Hospital of Philadelphia

A novel approach can restore hematopoietic stem cell (HSC) function in Fanconi anemia (FA), according to preclinical research published in Nature Communications.

The investigators showed that Lnk (Sh2b3) deficiency restores HSC proliferation and survival in Fancd2-deficient mice.

And it does so, in part, by alleviating blocks to cytokine-mediated JAK2 signaling.

These findings, the researchers wrote, “highlight a new role for cytokine/JAK signaling” and have therapeutic implications for FA.

The investigators noted that FA is caused by mutations in genes that are essential for DNA interstrand crosslink repair and replication stress tolerance.

Allogeneic transplant can replace defective HSCs in patients with FA, the researchers said, but there are no interventions that mitigate defects in HSCs. So the investigators decided to test whether Lnk deficiency ameliorates HSC defects in FA.

Using a model of FA in which mice lacked Fancd2, the researchers inhibited the regulatory protein Sh2b3/Lnk.

The investigators said Lnk deficiency restored the proliferation and survival of Fancd2⁻/⁻ HSCs while also reducing replication stress and genomic instability. Lnk deficiency did not, however, affect DNA interstrand crosslink repair.

“We expected that inhibiting Lnk would restore the ability of FA cells to repair DNA damage, but this was not the case,” said study author Wei Tong, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.

“Instead, inhibiting Lnk stabilized the stalled replication machinery, allowing affected cells to continue to copy DNA, and to prevent small errors from cascading into a catastrophic failure. The most exciting aspect of this discovery is that Lnk is part of a well-known growth pathway that can be manipulated by existing drugs in other diseases.”

That pathway is the TPO/MPL/JAK2 pathway, which is already targeted by eltrombopag and romiplostin for immune thrombocytopenia and eltrombopag for aplastic anemia.

The researchers plan to continue their work with animal models of FA and Lnk.

“Our ultimate goal is to translate our knowledge into treatments for both Fanconi anemia and for the broader problem of bone marrow failure,” Dr. Tong said.

This research was supported by the National Institutes of Health, the Fanconi Anemia Research Fund, the Department of Defense, the Basser Center for BRCA Team Science Grant, the Leukemia Lymphoma Society Scholar Award, and the Patel Family Award.

The researchers declared no competing interests.

Hospital of Philadelphia

A novel approach can restore hematopoietic stem cell (HSC) function in Fanconi anemia (FA), according to preclinical research published in Nature Communications.

The investigators showed that Lnk (Sh2b3) deficiency restores HSC proliferation and survival in Fancd2-deficient mice.

And it does so, in part, by alleviating blocks to cytokine-mediated JAK2 signaling.

These findings, the researchers wrote, “highlight a new role for cytokine/JAK signaling” and have therapeutic implications for FA.

The investigators noted that FA is caused by mutations in genes that are essential for DNA interstrand crosslink repair and replication stress tolerance.

Allogeneic transplant can replace defective HSCs in patients with FA, the researchers said, but there are no interventions that mitigate defects in HSCs. So the investigators decided to test whether Lnk deficiency ameliorates HSC defects in FA.

Using a model of FA in which mice lacked Fancd2, the researchers inhibited the regulatory protein Sh2b3/Lnk.

The investigators said Lnk deficiency restored the proliferation and survival of Fancd2⁻/⁻ HSCs while also reducing replication stress and genomic instability. Lnk deficiency did not, however, affect DNA interstrand crosslink repair.

“We expected that inhibiting Lnk would restore the ability of FA cells to repair DNA damage, but this was not the case,” said study author Wei Tong, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.

“Instead, inhibiting Lnk stabilized the stalled replication machinery, allowing affected cells to continue to copy DNA, and to prevent small errors from cascading into a catastrophic failure. The most exciting aspect of this discovery is that Lnk is part of a well-known growth pathway that can be manipulated by existing drugs in other diseases.”

That pathway is the TPO/MPL/JAK2 pathway, which is already targeted by eltrombopag and romiplostin for immune thrombocytopenia and eltrombopag for aplastic anemia.

The researchers plan to continue their work with animal models of FA and Lnk.

“Our ultimate goal is to translate our knowledge into treatments for both Fanconi anemia and for the broader problem of bone marrow failure,” Dr. Tong said.

This research was supported by the National Institutes of Health, the Fanconi Anemia Research Fund, the Department of Defense, the Basser Center for BRCA Team Science Grant, the Leukemia Lymphoma Society Scholar Award, and the Patel Family Award.

The researchers declared no competing interests.

Hospital of Philadelphia

A novel approach can restore hematopoietic stem cell (HSC) function in Fanconi anemia (FA), according to preclinical research published in Nature Communications.

The investigators showed that Lnk (Sh2b3) deficiency restores HSC proliferation and survival in Fancd2-deficient mice.

And it does so, in part, by alleviating blocks to cytokine-mediated JAK2 signaling.

These findings, the researchers wrote, “highlight a new role for cytokine/JAK signaling” and have therapeutic implications for FA.

The investigators noted that FA is caused by mutations in genes that are essential for DNA interstrand crosslink repair and replication stress tolerance.

Allogeneic transplant can replace defective HSCs in patients with FA, the researchers said, but there are no interventions that mitigate defects in HSCs. So the investigators decided to test whether Lnk deficiency ameliorates HSC defects in FA.

Using a model of FA in which mice lacked Fancd2, the researchers inhibited the regulatory protein Sh2b3/Lnk.

The investigators said Lnk deficiency restored the proliferation and survival of Fancd2⁻/⁻ HSCs while also reducing replication stress and genomic instability. Lnk deficiency did not, however, affect DNA interstrand crosslink repair.

“We expected that inhibiting Lnk would restore the ability of FA cells to repair DNA damage, but this was not the case,” said study author Wei Tong, PhD, of Children’s Hospital of Philadelphia in Pennsylvania.

“Instead, inhibiting Lnk stabilized the stalled replication machinery, allowing affected cells to continue to copy DNA, and to prevent small errors from cascading into a catastrophic failure. The most exciting aspect of this discovery is that Lnk is part of a well-known growth pathway that can be manipulated by existing drugs in other diseases.”

That pathway is the TPO/MPL/JAK2 pathway, which is already targeted by eltrombopag and romiplostin for immune thrombocytopenia and eltrombopag for aplastic anemia.

The researchers plan to continue their work with animal models of FA and Lnk.

“Our ultimate goal is to translate our knowledge into treatments for both Fanconi anemia and for the broader problem of bone marrow failure,” Dr. Tong said.

This research was supported by the National Institutes of Health, the Fanconi Anemia Research Fund, the Department of Defense, the Basser Center for BRCA Team Science Grant, the Leukemia Lymphoma Society Scholar Award, and the Patel Family Award.

The researchers declared no competing interests.

Photo by Sage Ross

Putting patients on aspirin following a knee replacement is a safe, cost-effective alternative to treatment with anticoagulants, according to researchers.

