the current study, researchers took into account factors that influence the development of anemia in pregnancy (such as blood loss or malaria infection) and still found a significant association between anemia and death.

“Anemia in pregnancy is one of the most common medical problems pregnant women encounter, both in low- and high-income countries,” said study author Jahnavi Daru, MBBS, from Queen Mary University of London in the UK.

“We’ve now shown that, if a woman develops severe anemia at any point in her pregnancy or in the 7 days after delivery, she is at a higher risk of dying, making urgent treatment even more important.”

To make this discovery, Dr Daru and her colleagues analyzed World Health Organization data on 312,281 pregnancies in 29 countries* across Latin America, Africa, the Western Pacific region, the Eastern Mediterranean, and South East Asia.

There were 4687 cases of severe anemia (a blood count of less than 70 g/L) and 341 deaths in this group. Deaths were included if they occurred any time after hospital admission until the seventh day post-partum or post-discharge.

The researchers matched 4189 of the women with severe anemia to 8218 women without severe anemia and found a significantly increased risk of death among the women with anemia, both in a crude analysis and an analysis adjusted for potential confounding variables.

In the crude analysis, the odds ratio (OR) for death was 43.35 for women with severe anemia (P<0.0001). In the adjusted analysis, the OR was 2.36 (P<0.0001).

The researchers also conducted a propensity score analysis, matching women with severe anemia to their non-anemic counterparts 1:2. In this analysis, the OR for death was 1.86 (P<0.0001) for the women with severe anemia.

“Anemia is a readily treatable condition, but the existing approaches so far have not been able to tackle the problem,” Dr Daru pointed out. “Clinicians, policy makers, and healthcare professionals should now focus their attention on preventing anemia using a multifaceted approach, not just hoping that iron tablets will solve the problem.”

* The countries included were Afghanistan, Angola, Argentina, Brazil, Cambodia, China, Democratic Republic of the Congo, Ecuador, India, Japan, Jordan, Kenya, Lebanon, Mexico, Mongolia, Nepal, Nicaragua, Niger, Nigeria, Pakistan, Palestine, Paraguay, Peru, Philippines, Qatar, Sri Lanka, Thailand, Uganda, and Vietnam.

Photo by Nina Matthews

Pregnant women with severe anemia are twice as likely as those without it to die during or shortly after pregnancy, according to research published in The Lancet Global Health.

Previous studies suggested anemia was strongly associated with death, but this was due to other clinical reasons.

For the current study, researchers took into account factors that influence the development of anemia in pregnancy (such as blood loss or malaria infection) and still found a significant association between anemia and death.

“Anemia in pregnancy is one of the most common medical problems pregnant women encounter, both in low- and high-income countries,” said study author Jahnavi Daru, MBBS, from Queen Mary University of London in the UK.

“We’ve now shown that, if a woman develops severe anemia at any point in her pregnancy or in the 7 days after delivery, she is at a higher risk of dying, making urgent treatment even more important.”

To make this discovery, Dr Daru and her colleagues analyzed World Health Organization data on 312,281 pregnancies in 29 countries* across Latin America, Africa, the Western Pacific region, the Eastern Mediterranean, and South East Asia.

There were 4687 cases of severe anemia (a blood count of less than 70 g/L) and 341 deaths in this group. Deaths were included if they occurred any time after hospital admission until the seventh day post-partum or post-discharge.

The researchers matched 4189 of the women with severe anemia to 8218 women without severe anemia and found a significantly increased risk of death among the women with anemia, both in a crude analysis and an analysis adjusted for potential confounding variables.

In the crude analysis, the odds ratio (OR) for death was 43.35 for women with severe anemia (P<0.0001). In the adjusted analysis, the OR was 2.36 (P<0.0001).

The researchers also conducted a propensity score analysis, matching women with severe anemia to their non-anemic counterparts 1:2. In this analysis, the OR for death was 1.86 (P<0.0001) for the women with severe anemia.

“Anemia is a readily treatable condition, but the existing approaches so far have not been able to tackle the problem,” Dr Daru pointed out. “Clinicians, policy makers, and healthcare professionals should now focus their attention on preventing anemia using a multifaceted approach, not just hoping that iron tablets will solve the problem.”

* The countries included were Afghanistan, Angola, Argentina, Brazil, Cambodia, China, Democratic Republic of the Congo, Ecuador, India, Japan, Jordan, Kenya, Lebanon, Mexico, Mongolia, Nepal, Nicaragua, Niger, Nigeria, Pakistan, Palestine, Paraguay, Peru, Philippines, Qatar, Sri Lanka, Thailand, Uganda, and Vietnam.

Photo by Nina Matthews

Pregnant women with severe anemia are twice as likely as those without it to die during or shortly after pregnancy, according to research published in The Lancet Global Health.

Previous studies suggested anemia was strongly associated with death, but this was due to other clinical reasons.

For the current study, researchers took into account factors that influence the development of anemia in pregnancy (such as blood loss or malaria infection) and still found a significant association between anemia and death.

“Anemia in pregnancy is one of the most common medical problems pregnant women encounter, both in low- and high-income countries,” said study author Jahnavi Daru, MBBS, from Queen Mary University of London in the UK.

“We’ve now shown that, if a woman develops severe anemia at any point in her pregnancy or in the 7 days after delivery, she is at a higher risk of dying, making urgent treatment even more important.”

To make this discovery, Dr Daru and her colleagues analyzed World Health Organization data on 312,281 pregnancies in 29 countries* across Latin America, Africa, the Western Pacific region, the Eastern Mediterranean, and South East Asia.

There were 4687 cases of severe anemia (a blood count of less than 70 g/L) and 341 deaths in this group. Deaths were included if they occurred any time after hospital admission until the seventh day post-partum or post-discharge.

The researchers matched 4189 of the women with severe anemia to 8218 women without severe anemia and found a significantly increased risk of death among the women with anemia, both in a crude analysis and an analysis adjusted for potential confounding variables.

In the crude analysis, the odds ratio (OR) for death was 43.35 for women with severe anemia (P<0.0001). In the adjusted analysis, the OR was 2.36 (P<0.0001).

The researchers also conducted a propensity score analysis, matching women with severe anemia to their non-anemic counterparts 1:2. In this analysis, the OR for death was 1.86 (P<0.0001) for the women with severe anemia.

“Anemia is a readily treatable condition, but the existing approaches so far have not been able to tackle the problem,” Dr Daru pointed out. “Clinicians, policy makers, and healthcare professionals should now focus their attention on preventing anemia using a multifaceted approach, not just hoping that iron tablets will solve the problem.”

* The countries included were Afghanistan, Angola, Argentina, Brazil, Cambodia, China, Democratic Republic of the Congo, Ecuador, India, Japan, Jordan, Kenya, Lebanon, Mexico, Mongolia, Nepal, Nicaragua, Niger, Nigeria, Pakistan, Palestine, Paraguay, Peru, Philippines, Qatar, Sri Lanka, Thailand, Uganda, and Vietnam.

mycosis fungoides

The US Food and Drug Administration (FDA) has granted orphan drug designation to TTI-621 for the treatment of cutaneous T-cell lymphoma (CTCL).

TTI-621 is designed to activate the innate immune system by blocking the activity of CD47, a protein commonly found on the surface of cancer cells.

TTI-621 is a SIRPaFc fusion protein that consists of the CD47-binding domain of human SIRPa linked to the Fc region of a human immunoglobulin.