A study of more than 40,000 patients revealed a similar incidence of venous thromboembolism (VTE) or death after total knee arthroplasty (TKA) in patients receiving aspirin and patients receiving anticoagulants.

“Aspirin alone may provide similar protection compared to anticoagulation treatments,” said Brian R. Hallstrom, MD, of the University of Michigan in Ann Arbor.

He and his colleagues compared aspirin to anticoagulants after TKA and detailed their findings in JAMA Surgery.

The researchers evaluated 41,537 patients who underwent TKA and received:

• No pharmacological VTE prophylaxis (n=668; 1.6%)
• Aspirin only (n=12,831; 30.9%)
• Only an anticoagulant (n=22,620; 54.5%)
• Both aspirin and an anticoagulant (n=5418; 13.0%).

Anticoagulants included low-molecular-weight heparin, warfarin, and factor Xa inhibitors.

About 87% of all patients (n=36,113) were also using intermittent pneumatic compression stockings.

Safety and efficacy

The study’s primary outcome was a composite of VTE and death. It occurred in:

• 4.79% (32/668) of patients not on pharmacological prophylaxis
• 1.16% (149/12,831) of patients who received aspirin alone
• 1.42% (321/22,620) of patients on anticoagulation alone
• 1.31% (71/5418) of patients who received both aspirin and anticoagulation.

In a multivariable analysis adjusted for confounding, aspirin was noninferior to the other prophylaxis regimens for the outcome of VTE or death. The adjusted odds ratio was 0.85 (P=0.007).

Bleeding was a secondary outcome of this study, and it occurred in:

• 1.50% (10/668) of patients not on pharmacological prophylaxis
• 0.90% (116/12,831) of patients who received aspirin alone
• 1.14% (258/22,620) of patients who received anticoagulation
• 1.35% (73/5,418) of patients who received both aspirin and anticoagulation.

In an adjusted analysis, aspirin was noninferior to the other prophylaxis regimens for the outcome of bleeding. The adjusted odds ratio was 0.80 (P<0.001).

Other benefits

Aspirin provides other benefits aside from similar safety and efficacy as anticoagulants, according to the researchers.

“Aspirin is easy to take and much less expensive,” Dr. Hallstrom noted. “Patients can get it over the counter for pennies, while the other anticoagulants require monitoring, injections, frequent dose adjustments and are extremely expensive.”

Dr. Hallstrom and his colleagues said the reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450, and the estimated cost of heparin is $450 to $890.

Although warfarin costs a few dollars for a 30-day supply, its cost approaches that of the other anticoagulants when doctor visits for monitoring are factored in, the researchers noted.

In contrast, aspirin costs approximately $2 a month.

Dr. Hallstrom and his colleagues did note that, although this study suggests aspirin can prevent VTE as well as anticoagulants, doctors need to consider factors such as a patient’s history of clots, obesity, and ability to mobilize after surgery.

Photo by Sage Ross

Putting patients on aspirin following a knee replacement is a safe, cost-effective alternative to treatment with anticoagulants, according to researchers.

A study of more than 40,000 patients revealed a similar incidence of venous thromboembolism (VTE) or death after total knee arthroplasty (TKA) in patients receiving aspirin and patients receiving anticoagulants.

“Aspirin alone may provide similar protection compared to anticoagulation treatments,” said Brian R. Hallstrom, MD, of the University of Michigan in Ann Arbor.

He and his colleagues compared aspirin to anticoagulants after TKA and detailed their findings in JAMA Surgery.

The researchers evaluated 41,537 patients who underwent TKA and received:

• No pharmacological VTE prophylaxis (n=668; 1.6%)
• Aspirin only (n=12,831; 30.9%)
• Only an anticoagulant (n=22,620; 54.5%)
• Both aspirin and an anticoagulant (n=5418; 13.0%).

Anticoagulants included low-molecular-weight heparin, warfarin, and factor Xa inhibitors.

About 87% of all patients (n=36,113) were also using intermittent pneumatic compression stockings.

Safety and efficacy

The study’s primary outcome was a composite of VTE and death. It occurred in:

• 4.79% (32/668) of patients not on pharmacological prophylaxis
• 1.16% (149/12,831) of patients who received aspirin alone
• 1.42% (321/22,620) of patients on anticoagulation alone
• 1.31% (71/5418) of patients who received both aspirin and anticoagulation.

In a multivariable analysis adjusted for confounding, aspirin was noninferior to the other prophylaxis regimens for the outcome of VTE or death. The adjusted odds ratio was 0.85 (P=0.007).

Bleeding was a secondary outcome of this study, and it occurred in:

• 1.50% (10/668) of patients not on pharmacological prophylaxis
• 0.90% (116/12,831) of patients who received aspirin alone
• 1.14% (258/22,620) of patients who received anticoagulation
• 1.35% (73/5,418) of patients who received both aspirin and anticoagulation.

In an adjusted analysis, aspirin was noninferior to the other prophylaxis regimens for the outcome of bleeding. The adjusted odds ratio was 0.80 (P<0.001).

Other benefits

Aspirin provides other benefits aside from similar safety and efficacy as anticoagulants, according to the researchers.

“Aspirin is easy to take and much less expensive,” Dr. Hallstrom noted. “Patients can get it over the counter for pennies, while the other anticoagulants require monitoring, injections, frequent dose adjustments and are extremely expensive.”

Dr. Hallstrom and his colleagues said the reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450, and the estimated cost of heparin is $450 to $890.

Although warfarin costs a few dollars for a 30-day supply, its cost approaches that of the other anticoagulants when doctor visits for monitoring are factored in, the researchers noted.

In contrast, aspirin costs approximately $2 a month.

Dr. Hallstrom and his colleagues did note that, although this study suggests aspirin can prevent VTE as well as anticoagulants, doctors need to consider factors such as a patient’s history of clots, obesity, and ability to mobilize after surgery.

Photo by Sage Ross

Putting patients on aspirin following a knee replacement is a safe, cost-effective alternative to treatment with anticoagulants, according to researchers.

A study of more than 40,000 patients revealed a similar incidence of venous thromboembolism (VTE) or death after total knee arthroplasty (TKA) in patients receiving aspirin and patients receiving anticoagulants.

“Aspirin alone may provide similar protection compared to anticoagulation treatments,” said Brian R. Hallstrom, MD, of the University of Michigan in Ann Arbor.

He and his colleagues compared aspirin to anticoagulants after TKA and detailed their findings in JAMA Surgery.

The researchers evaluated 41,537 patients who underwent TKA and received:

• No pharmacological VTE prophylaxis (n=668; 1.6%)
• Aspirin only (n=12,831; 30.9%)
• Only an anticoagulant (n=22,620; 54.5%)
• Both aspirin and an anticoagulant (n=5418; 13.0%).

Anticoagulants included low-molecular-weight heparin, warfarin, and factor Xa inhibitors.

About 87% of all patients (n=36,113) were also using intermittent pneumatic compression stockings.