The drug is intended to act as a soluble decoy receptor, preventing CD47 from delivering its inhibitory signal, thereby enabling the activation of macrophage anti-tumor effects by pro-phagocytic signals.

TTI-621 is under investigation in a phase 1 trial of patients with relapsed/refractory solid tumors and CTCL (NCT02890368). Results from the dose-escalation portion of this study were presented at the 2017 ASH Annual Meeting (abstract 4076*).

The dose-escalation portion had a 3+3 design. TTI-621 was first given as a single intratumoral injection at 1 mg, 3 mg, or 10 mg. Then, it was given at 10 mg on Monday, Wednesday, and Friday for 1 week. Next, it was given on the same 3-day schedule for 2 weeks.

Results were reported for 18 patients, 56% of whom were male. They had a median age of 69 (range, 32-85) and a median number of 3 prior therapies (range, 1-16), including radiation (39%).

Eleven patients had CTCL, and 10 were evaluable. Researchers said they observed “rapid decreases in circulating Sézary cells and/or the size of mycosis fungoides tumors” after treatment with TTI-621.

Nine of the 10 patients had a reduction in CAILS score from baseline, and 3 had a reduction in circulating Sézary cells.

There were no dose-limiting toxicities, so the 10 mg dose given 3 times a week for 2 weeks was considered the optimal dose schedule.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

*Data in the abstract differ from the presentation.

mycosis fungoides

The US Food and Drug Administration (FDA) has granted orphan drug designation to TTI-621 for the treatment of cutaneous T-cell lymphoma (CTCL).

TTI-621 is designed to activate the innate immune system by blocking the activity of CD47, a protein commonly found on the surface of cancer cells.

TTI-621 is a SIRPaFc fusion protein that consists of the CD47-binding domain of human SIRPa linked to the Fc region of a human immunoglobulin.

The drug is intended to act as a soluble decoy receptor, preventing CD47 from delivering its inhibitory signal, thereby enabling the activation of macrophage anti-tumor effects by pro-phagocytic signals.

TTI-621 is under investigation in a phase 1 trial of patients with relapsed/refractory solid tumors and CTCL (NCT02890368). Results from the dose-escalation portion of this study were presented at the 2017 ASH Annual Meeting (abstract 4076*).

The dose-escalation portion had a 3+3 design. TTI-621 was first given as a single intratumoral injection at 1 mg, 3 mg, or 10 mg. Then, it was given at 10 mg on Monday, Wednesday, and Friday for 1 week. Next, it was given on the same 3-day schedule for 2 weeks.

Results were reported for 18 patients, 56% of whom were male. They had a median age of 69 (range, 32-85) and a median number of 3 prior therapies (range, 1-16), including radiation (39%).

Eleven patients had CTCL, and 10 were evaluable. Researchers said they observed “rapid decreases in circulating Sézary cells and/or the size of mycosis fungoides tumors” after treatment with TTI-621.

Nine of the 10 patients had a reduction in CAILS score from baseline, and 3 had a reduction in circulating Sézary cells.

There were no dose-limiting toxicities, so the 10 mg dose given 3 times a week for 2 weeks was considered the optimal dose schedule.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

*Data in the abstract differ from the presentation.

mycosis fungoides

The US Food and Drug Administration (FDA) has granted orphan drug designation to TTI-621 for the treatment of cutaneous T-cell lymphoma (CTCL).

TTI-621 is designed to activate the innate immune system by blocking the activity of CD47, a protein commonly found on the surface of cancer cells.

TTI-621 is a SIRPaFc fusion protein that consists of the CD47-binding domain of human SIRPa linked to the Fc region of a human immunoglobulin.

The drug is intended to act as a soluble decoy receptor, preventing CD47 from delivering its inhibitory signal, thereby enabling the activation of macrophage anti-tumor effects by pro-phagocytic signals.

TTI-621 is under investigation in a phase 1 trial of patients with relapsed/refractory solid tumors and CTCL (NCT02890368). Results from the dose-escalation portion of this study were presented at the 2017 ASH Annual Meeting (abstract 4076*).

The dose-escalation portion had a 3+3 design. TTI-621 was first given as a single intratumoral injection at 1 mg, 3 mg, or 10 mg. Then, it was given at 10 mg on Monday, Wednesday, and Friday for 1 week. Next, it was given on the same 3-day schedule for 2 weeks.

Results were reported for 18 patients, 56% of whom were male. They had a median age of 69 (range, 32-85) and a median number of 3 prior therapies (range, 1-16), including radiation (39%).

Eleven patients had CTCL, and 10 were evaluable. Researchers said they observed “rapid decreases in circulating Sézary cells and/or the size of mycosis fungoides tumors” after treatment with TTI-621.

Nine of the 10 patients had a reduction in CAILS score from baseline, and 3 had a reduction in circulating Sézary cells.

There were no dose-limiting toxicities, so the 10 mg dose given 3 times a week for 2 weeks was considered the optimal dose schedule.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

*Data in the abstract differ from the presentation.

Health South Florida

LISBON—Post-transplant therapy including galinpepimut-S (GPS) may prolong progression-free survival (PFS) in patients with high-risk multiple myeloma (MM), according to new research.

In a phase 2 trial, MM patients who received GPS and lenalidomide or bortezomib after autologous stem cell transplant (ASCT) had a median PFS of 23.6 months.

“Currently, post-transplant maintenance therapies for these difficult-to-treat patients are seemingly limited, with PFS rarely exceeding 12 to 14 months,” said Guenther Koehne, MD, PhD, from Miami Cancer Institute of Baptist Health South Florida.

Dr Koehne presented results observed with lenalidomide/bortezomib maintenance plus GPS consolidation at the 44th Annual Meeting of the EBMT (abstract OS4-6).

The trial was supported by the Leo A. Guthart and Kathryn Medina Research Fund and SELLAS Life Sciences Group, the company developing GPS.

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after ASCT.

The goal of GPS therapy was to stimulate an immune response to prevent or delay MM progression. GPS is a cancer immunotherapeutic consisting of 4 modified peptide chains that induce an innate immune response against the WT1 antigen.

Patients began receiving GPS within 22 days of ASCT. They received 6 doses, administered subcutaneously with the oil emulsifier montanide every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent clinical, immune response, and correlative assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS as well as lenalidomide (n=18) or bortezomib (n=1) maintenance, starting on day 100 post-ASCT. They underwent clinical, immune response, and correlative assessment again, 2 to 4 weeks after the 12th GPS dose.

Results

Dr Koehne said GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. And 75% of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

Dr Koehne also said immune responses were linked to clinical activity. In patients who received all 12 doses of GPS (n=12), there was a “strong and bidirectional association” between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses and 81.8% (n=9) had CD8 immune responses.

Among patients who maintained immune response positivity, the CR/VGPR rate was 54.6% if CD4 immune response positivity to any of the 4 native GPS peptides was maintained and 44.0% if CD8 immune response positivity to any of the 4 native GPS peptides was maintained.

The PFS was 81% at 12 months and 62% at 18 months. The median PFS was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

Health South Florida

LISBON—Post-transplant therapy including galinpepimut-S (GPS) may prolong progression-free survival (PFS) in patients with high-risk multiple myeloma (MM), according to new research.

In a phase 2 trial, MM patients who received GPS and lenalidomide or bortezomib after autologous stem cell transplant (ASCT) had a median PFS of 23.6 months.

“Currently, post-transplant maintenance therapies for these difficult-to-treat patients are seemingly limited, with PFS rarely exceeding 12 to 14 months,” said Guenther Koehne, MD, PhD, from Miami Cancer Institute of Baptist Health South Florida.

Dr Koehne presented results observed with lenalidomide/bortezomib maintenance plus GPS consolidation at the 44th Annual Meeting of the EBMT (abstract OS4-6).

The trial was supported by the Leo A. Guthart and Kathryn Medina Research Fund and SELLAS Life Sciences Group, the company developing GPS.

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after ASCT.

The goal of GPS therapy was to stimulate an immune response to prevent or delay MM progression. GPS is a cancer immunotherapeutic consisting of 4 modified peptide chains that induce an innate immune response against the WT1 antigen.

Patients began receiving GPS within 22 days of ASCT. They received 6 doses, administered subcutaneously with the oil emulsifier montanide every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent clinical, immune response, and correlative assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS as well as lenalidomide (n=18) or bortezomib (n=1) maintenance, starting on day 100 post-ASCT. They underwent clinical, immune response, and correlative assessment again, 2 to 4 weeks after the 12th GPS dose.

Results

Dr Koehne said GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. And 75% of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

Dr Koehne also said immune responses were linked to clinical activity. In patients who received all 12 doses of GPS (n=12), there was a “strong and bidirectional association” between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses and 81.8% (n=9) had CD8 immune responses.

Among patients who maintained immune response positivity, the CR/VGPR rate was 54.6% if CD4 immune response positivity to any of the 4 native GPS peptides was maintained and 44.0% if CD8 immune response positivity to any of the 4 native GPS peptides was maintained.

The PFS was 81% at 12 months and 62% at 18 months. The median PFS was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

Health South Florida

LISBON—Post-transplant therapy including galinpepimut-S (GPS) may prolong progression-free survival (PFS) in patients with high-risk multiple myeloma (MM), according to new research.

In a phase 2 trial, MM patients who received GPS and lenalidomide or bortezomib after autologous stem cell transplant (ASCT) had a median PFS of 23.6 months.

“Currently, post-transplant maintenance therapies for these difficult-to-treat patients are seemingly limited, with PFS rarely exceeding 12 to 14 months,” said Guenther Koehne, MD, PhD, from Miami Cancer Institute of Baptist Health South Florida.

Dr Koehne presented results observed with lenalidomide/bortezomib maintenance plus GPS consolidation at the 44th Annual Meeting of the EBMT (abstract OS4-6).

The trial was supported by the Leo A. Guthart and Kathryn Medina Research Fund and SELLAS Life Sciences Group, the company developing GPS.

The study enrolled 19 MM patients. Fifteen of them had high-risk cytogenetics at diagnosis, and 18 were at least minimal residual disease-positive after ASCT.

The goal of GPS therapy was to stimulate an immune response to prevent or delay MM progression. GPS is a cancer immunotherapeutic consisting of 4 modified peptide chains that induce an innate immune response against the WT1 antigen.

Patients began receiving GPS within 22 days of ASCT. They received 6 doses, administered subcutaneously with the oil emulsifier montanide every 2 weeks. Injection sites were pre-stimulated with granulocyte-macrophage colony-stimulating factor (70 μg) on days -2 (± 1 day) and 0 of each GPS vaccination.

The patients underwent clinical, immune response, and correlative assessment 2 to 4 weeks after the 6th GPS dose. Then, they received 6 additional monthly doses of GPS as well as lenalidomide (n=18) or bortezomib (n=1) maintenance, starting on day 100 post-ASCT. They underwent clinical, immune response, and correlative assessment again, 2 to 4 weeks after the 12th GPS dose.

Results

Dr Koehne said GPS stimulated time-dependent CD4+ or CD8+ T-cell immune responses specific for all 4 WT1 peptides within GPS, 2 of which are heteroclitic.

Immune responses were confirmed in up to 91% of patients, with multivalent immune responses in up to 64% of patients. And 75% of patients had multifunctional cross-epitope T-cell reactivity to antigenic epitopes against which the hosts were not specifically immunized, in a pattern akin to epitope spreading.

Dr Koehne also said immune responses were linked to clinical activity. In patients who received all 12 doses of GPS (n=12), there was a “strong and bidirectional association” between clinical benefit—defined as complete response (CR) or very good partial response (VGPR)—and frequency of CD4/CD8 immune responses.

Of those patients who had achieved CR/VGPR upon completion of GPS treatment, 100% (n=11) had CD4 immune responses and 81.8% (n=9) had CD8 immune responses.

Among patients who maintained immune response positivity, the CR/VGPR rate was 54.6% if CD4 immune response positivity to any of the 4 native GPS peptides was maintained and 44.0% if CD8 immune response positivity to any of the 4 native GPS peptides was maintained.

The PFS was 81% at 12 months and 62% at 18 months. The median PFS was 23.6 months (range, 15.2 to not reached).

The overall survival was 88% at 18 months, and the median overall survival was not reached.

Image from CDC/Mae Melvin

A human antibody can protect mice from infection with the malaria parasite Plasmodium falciparum, according to research published in Nature Medicine.

Researchers isolated the antibody, CIS43, from the blood of a volunteer who had received the PfSPZ Vaccine (Sanaria Inc.), an experimental vaccine made from whole, weakened malaria parasites.

The volunteer was later exposed to infectious malaria-carrying mosquitoes under carefully controlled conditions and did not become infected.

Researchers tested CIS43 in 2 different mouse models and found the antibody provided “high-level” protection from malaria infection.

In fact, CIS43 protects against malaria better than any antibody that has been described before, according to study author Marie Pancera, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

She and her colleagues found that CIS43 works by binding to an epitope located between the N terminus and central repeat domains of PfCP (P falciparum circumsporozoite protein).

This epitope is conserved across 99.8% of all known P falciparum strains, which, according to the researchers, makes it an attractive target for next-generation vaccines designed to elicit production of CIS43.

Researchers at the National Institute of Allergy and Infectious Diseases Vaccine Research Center are planning to conduct clinical trials of CIS43 next year.

Image from CDC/Mae Melvin

A human antibody can protect mice from infection with the malaria parasite Plasmodium falciparum, according to research published in Nature Medicine.

Researchers isolated the antibody, CIS43, from the blood of a volunteer who had received the PfSPZ Vaccine (Sanaria Inc.), an experimental vaccine made from whole, weakened malaria parasites.

The volunteer was later exposed to infectious malaria-carrying mosquitoes under carefully controlled conditions and did not become infected.

Researchers tested CIS43 in 2 different mouse models and found the antibody provided “high-level” protection from malaria infection.

In fact, CIS43 protects against malaria better than any antibody that has been described before, according to study author Marie Pancera, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

She and her colleagues found that CIS43 works by binding to an epitope located between the N terminus and central repeat domains of PfCP (P falciparum circumsporozoite protein).

This epitope is conserved across 99.8% of all known P falciparum strains, which, according to the researchers, makes it an attractive target for next-generation vaccines designed to elicit production of CIS43.

Researchers at the National Institute of Allergy and Infectious Diseases Vaccine Research Center are planning to conduct clinical trials of CIS43 next year.