Safety and efficacy

The study’s primary outcome was a composite of VTE and death. It occurred in:

• 4.79% (32/668) of patients not on pharmacological prophylaxis
• 1.16% (149/12,831) of patients who received aspirin alone
• 1.42% (321/22,620) of patients on anticoagulation alone
• 1.31% (71/5418) of patients who received both aspirin and anticoagulation.

In a multivariable analysis adjusted for confounding, aspirin was noninferior to the other prophylaxis regimens for the outcome of VTE or death. The adjusted odds ratio was 0.85 (P=0.007).

Bleeding was a secondary outcome of this study, and it occurred in:

• 1.50% (10/668) of patients not on pharmacological prophylaxis
• 0.90% (116/12,831) of patients who received aspirin alone
• 1.14% (258/22,620) of patients who received anticoagulation
• 1.35% (73/5,418) of patients who received both aspirin and anticoagulation.

In an adjusted analysis, aspirin was noninferior to the other prophylaxis regimens for the outcome of bleeding. The adjusted odds ratio was 0.80 (P<0.001).

Other benefits

Aspirin provides other benefits aside from similar safety and efficacy as anticoagulants, according to the researchers.

“Aspirin is easy to take and much less expensive,” Dr. Hallstrom noted. “Patients can get it over the counter for pennies, while the other anticoagulants require monitoring, injections, frequent dose adjustments and are extremely expensive.”

Dr. Hallstrom and his colleagues said the reported cost for a 30-day supply of rivaroxaban is approximately $379 to $450, and the estimated cost of heparin is $450 to $890.

Although warfarin costs a few dollars for a 30-day supply, its cost approaches that of the other anticoagulants when doctor visits for monitoring are factored in, the researchers noted.

In contrast, aspirin costs approximately $2 a month.

Dr. Hallstrom and his colleagues did note that, although this study suggests aspirin can prevent VTE as well as anticoagulants, doctors need to consider factors such as a patient’s history of clots, obesity, and ability to mobilize after surgery.

Photo by Chad McNeeley

The U.S. Food and Drug Administration (FDA) has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.

Omeros Corporation, the company developing OMS721, has established a compassionate-use program for OMS721, which is active in the United States and Europe.

Clinical trials

Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721—one in TMA and one in immunoglobulin A nephropathy—are ongoing.

Omeros released results from the phase 2 TMA trial (NCT02222545) in February.

The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. Patients receive weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.

At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated on this study.

These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P=0.017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).

Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.

The most commonly reported adverse events were diarrhea and neutropenia.

Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721. The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).

About orphan and breakthrough designations

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

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.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo by Chad McNeeley

The U.S. Food and Drug Administration (FDA) has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.

Omeros Corporation, the company developing OMS721, has established a compassionate-use program for OMS721, which is active in the United States and Europe.

Clinical trials

Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721—one in TMA and one in immunoglobulin A nephropathy—are ongoing.

Omeros released results from the phase 2 TMA trial (NCT02222545) in February.

The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. Patients receive weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.

At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated on this study.

These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P=0.017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).

Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.

The most commonly reported adverse events were diarrhea and neutropenia.

Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721. The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).

About orphan and breakthrough designations

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

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.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo by Chad McNeeley

The U.S. Food and Drug Administration (FDA) has granted OMS721 orphan designation for the treatment of hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The FDA previously granted OMS721 breakthrough therapy designation for HSCT-TMA and orphan designation for the prevention of complement-mediated TMA, including HSCT-TMA.

Omeros Corporation, the company developing OMS721, has established a compassionate-use program for OMS721, which is active in the United States and Europe.

Clinical trials

Phase 3 clinical programs are in progress for OMS721 in atypical hemolytic uremic syndrome, immunoglobulin A nephropathy, and HSCT-TMA. Two phase 2 trials of OMS721—one in TMA and one in immunoglobulin A nephropathy—are ongoing.

Omeros released results from the phase 2 TMA trial (NCT02222545) in February.

The study includes adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. Patients receive weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.

At the time of Omeros’s announcement, 18 HSCT-TMA patients had been treated on this study.

These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P=0.017). The mean lactate dehydrogenase decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).

Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.

The most commonly reported adverse events were diarrhea and neutropenia.

Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721. The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).

About orphan and breakthrough designations

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

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.

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

A new diagnostic test that can help clinicians ascertain a patient’s menopausal status has been approved for marketing by the Food and Drug Administration.

The PicoAMH Elisa diagnostic test measures circulating levels of anti-Müllerian hormone (AMH), a granulosa cell product in ovaries that is present only until menopause. In research settings, AMH levels have been used to predict menopause and to confirm the occurrence of menopause; levels have been shown to track well with antral follicle count (J Clin Endocrinol Metab. 2011 Aug 1;96[8]:2532-9).

“Diagnostic results about a woman’s menopausal status may prompt discussions about preventative care for women experiencing menopausal symptoms,” Courtney H. Lias, PhD, director of the division of chemistry and toxicology devices in the FDA’s Center for Devices and Radiological Health, said in a press release announcing the marketing permission. “This test, when used in conjunction with other clinical assessments and laboratory findings, can help inform discussions about preventative care, such as ways to help prevent loss in bone mineral density or to address cardiovascular disease, both of which are known to increase after menopause.”

As Dr. Lias emphasized, the new test is designed to be used along with a thorough clinical assessment and other laboratory tests. Having a reliable test for circulating AMH for clinical use allows measurement of a hormone that, unlike follicle stimulating hormone and luteinizing hormone, does not fluctuate throughout the menstrual cycle for premenopausal women.

JoAnn Pinkerton, MD, executive director of the North American Menopause Society, provided clinical context about the utility of the new assay. “AMH levels appear to provide valuable information about timing of menopause. While not needed for women undergoing a natural menopause at age 51, it will be very helpful for women at risk of early ovarian failure, such as following chemotherapy for cancer or genetic or endocrine reasons,” said Dr. Pinkerton. “Women desiring pregnancy who are skipping periods can be more reassured if their AMH is normal, as studies suggest, that AMH is highly predictive of timing of menopause.”*

In permitting marketing of the PicoAMH Elisa assay, the FDA looked at data drawn from the Study of Women’s Health Across the Nation. For 690 women aged 42-62 years, “the PicoAMH Elisa test performed reasonably well at determining levels of AMH in the blood,” the FDA said in the press release. The test also was able to identify women who had already had their last menstrual period, and to determine women who were at least 5 years away from stopping menstruation, according to the longitudinal study.

The PicoAMH Elisa test will be marketed by Ansh Labs. Since the device’s review went through a de novo premarket pathway designed for novel devices of low to medium risk, there will be an additional set of criteria, called special controls, put in place to monitor the safety and effectiveness of the test.

*This article was updated on 10/26/2018.

A new diagnostic test that can help clinicians ascertain a patient’s menopausal status has been approved for marketing by the Food and Drug Administration.