Image from CDC/Mae Melvin

A human antibody can protect mice from infection with the malaria parasite Plasmodium falciparum, according to research published in Nature Medicine.

Researchers isolated the antibody, CIS43, from the blood of a volunteer who had received the PfSPZ Vaccine (Sanaria Inc.), an experimental vaccine made from whole, weakened malaria parasites.

The volunteer was later exposed to infectious malaria-carrying mosquitoes under carefully controlled conditions and did not become infected.

Researchers tested CIS43 in 2 different mouse models and found the antibody provided “high-level” protection from malaria infection.

In fact, CIS43 protects against malaria better than any antibody that has been described before, according to study author Marie Pancera, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington.

She and her colleagues found that CIS43 works by binding to an epitope located between the N terminus and central repeat domains of PfCP (P falciparum circumsporozoite protein).

This epitope is conserved across 99.8% of all known P falciparum strains, which, according to the researchers, makes it an attractive target for next-generation vaccines designed to elicit production of CIS43.

Researchers at the National Institute of Allergy and Infectious Diseases Vaccine Research Center are planning to conduct clinical trials of CIS43 next year.

Photo courtesy of the CDC

The European Heart Rhythm Association (EHRA) has released a new version of its “practical guide” for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation.

The guide, now in its third edition, gives concrete advice on how to use NOACs in specific clinical situations.

It was published in European Heart Journal and presented at EHRA 2018 in Barcelona, Spain.

The 2018 edition of the guide has several new chapters.

One chapter summarizes the correct dosing of NOACs in conditions other than atrial fibrillation, such as for the prevention of deep vein thrombosis and treatment of venous thromboembolism.

“The dosing for each condition is different, which may lead to confusion, so we have outlined this clearly,” said author Hein Heidbüchel, MD, PhD, of Hasselt University in Hasselt, Belgium.

Another chapter outlines how to use NOACs in particular groups of patients, including those with very low body weight, the very obese, athletes, frail patients in whom there is concern about bleeding, and patients with cognitive impairment who may forget to take their pills.

The guide also includes updated advice on the combined use of antiplatelet agents and NOACs in patients with coronary artery disease, particularly those with an acute coronary syndrome or patients scheduled for percutaneous coronary intervention with stenting.

“We provide guidance around which and how many antiplatelets, for how long, with which NOAC, and at what dose of that NOAC,” Dr Heidbüchel said.

In addition, the guide now includes more scientific evidence on the use of anticoagulants around cardioversion. The document gives detailed advice on what to do in patients on long-term NOAC treatment who need cardioversion, as compared to patients newly diagnosed with atrial fibrillation and started on a NOAC before cardioversion.

Since the previous edition of the guide was published, the first NOAC reversal agent has received market approval. Therefore, the new edition includes advice on how to use this agent, idarucizumab—which reverses the anticoagulant effect of dabigatran—when there is acute bleeding, when urgent surgery is required, or when the patient has a stroke.

The guide also includes advice on andexanet alfa, another reversal agent expected to receive market approval, with the caveat that the instructions on the label should be followed.

Additionally, the guide describes scenarios in which physicians might want to know the NOAC plasma level. One scenario concerns patients undergoing major surgery in whom it is unclear—for example, because of other drugs or renal dysfunction—whether the usual practice of stopping the NOAC 48 hours in advance is sufficient. The plasma level of the NOAC could be measured just before surgery to confirm the anticoagulant effect has waned.

Finally, the chapter on drug-drug interactions has been expanded with anticancer and antiepileptic drugs.

“While this is mostly based on potential pharmacokinetic interactions and case reports, it is the first of its kind,” said author Jan Steffel, MD, of University Heart Center Zurich in Switzerland.

“This is likely to be adapted and become more complete over the years as our experience increases at this new frontier.”

EHRA received unconditional grants from Pfizer/BMS, Daiichi-Sankyo, Boehringer-Ingelheim, and Bayer.

Photo courtesy of the CDC

The European Heart Rhythm Association (EHRA) has released a new version of its “practical guide” for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation.

The guide, now in its third edition, gives concrete advice on how to use NOACs in specific clinical situations.

It was published in European Heart Journal and presented at EHRA 2018 in Barcelona, Spain.

The 2018 edition of the guide has several new chapters.

One chapter summarizes the correct dosing of NOACs in conditions other than atrial fibrillation, such as for the prevention of deep vein thrombosis and treatment of venous thromboembolism.

“The dosing for each condition is different, which may lead to confusion, so we have outlined this clearly,” said author Hein Heidbüchel, MD, PhD, of Hasselt University in Hasselt, Belgium.

Another chapter outlines how to use NOACs in particular groups of patients, including those with very low body weight, the very obese, athletes, frail patients in whom there is concern about bleeding, and patients with cognitive impairment who may forget to take their pills.

The guide also includes updated advice on the combined use of antiplatelet agents and NOACs in patients with coronary artery disease, particularly those with an acute coronary syndrome or patients scheduled for percutaneous coronary intervention with stenting.

“We provide guidance around which and how many antiplatelets, for how long, with which NOAC, and at what dose of that NOAC,” Dr Heidbüchel said.

In addition, the guide now includes more scientific evidence on the use of anticoagulants around cardioversion. The document gives detailed advice on what to do in patients on long-term NOAC treatment who need cardioversion, as compared to patients newly diagnosed with atrial fibrillation and started on a NOAC before cardioversion.

Since the previous edition of the guide was published, the first NOAC reversal agent has received market approval. Therefore, the new edition includes advice on how to use this agent, idarucizumab—which reverses the anticoagulant effect of dabigatran—when there is acute bleeding, when urgent surgery is required, or when the patient has a stroke.

The guide also includes advice on andexanet alfa, another reversal agent expected to receive market approval, with the caveat that the instructions on the label should be followed.

Additionally, the guide describes scenarios in which physicians might want to know the NOAC plasma level. One scenario concerns patients undergoing major surgery in whom it is unclear—for example, because of other drugs or renal dysfunction—whether the usual practice of stopping the NOAC 48 hours in advance is sufficient. The plasma level of the NOAC could be measured just before surgery to confirm the anticoagulant effect has waned.

Finally, the chapter on drug-drug interactions has been expanded with anticancer and antiepileptic drugs.

“While this is mostly based on potential pharmacokinetic interactions and case reports, it is the first of its kind,” said author Jan Steffel, MD, of University Heart Center Zurich in Switzerland.

“This is likely to be adapted and become more complete over the years as our experience increases at this new frontier.”

EHRA received unconditional grants from Pfizer/BMS, Daiichi-Sankyo, Boehringer-Ingelheim, and Bayer.

Photo courtesy of the CDC

The European Heart Rhythm Association (EHRA) has released a new version of its “practical guide” for the use of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation.

The guide, now in its third edition, gives concrete advice on how to use NOACs in specific clinical situations.

It was published in European Heart Journal and presented at EHRA 2018 in Barcelona, Spain.

The 2018 edition of the guide has several new chapters.

One chapter summarizes the correct dosing of NOACs in conditions other than atrial fibrillation, such as for the prevention of deep vein thrombosis and treatment of venous thromboembolism.

“The dosing for each condition is different, which may lead to confusion, so we have outlined this clearly,” said author Hein Heidbüchel, MD, PhD, of Hasselt University in Hasselt, Belgium.

Another chapter outlines how to use NOACs in particular groups of patients, including those with very low body weight, the very obese, athletes, frail patients in whom there is concern about bleeding, and patients with cognitive impairment who may forget to take their pills.

The guide also includes updated advice on the combined use of antiplatelet agents and NOACs in patients with coronary artery disease, particularly those with an acute coronary syndrome or patients scheduled for percutaneous coronary intervention with stenting.

“We provide guidance around which and how many antiplatelets, for how long, with which NOAC, and at what dose of that NOAC,” Dr Heidbüchel said.

In addition, the guide now includes more scientific evidence on the use of anticoagulants around cardioversion. The document gives detailed advice on what to do in patients on long-term NOAC treatment who need cardioversion, as compared to patients newly diagnosed with atrial fibrillation and started on a NOAC before cardioversion.

Since the previous edition of the guide was published, the first NOAC reversal agent has received market approval. Therefore, the new edition includes advice on how to use this agent, idarucizumab—which reverses the anticoagulant effect of dabigatran—when there is acute bleeding, when urgent surgery is required, or when the patient has a stroke.

The guide also includes advice on andexanet alfa, another reversal agent expected to receive market approval, with the caveat that the instructions on the label should be followed.

Additionally, the guide describes scenarios in which physicians might want to know the NOAC plasma level. One scenario concerns patients undergoing major surgery in whom it is unclear—for example, because of other drugs or renal dysfunction—whether the usual practice of stopping the NOAC 48 hours in advance is sufficient. The plasma level of the NOAC could be measured just before surgery to confirm the anticoagulant effect has waned.

Finally, the chapter on drug-drug interactions has been expanded with anticancer and antiepileptic drugs.

“While this is mostly based on potential pharmacokinetic interactions and case reports, it is the first of its kind,” said author Jan Steffel, MD, of University Heart Center Zurich in Switzerland.

“This is likely to be adapted and become more complete over the years as our experience increases at this new frontier.”

EHRA received unconditional grants from Pfizer/BMS, Daiichi-Sankyo, Boehringer-Ingelheim, and Bayer.

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”

Photo by Rhoda Baer

New research suggests patients with acute myeloid leukemia (AML) may have a lower risk of early mortality if they receive treatment at a National Cancer Institute (NCI) cancer center.

In a study of AML patients in California, the risk of 60-day mortality was 53% lower among patients treated at NCI cancer centers than among those treated at other centers.

These findings were reported in Cancer.

“We found the early mortality, deaths less than 60 days after diagnosis, was significantly lower at the NCI-designated cancer centers compared to non-NCI-designated cancer centers in California,” said study author Brian Jonas, MD, PhD, of the University of California at Davis School of Medicine in Sacramento, California.

To conduct this study, Dr Jonas and his colleagues analyzed data from the California Cancer Registry and the California Office of Statewide Health Planning and Development Patient Discharge Database.

The California Cancer Registry provides sociodemographic and clinical data for all California cancer patients. The California Office of Statewide Health Planning and Development Patient Discharge Database has data on diagnoses and procedures for all hospital patients in California, excluding 14 Veterans Affairs and military hospitals.

Patients

The study included data on AML patients 18 and older who received inpatient chemotherapy between 1999 and 2014. There were 7007 patients, 1762 (25%) of whom were treated at NCI-designated cancer centers.

The median number of new AML patients per year was 13.5 (range, 0-43) at the NCI centers and 2 (range, 1-17) at non-NCI centers that admitted at least 1 patient with AML. More than half of the non-NCI centers had a median of 0 new AML patients per year.

NCI patients were more likely to be younger (≤65) than non-NCI patients (P<0.0001), to live in neighborhoods with higher socioeconomic status (P<0.0001), have fewer comorbidities (P<0.0001), and have public health insurance (P<0.0001).

Results

There were several types of complications that differed significantly between center types.

Patients treated at NCI centers were significantly more likely to have leukapheresis (5.5% vs 2.7%; P<0.001) and renal failure (22.8% vs 19.9%; P=0.010).

But they were significantly less likely to have respiratory failure (11.6% vs 14.3%; P=0.003) and cardiac arrest (1.1% vs 2.0%; P=0.014).

Sixty-day survival was significantly higher among NCI patients (88.0% vs 76.3%; P<0.001).

In an inverse-probability-weighted analysis adjusted for sociodemographic factors and comorbidities, treatment at an NCI center was associated with significantly lower early mortality, with an odds ratio (OR) of 0.46 (P<0.001).

This analysis also revealed a significant association between increased early mortality and major bleeding (OR=1.79, P<0.001), renal failure (OR=2.33, P<0.001), respiratory failure (OR=6.46, P<0.001), and cardiac arrest (OR=13.33, P<0.001).

For the most part, the impact of complications on early mortality did not differ significantly by treatment center.

The exception was respiratory failure. Patients with respiratory failure had a significantly greater risk of early mortality if they were treated at a non-NCI center (OR=9.48) than at an NCI center (OR=4.20).

Potential explanations

The researchers believe the variations in early mortality they observed point to inconsistent supportive care. However, more work must be done to fully understand the differences in care driving these issues.

“This is clearly provocative data that makes you want to understand exactly why,” Dr Jonas said. “We’re going to have to dive into that question in a more significant way.”

In the absence of data that could identify the exact causes, the researchers noted that other studies have shown higher patient volumes may contribute to better care.

“I see 60 or more AML cases per year,” Dr Jonas said. “High volume/low volume must play a role.”

The researchers believe other potential contributing factors could be access to clinical trials, better nursing ratios, and more sophisticated intensive care units.

The team hopes this research will spawn more intensive efforts to identify the causes that underlie variations in early mortality between hospital sites.

“This is a provocative and hopeful paper in terms of improving outcomes,” Dr Jonas said. “It sends a positive message that there are things we could probably do that could help everyone.”

Photo by Sage Ross

Aspirin seems to be as effective as rivaroxaban for preventing venous thromboembolism (VTE) after total hip or knee replacement, according to research published in NEJM.

Researchers observed a similar incidence of VTE whether patients were randomized to receive aspirin or rivaroxaban prophylaxis starting 5 days after surgery, with all patients receiving rivaroxaban for the first 5 days after surgery.

There was no significant difference between the aspirin and rivaroxaban groups with regard to major bleeding or clinically important bleeding.

“We have always been very concerned about preventing blood clots in patients following major orthopedic surgery,” said study author David Zukor, MD, of Jewish General Hospital in Montreal, Quebec, Canada.

“It is the leading cause of preventable in-hospital death, so we always administer preventive therapy in conjunction with such surgeries. Rivaroxaban is known to be effective, but the great advantage of aspirin is that it is far less expensive, easily available, and has an excellent safety profile.”

Dr Zukor and his colleagues set out to compare aspirin and rivaroxaban in 3424 patients, 1804 who underwent hip replacement and 1620 who underwent knee replacement.

All patients took rivaroxaban (10 mg) for 5 days after surgery before being randomized to receive aspirin (81 mg daily, n=1707) or to continue with rivaroxaban (n=1717). The patients received this prophylaxis for an additional 9 days if they had knee replacement or for 30 days if they had hip replacement.

The researchers followed patients for 90 days, monitoring them for symptomatic VTE and major or clinically relevant nonmajor bleeding.

The rate of VTE was 0.64% (n=11) in the aspirin group and 0.70% (n=12) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], −0.55 to 0.66; P<0.001 for noninferiority, P=0.84 for superiority).