The PicoAMH Elisa diagnostic test measures circulating levels of anti-Müllerian hormone (AMH), a granulosa cell product in ovaries that is present only until menopause. In research settings, AMH levels have been used to predict menopause and to confirm the occurrence of menopause; levels have been shown to track well with antral follicle count (J Clin Endocrinol Metab. 2011 Aug 1;96[8]:2532-9).

“Diagnostic results about a woman’s menopausal status may prompt discussions about preventative care for women experiencing menopausal symptoms,” Courtney H. Lias, PhD, director of the division of chemistry and toxicology devices in the FDA’s Center for Devices and Radiological Health, said in a press release announcing the marketing permission. “This test, when used in conjunction with other clinical assessments and laboratory findings, can help inform discussions about preventative care, such as ways to help prevent loss in bone mineral density or to address cardiovascular disease, both of which are known to increase after menopause.”

As Dr. Lias emphasized, the new test is designed to be used along with a thorough clinical assessment and other laboratory tests. Having a reliable test for circulating AMH for clinical use allows measurement of a hormone that, unlike follicle stimulating hormone and luteinizing hormone, does not fluctuate throughout the menstrual cycle for premenopausal women.

JoAnn Pinkerton, MD, executive director of the North American Menopause Society, provided clinical context about the utility of the new assay. “AMH levels appear to provide valuable information about timing of menopause. While not needed for women undergoing a natural menopause at age 51, it will be very helpful for women at risk of early ovarian failure, such as following chemotherapy for cancer or genetic or endocrine reasons,” said Dr. Pinkerton. “Women desiring pregnancy who are skipping periods can be more reassured if their AMH is normal, as studies suggest, that AMH is highly predictive of timing of menopause.”*

In permitting marketing of the PicoAMH Elisa assay, the FDA looked at data drawn from the Study of Women’s Health Across the Nation. For 690 women aged 42-62 years, “the PicoAMH Elisa test performed reasonably well at determining levels of AMH in the blood,” the FDA said in the press release. The test also was able to identify women who had already had their last menstrual period, and to determine women who were at least 5 years away from stopping menstruation, according to the longitudinal study.

The PicoAMH Elisa test will be marketed by Ansh Labs. Since the device’s review went through a de novo premarket pathway designed for novel devices of low to medium risk, there will be an additional set of criteria, called special controls, put in place to monitor the safety and effectiveness of the test.

*This article was updated on 10/26/2018.

A new diagnostic test that can help clinicians ascertain a patient’s menopausal status has been approved for marketing by the Food and Drug Administration.

The PicoAMH Elisa diagnostic test measures circulating levels of anti-Müllerian hormone (AMH), a granulosa cell product in ovaries that is present only until menopause. In research settings, AMH levels have been used to predict menopause and to confirm the occurrence of menopause; levels have been shown to track well with antral follicle count (J Clin Endocrinol Metab. 2011 Aug 1;96[8]:2532-9).

“Diagnostic results about a woman’s menopausal status may prompt discussions about preventative care for women experiencing menopausal symptoms,” Courtney H. Lias, PhD, director of the division of chemistry and toxicology devices in the FDA’s Center for Devices and Radiological Health, said in a press release announcing the marketing permission. “This test, when used in conjunction with other clinical assessments and laboratory findings, can help inform discussions about preventative care, such as ways to help prevent loss in bone mineral density or to address cardiovascular disease, both of which are known to increase after menopause.”

As Dr. Lias emphasized, the new test is designed to be used along with a thorough clinical assessment and other laboratory tests. Having a reliable test for circulating AMH for clinical use allows measurement of a hormone that, unlike follicle stimulating hormone and luteinizing hormone, does not fluctuate throughout the menstrual cycle for premenopausal women.

JoAnn Pinkerton, MD, executive director of the North American Menopause Society, provided clinical context about the utility of the new assay. “AMH levels appear to provide valuable information about timing of menopause. While not needed for women undergoing a natural menopause at age 51, it will be very helpful for women at risk of early ovarian failure, such as following chemotherapy for cancer or genetic or endocrine reasons,” said Dr. Pinkerton. “Women desiring pregnancy who are skipping periods can be more reassured if their AMH is normal, as studies suggest, that AMH is highly predictive of timing of menopause.”*

In permitting marketing of the PicoAMH Elisa assay, the FDA looked at data drawn from the Study of Women’s Health Across the Nation. For 690 women aged 42-62 years, “the PicoAMH Elisa test performed reasonably well at determining levels of AMH in the blood,” the FDA said in the press release. The test also was able to identify women who had already had their last menstrual period, and to determine women who were at least 5 years away from stopping menstruation, according to the longitudinal study.

The PicoAMH Elisa test will be marketed by Ansh Labs. Since the device’s review went through a de novo premarket pathway designed for novel devices of low to medium risk, there will be an additional set of criteria, called special controls, put in place to monitor the safety and effectiveness of the test.

*This article was updated on 10/26/2018.

Why wire-dependent fractional flow reserve may soon be obsolete; stroke risk after a myocardial infarction goes on three times longer than previously thought; poststroke dual-antiplatelet therapy should be cut short; and emergency departments are seeing results from greater use of high-sensitivity troponin T in chest pain patients.

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Why wire-dependent fractional flow reserve may soon be obsolete; stroke risk after a myocardial infarction goes on three times longer than previously thought; poststroke dual-antiplatelet therapy should be cut short; and emergency departments are seeing results from greater use of high-sensitivity troponin T in chest pain patients.

Subscribe to Cardiocast wherever you get your podcasts:
Amazon Alexa
Apple Podcasts

Why wire-dependent fractional flow reserve may soon be obsolete; stroke risk after a myocardial infarction goes on three times longer than previously thought; poststroke dual-antiplatelet therapy should be cut short; and emergency departments are seeing results from greater use of high-sensitivity troponin T in chest pain patients.

Subscribe to Cardiocast wherever you get your podcasts:
Amazon Alexa
Apple Podcasts

Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.

Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.

“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”

In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.

The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.

For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.

The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.

“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.

The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.

“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.

The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.

SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.

Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.

Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.

“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”

In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.

The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.

For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.

The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.

“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.

The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.

“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.

The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.

SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.

Concerns may be unfounded for risks of earlier-onset cardiovascular disease in men with hemophilia A, according to investigators.

Cardiovascular comorbidities between groups were generally comparable, regardless of hemophilia A status, reported lead author Thomas J. Humphries, MD, of Bayer, and his colleagues.

“To date, there have been conflicting data in the literature regarding the risks of [cardiovascular] comorbidities in patients with hemophilia A, compared with the general population,” the investigators wrote in Advances in Medical Sciences. “Some studies have reported lower mortality from [cardiovascular] diseases and/or decreased atherogenesis in patients with hemophilia … conversely, other reports indicate comparable or higher [cardiovascular] comorbidities in patients with hemophilia, compared with the general population.”