Major bleeding occurred in 0.47% (n=8) of patients in the aspirin group and in 0.29% (n=5) of those in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, −0.65 to 0.29; P=0.42).

Clinically relevant nonmajor bleeding occurred in 1.29% (n=22) and 0.99% (n=17), respectively (difference, 0.30 percentage points; 95% CI, −1.07 to 0.47; P=0.43).

All bleeding events occurred at the surgical site, and most occurred within 10 days of randomization.

“These results are important,” said study author Susan Kahn, MD, of McGill University in Montreal.

“The protocols for preventing clots following major orthopedic surgery are well established. However, we are always interested in determining whether there are better options for treating our patients. We could well see aspirin emerge as a practical alternative to more expensive anticoagulants.”

Drs Kahn and Zukor both noted the need for additional trials that would include a randomized group of patients prescribed aspirin exclusively so as to test its efficacy directly against rivaroxaban.

Photo by Sage Ross

Aspirin seems to be as effective as rivaroxaban for preventing venous thromboembolism (VTE) after total hip or knee replacement, according to research published in NEJM.

Researchers observed a similar incidence of VTE whether patients were randomized to receive aspirin or rivaroxaban prophylaxis starting 5 days after surgery, with all patients receiving rivaroxaban for the first 5 days after surgery.

There was no significant difference between the aspirin and rivaroxaban groups with regard to major bleeding or clinically important bleeding.

“We have always been very concerned about preventing blood clots in patients following major orthopedic surgery,” said study author David Zukor, MD, of Jewish General Hospital in Montreal, Quebec, Canada.

“It is the leading cause of preventable in-hospital death, so we always administer preventive therapy in conjunction with such surgeries. Rivaroxaban is known to be effective, but the great advantage of aspirin is that it is far less expensive, easily available, and has an excellent safety profile.”

Dr Zukor and his colleagues set out to compare aspirin and rivaroxaban in 3424 patients, 1804 who underwent hip replacement and 1620 who underwent knee replacement.

All patients took rivaroxaban (10 mg) for 5 days after surgery before being randomized to receive aspirin (81 mg daily, n=1707) or to continue with rivaroxaban (n=1717). The patients received this prophylaxis for an additional 9 days if they had knee replacement or for 30 days if they had hip replacement.

The researchers followed patients for 90 days, monitoring them for symptomatic VTE and major or clinically relevant nonmajor bleeding.

The rate of VTE was 0.64% (n=11) in the aspirin group and 0.70% (n=12) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], −0.55 to 0.66; P<0.001 for noninferiority, P=0.84 for superiority).

Major bleeding occurred in 0.47% (n=8) of patients in the aspirin group and in 0.29% (n=5) of those in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, −0.65 to 0.29; P=0.42).

Clinically relevant nonmajor bleeding occurred in 1.29% (n=22) and 0.99% (n=17), respectively (difference, 0.30 percentage points; 95% CI, −1.07 to 0.47; P=0.43).

All bleeding events occurred at the surgical site, and most occurred within 10 days of randomization.

“These results are important,” said study author Susan Kahn, MD, of McGill University in Montreal.

“The protocols for preventing clots following major orthopedic surgery are well established. However, we are always interested in determining whether there are better options for treating our patients. We could well see aspirin emerge as a practical alternative to more expensive anticoagulants.”

Drs Kahn and Zukor both noted the need for additional trials that would include a randomized group of patients prescribed aspirin exclusively so as to test its efficacy directly against rivaroxaban.

Photo by Sage Ross

Aspirin seems to be as effective as rivaroxaban for preventing venous thromboembolism (VTE) after total hip or knee replacement, according to research published in NEJM.

Researchers observed a similar incidence of VTE whether patients were randomized to receive aspirin or rivaroxaban prophylaxis starting 5 days after surgery, with all patients receiving rivaroxaban for the first 5 days after surgery.

There was no significant difference between the aspirin and rivaroxaban groups with regard to major bleeding or clinically important bleeding.

“We have always been very concerned about preventing blood clots in patients following major orthopedic surgery,” said study author David Zukor, MD, of Jewish General Hospital in Montreal, Quebec, Canada.

“It is the leading cause of preventable in-hospital death, so we always administer preventive therapy in conjunction with such surgeries. Rivaroxaban is known to be effective, but the great advantage of aspirin is that it is far less expensive, easily available, and has an excellent safety profile.”

Dr Zukor and his colleagues set out to compare aspirin and rivaroxaban in 3424 patients, 1804 who underwent hip replacement and 1620 who underwent knee replacement.

All patients took rivaroxaban (10 mg) for 5 days after surgery before being randomized to receive aspirin (81 mg daily, n=1707) or to continue with rivaroxaban (n=1717). The patients received this prophylaxis for an additional 9 days if they had knee replacement or for 30 days if they had hip replacement.

The researchers followed patients for 90 days, monitoring them for symptomatic VTE and major or clinically relevant nonmajor bleeding.

The rate of VTE was 0.64% (n=11) in the aspirin group and 0.70% (n=12) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], −0.55 to 0.66; P<0.001 for noninferiority, P=0.84 for superiority).

Major bleeding occurred in 0.47% (n=8) of patients in the aspirin group and in 0.29% (n=5) of those in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, −0.65 to 0.29; P=0.42).

Clinically relevant nonmajor bleeding occurred in 1.29% (n=22) and 0.99% (n=17), respectively (difference, 0.30 percentage points; 95% CI, −1.07 to 0.47; P=0.43).

All bleeding events occurred at the surgical site, and most occurred within 10 days of randomization.

“These results are important,” said study author Susan Kahn, MD, of McGill University in Montreal.

“The protocols for preventing clots following major orthopedic surgery are well established. However, we are always interested in determining whether there are better options for treating our patients. We could well see aspirin emerge as a practical alternative to more expensive anticoagulants.”

Drs Kahn and Zukor both noted the need for additional trials that would include a randomized group of patients prescribed aspirin exclusively so as to test its efficacy directly against rivaroxaban.

Photo courtesy of NIH

The US has similar healthcare utilization as other high-income countries but spends more and tends to have worse health outcomes, according to a new study.

In 2016, the US spent 17.8% of its gross domestic product on healthcare. For 10 other high-income countries, spending ranged from 9.6% to 12.4%.

However, sizes of physician and nursing workforces were comparable between the countries, numbers of hospital discharges were similar, and lengths of hospital stay were lower in the US than in most other countries.

Meanwhile, the US had the lowest life expectancy and the highest rate of infant mortality.

This research was published in JAMA.

“There’s been a lot of interest in international comparisons between America and other high-income countries, and there’s been a lot of vagueness about why exactly our [US] spending is so much higher and our health outcomes are not necessarily better and often worse,” said study author Ashish K. Jha, MD, of Harvard T. H. Chan School of Public Health in Boston, Massachusetts.

“This study really tries to fill in gaps, I think, across a wide range of issues, from structural capacity to utilization to prices to outcomes.”

For this study, Dr Jha and his colleagues analyzed recent healthcare data, primarily from 2013 to 2016. The team compared differences in healthcare spending, performance, and structural features between the US and 10 high-income countries—UK, Canada, Germany, Australia, Japan, Sweden, France, Netherlands, Switzerland, and Denmark.