In two previous commercial database reviews conducted by Dr. Humphries and his colleagues, cardiovascular disease appeared to occur more commonly and at a younger age in men with hemophilia A. More concerning, patients aged under 40 years showed elevated incidence of stroke and thrombosis. The authors sought to clarify these findings in the present study.

The retrospective chart review involved 74 men with hemophilia A and 222 men without the condition, matched by study year, payer type, race, and age. Patients presented at any of 31 medical facilities within the Henry Ford Health System in Detroit. Diagnoses were made between Jan. 1, 1995, and Dec. 31, 2014.

For the most part there were no significant differences in cardiovascular disease prevalence between the two cohorts. Rates of hypertension, obesity, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease were numerically higher in the control group, but those differences were not statistically significant. There were significantly higher prevalence rates for diabetes (P = .0108) and hyperlipidemia (P = .0001) in the control group versus patients with hemophilia A.

The investigators pointed out that meaningful statistical differences using standardized differences were not reached for venous and arterial thrombosis and atrial fibrillation.

“It is worth noting that in the hemophilia A group, hypertension appeared first in the 18- to 29-year age group, as did venous thrombosis,” the investigators wrote, suggesting that monitoring, starting in the late teens, may be warranted.

The investigators also noted multiple study limitations, notably the small sample size, compared with commercial databases that were reviewed in previous studies. Additionally, the severity of disease was unknown for some of the hemophilia A patients and the study only followed patients for 1 year.

“The results of this retrospective chart review did not confirm diffuse statistically significant differences in [cardiovascular] comorbidities and their earlier onset in hemophilia A versus controls,” the investigators concluded.

The study was funded by Bayer. Three of the authors were employed by Bayer when the study was conducted. Other authors reported employment with Xcenda and the Henry Ford Health System and research funding from Xcenda.

SOURCE: Humphries TJ et al. Adv Med Sci. 2018;63(2):329-33.

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

Dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R), which is used to treat several types of aggressive non-Hodgkin lymphomas, is associated with high rates of line-associated complications, a new study suggests.

MrArifnajafov/CC-BY-3.0

These findings, published in Clinical Lymphoma, Myeloma & Leukemia, confirm other recent findings that DA-EPOCH-R has a significantly greater rate of complications, compared with that of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy.

The authors note that the use of DA-EPOCH-R is based on data from early phase trials, as well as retrospective data, that support its use as induction chemotherapy in high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 translocations. But currently, there are no data published from randomized trials that support the use of upfront DA-EPOCH-R therapy.

DA-EPOCH-R is an infusion-based therapy that requires a central venous catheter.

In their study, Rachel J. David, MD, of Wilmot Cancer Institute, Rochester, N.Y., and her colleagues conducted a retrospective study that included all patients treated with DA-EPOCH-R at their institution between March 2011 and July 2016, and also included a concurrent cohort of patients with diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP. The goal was to identify the rates and predictors of line-associated complications linked with the use of DA-EPOCH-R therapy in this population.

The patient cohort comprised 43 patients who received DA-EPOCH-R and 44 patients who received RCHOP.

Patients in the DA-EPOCH-R cohort experienced a significantly higher rate of complications (P =.03), compared with the R-CHOP group.

In the DA-EPOCH-R cohort, 17 patients (39.5%) reported at least one LAC, which included venous thromboembolism, chemotherapy extravasation, and line-associated infection, during the study period. Grade 3 toxicity was observed in 41% of these patients.

In contrast, eight patients (18.2%) in the R-CHOP arm experienced at least one complication, with five of the eight patients experiencing grade 3-4 toxicity.

In a univariate analysis, body mass index of 35 kg/m² and the use of a peripherally inserted central catheter line were both significantly associated with a higher risk of venous thromboembolism (P = .04 and P = .02, respectively).

“For patients undergoing treatment with DA-EPOCH-R in whom the use of [central venous catheters] cannot be avoided, the morbidity of [line-associated complications] should be factored in by the clinician when determining upfront treatment,” the researchers wrote.

They reported having no conflicts of interest.
 

SOURCE: David RJ et al. Clin Lymphoma Myeloma Leuk. 2018 Aug 29. doi: 10.1016/j.clml.2018.08.014.

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3

SAN FRANCISCO – Daptomycin plus fosfomycin is more effective than daptomycin alone for methicillin-resistant Staphylococcus aureus bacteremia, according to a multicenter, randomized trial from Spain.

M. Alexander Otto/MDedge News

“I think this is really an important study; I think it will change clinical practice for this infection” once it’s published, said lead investigator Miquel Pujol, MD, PhD, clinical head of infectious diseases at Bellvitge University Hospital in Barcelona.

The current standard for MRSA bacteremia is daptomycin (Cubicin) or vancomycin (Vancocin) monotherapy on both sides of the Atlantic, but mortality rates are way too high, more than 30% in some reviews. Dr. Pujol and his colleagues wanted to find something better.

Their lab work showed that daptomycin and fosfomycin (Monurol) were synergistic and rapidly bactericidal against MRSA, and anecdotal experience in Spain suggested the drugs improved bacteremia outcomes, so they decided to put the combination to the test.

They randomized 74 MRSA bacteremia patients to the combination, daptomycin 10mg/kg IV daily plus fosfomycin 2g IV q 6h. They randomized 81 other subjects to standard of care with daptomycin monotherapy, also at 10mg/kg IV daily. Treatment was 10-14 days for uncomplicated and 28-42 days for complicated bacteremia.

The open-label trial was conducted at 18 medical centers in Spain, where fosfomycin was discovered in dirt samples in the late 1960s and remains a matter of pride.

At day 7, 69 of the 74 combination patients (93.2%) were alive with clinical improvement, clearance of bacteremia, and no subsequent relapse, versus 62 of 81 patients (76.5%) on monotherapy (absolute difference 16.7%; 95% confidence interval, 5.4%-27.7%). Three people in the combination arm (4.1%) had died by day 7, versus six on monotherapy (7.4%).

Six weeks after the end of treatment at the test-of-cure visit, 40 of 74 combination patients (54.1%) were alive with resolution of all clinical signs and symptoms, negative blood cultures, and no previous or subsequent relapses; just 34 of 81 patients (42%) in the monotherapy arm hit that mark. The 12.1% difference was not statistically significant, nor was the difference in 12-week survival.

However, patients in the combination arm were 70% less likely to have complicated bacteremia at the test-of-cure visit (9.5% vs. 28.4%; relative risk 0.3; 95% CI, 0.2-0.7). There were no cases of persistent or recurrent infection in the combination arm, but nine persistent (11.1%) and five recurrent (6.2%) cases with daptomycin monotherapy. The differences were statistically significant.

The subjects all had at least one positive MRSA blood culture within 72 hours of randomization. Exclusion criteria included MRSA pneumonia, prosthetic valve endocarditis, end-stage liver disease, and moderate to severe heart failure.

There were no significant baseline differences between the groups. About half the subjects were men, and the mean age was about 73 years. The mean Charlson Comorbidity Index score was a bit under 4, and the mean Pitt bacteremia score a bit over 1. The leading source of infection was vascular catheter; acquisition was thought to be nosocomial in more than 40% of patients.

There were no discontinuations from drug side effects in the daptomycin arm, but there were five in the combination arm, including two for heart failure, two for respiratory insufficiency, and one for GI bleeding. Even so, the benefit outweighed the risk, Dr. Pujol said.

Intravenous fosfomycin is available in Europe, but the drug is approved in the United States only as an oral formulation. That could change soon; Nabriva Therapeutics plans to file its IV formulation (Contepo) for Food and Drug Administration approval in late 2018.

Though it is not standard of practice yet, the combination is increasingly being used in Spain for MRSA bacteremia, according to Dr. Pujol. “Patients probably need the combination [at least] initially, especially if they have complicated bacteremia” or fail monotherapy, he said at ID week, an annual scientific meeting on infectious diseases.

The work was funded by the Spanish government. Dr. Pujol said he had no relevant disclosures.
 

[email protected]

SOURCE: Pujol M et al. 2018 ID Week abstract LB3

Babies evolved to cry to get their needs met and adults evolved to be aroused by the sound. Perfect match, right? But crying/fussing was rated the No. 1 hardest part of parenting for 0- to 3-year-olds in our data from more than 68,000 parents.

Petro Feketa/iStockphoto

As clinicians, we become amazingly immune to the crying in our offices, but hopefully not to crying as a concern of parents. Our training directs us to look for pathology such as under- or overfeeding, infection, gastroesophageal reflux disease (GERD), volvulus, a hair tourniquet, or an injury as causes of crying. Having ruled these out, the bigger task is making sure that parents learn to read their infants’ crying and find ways to console them. Learning to handle crying can be tense, frustrating, and upsetting for parents, but success is ultimately satisfying and an important part of the reciprocal interaction that builds attachment for both parent and child.

“Developmental crying” is a great term for explaining crying in the first 3 months to families, as it is age related. The acronym PURPLE was created to teach about this normal crying.
 

• “P” is for peak of crying – babies may cry more each week, most in month 2, then less in months 3-5.
• “U” is for unexpected – crying can come and go without explanation.
• “R” is for resists soothing – babies may not stop crying no matter what is tried.
• “P” is for pain-like face – babies appear to be in pain, even if they are not.
• “L” is for long lasting – crying can last 5 hours a day or more.
• “E” is for evening – the baby might cry more in the late afternoon and evening.

The 1- to 2-week visit is a key time to teach parents about the expected upcoming crying and ways to manage it. I lean on the evidence-based steps for soothing, using the 5 S’s described by Harvey Karp, MD, based on the wisdom of T. Berry Brazelton, MD. These include:

• Swaddling in a wrap that constrains arms and legs.
• Side or stomach holding (but not for sleeping).
• Shushing sounds of voice, radio static, fan, air conditioner, or car ride.
• Swinging gently (point out to never shake a baby).
• Sucking on a pacifier, finger, or hand.

Because babies change state slowly and also respond to high caregiver emotion such as anxiety, it is important for parents to take some deep breaths and give each “S” several minutes to have an effect.

Some of our patients will go beyond typical crying to colic, defined as crying for at least 3 hours per day, at least 3 days per week, starting before 3 months post term. While typically easing by age 3 months, colic can in nightmare cases persist to age 1 year. Needless to say, prolonged crying can be an enormous stress for families. Researchers in the Fussy Baby Network consulting on infant crying have found value in a family prescription for REST: Reassurance, Empathy, Support, and Time away. Reassurance that the child is not ill should be provided after a careful history, including asking why parents think the baby is crying, and a physical exam, even if we think we can tell at a glance that the baby is okay. Remember that every parent’s first concern is whether the baby is okay, and crying indicates otherwise. Parents are counting on us for a thorough exam before we reassure them. Exhausted new parents deserve empathy – acknowledgment of how difficult, scary, and maddening it is to not be able to console their newborns.

While friends are saying “You must be so happy!” after a child is born, ambivalence (What have I done to my life?) is very common, but not easy to admit. We can point out that the typical age at which parents report “loving” their infants is actually more like 6 weeks, when they finally smile! To acknowledge ambivalence, I may say, “When you feel like throwing him out the window, it’s okay to lay him in the crib and put on headphones for a few minutes.” Music, meditation, yoga, or exercise are break activities that also can reduce parent stress.

Support for the parents is one of the most important protections for children at all ages, but can’t be assumed. Unfortunately, crying tends to increase beginning at 2 weeks post term, right when the partner returns to work or relatives leave. It is important to ask, “Who is helping you with the baby?” Just having a partner doesn’t mean that person is taking a turn! Fathers may be afraid of holding a baby, or may have no experience and try to defer. We need to encourage fathers in all aspects of care but especially to “find at least one way to console your baby.” Sometimes mothers “rescue” dads too quickly. While mothers may have both more experience with infants and the magic of breastfeeding for consoling, depriving fathers of working through the struggle of managing crying can result in their developing less confidence in caregiving. It also can cause them to miss out on supporting the mother at this delicate time, a chance to profoundly strengthen the partnership.

Taking into account the importance for parents of finding ways to console crying babies, getting some “time away” can be helpful, especially if crying goes on for months. Maybe those friends who asked, “What can I do to help?” could come over for an hour in the evening (peak crying time) to hold the baby. This also can be a chance for parent time together, a newly rare commodity.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Babies evolved to cry to get their needs met and adults evolved to be aroused by the sound. Perfect match, right? But crying/fussing was rated the No. 1 hardest part of parenting for 0- to 3-year-olds in our data from more than 68,000 parents.

Petro Feketa/iStockphoto

As clinicians, we become amazingly immune to the crying in our offices, but hopefully not to crying as a concern of parents. Our training directs us to look for pathology such as under- or overfeeding, infection, gastroesophageal reflux disease (GERD), volvulus, a hair tourniquet, or an injury as causes of crying. Having ruled these out, the bigger task is making sure that parents learn to read their infants’ crying and find ways to console them. Learning to handle crying can be tense, frustrating, and upsetting for parents, but success is ultimately satisfying and an important part of the reciprocal interaction that builds attachment for both parent and child.

“Developmental crying” is a great term for explaining crying in the first 3 months to families, as it is age related. The acronym PURPLE was created to teach about this normal crying.
 

• “P” is for peak of crying – babies may cry more each week, most in month 2, then less in months 3-5.
• “U” is for unexpected – crying can come and go without explanation.
• “R” is for resists soothing – babies may not stop crying no matter what is tried.
• “P” is for pain-like face – babies appear to be in pain, even if they are not.
• “L” is for long lasting – crying can last 5 hours a day or more.
• “E” is for evening – the baby might cry more in the late afternoon and evening.