Spending

In 2016, healthcare spending, as a percentage of gross domestic product, was as follows:

US—17.8%

Switzerland—12.4%

Sweden—11.9%

Germany—11.3%

France—11%

Japan—10.9%

Denmark—10.8%

Netherlands—10.5%

Canada—10.3%

UK—9.7%

Australia—9.6%.

“The big differences in spending really seem to be driven by prices,” Dr Jha said, noting that salaries for doctors and nurses, administrative expenditures, and pharmaceutical costs are “much higher” in the US.

The total spending on pharmaceuticals per capita was $1443 in the US but ranged from $466 (Netherlands) to $939 (Switzerland) in the other countries.

Administrative costs accounted for 8% of the total national health expenditure in the US but 1% (France, Japan) to 3% (Germany) in the other countries.

Outpatient care expenditures ranged from 22% (Netherlands) to 42% (US). Inpatient care expenditures ranged from 17% (Canada) to 32% (Netherlands), with 19% for the US. And expenditures for medical goods ranged from 10% (Denmark) to 20% (Germany), with the US at 14%.

Physicians’ and nurses’ salaries were higher in the US than other countries. For example, generalist physicians earned $218,173 in the US in 2016 but anywhere from $86,607 (Sweden) to $154,126 (Germany) in the other countries.

Utilization

Although US doctors and nurses earned more than their counterparts in comparator countries, there were no substantial between-country differences in the size of the physician and nursing workforces.

The number of working physicians for every 1000 people ranged from 2.1 (UK) to 4.3 (Switzerland), with the US at 2.6. The number of working nurses for every 1000 people ranged from 8.2 (UK) to 17.4 (Switzerland), with 11.1 for the US.

The US had comparable numbers of hospital beds as some of the other countries. The range was 2.5 (Sweden) to 13.2 (Japan) beds per 1000 people, with the US at 2.8.

The US ranked 6th when it came to hospital discharges for acute myocardial infarction (AMI, 192 per 100,000 people; range, 89 to 287), mental and behavioral issues (679 per 100,000 people; range, 119 to 1719), pneumonia (365 per 100,000 people; range, 187 to 567), and chronic obstructive pulmonary disease (230 per 100,000 people; range, 45 to 352).

The US had greater utilization of computed tomography than the other countries, with 245 examinations per 1000 people (range for other countries, 79 to 231). And US utilization of magnetic resonance imaging was higher than most countries, with 118 examinations per 1000 people (range, 41 to 131).

However, the US ranked on the lower end of the spectrum for length of hospital stay. The length of stay for a “normal delivery” childbirth ranged from a median of 1.5 days (UK) to 5.7 days (Japan), with the US clocking in at 2 days. The median length of stay for AMI ranged from a median of 3.9 days (Netherlands) to 10.3 days (Germany), with the US at 5.4 days.

“So much of the debate about healthcare these days is about over-utilization—that somehow our health system is uniquely bad at avoiding unnecessary services,” Dr Jha said. “I think these data really put that argument to rest. Except for a few pockets, utilization is not really different between us and these high-income Northern European countries, so maybe we need to spend a little less time focusing on that and a little bit more time focusing on prices of our healthcare system.”

Outcomes

The US ranked on the lower end of the spectrum for some mortality outcomes. Thirty-day stroke mortality per 1000 patients ranged from 4.2 in the US to 10 in Canada. Thirty-day AMI mortality per 1000 ranged from 4.1 (Australia) to 8.7 (Germany), with the US at 5.5.

However, infant mortality was highest in the US, at 5.8 deaths per 1000 live births (range for other countries, 2.1 to 5.1). And life expectancy was lowest in the US, at 78.8 years (range for other countries, 80.7 to 83.9).

The researchers noted that the US had the highest percentage of overweight or obese individuals age 15 and older, at 70.1% (range for other countries, 23.8% to 63.4%), but a low percentage of smokers (11.4%; range, 11.2% to 22.4%) and moderate alcohol consumption (8.8 L per capita; range, 7.2 to 11.9).

Limitations of this study include some differences in approaches to collecting and standardizing data across countries, as well as missing data for some countries.

Photo courtesy of NIH

The US has similar healthcare utilization as other high-income countries but spends more and tends to have worse health outcomes, according to a new study.

In 2016, the US spent 17.8% of its gross domestic product on healthcare. For 10 other high-income countries, spending ranged from 9.6% to 12.4%.

However, sizes of physician and nursing workforces were comparable between the countries, numbers of hospital discharges were similar, and lengths of hospital stay were lower in the US than in most other countries.

Meanwhile, the US had the lowest life expectancy and the highest rate of infant mortality.

This research was published in JAMA.

“There’s been a lot of interest in international comparisons between America and other high-income countries, and there’s been a lot of vagueness about why exactly our [US] spending is so much higher and our health outcomes are not necessarily better and often worse,” said study author Ashish K. Jha, MD, of Harvard T. H. Chan School of Public Health in Boston, Massachusetts.

“This study really tries to fill in gaps, I think, across a wide range of issues, from structural capacity to utilization to prices to outcomes.”

For this study, Dr Jha and his colleagues analyzed recent healthcare data, primarily from 2013 to 2016. The team compared differences in healthcare spending, performance, and structural features between the US and 10 high-income countries—UK, Canada, Germany, Australia, Japan, Sweden, France, Netherlands, Switzerland, and Denmark.

Spending

In 2016, healthcare spending, as a percentage of gross domestic product, was as follows:

US—17.8%

Switzerland—12.4%

Sweden—11.9%

Germany—11.3%

France—11%

Japan—10.9%

Denmark—10.8%

Netherlands—10.5%

Canada—10.3%

UK—9.7%

Australia—9.6%.

“The big differences in spending really seem to be driven by prices,” Dr Jha said, noting that salaries for doctors and nurses, administrative expenditures, and pharmaceutical costs are “much higher” in the US.

The total spending on pharmaceuticals per capita was $1443 in the US but ranged from $466 (Netherlands) to $939 (Switzerland) in the other countries.

Administrative costs accounted for 8% of the total national health expenditure in the US but 1% (France, Japan) to 3% (Germany) in the other countries.

Outpatient care expenditures ranged from 22% (Netherlands) to 42% (US). Inpatient care expenditures ranged from 17% (Canada) to 32% (Netherlands), with 19% for the US. And expenditures for medical goods ranged from 10% (Denmark) to 20% (Germany), with the US at 14%.

Physicians’ and nurses’ salaries were higher in the US than other countries. For example, generalist physicians earned $218,173 in the US in 2016 but anywhere from $86,607 (Sweden) to $154,126 (Germany) in the other countries.

Utilization

Although US doctors and nurses earned more than their counterparts in comparator countries, there were no substantial between-country differences in the size of the physician and nursing workforces.

The number of working physicians for every 1000 people ranged from 2.1 (UK) to 4.3 (Switzerland), with the US at 2.6. The number of working nurses for every 1000 people ranged from 8.2 (UK) to 17.4 (Switzerland), with 11.1 for the US.

The US had comparable numbers of hospital beds as some of the other countries. The range was 2.5 (Sweden) to 13.2 (Japan) beds per 1000 people, with the US at 2.8.

The US ranked 6th when it came to hospital discharges for acute myocardial infarction (AMI, 192 per 100,000 people; range, 89 to 287), mental and behavioral issues (679 per 100,000 people; range, 119 to 1719), pneumonia (365 per 100,000 people; range, 187 to 567), and chronic obstructive pulmonary disease (230 per 100,000 people; range, 45 to 352).