The 1- to 2-week visit is a key time to teach parents about the expected upcoming crying and ways to manage it. I lean on the evidence-based steps for soothing, using the 5 S’s described by Harvey Karp, MD, based on the wisdom of T. Berry Brazelton, MD. These include:

• Swaddling in a wrap that constrains arms and legs.
• Side or stomach holding (but not for sleeping).
• Shushing sounds of voice, radio static, fan, air conditioner, or car ride.
• Swinging gently (point out to never shake a baby).
• Sucking on a pacifier, finger, or hand.

Because babies change state slowly and also respond to high caregiver emotion such as anxiety, it is important for parents to take some deep breaths and give each “S” several minutes to have an effect.

Some of our patients will go beyond typical crying to colic, defined as crying for at least 3 hours per day, at least 3 days per week, starting before 3 months post term. While typically easing by age 3 months, colic can in nightmare cases persist to age 1 year. Needless to say, prolonged crying can be an enormous stress for families. Researchers in the Fussy Baby Network consulting on infant crying have found value in a family prescription for REST: Reassurance, Empathy, Support, and Time away. Reassurance that the child is not ill should be provided after a careful history, including asking why parents think the baby is crying, and a physical exam, even if we think we can tell at a glance that the baby is okay. Remember that every parent’s first concern is whether the baby is okay, and crying indicates otherwise. Parents are counting on us for a thorough exam before we reassure them. Exhausted new parents deserve empathy – acknowledgment of how difficult, scary, and maddening it is to not be able to console their newborns.

While friends are saying “You must be so happy!” after a child is born, ambivalence (What have I done to my life?) is very common, but not easy to admit. We can point out that the typical age at which parents report “loving” their infants is actually more like 6 weeks, when they finally smile! To acknowledge ambivalence, I may say, “When you feel like throwing him out the window, it’s okay to lay him in the crib and put on headphones for a few minutes.” Music, meditation, yoga, or exercise are break activities that also can reduce parent stress.

Support for the parents is one of the most important protections for children at all ages, but can’t be assumed. Unfortunately, crying tends to increase beginning at 2 weeks post term, right when the partner returns to work or relatives leave. It is important to ask, “Who is helping you with the baby?” Just having a partner doesn’t mean that person is taking a turn! Fathers may be afraid of holding a baby, or may have no experience and try to defer. We need to encourage fathers in all aspects of care but especially to “find at least one way to console your baby.” Sometimes mothers “rescue” dads too quickly. While mothers may have both more experience with infants and the magic of breastfeeding for consoling, depriving fathers of working through the struggle of managing crying can result in their developing less confidence in caregiving. It also can cause them to miss out on supporting the mother at this delicate time, a chance to profoundly strengthen the partnership.

Taking into account the importance for parents of finding ways to console crying babies, getting some “time away” can be helpful, especially if crying goes on for months. Maybe those friends who asked, “What can I do to help?” could come over for an hour in the evening (peak crying time) to hold the baby. This also can be a chance for parent time together, a newly rare commodity.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Babies evolved to cry to get their needs met and adults evolved to be aroused by the sound. Perfect match, right? But crying/fussing was rated the No. 1 hardest part of parenting for 0- to 3-year-olds in our data from more than 68,000 parents.

Petro Feketa/iStockphoto

As clinicians, we become amazingly immune to the crying in our offices, but hopefully not to crying as a concern of parents. Our training directs us to look for pathology such as under- or overfeeding, infection, gastroesophageal reflux disease (GERD), volvulus, a hair tourniquet, or an injury as causes of crying. Having ruled these out, the bigger task is making sure that parents learn to read their infants’ crying and find ways to console them. Learning to handle crying can be tense, frustrating, and upsetting for parents, but success is ultimately satisfying and an important part of the reciprocal interaction that builds attachment for both parent and child.

“Developmental crying” is a great term for explaining crying in the first 3 months to families, as it is age related. The acronym PURPLE was created to teach about this normal crying.
 

• “P” is for peak of crying – babies may cry more each week, most in month 2, then less in months 3-5.
• “U” is for unexpected – crying can come and go without explanation.
• “R” is for resists soothing – babies may not stop crying no matter what is tried.
• “P” is for pain-like face – babies appear to be in pain, even if they are not.
• “L” is for long lasting – crying can last 5 hours a day or more.
• “E” is for evening – the baby might cry more in the late afternoon and evening.

The 1- to 2-week visit is a key time to teach parents about the expected upcoming crying and ways to manage it. I lean on the evidence-based steps for soothing, using the 5 S’s described by Harvey Karp, MD, based on the wisdom of T. Berry Brazelton, MD. These include:

• Swaddling in a wrap that constrains arms and legs.
• Side or stomach holding (but not for sleeping).
• Shushing sounds of voice, radio static, fan, air conditioner, or car ride.
• Swinging gently (point out to never shake a baby).
• Sucking on a pacifier, finger, or hand.

Because babies change state slowly and also respond to high caregiver emotion such as anxiety, it is important for parents to take some deep breaths and give each “S” several minutes to have an effect.

Some of our patients will go beyond typical crying to colic, defined as crying for at least 3 hours per day, at least 3 days per week, starting before 3 months post term. While typically easing by age 3 months, colic can in nightmare cases persist to age 1 year. Needless to say, prolonged crying can be an enormous stress for families. Researchers in the Fussy Baby Network consulting on infant crying have found value in a family prescription for REST: Reassurance, Empathy, Support, and Time away. Reassurance that the child is not ill should be provided after a careful history, including asking why parents think the baby is crying, and a physical exam, even if we think we can tell at a glance that the baby is okay. Remember that every parent’s first concern is whether the baby is okay, and crying indicates otherwise. Parents are counting on us for a thorough exam before we reassure them. Exhausted new parents deserve empathy – acknowledgment of how difficult, scary, and maddening it is to not be able to console their newborns.

While friends are saying “You must be so happy!” after a child is born, ambivalence (What have I done to my life?) is very common, but not easy to admit. We can point out that the typical age at which parents report “loving” their infants is actually more like 6 weeks, when they finally smile! To acknowledge ambivalence, I may say, “When you feel like throwing him out the window, it’s okay to lay him in the crib and put on headphones for a few minutes.” Music, meditation, yoga, or exercise are break activities that also can reduce parent stress.

Support for the parents is one of the most important protections for children at all ages, but can’t be assumed. Unfortunately, crying tends to increase beginning at 2 weeks post term, right when the partner returns to work or relatives leave. It is important to ask, “Who is helping you with the baby?” Just having a partner doesn’t mean that person is taking a turn! Fathers may be afraid of holding a baby, or may have no experience and try to defer. We need to encourage fathers in all aspects of care but especially to “find at least one way to console your baby.” Sometimes mothers “rescue” dads too quickly. While mothers may have both more experience with infants and the magic of breastfeeding for consoling, depriving fathers of working through the struggle of managing crying can result in their developing less confidence in caregiving. It also can cause them to miss out on supporting the mother at this delicate time, a chance to profoundly strengthen the partnership.