The US had greater utilization of computed tomography than the other countries, with 245 examinations per 1000 people (range for other countries, 79 to 231). And US utilization of magnetic resonance imaging was higher than most countries, with 118 examinations per 1000 people (range, 41 to 131).

However, the US ranked on the lower end of the spectrum for length of hospital stay. The length of stay for a “normal delivery” childbirth ranged from a median of 1.5 days (UK) to 5.7 days (Japan), with the US clocking in at 2 days. The median length of stay for AMI ranged from a median of 3.9 days (Netherlands) to 10.3 days (Germany), with the US at 5.4 days.

“So much of the debate about healthcare these days is about over-utilization—that somehow our health system is uniquely bad at avoiding unnecessary services,” Dr Jha said. “I think these data really put that argument to rest. Except for a few pockets, utilization is not really different between us and these high-income Northern European countries, so maybe we need to spend a little less time focusing on that and a little bit more time focusing on prices of our healthcare system.”

Outcomes

The US ranked on the lower end of the spectrum for some mortality outcomes. Thirty-day stroke mortality per 1000 patients ranged from 4.2 in the US to 10 in Canada. Thirty-day AMI mortality per 1000 ranged from 4.1 (Australia) to 8.7 (Germany), with the US at 5.5.

However, infant mortality was highest in the US, at 5.8 deaths per 1000 live births (range for other countries, 2.1 to 5.1). And life expectancy was lowest in the US, at 78.8 years (range for other countries, 80.7 to 83.9).

The researchers noted that the US had the highest percentage of overweight or obese individuals age 15 and older, at 70.1% (range for other countries, 23.8% to 63.4%), but a low percentage of smokers (11.4%; range, 11.2% to 22.4%) and moderate alcohol consumption (8.8 L per capita; range, 7.2 to 11.9).

Limitations of this study include some differences in approaches to collecting and standardizing data across countries, as well as missing data for some countries.

Photo courtesy of NIH

The US has similar healthcare utilization as other high-income countries but spends more and tends to have worse health outcomes, according to a new study.

In 2016, the US spent 17.8% of its gross domestic product on healthcare. For 10 other high-income countries, spending ranged from 9.6% to 12.4%.

However, sizes of physician and nursing workforces were comparable between the countries, numbers of hospital discharges were similar, and lengths of hospital stay were lower in the US than in most other countries.

Meanwhile, the US had the lowest life expectancy and the highest rate of infant mortality.

This research was published in JAMA.

“There’s been a lot of interest in international comparisons between America and other high-income countries, and there’s been a lot of vagueness about why exactly our [US] spending is so much higher and our health outcomes are not necessarily better and often worse,” said study author Ashish K. Jha, MD, of Harvard T. H. Chan School of Public Health in Boston, Massachusetts.

“This study really tries to fill in gaps, I think, across a wide range of issues, from structural capacity to utilization to prices to outcomes.”

For this study, Dr Jha and his colleagues analyzed recent healthcare data, primarily from 2013 to 2016. The team compared differences in healthcare spending, performance, and structural features between the US and 10 high-income countries—UK, Canada, Germany, Australia, Japan, Sweden, France, Netherlands, Switzerland, and Denmark.

Spending

In 2016, healthcare spending, as a percentage of gross domestic product, was as follows:

US—17.8%

Switzerland—12.4%

Sweden—11.9%

Germany—11.3%

France—11%

Japan—10.9%

Denmark—10.8%

Netherlands—10.5%

Canada—10.3%

UK—9.7%

Australia—9.6%.

“The big differences in spending really seem to be driven by prices,” Dr Jha said, noting that salaries for doctors and nurses, administrative expenditures, and pharmaceutical costs are “much higher” in the US.

The total spending on pharmaceuticals per capita was $1443 in the US but ranged from $466 (Netherlands) to $939 (Switzerland) in the other countries.

Administrative costs accounted for 8% of the total national health expenditure in the US but 1% (France, Japan) to 3% (Germany) in the other countries.

Outpatient care expenditures ranged from 22% (Netherlands) to 42% (US). Inpatient care expenditures ranged from 17% (Canada) to 32% (Netherlands), with 19% for the US. And expenditures for medical goods ranged from 10% (Denmark) to 20% (Germany), with the US at 14%.

Physicians’ and nurses’ salaries were higher in the US than other countries. For example, generalist physicians earned $218,173 in the US in 2016 but anywhere from $86,607 (Sweden) to $154,126 (Germany) in the other countries.

Utilization

Although US doctors and nurses earned more than their counterparts in comparator countries, there were no substantial between-country differences in the size of the physician and nursing workforces.

The number of working physicians for every 1000 people ranged from 2.1 (UK) to 4.3 (Switzerland), with the US at 2.6. The number of working nurses for every 1000 people ranged from 8.2 (UK) to 17.4 (Switzerland), with 11.1 for the US.

The US had comparable numbers of hospital beds as some of the other countries. The range was 2.5 (Sweden) to 13.2 (Japan) beds per 1000 people, with the US at 2.8.

The US ranked 6th when it came to hospital discharges for acute myocardial infarction (AMI, 192 per 100,000 people; range, 89 to 287), mental and behavioral issues (679 per 100,000 people; range, 119 to 1719), pneumonia (365 per 100,000 people; range, 187 to 567), and chronic obstructive pulmonary disease (230 per 100,000 people; range, 45 to 352).

The US had greater utilization of computed tomography than the other countries, with 245 examinations per 1000 people (range for other countries, 79 to 231). And US utilization of magnetic resonance imaging was higher than most countries, with 118 examinations per 1000 people (range, 41 to 131).

However, the US ranked on the lower end of the spectrum for length of hospital stay. The length of stay for a “normal delivery” childbirth ranged from a median of 1.5 days (UK) to 5.7 days (Japan), with the US clocking in at 2 days. The median length of stay for AMI ranged from a median of 3.9 days (Netherlands) to 10.3 days (Germany), with the US at 5.4 days.

“So much of the debate about healthcare these days is about over-utilization—that somehow our health system is uniquely bad at avoiding unnecessary services,” Dr Jha said. “I think these data really put that argument to rest. Except for a few pockets, utilization is not really different between us and these high-income Northern European countries, so maybe we need to spend a little less time focusing on that and a little bit more time focusing on prices of our healthcare system.”

Outcomes

The US ranked on the lower end of the spectrum for some mortality outcomes. Thirty-day stroke mortality per 1000 patients ranged from 4.2 in the US to 10 in Canada. Thirty-day AMI mortality per 1000 ranged from 4.1 (Australia) to 8.7 (Germany), with the US at 5.5.

However, infant mortality was highest in the US, at 5.8 deaths per 1000 live births (range for other countries, 2.1 to 5.1). And life expectancy was lowest in the US, at 78.8 years (range for other countries, 80.7 to 83.9).

The researchers noted that the US had the highest percentage of overweight or obese individuals age 15 and older, at 70.1% (range for other countries, 23.8% to 63.4%), but a low percentage of smokers (11.4%; range, 11.2% to 22.4%) and moderate alcohol consumption (8.8 L per capita; range, 7.2 to 11.9).

Limitations of this study include some differences in approaches to collecting and standardizing data across countries, as well as missing data for some countries.