Taking into account the importance for parents of finding ways to console crying babies, getting some “time away” can be helpful, especially if crying goes on for months. Maybe those friends who asked, “What can I do to help?” could come over for an hour in the evening (peak crying time) to hold the baby. This also can be a chance for parent time together, a newly rare commodity.

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to MDedge News. E-mail her at [email protected].

Physician groups are pushing back against a proposal to implement site-neutral payments, despite the fact that they generally support the concept of it.

TheaDesign/Thinkstock

In the proposed update to the Hospital Outpatient Prospective Payment System (OPPS) for 2019, the Centers for Medicare & Medicaid Services introduced a physician fee schedule–equivalent payment for clinic visit services when provided at an off-campus, provider-based department that is paid under the OPPS.

The American Medical Association said in a letter to the CMS that, while it “generally supports site-neutral payments, we do not believe that it is possible to sustain a high-quality health care system if site neutrality is defined as shrinking all payments to the lowest amount paid in any setting.” The AMA said that the current proposed rule is “complex, confusing, and is not truly site neutral because the policies do not apply equally to all hospital outpatient clinics,” adding that a contributor to the differential between private practice and hospital outpatient departments (HOPD) stems from physicians being underpaid in the physician fee schedule.

In a letter signed by the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy, they wrote that, “while ambulatory surgical centers (ASCs) are a more efficient and lower-cost alternative to the HOPD for a number of gastroenterology procedures, it does not mean, however, that reimbursement rates for services provided in both the ASC and the HOPD should be the same. Our societies support payment rates appropriate for each site of service and using appropriate policy and payment levers that result in patients receiving care in the most cost-efficient site of service.”

The American Academy of Family Physicians stated in a letter to Seema Verma, current administrator of the CMS, that, while it supports the idea of site-neutral payments, “we note that the payment methodology for 2019 will not assure equal payments for the same service, regardless of site of service.” The AAFP noted that the goal of curbing hospital acquisition of independent physician practices may not come to fruition and that “hospitals may still be incentivized to buy physician practices based on the mix of services they provide and bill them as PBDs [provider-based departments] at Medicare rates higher than would have been paid had the practice not been bought by the hospital.”

The American College of Cardiology offered support for site-neutral payments and, while it did not come out against the CMS’s proposal, it did offer a series of recommendations to consider, including determining that payments reflect “the resources required to provide patient care in each setting” and that “payment differences across sites should be related to documented differences in the resources needed to ensure patient access and high-quality care.”

The American Academy of Dermatology Association voiced its support for the proposal to the agency.

[email protected]

Physician groups are pushing back against a proposal to implement site-neutral payments, despite the fact that they generally support the concept of it.

TheaDesign/Thinkstock

In the proposed update to the Hospital Outpatient Prospective Payment System (OPPS) for 2019, the Centers for Medicare & Medicaid Services introduced a physician fee schedule–equivalent payment for clinic visit services when provided at an off-campus, provider-based department that is paid under the OPPS.

The American Medical Association said in a letter to the CMS that, while it “generally supports site-neutral payments, we do not believe that it is possible to sustain a high-quality health care system if site neutrality is defined as shrinking all payments to the lowest amount paid in any setting.” The AMA said that the current proposed rule is “complex, confusing, and is not truly site neutral because the policies do not apply equally to all hospital outpatient clinics,” adding that a contributor to the differential between private practice and hospital outpatient departments (HOPD) stems from physicians being underpaid in the physician fee schedule.

In a letter signed by the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy, they wrote that, “while ambulatory surgical centers (ASCs) are a more efficient and lower-cost alternative to the HOPD for a number of gastroenterology procedures, it does not mean, however, that reimbursement rates for services provided in both the ASC and the HOPD should be the same. Our societies support payment rates appropriate for each site of service and using appropriate policy and payment levers that result in patients receiving care in the most cost-efficient site of service.”

The American Academy of Family Physicians stated in a letter to Seema Verma, current administrator of the CMS, that, while it supports the idea of site-neutral payments, “we note that the payment methodology for 2019 will not assure equal payments for the same service, regardless of site of service.” The AAFP noted that the goal of curbing hospital acquisition of independent physician practices may not come to fruition and that “hospitals may still be incentivized to buy physician practices based on the mix of services they provide and bill them as PBDs [provider-based departments] at Medicare rates higher than would have been paid had the practice not been bought by the hospital.”

The American College of Cardiology offered support for site-neutral payments and, while it did not come out against the CMS’s proposal, it did offer a series of recommendations to consider, including determining that payments reflect “the resources required to provide patient care in each setting” and that “payment differences across sites should be related to documented differences in the resources needed to ensure patient access and high-quality care.”

The American Academy of Dermatology Association voiced its support for the proposal to the agency.

[email protected]

Physician groups are pushing back against a proposal to implement site-neutral payments, despite the fact that they generally support the concept of it.

TheaDesign/Thinkstock

In the proposed update to the Hospital Outpatient Prospective Payment System (OPPS) for 2019, the Centers for Medicare & Medicaid Services introduced a physician fee schedule–equivalent payment for clinic visit services when provided at an off-campus, provider-based department that is paid under the OPPS.

The American Medical Association said in a letter to the CMS that, while it “generally supports site-neutral payments, we do not believe that it is possible to sustain a high-quality health care system if site neutrality is defined as shrinking all payments to the lowest amount paid in any setting.” The AMA said that the current proposed rule is “complex, confusing, and is not truly site neutral because the policies do not apply equally to all hospital outpatient clinics,” adding that a contributor to the differential between private practice and hospital outpatient departments (HOPD) stems from physicians being underpaid in the physician fee schedule.

In a letter signed by the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy, they wrote that, “while ambulatory surgical centers (ASCs) are a more efficient and lower-cost alternative to the HOPD for a number of gastroenterology procedures, it does not mean, however, that reimbursement rates for services provided in both the ASC and the HOPD should be the same. Our societies support payment rates appropriate for each site of service and using appropriate policy and payment levers that result in patients receiving care in the most cost-efficient site of service.”

The American Academy of Family Physicians stated in a letter to Seema Verma, current administrator of the CMS, that, while it supports the idea of site-neutral payments, “we note that the payment methodology for 2019 will not assure equal payments for the same service, regardless of site of service.” The AAFP noted that the goal of curbing hospital acquisition of independent physician practices may not come to fruition and that “hospitals may still be incentivized to buy physician practices based on the mix of services they provide and bill them as PBDs [provider-based departments] at Medicare rates higher than would have been paid had the practice not been bought by the hospital.”

The American College of Cardiology offered support for site-neutral payments and, while it did not come out against the CMS’s proposal, it did offer a series of recommendations to consider, including determining that payments reflect “the resources required to provide patient care in each setting” and that “payment differences across sites should be related to documented differences in the resources needed to ensure patient access and high-quality care.”

The American Academy of Dermatology Association voiced its support for the proposal to the agency.

[email protected]